Ebook British national formulary 70 (BNF) Part 2

(BQ) Part 2 book British national formulary 70 (BNF) presentation of content: Genitourinary system, malignant disease, blood and nutrition, musculoskeletal system, ear, nose and oropharynx, eye, skin, vaccines, emergency treatment of poisoning, anaesthesia. Invite you to consult.

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Chapter 7

Genito-urinary system

CONTENTS

1 Bladder and urinary disorders page667

1.1 Urinary frequency, enuresis, and incontinence 667

3.3 Contraception, oral progestogen-only 691

3.4 Contraception, parenteral progestogen-only 694

4 Erectile and ejaculatory conditions 697

Urinary frequency and incontinence

Incontinence in adults which arises from detrusor instability

is managed by combining drug therapy with conservative

methods for managing urge incontinence such as pelvic

floor exercises and bladder training; stress incontinence is

generally managed by non-drug methods Duloxetine p.288

can be added and is licensed for the treatment of moderate

to severe stress incontinence in women; it may be more

effective when used as an adjunct to pelvic floor exercises

Antimuscarinic drugs reduce symptoms of urgency and

urge incontinence and increase bladder capacity

Oxybutynin hydrochloride p.669also has a direct relaxant

effect on urinary smooth muscle Side-effects limit the use

of oxybutynin hydrochloride, but they may be reduced by

starting at a lower dose A modified-release preparation of

oxybutynin hydrochloride is effective and has fewer

side-effects; a transdermal patch is also available The efficacy

and side-effects of tolterodine tartrate p.671are

comparable to those of modified-release oxybutynin

hydrochloride Flavoxate hydrochloride p.669has less

marked side-effects but it is also less effective Darifenacin

p.668, fesoterodine fumarate p.668, propiverine

hydrochloride p.670, solifenacin succinate p.670, and

trospium chloride p.671are newer antimuscarinic drugs

licensed for urinary frequency, urgency, and incontinence

The need for continuing antimuscarinic drug therapy should

be reviewed every4–6weeks until symptoms stabilise, and

then every6–12months

Propantheline bromide p.74and tricyclic antidepressants

were used for urge incontinence but they are little used now

hydrochloride p.296is limited by its potential to causecardiac side-effects

Mirabegron p.671, a selective beta3agonist, is licensedfor the treatment of urinary frequency, urgency, and urgeincontinence associated with overactive bladder syndrome.Purified bovine collagen implant (Contigen®, Bard) isindicated for urinary incontinence caused by intrinsicsphincter deficiency (poor or non-functioning bladderoutlet mechanism) The implant should be inserted only bysurgeons or physicians trained in the technique for injection

of the implant

Nocturnal enuresis in childrenNocturnal enuresis is common in young children, butpersists in a small proportion by10years of age Forchildren under5years, reassurance and advice on themanagement of nocturnal enuresis can be useful for somefamilies Treatment may be considered in children over

5years depending on their maturity and motivation, thefrequency of nocturnal enuresis, and the needs of the childand their family

Initially, advice should be given on fluid intake, diet,toileting behaviour, and reward systems; for children who

do not respond to this advice, further treatment may benecessary An enuresis alarm should be first line treatmentfor motivated, well-supported children; alarms have a lowerrelapse rate than drug treatment when discontinued

Treatment should be reviewed after4weeks, and, if thereare early signs of response, continued until a minimum of

2weeks’ uninterrupted dry nights have been achieved Ifcomplete dryness is not achieved after3months, onlycontinue if the condition is still improving and the childremains motivated to use the alarm If initial alarmtreatment is unsuccessful, consider combination treatmentwith desmopressin p.574, or desmopressin alone if thealarm is no longer appropriate or desirable

Desmopressin is given by oral or by sublingualadministration Desmopressin alone can be offered tochildren over5years of age if an alarm is inappropriate orundesirable, or when rapid or short-term results are thepriority (for example to cover periods away from home);desmopressin alone can also be used if there has been apartial response to a combination of desmopressin and analarm following initial treatment with an alarm Treatmentshould be assessed after4weeks and continued for

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3months if there are signs of response Desmopressin

should be withdrawn at regular intervals (for1week every

3months) for full reassessment When stopping treatment

with desmopressin, gradual withdrawal should be

considered

Nocturnal enuresis associated with daytime symptoms

(overactive bladder) can be managed with antimuscarinic

drugs (see Urinary incontinence) in combination with

desmopressin Treatment should be prescribed only after

specialist assessment and should be continued for

3months; the course can be repeated if necessary

The tricyclic antidepressant imipramine hydrochloride

p.296may be considered for children who have not

responded to all other treatments and have undergone

specialist assessment, however, behavioural disturbances

can occur and relapse is common after withdrawal

Treatment should not normally exceed3months unless a

physical examination is made and the child is fully

reassessed; toxicity following overdosage with tricyclics is of

particular concern

ANTIMUSCARINICS

Antimuscarinics (systemic) f

lCONTRA-INDICATIONSGastro-intestinal obstruction.

intestinal atony.myasthenia gravis (but some

antimuscarinics may be used to decrease muscarinic

side-effects of anticholinesterases).paralytic ileus.prostatic

enlargement.pyloric stenosis.severe ulcerative colitis.

significant bladder outflow obstruction.toxic megacolon.

urinary retention

lCAUTIONSAcute myocardial infarction.arrhythmias (may

be worsened).autonomic neuropathy.cardiac

insufficiency (due to association with tachycardia).

cardiac surgery (due to association with tachycardia).

conditions characterised by tachycardia.congestive heart

failure (may be worsened).coronary artery disease (may

be worsened).diarrhoea.elderly (especially if frail).

gastro-oesophageal reflux disease.hiatus hernia with

reflux oesophagitis.hypertension.hyperthyroidism (due

to association with tachycardia).individuals susceptible

to angle-closure glaucoma.prostatic hyperplasia.pyrexia

.ulcerative colitis

lINTERACTIONS→ Appendix1(antimuscarinics)

Many drugs have antimuscarinic effects; concomitant use

of two or more such drugs can increase side-effects such

as dry mouth, urine retention, and constipation

Concomitant use of other drugs with antimuscarinic

effects can also lead to confusion in the elderly

lSIDE-EFFECTS

▶Common or very commonConstipation.dilation of pupils

with loss of accommodation.dry mouth.photophobia.

reduced bronchial secretions.skin dryness.skin flushing

.transient bradycardia (followed by tachycardia,

palpitation and arrhythmias).urinary retention.urinary

urgency

▶UncommonConfusion (particularly in the elderly).

giddiness.nausea.vomiting

▶Very rareAngle-closure glaucoma

▶Frequency not knownAngioedema.blurred vision.blurred

vision.central nervous system stimulation.convulsion.

diarrhoea.difficulty in micturition.disorientation.

dizziness.drowsiness.dry eyes.euphoria.fatigue.

flatulence.hallucinations.headache.impaired memory.

palpitation.photosensitivity.rash.reduced sweating

(may lead to heat sensations and fainting in hot

environments or patients with fever).restlessness.taste

▶UncommonCough.dyspnoea.hypertension.impotence.

insomnia.oedema.rhinitis.ulcerative stomatitis.

lMEDICINAL FORMSThere can be variation in the licensing of different medicinescontaining the same drug

Modified-release tabletCAUTIONARY AND ADVISORY LABELS3, 25

▶Emselex(Merus Labs Luxco S.a R.L.)Darifenacin (as Darifenacin hydrobromide) 7.5 mg Emselex7.5mgmodified-release tablets|28tabletP£25.48DT price = £25.48Darifenacin (as Darifenacin hydrobromide) 15 mg Emselex15mgmodified-release tablets|28tabletP£25.48

In patients with hepatic or renal impairment, consultproduct literature before concomitant use withamprenavir, aprepitant, atazanavir, clarithromycin,diltiazem, erythromycin, fluconazole, fosamprenavir,indinavir, itraconazole, ritonavir, saquinavir,telithromycin, verapamil, or grapefruit juice

lSIDE-EFFECTS

▶Common or very commonInsomnia

▶UncommonCough.nasal dryness.pharyngolaryngealpain.vertigo

lPREGNANCYManufacturer advises avoid—toxicity inanimal studies

lBREAST FEEDINGManufacturer advises avoid—noinformation available

lHEPATIC IMPAIRMENTManufacturer advises increase dosecautiously; max.4mg daily in moderate impairment.Avoid in severe impairment Consult product literaturebefore concomitant use of cytochrome P450enzymeinhibitors

lRENAL IMPAIRMENTIncrease dose cautiously if eGFR

30–80mL/minute/1.73m2; max.4mg daily if eGFR lessthan30mL/minute/1.73m2 Consult product literaturebefore concomitant use of cytochrome P450enzymeinhibitors

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lPRESCRIBING AND DISPENSING INFORMATIONThe need

for continuing therapy for urinary incontinence should be

reviewed every4–6weeks until symptoms stabilise, and

lNATIONAL FUNDING/ACCESS DECISIONS

Scottish Medicines Consortium (SMC) Decisions

The Scottish Medicines Consortium has advised (June

2008) that fesoterodine (Toviaz®) is accepted for

restricted use within NHS Scotland as a second-line

treatment for overactive bladder syndrome

lMEDICINAL FORMS

There can be variation in the licensing of different medicines

containing the same drug

Modified-release tablet

CAUTIONARY AND ADVISORY LABELS3, 25

▶Toviaz(Pfizer Ltd)

Fesoterodine fumarate 4 mg Toviaz4mg modified-release

tablets|28tabletP£25.78DT price = £25.78

Fesoterodine fumarate 8 mg Toviaz8mg modified-release

INDICATIONS AND DOSE

Urinary frequency| Urinary incontinence | Dysuria | Urinary

urgency| Bladder spasm due to catheterisation, cytoscopy,

or surgery

BY MOUTH

▶Adult:200mg3times a day

lCONTRA-INDICATIONSGastro-intestinal haemorrhage

lSIDE-EFFECTSEosinophilia.erythema.leucopenia.

pruritus.urticaria.vertigo

lPREGNANCYManufacturer advises avoid unless no safer

alternative

lBREAST FEEDINGManufacturer advises caution—no

information available

for continuing therapy for urinary incontinence should be

reviewed every4–6weeks until symptoms stabilise, and

lMEDICINAL FORMS

containing the same drug Forms available from special-order

manufacturers include: oral solution, oral suspension

Tablet

CAUTIONARY AND ADVISORY LABELS3

▶Urispas(Recordati Pharmaceuticals Ltd)

Flavoxate hydrochloride 200 mg Urispas200tablets|

90tabletP£11.67DT price = £11.67

Urinary frequency| Urinary urgency | Urinary incontinence |

Neurogenic bladder instability

BY MOUTH USING IMMEDIATE-RELEASE MEDICINES

▶Child 5–11 years: Initially2.5–3mg twice daily,

increased to5mg2–3times a day

▶Child 12–17 years: Initially5mg2–3times a day,

increased if necessary up to5mg4times a day

▶Adult:Initially5mg2–3times a day, increased if

necessary up to5mg4times a day

▶Elderly:Initially2.5–3mg twice daily, increased if

tolerated to5mg twice daily, adjusted according to

response

BY MOUTH USING MODIFIED-RELEASE TABLETS

▶Child 5–17 years: Initially5mg once daily, adjusted insteps of5mg every1week, adjusted according toresponse; maximum15mg per day

▶Adult:Initially5mg once daily, increased in steps of

5mg every1week, adjusted according to response;

maximum20mg per day

BY TRANSDERMAL APPLICATION USING PATCHES

▶Adult:Apply1patch twice weekly, patch is to beapplied to clean, dry unbroken skin on abdomen, hip

or buttock Patch should be removed every3-4daysand site replacement patch on a different area Thesame area should be avoided for7days

Nocturnal enuresis associated with overactive bladder

▶Child 5–17 years: 2.5–3mg twice daily, increased to

5mg2–3times a day, last dose to be taken beforebedtime

▶Child 5–17 years: Initially5mg once daily, adjusted insteps of5mg every1week, adjusted according toresponse; maximum15mg per day

Dose equivalence and conversionPatients taking immediate-release oxybutynin may betransferred to the nearest equivalent daily dose of Lyrinel

®XL

lUNLICENSED USENot licensed for use in children under

5years Intravesical instillation not licensed for use inchildren

lCAUTIONSAcute porphyrias p.864

lSIDE-EFFECTSGENERAL SIDE-EFFECTS

▶UncommonAnorexia.facial flushing

▶RareNight terrors

▶Frequency not knownCognitive impairmentSPECIFIC SIDE-EFFECTS

lHEPATIC IMPAIRMENTManufacturer advises caution

lRENAL IMPAIRMENTManufacturer advises caution

lDIRECTIONS FOR ADMINISTRATION

▶With transdermal useApply patches to clean, dry, unbrokenskin on abdomen, hip or buttock, remove after every

3–4days and site replacement patch on a different area(avoid using same area for7days)

lPRESCRIBING AND DISPENSING INFORMATION

▶In adultsThe need for continuing therapy for urinaryincontinence should be reviewed every4–6weeks untilsymptoms stabilise, and then every6–12months

▶In childrenThe need for therapy for urinary indicationsshould be reviewed soon after it has been commenced andthen at regular intervals; a response usually occurs within

6months but may take longer

lPATIENT AND CARER ADVICEMedicines for Children leaflet: Oxybutynin for daytime urinarysymptomswww.medicinesforchildren.org.uk/

oxybutynin-for-daytime-urinary-symptomsPatients or carers should be given advice on how toadminister oxybutynin transdermal patches

lNATIONAL FUNDING/ACCESS DECISIONSScottish Medicines Consortium (SMC) DecisionsThe Scottish Medicines Consortium has advised (July2005)that Kentera®should be restricted for use in adults who

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benefit from oral oxybutynin but cannot tolerate its

side-effects

lMEDICINAL FORMS

manufacturers include: oral suspension, oral solution

Tablet

▶OXYBUTYNIN HYDROCHLORIDE (Non-proprietary)

Oxybutynin hydrochloride 2.5 mg Oxybutynin2.5mg tablets|

56tabletP£6.58DT price = £1.75|84tabletP£10.75

Oxybutynin hydrochloride 3 mg Oxybutynin3mg tablets|

56tabletP£14.00–£16.80DT price = £16.80

Oxybutynin hydrochloride 5 mg Oxybutynin5mg tablets|

▶OXYBUTYNIN HYDROCHLORIDE (Non-proprietary)

Oxybutynin hydrochloride 500 microgram per 1 ml Oxybutynin

2.5mg/5ml oral solution sugar free (sugar-free)|150mlP

£128.15

Oxybutynin hydrochloride 1 mg per 1 ml Oxybutynin5mg/5ml oral

solution sugar free (sugar-free)|150mlP£128.15–£168.00

▶Ditropan(Sanofi)

Oxybutynin hydrochloride 500 microgram per 1 ml Ditropan

2.5mg/5ml elixir|150mlP£6.88DT price = £6.88

Transdermal patch

▶Kentera(Orion Pharma (UK) Ltd)

Oxybutynin 3.9 mg per 24 hour Kentera3.9mg/24hours patches|

8patchP£27.20DT price = £27.20

Propiverine hydrochloride F

Urinary frequency, urgency and incontinence associated

with overactive bladder

INITIALLY BY MOUTH USING IMMEDIATE-RELEASE MEDICINES

▶Adult:15mg1–2times a day, increased if necessary up

to15mg3times a day

BY MOUTH USING MODIFIED-RELEASE CAPSULES

▶Adult:30mg once daily

Urinary frequency, urgency and incontinence associated

with neurogenic bladder instability

▶Adult:15mg3times a day

lPREGNANCYManufacturer advises avoid (restriction of

skeletal development in animals)

lBREAST FEEDINGManufacturer advises avoid—present in

milk in animal studies

lHEPATIC IMPAIRMENTAvoid in moderate to severe

impairment

lRENAL IMPAIRMENTMax daily dose30mg if eGFR less

than30mL/minute/1.73m2 Manufacturer advises caution

in mild or moderate impairment

reviewed every4–6weeks until symptoms stabilise, andthen every6–12months

TabletCAUTIONARY AND ADVISORY LABELS3

▶Detrunorm(AMCo)Propiverine hydrochloride 15 mg Detrunorm15mg tablets|

56tabletP£18.00DT price = £18.00Modified-release capsuleCAUTIONARY AND ADVISORY LABELS3, 25

▶Detrunorm XL(AMCo)Propiverine hydrochloride 30 mg Detrunorm XL30mg capsules|

28capsuleP£24.45DT price = £24.45Propiverine hydrochloride 45 mg Detrunorm XL45mg capsules|

lCAUTIONSNeurogenic bladder disorder.susceptibility toQT-interval prolongation

lSIDE-EFFECTS

▶UncommonGastro-oesophageal reflux.oedema

▶Frequency not knownDysphonia.hepatic impairment.

hyperkalaemia.muscle weakness.reduced appetite.

in severe impairment

lRENAL IMPAIRMENTMax.5mg daily if eGFR less than

30mL/minute/1.73m2; avoid if eGFR less than

30mL/minute/1.73m2in those already taking potentinhibitors of cytochrome P450enzyme CYP3A4(such asitraconazole or ritonavir)

lPRESCRIBING AND DISPENSING INFORMATIONThe needfor continuing therapy for urinary incontinence should bereviewed every4–6weeks until symptoms stabilise, andthen every6–12months

lMEDICINAL FORMSThere can be variation in the licensing of different medicinescontaining the same drug Forms available from special-ordermanufacturers include: oral solution, oral suspensionTablet

▶Vesicare(Astellas Pharma Ltd)Solifenacin succinate 5 mg Vesicare5mg tablets|30tabletP

£27.62DT price = £27.62Solifenacin succinate 10 mg Vesicare10mg tablets|

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Tolterodine tartrate F

Urinary frequency| Urinary urgency | Urinary incontinence

INITIALLY BY MOUTH USING IMMEDIATE-RELEASE MEDICINES

▶Adult:2mg twice daily, reduced if not tolerated to

1mg twice daily

BY MOUTH USING MODIFIED-RELEASE CAPSULES

lCAUTIONSHistory of QT-interval prolongation

lINTERACTIONSCaution with concomitant use with other

drugs known to prolong QT interval

lSIDE-EFFECTS

▶Common or very commonBronchitis.chest pain.fatigue.

paraesthesia.peripheral oedema.sinusitis.vertigo.

weight gain

▶UncommonMemory impairment

▶Frequency not knownFlushing

lPREGNANCYManufacturer advises avoid—toxicity in

animal studies

lBREAST FEEDINGManufacturer advises avoid—no

lHEPATIC IMPAIRMENTReduce dose to1mg twice daily

Avoid modified-release preparations

lRENAL IMPAIRMENTReduce dose to1mg twice daily if

eGFR less than30mL/minute/1.73m2 Avoid

modified-release preparations if eGFR less than

30mL/minute/1.73m2

The need for continuing therapy for urinary incontinence

should be reviewed every4–6weeks until symptoms

stabilise, and then every6–12months

lMEDICINAL FORMS

manufacturers include: oral suspension, oral solution, powder

Tablet

▶TOLTERODINE TARTRATE (Non-proprietary)

Tolterodine tartrate 1 mg Tolterodine1mg tablets|

▶Brands may include Blerone XL; Efflosomyl XL; Inconex XL; Mariosea

XL; Neditol XL; Preblacon XL; Santizor X

Urinary frequency| Urinary urgency | Urinary incontinence

▶Adult:20mg twice daily, to be taken before food

BY MOUTH USING MODIFIED-RELEASE MEDICINES

lSIDE-EFFECTS

▶RareAsthenia.chest pain.dyspnoea

▶Very rareArthralgia.myalgia

lPREGNANCYManufacturer advises caution

lBREAST FEEDINGManufacturer advises caution

lHEPATIC IMPAIRMENTManufacturer advises caution inmild to moderate impairment Avoid in severeimpairment

lRENAL IMPAIRMENTReduce dose to20mg once daily or

20mg on alternate days if eGFR

10–30mL/minute/1.73m2 Use with caution AvoidRegurin®XL

lPRESCRIBING AND DISPENSING INFORMATIONThe needfor continuing therapy for urinary incontinence should bereviewed every4–6weeks until symptoms stabilise, andthen every6–12months

lMEDICINAL FORMSThere can be variation in the licensing of different medicinescontaining the same drug Forms available from special-ordermanufacturers include: oral solution

TabletCAUTIONARY AND ADVISORY LABELS23

▶TROSPIUM CHLORIDE (Non-proprietary)Trospium chloride 20 mg Trospium chloride20mg tablets|

▶TROSPIUM CHLORIDE (Non-proprietary)Trospium chloride 60 mgTrospium chloride60mg modified-releasecapsules|28capsulePno price available|30capsulePnoprice available

▶Regurin XL(Speciality European Pharma Ltd)Trospium chloride 60 mg Regurin XL60mg capsules|

28capsuleP£23.05BETA3-ADRENOCEPTOR AGONISTS Mirabegron

INDICATIONS AND DOSEUrinary frequency, urgency, and urge incontinence

BY MOUTH

lCONTRA-INDICATIONSSevere hypertension

lCAUTIONSHistory of QT-interval prolongation

lINTERACTIONS→ Appendix1(mirabegron)

Caution with concomitant use with drugs that prolong the

QT interval

lHEPATIC IMPAIRMENTWith concomitant use of strongcytochrome P450inhibitors such as itraconazole,ketoconazole, ritonavir, or clarithromycin reduce dose to

25mg once daily in mild impairment, and avoid inmoderate impairment

lRENAL IMPAIRMENTWith concomitant use of strongcytochrome P450inhibitors such as itraconazole,ketoconazole, ritonavir, or clarithromycin reduce dose to

25mg once daily if eGFR less than

30–89mL/minute/1.73m2, and avoid if eGFR less than

30mL/minute/1.73m2

lSIDE-EFFECTS

▶Common or very commonTachycardia.urinary-tractinfection

▶UncommonAtrial fibrillation.dyspepsia.gastritis.

hypertension.joint swelling.palpitation.pruritus.rash.

vulvovaginal infection.vulvovaginal pruritus

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lCONCEPTION AND CONTRACEPTIONContraception advised

in women of child-bearing potential

lPREGNANCYAvoid—toxicity in animal studies

lBREAST FEEDINGAvoid—present in milk in animal

studies

lHEPATIC IMPAIRMENTReduce dose to25mg once daily in

moderate impairment Avoid in severe impairment—no

lRENAL IMPAIRMENTReduce dose to25mg once daily if

eGFR15–29mL/minute/1.73m2 Avoid if eGFR less than

15mL/ minute/1.73m2—no information available

NICE technology appraisals (TAs)

▶Mirabegron for treating symptoms of overactive bladder

(June2013) NICE TA290

Mirabegron is recommended as an option only for

patients in whom antimuscarinic drugs are ineffective,

contra-indicated, or not tolerated; patients currently

receiving mirabegron who do not meet these criteria

should have the option to continue until they and their

clinician consider it appropriate to stop.www.nice.org.uk/

TA290

lMEDICINAL FORMS

▶Betmiga(Astellas Pharma Ltd)A

Mirabegron 25 mg Betmiga25mg modified-release tablets|

Mirabegron 50 mg Betmiga50mg modified-release tablets|

1.2 Urinary retention

Drugs for urinary retention

Acute retention is painful and is treated by catheterisation

Chronic retention is painless and often long-standing

Catheterisation is unnecessary unless there is deterioration

of renal function After the cause has initially been

established and treated, drugs may be required to increase

detrusor muscle tone

Benign prostatic hyperplasia is treated either surgically or

medically with alpha-blockers Dutasteride p.676and

finasteride p.676are alternatives to alpha-blockers,

particularly in men with a significantly enlarged prostate

Tadalafil p.700, a phosphodiesterase type-5inhibitor, may

also be used in the management of benign prostatic

hyperplasia

Alpha-blockers

The alpha1-selective alpha blockers, alfuzosin hydrochloride

below, doxazosin p.673, indoramin p.673, prazosin p.674,

tamsulosin hydrochloride p.674and terazosin p.675relax

smooth muscle in benign prostatic hyperplasia producing

an increase in urinary flow-rate and an improvement in

obstructive symptoms

Parasympathomimetics

The parasympathomimetic bethanechol chloride p.676

increases detrusor muscle contraction However, it has only

a limited role in the relief of urinary retention; its use has

been superseded by catheterisation

ALPHA-ADRENOCEPTOR BLOCKERS Alfuzosin hydrochlorideINDICATIONS AND DOSEBenign prostatic hyperplasia

