1502 on Drugs and Therapeutics AspireAssist —A New Device for Weight Loss ...p 109 Lifi tegrast Xiidra for Dry Eye Disease ...p 110 Sugammadex Bridion for Rapid Reversal of Neuromuscular
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IN THIS ISSUE
ISSUE
1433
Volume 56
Published by The Medical Letter, Inc • A Nonprofi t Organization
ISSUE No
1502
on Drugs and Therapeutics
AspireAssist —A New Device for Weight Loss p 109
Lifi tegrast (Xiidra) for Dry Eye Disease p 110
Sugammadex (Bridion) for Rapid Reversal of Neuromuscular Blockade p 112
An Oral Cholera Vaccine for Travelers (Vaxchora) p 113
Addendum: Cannabis and Cannabinoids p 114
Trang 2
109
on Drugs and Therapeutics
Take CME Exams
ISSUE
1433
Volume 56
ISSUE No
1502 Lifi tegrast (Xiidra) for Dry Eye Disease Sugammadex (Bridion) for Rapid Reversal of Neuromuscular Blockade p 110p 112
An Oral Cholera Vaccine for Travelers (Vaxchora) p 113
Addendum: Cannabis and Cannabinoids p 114
ALSO IN THIS ISSUE
AspireAssist — A New Device for
Weight Loss
▶
The FDA has approved AspireAssist (Aspire
Bariatrics), a weight-loss device that permits patients
to drain a portion of their stomach contents through
a gastrostomy tube into a toilet after each meal It
is approved for long-term use in combination with
lifestyle modifi cations in adults ≥22 years old who
have a body mass index (BMI) of 35 to 55 and have
not been able to achieve and maintain weight loss with
nonsurgical therapy
WEIGHT LOSS PROCEDURES — Surgical treatment of
obesity is generally limited to patients with a BMI ≥40,
or a BMI ≥35 with an obesity-related comorbidity such
as diabetes, hypertension, or hypercholesterolemia
Procedures that cause malabsorption (Roux-en-Y
gastric bypass and biliopancreatic diversion) lead to
greater weight loss, but more adverse effects, than
purely restrictive procedures such as adjustable gastric
banding or sleeve gastrectomy.1 Gastric balloon devices
are inserted endoscopically and can be left in place for
up to 6 months; when they are removed, patients
gen-erally regain a substantial fraction of the lost weight.2
The subcutaneously implanted Maestro Rechargeable
System, which utilizes high-frequency electrical pulses
to block vagus nerve signals between the stomach and
the brain, is less effective than bariatric surgery.3
THE NEW DEVICE — The AspireAssist device facilitates
weight loss in obese patients by allowing them to
partially drain their stomach contents after each main
meal, reducing the amount of absorbed calories by
approximately 30%.4 The device consists of a tube
similar to a percutaneous endoscopic gastrostomy
(PEG) feeding tube, a port valve, and an external
device that contains a connector, a drainage tube
with a clamp, and a water reservoir The PEG tube is
inserted endoscopically into the stomach and pulled
Table 1 Effi cacy of Weight Loss Procedures/Devices
Procedure/Device Weight 1 Lost
Gastric aspiration (AspireAssist) 32%3
Gastric balloon (Orbera, ReShape) 27-28%4
(Maestro Rechargeable System)
