Download Antiobesity

Antiobesity Agents
Formulary Exception
Program Summary
This program applies to FlexRx Closed and GenRx Closed formularies.
FDA APPROVED INDICATIONS AND DOSAGE1,2,11,21,23-28,30,34,35
Available
Agent
Indication
strengths
Belviq™
10 mg
Adjunct to a reduced-calorie diet and
(lorcaserin)
increased physical activity for chronic
weight management in adults with an
tablets
initial BMI of:
 ≥30 kg/m2
 ≥27 kg/m2 in the presence of at least
one weight-related comorbid condition
Bontril PDM,
35 mg
Short-term (a few weeks) adjunct in a
Bontril Slow
105 mg
regimen of weight reduction based on
Release
exercise, behavioral modification and
(phendimetrazine)
caloric restriction in the management of
exogenous obesity for patients with an
tablets, capsules ER
initial body mass index ≥ 30 kg/m2 or
higher and who have not responded to
appropriate weight reducing regimen
alone.
Contrave®
8 mg / 90
(naltrexone/bupropio mg
n)
tablets ER
Didrex, Regimex
(benzphetamine)
tablets
25 mg
50 mg
Adjunct to a reduced-calorie diet and
increased physical activity for chronic
weight management in adults with an
initial body mass index (BMI) of:
• 30 kg/m2 or greater (obese)
• 27 kg/m2 or greater (overweight) in
the presence of at least one weightrelated comorbidity (e.g., hypertension,
type 2 diabetes mellitus, or
dyslipidemia)
Short-term (a few weeks) adjunct in a
regimen of weight reduction based on
exercise, behavioral modification and
caloric restriction in the management of
exogenous obesity for patients with an
initial body mass index ≥ 30 kg/m2 or
higher and who have not responded to
appropriate weight reducing regimen
alone.
Dosage
Twice daily
 Discontinue at 12 weeks if
5% weight loss is not
achieved
 Immediate release (35 mg)
1 tablet twice or three
times daily, 1 hour before
meals; dosage should be
individualized to lowest
effective dosage; maximum
dose is 2 tablets three
times daily
 Slow release (105 mg) once
daily in the morning, 30 –
60 minutes before morning
meal
Dose escalation schedule:
 Week 1 – 1 tablet in the
morning
 Week 2 – 1 tablet in the
morning and 1 tablet in the
evening
 Week 3 – 2 tablets in the
morning and 1 tablet in the
evening
 Week 4 and Onward – 2
tablets in the morning and
2 tablets in the evening
 Discontinue at 12 weeks if
5% weight loss is not
achieved
 25 to 50 mg one to three
times daily; dosage should
be individualized according
to patient response
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Agent
Diethylpropion
Available
strengths
25 mg
75 mg
tablets, capsules ER
Phentermine
tablets, capsules
Qsymia™
(phentermine/
topiramate)
15 mg
30 mg
37.5 mg
capsules
3.75/23mg
7.5/46mg
11.25/69m
g
15/92mg
Saxenda®
(liraglutide)
6 mg/ml,
3 ml/pens
Suprenza
(phentermine)
15 mg
30 mg
37.5 mg
orally disintegrating
tablets
Indication
Dosage
Short-term (a few weeks) adjunct in a
regimen of weight reduction based on
exercise, behavioral modification and
caloric restriction in the management of
exogenous obesity for patients with an
initial body mass index ≥ 30 kg/m2 or
higher and who have not responded to
appropriate weight reducing regimen
alone.
Management of exogenous obesity as a
short-term adjunct (a few weeks, up to
12 weeks based on agent) in a regimen
of weight reduction based on caloric
restriction in patients with an initial BMI
of 30 kg/m2 or higher, or BMI greater
than 27 kg/m2 in the presence of other
risk factors (e.g., hypertension,
diabetes mellitus, or dyslipidemia), and
who have not responded to appropriate
weight reducing regimen (diet and/or
exercise) alone
Adjunct to a reduced-calorie diet and
increased physical activity for chronic
weight management in adults with an
initial BMI of:
 ≥30 kg/m2
 ≥27 kg/m2 in the presence of at least
one weight-related comorbid condition
 Immediate release (25 mg)
three times daily, 1 hour
before meals
 Controlled release (75 mg)
once daily in midmorning
Adjunct to a reduced-calorie diet and
increased physical activity for chronic
weight management in adult patients
with an initial body mass index (BMI) of
 30 kg/m2 or greater (obese) or
 27 kg/m2 or greater (overweight) in
the presence of at least one weightrelated comorbid condition (e.g.
hypertension, type 2 diabetes mellitus,
or dyslipidemia)
Short-term (a few weeks) adjunct in a
regimen of weight reduction based on
exercise, behavioral modification and
caloric restriction in the management of
exogenous obesity for patients with an
initial body mass index ≥ 30 kg/m2 or
≥27 kg/m2 in the presence of other risk
Once or twice daily,
depending on agent.
