The medical letter on drugs and therapeutics december 5 2016

1509 on Drugs and Therapeutics In Brief: PPIs and Torsades de Pointes ...p 153 Ciprofloxacin/Fluocinolone Otovel for Otitis Media with Tympanostomy Tubes ...p 153 Ameluz for Actinic Kera

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IN THIS ISSUE

ISSUE

1433

Volume 56

Published by The Medical Letter, Inc • A Nonprofi t Organization

ISSUE No

1509

on Drugs and Therapeutics

In Brief: PPIs and Torsades de Pointes p 153

Ciprofloxacin/Fluocinolone (Otovel) for Otitis Media with Tympanostomy Tubes p 153

Ameluz for Actinic Keratoses p 155

Sublingual Nitroglycerin Powder (GoNitro) p 156

In Brief: Phentermine (Lomaira) for Weight Loss p 158

Addendum: Statins for Primary Prevention of Cardiovascular Disease p 158

153

on Drugs and Therapeutics

Take CME Exams

ISSUE

1433

Volume 56

ISSUE No

1509 Ameluz for Actinic Keratoses Sublingual Nitroglycerin Powder (GoNitro) p 155p 156

In Brief: Phentermine (Lomaira) for Weight Loss p 158

Addendum: Statins for Primary Prevention of Cardiovascular Disease p 158

ALSO IN THIS ISSUE

IN BRIEF

PPIs and Torsades de Pointes

The Arizona Center for Education and Research on

Therapeutics (AZCERT) has recently added the proton

pump inhibitors (PPIs) omeprazole (Prilosec, and others),

esomeprazole (Nexium, and others), lansoprazole

(Prevacid, and others), and pantoprazole (Protonix, and

generics) to its lists of Drugs with Conditional Risk of

Torsades de Pointes (TdP) and Drugs to Avoid in Patients

with Congenital Long QT Syndrome 1

PPIs do not directly cause prolongation of the QT interval,

but they can cause hypomagnesemia, which is often

accompanied by hypocalcemia and hypokalemia and can

result in cardiac repolarization disturbances such as QT

interval prolongation 2 Reports have described cases of QT

interval prolongation and TdP associated with severe

PPI-induced hypomagnesemia 3,4 TdP has also been reported in

patients taking a PPI concomitantly with drugs that directly

prolong the QT interval 5,6 The newer PPIs dexlansoprazole

(Dexilant) and rabeprazole (Aciphex, and generics) have not

been linked to QT interval prolongation or TdP to date, but

they can cause hypomagnesemia.

Serum magnesium levels should be monitored periodically

in patients taking a PPI for an extended period of time

(>2 weeks) If possible, extended PPI therapy should be

avoided in patients who require treatment with drugs

that carry a known risk of TdP 7 and in those with long QT

syndrome If extended PPI therapy must be used with a

drug that prolongs the QT interval, close monitoring of

magnesium levels and the QT interval is recommended ■

1 AZCERT New drugs added to CredibleMeds drugs lists November

2, 2016 Available at:

www.crediblemeds.org/blog/news-drugs-added-qtdrugs-lists Accessed November 22, 2016.

2 In brief: PPIs and hypomagnesemia Med Lett Drugs Ther 2011;

53:25.

3 EJ Hoorn et al A case series of proton pump inhibitor-induced

hy-pomagnesemia Am J Kidney Dis 2010; 56:112.

4 BA Hansen and Ø Bruserud Hypomagnesemia as a potentially

life-threatening adverse effect of omeprazole Oxf Med Case Reports

2016; 2016:147.

5 H Asajima et al Lansoprazole precipitated QT prolongation and

tor-sade de pointes associated with disopyramide Eur J Clin

Pharma-col 2012; 68:331.

6 JN Bibawy et al Pantoprazole (proton pump inhibitor) contributing

to torsades de pointes storm Circ Arrhythm Electrophysiol 2013;

6:e17.

7 RL Woosley and KA Romero QT drugs list Available at:

www.credi-blemeds.org Accessed November 22, 2016.