1 Defi ned as weight above the weight at a BMI of 25.
2 Diet, drugs, and surgery for weight loss Med Lett Drugs Ther 2015; 57:21.
3 CC Thompson et al Gastroenterology 2016; 150(suppl 1): S86, abstract 381.
4 ReShape and Orbera – two gastric balloon devices for weight loss Med Lett Drugs Ther 2015; 57:122.
5 Maestro Rechargeable System for weight loss Med Lett Drugs Ther 2016; 58:54.
through a percutaneous incision while the patient is under twilight sedation The disk-shaped port valve is connected to the tube at skin level to hold it in place Approximately 20-30 minutes after a meal, the patient attaches the connector of the external device to the port valve and opens the valve, allowing the stomach contents to drain by gravity into a toilet Food must be thoroughly chewed to fi t through the 6-mm drainage tube When drainage stops, the patients flushes the tube and stomach with potable water from the reservoir The process takes 5-10 minutes to complete The connector contains a counter that tracks the num-ber of times the valve is opened; it stops working after
115 cycles (about 5-6 weeks) Follow-up appointments are necessary to replace the connector, confirm that the device is working properly, adjust the length of the tube as the patient loses weight, and provide diet and lifestyle counseling The initial procedure and
follow-up during the fi rst year are expected to cost $8000 to
$13,000, according to the manufacturer
CLINICAL STUDY — In an open-label, 52-week trial
(PATHWAY), available only as an abstract, 171 patients were randomized in a 2:1 ratio to active treatment
Trang 3Lifi tegrast (Xiidra) for Dry Eye
Disease
▶
Pronunciation Key Lifi tegrast: lif" i teg' rast Xiidra: zye' dra
The FDA has approved a 5% ophthalmic solution of
lifi tegrast (Xiidra – Shire), a lymphocyte
function-associated antigen-1 (LFA-1) antagonist, for treatment
of the signs and symptoms of dry eye disease Lifi tegrast is the fi rst LFA-1 antagonist to be approved for any indication in the US
DRY EYE DISEASE — Ocular surface inflammation
leading to dry eyes can be caused by altered
tear-fi lm composition, reduced tear production, poor lid function, environmental conditions, or diseases such as Sjögren’s syndrome Anticholinergic drugs, estrogens, and selective serotonin reuptake inhibitors (SSRIs) can also cause dry eyes Older age and female sex are risk factors
STANDARD TREATMENT — Treatments for dry eye
disease include artifi cial tears, ocular insert devices
such as Lacrisert, and ophthalmic anti-inflammatory drugs such as cyclosporine (Restasis), corticosteroids,
and tetracyclines.1,2 Artifi cial tear preparations are usually administered every 4-6 hours, but can be used as often as hourly; some clinicians recommend
Table 1 Some Prescription Products for Dry Eye Disease
Drug Formulation Dosage Cost 1
Cyclosporine 0.05% unit 1 drop in ophthalmic emulsion – dose vials each eye
Restasis (Allergan) q12h 2,3 $426.70 Hydroxypropyl cellulose 5 mg inserts 1 insert in
ophthalmic insert – each eye
Lacrisert (Valeant) once/d 4 398.10 Lifi tegrast ophthalmic 5% single-use 1 drop in
solution – Xiidra containers each eye 426.70
1 Approximate WAC for 30 days' treatment at the usual adult dosage
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 August 5, 2016 Reprinted with permission by First Databank, Inc All rights reserved ©2016 www.fdbhealth.com/policies/drug-pric-ing-policy.
2 Before use, the unit-dose vial should be inverted repeatedly until a uniform, white, opaque emulsion forms.
3 Contact lenses should be removed before instilling the drops, but may be replaced 15 minutes after administration.
4 Some patients may require twice-daily use.
with AspireAssist plus lifestyle counseling (behavior
education, diet, and exercise) or lifestyle counseling
alone The active treatment group lost 31.5% of excess
weight (12.1% of total body weight), compared to 9.8%
(3.5% of total body weight) in the control group, a
signifi cant difference A second primary endpoint, at least
a 50% response rate (defi ned as ≥25% excess weight
lost) in the active treatment group, was not met because
the lower end of the confi dence interval was 49%.5,6
ADVERSE EFFECTS — In the PATHWAY trial, adverse
effects that occurred in >5% of patients using
AspireAssist included abdominal pain or discomfort,
peristomal granulation tissue, nausea/vomiting,
change in bowel habits, peristomal infection or
pos-sible infection, and peristomal bleeding, discharge,
inflammation, or irritation Most of these resolved
within 30 days Serious adverse events (replacement of
the tube, peritonitis without abscess, post-procedure
abdominal pain, and nonbleeding prepyloric ulceration)
occurred in 3.6% of patients (4 of 111); none of these
resulted in death or permanent injury
CONCLUSION — The AspireAssist device is less invasive
than bariatric surgery for treatment of obesity and
might be effective for some patients, but available data
are limited and the list of contraindications is exten
-sive The effects of the device on long-term weight loss
and quality of life remain to be determined ■
1 Diet, drugs, and surgery for weight loss Med Lett Drugs Ther
2015; 57:21.