 18.75 mg twice daily, onehalf hour before meals;
 15-37.5 mg once daily
before or after breakfast or
at least 10-14 hours before
bedtime
Once daily
Titration schedule:
3.75mg/23mg once daily for
14 days, then increase to
7.5mg/46mg daily
 Discontinue or escalate the
dose if 3% weight loss is
not achieved after 12 weeks
on 7.5mg/46mg daily
 Discontinue if 5% weight
loss is not achieved after 12
weeks on maximum daily
dose of 15mg/92mg
Initiate at 0.6 mg per day for
one week. In weekly
intervals, increase the dose
until a dose of 3 mg per day
is reached
Once daily
 Dosage should be
individualized to obtain an
adequate response with the
lowest effective dose.
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Agent
Xenical (orlistat)
capsules
Available
strengths
120 mg
Indication
factors (e.g., controlled hypertension,
diabetes, hyperlipidemia)
Not for use in pediatric patients < 16
years of age
Obesity management including weight
loss and weight maintenance when used
in conjunction with a reduced-calorie
diet and to reduce the risk for weight
regain after prior weight loss. It is
indicated for obese patients with an
initial body mass index (BMI) ≥30
kg/m2 or >27 kg/m2 in the presence of
other risk factors (e.g., hypertension,
diabetes, dyslipidemia)
Safety/effectiveness in patients <12
years of age not established
Dosage
 120 mg three times daily
with each main meal
containing fat (during or up
to 1 hour after the meal)
CLINICAL RATIONALE:
Disease state
Obesity, a complex, multi-factorial condition and is a fast growing epidemic among adults,
adolescents and children. It increases the risk of morbidity and mortality from hypertension,
dyslipidemia, type 2 diabetes, coronary heart disease, stroke, gallbladder disease,
osteoarthritis, sleep apnea and respiratory problems. 3
Adults with body mass index (BMI) 25-29.9 kg/m2 are considered overweight; those with BMI
≥30 kg/m2 are considered obese. Losing even a small amount of weight and increasing
physical activity can prevent some complications of obesity, particularly type 2 diabetes. Diet
and exercise are the preferred methods for losing weight, but long-term failure rates are
high. Pharmacologic treatment of obesity has been limited by modest efficacy, adverse
effects, low adherence rates, and regain of weight with drug cessation. 33
The Canadian Task Force on Preventive Health Care (2015) states lifestyle interventions
(e.g., behavioral therapies, dietary and physical activity programming and support) are the
first line of treatment for most patients with overweight or obesity as the benefit-to-harm
ratio appears more favorable than for pharmacologic interventions. Pharmacotherapy and
surgery are options for more severe cases of obesity. 20
The Endocrine Society (U.S., 2015) suggests medications approved for chronic weight
management can be useful adjuncts to lifestyle change for patients who have been
unsuccessful with diet and exercise alone. They recommend adherence to American Heart
Association Guidelines (2013) [see below] which include advice for assessment and treatment
with diet and exercise, as well as bariatric surgery for appropriate candidates. 32
 Diet, exercise, and behavioral modification should be included in all overweight and
obesity management approaches for BMI >25 kg/m2 and other tools [e.g.,
pharmacotherapy (if BMI >27 kg/m2 with comorbidity or BMI >30 kg/m2) and bariatric
surgery (BMI >35 kg/m2 with comorbidity or BMI >40 kg/m2)] should be used as
adjuncts to behavioral modification to reduce food intake and increase physical activity
when possible. Drugs may amplify adherence to behavior change and may improve
physical functioning such that increased physical activity is easier in those who cannot
exercise initially.
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

Patients who have a history of being unable to successfully lose and maintain weight and
who meet label indications are candidates for weight loss medications.
Given the wide clinical prescribing of phentermine for >20 years and lack of evidence of
serious side effects, even in the absence of long-term controlled safety and efficacy data,
it seems reasonable for clinicians to prescribe phentermine long term as long as the
patient: 1) has no evidence of serious cardiovascular disease; 2) does not have serious
psychiatric disease or a history of substance abuse; 3) has been informed about weight
loss medications that are FDA approved for long-term use and told that these have been
documented to be safe and effective whereas phentermine has not; 4) does not
demonstrate a clinically significant increase in pulse or BP when taking phentermine; and
5) demonstrates a significant weight loss while using the medication. These aspects of
care should be documented in the patient’s medical record, and the off-label nature of the
prescribing should be documented at each visit. Medication should be started at 7.5 or 15
mg/day initially and only increased if the patient is not achieving clinically significant
weight loss. Patients should be followed at least monthly during dose escalation and then
at least every 3 months when on a stable dose.