The FDA has approved Otovel (Arbor), a combination

of the fluoroquinolone antibiotic ciprofloxacin 0.3% and the corticosteroid fluocinolone acetonide 0.025%, for otic treatment of acute otitis media with tympanostomy tubes (AOMT) in children ≥6 months old It is the second fluoroquinolone/corticosteroid combination

to be approved for this indication; ciprofloxacin 0.3%/

dexamethasone 0.1% (Ciprodex) has been available

for many years In December 2015, a suspension

of ciprofloxacin 6% (Otiprio) was approved for otic

treatment of bilateral otitis media with effusion in children undergoing tympanostomy tube placement.1

Ciprofloxacin/Fluocinolone

(Otovel) for Otitis Media with

Tympanostomy Tubes

▶

Pronunciation Key Ciprofloxacin: sip” roe flox’ a sin Otovel: oh' toe vel

Fluocinolone acetonide: floo” oh sin’ oh lone a seet’ oh nide

STANDARD TREATMENT — Insertion of tympanostomy

tubes is a common surgical procedure for children who experience recurrent acute otitis media or otitis media with effusion Otorrhea, primarily due to bacterial infection, is the most common complication of tympanostomy tubes.Topical antibiotics are preferred over oral antibiotics for treatment of uncomplicated acute tympanostomy tube otorrhea because they have been shown to be more effective, safer, and less likely

to promote bacterial resistance.2 Addition of topical corticosteroids may increase cure rates.3

MECHANISM OF ACTION — Ciprofloxacin is active

against most strains of the pathogens that typically

cause AOMT, including Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Staph-ylococcus aureus, and Pseudomonas aeruginosa.2 Corticosteroids such as fluocinolone acetonide have anti-inflammatory effects that can reduce middle ear secretions

PHARMACOKINETICS — Analyses of blood samples

from 30 children 6 months to 12 years old with AOMT

who were treated with Otovel for 7 days in the clinical

trials found detectable plasma concentrations of

ciprofloxacin in only one sample, which was taken from

a patient with bilateral AOMT; all of the other samples

were from children with unilateral AOMT Fluocinolone

acetonide was not detected in any blood samples

CLINICAL STUDIES — Ciprofloxacin 0.3%/fluocinolone

acetonide 0.025% was compared to its individual

components in two unpublished, randomized,

double-blind trials (summarized in the package insert) in 662

patients 6 months to 12 years old with AOMT The

median duration of treatment was 7 days In both

trials, the median time to cessation of otorrhea (the

primary endpoint) was signifi cantly shorter with the

combination than with ciprofloxacin or fluocinolone

acetonide alone Signifi cantly more patients treated

with ciprofloxacin/fluocinolone acetonide had no

otorrhea by day 22 compared to those who received

either drug alone (Table 1)

Table 1 AOMT Clinical Trials

Median Time Otorrhea Drug to Cessation Cessation Rate

Trial 1 (n=331)

Ciprofloxacin/ 3.75 days* 79%*

fluocinolone acetonide

Ciprofloxacin 7.69 days 67%

Fluocinolone acetonide N.R 48%

Trial 2 (n=331)

Ciprofloxacin/ 4.94 days* 78%*

fluocinolone acetonide

Ciprofloxacin 6.83 days 69%

Fluocinolone acetonide N.R 44%

N.R = No results available because the number of patients with otorrhea

exceeded the number without otorrhea at day 22

* Statistically signifi cant difference vs ciprofloxacin or fluocinolone acetonide

alone.

Table 2 Some Otic Fluoroquinolone Products for Otitis Media

Ciprofloxacin 6% – Otiprio2 (Otonomy) 60 mg/1 mL single-use vial 3 0.1 mL in each ear once, intratympanically $283.20 Ciprofloxacin 0.3%/dexamethasone 0.1% – 7.5 mL bottle 4 drops in affected ear bid x 7 days

Ciprofloxacin 0.3%/fluocinolone acetonide 0.025% – 0.25 mL single-dose vial 5 0.25 mL in affected ear bid x 7 days

Ofloxacin 0.3% 4 – generic 5, 10 mL bottles 5 drops in affected ear bid x 10 days 131.50

1 Approximate WAC for the smallest-size bottle or vial WAC = wholesaler acquisition cost or manufacturer’s published price to wholesalers; WAC represents

a published catalogue or list price and may not represent an actual transactional price Source: AnalySource® Monthly November 5, 2016 Reprinted with permission by First Databank, Inc All rights reserved ©2016 www.fdbhealth.com/policies/drug-pricing-policy.

2 FDA-approved for treatment of children with bilateral otitis media with effusion who are undergoing tympanostomy tube placement.