2 ReShape and Orbera – two gastric balloon devices for weight
loss Med Lett Drugs Ther 2015; 57:122.
3 Maestro Rechargeable System for weight loss Med Lett Drugs
Ther 2016; 58:54.
4 S Sullivan et al Aspiration therapy leads to weight loss in obese
subjects: a pilot study Gastroenterology 2013; 145:1245.
Table 2 Contraindications
▶ Previous abdominal surgery that increases the risks
associated with gastrostomy tube placement
▶ Esophageal stricture, pseudo-obstruction, severe
gastroparesis or gastric outlet obstruction
▶ Inflammatory bowel disease, ulcers, bleeding lesions, or
tumors discovered upon endoscopic exam
▶ History of refractory gastric ulcers
▶ History or evidence of serious pulmonary or
cardiovascular disease
▶ Uncontrolled hypertension, coagulation disorders,
anemia, severe organ dysfunction such as cirrhosis or
severe chronic kidney disease, chronic abdominal pain,
or poor general health
▶ Bulimia, binge eating disorder, or night eating syndrome
▶ A physical or mental disability that would affect
compliance with therapy
▶ Pregnant or lactating women
5 CC Thompson et al The AspireAssist is an effective tool in the treatment of class II and class III obesity: results of a one-year clini-cal trial Gastroenterology 2016; 150(suppl1):S86, abstract 381
6 FDA summary of safety and effectiveness data Available at: www.accessdata.fda.gov/cdrh_docs/pdf15/p150024b.pdf Accessed August 11, 2016
Trang 4in 5-25% of patients) were eye irritation, dysgeusia, and reduced visual acuity; most reactions were mild
to moderate in severity In a one-year safety study (SONATA), no serious treatment-related adverse events occurred among 220 patients who used lifi tegrast.9
DOSAGE AND ADMINISTRATION — Lifi tegrast 5%
ophthalmic solution is supplied in cartons of 60 single-use containers The recommended dosage is one drop
of solution instilled in each eye twice daily Contact lenses should be removed before instilling the drops, but may be replaced 15 minutes after administration
CONCLUSION — Twice-daily lifi tegrast ophthalmic
solution (Xiidra) appears to be safe and at least
modestly effective in treating the signs and symptoms
of dry eye disease How it compares to other ophthalmic products for this indication, such as
cyclosporine (Restasis), remains to be determined ■
preservative-free formulations for patients who
need treatment ≥4 times daily, but they are relatively
expensive Lacrisert gradually releases hydroxypropyl
cellulose into the inferior conjunctival sac; it can be
used daily in patients with moderate to severe disease
whose symptoms do not respond to artifi cial tears
Restasis has been safe and effective in treating the
signs and symptoms of dry eye disease, but it may
take up to 3 months to achieve its full effect, and it
can cause ocular burning and stinging.3 In cases of
severe tear defi ciency, the tear ducts can be partially
or completely occluded to increase tear volume
MECHANISM OF ACTION — LFA-1 is a protein
expressed on leukocyte surfaces that binds to
intercellular adhesion molecule-1 (ICAM-1), which
may be overexpressed in the corneal and conjunctival
tissue of patients with dry eye disease The resulting
interaction is believed to stimulate T-cell activation
and migration, leading to propagation of
pro-inflammatory factors and inflammation of the ocular
surface Lifi tegrast is thought to reduce ocular surface
inflammation by binding to LFA-1, preventing its
interaction with ICAM-1.4
CLINICAL STUDIES — Lifi tegrast 5% ophthalmic
solution was studied in four 12-week, randomized,
double-blind, vehicle-controlled clinical trials (three
published, one summarized in the package insert) in a
total of 2133 adults with dry eye disease Use of other
ophthalmic medications, including artifi cial tears, was
not permitted during the trials The effects of the active
drug compared to the vehicle alone on inferior corneal
fluorescein staining score and patient-reported eye
dryness are summarized in Table 2.5-8
ADVERSE EFFECTS — The most common adverse
effects associated with use of lifi tegrast (reported
Table 2 Some Lifi tegrast Clinical Trials
Inferior Corneal Fluorescein Staining Score 1 Eye Dryness Score 2
Study Arms Baseline Change at Day 84 Baseline Change at Day 84
*p<0.05 vs vehicle
1 Mean scores rated on a scale of 0-4, with higher scores indicating more severe disease.
2 Mean scores rated on a visual analog scale of 0-100, with higher scores indicating more eye dryness.
3 CP Semba et al A phase 2 randomized, double-masked, placebo-controlled study of a novel integrin antagonist (SAR 1118) for the treatment of dry eye Am J Ophthalmol 2012; 153:1050.