▶Adult:2.5mg3times a day; maximum10mg per day

▶Elderly:Initially2.5mg twice daily, adjusted according

to response; maximum10mg per day

▶Adult:10mg once dailyAcute urinary retention associated with benign prostatichyperplasia

▶Elderly:10mg once daily for2–3days duringcatheterisation and for one day after removal; max.4days

lCONTRA-INDICATIONSAvoid if history micturitionsyncope.avoid if history of postural hypotension

lCAUTIONSAcute heart failure.concomitantantihypertensives (reduced dosage and specialistsupervision may be required).discontinue if anginaworsens.elderly.history of QT-interval prolongation.

patients undergoing cataract surgery (risk of operative floppy iris syndrome)

intra-lINTERACTIONS→ Appendix1(alpha-blockers)

Caution with concomitant use with other drugs known toprolong QT interval

lSIDE-EFFECTS

▶UncommonChest pain.flushes

▶Frequency not knownAngioedema.asthenia.blurredvision.cholestasis.depression.dizziness.drowsiness.

dry mouth.erectile disorders (including priapism).

gastro-intestinal disturbances.headache.

hypersensitivity.hypotension (notably posturalhypotension).intra-operative floppy iris syndrome.liverdamage.oedema.palpitations.pruritus.rash.rhinitis.

syncope.tachycardiaSIDE-EFFECTS, FURTHER INFORMATIONFirst dose effectFirst dose may cause collapse due tohypotensive effect (therefore should be taken on retiring

to bed) Patient should be warned to lie down if symptomssuch as dizziness, fatigue or sweating develop, and toremain lying down until they abate completely

lHEPATIC IMPAIRMENTInitial dose2.5mg once daily,adjusted according to response to2.5mg twice daily inmild to moderate impairment—avoid if severe

Avoid modified-release preparations

lRENAL IMPAIRMENTInitial dose2.5mg twice daily andadjust according to response Manufacturers advise avoiduse of modified-release preparations if eGFR less than

30mL/minute/1.73m2as limited experience

lPATIENT AND CARER ADVICEMay affect performance ofskilled tasks e.g driving Patient should be counselled onthe first dose effect

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▶ALFUZOSIN HYDROCHLORIDE (Non-proprietary)

Alfuzosin hydrochloride 10 mg Alfuzosin10mg modified-release

tablets|30tabletPno price available DT price = £12.51

▶Xatral XL(Sanofi)

Alfuzosin hydrochloride 10 mg Xatral XL10mg tablets|

10tabletP£4.17|30tabletP£12.51DT price = £12.51

▶Brands may include Besavar X; Fuzatal XL; Vasran XL

Doxazosin

Hypertension

▶Adult:Initially1mg once daily for1–2weeks, then

increased to2mg once daily, then increased if

necessary to4mg once daily; maximum16mg per day

▶Adult:Initially4mg once daily, dose can be adjusted

after4weeks, then increased if necessary to8mg once

daily

Benign prostatic hyperplasia

▶Adult:Initially1mg daily, dose may be doubled at

intervals of1–2weeks according to response; usual

maintenance2–4mg daily; maximum8mg per day

▶Adult:Initially4mg once daily, dose can be adjusted

after4weeks, then increased if necessary to8mg once

daily

Dose adjustments due to interactions

Caution with concomitant antihypertensives in benign

prostatic hyperplasia—reduced dosage and specialist

supervision may be required

lCONTRA-INDICATIONS History of micturition syncope (in

patients with benign prostatic hypertrophy).history of

postural hypotension.monotherapy in patients with

overflow bladder or anuria

lCAUTIONSCare with initial dose (postural hypotension).

cataract surgery (risk of intra-operative floppy iris

syndrome).elderly.heart failure.pulmonary oedema due

to aortic or mitral stenosis

lINTERACTIONS→ Appendix1(alpha-blockers)

lSIDE-EFFECTS

▶Common or very commonAnxiety.back pain.coughing.

dyspnoea.fatigue.influenza-like symptoms.myalgia.

paraesthesia.sleep disturbance.vertigo

▶UncommonAgitation.angina.arthralgia.epistaxis.gout

.hypoaesthesia.micturition disturbance.myocardial

infarction.tinnitus.tremor.weight changes

▶Very rareAbnormal ejaculation.alopecia.arrhythmias.

bradycardia.bronchospasm.cholestasis.gynaecomastia.

hepatitis.hot flushes.jaundice.leucopenia.

thrombocytopenia

▶Frequency not knownAngioedema.asthenia.blurred

vision.depression.dizziness.drowsiness.dry mouth.

erectile disorders.gastro-intestinal disturbances.

headache.hypersensitivity.hypotension.intra-operative

floppy iris syndrome.oedema.palpitations.postural

hypotension.priapism.pruritus.rash.rhinitis.syncope.

tachycardia

lPREGNANCYNo evidence of teratogenicity; manufacturers

advise use only when potential benefit outweighs risk

lBREAST FEEDINGAccumulates in milk in animal studies—

manufacturer advises avoid

lHEPATIC IMPAIRMENTUse with caution Manufacturer

advises avoid in severe impairment—no information

available

lPATIENT AND CARER ADVICEMay affect performance ofskilled tasks e.g driving Patient counselling is advised fordoxazosin tablets (initial dose)

lMEDICINAL FORMSThere can be variation in the licensing of different medicinescontaining the same drug Forms available from special-ordermanufacturers include: oral suspension, oral solution, capsuleTablet

▶DOXAZOSIN (Non-proprietary)Doxazosin (as Doxazosin mesilate) 1 mg Doxazosin1mg tablets|

28tabletP£10.56DT price = £0.92Doxazosin (as Doxazosin mesilate) 2 mg Doxazosin2mg tablets|

28tabletP£14.08DT price = £0.95Doxazosin (as Doxazosin mesilate) 4 mg Doxazosin4mg tablets|

▶Cardura(Pfizer Ltd)Doxazosin (as Doxazosin mesilate) 1 mg Cardura1mg tablets|

28tabletP£10.56DT price = £0.92Doxazosin (as Doxazosin mesilate) 2 mg Cardura2mg tablets|

▶Brands may include DoxaduraModified-release tabletCAUTIONARY AND ADVISORY LABELS25

▶Cardura XL(Pfizer Ltd)Doxazosin (as Doxazosin mesilate) 4 mg Cardura XL4mgtablets|28tabletP£5.00DT price = £5.00Doxazosin (as Doxazosin mesilate) 8 mg Cardura XL8mgtablets|28tabletP£9.98DT price = £9.98

▶Brands may include Cardozin XL; Doxadura XL; Doxzogen XL; LarbexXL; Raporsin XL; Slocinx XL

IndoraminINDICATIONS AND DOSEHypertension

BY MOUTH

▶Adult:Initially25mg twice daily, increased in steps of

25–50mg every2weeks, maximum daily dose should

be given in divided doses; maximum200mg per dayBenign prostatic hyperplasia

BY MOUTH

▶Adult:20mg twice daily, increased in steps of20mgevery2weeks if required, increased if necessary up to

100mg daily in divided doses

▶Elderly:20mg daily, dose to be taken at nightDose adjustments due to interactions

Caution with concomitant antihypertensives in benignprostatic hyperplasia—reduced dosage and specialistsupervision may be required

lCONTRA-INDICATIONSEstablished heart failure.historymicturition syncope (when used for benign prostatichyperplasia).history of postural hypotension (when usedfor benign prostatic hyperplasia)

lCAUTIONSCataract surgery (risk of intra-operative floppyiris syndrome).control incipient heart failure beforeinitiating indoramin.elderly.epilepsy (convulsions inanimal studies).history of depression.Parkinson’sdisease (extrapyramidal disorders reported)

Avoid alcohol (enhances rate and extent of absorption)

lSIDE-EFFECTS

▶Common or very commonSedation

▶UncommonFailure of ejaculation.fatigue.weight gain

▶Frequency not knownAngioedema.asthenia.blurredvision.depression.dizziness.drowsiness.dry mouth.

erectile disorders.extrapyramidal disorders.intestinal disturbances.headache.hypersensitivityreactions.hypotension.incontinence.intra-operativefloppy iris syndrome.oedema.palpitations.posturalhypotension.priapism.pruritus.rash.rhinitis.syncope.

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lPREGNANCYNo evidence of teratogenicity; manufacturers

advise use only when potential benefit outweighs risk

lBREAST FEEDINGNo information available

lHEPATIC IMPAIRMENTManufacturer advises caution

lRENAL IMPAIRMENTManufacturer advises caution

lPATIENT AND CARER ADVICEDrowsiness may affect

performance of skilled tasks (e.g driving); effects of

alcohol may be enhanced

lMEDICINAL FORMS

Indoramin (as Indoramin hydrochloride) 25 mg Indoramin25mg

▶Doralese Tiltab(Chemidex Pharma Ltd)

Indoramin hydrochloride 20 mg Doralese Tiltab20mg tablets|

▶Adult:Initially500micrograms2–3times a day for3–7

days, the initial dose should be taken on retiring to

bed at night to avoid collapse, increased to1mg2–3

times a day for a further3–7days, then increased if

necessary up to20mg daily in divided doses

Congestive heart failure (rarely used)

BY MOUTH

▶Adult:500micrograms2–4times a day, initial dose to

be taken at bedtime, then increased to4mg daily in

divided doses; maintenance4–20mg daily in divided

doses

Raynaud’s syndrome (but efficacy not established)

BY MOUTH

▶Adult:Initially500micrograms twice daily, initial dose

to be taken at bedtime, dose may be increased after

3–7days, then increased if necessary to1–2mg twice

daily

BY MOUTH

▶Adult:Initially500micrograms twice daily for3–7

days, subsequent doses should be adjusted according

to response, maintenance2mg twice daily, initiate

with lowest possible dose in elderly patients

Caution with concomitant antihypertensives in benign

prostatic hyperplasia—reduced dosage and specialist

supervision may be required

lCONTRA-INDICATIONSHistory of micturition syncope.

history of postural hypotension.not recommended for

congestive heart failure due to mechanical obstruction

(e.g aortic stenosis)

lCAUTIONSCataract surgery (risk of intra-operative floppy

iris syndrome).elderly.first dose hypotension

lSIDE-EFFECTS

▶Common or very commonBlurred vision.depression.

dizziness.drowsiness.dry mouth.dyspnoea.

gastro-intestinal disturbances.headache.nasal congestion.

nervousness.oedema.palpitations.syncope.urinary

frequency.vertigo.weakness

▶UncommonArthralgia.epistaxis.eye disorders.insomnia

.paraesthesia.pruritus.rash.sweating.tachycardia.

tinnitus.urticaria

▶RareAlopecia.bradycardia.flushing.gynaecomastia.

hallucinations.pancreatitis.priapism.urinaryincontinence.vasculitis.worsening of narcolepsy

▶Frequency not knownAngioedema.asthenia.erectiledisorders.hypersensitivity reactions.hypotension.intra-operative floppy iris syndrome.postural hypotension.

rhinitisSIDE-EFFECTS, FURTHER INFORMATIONFirst dose effectFirst dose may cause collapse due tohypotensive effect (therefore should be taken on retiring

to bed) Patients should be warned to lie down ifsymptoms such as dizziness, fatigue or sweating develop,and to remain lying down until they abate completely

lPREGNANCYNo evidence of teratogenicity; manufacturersadvise use only when potential benefit outweighs risk

lBREAST FEEDINGPresent in milk, amount probably toosmall to be harmful; manufacturer advises use withcaution

lHEPATIC IMPAIRMENTInitially500micrograms daily;increased with caution

lRENAL IMPAIRMENTInitially500micrograms daily inmoderate to severe impairment; increased with caution

lPATIENT AND CARER ADVICEMay affect performance ofskilled tasks e.g driving

First dose effectFirst dose may cause collapse due tohypotensive effect (therefore should be taken on retiring tobed) Patients should be warned to lie down if symptomssuch as dizziness, fatigue or sweating develop, and toremain lying down until they abate completely

lMEDICINAL FORMSThere can be variation in the licensing of different medicinescontaining the same drug Forms available from special-ordermanufacturers include: oral solution, oral suspension, tabletTablet

▶Hypovase(Pfizer Ltd)Prazosin (as Prazosin hydrochloride) 500 microgram Hypovase

500microgram tablets|60tabletP£2.69DT price = £2.69Prazosin (as Prazosin hydrochloride) 1 mg Hypovase1mgtablets|60tabletP£3.46DT price = £3.46Tamsulosin hydrochlorideINDICATIONS AND DOSE

▶Adult:400micrograms once daily

lCONTRA-INDICATIONSHistory of micturition syncope.

history of postural hypotension

lCAUTIONSCataract surgery (risk of intra-operative floppyiris syndrome).concomitant antihypertensives (reduceddosage and specialist supervision may be required).

elderly

lSIDE-EFFECTSAngioedema.asthenia.blurred vision.

depression.dizziness.drowsiness.dry mouth.erectiledisorders.gastro-intestinal disturbances.headache.

hypersensitivity reactions.hypotension (notably posturalhypotension).intra-operative floppy iris syndrome.

oedema.palpitations.priapism.pruritus.rash.rhinitis.

syncope.tachycardia

lHEPATIC IMPAIRMENTAvoid in severe impairment

lRENAL IMPAIRMENTUse with caution if eGFR less than

10mL/minute/1.73m2

lPATIENT AND CARER ADVICEMay affect performance of

7

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lEXCEPTIONS TO LEGAL CATEGORYTamsulosin

hydrochloride400microgram capsules can be sold to the

public for the treatment of functional symptoms of

benign prostatic hyperplasia in men aged45–75years to

be taken for up to6weeks before clinical assessment by a

doctor

lMEDICINAL FORMS

manufacturers include: oral solution, powder

▶TAMSULOSIN HYDROCHLORIDE (Non-proprietary)

Tamsulosin hydrochloride 400 microgram Tamsulosin

400microgram modified-release tablets|30tabletP£10.47DT

price = £10.47

▶Flomaxtra XL(Astellas Pharma Ltd)

Tamsulosin hydrochloride 400 microgram Flomaxtra XL

400microgram tablets|30tabletP£10.47DT price = £10.47

▶Brands may include Cositam XL; Faramsil; Flectone XL

Modified-release capsule

▶TAMSULOSIN HYDROCHLORIDE (Non-proprietary)

Tamsulosin hydrochloride 400 microgramTamsulosin

400microgram modified-release capsules|30capsuleP£6.15DT

price = £4.52

▶Brands may include Contiflo XL; Diffundox XL; Flomax MR; Galebon;

Losinate MR; Pamsvax XL; Petyme MR; Pinexel PR; Prosurin XL;

Tabphyn MR; Tamfrex XL; Tamurex

Dutasteride with tamsulosin

The properties listed below are those particular to the

combination only For the properties of the components please

consider, dutasteride p.676, tamsulosin hydrochloride p.674

BY MOUTH

▶Adult (male):1capsule daily

lPATIENT AND CARER ADVICEMay affect performance of

skilled tasks e.g driving

lMEDICINAL FORMS

Capsule

▶Combodart(GlaxoSmithKline UK Ltd)

Dutasteride 500 microgram, Tamsulosin hydrochloride 400

microgram Combodart0.5mg/0.4mg capsules|30capsuleP

£19.80DT price = £19.80

Solifenacin with tamsulosin

consider, solifenacin succinate p.670, tamsulosin

hydrochloride p.674

Moderate to severe urinary frequency, urgency, and

obstructive symptoms associated with benign prostatic

hyperplasia when monotherapy ineffective

BY MOUTH

▶Adult (male):1tablet daily

Max.1Vesomni®tablet daily with concomitant potent

inhibitors of cytochrome P450enzyme CYP3A4(such as

itraconazole or ritonavir)

lHEPATIC IMPAIRMENTMax.1Vesomni®tablet daily in

lRENAL IMPAIRMENTMax.1Vesomni®tablet daily if eGFRless than30mL/minute/1.73m2

Modified-release tabletCAUTIONARY AND ADVISORY LABELS3, 25

▶Vesomni(Astellas Pharma Ltd)Solifenacin succinate 6 mg, Tamsulosin hydrochloride 400microgram Vesomni6mg/0.4mg modified-release tablets|

30tabletP£27.62TerazosinINDICATIONS AND DOSEMild to moderate hypertension

BY MOUTH

▶Adult:1mg daily for7days, then increased ifnecessary to2mg daily, dose should be taken atbedtime; maintenance2–10mg once daily, dosesabove20mg rarely improve efficacy

BY MOUTH

▶Adult:Initially1mg daily, dose should be taken atbedtime, if necessary dose may be doubled at intervals

of1–2weeks according to response; maintenance

5–10mg daily; maximum10mg per day

lCONTRA-INDICATIONSHistory of micturition syncope (inbenign prostatic hyperplasia).history of posturalhypotension (in benign prostatic hyperplasia)

lCAUTIONSCataract surgery (risk of intra-operative floppyiris syndrome).elderly.first dose

CAUTIONS, FURTHER INFORMATIONFirst doseFirst dose may cause collapse due tohypotension within30–90minutes, therefore should betaken on retiring to bed; may also occur with rapid doseincrease

lSIDE-EFFECTSAngioedema.asthenia.back pain.blurredvision.decreased libido.depression.dizziness.

drowsiness.dry mouth.dyspnoea.erectile disorders.

gastro-intestinal disturbances.headache.

hypersensitivity reactions.hypotension.intra-operativefloppy iris syndrome.nervousness.oedema.pain inextremities.palpitations.paraesthesia.posturalhypotension.priapism.pruritus.rash.rhinitis.syncope.

tachycardia.thrombocytopenia.weight gain

lPREGNANCYNo evidence of teratogenicity; manufacturersadvise use only when potential benefit outweighs risk

lBREAST FEEDINGNo information available

lPATIENT AND CARER ADVICEMay affect performance ofskilled tasks e.g driving Patient counselling is advised forterazosin tablets (initial dose)

First dose effectFirst dose may cause collapse due tohypotensive effect (therefore should be taken on retiring

to bed) Patient should be warned to lie down if symptomssuch as dizziness, fatigue or sweating develop, and toremain lying down until they abate completely

Tablet

▶TERAZOSIN (Non-proprietary)Terazosin (as Terazosin hydrochloride) 2 mg Terazosin2mgtablets|28tabletP£4.50DT price = £2.45

Terazosin (as Terazosin hydrochloride) 5 mg Terazosin5mgtablets|28tabletP£6.57DT price = £2.80

7

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Terazosin (as Terazosin hydrochloride) 10 mg Terazosin10mg

▶Hytrin(AMCo)

Terazosin (as Terazosin hydrochloride) 1 mg Hytrin1mg tablets|

7tabletPno price available

Terazosin (as Terazosin hydrochloride) 2 mg Hytrin2mg

tablets|14tabletPno price available|21tabletPno price

available|28tabletP£2.20DT price = £2.45

tablets|7tabletPno price available|28tabletP£4.13DT

price = £2.80

▶Hytrin(AMCo)

Hytrin BPH tablets starter pack|28tabletP£10.97

Hytrin tablets starter pack|28tabletP£13.00

▶Adult:10–25mg3–4times a day, to be taken30

minutes before food

lCONTRA-INDICATIONSBradycardia.cardiovascular

disorders.conditions where increased motility of the

gastro-intestinal tract could be harmful.conditions where

increased motility of the urinary tract could be harmful.

epilepsy.heart block.hyperthyroidism.hypotension.

intestinal obstruction.obstructive airways disease.

parkinsonism.peptic ulcer.recent myocardial infarction.

urinary obstruction

lCAUTIONSAutonomic neuropathy (use lower initial dose)

lINTERACTIONS→ Appendix1(parasympathomimetics)

lSIDE-EFFECTSAbdominal pain.bradycardia.

bronchoconstriction.diarrhoea.eructation.flushing.

headache.hypotension.increased lacrimation.increased

salivation.increased sweating.nausea.rhinorrhoea.

vomiting

lPREGNANCYManufacturer advises avoid—no information

available

lBREAST FEEDINGManufacturer advises avoid;

gastrointestinal disturbances in infant reported

lLESS SUITABLE FOR PRESCRIBINGLess suitable for

prescribing

lMEDICINAL FORMS

manufacturers include: oral solution, oral suspension

Tablet

▶Myotonine(Cheplapharm Arzneimittel GmbH)

Bethanechol chloride 10 mg Myotonine10mg tablets|

lDRUG ACTIONA specific inhibitor of the enzyme5

a-reductase, which metabolises testosterone into the more

potent androgen, dihydrotestosterone

INDICATIONS AND DOSEBenign prostatic hyperplasia

BY MOUTH

▶Adult:500micrograms daily, review treatment at

3–6months and then every6–12months (may requireseveral months treatment before benefit is obtained)

lINTERACTIONS→ Appendix1(dutasteride)

lSIDE-EFFECTSBreast enlargement.breast tenderness.

decreased libido.ejaculation disorders.impotence

lCONCEPTION AND CONTRACEPTIONDutasteride is excreted

in semen and use of a condom is recommended if sexualpartner is pregnant or likely to become pregnant

lHEPATIC IMPAIRMENTAvoid in severe impairment—noinformation available

lEFFECT ON LABORATORY TESTSMay decrease serumconcentration of prostate cancer markers such asprostate-specific antigen; reference values may needadjustment

lHANDLING AND STORAGEWomen of childbearingpotential should avoid handling leaking capsules ofdutasteride

lPATIENT AND CARER ADVICECases of male breast cancerhave been reported Patients or their carers should be told

to promptly report to their doctor any changes in breasttissue such as lumps, pain, or nipple discharge

CapsuleCAUTIONARY AND ADVISORY LABELS25

▶Avodart(GlaxoSmithKline UK Ltd)Dutasteride 500 microgram Avodart500microgram capsules|

30capsuleP£14.60DT price = £14.60Also available in combination withtamsulosin, p.675Finasteride

lDRUG ACTIONA specific inhibitor of the enzyme5reductase, which metabolises testosterone into the morepotent androgen, dihydrotestosterone

a-INDICATIONS AND DOSEBenign prostatic hyperplasia

BY MOUTH

▶Adult:5mg daily, review treatment at3–6months andthen every6–12months (may require several monthstreatment before benefit is obtained)

Androgenetic alopecia in men

BY MOUTH

▶Adult:1mg daily

lCAUTIONSObstructive uropathy

lSIDE-EFFECTSBreast enlargement.breast tenderness.

decreased libido.ejaculation disorders.face swelling.

hypersensitivity reactions.impotence.lip swelling.malebreast cancer.pruritus.rash.testicular pain

lCONCEPTION AND CONTRACEPTIONFinasteride is excreted

in semen and use of a condom is recommended if sexualpartner is pregnant or likely to become pregnant

lEFFECT ON LABORATORY TESTSDecreases serumconcentration of prostate cancer markers such asprostate-specific antigen; reference values may needadjustment

lHANDLING AND STORAGEWomen of childbearingpotential should avoid handling crushed or broken tablets

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lPATIENT AND CARER ADVICECases of male breast cancer

have been reported Patients or their carers should be told

to promptly report to their doctor any changes in breast

tissue such as lumps, pain, or nipple discharge

NHS restrictionsFinasteride is not prescribable under the

NHS for the treatment of androgenetic alopecia in men

lMEDICINAL FORMS

manufacturers include: oral suspension, powder

▶Propecia(Merck Sharp & Dohme Ltd)

Finasteride 1 mg Propecia1mg tablets|28tabletPno price

available|84tabletPno price available

▶Proscar(Merck Sharp & Dohme Ltd)