3 Includes suffi cient syringes and needles to treat both ears.

4 FDA-approved for treatment of acute otitis media in children with tympanostomy tubes Ciprodex is also approved for treatment of acute otitis externa

Ofloxacin 0.3% is also approved for treatment of otitis externa and of chronic suppurative otitis media in patients with perforated tympanic membranes

5 Sold in cartons containing 14 single-dose vials.

In another trial, 590 patients ≥7 years old with diffuse

otitis externa (swimmer’s ear) were randomized

to combination treatment with ciprofloxacin 0.3%/ fluocinolone acetonide 0.025% or to ciprofloxacin 0.3% monotherapy.4 The dosage for both treatments was 4-6 drops instilled into the ear canal every 8 hours for 8 days Clinical cure (score of 0 for symptoms of otalgia, edema, and otorrhea at the end of treatment), the primary endpoint, was reported in 80% of patients who received ciprofloxacin/fluocinolone acetonide, compared to 71% of those who received ciprofloxacin alone, a statistically signifi cant difference The combination has not been approved by the FDA for treatment of acute otitis externa

ADVERSE EFFECTS — Both ciprofloxacin and

fluocino-lone acetonide are well tolerated when administered topically Use of the combination is contraindicated in patients with viral or fungal infections of the external ear canal

PREGNANCY AND LACTATION — Systemic absorption

of ciprofloxacin/fluocinolone acetonide following otic administration is negligible Use of the combination is not expected to result in exposure of the fetus or the breastfed infant to either drug

DOSAGE AND ADMINISTRATION — Otovel is available

in single-dose vials that deliver the equivalent of ciprofloxacin 0.75 mg and fluocinolone acetonide 0.0625 mg in 0.25 mL of solution The recommended dosage is instillation of one vial into the affected ear(s) twice daily for 7 days To prevent dizziness resulting

from instillation of a cold solution, Otovel vials should

be warmed by holding them in the palm of the hand for 1-2 minutes before use With the child's head tilted

to the side, the caregiver should empty the contents

of the vial into the affected ear and press the tragus

4 times with a pumping motion to aid delivery of the

drug to the middle ear The child should not move his

or her head for 1 minute after administration

CONCLUSION — An otic solution containing

cipro-floxacin 0.3% and fluocinolone acetonide 0.025%

(Otovel) is more effective than either of its components

alone in decreasing otorrhea in children with acute

otitis media with tympanostomy tubes How it

compares with other otic fluoroquinolone products for

this indication remains to be determined ■

1 Ciprofloxacin (Otiprio) for tympanostomy tube insertion Med Lett Drugs Ther 2016; 58:69.

2 RM Rosenfeld et al Clinical practice guideline: tympanostomy tubes in children Otolaryngol Head Neck Surg 2013; 149 (1 Suppl):S1.

3 J Chee et al Topical versus oral antibiotics, with or without cor-ticosteroids, in the treatment of tympanostomy tube otorrhea Int J Pediatr Otorhinolaryngol 2016; 86:183.

4 J Lorente et al Ciprofloxacin plus fluocinolone acetonide ver-sus ciprofloxacin alone in the treatment of diffuse otitis

exter-na J Laryngol Otol 2014; 128:591.

Ameluz for Actinic Keratoses

▶

The FDA has approved a 10% nanoemulsion gel

formulation of the porphyrin-based photosensitizer

aminolevulinic acid hydrochloride (ALA; Ameluz –

Biofrontera) for use in combination with a narrowband

red light photodynamic therapy (PDT) lamp

(BF-RhodoLED) for treatment of actinic keratoses (AKs)

of mild to moderate severity on the face and scalp

A 20% ALA solution (Levulan Kerastick) approved for

use in combination with blue light PDT (BLU-U) has

been available in the US since 2002.1

Pronunciation Key

Aminolevulinic acid: a mee" noe lev" ue lin' ik as' id

Ameluz: am' e looz"