4 JD Sheppard et al Lifi tegrast ophthalmic solution 5.0% for treatment of dry eye disease: results of the OPUS-1 phase 3 study Ophthalmology 2014; 121:475.
5 J Tauber et al Lifi tegrast ophthalmic solution 5.0% versus placebo for treatment of dry eye disease: results of the randomized phase III OPUS-2 study
Ophthalmology 2015; 122:2423.
6 Summarized in the package insert.
1 WB Jackson Management of dysfunctional tear syndrome: a Canadian consensus Can J Ophthalmol 2009; 44:385.
2 Drugs for some common eye disorders Treat Guidel Med Lett 2012; 10:79.
3 HD Perry et al Evaluation of topical cyclosporine for the treat-ment of dry eye disease Arch Ophthalmol 2008; 126:1046.
4 VL Perez et al Lifi tegrast, a novel integrin antagonist for treat-ment of dry eye disease Ocul Surf 2016; 14:207.
5 CP Semba et al A phase 2 randomized, double-masked, place-bo-controlled study of a novel integrin antagonist (SAR 1118) for the treatment of dry eye Am J Ophthalmol 2012; 153:1050.
6 JD Sheppard et al Lifi tegrast ophthalmic solution 5.0% for treatment of dry eye disease: results of the OPUS-1 phase 3 study Ophthalmology 2014; 121:475.
7 J Tauber et al Lifi tegrast ophthalmic solution 5.0% versus pla-cebo for treatment of dry eye disease: results of the randomized phase III OPUS-2 study Ophthalmology 2015; 122:2423
8 EJ Holland et al Lifi tegrast clinical effi cacy for treatment of signs and symptoms of dry eye disease across three random-ized controlled trials Curr Med Res Opin 2016 July 22 (epub).
9 ED Donnenfeld et al Safety of lifi tegrast ophthalmic solution 5.0% in patients with dry eye disease: a 1-year, multicenter, ran-domized, placebo-controlled study Cornea 2016; 35:741.
Trang 5Sugammadex (Bridion) for Rapid
Reversal of Neuromuscular
Blockade
▶
The FDA has approved sugammadex (Bridion – Merck),
a selective relaxant binding agent, for reversal of
rocuronium- or vecuronium-induced neuromuscular
blockade in adult surgical patients It is the fi rst
selective relaxant binding agent to be approved in the
US Sugammadex has been available in the European
Union, Japan, and elsewhere for several years Pre vious
FDA reviews of sugammadex did not result in approval
because of concerns about a risk of anaphylaxis and
other hypersensitivity reactions with its use
Pronunciation Key Sugammadex: soo gam' ma dex Bridion: bry' dee on
STANDARD TREATMENT — Rocuronium and vecuronium
are steroidal nondepolarizing neuromuscular blocking
agents; they have a slower onset and longer duration
of action than the nonsteroidal depolarizing drug
succinylcholine, but are less likely to cause serious
adverse effects such as hyperkalemia and malignant
hyperthermia The acetylcholinesterase inhibitor
neostigmine (Bloxiverz, and generics) can be used to
reverse the effects of nondepolarizing blocking agents;
response time and intensity can be unpredictable, and
adverse effects such as hypotension and bradycardia
can occur.1
PHARMACOLOGY — Sugammadex forms complexes
with rocuronium and vecuronium, preventing them
from binding to nicotinic receptors and inducing
neuromuscular blockade It is not signifi cantly