Finasteride 5 mg Proscar5mg tablets|28tabletP£13.94DT

price = £1.65

1.3 Urological pain

Urological pain

The acute pain of ureteric colic may be relieved with

pethidine hydrochloride p.372 Diclofenac by injection or

as suppositories is also effective and compares favourably

with pethidine hydrochloride; other non-steroidal

anti-inflammatory drugs are occasionally given by injection

Lidocaine hydrochloride gel p.1116is a useful topical

application in urethral pain or to relieve the discomfort of

catheterisation

Alkalinisation of urine

Alkalinisation of urine can be undertaken with potassium

citrate The alkalinising action may relieve the discomfort of

cystitis caused by lower urinary tract infections Sodium

bicarbonate p.848is used as a urinary alkalinising agent in

some metabolic and renal disorders

Drugs used for Urological pain not listed below;Sodium

bicarbonate, p.848

ALKALINISING DRUGS

Citric acid with potassium citrate

Relief of discomfort in mild urinary-tract infections|

Alkalinisation of urine

BY MOUTH USING ORAL SOLUTION

▶Adult:10mL3times a day, diluted well with water

lCAUTIONSCardiac disease.elderly

lINTERACTIONS→ Appendix1(potassium salts)

lSIDE-EFFECTSHyperkalaemia on prolonged high dosage.

mild diuresis

lRENAL IMPAIRMENTAvoid in severe impairment Close

monitoring required in renal impairment—high risk of

hyperkalaemia

lPRESCRIBING AND DISPENSING INFORMATIONWhen

prepared extemporaneously, the BP states Potassium

Citrate Mixture BP consists of potassium citrate30%,

citric acid monohydrate5% in a suitable vehicle with alemon flavour Extemporaneous preparations should berecently prepared according to the following formula:

potassium citrate3g, citric acid monohydrate500mg,syrup2.5mL, quillaia tincture0.1mL, lemon spirit

0.05mL, double-strength chloroform water3mL, water to

10mL Contains about28mmol K+/10mL Flavours oforal liquid formulations may include lemon

lEXCEPTIONS TO LEGAL CATEGORYProprietary brands ofpotassium citrate are on sale to the public for the relief ofdiscomfort in mild urinary-tract infections

Effervescent tablet

▶Effercitrate(Cambridge Healthcare Supplies Ltd)Citric acid 250 mg, Potassium citrate 1.5 gram Effercitrate tablets(sugar-free)|12tabletp£3.51

Oral solutionCAUTIONARY AND ADVISORY LABELS27

▶CITRIC ACID WITH POTASSIUM CITRATE (Non-proprietary)Citric acid monohydrate 50 mg per 1 ml, Potassium citrate

300 mg per 1 ml Potassium citrate mixture|200mlp£1.29DTprice = £1.29

Sodium citrateINDICATIONS AND DOSEBladder washouts

▶Adult:(consult product literature)Relief of discomfort in mild urinary-tract infections

▶Child 3–17 years: 5mL for1dose

▶Adult:5mL for1doseMICOLETTE®Constipation

BY RECTUM

▶Child 3–17 years: 5–10mL for1dose

▶Adult:5–10mL for1doseRELAXIT®

Constipation

BY RECTUM

▶Child 1 month–2 years:5mL for1dose, insert only halfthe nozzle length

▶Child 3–17 years: 5mL for1dose

▶Adult:5mL for1dose

lCONTRA-INDICATIONS

▶With rectal useAcute gastro-intestinal conditions

lCAUTIONS

▶With oral useCardiac disease.elderly.hypertension.

patients on a sodium-restricted diet

▶With rectal useDebilitated patients.sodium and waterretention in susceptible individuals

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lPRESCRIBING AND DISPENSING INFORMATIONSodium

citrate300mmol/litre (88.2mg/mL) oral solution is

licensed for use before general anaesthesia for caesarean

section (available from Viridian)

lEXCEPTIONS TO LEGAL CATEGORYProprietary brands of

sodium citrate are on sale to the public for the relief of

discomfort in mild urinary-tract infections

lMEDICINAL FORMS

manufacturers include: oral solution

Granules

▶SODIUM CITRATE (Non-proprietary)

Sodium citrate 4 gram Cystitis Relief4g oral granules sachets|

6sachetG£2.33

Lloydspharmacy Cystitis Relief4g oral granules sachets|

6sachetGno price available

▶Brands may include Canesten Oasis, Cymalon (sodium citrate),

Cystocalm

Oral solution

Sodium citrate 88.23 mg per 1 ml Sodium citrate0.3M oral

solution|30mlP£39.60

Sodium citrate441.17mg/5ml oral solution|30mlPno price

available

Enema

Sodium citrate 90 mg per 1 ml Sodium citrate compound5ml

enema|12enemapno price available

▶Micolette Micro-enema(Wockhardt UK Ltd)

Sodium citrate 90 mg per 1 ml Micolette Micro-enema5ml|

12enemap£4.95

▶Micralax Micro-enema(Focus Pharmaceuticals Ltd)

Sodium citrate 90 mg per 1 ml Micralax Micro-enema5ml|

12enemap£4.87

▶Relaxit(Supra Enterprises Ltd)

Sodium citrate 90 mg per 1 ml Relaxit Micro-enema5ml|

12enema £5.21

Irrigation solution

Sodium citrate3% irrigation solution1litre bags|1bag no price

available

Powder

Sodium citrate 4 gram Numark cystitis treatment4g oral powder

sachets|6sachetG£1.55

Sodium citrate 1 mg per 1 mg Sodium citrate powder|

500gramG£5.28DT price = £5.28

TERPENES

Anethol with borneol, camphene,

cineole, fenchone and pinene

Urolithiasis for the expulsion of calculi

BY MOUTH

▶Adult:1–2capsules3–4times a day, to be taken before

food

lLESS SUITABLE FOR PRESCRIBINGPreparation is less

suitable for prescribing

lMEDICINAL FORMS

Capsule

▶Rowatinex(Meadow Laboratories Ltd)

Anethol 4 mg, Borneol 10 mg, Camphene 15 mg, Cineole 3 mg,

Fenchone 4 mg, Pinene 31 mg Rowatinex capsules|

50capsuleP£7.35

urological surgery Bladder instillations and urological surgery

Bladder infectionVarious solutions are available as irrigations or washouts.Aqueous chlorhexidine p.1051can be used in themanagement of common infections of the bladder but it isineffective against most Pseudomonas spp Solutionscontaining chlorhexidine1in5000(0.02%) are used butthey may irritate the mucosa and cause burning andhaematuria (in which case they should be discontinued);sterile sodium chloride solution0.9% p.851(physiologicalsaline) is usually adequate and is preferred as a mechanicalirrigant

Continuous bladder irrigation with amphotericin

50micrograms/mL p.517may be of value in mycoticinfections in adults

Dissolution of blood clotsClot retention is usually treated by irrigation with sterilesodium chloride solution0.9% but sterile sodium citratesolution for bladder irrigation3% may also be helpful.Bladder cancer

Bladder instillations of doxorubicin hydrochloride p.754and mitomycin p.767are used for recurrent superficialbladder tumours Such instillations reduce systemic side-effects; adverse effects on the bladder (e.g micturitiondisorders and reduction in bladder capacity) may occur.Instillation of epirubicin hydrochloride p.756is used fortreatment and prophylaxis of certain forms of superficialbladder cancer; instillation of doxorubicin hydrochloride

p.754is also used for some papillary tumours

Instillation of BCG (bacillus calmette-guérin p.794), a liveattenuated strain derived from Mycobacterium bovis islicensed for the treatment of primary or recurrent bladdercarcinoma in-situ and for the prevention of recurrencefollowing transurethral resection

Urological surgeryGlycine irrigation solution1.5% p.679is the irrigant ofchoice for transurethral resection of the prostate gland andbladder tumours; sterile sodium chloride solution0.9%(physiological saline) is used for percutaneous renal surgery.Maintenance of indwelling urinary cathetersThe deposition which occurs in catheterised patients isusually chiefly composed of phosphate and to minimise thisthe catheter (if latex) should be changed at least as often asevery6weeks If the catheter is to be left for longer periods

a silicone catheter should be used together with theappropriate use of catheter maintenance solutions.Repeated blockage usually indicates that the catheter needs

to be changed

Chlorhexidine with lidocaine

The properties listed below are those particular to thecombination only For the properties of the components pleaseconsider, chlorhexidine p.1051, lidocaine hydrochloride p

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Urethral sounding and catheterisation

Gel

EXCIPIENTS:May contain Hydroxybenzoates (parabens)

▶Instillagel(CliniMed Ltd)

Chlorhexidine gluconate 500 microgram per 1 ml, Lidocaine

hydrochloride 20 mg per 1 ml Instillagel gel|60mlp£14.05DT

price = £14.05|110mlp£15.76DT price = £15.76

IRRIGATING SOLUTIONS

Glycine

Bladder irrigation during urological surgery| Irrigation for

transurethral resection of the prostate gland and bladder

tumours

▶Adult:(consult product literature)

lCAUTIONS

CAUTIONS, FURTHER INFORMATION

Urological surgeryThere is a high risk of fluid absorption

from the irrigant used in endoscopic surgery within the

urinary tract

lSIDE-EFFECTSHaemolysis.hypervolaemia.renal failure

lMEDICINAL FORMS

Irrigation solution

▶GLYCINE (Non-proprietary)

Glycine1.5% irrigation solution3litre Easyflow bags|1bag no price

available Glycine1.5% irrigation solution1litre Flowfusor bottles|

1bottle no price available Glycine1.5% irrigation solution1litre

Easyflow bags|1bag no price available Glycine1.5% irrigation

solution2litre Flowfusor bottles|1bottle no price available

UROLOGICAL ANTI-INFLAMMATORY DRUGS

Dimethyl sulfoxide

Symptomatic relief in interstitial cystitis (Hunner’s ulcer)

BY INTRAVESICAL INSTILLATION

▶Adult:50mL every2weeks retained for15minutes

then voided by the patient,50% solution is used and

instilled into the bladder

lINTERACTIONS→ Appendix1(dimethyl sulfoxide)

lSIDE-EFFECTSBladder spasm.hypersensitivity

lMONITORING REQUIREMENTSOphthalmic, renal and

hepatic assessments at intervals of6months are required

in long-term treatment

lMEDICINAL FORMS

Liquid

▶Rimso-50(Thornton & Ross Ltd)

Dimethyl sulfoxide 500 mg per 1 ml Rimso-50solution for

instillation|50mlPno price available

Catheter maintenance solutions

lCATHETER MAINTENANCE SOLUTIONS

▶OptiFlo R citric acid6% catheter maintenance solution (BardLtd)

50ml.NHS indicative price = £3.53.Drug Tariff (Part IXa)100ml.NHS indicative price = £3.53.Drug Tariff (Part IXa)

▶OptiFlo S saline0.9% catheter maintenance solution (Bard Ltd)

▶Uro-Tainer M sodium chloride0.9% catheter maintenancesolution (B.Braun Medical Ltd)

50ml.No NHS indicative price available.Drug Tariff (Part IXa)

100ml.No NHS indicative price available.Drug Tariff (Part IXa)

▶Uro-Tainer Twin Solutio R citric acid6% catheter maintenancesolution (B.Braun Medical Ltd)

60ml.NHS indicative price = £4.76.Drug Tariff (Part IXa)

▶Uro-Tainer sodium chloride0.9% catheter maintenance solution(B.Braun Medical Ltd)

Contraceptives, hormonal

The Fraser Guidelines (Department of Health Guidance (July

2004): Best practice guidance for doctors and other healthprofessionals on the provision of advice and treatment toyoung people under16on contraception, sexual andreproductive health, available atwww.tinyurl.com/bpg16)should be followed when prescribing contraception forwomen under16years The UK Medical Eligibility Criteriafor Contraceptive Use (available atwww.fsrh.org) ispublished by the Faculty of Sexual and ReproductiveHealthcare; it categorises the risks of using contraceptivemethods with pre-existing medical conditions

Hormonal contraception is the most effective method offertility control, but can have major and minor side-effects,especially for certain groups of women Hormonalcontraception should only be used by adolescents aftermenarche

Intra-uterine devices are a highly effective method ofcontraception but may produce undesirable local side-effects They may be used in women of all ages irrespective

of parity, but are less appropriate for those with anincreased risk of pelvic inflammatory disease

Barrier methods alone (condoms, diaphragms, and caps)are less effective but can be reliable for well-motivatedcouples if used in conjunction with a spermicide

Occasionally sensitivity reactions occur A female condom(Femidom®) is also available; it is pre-lubricated but doesnot contain a spermicide

Combined hormonal contraceptivesOral contraceptives containing an oestrogen and aprogestogen (‘combined oral contraceptives’) are effectivepreparations for general use Advantages of combined oralcontraceptives include:

reliable and reversible;

reduced dysmenorrhoea and menorrhagia;

reduced incidence of premenstrual tension;

less symptomatic fibroids and functional ovarian cysts; less benign breast disease;

reduced risk of ovarian and endometrial cancer;

reduced risk of pelvic inflammatory disease

Combined oral contraceptives containing a fixed amount

of an oestrogen and a progestogen in each active tablet aretermed‘monophasic’; those with varying amounts of thetwo hormones are termed‘phasic’ A transdermal patch and

a vaginal ring, both containing an oestrogen with a

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Combined Oral Contraceptives

Monophasic 21-day preparations

Oestrogen content Progestogen content Brand

Combined Oral Contraceptives

Monophasic 28-day preparations

Oestrogen content Progestogen content Brand

40micrograms

Gestodene

70microgramsEthinylestradiol

30micrograms

Gestodene

30micrograms

Levonorgestrel

50micrograms

Logynon®;TriRegol®

Ethinylestradiol

40micrograms

Levonorgestrel

30micrograms

Levonorgestrel

35micrograms

Norethisterone

500micrograms

BiNovum®Ethinylestradiol

35micrograms

Norethisterone

1mgEthinylestradiol

35micrograms

Norethisterone

500micrograms

Synphase®Ethinylestradiol

35micrograms

Norethisterone

1mgEthinylestradiol

35micrograms

Norethisterone

35micrograms

Norethisterone

500micrograms

TriNovum®Ethinylestradiol

35micrograms

Norethisterone

40micrograms

Levonorgestrel

30micrograms

Levonorgestrel

125microgramsEstradiol valerate

3mgEstradiol valerate

1mgChoiceThe majority of combined oral contraceptives containethinylestradiol p.655as the oestrogen component;mestranol and estradiol are also used The ethinylestradiolcontent of combined oral contraceptives ranges from

20to40micrograms Generally a preparation with thelowest oestrogen and progestogen content which gives goodcycle control and minimal side-effects in the individualwoman is chosen It is recommended that combinedhormonal contraceptives are not continued beyond50years

of age since more suitable alternatives exist

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Low strength preparations (containing ethinylestradiol

20micrograms) are particularly appropriate for women

with risk factors for circulatory disease, provided a

combined oral contraceptive is otherwise suitable

Standard strength preparations (containing

ethinylestradiol30or35micrograms or in

30–40microgram phased preparations) are appropriate

for standard use Phased preparations are generally

reserved for women who either do not have withdrawal

bleeding or who have breakthrough bleeding with

monophasic products

The progestogens desogestrel with ethinylestradiol p.685,

drospirenone with ethinylestradiol p.686, and

ethinylestradiol with gestodene p.687may be considered

for women who have side-effects (such as acne, headache,

depression, breast symptoms, and breakthrough bleeding)

with other progestogens Drospirenone, a derivative of

spironolactone, has androgenic and

anti-mineralocorticoid activity; it should be used with care if an

increased plasma-potassium concentration might be

hazardous

Dienogest with estradiol valerate p.685is in the

combined oral contraceptive Qlaira® Nomegestrol is the

progestogen contained in the combined oral contraceptive

Zoely®, in combination with estradiol

The progestogen norelgestromin is combined with

ethinylestradiol in a transdermal patch (Evra®) The vaginal

contraceptive ring contains the progestogen etonogestrel

combined with ethinylestradiol (NuvaRing®)

Surgery

Oestrogen-containing contraceptives should preferably be

discontinued (and adequate alternative contraceptive

arrangements made)4weeks before major elective surgery

and all surgery to the legs or surgery which involves

prolonged immobilisation of a lower limb; they should

normally be recommenced at the first menses occurring at

least2weeks after full mobilisation A progestogen-only

contraceptive may be offered as an alternative and the

oestrogen-containing contraceptive restarted after

mobilisation When discontinuation of an

oestrogen-containing contraceptive is not possible, e.g after trauma or

if a patient admitted for an elective procedure is still on an

oestrogen- containing contraceptive, thromboprophylaxis

(with unfractionated or low molecular weight heparin and

graduated compression hosiery) is advised These

recommendations do not apply to minor surgery with short

duration of anaesthesia, e.g laparoscopic sterilisation or

tooth extraction, or to women using oestrogen-free

hormonal contraceptives

Reason to stop immediately

Combined hormonal contraceptives or hormone

replacement therapy (HRT) should be stopped (pending

investigation and treatment), if any of the following occur:

sudden severe chest pain (even if not radiating to left

arm);

sudden breathlessness (or cough with blood-stained

sputum);

unexplained swelling or severe pain in calf of one leg;

severe stomach pain;

serious neurological effects including unusual severe,

prolonged headache especially if first time or getting

progressively worse or sudden partial or complete loss

of vision or sudden disturbance of hearing or other

perceptual disorders or dysphasia or bad fainting attack

or collapse or first unexplained epileptic seizure or

weakness, motor disturbances, very marked numbness

suddenly affecting one side or one part of body;

hepatitis, jaundice, liver enlargement;

blood pressure above systolic160mmHg or diastolic

95mmHg; (in adolescents stop if blood pressure very

high);

prolonged immobility after surgery or leg injury;

detection of a risk factor which contra-indicatestreatment

Progestogen-only contraceptivesOral progestogen-only contraceptivesOral progestogen-only preparations alter cervical mucus toprevent sperm penetration and may inhibit ovulation insome women; oral desogestrel-only preparationsconsistently inhibit ovulation and this is their primarymechanism of action There is insufficient clinical trialevidence to compare the efficacy of oral progestogen-onlycontraceptives with each other or with combined hormonalcontraceptives Progestogen-only contraceptives offer asuitable alternative to combined hormonal contraceptiveswhen oestrogens are contra-indicated (including those withvenous thrombosis or a past history or predisposition tovenous thrombosis, heavy smokers, those with hypertensionabove systolic160mmHg or diastolic95mmHg, valvularheart disease, diabetes mellitus with complications, andmigraine with aura)

Parenteral progestogen-only contraceptivesMedroxyprogesterone acetate (Depo-Provera®, SAYANAPRESS®) p.695is a long-acting progestogen given byinjection; it is at least as effective as the combined oralpreparations but because of its prolonged action it shouldnever be given without full counselling backed by the patientinformation leaflet It may be used as a short-term or long-term contraceptive for women who have been counselledabout the likelihood of menstrual disturbance and thepotential for a delay in return to full fertility Delayed return

of fertility and irregular cycles may occur afterdiscontinuation of treatment but there is no evidence ofpermanent infertility Troublesome bleeding has beenreported in patients given medroxyprogesterone acetate inthe immediate puerperium; delaying the first injection until

6weeks after birth may minimise bleeding problems If thewoman is not breast-feeding, the first injection may begiven within5days postpartum (she should be warned thatthe risk of troublesome bleeding may be increased)

In adolescents, medroxyprogesterone acetate Provera®, SAYANA PRESS®) should be used only whenother methods of contraception are inappropriate;

(Depo- in all women, the benefits of usingmedroxyprogesterone acetate beyond2years should beevaluated against the risks;

in women with risk factors for osteoporosis, a method

of contraception other than medroxyprogesteroneacetate should be considered

Norethisterone enantate (Noristerat®) is a long-actingprogestogen given as an oily injection which providescontraception for8weeks; it is used as short-term interimcontraception e.g before vasectomy becomes effective

An etonogestrel-releasing implant (Nexplanon®) is alsoavailable It is a highly effective long-acting contraceptive,consisting of a single flexible rod that is insertedsubdermally into the lower surface of the upper arm andprovides contraception for up to3years The manufactureradvises that in heavier women, blood-etonogestrelconcentrations are lower and therefore the implant may notprovide effective contraception during the third year; theyadvise that earlier replacement may be considered in suchpatients—however, evidence to support this

recommendation is lacking Local reactions such as bruisingand itching can occur at the insertion site The

contraceptive effect of etonogestrel is rapidly reversed onremoval of the implant

Intra-uterine progestogen-only deviceThe progestogen-only intra-uterine systems, Mirena®andJaydess®, releases levonorgestrel p.692directly into theuterine cavity Mirena®is licensed for use as acontraceptive, for the treatment of primary menorrhagia,and for the prevention of endometrial hyperplasia during

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oestrogen replacement therapy Jaydess®is licensed for

contraception These may therefore be a contraceptive

method of choice for women who have excessively heavy

menses

The effects of the progestogen-only intra-uterine system

are mainly local and hormonal including prevention of

endometrial proliferation, thickening of cervical mucus, and

suppression of ovulation in some women (in some cycles)

In addition to the progestogenic activity, the intra-uterine

system itself may contribute slightly to the contraceptive

effect Return of fertility after removal is rapid and appears

to be complete

Advantages of the progestogen-only intra-uterine system

over copper intra-uterine devices are that there may be an

improvement in any dysmenorrhoea and a reduction in

blood loss; there is also evidence that the frequency of

pelvic inflammatory disease may be reduced (particularly in

the youngest age groups who are most at risk)

In primary menorrhagia, menstrual bleeding is reduced

significantly within3–6months of inserting the

progestogen-only intra-uterine system, probably because it

prevents endometrial proliferation Another treatment

should be considered if menorrhagia does not improve

within this time

Surgery

All progestogen-only contraceptives (including those given

by injection) are suitable for use as an alternative to

combined hormonal contraceptives before major elective

surgery, before all surgery to the legs, or before surgery

which involves prolonged immobilisation of a lower limb

Emergency contraception

Hormonal methods

Hormonal emergency contraceptives include levonorgestrel

p.692and ulipristal acetate p.691; either drug should be

taken as soon as possible after unprotected intercourse to

increase efficacy

Levonorgestrel is effective if taken within72hours

(3days) of unprotected intercourse and may also be used

between72and96hours after unprotected intercourse

[unlicensed use], but efficacy decreases with time Ulipristal

acetate, a progesterone receptor modulator, is effective if

taken within120hours (5days) of unprotected intercourse

Levonorgestrel is less effective than insertion of an

intra-uterine device Ulipristal acetate is as effective as

levonorgestrel, but its efficacy compared to an intra-uterine

device is not yet known

Intra–uterine device

Insertion of an intra-uterine device is more effective than

oral levonorgestrel p.692for emergency contraception A

copper intra-uterine contraceptive device can be inserted up

to120hours (5days) after unprotected intercourse; sexually

transmitted infections should be tested for and insertion of

the device should usually be covered by antibacterial

prophylaxis (e.g azithromycin p.469) If intercourse has

occurred more than5days previously, the device can still be

inserted up to5days after the earliest likely calculated

ovulation (i.e within the minimum period before

implantation), regardless of the number of episodes of

unprotected intercourse earlier in the cycle

Contraceptives, interactions

Combined hormonal contraceptives interactions

The effectiveness of combined oral contraceptives,

progestogen-only oral contraceptives, contraceptive patches,

and vaginal rings can be considerably reduced by

interaction with drugs that induce hepatic enzyme activity

(e.g carbamazepine p.387, eslicarbazepine acetate p.390,

nevirapine p.560, oxcarbazepine p.397, phenytoin p.398,

phenobarbital p.409, primidone p.401, ritonavir p.570,

St John’s Wort, topiramate p.406and, above all, rifabutin

p.507and rifampicin p.508) A condom together with along-acting method, such as an injectable contraceptive,may be more suitable for patients with HIV infection or atrisk of HIV infection; advice on the possibility of interactionwith antiretroviral drugs should be sought from HIVspecialists

