The medical letter on drugs and therapeutics august 29 2016

The Medical Letter

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on Drugs and Therapeutics
Volume 58

ISSUE
ISSUE
No.

1433
1502
Volume 56

August 29, 2016

IN THIS ISSUE

AspireAssist — A New Device for Weight Loss ................................................................. p 109
Lifitegrast (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

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The Medical Letter

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on Drugs and Therapeutics
Volume 58

August 29, 2016
Take CME Exams

ISSUE

ISSUE No.

1433
1502

Volume 56

▶

ALSO IN THIS ISSUE

Lifitegrast (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

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 modifications 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 generally 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. Efficacy of Weight Loss Procedures/Devices
Procedure/Device
Biliopancreatic diversion
Roux-en-Y gastric bypass
Sleeve gastrectomy
Adjustable gastric banding
Gastric aspiration (AspireAssist)
Gastric balloon (Orbera, ReShape)
Vagal blocking therapy
(Maestro Rechargeable System)

Mean Excess
Weight1 Lost
≥70%2
66%2
59%2
47%2
32%3
27-28%4
25%5

1.
2.
3.
4.

Defined as weight above the weight at a BMI of 25.
Diet, drugs, and surgery for weight loss. Med Lett Drugs Ther 2015; 57:21.
CC Thompson et al. Gastroenterology 2016; 150(suppl 1): S86, abstract 381.
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 fit 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 number 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 followup during the first 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
109

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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

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
significant difference. A second primary endpoint, at least
a 50% response rate (defined as ≥25% excess weight
lost) in the active treatment group, was not met because
the lower end of the confidence 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 possible 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 extensive. 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.

110

August 29, 2016

Vol. 58 (1502)

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 clinical 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.

▶

Lifitegrast (Xiidra) for Dry Eye
Disease

The FDA has approved a 5% ophthalmic solution of
lifitegrast (Xiidra – Shire), a lymphocyte functionassociated antigen-1 (LFA-1) antagonist, for treatment
of the signs and symptoms of dry eye disease.
Lifitegrast is the first LFA-1 antagonist to be approved
for any indication in the US.
Pronunciation Key
Lifitegrast: lif" i teg' rast
Xiidra: zye' dra

DRY EYE DISEASE — Ocular surface inflammation
leading to dry eyes can be caused by altered tearfilm 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 artificial tears, ocular insert devices
such as Lacrisert, and ophthalmic anti-inflammatory
drugs such as cyclosporine (Restasis), corticosteroids,
and tetracyclines.1,2 Artificial 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
Usual Adult
Dosage

Cost1

Cyclosporine
0.05% unit
ophthalmic emulsion – dose vials
Restasis (Allergan)

1 drop in
each eye
q12h2,3

$426.70

Hydroxypropyl cellulose 5 mg inserts
ophthalmic insert –
Lacrisert (Valeant)

1 insert in
each eye
once/d4

398.10

Lifitegrast ophthalmic

solution – Xiidra
(Shire)

1 drop in
each eye
q12h3

Drug

Formulation

5% single-use
containers

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-pricing-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.


The Medical Letter

Vol. 58 (1502)

®

August 29, 2016

Table 2. Some Lifitegrast Clinical Trials
Inferior Corneal Fluorescein Staining Score1
Baseline
Change at Day 84

Study

Arms

Phase 23
(n=116)

Lifitegrast 5%
Vehicle

1.77
1.65

OPUS-14
(n=588)

Lifitegrast 5%
Vehicle

1.84
1.81

OPUS-25
(n=718)

Lifitegrast 5%
Vehicle

2.39
2.40

OPUS-36
(n=711)

Lifitegrast 5%
Vehicle

2.46
2.46

Eye Dryness Score2
Baseline
Change at Day 84

+0.04*
+0.38
-0.07*
+0.17

51.6
51.8

-0.73
-0.71
-0.80*
-0.63

69.7
69.2

40.2
41.6

68.3
69.0

-14.4
-7.2
-15.2*
-11.2
-35.3*
-22.8
-37.7*
-30.5

*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. Lifitegrast 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. Lifitegrast 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.