meta-bolized and is excreted in urine
CLINICAL STUDIES — In randomized clinical trials, the
time required to reverse moderate and deep
neuromus-cular blockade induced by rocuronium and vecuronium
was less variable and signifi cantly shorter with
sugammadex than with neostigmine (see Table 1).2-5
In a randomized trial in 110 adults who required a short
duration of neuromuscular relaxation, the time required
to achieve the primary reversal endpoint (return of fi rst
twitch to 10% of baseline) was signifi cantly shorter
with sugammadex 16 mg/kg given 3 minutes after
rocuronium 1.2 mg/kg than with succinylcholine
1 mg/kg (mean 4.4 vs 7.1 minutes).6
ADVERSE EFFECTS — The most common adverse
effects of sugammadex in clinical trials were pain,
nausea, and vomiting Hypersensitivity reactions,
including anaphylaxis, have been reported In a
repeat-dose study (summarized in the package insert), anaphylaxis occurred in 1 of 299 healthy volunteers who received the drug Marked bradycardia, sometimes resulting in cardiac arrest, has also been reported rarely with use of sugammadex
Sugammadex increases activated partial thrombo-plastin time (aPTT), prothrombin time (PT), and the INR in healthy subjects, but the drug has not been found to increase the risk of bleeding complications
in patients receiving heparin or low molecular weight heparin for thromboprophylaxis
PREGNANCY AND LACTATION — Use of sugammadex
in pregnant or lactating women has not been studied Bone development abnormalities and decreased body weight were observed in fetal rabbits exposed to supratherapeutic doses of the drug Sugammadex is secreted in rat breastmilk, but no adverse effects were observed in exposed rat pups
DRUG INTERACTIONS — Sugammadex may bind
to progestogens, including progesterone Women taking hormonal contraceptives should also use a nonhormonal contraceptive method for 7 days after receiving sugammadex
The selective estrogen receptor modulator toremifene
(Fareston) has a high binding affi nity for sugammadex
and could displace rocuronium or vecuronium; sugammadex activity may be delayed in patients who took toremifene on the day of surgery
DOSAGE, ADMINISTRATION, AND COST —
Sugam-madex should only be used to reverse neuromuscular blockade caused by rocuronium or vecuronium It is
Table 1 Some Clinical Trials
Minutes to Blocking Agent Reversal Regimen Recovery 1
Moderate Blockade 2
Rocuronium Sugammadex 2 mg/kg 1.5 (1.3-1.6) (n=98) 3 Neostigmine 50 mcg/kg 18.6 (14.2-24.4) Vecuronium Sugammadex 2 mg/kg 2.7 (2.2-3.3) (n=93) 4 Neostigmine 50 mcg/kg 17.9 (13.1-24.3)
Deep Blockade 5
Rocuronium Sugammadex 4 mg/kg 2.7 (2.1-4.1) (n=74) 6 Neostigmine 70 mcg/kg 49.0 (35.7-65.6) Vecuronium Sugammadex 4 mg/kg 3.3 (1.8-4.4) (n=83) 7 Neostigmine 70 mcg/kg 58.9 (42.9-79.8)
1 Geometric mean time to recovery of train-of-four ratio to 0.9, with 95% confi dence intervals for moderate blockade trials and interquartile ranges for deep blockade trials
2 Defi ned as reappearance of the second twitch (T2) in response to train-of-four stimulation after the last dose of the blocking agent.