Women taking combined hormonal contraceptives whorequire enzyme-inducing drugs should be advised to change

to a contraceptive method that is unaffected by inducers (e.g some parenteral progestogen-onlycontraceptives, intra-uterine devices) for the duration oftreatment and for4weeks after stopping If a change incontraceptive method is undesirable or inappropriate thefollowing options should be discussed:

enzyme- For a short course (2months or less) of an inducing drug, continue with a combined oralcontraceptive providing ethinylestradiol30micrograms

enzyme-or menzyme-ore daily and use a‘tricycling’ regimen (i.e taking

3packets of monophasic tablets without a breakfollowed by a shortened tablet-free interval of4days[unlicensed use]) Additional contraceptive precautionsshould also be used whilst taking the enzyme-inducingdrug and for4weeks after stopping Another option(except for rifampicin or rifabutin) is to follow theadvice for long-term courses

For women using combined hormonal contraceptivepatches or vaginal rings, additional contraceptiveprecautions are also required whilst taking the enzyme-inducing drug and for4weeks after stopping Ifconcomitant administration runs beyond the3weeks ofpatch or vaginal ring use, a new treatment cycle should bestarted immediately, without a patch-free or ring-freebreak

For a long-term course (over2months) of an inducing drug (except rifampicin or rifabutin), adjust thedose of combined oral contraceptive to provideethinylestradiol50micrograms or more daily[unlicensed use] and use a‘tricycling’ regimen;continue for the duration of treatment with theenzyme-inducing drug and for4weeks after stopping

enzyme-If breakthrough bleeding occurs (and all other causes areruled out) it is recommended that the dose of

ethinylestradiol is increased by increments of

10micrograms up to a maximum of70micrograms daily[unlicensed use], or to use additional precautions, or tochange to a method unaffected by enzyme-inducing drugs.Contraceptive patches and vaginal rings are notrecommended for women taking enzyme-inducing drugsover a long period

For a long-term course (over2months) of rifampicin orrifabutin, an alternative method of contraception (such

as an IUD) is always recommended because they aresuch potent enzyme-inducing drugs; the alternativemethod of contraception should be continued for

4weeks after stopping the enzyme-inducing drug.Antibacterials that do not induce liver enzymesLatest recommendations are that no additionalcontraceptive precautions are required when combined oralcontraceptives are used with antibacterials that do notinduce liver enzymes, unless diarrhoea or vomiting occur.These recommendations should be discussed with thewoman, who should also be advised that guidance in patientinformation leaflets may differ

It is also currently recommended that no additionalcontraceptive precautions are required when contraceptivepatches or vaginal rings are used with antibacterials that donot induce liver enzymes There have been concerns thatsome antibacterials that do not induce liver enzymes (e.g.ampicillin p.483, doxycycline p.496) reduce the efficacy ofcombined oral contraceptives by impairing the bacterial flora

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responsible for recycling ethinylestradiol from the large

bowel However, there is a lack of evidence to support this

interaction

Oral progestogen-only contraceptives interactions

Effectiveness of oral progestogen-only preparations is not

affected by antibacterials that do not induce liver enzymes

The efficacy of oral progestogen-only preparations is,

however, reduced by enzyme-inducing drugs and an

alternative contraceptive method, unaffected by the

interacting drug, is recommended during treatment with an

enzyme-inducing drug and for at least4weeks afterwards

For a short course of an enzyme-inducing drug, if a change

in contraceptive method is undesirable or inappropriate, the

progestogen-only oral method may be continued in

combination with additional contraceptive precautions (e.g

barrier methods) for the duration of treatment with the

enzyme-inducing drug and for4weeks after stopping

Parenteral progestogen-only contraceptives

interactions

Effectiveness of parenteral progestogen-only contraceptives

is not affected by antibacterials that do not induce liver

enzymes The effectiveness of norethisterone intramuscular

injection p.656and medroxyprogesterone acetate

intramuscular and subcutaneous injections p.695is not

affected by enzyme-inducing drugs and they may be

continued as normal during courses of these drugs

However, effectiveness of the etonogestrel-releasing

implant p.695may be reduced by enzyme-inducing drugs

and an alternative contraceptive method, unaffected by the

interacting drug, is recommended during treatment with the

enzyme-inducing drug and for at least4weeks after

stopping For a short course of an enzyme-inducing drug, if

a change in contraceptive method is undesirable or

inappropriate, the implant may be continued in

combination with additional contraceptive precautions (e.g

condom) for the duration of treatment with the

enzyme-inducing drug and for4weeks after stopping it

Hormonal emergency contraception interactions

The effectiveness of levonorgestrel p.692, and possibly

ulipristal acetate p.691, is reduced in women taking

enzyme-inducing drugs (and possibly for4weeks after

stopping); a copper intra-uterine device can be offered

instead If the copper intra-uterine device is undesirable or

inappropriate, the dose of levonorgestrel should be

increased to a total of3mg taken as a single dose

[unlicensed dose—advise women accordingly] There is no

need to increase the dose for emergency contraception if

the patient is taking antibacterials that are not enzyme

inducers

Contraceptives, non-hormonal

Spermicidal contraceptives

Spermicidal contraceptives are useful additional safeguards

but do not give adequate protection if used alone unless

fertility is already significantly diminished They have two

components: a spermicide and a vehicle which itself may

have some inhibiting effect on sperm activity They are

suitable for use with barrier methods, such as diaphragms or

caps; however, spermicidal contraceptives are not generally

recommended for use with condoms, as there is no evidence

of any additional protection compared with non-spermicidal

lubricants

Spermicidal contraceptives are not suitable for use in

those with or at high risk of sexually transmitted infections

(including HIV); high frequency use of the spermicide

nonoxinol‘9’ p.697has been associated with genital

lesions, which may increase the risk of acquiring theseinfections

Products such as petroleum jelly (Vaseline®), baby oil andoil-based vaginal and rectal preparations are likely todamage condoms and contraceptive diaphragms made fromlatex rubber, and may render them less effective as a barriermethod of contraception and as a protection from sexuallytransmitted infections (including HIV)

Contraceptive devicesThe intra-uterine device (IUD) is a suitable contraceptive forwomen of all ages irrespective of parity; however, it is lessappropriate for those with an increased risk of pelvicinflammatory disease e.g women under25years

The most effective intra-uterine devices have at least

380mm2of copper and have banded copper on the arms.Smaller devices have been introduced to minimise side-effects; these consist of a plastic carrier wound with copperwire or fitted with copper bands; some also have a centralcore of silver to prevent fragmentation of the copper

Fertility declines with age and therefore a copper uterine device which is fitted in a woman over the age of40,may remain in the uterus until menopause

intra-A frameless, copper-bearing intra-uterine device (GyneFix®) is also available It consists of a knotted,polypropylene thread with6copper sleeves; the device isanchored in the uterus by inserting the knot into theuterine fundus

3.1 Contraception, combined

OESTROGENS

Combined hormonal

lCONTRA-INDICATIONSAcute porphyrias p.864.gallstones

.heart disease associated with pulmonary hypertension orrisk of embolus.history during pregnancy of cholestaticjaundice.history during pregnancy of chorea.historyduring pregnancy of pemphigoid gestationis.historyduring pregnancy of pruritus.history of breast cancer(but can be used after 5 years if no evidence of diseaseand non-hormonal methods unacceptable).history ofhaemolytic uraemic syndrome.migraine with aura.

personal history of venous or arterial thrombosis.

sclerosing treatment for varicose veins.severe or multiplerisk factors for arterial disease.severe or multiple riskfactors for venous thromboembolism.systemic lupuserythematosus with (or unknown) antiphospholipidantibodies.transient cerebral ischaemic attacks withoutheadaches.undiagnosed vaginal bleeding

lCAUTIONSActive trophoblastic disease (until return tonormal of urine- and plasma-gonadotrophinconcentration)—seek specialist advice.Crohn’s disease.

gene mutations associated with breast cancer (e.g BRCA 1).

history of severe depression especially if induced byhormonal contraceptive.hyperprolactinaemia (seekspecialist advice).inflammatory bowel disease.migraine.

personal or family history of hypertriglyceridaemia(increased risk of pancreatitis).risk factors for arterialdisease.risk factors for venous thromboembolism.sickle-cell disease.undiagnosed breast mass

CAUTIONS, FURTHER INFORMATIONRisk of venous thromboembolismThere is an increased risk

of venous thromboembolic disease in users of combinedhormonal contraceptives particularly during the first year

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contraceptives following a break of four weeks or more.

This risk is considerably smaller than that associated with

pregnancy (about60cases of venous thromboembolic

disease per100 000pregnancies) In all cases the risk of

venous thromboembolism increases with age and in the

presence of other risk factors, such as obesity The risk

also varies depending on the type of progestogen

Provided that women are informed of the relative risks of

venous thromboembolism and accept them, the choice of

oral contraceptive is for the woman together with the

prescriber jointly to make in light of her individual

medical history and any contra-indications

Combined hormonal contraceptives also slightly increase

the risk of arterial thromboembolism; however, there is no

evidence to suggest that this risk varies between different

preparations

Risk factors for venous thromboembolismUse with caution

if any of following factors present but avoid if two or

more factors present:

family history of venous thromboembolism in first-degree

relative aged under45years (avoid contraceptive

containing desogestrel or gestodene, or avoid if known

prothrombotic coagulation abnormality e.g factor V

Leiden or antiphospholipid antibodies (including lupus

anticoagulant));

obesity; body mass index 30kg/m2(avoid if body mass

index35kg/m2unless no suitable alternative); (in

adolescents, caution if obese according to BMI (adjusted

for age and gender); in those who are markedly obese,

avoid unless no suitable alternative);

long-term immobilisation e.g in a wheelchair (avoid if

confined to bed or leg in plaster cast);

history of superficial thrombophlebitis;

age over35years (avoid if over50years);

smoking

Combined Hormonal Contraception

and Risk of Venous Thromboembolism

Progestogen in Combined

Hormonal Contraceptive

Estimated incidence per10 000women per year of useNon-pregnant, not using

Dienogest2 Not known—insufficient data

Nomegestrol2 Not known—insufficient data

1Combined with ethinylestradiol2Combined with estradiol

Risk factors for arterial diseaseUse with caution if any

one of following factors present but avoid if two or more

factors present:

family history of arterial disease in first degree relative

aged under45years (avoid if atherogenic lipid profile);

diabetes mellitus (avoid if diabetes complications

present);

hypertension; blood pressure above systolic140mmHg or

diastolic90mmHg (avoid if blood pressure above systolic

160mmHg or diastolic95mmHg); (in adolescents, avoid

if blood pressure very high);

smoking (avoid if smoking40or more cigarettes daily);

age over35years (avoid if over50years);

obesity (avoid if body mass index 35kg/m2unless nosuitable alternative); (in adolescents, caution if obeseaccording to BMI (adjusted for age and gender); inthose who are markedly obese, avoid unless no suitablealternative);

migraine without aura (avoid if migraine with aura (focalsymptoms), or severe migraine frequently lasting over

72hours despite treatment, or migraine treated withergot derivatives)

MigraineWomen should report any increase in headachefrequency or onset of focal symptoms (discontinueimmediately and refer urgently to neurology expert iffocal neurological symptoms not typical of aura persist formore than1hour)

Combined hormonal contraceptives should be stopped(pending investigation and treatment), if seriousneurological effects occur, including unusual severe,prolonged headache especially if first time or gettingprogressively worse or sudden partial or complete loss ofvision or sudden disturbance of hearing or otherperceptual disorders or dysphasia or bad fainting attack orcollapse or first unexplained epileptic seizure orweakness, motor disturbances, very marked numbnesssuddenly affecting one side or one part of body

lINTERACTIONS→ Appendix1(oestrogens, progestogens)

lSIDE-EFFECTS

▶RareGallstones.systemic lupus erythematosus

▶Frequency not knownAbdominal cramps.absence ofwithdrawal bleeding.amenorrhoea after discontinuation.

breast enlargement.breast secretion.breast tenderness.

cervical erosion.changes in libido.changes in lipidmetabolism.changes in vaginal discharge.chloasma.

chorea.contact lenses may irritate.depression.fluidretention.headache.hepatic tumours.hypertension.

irritability.leg cramps.liver impairment.nausea.

nervousness.photosensitivity.reduced menstrual loss.

skin reactions.thrombosis (more common when factor VLeiden present or in blood groups A, B, and AB).visualdisturbances.vomiting.‘spotting’ in early cyclesSIDE-EFFECTS, FURTHER INFORMATIONBreast cancerThere is a small increase in the risk ofhaving breast cancer diagnosed in women taking thecombined oral contraceptive pill; this relative risk may bedue to an earlier diagnosis In users of combined oralcontraceptive pills the cancers are more likely to belocalised to the breast The most important factor fordiagnosing breast cancer appears to be the age at whichthe contraceptive is stopped rather than the duration ofuse; any increase in the rate of diagnosis diminishesgradually during the10years after stopping anddisappears by10years

Cervical cancerUse of combined oral contraceptives for

5years or longer is associated with a small increased risk

of cervical cancer; the risk diminishes after stopping anddisappears by about10years The possible small increase

in the risk of breast cancer and cervical cancer should beweighed against the protective effect against cancers ofthe ovary and endometrium

lPREGNANCYNot known to be harmful

lBREAST FEEDINGAvoid until weaning or for6monthsafter birth (adverse effects on lactation)

lHEPATIC IMPAIRMENTAvoid in active liver diseaseincluding disorders of hepatic excretion (e.g Dubin-Johnson or Rotor syndromes), infective hepatitis (untilliver function returns to normal), liver tumours

▶With oral useEach tablet should be taken at approximatelysame time each day; if delayed, contraceptive protectionmay be lost.21-day combined preparations,1tablet dailyfor21days; subsequent courses repeated after a7-day

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interval (during which withdrawal bleeding occurs); if

reasonably certain woman is not pregnant, first course

can be started on any day of cycle—if starting on day6of

cycle or later, additional precautions (barrier methods)

necessary during first7days Every day (ED) combined

preparations,1active tablet daily for21days, followed by

1inactive tablet daily for7days; subsequent courses

repeated without interval (withdrawal bleeding occurs

when inactive tablets being taken); if reasonably certain

woman is not pregnant, first course can be started on any

day of cycle—if starting on day6of cycle or later,

additional precautions (barrier methods) necessary during

first7days

Changing to combined preparation containing different

progestogenIf previous contraceptive used correctly, or

pregnancy can reasonably be excluded, start the first active

tablet of new brand immediately See individual monographs

for requirements of specific preparations

Changing from progestogen-only tabletIf previous

contraceptive used correctly, or pregnancy can reasonably be

excluded, start new brand immediately, additional

precautions (barrier methods) necessary for first7days

Secondary amenorrhoea (exclude pregnancy)Start any day,

additional precautions (barrier methods) necessary during

first7days (9days for Qlaira®)

After childbirth (not breast-feeding)Start3weeks after birth

(increased risk of thrombosis if started earlier); later than3

weeks postpartum additional precautions (barrier methods)

necessary for first7days (9days for Qlaira®)

After abortion or miscarriageStart same day

lPATIENT AND CARER ADVICE

Missed pillThe critical time for loss of contraceptive

protection is when a pill is omitted at the beginning or end

of a cycle (which lengthens the pill-free interval)

If a woman forgets to take a pill, it should be taken as

soon as she remembers, and the next one taken at the

normal time (even if this means taking2pills together) A

missed pill is one that is24or more hours late If a

woman misses only one pill, she should take an active pill

as soon as she remembers and then resume normal

pill-taking No additional precautions are necessary

If a woman misses2or more pills (especially from the first

7in a packet), she may not be protected She should take

an active pill as soon as she remembers and then resume

normal pill-taking In addition, she must either abstain

from sex or use an additional method of contraception

such as a condom for the next7days If these7days run

beyond the end of the packet, the next packet should be

started at once, omitting the pill-free interval (or, in the

case of everyday (ED) pills, omitting the7inactive tablets)

Emergency contraception is recommended if2or more

combined oral contraceptive tablets are missed from the

first7tablets in a packet and unprotected intercourse has

occurred since finishing the last packet

TravelWomen taking oral contraceptives are at an increased

risk of deep vein thrombosis during travel involving long

periods of immobility (over3hours) The risk may be

reduced by appropriate exercise during the journey and

possibly by wearing graduated compression hosiery

Diarrhoea and vomitingVomiting and persistent, severe

diarrhoea can interfere with the absorption of combined oral

contraceptives If vomiting occurs within2hours of taking a

combined oral contraceptive another pill should be taken as

soon as possible In cases of persistent vomiting or severe

diarrhoea lasting more than24hours, additional precautions

should be used during and for7days after recovery If the

vomiting and diarrhoea occurs during the last7tablets, the

next pill-free interval should be omitted (in the case of ED

tablets the inactive ones should be omitted)

Dienogest with estradiol valerate FINDICATIONS AND DOSE

Contraception with28-day combined preparations|Menstrual symptoms with28-day combined preparations

BY MOUTH

▶Females of childbearing potential:1active tablet oncedaily for26days, followed by1inactive tablet daily for

2days, withdrawal bleeding may occur during the

2-day interval of inactive tablets, tablets should betaken at approximately the same time each day

lDIRECTIONS FOR ADMINISTRATIONCombined hormonal contraceptivesEach tablet should betaken at approximately same time each day; if delayed,contraceptive protection may be lost

Qlaira®,1active tablet daily for26days, followed by1inactive tablet daily for2days starting on day1of cyclewith first active tablet; subsequent courses repeatedwithout interval (withdrawal bleeding occurs wheninactive tablets being taken)

Changing to combined preparation containing differentprogestogenIf previous contraceptive used correctly, orpregnancy can reasonably be excluded, start the first activetablet of new brand immediately

Changing to Qlaira®: start the first active Qlaira®tablet

on the day after taking the last active tablet of theprevious brand

Changing from progestogen-only tabletChanging to Qlaira®:start any day, additional precautions (barrier methods)necessary for first9days

Secondary amenorrhoea (exclude pregnancy)Start any day,additional precautions (barrier methods) necessary duringfirst9days for Qlaira®

After childbirth (not breast-feeding)Start3weeks after birth(increased risk of thrombosis if started earlier); later than

3weeks postpartum additional precautions (barriermethods) necessary for first9days for Qlaira®.After abortion or miscarriageStart same day

lPATIENT AND CARER ADVICEMissed doseA missed pill for a patient taking Qlaira®isone that is12hours or more late; for information on how

to manage missed pills in women taking Qlaira®, refer toproduct literature

Diarrhoea and vomitingIn cases of persistent vomiting orsevere diarrhoea lasting more than12hours in womentaking Qlaira®, refer to product literature

Tablet

▶Qlaira(Bayer Plc)Qlaira tablets| 84tabletP £25.18Desogestrel with ethinylestradiol FThe properties listed below are those particular to thecombination only For the properties of the components pleaseconsider, ethinylestradiol p.655, desogestrel p.691.INDICATIONS AND DOSE

Contraception with21-day combined preparations|

Menstrual symptoms with21-day combined preparations

BY MOUTH

▶Females of childbearing potential:1tablet once daily for

21days; subsequent courses repeated after7-dayinterval, withdrawal bleeding occurs during the7-dayinterval, if reasonably certain woman is not pregnant,first course can be started on any day of cycle—ifstarting on day6of cycle or later, additional continued→

7

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precautions (barrier methods) necessary during first

7days, tablets should be taken at approximately the

same time each day

lMEDICINAL FORMS

Tablet

▶Gedarel(Consilient Health Ltd)

Desogestrel 150 microgram, Ethinylestradiol 20

microgram Gedarel20microgram/150microgram tablets|

63tabletP£5.08

microgram Gedarel30microgram/150microgram tablets|

63tabletP£4.19

▶Marvelon(Merck Sharp & Dohme Ltd)

microgram Marvelon tablets|63tabletP£7.10

▶Mercilon(Merck Sharp & Dohme Ltd)

microgram Mercilon150microgram/20microgram tablets|

63tabletP£8.44

▶Brands may include Alenini; Cimizt; Lestramyl; Munalea

Drospirenone with ethinylestradiol F

consider, ethinylestradiol p.655

BY MOUTH

21days; subsequent courses repeated after7-day

interval

lMEDICINAL FORMS

Tablet

▶Yasmin(Bayer Plc)

Drospirenone 3 mg, Ethinylestradiol 30 microgram Yasmin

tablets|63tabletP£14.70

▶Brands may include Acondro; Cleosensa; Dretine; Lucette

Estradiol with nomegestrol F

consider, estradiol p.649

Contraception

BY MOUTH

▶Females of childbearing potential:1active tablet daily for

24days, followed by1inactive tablet daily for4days,

to be started on day1of cycle with first active tablet

(withdrawal bleeding occurs when inactive tablets

being taken); subsequent courses repeated without

interval

lDIRECTIONS FOR ADMINISTRATIONZoely®(every day (ED)

combined (monophasic) preparation),1active tablet daily

for24days, followed by1inactive tablet daily for4days,

starting on day1of cycle with first active tablet;

subsequent courses repeated without interval (withdrawal

bleeding occurs when inactive tablets being taken)

Changing to combined preparation containing different

progestogenIf previous contraceptive used correctly, or

pregnancy can reasonably be excluded, start the first active

Changing to Zoely®: start the first active Zoely®tablet

on the day after taking the last active tablet of theprevious brand or, at the latest, the day after the tablet-free or inactive tablet interval of the previous brand

lPATIENT AND CARER ADVICEMissed doseA missed pill for a patient taking Zoely®isone that is12hours or more late; for information on how

to manage missed pills in women taking Zoely®, refer toproduct literature

Diarrhoea and vomitingIn cases of persistent vomiting orsevere diarrhoea lasting more than12hours in womentaking Zoely®, refer to product literature

Tablet

▶Zoely(Merck Sharp & Dohme Ltd)A

Estradiol (as Estradiol hemihydrate) 1.5 mg, Nomegestrol2.5 mg Zoely2.5mg/1.5mg tablets|84tabletP£19.80DT price

= £19.80Ethinylestradiol with etonogestrel FThe properties listed below are those particular to thecombination only For the properties of the components pleaseconsider, ethinylestradiol p.655, etonogestrel p.695.INDICATIONS AND DOSE

Contraception| Menstrual symptoms

BY VAGINA

▶Females of childbearing potential:1unit, insert the ringinto the vagina on day1of cycle and leave in for3weeks; remove ring on day22; subsequent coursesrepeated after7-day ring free interval (during whichwithdrawal bleeding occurs)

lDIRECTIONS FOR ADMINISTRATIONChanging method of contraception to vaginal ringInsert ring atthe latest on the day after the usual tablet-free, patch-free,

or inactive-tablet interval If previous contraceptive usedcorrectly, or pregnancy can reasonably be excluded, canswitch to ring on any day of cycle

Changing from progestogen-only methodFrom an implant orintra-uterine progestogen-only device, insert ring on the dayimplant or intra-uterine progestogen-only device removed;from an injection, insert ring when next injection due; fromoral preparation, first ring may be inserted on any day afterstopping pill For all methods additional precautions (barriermethods) should be used concurrently for first7days.After first trimester abortionStart immediately

After childbirth (not breast-feeding) or second trimesterabortionStart4weeks after birth or abortion; if started laterthan4weeks after birth or abortion, additional precautions(barrier methods) should be used for first7days

lPATIENT AND CARER ADVICEExpulsion, delayed insertion or removal, or broken vaginalringIf the vaginal ring is expelled for less than3hours,rinse the ring with cool water and reinsert immediately;

no additional contraception is needed

If the ring remains outside the vagina for more than

3hours or if the user does not know when the ring wasexpelled, contraceptive protection may be reduced: If ring expelled during week1or2of cycle, rinse ringwith cool water and reinsert; use additional precautions(barrier methods) for next7days;

If ring expelled during week3of cycle, either insert anew ring to start a new cycle or allow a withdrawalbleed and insert a new ring no later than7days afterring was expelled; latter option only available if ringwas used continuously for at least7days beforeexpulsion