ACTINIC KERATOSES — Common in older,

lighter-skinned persons with a long history of sun exposure,

AKs are gritty, scaly, red- or flesh-colored papules or

plaques caused by UV radiation-induced abnormal

keratinocyte proliferation AKs commonly regress

and reappear, and most only cause cosmetic harm,

but they are considered precancerous with a risk of

progression to squamous cell carcinoma.2

STANDARD TREATMENT — Few studies directly

comparing the various treatments for AKs are

available Liquid nitrogen cryosurgery is the most

commonly used technique; it is effective, but can

cause hypopigmentation Field therapy with topical

fluorouracil (5-FU) or imiquimod (Aldara, Zyclara, and

generics) is effective, but requires weeks to months

of treatment and can cause disfi guring erythema,

vesicles, and ulceration Topical ingenol mebutate

gel (Picato) is also effective and requires only 2-3

days of treatment Ingenol can cause severe local reactions, which are usually of shorter duration than those caused by 5-FU or imiquimod; it has also been associated with severe allergic reactions, including anaphylaxis, and with herpes zoster reactivation

Diclofenac gel (Solaraze) is relatively well tolerated

but only modestly effective, and requires months

of application Use of Levulan Kerastick and BLU-U

is highly effective and well tolerated, with skin inflammation usually lasting only about a week after treatment.2-5

MECHANISM — ALA is a prodrug that is metabolized

to protoporphyrin IX (PpIX) when applied to skin under occlusion Activation of PpIX by red light causes formation of reactive oxygen species that damage and destroy the treated cells

CLINICAL STUDIES — FDA approval of Ameluz and the

BF-RhodoLED lamp was based on three randomized

trials including a total of 299 patients with 4-8 mild

to moderate AK lesions on the face, forehead, or scalp who received red light treatment with either ALA or the drug vehicle Complete clearance of AK lesions

12 weeks after the last treatment, the primary endpoint, occurred in 183 of 212 patients (86%) who received ALA and in 14 of 87 patients (16%) who received the vehicle alone.6-8

In a follow-up study that included responders from two of the trials, 69% and 53% of those who had

Table 1 Aminolevulinic Acid (ALA) Formulations

PDT = photodynamic therapy

1 Approximate WAC for one dosage unit Cost of PDT not included WAC = wholesaler acquisition cost or manufacturer’s published price to wholesalers; WAC represents a published catalogue or list price and may not represent an actual transactional price Source: AnalySource® Monthly November 5, 2016 Re-printed with permission by First Databank, Inc All rights reserved ©2016 www.fdbhealth.com/policies/drug-pricing-policy.

1 New treatments for actinic keratoses Med Lett Drugs Ther 2002; 44:57.

2 JA Siegel et al Current perspective on actinic keratosis: a re-view Br J Dermatol 2016 August 8 (epub).

3 B Berman et al Pharmacotherapy of actinic keratosis Expert Opin Pharmacother 2009; 10:3015.

4 Ingenol mebutate (Picato) for actinic keratoses Med Lett Drugs Ther 2012; 54:35.

5 FDA Drug Safety Communication: FDA warns of severe adverse events with application of Picato (ingenol mebutate) gel for skin conditions requires label changes Available at: www.fda.gov/ Drugs/DrugSafety/ucm459142.htm Accessed November 22, 2016.

6 RM Szeimies et al Photodynamic therapy with BF-200 ALA for the treatment of actinic keratosis: results of a prospective, ran-domized, double-blind, placebo-controlled phase III study Br J Dermatol 2010; 163:386

7 T Dirschka et al Photodynamic therapy with BF-200 ALA for the treatment of actinic keratosis: results of a multicentre, ran-domized, observer-blind phase III study in comparison with a registered methyl-5-aminolaevulinate cream and placebo Br J Dermatol 2012; 166:137.

8 U Reinhold et al A randomized, double-blind, phase III, mul-ticentre study to evaluate the safety and effi cacy of BF-200 ALA (Ameluz®) vs placebo in the fi eld-directed treatment of mild-to-moderate actinic keratosis with photodynamic

thera-py (PDT) when using the BF-RhodoLED® lamp Br J Dermatol 2016; 175:696.

9 T Dirschka et al Long-term (6 and 12 months) follow-up of two prospective, randomized, controlled phase III trials of photody-namic therapy with BF-200 ALA and methyl aminolaevulinate for the treatment of actinic keratosis Br J Dermatol 2013; 168:825.

10 AK Gupta and M Paquet Network meta-analysis of the out-come ‘participant complete clearance’ in nonimmunosup-pressed participants of eight interventions for actinic keratosis:

a follow-up on a Cochrane review Br J Dermatol 2013; 169:250.