3 M Blobner et al Eur J Anaesthesiol 2010; 27:874.
4 KS Khuenl-Brady et al Anesth Analg 2010; 110:64.
5 Defi ned as reappearance of 1-2 post-tetanic counts after the last dose of the blocking agent.
6 RK Jones et al Anesthesiology 2008; 109:816.
7 HJ Lemmens et al BMC Anesthesiol 2010; 10:15.
Trang 6given as a single IV bolus injection over 10 seconds
The recommended dosage is 2 mg/kg for patients
with moderate rocuronium- or vecuronium-induced
blockade, and 4 mg/kg for those with deep blockade
A 16-mg/kg dose of sugammadex can be used if there
is a need to reverse blockade shortly (~3 minutes) after
administration of 1.2 mg/kg of rocuronium; use of this
dose to reverse vecuronium-induced blockade has not
been studied Sugammadex is not recommended for
use in patients with severe renal impairment
Recurrence of neuromuscular blockade after recovery
is possible; respiratory function and ventilation should
be closely monitored Steroidal neuromuscular blocking
agents given after sugammadex could have a delayed
onset or shorter duration of action A nonsteroidal
blocking agent such as succinylcholine should be used
if more immediate blockade is necessary, as in patients
who require reintubation.7
Bridion is supplied in 200 mg/2 mL and 500 mg/
5 mL single-dose vials One vial containing 200 mg of
sugammadex costs $95; a 500-mg vial costs $174.8
CONCLUSION — Sugammadex (Bridion) reverses
neuromuscular blockade induced by rocuronium
and vecuronium more quickly and consistently
than neostigmine Use of sugammadex shortly
after rocuronium appears to be at least as effective
as succinylcholine in providing short durations of
neuromuscular blockade Hypersensitivity reactions,
including anaphylaxis, and marked bradycardia have
been reported ■
1 JM van Vlymen and JL Parlow The effects of reversal
of neuromuscular blockade on autonomic control in the
perioperative period Anesth Analg 1997; 84:148.
2 M Blobner et al Reversal of rocuronium-induced neuromuscular
blockade with sugammadex compared with neostigmine during
sevoflurane anaesthesia: results of a randomised, controlled
trial Eur J Anaesthesiol 2010; 27:874.
3 KS Khuenl-Brady et al Sugammadex provides faster reversal of
vecuronium-induced neuromuscular blockade compared with
neostigmine: a multicenter, randomized, controlled trial Anesth
Analg 2010; 110:64.
4 RK Jones et al Reversal of profound rocuronium-induced
blockade with sugammadex: a randomized comparison with
neostigmine Anesthesiology 2008; 109:816.
5 HJ Lemmens et al Reversal of profound vecuronium-induced
neuromuscular block under sevoflurane anesthesia:
sugam-madex versus neostigmine BMC Anesthesiol 2010; 10:15.
6 C Lee et al Reversal of profound neuromuscular block by
sugammadex administered three minutes after rocuronium: a
comparison with spontaneous recovery from succinylcholine
Anesthesiology 2009; 110:1020.
7 HD de Boer et al Non-steroidal neuromuscular blocking agents
to re-establish paralysis after reversal of rocuronium-induced
neuromuscular block with sugammadex Can J Anaesth 2008;
55:124.
8 Approximate WAC WAC = wholesaler acquisition cost or manufac-turer’s published price to wholesalers; WAC represents a published catalogue or list price and may not represent an actual
transaction-al price Source: Antransaction-alySource® Monthly August 5, 2016 Reprinted with permission by First Databank, Inc All rights reserved ©2016 www.fdbhealth.com/policies/drug-pricing-policy.
An Oral Cholera Vaccine for
Travelers (Vaxchora)
▶
The FDA has approved Vaxchora (PaxVax), a
single-dose, oral, live-attenuated cholera vaccine, to protect
against disease caused by Vibrio cholerae serogroup
O1 in adults 18-64 years old traveling to
cholera-affected areas Vaxchora is the only cholera vaccine
available in the US A whole-cell killed injectable vaccine was previously approved, but is no longer available in the US
Pronunciation Key
Vaxchora: vax kor' uh
CHOLERA INFECTION — Cholera is endemic in over 50
countries, primarily in Africa and South and Southeast Asia In recent years, there have been outbreaks of cholera in some Caribbean nations, such as Haiti.1
V cholerae is spread mainly by fecal contamination of
water and food in countries without proper sanitation
or clean drinking water Ingestion of the toxigenic
V cholerae serogroups O1 or (less commonly) O139