7

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If insertion of a new ring at the start of a new cycle is

delayed, contraceptive protection is lost A new ring

should be inserted as soon as possible; additional

precautions (barrier methods) should be used for the first

7days of the new cycle If intercourse occurred during the

extended ring-free interval, pregnancy should be

considered No additional contraception is required if

removal of the ring is delayed by up to1week (4weeks of

continuous use) The7-day ring-free interval should be

observed and subsequently a new ring should be inserted

Contraceptive protection may be reduced with continuous

use of the ring for more than4weeks—pregnancy should

be ruled out before inserting a new ring If the ring breaks

during use, remove it and insert a new ring immediately;

additional precautions (barrier methods) should be used

for the first7days of the new cycle

Patients or carers should be given advice on how to

administer vaginal ring

CounsellingThe presence of the ring should be checked

regularly

TravelWomen using the vaginal ring are at an increased risk

of deep vein thrombosis during travel involving long periods

of immobility (over3hours) The risk may be reduced by

appropriate exercise during the journey and possibly by

wearing graduated compression hosiery

lMEDICINAL FORMS

Vaginal delivery system

▶NuvaRing(Merck Sharp & Dohme Ltd)

Ethinylestradiol 2.7 mg, Etonogestrel 11.7 mg NuvaRing

0.12mg/0.015mg per day vaginal delivery system|3systemP

£29.70

Ethinylestradiol with gestodene F

BY MOUTH

interval, withdrawal bleeding occurs during the7-day

interval, if reasonably certain woman is not pregnant,

first course can be started on any day of cycle—if

starting on day6of cycle or later, additional

same time each day

BY MOUTH

▶Females of childbearing potential:1active tablet once

daily for21days, followed by1inactive tablet daily for

7days; subsequent courses repeated without interval,

withdrawal bleeding occurs during the7-day interval

of inactive tablets being taken, if reasonably certain

woman is not pregnant, first course can be started on

any day of cycle—if starting on day6of cycle or later,

additional precautions (barrier methods) necessary

during first7days, tablets should be taken at

approximately the same time each day

lMEDICINAL FORMS

Tablet

▶Femodene(Bayer Plc)Ethinylestradiol 30 microgram, Gestodene 75microgram Femodene tablets|63tabletP£6.73

▶Femodette(Bayer Plc)Ethinylestradiol 20 microgram, Gestodene 75microgram Femodette tablets|63tabletP£8.85

▶Katya(Stragen UK Ltd)Ethinylestradiol 30 microgram, Gestodene 75 microgram Katya

30/75tablets|63tabletP£5.03

▶Millinette(Consilient Health Ltd)Ethinylestradiol 30 microgram, Gestodene 75microgram Millinette30microgram/75microgram tablets|

63tabletP£4.12Ethinylestradiol 20 microgram, Gestodene 75microgram Millinette20microgram/75microgram tablets|

63tabletP£5.41

▶Sunya(Stragen UK Ltd)Ethinylestradiol 20 microgram, Gestodene 75 microgram Sunya

20/75tablets|63tabletP£6.62

▶Brands may include Aidulan

Ethinylestradiol with levonorgestrel FThe properties listed below are those particular to thecombination only For the properties of the components pleaseconsider, ethinylestradiol p.655, levonorgestrel p.692.INDICATIONS AND DOSE

BY MOUTH

21days; subsequent courses repeated after7-dayinterval, withdrawal bleeding occurs during the7-dayinterval, if reasonably certain woman is not pregnant,first course can be started on any day of cycle—ifstarting on day6of cycle or later, additionalprecautions (barrier methods) necessary during first

7days, tablets should be taken at approximately thesame time each day

Contraception with28-day combined preparations|Menstrual symptoms with28-day combined preparations

BY MOUTH

▶Females of childbearing potential:1active tablet oncedaily for21days, followed by1inactive tablet oncedaily for7days, withdrawal bleeding occurs during the

7-day interval of inactive tablets being taken, ifreasonably certain woman is not pregnant, first coursecan be started on any day of cycle—if starting on day

6of cycle or later, additional precautions (barriermethods) necessary during first7days, tablets should

be taken at approximately the same time each day

Subsequent courses repeated without interval

Tablet

▶Levest(Morningside Healthcare Ltd)Ethinylestradiol 30 microgram, Levonorgestrel 150microgram Levest150/30tablets|21tabletP£0.85(Hospitalonly)|63tabletP£1.80DT price = £2.82

▶Microgynon30(Bayer Plc)Ethinylestradiol 30 microgram, Levonorgestrel 150microgramMicrogynon30tablets|63tabletP£2.82DT price =

£2.82

▶Ovranette(Pfizer Ltd)Ethinylestradiol 30 microgram, Levonorgestrel 150microgram Ovranette150microgram/30microgram tablets|

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▶Rigevidon(Consilient Health Ltd)

Ethinylestradiol 30 microgram, Levonorgestrel 150

microgram Rigevidon tablets|63tabletP£1.89DT price =

£2.82

▶Brands may include Elevin; Erlibelle; Maexeni

Ethinylestradiol with norethisterone F

consider, ethinylestradiol p.655, norethisterone p.656

BY MOUTH

same time each day

lMEDICINAL FORMS

Tablet

▶Brevinor(Pfizer Ltd)

Ethinylestradiol 35 microgram, Norethisterone 500

microgram Brevinor500microgram/35microgram tablets|

63tabletP£1.99

▶Loestrin20(Galen Ltd)

Ethinylestradiol 20 microgram, Norethisterone acetate

1 mg Loestrin20tablets|63tabletP£2.30

▶Loestrin30(Galen Ltd)

Ethinylestradiol 30 microgram, Norethisterone acetate

1.5 mg Loestrin30tablets|63tabletP£3.32

▶Norimin(Pfizer Ltd)

Ethinylestradiol 35 microgram, Norethisterone 1 mg Norimin

1mg/35microgram tablets|63tabletP£2.28DT price = £2.28

▶Ovysmen(Janssen-Cilag Ltd)

Ethinylestradiol 35 microgram, Norethisterone 500

microgram Ovysmen500microgram/35microgram tablets|

63tabletP£1.89

Ethinylestradiol with norgestimate F

BY MOUTH

same time each day

lMEDICINAL FORMS

Tablet

▶Cilest(Janssen-Cilag Ltd)Ethinylestradiol 35 microgram, Norgestimate 250microgram Cilest250microgram/35microgram tablets|

63tabletP£7.16

▶Brands may include Lizinna

Ethinylestradiol with norelgestromin FThe properties listed below are those particular to thecombination only For the properties of the components pleaseconsider, ethinylestradiol p.655

INDICATIONS AND DOSEContraception| Menstrual symptoms

BY TRANSDERMAL APPLICATION

▶Females of childbearing potential:Apply1patch onceweekly for3weeks, apply first patch on day1of cycle,change patch on days8and15; remove third patch onday22and apply new patch after7-day patch-freeinterval to start subsequent contraceptive cycle,subsequent courses repeated after a7-day patch freeinterval (during which withdrawal bleeding occurs)

lDIRECTIONS FOR ADMINISTRATIONAdhesives or bandagesshould not be used to hold patch in place If no longersticky do not reapply but use a new patch

Changing to a transdermal combined hormonal contraceptiveChanging from combined oral contraception Applypatch on the first day of withdrawal bleeding; if nowithdrawal bleeding within5days of taking last activetablet, rule out pregnancy before applying first patch.Unless patch is applied on first day of withdrawalbleeding, additional precautions (barrier methods) should

be used concurrently for first7days

Changing from progestogen-only method from an implant, apply first patch on the day implantremoved

from an injection, apply first patch when next injectiondue

from oral progestogen, first patch may be applied onany day after stopping pill

For all methods additional precautions (barrier methods)should be used concurrently for first7days

After childbirth (not breast-feeding) Start4weeks afterbirth; if started later than4weeks after birth additionalprecautions (barrier methods) should be used for first

7days

After abortion or miscarriage Before20weeks’gestation start immediately; no additional contraceptionrequired if started immediately After20weeks’ gestationstart on day21after abortion or on the first day of firstspontaneous menstruation; additional precautions(barrier methods) should be used for first7days afterapplying the patch

lPATIENT AND CARER ADVICEDelayed application or detached patchIf a patch is partlydetached for less than24hours, reapply to the same site

or replace with a new patch immediately; no additionalcontraception is needed and the next patch should beapplied on the usual‘change day’ If a patch remainsdetached for more than24hours or if the user is notaware when the patch became detached, then stop thecurrent contraceptive cycle and start a new cycle byapplying a new patch, giving a new‘Day1’; an additionalnon-hormonal contraceptive must be used concurrentlyfor the first7days of the new cycle

If application of a new patch at the start of a new cycle isdelayed, contraceptive protection is lost A new patchshould be applied as soon as remembered giving a new

‘Day1’; additional non-hormonal methods ofcontraception should be used for the first7days of the

7

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new cycle If application of a patch in the middle of the

cycle is delayed (i.e the patch is not changed on day8or

day15):

for up to48hours, apply a new patch immediately; next

patch‘change day’ remains the same and no additional

contraception is required;

for more than48hours, contraceptive protection may

have been lost Stop the current cycle and start a new

4-week cycle immediately by applying a new patch

giving a new‘Day1’; additional non-hormonal

contraception should be used for the first7days of the

new cycle

If the patch is not removed at the end of the cycle (day

22), remove it as soon as possible and start the next cycle

on the usual‘change day’, the day after day28; no

additional contraception is required

Patients and carers should be given advice on how to

administer patches

TravelWomen using patches are at an increased risk of deep

vein thrombosis during travel involving long periods of

immobility (over3hours) The risk may be reduced by

appropriate exercise during the journey and possibly by

wearing graduated compression hosiery

Scottish Medicines Consortium (SMC) Decisions

The Scottish Medicines Consortium has advised (September

2003) that Evra®patches should be restricted for use in

women who are likely to comply poorly with combined

oral contraceptives

lMEDICINAL FORMS

Transdermal patch

▶Evra(Janssen-Cilag Ltd)

Ethinylestradiol 33.9 microgram per 24 hour, Norelgestromin

203 microgram per 24 hour Evra transdermal patches|

9patchP£19.51DT price = £19.51

Mestranol with norethisterone F

consider, norethisterone p.656

Contraception| Menstrual symptoms

BY MOUTH

interval, withdrawal bleeding can occur during the

7-day interval, if reasonably certain woman is not

pregnant, first course can be started on any day of

cycle—if starting on day6of cycle or later, additional

7days, tablets should be taken at the same time each

day

lMEDICINAL FORMS

Tablet

▶Norinyl-1(Pfizer Ltd)

Mestranol 50 microgram, Norethisterone 1 mg Norinyl-1

3.2 Contraception, devices

Drugs used for Contraception, devices not listed below;

Levonorgestrel, p.692

CONTRACEPTIVE DEVICES Intra-uterine contraceptive devices (copper)

INDICATIONS AND DOSEContraception

medical diathermy.pelvic inflammatory disease.recentsexually transmitted infection (if not fully investigatedand treated).severe anaemia.small uterine cavity.

unexplained uterine bleeding.Wilson’s disease

lCAUTIONSAnaemia.anticoagulant therapy (avoid ifpossible).diabetes.disease-induced immunosuppression(risk of infection—avoid if marked immunosuppression).

drug-induced immunosuppression (risk of infection—avoid if marked immunosuppression).endometriosis.

epilepsy (risk of seizure at time of insertion).fertilityproblems.history of pelvic inflammatory disease.

increased risk of expulsion if inserted before uterineinvolution.menorrhagia (progestogen intra-uterinesystem might be preferable).nulliparity.severe cervicalstenosis.severe primary dysmenorrhoea.severely scarreduterus (including after endometrial resection).young ageCAUTIONS, FURTHER INFORMATION

Risk of infectionThe main excess risk of infection occurs

in the first20days after insertion and is believed to berelated to existing carriage of a sexually transmittedinfection Women are considered to be at a higher risk ofsexually transmitted infections if:

they are under25years old or they are over25years old and have a new partner or have had more than one partner in the past year or theirregular partner has other partners

In these women, pre-insertion screening (for chlamydiaand, depending on sexual history and local prevalence ofdisease, Neisseria gonorrhoeae) should be performed Ifresults are unavailable at the time of fitting an intra-uterine device for emergency contraception, appropriateprophylactic antibacterial cover should be given Thewoman should be advised to attend as an emergency if sheexperiences sustained pain during the next20days

An intra-uterine device should not be removed in cycle unless an additional contraceptive was used for theprevious7days If removal is essential post-coitalcontraception should be considered

mid-lSIDE-EFFECTSAllergy.bleeding (on insertion).cervicalperforation.displacement.dysmenorrhoea.expulsion.

menorrhagia.occasionally epileptic seizure (on insertion)

.pain (on insertion, alleviated by NSAID such asibuprofen 30 minutes before insertion).pelvic infectionmay be exacerbated.uterine perforation.vasovagalattack (on insertion)

SIDE-EFFECTS, FURTHER INFORMATIONPresence of significant symptoms (especially pain)Advisethe patient to seek medical attention promptly in case ofsignificant symptoms

lALLERGY AND CROSS-SENSITIVITYContraindicated ifpatient has a copper allergy

lPREGNANCYIf an intra-uterine device fails and thewoman wishes to continue to full-term the device should

be removed in the first trimester if possible Remove

7

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device; if pregnancy occurs, increased likelihood that it

may be ectopic

lBREAST FEEDINGNot known to be harmful

lMONITORING REQUIREMENTSGynaecological examination

before insertion,6–8weeks after insertion, then annually

lDIRECTIONS FOR ADMINISTRATIONThe timing and

technique of fitting an intra-uterine device are critical for

its subsequent performance The healthcare professional

inserting (or removing) the device should be fully trained in

the technique and should provide full counselling backed,

where available, by the patient information leaflet Devices

should not be fitted during the heavy days of the period;

they are best fitted after the end of menstruation and

before the calculated time of implantation

‘Mini’ size for minimum uterine length5cm;‘Normal’

size for uterine length6.5–9cm; replacement every

5years

NOVAPLUS T 380®CU

‘Mini’ size for minimum uterine length5cm;‘Normal’

size for uterine length6.5–9cm; replacement every

5years

NOVA-T®380 PRODUCTS

For uterine length6.5–9cm; replacement every5years

T-SAFE®380A QL PRODUCTS

TT380®SLIMLINE PRODUCTS

UT380 SHORT®PRODUCTS

For uterine length5–7cm; replacement every5years

UT380 STANDARD®PRODUCTS

lMEDICINAL FORMS

Contraceptive devices

▶INTRA-UTERINE CONTRACEPTIVE DEVICES (COPPER)

(Non-proprietary)

Copper T380A intra-uterine contraceptive device|1device £8.95

Steriload intra-uterine contraceptive device|1device £9.65

Load375intra-uterine contraceptive device|1device £8.52

Novaplus T380Ag intra-uterine contraceptive device mini|1device

£12.50

T-Safe380A QL intra-uterine contraceptive device|1device £10.47

UT380Standard intra-uterine contraceptive device|1device £11.22

Flexi-T+380intra-uterine contraceptive device|1device £10.06Mini TT380Slimline intra-uterine contraceptive device|1device

£12.46Flexi-T300intra-uterine contraceptive device|1device £9.47Multi-Safe375intra-uterine contraceptive device|1device £8.96Multiload Cu375intra-uterine contraceptive device|1device £9.24Optima TCu380A intra-uterine contraceptive device|1device £9.65Novaplus T380Ag intra-uterine contraceptive device normal|

1device £12.50GyneFix intra-uterine contraceptive device|1device £27.11Novaplus T380Cu intra-uterine contraceptive device mini|1device

£10.95

TT380Slimline intra-uterine contraceptive device|1device £12.46Ancora375Cu intra-uterine contraceptive device|1device £7.95Novaplus T380Cu intra-uterine contraceptive device normal|

1device £10.95Neo-Safe T380intra-uterine contraceptive device|1device £13.31

UT380Short intra-uterine contraceptive device|1device £11.22Vaginal contraceptives

lSILICONE CONTRACEPTIVE DIAPHRAGMS

▶Milex arcing spring silicone diaphragm60mm (Durbin Plc)

1device.NHS indicative price = £9.31.Drug Tariff (Part IXa)

▶Milex omniflex coil spring silicone diaphragm60mm (DurbinPlc)

▶Ortho All-Flex arcing spring silicone diaphragm65mm Cilag Ltd)

(Janssen-1device.NHS indicative price = £8.35.Drug Tariff (Part IXa)

lSILICONE CONTRACEPTIVE PESSARIES

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3.3 Contraception, oral

progestogen-only

Drugs used for Contraception, oral progestogen-only not

listed below;Norethisterone, p.656

Ulipristal acetate

lDRUG ACTIONUlipristal acetate is a progesterone receptor

modulator with a partial progesterone antagonist effect

Emergency contraception

BY MOUTH

▶Females of childbearing potential:30mg for1dose, to be

take as soon as possible after coitus, but no later than

after120hours

Pre-operative treatment of moderate to severe symptoms of

uterine fibroids

BY MOUTH

▶Adult:5mg daily for up to3months starting during

the first week of menstruation, course may be

repeated once if necessary, starting during the second

menstruation after the first course completed,

maximum2courses of3months

▶When used for uterine fibroidsBreast cancer.cervical cancer.

ovarian cancer.undiagnosed vaginal bleeding.uterine

cancer.vaginal bleeding not caused by uterine fibroids

lCAUTIONSUncontrolled severe asthma

lINTERACTIONS→ Appendix1(ulipristal)

The effectiveness of ulipristal as an emergency

contraceptive is possibly reduced in women taking

enzyme-inducing drugs (and possibly for4weeks after

stopping); a copper intra-uterine device can be offered

instead There is no need to increase the dose for

emergency contraception if the patient is taking

antibacterials that are not enzyme inducers

lSIDE-EFFECTS

▶Common or very common

▶When used for emergency contraceptionAbdominal pain.

back pain.diarrhoea.dizziness.fatigue.

gastro-intestinal disturbances.headache.menstrual

irregularities.muscle spasms.nausea.vomiting

▶When used for uterine fibroidsAbdominal pain.acne.

breast pain.dizziness.endometrial thickening.headache

.hot flushes.hyperhidrosis.malaise.menstrual

disturbances.myalgia.nausea.oedema.ovarian cyst

(including rupture).pelvic pain.uterine haemorrhage

▶Uncommon

▶When used for emergency contraceptionBlurred vision.

breast tenderness.dry mouth.hot flushes.pruritus.rash

.tremor.uterine spasm

▶When used for uterine fibroidsAnxiety.constipation.dry

mouth.dyspepsia.epistaxis.flatulence.urinary

incontinence

lCONCEPTION AND CONTRACEPTIONWhen ulipristal is

given as an emergency contraceptive the effectiveness of

combined hormonal and progestogen-only contraceptives

may be reduced—additional precautions (barrier methods)

required for14days for combined and parenteral

progestogen-only hormonal contraceptives (16days for

Qlaira®) and9days for oral progestogen-only

contraceptives When ulipristal is given for uterinefibroids non-hormonal contraceptive methods (barriermethods or intra-uterine device) should be used bothduring treatment and for12days after stopping, ifrequired

lPREGNANCYManufacturer advises avoid for uterinefibroids—no information available Limited informationavailable when used as an emergency contraceptive

lBREAST FEEDINGWhen used for uterine fibroids,manufacturer advises avoid—no information available

In emergency contraception manufacturer advises avoidfor1week after administration—present in milk

lHEPATIC IMPAIRMENTCaution with use in uterine fibroids

in moderate to severe hepatic impairment—noinformation available Manufacturer advises avoiding use

as an emergency contraceptive in severe hepaticimpairment—no information available

lRENAL IMPAIRMENTCaution in severe renal impairmentwhen used for uterine fibroids—no information available

lPATIENT AND CARER ADVICEWhen ulipristal is given as anemergency contraceptive, if vomiting occurs within3hours of taking a dose, a replacement dose should begiven When prescribing or supplying hormonalemergency contraception, women should be advised:

that their next period may be early or late;

that a barrier method of contraception needs to be useduntil the next period;

to seek medical attention promptly if any lowerabdominal pain occurs because this could signify anectopic pregnancy;

to return in3to4weeks if the subsequent menstrualbleed is abnormally light, heavy or brief, or is absent, or

if she is otherwise concerned (if there is any doubt as towhether menstruation has occurred, a pregnancy testshould be performed at least3weeks after unprotectedintercourse)

BY MOUTH

▶Females of childbearing potential:75micrograms daily,dose to be taken at same time each day, starting onday1of cycle then continuously, if administrationdelayed for12hours or more it should be regarded as a

lCAUTIONSActive trophoblastic disease (until return tonormal of urine- and plasma-gonadotrophinconcentration)—seek specialist advice.arterial disease.

functional ovarian cysts.history of jaundice in pregnancy

.malabsorption syndromes.past ectopic pregnancy.steroid dependent cancer.systemic lupus erythematosus

7

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Other conditionsThe product literature advises caution in

patients with history of thromboembolism, hypertension,

diabetes mellitus and migraine; evidence for caution in

these conditions is unsatisfactory

lINTERACTIONS→ Appendix1(progestogens)

lSIDE-EFFECTSBreast discomfort.changes in libido.

depression.disturbance of appetite.dizziness.headache

.menstrual irregularities.nausea.skin disorders.

vomiting

SIDE-EFFECTS, FURTHER INFORMATION

Breast cancerThere is a small increase in the risk of

having breast cancer diagnosed in women using, or who

have recently used, a progestogen-only contraceptive pill;

this relative risk may be due to an earlier diagnosis The

most important risk factor appears to be the age at which

the contraceptive is stopped rather than the duration of

use; the risk disappears gradually during the10years after

stopping and there is no excess risk by10years A

possible small increase in the risk of breast cancer should

be weighed against the benefits

lPREGNANCYNot known to be harmful

lBREAST FEEDINGProgestogen-only contraceptives do not

affect lactation

lHEPATIC IMPAIRMENTCaution in severe liver disease and

recurrent cholestatic jaundice Avoid in liver tumour

Missed pillThe following advice is recommended:‘If you

forget a pill, take it as soon as you remember and carry on

with the next pill at the right time If the pill was more

than3hours (12hours for desogestrel) overdue you are

not protected Continue normal pill-taking but you must

also use another method, such as the condom, for the

next2days

The Faculty of Sexual and Reproductive Healthcare

recommends emergency contraception if one or more

progestogen-only contraceptive tablets are missed or

taken more than3hours (12hours for desogestrel) late

and unprotected intercourse has occurred before2further

tablets have been correctly taken

SurgeryAll progestogen-only contraceptives (including

those given by injection) are suitable for use as an

alternative to combined hormonal contraceptives before

major elective surgery, before all surgery to the legs, or

before surgery which involves prolonged immobilisation of a

lower limb

Starting routineOne tablet daily, on a continuous basis,

starting on day1of cycle and taken at the same time each

day (if delayed by longer than3hours (12hours for

desogestrel) contraceptive protection may be lost)

Additional contraceptive precautions are not necessary when

initiating treatment

Changing from a combined oral contraceptiveStart on the day

following completion of the combined oral contraceptive

course without a break (or in the case of ED tablets omitting

the inactive ones)

After childbirthOral progestogen-only contraceptives can be

started up to and including day21postpartum without the

need for additional contraceptive precautions If started

more than21days postpartum, additional contraceptive

precautions are required for2days

diarrhoea can interfere with the absorption of oral

progestogen-only contraceptives If vomiting occurs within

2hours of taking an oral progestogen-only contraceptive,

another pill should be taken as soon as possible If a

replacement pill is not taken within3hours (12hours for

desogestrel) of the normal time for taking the

progestogen-only pill, or in cases of persistent vomiting or very severe

diarrhoea, additional precautions should be used during

illness and for2days after recovery

lNATIONAL FUNDING/ACCESS DECISIONSScottish Medicines Consortium (SMC) DecisionsThe Scottish Medicines Consortium has advised (September

2003) that Cerazette®should be restricted for use inwomen who cannot tolerate oestrogen-containingcontraceptives or in whom such preparations are contra-indicated

Tablet

▶DESOGESTREL (Non-proprietary)Desogestrel 75 microgram Desogestrel75microgram tablets|