11 S Vegter and K Tolley A network meta-analysis of the relative effi cacy of treatments for actinic keratosis of the face or scalp

in Europe PLoS One 2014; 9:e96829.

received ALA and red light PDT remained completely

clear for 12 months after the last treatment.9

In one network meta-analysis, 5-FU was found to

have the highest rate of complete clearance, followed

by ALA/PDT and then imiquimod.10 In another, which

distinguished between ALA dosage forms, Ameluz had

better clearance rates than 5-FU, and imiquimod had

better rates than Levulan Kerastick.11

ADVERSE EFFECTS — Application-site erythema,

pain/burning, and irritation occurred in most patients

receiving ALA/PDT in the randomized clinical trials;

30% of patients reported severe pain/burning Other

application-site adverse effects reported in ≥10%

of patients receiving the active treatment and more

frequently than with the vehicle included edema,

pruritus, scabbing, exfoliation, induration, and

vesicles Most reactions were mild to moderate in

severity and lasted for 1-4 days, but some persisted

for >2 weeks

Patients treated with ALA gel should avoid exposure to

sunlight for 48 hours after application Eyelid edema

and mucous membrane inflammation can occur

Patients with coagulation disorders were excluded

from clinical trials Practitioners should take care

to avoid bleeding during preparation of lesions for

treatment, and bleeding must be stopped before the

gel is applied

DRUG INTERACTIONS — Concomitant use of

photosensitizing drugs such as thiazide diuretics,

fluoroquinolones, or tetracyclines could exacerbate

the phototoxic effect of PDT

DOSAGE AND ADMINISTRATION — Ameluz is

supplied in 2-g tubes, which should be refrigerated

and used within 12 weeks after opening A 1-mm

layer of gel should be applied to the affected lesions

or field and to a 5-mm radius of surrounding skin,

avoiding the eyes, nose, mouth, and ears No more

than 2 g of gel should be applied per treatment

After allowing the gel to dry for 10 minutes, the

treated areas should be occluded for 3 hours and

then illuminated with the BF-RhodoLED lamp, which

delivers 37 J/cm2 of red light (~635 nm) within

10 minutes Both the patient and the provider must

wear protective eye equipment during PDT Lesions

that have not resolved may be retreated once,

3 months after the initial dose

CONCLUSION — The combination of the new gel

formulation of aminolevulinic acid (Ameluz) and red

light photodynamic therapy is effective for treatment

of actinic keratoses on the face and scalp and better tolerated than 5-FU or imiquimod Whether it offers

any advantage over Levulan Kerastick, an older

aminolevulinic acid formulation that uses blue light photodynamic therapy, remains to be established ■

Sublingual Nitroglycerin

Powder (GoNitro)

▶

The FDA has approved a sublingual powder formulation

of nitroglycerin (GoNitro – Espero) for prevention

or acute relief of an attack of angina pectoris It

is the fi rst powder formulation of nitroglycerin to become available in the US Most patients with

angina use sublingual nitroglycerin tablets (Nitrostat,

and generics) Translingual spray formulations of

nitroglycerin (NitroMist, Nitrolingual Pumpspray, and

generics) are also available.1

CLINICAL STUDIES — In an unpublished, randomized,

double-blind, crossover trial in 51 patients with

exertional angina pectoris (summarized in the

package insert), doses of nitroglycerin powder

ranging from 200-1600 mcg pro duced significant,

dose-related increases in exercise tolerance,

time to onset of angina, and time to ST-segment

depression, compared to placebo No clinical

studies comparing nitroglycerin sublingual powder

with other formulations of the drug are available

ADVERSE EFFECTS — As with other nitroglycerin

formulations, headache (which may be severe and

persistent), flushing, dizziness, postural hypotension,

and paresthesia can occur with use of nitroglycerin

sublingual powder

DRUG INTERACTIONS — Concurrent use of nitroglycerin

with antihypertensive drugs can result in additive

hypotensive effects Phosphodiesterase type 5

(PDE-5) inhibitors such as sildenafi l (Revatio, and generics;