causes diarrhea that can be severe and can rapidly lead to life-threatening dehydration.2 For most tourists, the risk of cholera is very low.3 Preventive measures include safe food and water precautions and fre quent handwashing
CLINICAL STUDIES — In a double-blind challenge
trial, 197 volunteers 18-45 years old with no history
of cholera infection or travel to cholera-endemic areas in the past 5 years were randomized to receive
one dose of Vaxchora or placebo Ten days or 3
months after vaccination, a total of 134 subjects
were challenged with wild-type V cholerae O1 El Tor
Inaba strain N16961 Moderate (≥3 L) to severe (≥5 L) diarrhea, the primary endpoint, occurred in 2 of 35 (5.7%) subjects vaccinated 10 days previously, in 4
of 33 (12.1%) vaccinated 3 months previously, and
in 39 of 66 (59.1%) who received placebo Vaccine effi cacy was 90.3% at 10 days and 79.5% at 3 months Among vaccinated subjects, the vibriocidal antibody seroconversion rate was 89.4% at 10 days after vaccination and 90.4% at 180 days after vaccination.4
In a double-blind immunogenicity trial, summarized
in the package insert, 3146 subjects 18-45 years old
Trang 7were randomized in an 8:1 ratio to receive one dose of
Vaxchora or placebo The seroconversion rate 10 days
after vaccination was 93.5% in subjects who received
the vaccine and 4% in those who received placebo
In a similar study, summarized in the package insert,
the seroconversion rate in 291 vaccinees 46-64 years
old was noninferior to that in vaccine recipients 18-45
years old (90.4% vs 93.5%)
ADVERSE EFFECTS — The most common adverse
effects reported with Vaxchora in subjects 18-64 years
old were tiredness, headache, abdominal pain, nausea,
vomiting, and diarrhea, but except for diarrhea, which
was reported more frequently in subjects who received
the vaccine, the rates of these adverse effects were
similar to those reported with placebo The vaccine
strain may be shed in the stool for at least 7 days and
potentially could be transmitted to close contacts In
a phase I study, 11% of vaccinees shed the vaccine
in stool; there was no evidence of transmission to
household contacts.5
PREGNANCY — There are no data on the use of
Vaxchora during pregnancy Maternal use of Vaxchora
is not expected to result in fetal exposure because
the vaccine is not systemically absorbed after oral
administration Since the vaccine strain is shed in the
stool, it could potentially be transmitted to the infant
during vaginal delivery
DRUG INTERACTIONS — Antibiotics may be active
against the vaccine strain in Vaxchora and could
decrease the immune response; the vaccine should not
1 M Ali et al Updated global burden of cholera in endemic coun-tries PLoS Negl Trop Dis 2015; 9:e0003832.
2 Cholera vaccines: WHO position paper Wkly Epidemiol Rec 2010; 85:117
3 Vaccines for travelers Med Lett Drugs Ther 2014; 56:115.
4 WH Chen et al Single-dose live oral cholera vaccine CVD 103-HgR protects against human experimental infection with Vibrio cholerae O1 El Tor Clin Infect Dis 2016; 62:1329.
5 WH Chen et al Safety and immunogenicity of single-dose live oral cholera vaccine strain CVD 103-HgR, prepared from new master and working cell banks Clin Vaccine Immunol 2014; 21:66.
6 Approximate wholesaler acquisition cost (WAC) according to the manufacturer.
▶ Not recommended for most tourists
▶ Recommended for travelers to endemic or epidemic areas
who are at high risk of exposure to Vibrio cholerae O1 or
at high risk for poor clinical outcomes if infected
▶ Travelers at high risk of exposure include those:
– visiting friends and relatives who cannot follow safe
food, water, and handwashing practices
– who frequently visit or stay for extended periods of time
in endemic areas
– who plan to work in refugee camps, in outbreak settings,
or as healthcare providers
▶ Travelers at high risk for poor clinical outcomes include those:
– without rapid access to medical care
or kidney disease, who would tolerate dehydration poorly
– with blood type O
– with low gastric acidity
1 Cholera Vaccine Workgroup Cholera vaccine update and proposed
recommendations Advisory Committee on Immunization Practices Meeting
June 2016 Available at: www.cdc.gov/vaccines/acip/meetings/downloads/
slides-2016-06/cholera-02-wong.pdf Accessed August 11, 2016.