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 artificial 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 deficiency, 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 proinflammatory factors and inflammation of the ocular
surface. Lifitegrast is thought to reduce ocular surface
inflammation by binding to LFA-1, preventing its
interaction with ICAM-1.4
CLINICAL STUDIES — Lifitegrast 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 artificial 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 lifitegrast (reported

in 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 lifitegrast.9
DOSAGE AND ADMINISTRATION — Lifitegrast 5%
ophthalmic solution is supplied in cartons of 60 singleuse 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 lifitegrast 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. ■
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 treatment of dry eye disease. Arch Ophthalmol 2008; 126:1046.
4. VL Perez et al. Lifitegrast, a novel integrin antagonist for treatment of dry eye disease. Ocul Surf 2016; 14:207.
5. 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.
6. JD Sheppard et al. Lifitegrast 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. Lifitegrast 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.
8. EJ Holland et al. Lifitegrast clinical efficacy for treatment of
signs and symptoms of dry eye disease across three randomized controlled trials. Curr Med Res Opin 2016 July 22 (epub).
9. ED Donnenfeld et al. Safety of lifitegrast ophthalmic solution
5.0% in patients with dry eye disease: a 1-year, multicenter, randomized, placebo-controlled study. Cornea 2016; 35:741.

111


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®

Sugammadex (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 first
selective relaxant binding agent to be approved in the
US. Sugammadex has been available in the European
Union, Japan, and elsewhere for several years. Previous
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 significantly metabolized and is excreted in urine.
CLINICAL STUDIES — In randomized clinical trials, the

time required to reverse moderate and deep neuromuscular blockade induced by rocuronium and vecuronium
was less variable and significantly 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 first
twitch to 10% of baseline) was significantly 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
112

August 29, 2016

Vol. 58 (1502)
Table 1. Some Clinical Trials
Blocking Agent

Reversal Regimen

Minutes to
Recovery1

Moderate Blockade2
Rocuronium
(n=98)3

Sugammadex 2 mg/kg
Neostigmine 50 mcg/kg

1.5 (1.3-1.6)
18.6 (14.2-24.4)

Vecuronium
(n=93)4

Sugammadex 2 mg/kg
Neostigmine 50 mcg/kg

2.7 (2.2-3.3)
17.9 (13.1-24.3)

Rocuronium
(n=74)6

Sugammadex 4 mg/kg
Neostigmine 70 mcg/kg

2.7 (2.1-4.1)
49.0 (35.7-65.6)

Vecuronium
(n=83)7

Sugammadex 4 mg/kg
Neostigmine 70 mcg/kg

3.3 (1.8-4.4)
58.9 (42.9-79.8)

Deep Blockade5

1. Geometric mean time to recovery of train-of-four ratio to 0.9, with 95%
confidence intervals for moderate blockade trials and interquartile ranges
for deep blockade trials.
2. Defined as reappearance of the second twitch (T2) in response to train-offour 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. Defined 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.

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 thromboplastin 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 affinity 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 — Sugammadex should only be used to reverse neuromuscular
blockade caused by rocuronium or vecuronium. It is


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®

given 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: sugammadex 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.

Vol. 58 (1502)

August 29, 2016

8. Approximate WAC. 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-pricing-policy.

▶

An Oral Cholera Vaccine for
Travelers (Vaxchora)

The FDA has approved Vaxchora (PaxVax), a singledose, oral, live-attenuated cholera vaccine, to protect
against disease caused by Vibrio cholerae serogroup
O1 in adults 18-64 years old traveling to choleraaffected 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.
Vaxchora: vax kor' uh

Pronunciation Key

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 frequent 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
efficacy 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
113


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®

Table 1. Recommendations for Use of Vaxchora1

▶ 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
– with chronic medical conditions, such as cardiovascular
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.

were 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
114

Vol. 58 (1502)

August 29, 2016

be given to patients who have taken oral or parenteral
antibiotics within 14 days before vaccination. Chloroquine 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 purified bottled water
first, 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 efficacy beyond 6 months
and re-immunization are lacking. Vaccination is not
recommended for most tourists. ■
1. M Ali et al. Updated global burden of cholera in endemic countries. 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 103HgR 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.

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
it appears online. You can access it here: www.medicalletter.
org/TML-article-1500a.

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Review the efficacy and safety of the AspireAssist device for weight loss.
Review the efficacy and safety of lifitegrast (Xiidra) for treatment of dry eye disease.
Review the efficacy and safety of sugammadex (Bridion) for reversal of neuromuscular blockade.
Review the efficacy, safety, and recommendations for use of Vaxchora for prevention of cholera infection in travelers.

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Issue 1502 Questions
(Correspond to questions #41-50 in Comprehensive Exam #75, available January 2017)
AspireAssist – A New Device for Weight Loss

Sugammadex (Bridion) for Rapid Reversal of Neuromuscular
Blockade

1. A 32-year-old woman with a BMI of 40 has not been able to
achieve and maintain weight loss with lifestyle modifications
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 first year of use
d. all of the above

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

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
Lifitegrast (Xiidra) for Dry Eye Disease
4. Lifitegrast 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

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%

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