Viagra) prevent the breakdown of cyclic guanosine

monophosphate (cGMP), prolonging nitrate-induced

vasodilation and hypotension; their use with nitroglycerin

is contraindicated

Use of nitroglycerin with ergot derivatives should be

avoided because nitroglycerin can decrease fi rst-pass

metabolism of dihydroergotamine and ergotamine can

precipitate angina pectoris

DOSAGE AND ADMINISTRATION — GoNitro is

supplied in single-use packets containing 0.4 mg

of nitroglycerin The packets should be stored at

room temperature

At the onset of an anginal attack, the contents of one

or two packets should be placed under the tongue

and allowed to dissolve, preferably with the patient

Table 1 Some Nitroglycerin Formulations

Sublingual powder – GoNitro (Espero) 0.4 mg single-use packets 7 min 1-2 packets, then $653.30

(12, 36, 96 packets/box) 1 packet q5 min PRN Sublingual tablets – generic 0.3, 0.4, 0.6 mg tabs 6.4-7.2 min 0.3-0.6 mg q5 min PRN 38.20

Nitrostat (Pfi zer) (100 tabs/package) 3 43.60

Translingual spray – generic 0.4 mg/spray 7.5 min 1-2 sprays, then 1 spray 279.30

Nitrolingual Pumpspray (Espero) (60, 200 sprays/unit) q5 min PRN 4 401.70

Translingual aerosol spray – generic 0.4 mg/spray 8 min 1-2 sprays, then 1 spray 279.00

NitroMist (Akrimax) (90, 230 sprays/unit) q5 min PRN 4 633.30

1 Maximum dose is 3 dosage units or 1.2 mg in a 15-minute period.

2 Approximate WAC for 96 packets of sublingual powder, 100 0.4-mg sublingual tabs, 200 translingual sprays, or 230 translingual aerosol sprays WAC =

whole-saler acquisition cost or manufacturer’s published price to wholewhole-salers; WAC represents a published catalogue or list price and may not represent an actual

transactional price Source: AnalySource® Monthly November 5, 2016 Reprinted with permission by First Databank, Inc All rights reserved ©2016 www.

fdbhealth.com/policies/drug-pricing-policy.

3 The 0.4-mg tablets are also supplied in packages containing 4 bottles of 25 tablets.

4 The dose should be sprayed onto or under the tongue.

1 NitroMist nitroglycerin spray for angina Med Lett Drugs Ther 2011; 53:23.

2 SD Fihn et al 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American Col-lege of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American College

of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society

of Thoracic Surgeons J Am Coll Cardiol 2012; 60:e44.

in a sitting position An additional packet can be used every 5 minutes as needed, up to a maximum

of 3 packets in a 15-minute period If angina does not begin to subside within 5 minutes or completely resolve within 15 minutes, the patient should seek immediate medical attention.2 The contents of one packet can be dissolved under the tongue 5-10 minutes before physical activity to prevent an acute attack of angina

STABILITY — Nitroglycerin is a volatile compound;

its degradation can be accelerated by exposure to heat or light Sublingual nitroglycerin tablets are dispensed in a tightly sealed amber glass bottle to prevent degradation and loss of potency Patients are usually instructed to discard unused tablets 6

to 12 months after first opening the bottle Because

GoNitro is supplied in single-use packets, use of one

dosage unit does not affect the stability of others

According to the manufacturer, unopened packets have an expiration date of up to 24 months from the date of manufacture

CONCLUSION — Sublingual nitroglycerin powder

(GoNitro) packets offer a very expensive alternative to nitroglycerin sublingual tablets (Nitrostat, and

gener-ics), with no demonstrated advantage in effi cacy ■

We Want to Know

Are there topics you would like us to review in an upcoming issue? We welcome your suggestions at:

articles@medicalletter.org

IN BRIEF

Phentermine (Lomaira) for Weight Loss

The FDA has approved Lomaira (KVK Tech), an 8-mg

tablet formulation of phentermine that can be taken

up to three times daily before meals, as an adjunct

to lifestyle modifications for weight loss It is only

approved for short-term use (a few weeks) in adults with

a body mass index (BMI) ≥30 kg/m 2 , or with a BMI ≥27

kg/m 2 in addition to a weight-related comorbidity such

as hypertension, dyslipidemia, or diabetes Phentermine

has been available alone and in combination with

topiramate for years 1

Table 1 Phentermine Products

Phentermine 2 – generic 15, 30, 37.5 mg caps; 37.5 mg $10.50

Adipex-P4 (Teva) 37.5 mg tabs once/d 3 63.50

Lomaira4 (KVK Tech) 8 mg tabs 8 mg tid 5 43.50

Phentermine/ 7.5/46, 15/92 mg 7.5/46 - 186.00

topiramate ER – ER caps 7 15/92 mg

Qsymia 6 (Vivus) once/d 8

ER = extended-release

1 Approximate WAC for 30 days’ treatment at the lowest usual dosage WAC =

wholesaler acquisition cost or manufacturer’s published price to

whole-salers; WAC represents a published catalogue or list price and may not

represent an actual transactional price Source: AnalySource® Monthly

November 5, 2016 Reprinted with permission by First Databank, Inc All rights

reserved ©2016 www.fdbhealth.com/policies/drug-pricing-policy

2 Only approved for short-term use (a few weeks).

3 Taken before breakfast or 1-2 hours after breakfast.

4 A branded generic.

5 Taken 30 minutes before meals, up to three times daily.

6 Approved for chronic weight management.

7 Also available in 3.75/23 mg and 11.25/69 mg capsules, which are intended for

use only during titration.

8 Taken before breakfast.

Lomaira was approved by the FDA under an

abbreviat-ed new drug application (ANDA) and is considerabbreviat-ed a

generic drug Its approval was based on the results

of earlier phentermine trials No studies are available

comparing the efficacy and safety of Lomaira to

standard doses of phentermine or to any other drug

approved for weight loss.

Like other sympathomimetic amines approved for weight

loss, Lomaira is classifi ed as a schedule IV controlled

substance All sympathomimetics can increase heart

rate, raise blood pressure, and cause nervousness and

insomnia 2 Phentermine is contraindicated for use in

patients with cardiovascular disease, hyperthyroidism,

glaucoma, or a history of drug abuse, and in pregnant

women It should not be used while taking, and for 14

days after stopping, a monoamine oxidase (MAO) inhibitor

because of the risk of hypertensive crisis ■

1 Diet, drugs, and surgery for weight loss Med Lett Drugs Ther

2015; 57:21.

2 SZ Yanovski and JA Yanovski Long-term drug treatment for

obesity: a systematic and clinical review JAMA 2014; 311:74

Addendum: Statins for Primary Prevention of Cardiovascular

Disease (Med Lett Drugs Ther 2016; 58:133)

In our recent article on Lipid-Lowering Drugs, 1 we said that statins can reduce the risk of fi rst cardiovascular events and death (primary prevention) in patients at high risk for atherosclerotic cardiovascular disease (CVD) and signifi cantly reduce the incidence of cardiovascular events

in patients at lower risk for CVD Now the United States Preventive Services Task Force (USPSTF) has issued new recommendations on the appropriate use of statins for primary prevention of CVD 2

The USPSTF states that clinicians should periodically screen all persons 40-75 years old for cardiovascular risk factors and evaluate their 10-year risk of CVD using the ACC/AHA Pooled Cohort Equation 3 It recommends starting low- to moderate-intensity statin therapy (low-intensity statin therapy lowers LDL-cholesterol <30%; moderate-intensity statin therapy lowers it 30-<50%) in adults 40-75 years old without CVD who have one or more CVD risk factors (dyslipidemia, diabetes, hypertension, or smoking) and a calculated 10-year CVD event risk of >10% For patients with the same characteristics but a 7.5-10% 10-year risk, the USPSTF recommends that clinicians

“selectively offer” the same treatment.

Table 1 USPSTF Recommendations for Primary Prevention of CVD in Patients with One or More Risk Factors 1

40-75 years >10% Initiate low- to moderate-intensity

statin therapy 3

7.5-10% Selectively offer low- to

moderate-intensity statin therapy 3,4

>75 years Any Evidence insuffi cient to

recommend initiating statin therapy

1 Dyslipidemia, diabetes, hypertension, or smoking.

2 Calculated using the ACC/AHA Pooled Cohort Equation (tools.acc.org/ ASCVD-Risk-Estimator)

3 Low-intensity statin therapy lowers LDL-cholesterol <30%; moderate-intensity statin therapy lowers it 30-<50%.

4 Based on professional judgment and patient preference.

The new recommendations do not apply to patients with familial hypercholesterolemia or LDL-cholesterol levels

≥190 mg/dL, who should take a statin regardless of calculated risk The USPSTF found the evidence insuffi cient

to recommend starting a statin for primary prevention in persons >75 years old ■

1 Lipid-lowering drugs Med Lett Drugs Ther 2016; 58:133.

2 US Preventive Services Task Force et al Statin use for the primary prevention of cardiovascular disease in adults: US Preventive Services Task Force Recommendation Statement JAMA 2016; 316:1997.