be given to patients who have taken oral or parenteral antibiotics within 14 days before vaccination Chloro-quine may also decrease the immune response to
the vaccine; Vaxchora should be administered at
least 10 days before starting antimalarial prophylaxis with chloroquine
DOSAGE, ADMINISTRATION, AND COST — Vaxchora
is given as a single oral dose at least 10 days before potential exposure to cholera Eating or drinking should be avoided within 60 minutes before and after
administration of the vaccine Vaxchora is supplied
in single-dose cartons containing buffer and active
component (lyophilized V cholerae CVD 103-HgR)
packets The vaccine should be reconstituted within
15 minutes after removing the carton from the freezer and administered in a healthcare setting within 15 minutes following reconstitution The buffer packet should be dissolved in 100 mL of purifi ed bottled water
fi rst, followed by the active component packet; if the vaccine is reconstituted in the wrong order it must be
discarded The cost for one dose of Vaxchora is $225.6
CONCLUSION — Taken as a single oral dose, Vaxchora
appears to be safe and effective for prevention of
cholera infection due to Vibrio cholerae serotype O1
in adults 18-64 years old not previously exposed to cholera Data on vaccine effi cacy beyond 6 months and re-immunization are lacking Vaccination is not recommended for most tourists ■
Addendum: Cannabis and Cannabinoids
A reader asked why our Cannabis and Cannabinoids article (Med Lett Drugs Ther 2016; 58:97) did not include our usual Dosage/Cost table We have now posted one in the article as
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Issue 1502 Questions
(Correspond to questions #41-50 in Comprehensive Exam #75, available January 2017)
Sugammadex (Bridion) for Rapid Reversal of Neuromuscular
Blockade
6 The time to recovery after sugammadex administration
in patients with deep blockade induced by vecuronium or rocuronium is about:
a 3 minutes
b 18 minutes
c 30 minutes
d 50 minutes
7 Which of the following has occurred following treatment with sugammadex?
a anaphylaxis
b bradycardia
c increased INR
d all of the above
An Oral Cholera Vaccine for Travelers (Vaxchora)
8 A 34-year-old man is planning a one-month trip to Southeast Asia to provide medical care in local clinics He has no chronic medical conditions, takes no medications, and has blood type O.
He asks you whether he should receive Vaxchora before
traveling You could tell him that:
a Vaxchora is recommended for travelers to endemic areas
who will be working in healthcare settings
b people with blood type O are at high risk for poor clinical outcomes if infected with cholera
c the vaccine appears to be effective for up to 6 months
d all of the above
9 Vaxchora:
a should be given as two IM doses at least one month before travel
b should be given as a single oral dose at least 10 days before travel
c can be administered at the same time as chloroquine for malaria prophylaxis
d is FDA-approved for use in children
10 In clinical trials, seroconversion rates 10 days after vaccination
with Vaxchora were approximately:
a 100%
b 90%
c 70%
d 50%
AspireAssist – A New Device for Weight Loss
1 A 32-year-old woman with a BMI of 40 has not been able to
achieve and maintain weight loss with lifestyle modifi cations
and pharmacologic therapy She has read about the
AspireAssist device and asks if it is suitable for her You could
tell her that:
a it requires draining stomach contents into a toilet
b it generally results in less weight loss than adjustable
gastric banding
c it could cost as much as $13,000 in the fi rst year of use
d all of the above
2 Use of the AspireAssist device results in approximately how
much excess weight lost?
a 5%
b 15%
c 30%
d 50%
3 AspireAssist is contraindicated for use in patients with:
a inflammatory bowel disease
b bulimia
c ulcers
d all of the above
Lifi tegrast (Xiidra) for Dry Eye Disease
4 Lifi tegrast is thought to reduce ocular inflammation by:
a blocking prostaglandin synthesis
b occluding the tear ducts and increasing tear volume
c interfering with stimulation of T-cell activation and
migration
d all of the above
5 Compared to Restasis, Xiidra:
a costs the same
b has been shown to be safer
c has been shown to be more effective
d all of the above
ACPE UPN: Per Issue Exam: 0379-0000-16-502-H01-P; Release: August 29, 2016, Expire: August 29, 2017 Comprehensive Exam 75: 0379-0000-17-075-H01-P; Release: January 2017, Expire: January 2018
PRESIDENT: Mark Abramowicz, M.D.; VICE PRESIDENT AND EXECUTIVE EDITOR: Gianna Zuccotti, M.D., M.P.H., F.A.C.P., Harvard Medical School; EDITOR IN CHIEF: Jean-Marie Pflomm,
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CONTRIBUTING EDITORS: Carl W Bazil, M.D., Ph.D., Columbia University College of Physicians and Surgeons; Vanessa K Dalton, M.D., M.P.H., University of Michigan Medical School;
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