BY MOUTH

▶Females of childbearing potential:1.5mg for1dose, taken

as soon as possible after coitus, preferably within

12hours but no later than after72hoursContraception

BY MOUTH

▶Females of childbearing potential:1tablet daily starting

on day1of the cycle then continuously, dose is to betaken at the same time each day, if administrationdelayed for3hours or more it should be regarded as a

be delayed until at least6weeks after delivery(12weeks if uterus involution is substantiallydelayed); effective for3years

MIRENA®20MICROGRAMS/24HOURS INTRA-UTERINEDEVICE

Contraception| Menorrhagia

BY INTRA-UTERINE ADMINISTRATION

▶Females of childbearing potential:Insert into uterinecavity within7days of onset of menstruation, or anytime if replacement, or any time if reasonably certainwoman is not pregnant and there is no risk ofconception (additional precautions (e.g barriermethods) necessary for next7days), or immediatelyafter first-trimester termination by curettage;postpartum insertions should be delayed until at least

4weeks after delivery; effective for5yearsPrevention of endometrial hyperplasia during oestrogenreplacement therapy

BY INTRA-UTERINE ADMINISTRATION

▶Females of childbearing potential:Insert during last days

of menstruation or withdrawal bleeding or at any time

if amenorrhoeic; effective for4years

lCONTRA-INDICATIONS

▶With intra-uterine useActive trophoblastic disease (untilreturn to normal of urine- and plasma-gonadotrophinconcentration.acute cervicitis.acute vaginitis.distorted

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malignancy.history of breast cancer but can be

considered for a woman in long-term remission who has

menorrhagia and requires effective contraception.

infected abortion during the previous three months.

marked immunosuppression.not suitable for emergency

contraception.pelvic inflammatory disease.postpartum

endometritis.recent sexually transmitted infection (if not

fully investigated and treated).severe anaemia.small

uterine cavity.unexplained uterine bleeding

▶With oral useAcute porphyrias p.864

▶With oral use for contraceptionHistory of breast cancer but

can be used after5years if no evidence of disease and

non-hormonal contraceptive methods unacceptable.

severe arterial disease.undiagnosed vaginal bleeding

lCAUTIONS

▶With intra-uterine useAnaemia.anticoagulant therapy

(avoid if possible).diabetes.disease-induced

immunosuppression (risk of infection—avoid if marked

immunosuppression).drug-induced immunosuppression

(risk of infection—avoid if marked immunosuppression).

endometriosis.epilepsy (risk of seizure at time of

insertion).fertility problems.history of pelvic

inflammatory disease.increased risk of expulsion if

inserted before uterine involution.menorrhagia

(progestogen intra-uterine system might be preferable).

nulliparity.severe cervical stenosis.severe primary

dysmenorrhoea.severely scarred uterus (including after

endometrial resection).young age

▶With oral use for contraceptionActive trophoblastic disease

(until return to normal of urine- and

plasma-gonadotrophin concentration)—seek specialist advice.

arterial disease.functional ovarian cysts.history of

jaundice in pregnancy.malabsorption syndromes.past

ectopic pregnancy.sex-steroid dependent cancer.

systemic lupus erythematosus with positive (or unknown)

antiphospholipid antibodies

▶When used for emergency contraceptionActive trophoblastic

disease (until return to normal of urine- and

plasma-gonadotrophin concentration)—seek specialist advice.past

ectopic pregnancy.severe malabsorption syndromes

Risk of infection with intra-uterine devicesThe main excess

risk of infection occurs in the first20days after insertion

and is believed to be related to existing carriage of a

sexually transmitted infection Women are considered to

be at a higher risk of sexually transmitted infections if:

they are under25years old or

they are over25years old and have a new partner or

have had more than one partner in the past year or

their regular partner has other partners

In these women, pre-insertion screening (for chlamydia

and, depending on sexual history and local prevalence of

disease, Neisseria gonorrhoeae) should be performed If

results are unavailable at the time of fitting an

intra-uterine device for emergency contraception, appropriate

prophylactic antibacterial cover should be given The

woman should be advised to attend as an emergency if she

experiences sustained pain during the next20days

An intra-uterine device should not be removed in

mid-cycle unless an additional contraceptive was used for the

previous7days If removal is essential post-coital

contraception should be considered

▶With oral use

Use as a contraceptive in co-morbiditiesThe product

literature advises caution in patients with history of

thromboembolism, hypertension, diabetes meillitus and

migraine; evidence for caution in these conditions is

is no need to increase the dose for emergencycontraception if the patient is taking antibacterials thatare not enzyme inducers

With the progestogen-only intra-uterine device,levonorgestrel is released close to the site of the maincontraceptive action (on cervical mucus andendometrium) and therefore progestogenic side-effectsand interactions are less likely; in particular, enzyme-inducing drugs are unlikley to significantly reduce thecontraceptive effect of the progestogen-only intra-uterinesystem and additional contraceptive precautions are notrequired

▶Common or very commonDepression (sometimes severe).

headache.nausea

▶Frequency not knownVomitingSPECIFIC SIDE-EFFECTS

▶With intra-uterine useAbdominal pain.acne.alopecia.

back pain.breast pain.changes in the pattern andduration of menstrual bleeding (spotting or prolongedbleeding).expulsion.hirsutism.migraine.nervousness.

pelvic pain.peripheral oedema.salpingitis

▶Uncommon

▶With intra-uterine useAbdominal distension.cervicitis.

eczema.pelvic inflammatory disease.pruritus.skinhyperpigmentation

▶Rare

▶With intra-uterine useRash.uterine perforation

▶Frequency not known

▶With intra-uterine useAllergy.bleeding (on insertion).

cervical perforation.displacement.dysmenorrhoea.

epileptic seizures (on insertion).functional ovarian cysts(usually asymptomatic and usually resolve

spontaneously—ultrasound monitoring recommended).

menorrhagia.pain (on insertion, alleviated by NSAIDsuch as ibuprofen 30 minutes before insertion).pelvicinfection may be exacerbated.vasovagal attack (oninsertion)

▶With oral useBreast discomfort.breast tenderness.

changes in libido.disturbances of appetite.dizziness.

fatigue.menstrual irregularities.skin disordersSIDE-EFFECTS, FURTHER INFORMATIONEndometrial disorders should be ruled out beforeinsertion and the patient should be fully counselled (andprovided with a patient information leaflet) Improvement

in progestogenic side-effects, such as mastalgia and in thebleeding pattern may often become very light or absent.Breast cancerThere is a small increase in the risk ofhaving breast cancer diagnosed in women using, or whohave recently used, a progestogen-only contraceptive pill;this relative risk may be due to an earlier diagnosis Themost important risk factor appears to be the age at whichthe contraceptive is stopped rather than the duration ofuse; the risk disappears gradually during the10years afterstopping and there is no excess risk by10years Apossible small increase in the risk of breast cancer should

Although the progestogen-only intra-uterine systemproduces little systemic progestogenic activity, it isusually avoided for5years after any evidence of breastcancer However, the system can be considered for a

7

Trang 28

woman in long-term remission from breast cancer who

has menorrhagia and requires effective contraception

Removal of the intra-uterine system should be considered

if the patient experiences migraine or severe headache,

jaundice, marked increase of blood pressure, or severe

arterial disease

lPREGNANCY

▶With oral useNot known to be harmful

▶With vaginal useIf an intra-uterine device fails and the

woman wishes to continue to full-term the device should

be removed in the first trimester if possible Avoid; if

pregnancy occurs remove intra-uterine system

lBREAST FEEDINGProgestogen-only contraceptives do not

affect lactation

lHEPATIC IMPAIRMENTCaution in severe liver disease and

recurrent cholestatic jaundice Avoid in liver tumour

lMONITORING REQUIREMENTSGynaecological examination

before insertion,4–6weeks after insertion, then annually

▶With intra-uterine useThe doctor or nurse administering (or

removing) the system should be fully trained in the technique

and should provide full counselling reinforced by the patient

information leaflet

JAYDESS®13.5MG INTRA-UTERINE DEVICE

When system is removed (and not replaced immediately)

and pregnancy is not desired, remove within7days of the

onset of menstruation; additional precautions (e.g barrier

methods) should be used if the system is removed at some

other time during the cycle and there is intercourse

within7days

MIRENA®20MICROGRAMS/24HOURS INTRA-UTERINE

DEVICE

When system is removed (and not immediately replaced)

and pregancy is not desired, remove during first few days

of menstruation, otherwise additional precautions (e.g

barrier methods) should be used for at least7days before

removal

Missed dosesWhen used as an oral contraceptive, the

following advice is recommended‘If you forget a pill, take

it as soon as you remember and carry on with the next pill

at the right time If the pill was more than3hours

overdue you are not protected Continue normal

pill-taking but you must also use another method, such as the

condom, for the next2days’ The Faculty of Sexual and

Reproductive Healthcare recommends emergency

contraception if one or more progestogen-only

contraceptive tablets are missed or taken more than3

hours late and unprotected intercourse has occurred

before2further tablets have been correctly taken

diarrhoea can interfere with the absorption of oral

progestogen-only contraceptives If vomiting occurs within2

hours of taking an oral progestogen-only contraceptive,

another pill should be taken as soon as possible If a

replacement pill is not taken within3hours of the normal

time for taking the progestogen-only pill, or in cases of

persistent vomiting or very severe diarrhoea, additional

precautions should be used during illness and for2days

after recovery

▶With oral use for Contraception

Starting routineOne tablet daily, on a continuous basis,

starting on day1of cycle and taken at the same time each

day (if delayed by longer than3hours contraceptive

protection may be lost) Additional contraceptive

precautions are not necessary when initiating treatment

Changing from a combined oral contraceptiveStart on the day

following completion of the combined oral contraceptive

course without a break (or in the case of ED tablets omittingthe inactive ones)

After childbirthOral progestogen-only contraceptives can bestarted up to and including day21postpartum without theneed for additional contraceptive precautions If startedmore than21days postpartum, additional contraceptiveprecautions are required for2days

▶With oral use for Emergency contraception

If vomiting occurs within2hours of taking levonorgestrel,

a replacement dose should be given

When prescribing or supplying hormonal emergencycontraception, women should be advised:

that their next period may be early or late;

that a barrier method of contraception needs to be useduntil the next period;

to seek medical attention promptly if any lowerabdominal pain occurs because this could signify anectopic pregnancy;

to return in3to4weeks if the subsequent menstrualbleed is abnormally light, heavy or brief, or is absent, or

if she is otherwise concerned (if there is any doubt as towhether menstruation has occurred, a pregnancy testshould be performed at least3weeks after unprotectedintercourse)

▶With intra-uterine useCounsel women to seek medicalattention promptly in case of significant symptoms,especially pain

Patient counselling advised Patient information leaflet to

be provided

lEXCEPTIONS TO LEGAL CATEGORYLevonelle®One Step can

be sold to women over16years; when supplyingemergency contraception to the public, pharmacistsshould refer to guidance issued by the RoyalPharmaceutical Society

Tablet

▶LEVONORGESTREL (Non-proprietary)Levonorgestrel 1.5 mg Levonorgestrel1.5mg tablets|1tabletp

£5.20–£13.83DT price = £5.20|1tabletP£5.20DT price = £5.20

▶Isteranda(Sandoz Ltd)Levonorgestrel 1.5 mg Isteranda1.5mg tablets|1tabletP

£5.20DT price = £5.20

▶Levonelle(Bayer Plc)Levonorgestrel 1.5 mg Levonelle1500microgram tablets|

1tabletP£5.20DT price = £5.20Levonelle One Step1.5mg tablets|1tabletp£13.83DT price =

£5.20

▶Norgeston(Bayer Plc)Levonorgestrel 30 microgram Norgeston30microgram tablets|

▶Upostelle(Consilient Health Ltd)Levonorgestrel 1.5 mg Upostelle1500microgram tablets|

1tabletP£3.75DT price = £5.20Intra-uterine device

▶Jaydess(Bayer Plc)A

Levonorgestrel 13.5 mg Jaydess13.5mg intra-uterine device|

1deviceP£69.22

▶Levosert(Actavis UK Ltd)Levonorgestrel 20 microgram per 24 hour Levosert

20micrograms/24hours intra-uterine device|1deviceP£66.00

▶Mirena(Bayer Plc)Levonorgestrel 20 microgram per 24 hour Mirena

20micrograms/24hours intra-uterine device|1deviceP£88.00

3.4 Contraception, parenteral progestogen-only

Drugs used for Contraception, parenteral only not listed below;Norethisterone, p.656

7

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Etonogestrel

Contraception (no hormonal contraceptive use in previous

month)

BY SUBDERMAL IMPLANTATION

▶Females of childbearing potential:1implant inserted

during first5days of cycle, implant should be removed

within3years of insertion

Contraception (postpartum)

▶Females of childbearing potential:1implant to be

inserted21–28days after delivery,1implant to be

inserted after28days postpartum in breast-feeding

mothers, implant should be removed within3years of

insertion

Contraception following abortion or miscarriage in the

second trimester

inserted21–28days after abortion or miscarriage,

implant should be removed within3years of insertion

Contraception following abortion or miscarriage in the first

trimester

inserted within5days, implant should be removed

within3years of insertion

Contraception (changing from other hormonal

contraceptive)

▶Females of childbearing potential:Implant should be

removed within3years of insertion (consult product

literature)

lCONTRA-INDICATIONSAcute porphyria.history of breast

cancer but can be used after 5 years if no evidence of

disease and non-hormonal contraceptive methods

unacceptable.severe arterial disease.undiagnosed

vaginal bleeding

lCAUTIONSActive trophoblastic disease (until return to

normal of urine- and plasma-gonadotrophin

concentration)—seek specialist advice.arterial disease.

disturbances of lipid metabolism.history during

pregnancy of deterioration of otosclerosis.history during

pregnancy of pruritus.history of jaundice in pregnancy.

malabsorption syndromes.possible risk of breast cancer.

sex-steroid dependent cancer.systemic lupus

erythematosus with positive (or unknown)

antiphospholipid antibodies

Effectiveness of parenteral progestogen-only

contraceptives is not affected by antibacterials that do not

induce liver enzymes Effectiveness of the

etonogestrel-releasing implant may be reduced by enzyme-inducing

drugs and an alternative contraceptive method,

unaffected by the interacting drug, is recommended

during treatment with the enzyme-inducing drug and for

at least4weeks after stopping For a short course of an

enzyme-inducing drug, if a change in contraceptive

method is undesirable or inappropriate, the implant may

be continued in combination with additional

contraceptive precautions (e.g condom) for the duration

of treatment with the enzyme-inducing drug and for4

weeks after stopping it

lSIDE-EFFECTSBreast discomfort.changes in libido.

depression.disturbance of appetite.dizziness.headache

.injection-site reactions.menstrual irregularities.nausea

.vomitingSIDE-EFFECTS, FURTHER INFORMATIONCervical cancerUse of injectable progestogen-onlycontraceptives may be associated with a small increasedrisk of cervical cancer, similar to that seen with combinedoral contraceptives The risk of cervical cancer with otherprogestogen-only contraceptives is not yet known

Breast cancerThere is a small increase in the risk ofhaving breast cancer diagnosed in women using, or whohave recently used, a progestogen-only contraceptive pill;this relative risk may be due to an earlier diagnosis Themost important risk factor appears to be the age at whichthe contraceptive is stopped rather than the duration ofuse; the risk disappears gradually during the10years afterstopping and there is no excess risk by10years Apossible small increase in the risk of breast cancer should

lPREGNANCYNot known to be harmful, remove implant ifpregnancy occurs

lBREAST FEEDINGProgestogen-only contraceptives do notaffect lactation

lDIRECTIONS FOR ADMINISTRATIONThe doctor or nurseadministering (or removing) the system should be fullytrained in the technique and should provide fullcounselling reinforced by the patient information leaflet

lPATIENT AND CARER ADVICEFull counselling backed bypatient information leaflet required before

administration

Implant

▶ETONOGESTREL (Non-proprietary)Etonogestrel 68 mgEtonogestrel68mg implant|1devicePnoprice available

▶Nexplanon(Merck Sharp & Dohme Ltd)Etonogestrel 68 mg Nexplanon68mg implant|1deviceP

£83.43Medroxyprogesterone acetateINDICATIONS AND DOSE

Dysfunctional uterine bleeding

BY MOUTH

▶Adult:2.5–10mg daily for5–10days, repeated for

2cycles, begin treatment on day16–21of cycleSecondary amenorrhoea

BY MOUTH

▶Adult:2.5–10mg daily for5–10days, repeated for

3cycles, begin treatment on day16–21of cycleMild to moderate endometriosis

BY MOUTH

▶Adult:0.4–1.5g daily continued→

7

Trang 30

BY DEEP INTRAMUSCULAR INJECTION

▶Females of childbearing potential:150mg, to be

administered within the first5days of cycle or within

first5days after parturition (delay until6weeks after

parturition if breast-feeding)

BY SUBCUTANEOUS INJECTION

▶Females of childbearing potential:104mg, to be

administered within first5days of cycle or within

5days postpartum (delay until6weeks postpartum if

breast-feeding), injected into anterior thigh or

abdomen, dose only suitable if no hormonal

contraceptive use in previous month

Long-term contraception

▶Females of childbearing potential:150mg every12weeks,

to be administered within the first5days of cycle or

within first5days after parturition (delay until

6weeks after parturition if breast-feeding)

BY SUBCUTANEOUS INJECTION

▶Females of childbearing potential:104mg every13weeks,

to be administered within first5days of cycle or

within5days postpartum (delay until6weeks

postpartum if breast-feeding), injected into anterior

thigh or abdomen, dose only suitable if no hormonal

contraceptive use in previous month

Contraception (when patient changing from other hormonal

Acute porphyrias p.864.severe arterial disease.

undiagnosed vaginal bleeding

SPECIFIC CONTRA-INDICATIONS

▶With intramuscular or subcutaneous useHistory of breast

cancer but can be used after5years if no evidence of disease

and non-hormonal contraceptive methods unacceptable

▶With oral useBreast cancer (unless progestogens are being

used in the management of this condition).genital cancer

(unless progestogens are being used in the management of

this condition).history of liver tumours

lCAUTIONS

GENERAL CAUTIONS:

Possible risk of breast cancer

SPECIFIC CAUTIONS:

▶With intramuscular or subcutaneous useHistory during

pregnancy in disturbances of lipid metabolism.history

during pregnancy of deterioration of otosclerosis.history

during pregnancy of pruritus

▶With oral useAsthma.cardiac dysfunction.conditions that

may worsen with fluid retention.diabetes (progestogens can

decrease glucose tolerance—monitor patient closely).

epilepsy.history of depression.hypertension.migraine.

susceptibility to thromboembolism (particular caution with

high dose)

Effectiveness of parenteral progestogen-only

contraceptives is not affected by antibacterials that do not

induce liver enzymes The effectiveness of

medroxyprogesterone acetate intramuscular and

subcutaneous injections is not affected by

enzyme-inducing drugs and they may be continued as normal

during courses of these drugs

lSIDE-EFFECTS

GENERAL SIDE-EFFECTSBreast discomfort.changes in

libido.depression.dizziness.headache.indigestion.loss

papilloedema or retinal vascular lesions).menstrualirregularities.nausea.pruritus.vomiting.weight gainSPECIFIC SIDE-EFFECTS

▶Rare

▶With intramuscular or subcutaneous useOsteoporosis.

osteoporotic fractures

▶With intramuscular or subcutaneous useDisturbance ofappetite.injection site-reactions.reduced bone mineraldensity.skin disorders

▶With oral useAcne.adrenergic-like effects (when used formalignant disease).alopecia.anaphylactoid reactions.

bloating.breast tenderness.cervical erosions (when usedfor malignant disease).confusion (when used formalignant disease).congestive heart failure (when usedfor malignant disease).constipation (when used formalignant disease).diarrhoea (when used for malignantdisease).drowsiness.dry mouth (when used formalignant disease).euphoria (when used for malignantdisease).fluid retention.galactorrhoea (when used formalignant disease).glucocorticoid effects may lead to acushingoid syndrome (with high doses for malignantdisease).hirsutism.hypercalcaemia (when used formalignant disease).hyperpyrexia (when used formalignant disease).hypertension (when used formalignant disease).insomnia.jaundice.loss ofconcentration (when used for malignant disease).

nervousness (when used for malignant disease).

palpitation (when used for malignant disease).

premenstrual-like syndrome.raised platelet count (whenused for malignant disease).raised white blood cell count(when used for malignant disease).rash.retinalthrombosis (when used for malignant disease).skinreactions.tachycardia (when used for malignant disease).

urticaria.vision disorders (when used for malignantdisease)

SIDE-EFFECTS, FURTHER INFORMATIONCervical cancerUse of injectable progestogen-onlycontraceptives may be associated with a small increasedrisk of cervical cancer, similar to that seen with combinedoral contraceptives The risk of cervical cancer with otherprogestogen-only contraceptives is not yet known.Reduction in bone mineral density occurs in the first

2–3years of use then stabilises

lCONCEPTION AND CONTRACEPTION

▶With intramuscular useIf interval between dose is greaterthan12weeks and5days (in long-term contraception),rule out pregnancy before next injection and advisepatient to use additional contraceptive measures (e.g.barrier) for14days after the injection

▶With subcutaneous useIf interval between dose is greaterthan13weeks and7days (in long-term contraception),rule out pregnancy before next injection

▶With intramuscular use or subcutaneous useThemanufacturers advise that in women who are breast-feeding, the first dose should be delayed until6weeksafter birth; however, evidence suggests no harmful effect

to infant if given earlier The benefits of usingmedroxyprogesterone acetate in breast-feeding womenoutweigh any risks

Trang 31

▶With intramuscular use or subcutaneous useCaution in severe

liver disease and recurrent cholestatic jaundice Avoid in

liver tumour

lRENAL IMPAIRMENTUse with caution

▶With intramuscular use or subcutaneous useFull counselling

backed by patient information leaflet required before

administration—likelihood of menstrual disturbance and

the potential for a delay in return to full fertility Delayed

return of fertility and irregular cycles may occur after

discontinuation of treatment but there is no evidence of

permanent infertility

lMEDICINAL FORMS

manufacturers include: oral suspension, oral solution

Tablet

▶Climanor(ReSource Medical UK Ltd)

Medroxyprogesterone acetate 5 mg Climanor5mg tablets|

28tabletP£3.27

▶Provera(Pfizer Ltd)

Medroxyprogesterone acetate 2.5 mg Provera2.5mg tablets|

Medroxyprogesterone acetate 5 mg Provera5mg tablets|

10tabletP£2.47|90tabletP£22.16DT price = £22.16|

100tabletP£24.73

60tabletP£29.98|100tabletP£49.94DT price = £49.94

Medroxyprogesterone acetate 150 mg per 1 ml Depo-Provera

150mg/1ml suspension for injection pre-filled syringes|1pre-filled

disposable injectionP£6.01DT price = £6.01

▶Sayana Press(Pfizer Ltd)

Medroxyprogesterone acetate 160 mg per 1 ml Sayana Press

104mg/0.65ml suspension for injection pre-filled disposable

devices|1pre-filled disposable injectionP£6.90

3.5 Contraception, spermicidal

SPERMICIDALS

Nonoxinol

Spermicidal contraceptive in conjunction with barrier

methods of contraception such as diaphragms or caps

BY VAGINA

▶Females of childbearing potential:(consult product

literature)

lSIDE-EFFECTSGenital lesions

High frequency use of the spermicide nonoxinol’9’ has

been associated with genital lesions, which may increase

the risk of acquiring these infections

lCONCEPTION AND CONTRACEPTIONNo evidence of harm

to latex condoms and diaphragms

lPREGNANCYToxicity in animal studies

lBREAST FEEDINGPresent in milk in animal studies

lMEDICINAL FORMS

GelEXCIPIENTS:May contain Hydroxybenzoates (parabens), propyleneglycol, sorbic acid

▶Gygel(Marlborough Pharmaceuticals Ltd)Nonoxinol-9 20 mg per 1 ml Gygel2% contraceptive jelly|

30gramG£4.25|81gramG£11.00

conditions 4.1 Erectile dysfunction Erectile dysfunction

Reasons for failure to produce a satisfactory erectioninclude psychogenic, vascular, neurogenic, and endocrineabnormalities; impotence can also be drug-induced