3 American Heart Association and American College of Cardiol-ogy ASCVD Risk Estimator Available at: tools.acc.org/ASCVD-Risk-Estimator Accessed November 22, 2016.

Questions on next page

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1 Discuss the association between proton pump inhibitor use and torsades de pointes.

2 Review the effi cacy and safety of ciprofloxacin 0.3%/fluocinolone acetonide 0.025% (Otovel) for treatment of acute otitis media with tympanostomy tubes.

3 Review the effi cacy and safety of aminolevulinic acid (Ameluz) for treatment of actinic keratoses.

4 Review the effi cacy and safety of sublingual nitroglycerin powder (GoNitro) for prevention or acute relief of an attack of angina pectoris.

5 Review the effi cacy and safety of phentermine 8-mg tablets (Lomaira) for weight loss.

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Issue 1509 Questions

(Correspond to questions #111-120 in Comprehensive Exam #75, available January 2017)

Each question has only one correct answer.

6 A balding 58-year-old man who played tennis for many years without wearing a cap has actinic keratoses on his scalp He asks your advice about the best treatment for removing them You could tell him that:

a 5-FU and imiquimod require months of administration and can cause disfi guring local reactions

b diclofenac gel is well tolerated but only modestly effective

c ALA combined with photodynamic therapy is effective and well tolerated

d all of the above

Sublingual Nitroglycerin Powder (GoNitro)

7 Nitroglycerin is available for patients with angina in which of the following formulations?

a sublingual tablets

b translingual spray

c sublingual powder

d all of the above

8 Compared to sublingual nitroglycerin tablets, the main advantage of the new nitroglycerin sublingual powder formulation appears to be its:

a effectiveness

b safety

c stability

d cost

9 Compared to sublingual nitroglycerin tablets, the main disadvantage

of the new nitroglycerin sublingual powder formulation is its:

a effectiveness

b safety

c stability

d cost

In Brief: Phentermine (Lomaira) for Weight Loss

10 Which of the following statements about Lomaira (phentermine

8-mg tablets) is true?

a It causes more weight loss than higher-dose once-daily phentermine formulations.

b It is less likely than higher-dose phentermine formulations to cause insomnia.

c It is more effective than phentermine/topiramate ER (Qsymia)

for long-term management of weight loss.

d It has not been compared to other phentermine products.

In Brief: PPIs and Torsades de Pointes

1 Some PPIs have been added to the list of Drugs with Conditional

Risk of TdP by AZCERT because they:

a prolong the QT interval directly

b prolong the PR interval directly

c increase serum concentrations of other drugs known to

prolong the QT interval

d cause hypomagnesemia resulting in cardiac repolarization

disturbances

Ciprofloxacin/Fluocinolone (Otovel) for Otitis Media with

Tympanostomy Tubes

2 Ciprofloxacin 0.3%/fluocinolone acetonide 0.025% otic solution

(Otovel) is FDA-approved for:

a single-dose prophylaxis before tympanostomy tube insertion

b acute otitis media

c acute otitis media with tympanostomy tubes

d otitis externa

3 Ciprofloxacin 0.3%/fluocinolone acetonide 0.025% otic solution

(Otovel) is:

a more effective than ciprofloxacin 0.3% alone in decreasing

otorrhea in children with acute otitis media with

tympanostomy tubes

b more effective than ciprofloxacin 0.3%/dexamethasone 0.1%

(Ciprodex) in decreasing otorrhea in children with acute otitis

media with tympanostomy tubes

c less effective than ciprofloxacin 0.3% alone for treatment of

acute otitis externa

d all of the above

Ameluz for Actinic Keratoses

4 In randomized trials, complete clearance of actinic keratoses

occurred in approximately what percentage of patients treated with

Ameluz?

a 45%

b 65%

c 85%

d 95%

5 Which of the following could exacerbate the phototoxic effect of

photodynamic therapy?

a thiazide diuretics

b oral contraceptives

c ACE inhibitors

d all of the above

ACPE UPN: Per Issue Exam: 0379-0000-16-509-H01-P; Release: December 5, 2016, Expire: December 5, 2017 Comprehensive Exam 75: 0379-0000-17-075-H01-P; Release: January 2017, Expire: January 2018

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