Intracavernosal, urethral or topical application of vasoactivedrugs under careful medical supervision are used for themanagement of erectile dysfunction Intracavernosal orintraurethral preparations can also be used in the diagnosis

of erectile dysfunction

Erectile disorders may also be treated with drugs given bymouth which increase the blood flow to the penis Drugsshould be used with caution if the penis is deformed (e.g inangulation, cavernosal fibrosis, and Peyronie’s disease)

on the opposite side

If initial aspiration is unsuccessful a second19–21gauge butterfly needle can be inserted into the oppositecorpus cavernosum and sterile physiological salineintroduced through the first needle and drainedthrough the second

If aspiration and lavage of corpora are unsuccessful,cautious intracavernosal injection of a

sympathomimetic with action on alpha-adrenergicreceptors, continuously monitoring blood pressure andpulse (extreme caution: coronary heart disease,hypertension, cerebral ischaemia or if takingantidepressant) can be given

If necessary the sympathomimetic injections can befollowed by further aspiration of blood through thesame butterfly needle

If sympathomimetics unsuccessful, urgent surgicalreferral for management (possibly including shuntprocedure)

Prescribing on the NHSSome drug treatments for erectile dysfunction may only beprescribed on the NHS under certain circumstances; fordetails see the criteria listed in part XVIIIB of the DrugTariff (Part XIb of the Northern Ireland Drug Tariff, Part12

of the Scottish Drug Tariff) The Drug Tariffs can beaccessed online at: National Health Service Drug Tariff forEngland and Wales:www.ppa.org.uk/ppa/edt_intro.htmHealth and Personal Social Services for Northern IrelandDrug Tariff:www.dhsspsni.gov.uk/pas-tariff

Scottish Drug Tariff:www.isdscotland.org/Health-Topics/Prescribing-and-Medicines/Scottish-Drug-Tariff/

7

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Alprostadil p.701(prostaglandin E1) is given by

intracavernosal injection, intraurethral application, or

topical application for the management of erectile

dysfunction (after exclusion of treatable medical causes)

Intracavernosal or intraurethral preparations can also be

used in the diagnosis of erectile dysfunction

Phosphodiesterase type-5 inhibitors

Avanafil below, sildenafil below, tadalafil p.700and

vardenafil p.701are phosphodiesterase type-5inhibitors

licensed for the treatment of erectile dysfunction; they are

not recommended for use with other treatments for erectile

dysfunction The patient should be assessed appropriately

before prescribing avanafil, sildenafil, tadalafil or vardenafil

Since these drugs are given by mouth there is a potential for

drug interactions

Papaverine and phentolamine

Although not licensed the smooth muscle relaxant

papaverine has also been given by intracavernosal injection

for erectile dysfunction Patients with neurological or

psychogenic impotence are more sensitive to the effect of

papaverine than those with vascular abnormalities

Phentolamine mesilate p.161is added if the response is

inadequate [unlicensed indication]

Persistence of the erection for longer than4hours is an

▶Adult:Initially100mg, to be taken approximately30

minutes before sexual activity, then adjusted

according to response to50–200mg (max per dose

200mg), to be taken as a single dose as needed;

maximum1dose per day

Erectile dysfunction in patients on alpha-blocker therapy

BY MOUTH

minutes before sexual activity, then adjusted

according to response to50–200mg (max per dose

200mg), to be taken as a single dose as needed;

maximum1dose per day

Max.100mg once every48hours with concomitant

moderate inhibitors of cytochrome P450enzyme

CYP3A4e.g aprepitant, diltiazem, erythromycin,

fluconazole, fosamprenavir, or verapamil

Concomitant treatment with a phosphodiesterase type-5

inhibitor and an alpha-blocker can increase the risk of

postural hypotension—initiate treatment with a

phosphodiesterase type-5inhibitor (at a low dose) only

once the patient is stable on the alpha-blocker

lCONTRA-INDICATIONSAvoid if systolic blood pressure

below90mmHg (no information available).blood

pressure>170/100 mmHg.hereditary degenerative

retinal disorders.history of non-arteritic anterior

ischaemic optic neuropathy.life-threatening arrhythmia

in previous 6 months.mild to severe heart failure.

patients in whom vasodilation or sexual activity are

inadvisable.recent history of myocardial infarction.

recent history of stroke.recent unstable angina

lCAUTIONSActive peptic ulceration.anatomical

deformation of the penis (e.g angulation, cavernosal

fibrosis, Peyronie’s disease).bleeding disorders.

cardiovascular disease.left ventricular outflowobstruction.predisposition to priapism (e.g in sickle-celldisease, multiple myeloma, or leukaemia)

lINTERACTIONS→ Appendix1(avanafil)

Avoid concomitant use of nitrates

lSIDE-EFFECTS

▶Common or very commonBack pain.dizziness.dyspepsia.

flushing.headache.migraine.myalgia.nasal congestion

.nausea.visual disturbances.vomiting

▶UncommonDrowsiness.epistaxis.hypertension.

hypotension.malaise.painful red eyes.palpitation.

Stevens-Johnson syndrome.syncope.weight gain

▶Frequency not knownArrhythmia.myocardial infarction.

non-arteritic anterior ischaemic optic neuropathy (stopdrug if sudden visual impairment occurs).retinal vascularocclusion.seizures.serious cardiovascular events.

sudden hearing loss (discontinue drug and seek medicaladvice).unstable angina

lHEPATIC IMPAIRMENTUse lowest effective initial dose inmild to moderate impairment, adjusted according toresponse Manufacturer advises avoid in severeimpairment—no information available

lRENAL IMPAIRMENTAvoid if eGFR less than

12of the Scottish Drug Tariff) The prescription must beendorsed’SLS’

The Drug Tariffs can be accessed online at: NationalHealth Service Drug Tariff for England and Wales:www.ppa.org.uk/ppa/edt_intro.htm; Health and PersonalSocial Services for Northern Ireland Drug Tariff:www.dhsspsni.gov.uk/pas-tariff; Scottish Drug Tariff:www.isdscotland.org/Health-Topics/Prescribing-and-Medicines/Scottish-Drug-Tariff/

Tablet

▶Spedra(A Menarini Farmaceutica Internazionale SRL)A

Avanafil 50 mg Spedra50mg tablets|4tabletP£10.94|

8tabletP£19.70Avanafil 100 mg Spedra100mg tablets|4tabletP£14.08|

8tabletP£26.26Avanafil 200 mg Spedra200mg tablets|4tabletP£21.90|

8tabletP£39.40SildenafilINDICATIONS AND DOSEPulmonary arterial hypertension

Trang 33

Erectile dysfunction

BY MOUTH

hour before sexual activity, adjusted according to

response to25–100mg (max per dose100mg) as

required, to be taken as a single dose; maximum

1dose per day

lCONTRA-INDICATIONS

GENERAL CONTRA-INDICATIONS

Hereditary degenerative retinal disorders.history of

non-arteritic anterior ischaemic optic neuropathy.recent

history of myocardial infarction.recent history of stroke

▶When used for erectile dysfunctionAvoid if systolic blood

pressure below90mmHg (no information available).

patients in whom vasodilation or sexual activity are

inadvisable.recent unstable angina

▶When used for pulmonary arterial hypertensionSickle-cell

anaemia

lCAUTIONS

GENERAL CAUTIONS

Active peptic ulceration.bleeding disorders.

cardiovascular disease.left ventricular outflow

obstruction

SPECIFIC CAUTIONS

▶When used for erectile dysfunctionAnatomical deformation of

the penis (e.g angulation, cavernosal fibrosis, Peyronie’s

disease).predisposition to priapism (e.g in sickle-cell

disease, multiple myeloma, or leukaemia)

▶When used for pulmonary arterial hypertensionAnatomical

deformation of the penis.autonomic dysfunction.

hypotension (avoid if systolic blood pressure below

90 mmHg).intravascular volume depletion.predisposition

to priapism.pulmonary veno-occlusive disease

lINTERACTIONS→ Appendix1(sildenafil)

lSIDE-EFFECTS

GENERAL SIDE-EFFECTS

Back pain.dyspepsia.flushing.migraine.myalgia.nasal

congestion.visual disturbances

▶Frequency not knownNon-arteritic anterior ischaemic

optic neuropathy (discontinue if sudden visual

impairment occurs).sudden hearing loss (advise patient

to seek medical help)

SPECIFIC SIDE-EFFECTS

▶When used for erectile dysfunctionNausea.dizziness.

vomiting

▶When used for pulmonary arterial hypertensionAbdominal

distension.alopecia.anaemia.anxiety.bronchitis.

cellulitis.cough.diarrhoea.dry mouth.epistaxis.fever.

gastritis.gastro-oesophageal reflux.haemorrhoids.

headache.influenza-like symptoms.insomnia.limb pain

.night sweats.oedema.painful red eyes.paraesthesia.

photophobia.retinal haemorrhage.tremor.vertigo

▶Uncommon

▶When used for erectile dysfunctionChest pain.drowsiness

.dry mouth.epistaxis.fatigue.hypertension.

hypoaesthesia.hypotension.painful red eyes.

palpitation.tachycardia.tinnitus.vertigo

▶When used for pulmonary arterial

hypertensionGynaecomastia.haematuria.penile

haemorrhage.priapism

▶Rare

▶When used for erectile dysfunctionAtrial fibrillation.

cerebrovascular accident.facial oedema.hypersensitivity

reactions.priapism.rash.Stevens-Johnson syndrome.

syncope

▶When used for erectile dysfunctionArrhythmia.myocardialinfarction.seizures.unstable angina

▶When used for pulmonary arterial hypertensionRash.

retinal vascular occlusion

lPREGNANCYUse only if potential benefit outweighs risk—

no evidence of harm in animal studies

lBREAST FEEDINGManufacturer advises avoid—noinformation available

lHEPATIC IMPAIRMENTIn pulmonary arterial hypertension,

if usual dose not tolerated, reduce oral dose to20mgtwice daily and intravenous dose to10mg twice daily

For erectile dysfunction, use initial dose of25mg

Manufacturer advises avoid in severe impairment

lRENAL IMPAIRMENTUse initial dose of25mg in erectiledysfunction if eGFR less than30mL/minute/1.73m2

In pulmonary hypertension, if usual dose not tolerated,reduce oral dose to20mg twice daily and intravenous dose

to10mg twice daily

lTREATMENT CESSATION

▶When used for Pulmonary arterial hypertensionConsidergradual withdrawal

▶When used for Erectile dysfunctionOnset of effect may bedelayed if taken with food

lNATIONAL FUNDING/ACCESS DECISIONSScottish Medicines Consortium (SMC) DecisionsThe Scottish Medicines Consortium has advised (January

2010and February2011) that sildenafil tablets (Revatio®)should be initiated for patients with pulmonary arterialhypertension only by specialists in the ScottishPulmonary Vascular Unit or other similar specialists andthat sildenafil injection (Revatio®) should be prescribedonly on the advice of specialists in the ScottishPulmonary Vascular Unit or the Scottish Adult CongenitalCardiac Service

NHS restrictionsViagra®is not prescribable under NHSfor treatment of erectile dysfunction except in men whomeet the criteria listed in part XVIIIB of the Drug Tariff(Part XIb of the Northern Ireland Drug Tariff, Part12ofthe Scottish Drug Tariff) The prescription must beendorsed’SLS’ For more information see Prices in theBNF, under How to use BNF publications p xi

lMEDICINAL FORMSThere can be variation in the licensing of different medicinescontaining the same drug Forms available from special-ordermanufacturers include: pessary, oral suspension, oral solutionTablet

▶SILDENAFIL (Non-proprietary)Sildenafil (as Sildenafil citrate) 25 mg Sildenafil25mg tablets|

4tabletP£16.59DT price = £1.09|8tabletP£33.19Sildenafil (as Sildenafil citrate) 50 mg Sildenafil50mg tablets|

4tabletP£21.27DT price = £1.15|8tabletP£42.54Sildenafil (as Sildenafil citrate) 100 mg Sildenafil100mgtablets|4tabletP£23.50DT price = £1.23|8tabletP

£46.99|12tabletP£7.85

▶Revatio(Pfizer Ltd)Sildenafil (as Sildenafil citrate) 20 mg Revatio20mg tablets|

90tabletP£446.33

▶Viagra(Pfizer Ltd)Sildenafil (as Sildenafil citrate) 25 mg Viagra25mg tablets|

4tabletP£16.59DT price = £1.09|8tabletP£33.19Sildenafil (as Sildenafil citrate) 50 mg Viagra50mg tablets|

4tabletP£21.27DT price = £1.15|8tabletP£42.54Sildenafil (as Sildenafil citrate) 100 mg Viagra100mg tablets|

▶Brands may include Vizarsin

7

Trang 34

Chewable tablet

EXCIPIENTS:May contain Aspartame

▶Nipatra(AMCo)

Sildenafil (as Sildenafil citrate) 25 mg Nipatra25mg chewable

tablets (sugar-free)|4tabletP£1.05(sugar-free)|

8tabletP£2.10

8tabletP£2.06

8tabletP£2.22

Oral suspension

▶Revatio(Pfizer Ltd)

Sildenafil (as Sildenafil citrate) 10 mg per 1 ml Revatio10mg/ml

oral suspension (sugar-free)|112mlP£186.75

Solution for injection

▶Revatio(Pfizer Ltd)

Sildenafil (as Sildenafil citrate).8 mg per 1 ml Revatio

10mg/12.5ml solution for injection vials|1vialP£45.28

Tadalafil

Pulmonary arterial hypertension

BY MOUTH

▶Adult:Initially10mg once daily (max per dose20mg),

to be taken at least30minutes before sexual activity,

subsequent doses adjusted according to response, the

effect of intermittent dosing may persist for longer

than24hours, daily dose of10–20mg not

recommended; maximum1dose per day

Erectile dysfunction; for patients who anticipate sexual

activity at least twice a week

BY MOUTH

▶Adult:5mg once daily, reduced to2.5mg once daily,

adjusted according to response, the effect of

intermittent dosing may persist for longer than

▶When used for benign prostatic hyperplasia or erectile

dysfunctionHypotension (avoid if systolic blood pressure

below90mmHg).mild to severe heart failure.myocardial

infarction.patients in whom vasodilation or sexual activity

are inadvisable.recent stroke.uncontrolled arrhythmias.

uncontrolled hypertension.unstable angina

▶When used for pulmonary arterial hypertensionAcute

myocardial infarction in past90days

lCAUTIONS

▶When used for benign prostatic hyperplasia or erectile

dysfunctionAnatomical deformation of the penis (e.g

angulation, cavernosal fibrosis, Peyronie’s disease).

cardiovascular disease.left ventricular outflow obstruction.

predisposition to priapism (e.g in sickle-cell disease,

multiple myeloma, or leukaemia)

▶When used for pulmonary arterial hypertensionAnatomical

deformation of the penis.aortic and mitral valve disease.

congestive cardiomyopathy.coronary artery disease.

hereditary degenerative retinal disorders.hypotension

(avoid if systolic blood pressure below 90 mmHg).leftventricular dysfunction.life-threatening arrhythmias.

pericardial constriction.predisposition to priapism.

pulmonary veno-occlusive disease.uncontrolledhypertension

lINTERACTIONS→ Appendix1(tadalafil)

▶Common or very commonBack pain.dyspepsia.flushing.

headache.myalgia.nausea.vomiting

▶UncommonHypertension.tachycardia

non-arteritic anterior ischaemic optic neuropathy (stopdrug if sudden visual impairment occurs).retinal vascularocclusion.sudden hearing loss (discontinue drug andseek medical advice).unstable angina

SPECIFIC SIDE-EFFECTS

▶When used for benign prostatic hyperplasia or erectiledysfunctionDizziness.migraine.nasal congestion.visualdisturbances

▶When used for pulmonary arterial hypertensionBlurredvision.chest pain.epistaxis.facial oedema.gastro-oesophageal reflux.hypotension.increased uterinebleeding.limb pain.nasopharyngitis.palpitation.rash

priapism.rash.Stevens-Johnson syndrome.syncope

▶When used for benign prostatic hyperplasia or erectiledysfunctionAbdominal pain.increased sweating.

seizures.serious cardiovascular events.transientamnesia

▶When used for pulmonary arterial hypertensionJohnson syndrome.stroke.visual field defect

Stevens-lPREGNANCYManufacturer advises avoid

lBREAST FEEDINGManufacturer advises avoid—present inmilk in animal studies

lHEPATIC IMPAIRMENTWhen used for pulmonary arterialhypertension use initial dose of20mg once daily in mild

to moderate impairment and avoid in severe impairment.Use maximum dose of10mg in erectile dysfunction andbenign prostatic hyperplasia Manufacturer advisescaution in severe impairment and for regular once-dailydosing in erectile dysfunction and benign prostatichyperplasia—no information available

lRENAL IMPAIRMENTIn pulmonary arterial hypertensionfor patients with mild to moderate impairment, initiallyuse20mg once daily, increased to40mg once daily iftolerated; avoid in severe impairment For erectiledysfunction and benign prostatic hyperplasia, maximumdose10mg if eGFR less than30mL/minute/1.73m2(avoid regular once-daily dosing)

lNATIONAL FUNDING/ACCESS DECISIONSScottish Medicines Consortium (SMC) DecisionsThe Scottish Medicines Consortium has advised (June2012)that tadalafil (Adcirca®) should be initiated only byspecialists in the Scottish Pulmonary Vascular Unit orother similar specialists

NHS restrictionsCialis®is not prescribable under the NHSfor treatment of erectile dysfunction except in men whomeet the criteria listed in part XVIIIB of the Drug Tariff(Part XIb of the Northern Ireland Drug Tariff, Part12of

7

Trang 35

the Scottish Drug Tariff) The prescription must be

endorsed’SLS’ For more information see Prices in the

BNF, under How to use BNF publications p xi

lMEDICINAL FORMS

Tablet

▶Adcirca(Eli Lilly and Company Ltd)

Tadalafil 20 mg Adcirca20mg tablets|56tabletP£491.22

▶Cialis(Eli Lilly and Company Ltd)

Tadalafil 2.5 mg Cialis2.5mg tablets|28tabletP£54.99DT

BY MOUTH USING TABLETS

▶Adult:Initially10mg (max per dose20mg), to be

taken approximately25–60minutes before sexual

activity, subsequent doses adjusted according to

response, onset of effect may be delayed if taken with

high-fat meal; maximum1dose per day

BY MOUTH USING ORODISPERSIBLE TABLET

▶Adult:10mg, to be taken approximately

25–60minutes before sexual activity; maximum10mg

per day

Erectile dysfunction (patients on alpha-blocker therapy)

BY MOUTH USING TABLETS

▶Adult:Initially5mg (max per dose20mg), to be taken

approximately25–60minutes before sexual activity,

subsequent doses adjusted according to response,

onset of effect may be delayed if taken with high-fat

meal; maximum1dose per day

Concomitant treatment with phosphodiesterase type-5

inhibitor and an alpha-blocker can increase the risk of

postural hypotension—initiate treatment with a

phosphodiesterase type-5inhibitor (at a low dose) only

once the patient is stable on the alpha-blocker

Dose equivalence and conversion

Levitra®10mg orodispersible tablets and Levitra®10mg

film coated tablets are not bioequivalent

lCONTRA-INDICATIONSAvoid if systolic blood pressure

below90mmHg.hereditary degenerative retinal

disorders.myocardial infarction.patients in whom

vasodilation or sexual activity are inadvisable.previous

history of non-arteritic anterior ischaemic optic

neuropathy.recent stroke.unstable angina

lCAUTIONSActive peptic ulceration.anatomical

deformation of the penis (e.g angulation, cavernosal

fibrosis, Peyronie’s disease).bleeding disorders.

cardiovascular disease.elderly.left ventricular outflow

obstruction.predisposition to priapism (e.g in sickle-cell

disease, multiple myeloma, or leukaemia).susceptibility

to prolongation of QT interval

lINTERACTIONS→ Appendix1(vardenafil)

Caution with concomitant use of drugs which prolong QT

interval Avoid concomitant use of nitrates

lSIDE-EFFECTS

▶Common or very commonBack pain.dizziness.dyspepsia.

flushing.headache.migraine.myalgia.nasal congestion

▶UncommonDrowsiness.dyspnoea.epistaxis.

hypertension.hypotension.increased lacrimation.

painful red eyes.palpitation.photosensitivity.

tachycardia

▶RareAnxiety.facial oedema.hypersensitivity reactions.

hypertonia.priapism.raised intra-ocular pressure.rash.

Stevens-Johnson syndrome.syncope.transient amnesia

non-arteritic anterior ischaemic optic neuropathy (stopdrug if sudden visual impairment occurs).retinal vascularocclusion.seizures.serious cardiovascular events.

sudden hearing loss (discontinue drug and seek medicaladvice).unstable angina

lHEPATIC IMPAIRMENTInitial dose5mg in mild tomoderate impairment, increased subsequently according

to response (max.10mg in moderate impairment)

Manufacturer advises avoid in severe impairment

Orodispersible tablets not suitable for patients withmoderate hepatic impairment

lRENAL IMPAIRMENTInitial dose5mg if eGFR less than

30mL/minute/1.73m2 Orodispersible tablets not suitable

if eGFR less than30mL/minute/1.73m2

lPRESCRIBING AND DISPENSING INFORMATIONOrodispersible tablets not suitable for initiation oftherapy in patients taking alpha-blockers

lNATIONAL FUNDING/ACCESS DECISIONSScottish Medicines Consortium (SMC) DecisionsThe Scottish Medicines Consortium has advised (September

2011) that vardenafil orodispersible tablets (Levitra®) areaccepted for restricted use within NHS Scotland for menfor whom an orodispersible tablet is an appropriateformulation

NHS restrictionsLevitra®is not prescribable under theNHS for the treatment of erectile dysfunction except inmen who meet the criteria listed in part XVIIIB of theDrug Tariff (Part XIb of the Northern Ireland Drug Tariff,Part12of the Scottish Drug Tariff) The prescription must

be endorsed’SLS’ For more information see Prices in theBNF, under How to use BNF publications p xi

Tablet

▶Levitra(Bayer Plc)Vardenafil (as Vardenafil hydrochloride trihydrate) 5 mg Levitra

5mg tablets|4tabletP£7.56DT price = £7.56|8tabletP

£15.12Vardenafil (as Vardenafil hydrochloride trihydrate)

10 mg Levitra10mg tablets|4tabletP£14.08DT price =

£14.08|8tabletP£28.16Vardenafil (as Vardenafil hydrochloride trihydrate)

20 mg Levitra20mg tablets|4tabletP£23.48DT price =

£23.48|8tabletP£46.96Orodispersible tabletEXCIPIENTS:May contain Aspartame

▶Levitra(Bayer Plc)Vardenafil (as Vardenafil hydrochloride trihydrate)

10 mg Levitra10mg orodispersible tablets (sugar-free)|

4tabletP£17.88DT price = £17.88PROSTAGLANDINS (ERECTILE DYSFUNCTION) Alprostadil

INDICATIONS AND DOSEErectile dysfunction (initiated under specialist supervision)

BY URETHRAL APPLICATION

▶Adult:Initially250micrograms, adjusted according toresponse; usual dose0.125–1mg; maximum2dosesper day; maximum7doses per week continued→

7

Trang 36

Aid to diagnosis of erectile dysfunction

BY URETHRAL APPLICATION

▶Adult:500micrograms for1dose

TO THE SKIN

▶Adult:Apply300micrograms, to the tip of the penis,

5–30minutes before sexual activity; max1dose in

24hours not more than2–3times per week

VIRIDAL®DUO STARTER PACK

Neurogenic erectile dysfunction

BY INTRACAVERNOSAL INJECTION

▶Adult:Initially2.5micrograms, increased in steps of

2.5–5micrograms, to obtain dose suitable for

producing erection not lasting more than1hour;

usual dose10–20micrograms (max per dose

40micrograms), maximum frequency of injection not

more than2–3times per week with at least24hour

interval between injections; reduce dose if erection

lasts longer than2hours

▶Adult:Initially5micrograms, increased in steps of

2.5–5micrograms, to obtain dose suitable for

producing erection not lasting more than1hour;

usual dose10–20micrograms (max per dose

40micrograms), maximum frequency of injection not

more than2–3times per week with at least24hour

interval between injections; reduce dose if erection

lasts longer than2hours

CAVERJECT®DUAL CHAMBER

▶Adult:Initially2.5micrograms for1dose (first dose),

followed by5micrograms for1dose (second dose), to

be given if some response to first dose, alternatively

7.5micrograms for1dose (second dose), to be given if

no response to first dose, then increased in steps of

5–10micrograms, to obtain a dose suitable for

producing erection lasting not more than1hour; if no

response to dose then next higher dose can be given

within1hour, if there is a response the next dose

should not be given for at least24hours; usual dose

5–20micrograms (max per dose60micrograms),

maximum frequency of injection not more than

3times per week with at least24hour interval

between injections

Erectile dysfunction associated with neurological

dysfunction

▶Adult:Initially1.25micrograms for1dose (first dose),

then2.5micrograms for1dose (second dose), then

5micrograms for1dose (third dose), increased in

steps of5–10micrograms, to obtain a dose suitable for

producing erection lasting not more than1hour; if no

response to dose then next higher dose can be given

within1hour, if there is a response the next dose

should not be given for at least24hours; usual dose

5–20micrograms (max per dose60micrograms),

maximum frequency of injection not more than

3times per week with at least24hour interval

▶Adult:Initially5micrograms (max per dose

10micrograms) for1dose, (consult product literature)

CAVERJECT®Erectile dysfunction

▶Adult:Initially2.5micrograms for1dose (first dose),followed by5micrograms for1dose (second dose), to

be given if some response to first dose, alternatively

7.5micrograms for1dose (second dose), to be given if

no response to first dose, then increased in steps of

5–10micrograms, to obtain a dose suitable forproducing erection lasting not more than1hour; if noresponse to dose then next higher dose can be givenwithin1hour, if there is a response the next doseshould not be given for at least24hours; usual dose

5–20micrograms (max per dose60micrograms),maximum frequency of injection not more than

3times per week with at least24hour intervalbetween injections

Erectile dysfunction associated with neurologicaldysfunction

5–20micrograms (max per dose60micrograms),maximum frequency of injection not more than

3times per week with at least24hour intervalbetween injections

▶Adult:Initially5micrograms (max per dose

10micrograms) for1dose (consult product literature)VIRIDAL®DUO CONTINUATION PACK

▶Adult:Initially5micrograms, increased in steps of

2.5–5micrograms, to obtain dose suitable forproducing erection not lasting more than1hour;usual dose10–20micrograms (max per dose

40micrograms), maximum frequency of injection notmore than2–3times per week with at least24hourinterval between injections; reduce dose if erectionlasts longer than2hours

Neurogenic erectile dysfunction

▶Adult:Initially2.5micrograms, increased in steps of

2.5–5micrograms, to obtain dose suitable forproducing erection not lasting more than1hour;usual dose10–20micrograms (max per dose

40micrograms), maximum frequency of injection notmore than2–3times per week with at least24hourinterval between injections; reduce dose if erectionlasts longer than2hours

lCONTRA-INDICATIONSGENERAL CONTRA-INDICATIONSNot for use in patients with penile implants or whensexual activity medically inadvisable (e.g orthostatichypotension, myocardial infarction, and syncope).not foruse with other agents for erectile dysfunction.

predisposition to prolonged erection (as inthrombocythemia, polycythemia, sickle cell anaemia,

7

Trang 37

multiple myeloma or leukaemia).urethral application

contra-indicated in balanitis.urethral application

contra-indicated in severe curvature.urethral application

contra-indicated in severe hypospadia.urethral

application contra-indicated in urethral stricture.

urethral application contra-indicated in urethritis

▶With topical useBalanitis.severe curvature.severe

hypospadia.urethral stricture.urethritis

lCAUTIONSAnatomical deformations of penis (painful

erection more likely)—follow up regularly to detect signs

of penile fibrosis (consider discontinuation if angulation,

cavernosal fibrosis or Peyronie’s disease develop).

priapism (patients should be instructed to report any

erection lasting 4 hours or longer)

lINTERACTIONS→ Appendix1(alprostadil)

lSIDE-EFFECTS

▶Common or very commonDizziness.haematoma.

haemosiderin deposits.headache.hypertension.

hypotension.influenza-like syndrome.injection site

reactions.other localised pain (buttocks, leg, testicular,

abdominal).penile fibrosis.penile oedema.penile pain.

penile rash.urethral bleeding.urethral burning

▶UncommonAbnormal ejaculation.asthenia.balantitis.

dry mouth.haematuria.irritation.leg cramps.local

reactions.micturation difficulties.mydriasis.nausea.

pelvic pain.penile numbness or sensitivity.penile

warmth.phimosis.priapism.pruritus.rapid pulse.

scrotal erythema.scrotal oedema.scrotal pain.

supraventricular extrasystole.sweating.syncope.

testicular oedema.testicular thickening.urethral

stenosis.vasodilatation

▶RareAnaphylaxis.erythema.hypersensitivity reactions.

rash.urinary-tract infection.urticaria.vertigo

lCONCEPTION AND CONTRACEPTION

▶With urethral useIf partner is pregnant, barrier

contraception should be used No evidence of harm to

latex condoms and diaphragms

▶With topical useCondoms should be used to avoid exposure

to women of child-bearing age, pregnant or lactating

women No evidence of harm to latex condoms

▶With intracavernosal useThe first dose of the

intracavernosal injection must be given by medically

trained personnel; self-administration may only be

undertaken after proper training

▶With urethral useDuring initiation of treatment the

urethral application should be used under medical

supervision; self-administration may only be undertaken

after proper training

lPATIENT AND CARER ADVICEPatients should be instructed

to report any erection lasting4hours or longer

▶With topical useCounsel patients that condoms should be

used to avoid local reactions and exposure of alprostadil

to women of childbearing age, pregnant, or lactating

women

NHS restrictionsCaverject®, Viridal®Duo, Vitaros®and

MUSE®are not prescribable under the NHS for treatment

of erectile dysfunction except in men who meet the

criteria listed in part XVIIIB of the Drug Tariff (Part XIb of

the Northern Ireland Drug Tariff, Part12of the Scottish

Drug Tariff) The prescription must be endorsed’SLS’ For

more information see Prices in the BNF, under How to use

BNF publications p xi

lMEDICINAL FORMS

Powder and solvent for solution for injection

▶Caverject(Pfizer Ltd)Alprostadil 5 microgram Caverject5microgram powder and solventfor solution for injection vials|1vialP£7.73DT price = £7.73Alprostadil 10 microgram Caverject10microgram powder andsolvent for solution for injection vials|1vialP£9.24DT price =

£9.24Caverject Dual Chamber10microgram powder and solvent forsolution for injection|2pre-filled disposable injectionP£14.70Alprostadil 20 microgram Caverject Dual Chamber20microgrampowder and solvent for solution for injection|2pre-filled disposableinjectionP£19.00

Caverject20microgram powder and solvent for solution for injectionvials|1vialP£11.94DT price = £11.94

Alprostadil 40 microgram Caverject40microgram powder andsolvent for solution for injection vials|1vialP£21.58DT price =

£21.58

▶Viridal(UCB Pharma Ltd)Alprostadil 10 microgram Viridal Duo Starter Pack10microgrampowder and solvent for solution for injection cartridges with device|

2cartridgeP£20.13(Hospital only)Viridal Duo Continuation Pack10microgram powder and solvent forsolution for injection cartridges|2cartridgeP£16.55Alprostadil 20 microgram Viridal Duo Starter Pack20microgrampowder and solvent for solution for injection cartridges with device|

2cartridgeP£24.54(Hospital only)Viridal Duo Continuation Pack20microgram powder and solvent forsolution for injection cartridges|2cartridgeP£21.39Alprostadil 40 microgram Viridal Duo Starter Pack40microgrampowder and solvent for solution for injection cartridges with device|

2cartridgeP£29.83(Hospital only)Viridal Duo Continuation Pack40microgram powder and solvent forsolution for injection cartridges|2cartridgeP£27.22Cream

▶Vitaros(Takeda UK Ltd)Alprostadil 3 mg per 1 gram Vitaros3mg/g cream|

4applicatorP£40.00Urethral application

▶Muse(Meda Pharmaceuticals Ltd)Alprostadil 250 microgram Muse250microgram urethral sticks|

1applicatorP£11.30DT price = £11.30|6applicatorP

£67.79Alprostadil 500 microgram Muse500microgram urethral sticks|

£67.79Alprostadil 1 mg Muse1000microgram urethral sticks|

BY MOUTH

▶Adult:Initially30mg, to be taken approximately

1–3hours before sexual activity, subsequent dosesadjusted according to response; review treatment after

4weeks (or6doses) and at least every6monthsthereafter, not recommended for adults65years andover; maximum1dose per day; maximum60mg per

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Premature ejaculation in men who meet all the following

criteria: poor control over ejaculation, a history of

premature ejaculation over the past6months, marked

distress or interpersonal difficulty as a consequence of

premature ejaculation, and an intravaginal ejaculatory

latency time of less than two minutes (with concomitant

aprepitant, clarithromycin, diltiazem, erythromycin,

fluconazole, fosamprenavir, and verapamil)

BY MOUTH

▶Adult:Up to30mg, to be taken approximately

1–3hours before sexual activity; review treatment

after4weeks (or6doses) and at least every6months

thereafter, not recommended for adults65years and

over; maximum1dose per day

Max single dose30mg with concomitant aprepitant,

clarithromycin, diltiazem, erythromycin, fluconazole,

fosamprenavir, and verapamil

Use60-mg dose with caution with concomitant potent

inhibitors of cytochrome P450enzyme CYP2D6

lCONTRA-INDICATIONSHistory of bipolar disorder.history

of mania.history of severe depression.history of syncope

.significant cardiac disease.uncontrolled epilepsy

lCAUTIONSBleeding disorders.epilepsy (discontinue if

convulsions develop).susceptibility to angle-closure

glaucoma

lINTERACTIONS→ Appendix1(dapoxetine)

Caution with concomitant use of drugs that increase risk

of bleeding

lSIDE-EFFECTS

▶Common or very commonAbdominal distension.

abdominal pain.abnormal dreams.agitation.anxiety.

constipation.diarrhoea.dizziness.drowsiness.dry

mouth.dyspepsia.flushing.headache.hypertension.

impaired attention.irritability.malaise.nausea.

paraesthesia.sexual dysfunction.sleep disturbances.

sweating.tinnitus.tremor.visual disturbances.vomiting

▶UncommonAbnormal thoughts.bradycardia.bruxism.

confusion.depression.eye pain.hypotension.mood

disturbances.mydriasis.postural hypotension.pruritus.

restlessness.sinus arrest.syncope.tachycardia.taste

disturbances.vertigo

▶RareDefaecation urgency.sudden onset of sleep

Discontinue if psychiatric disorder develops Avoid if

postural hypotension occurs during test dose

lHEPATIC IMPAIRMENTAvoid in moderate to severe

impairment

lRENAL IMPAIRMENTUse with caution if eGFR

30–80mL/minute/1.73m2; avoid if eGFR less than

30mL/minute/1.73m2

lPRE-TREATMENT SCREENINGTest for postural

hypotension before starting treatment

Postural hypotension and syncopePatients should be advised

to maintain hydration and to sit or lie down until prodromal

symptoms such as nausea, dizziness, and sweating abate

lMEDICINAL FORMS

Tablet

▶Priligy(A Menarini Farmaceutica Internazionale SRL)

Dapoxetine 30 mg Priligy30mg tablets|3tabletP£14.71|

p.706, ergometrine maleate p.707, and the prostaglandins.All induce uterine contractions with varying degrees of painaccording to the strength of contractions induced.Induction of abortion

Gemeprost p.709, a prostaglandin administered vaginally aspessaries, is suitable for the medical induction of latetherapeutic abortion; gemeprost is also used to ripen thecervix before surgical abortion, particularly inprimigravidas The prostaglandin misoprostol p.709isgiven by mouth, buccally, sublingually, or vaginally, toinduce medical abortion [unlicensed indication];

intravaginal use ripens the cervix before surgical abortion[unlicensed indication] Extra-amniotic dinoprostone p.706

is rarely used nowadays

Pre-treatment with mifepristone p.708can facilitate theprocess of medical abortion It sensitises the uterus tosubsequent administration of a prostaglandin and,therefore, abortion occurs in a shorter time and with a lowerdose of prostaglandin

Induction and augmentation of labourDinoprostone p.706is available as vaginal tablets, pessariesand vaginal gels for the induction of labour The

intravenous solution is rarely used; it is associated withmore side-effects

Oxytocin p.705(Syntocinon®) is administered by slowintravenous infusion, using an infusion pump, to induce oraugment labour, usually in conjunction with amniotomy.Uterine activity must be monitored carefully andhyperstimulation avoided Large doses of oxytocin mayresult in excessive fluid retention

Misoprostol p.709is given orally or vaginally for theinduction of labour [unlicensed indication]

NICE Guidance, Induction of labour (updated July2008),available atwww.nice.org.uk/guidance/CG70

Prevention and treatment of haemorrhageBleeding due to incomplete miscarriage or abortion can becontrolled with ergometrine maleate and oxytocin(Syntometrine®) given intramuscularly, the dose is adjustedaccording to the patient’s condition and blood loss This iscommonly used before surgical evacuation of the uterus,particularly when surgery is delayed Oxytocin andergometrine maleate combined are more effective in earlypregnancy than either drug alone

Active management of the third stage of labour reducesthe risk of postpartum haemorrhage; oxytocin is given byintramuscular injection [unlicensed] on delivery of theanterior shoulder or, at the latest, immediately after thebaby is delivered Alternatively, ergometrine maleate withoxytocin (Syntometrine®) can be given by intramuscularinjection in the absence of hypertension; oxytocin alonecauses less nausea, vomiting, and hypertension than whengiven with ergometrine maleate p.707

In excessive uterine bleeding, any placental productsremaining in the uterus should be removed Oxytocic drugsare used to treat postpartum haemorrhage caused byuterine atony; treatment options are as follows:

oxytocin by slow intravenous injection, followed insevere cases by intravenous infusion of oxytocin at arate that controls uterine atony or

ergometrine by intramuscular injection or

7

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ergometrine by slow intravenous injection (use with

caution—risk of hypertension) or

ergometrine with oxytocin (Syntometrine®) by

intramuscular injection

Carboprost p.706has an important role in severe

postpartum haemorrhage unresponsive to ergometrine

maleate and oxytocin

Misoprostol p.709[unlicensed] can be used in postpartum

haemorrhage when oxytocin, ergometrine maleate, and

carboprost are not available or are inappropriate

Mifepristone

For termination of pregnancy, a single dose of mifepristone

p.708is followed by administration of a prostaglandin

(gemeprost p.709or misoprostol p.709[unlicensed])

Guidelines of the Royal College of Obstetricians and

Gynaecologists (November2011) include [unlicensed]

regimens for inducing medical abortion

Myometrial relaxants

Tocolytic drugs postpone premature labour and they are

used with the aim of reducing harm to the child However,

there is no satisfactory evidence that the use of these drugs

reduces mortality The greatest benefit is gained by using

the delay to administer corticosteroid therapy or to

implement other measures which improve perinatal health

(including transfer to a unit with neonatal intensive care

facility)

The oxytocin receptor antagonist, atosiban p.708, is

licensed for the inhibition of uncomplicated premature

labour between24and33weeks of gestation Atosiban may

be preferable to a beta2agonist because it has fewer side

effects The dihydropyridine calcium-channel blocker

nifedipine p.154also has fewer side-effects than a beta2

agonist

The beta2agonists salbutamol p.222and terbutaline

sulfate p.225are licensed for inhibiting uncomplicated

premature labour between22and37weeks of gestation to

permit a delay in delivery of up to48hours Use of

high-dose short acting beta2agonists in obstetric indications has

been associated with serious, sometimes fatal

cardiovascular events in the mother and fetus, particularly

when used for a prolonged period of time Oral therapy is no

longer recommended and parenteral therapy should be

restricted to a maximum duration of48hours, given under

the supervision of a specialist, and with close monitoring

Indometacin p.929, a cyclo-oxygenase inhibitor, also

inhibits labour [unlicensed indication] and it can be useful

in situations where a beta2agonist is not appropriate;

however, there are concerns about neonatal complications

such as transient impairment of renal function and

premature closure of ductus arteriosus

5.1 Induction of labour

PROSTAGLANDINS AND OXYTOCICS

Oxytocin

Induction of labour for medical reasons| Stimulation of

labour in hypotonic uterine inertia

BY INTRAVENOUS INFUSION

▶Adult:Initially0.001–0.004units/minute, not to be

started for at least6hours after administration of

vaginal prostaglandin, dose increased at intervals of at

least30minutes until a maximum of3–4contractions

occur every10minutes (0.01units/minute is often

adequate) up to max.0.02units/minute, if regular

contractions not established after a total of5units,stop induction attempt (may be repeated next daystarting again at0.001–0.004units/minute)Caesarean section

BY SLOW INTRAVENOUS INJECTION

▶Adult:5units immediately after deliveryPrevention of postpartum haemorrhage after delivery ofplacenta

▶Adult:5units, if infusion previously used for induction

or enhancement of labour, increase rate during thirdstage and for next few hours

BY INTRAMUSCULAR INJECTION

▶Adult:10units, can be used instead of oxytocin withergometrine (Syntometrine®)

Treatment of postpartum haemorrhage

▶Adult:5units, repeated if necessaryTreatment of severe cases of postpartum haemorrhage(following intravenous injection)

▶Adult:5units, followed by (by intravenous infusion)

0.02–0.04units/minute if required, the rate of infusioncan be faster if necessary

lUNLICENSED USEOxytocin doses in the BNF may differfrom those in the product literature

Important safety informationProlonged intravenous administration at high doseswith large volume of fluid (which is possible ininevitable or missed miscarriage or postpartumhaemorrhage) may cause water intoxication withhyponatraemia To avoid: use electrolyte-containingdiluent (i.e not glucose), increase oxytocinconcentration to reduce fluid, restrict fluid intake bymouth; monitor fluid and electrolytes

lCONTRA-INDICATIONSAny condition where spontaneouslabour inadvisable.any condition where vaginal deliveryinadvisable.avoid intravenous injection during labour.

avoid prolonged administration in oxytocin-resistantuterine inertia.avoid rapid intravenous injection (maytransiently reduce blood pressure).fetal distress(discontinue immediately if this occurs).hypertonicuterine contractions (discontinue immediately if thisoccurs).severe cardiovascular disease.severe pre-eclamptic toxaemia

lCAUTIONSAvoid large infusion volumes and restrict fluidintake by mouth (risk of hyponatraemia and water-intoxication).enhancement of labour—presence ofborderline cephalopelvic disproportion (avoid ifsignificant).history of lower-uterine segment caesareansection.induction of labour—presence of borderlinecephalopelvic disproportion (avoid if significant).mildpregnancy-induced cardiac disease.mild pregnancy-induced hypertension.moderate pregnancy-inducedcardiac disease.moderate pregnancy-inducedhypertension.risk factors for disseminated intravascularcoagulation.secondary uterine inertia.women over 35years

lINTERACTIONS→ Appendix1(oxytocin)

Effects enhanced by concomitant prostaglandins (verycareful monitoring of uterine activity) Caudal blockanaesthesia (may enhance hypertensive effects ofsympathomimetic vasopressors)

7

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▶Common or very commonArrhythmia.headache.nausea.

vomiting

▶RareAnaphylactoid reactions (with dyspnoea,

hypotension, or shock).disseminated intravascular

coagulation.hyponatraemia associated with high doses

with large infusion volumes of electrolyte-free fluid.rash

.uterine hyperstimulation (usually with excessive doses—

may cause fetal distress, asphyxia, and death, or may lead

to hypertonicity, tetanic contractions, soft-tissue damage

or uterine rupture).uterine spasm (may occur at low

doses).water intoxication associated with high doses

with large infusion volumes of electrolyte-free fluid

Avoid rapid intravenous injection (may transiently reduce

blood pressure)

OverdosePlacental abruption and amniotic fluid

embolism reported on overdose

lMONITORING REQUIREMENTS

▶Careful monitoring of fetal heart rate and uterine motility

essential for dose titration

▶Monitor for disseminated intravascular coagulation after

parturition

lDIRECTIONS FOR ADMINISTRATIONFor intravenous infusion

(Syntocinon®), give continuously in Glucose5% or Sodium

chloride0.9% Preferably given via a variable-speed

infusion pump in a concentration appropriate to the

pump; if given by drip infusion for induction or

enhancement of labour, dilute5units in500mL infusion

fluid or for higher doses,10units in500mL; for treatment

of postpartum uterine haemorrhage dilute40units in

500mL; if high doses given for prolonged period (e.g for

inevitable or missed abortion or for postpartum

haemorrhage), use low volume of an

electrolyte-containing infusion fluid (not Glucose5%) given at higher

concentration than for induction or enhancement of

labour; close attention to patient’s fluid and electrolyte

status essential

lMEDICINAL FORMS

manufacturers include: solution for infusion, infusion

▶OXYTOCIN (Non-proprietary)

Oxytocin 10 unit per 1 ml Oxytocin10units/1ml concentrate for

solution for infusion ampoules|5ampouleP£4.55–£4.67

▶Syntocinon(Novartis Pharmaceuticals UK Ltd)

Oxytocin 5 unit per 1 ml Syntocinon5units/1ml solution for

injection ampoules|5ampouleP£4.01(Hospital only)

Oxytocin 10 unit per 1 ml Syntocinon10units/1ml solution for

injection ampoules|5ampouleP£4.53(Hospital only)

5.2 Postpartum haemorrhage

PROSTAGLANDINS AND OXYTOCICS

Carbetocin

Prevention of uterine atony after caesarean section

▶Adult:100micrograms for1dose, to be given over

1minute, administer as soon as possible after delivery,

preferably before removal of placenta

lCONTRA-INDICATIONSEclampsia.epilepsy.pre-eclampsia

lCAUTIONSAsthma.cardiovascular disease (avoid if

severe).hyponatraemia.migraine

lSIDE-EFFECTSAbdominal pain.anaemia.back pain.

chest pain.chills.dizziness.dyspnoea.feeling ofwarmth.flushing.headache.hypotension.metallic taste

.nausea.pruritus.sweating.tachycardia.tremor.

vomiting

lHEPATIC IMPAIRMENTManufacturer advises avoid

lRENAL IMPAIRMENTManufacturer advises avoid

▶Pabal(Ferring Pharmaceuticals Ltd)Carbetocin 100 microgram per 1 ml Pabal100micrograms/1mlsolution for injection ampoules|5ampouleP£88.20(Hospitalonly)

CarboprostINDICATIONS AND DOSEPostpartum haemorrhage due to uterine atony in patientsunresponsive to ergometrine and oxytocin

▶Adult:250micrograms at least every15minutes,repeated if necessary, total dose should not exceed

2mg (8doses)

lCONTRA-INDICATIONSCardiac disease.pulmonary disease

.untreated pelvic infection

lCAUTIONSExcessive dosage may cause uterine rupture.

history of anaemia.history of asthma.history of diabetes

.history of epilepsy.history of glaucoma.history ofhypertension.history of hypotension.history of jaundice

.history of raised intra-ocular pressure.uterine scars

lINTERACTIONS→ Appendix1(prostaglandins)

lSIDE-EFFECTSBronchospasm.cardiovascular collapse.

chills.diaphoresis.diarrhoea.dizziness.dyspnoea.

erythema at injection site.flushing.headache.

hyperthermia.nausea.pain at injection site.pulmonaryoedema.raised blood pressure.vomiting

lHEPATIC IMPAIRMENTManufacturer advises avoid

lRENAL IMPAIRMENTManufacturer advises avoid

▶Hemabate(Pfizer Ltd)Carboprost (as Carboprost trometamol) 250 microgram per 1

ml Hemabate250micrograms/1ml solution for injection ampoules|

10ampouleP£182.01(Hospital only)

DinoprostoneINDICATIONS AND DOSEPROSTIN E2®VAGINAL GELInduction of labour

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