The Department of Veteran’s Affairs (U.S., 2014) states controversy exists around optimal
timing of introducing pharmacotherapy into a weight loss program. Some favor prescribing
these agents only after Comprehensive Lifestyle Intervention (CLI) has failed to produce
weight loss consistent with goals. Others offer these agents earlier in treatment to assist in
the initiation of weight loss, boost patient self-confidence, and expedite reduction in risk for
obesity-associated conditions. Regardless of when pharmacotherapy is introduced, it should
always be in combination with a reduced calorie diet and other lifestyle changes. 4
 Note: In clinical trials, pharmacotherapy was started simultaneously with CLI.
Introduction of drugs very early in treatment is not suggested in clinical practice. Hence,
the initial weight loss may be less than demonstrated in studies when pharmacotherapy is
started after CLI. 4
 VA algorithm recommendations include the following. For obese patients (BMI >30
kg/m2), or overweight patients (BMI >25 kg/m2) with >1 obesity associated condition,
they recommend patients participate in CLI (i.e., combination dietary, physicial activity,
and behavioral components, including >12 intervention sessions over a 12 month period).
If patients do not meet goals with CLI, and meet appropriate criteria, then consider
pharmacotherapy and/or bariatric surgery as adjunct therapies. For overweight patients
(not obese) without obesity associated conditions, they recommend providing information
and behavioral counseling on healthy diet, physical activity, and behavior in order to
pursue and maintain a healthy weight. 4
The American Heart Association/American College of Cardiology/Obesity Society Guideline
(2013) suggests if history indicates the patient has never participated in a comprehensive
lifestyle intervention program as defined in the guidelines (i.e., trained interventionist or
nutritional professional supervision of diet, exercise, and behavior therapy), it is
recommended that the patient undertake such a program before addition of adjunctive
therapies (e.g., pharmacotherapy), since a substantial proportion of patients will lose
sufficient weight to improve health with comprehensive lifestyle management alone. If a
patient has been unable to lose weight or sustain weight loss with comprehensive lifestyle
intervention and has BMI >30 kg/m2 or >27 kg/m2 with comorbidity, adjunctive therapy may
be considered. The expert panel did not review comprehensive evidence on pharmacotherapy
for weight loss. Medications should be FDA approved and clinicians should be knowledgeable
about the product label. The provider should weigh potential risks of the medication vs.
potential benefits of successful weight loss for the individual patient. 13
A review (2015) suggests that although these agents have all shown efficacy in weight loss,
some may regard the amount of loss insufficient. It is important to recognize that clinical
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trials report means derived from intention-to-treat populations, whereas in clinical practice it
is “responder” populations that better reflect the target population. Significant metabolic, and
in the main cardiovascular, risk factors are improved, which may be related to weight loss
rather than independent effects of the drugs. Substantial barriers remain in successfully
integrating these agents into weight management practice, largely related to cost, patient
acceptability, and clinician willingness to be engaged in adjunctive lifestyle management.
Hard clinical outcome benefit has not yet been established. 36
Efficacy
Sympathomimetic Drugs
A 36 week trial compared placebo vs continuous phentermine or intermittent phentermine.
Both continuous and intermittent phentermine produced more weight loss vs placebo. In a
survey of bariatric physicians, use of these sympathomimetics was found to be more frequent
than sibutramine or orlistat, and they were often used for longer than approved by the FDA.
Despite the risk of adverse effects and the FDA recommendation for only short term use, data
suggest phentermine has been widely prescribed for weight loss in the United States, often
for durations longer than recommended. Published studies have provided longer term safety
and efficacy data on phentermine (used in combination with topiramate) in recent weight loss
trials.29
In a randomized trial, diethylpropion was compared with phentermine over 12 weeks in
patients on 1,500 calories/day (n = 99). Patients had to be >20% above an undefined
desirable weight, and were excluded if anorectic agents were used within one month of the
study. After 12 weeks of treatment, phentermine 30 mg/day resulted in a mean weight loss
of 1.96 kg more vs diethylpropion 75 mg/day (p <0.01). Patients taking diethylpropion
trended toward a lower baseline weight. Diethylpropion caused more dizziness/giddiness
(number needed to harm [NNH] = 25) and dry mouth (NNH = 17) vs phentermine;
phentermine caused more drowsiness (NNH = 25) and constipation (NNH = 25).14
A meta-analysis found a modest degree of weight loss in patients taking sibutramine (off
market), phentermine, or diethylpropion. A mean difference in weight loss of 4.45 kg (95%
CI 3.62 to 5.29) was found at 12 months with sibutramine. In patients taking phentermine or
diethylpropion, there was a reported pooled mean difference in weight loss at six months of
3.6 kg (95%CI 0.6 to 6.0) and 3.0 kg (95% CI –1.6 to 11.5), respectively.14
Lorcaserin
The efficacy of lorcaserin was evaluated in three phase III trials (BLOOM5, BLOSSOM6 and
BLOOM-DM7) in overweight adult patients with one co-existing condition or obese patients.
The efficacy and safety of phentermine/topiramate was evaluated in two phase III trials
(EQUIP8 and CONQUER9) and one long-term extension study (SEQUEL10) in uncomplicated,
severely obese patients and overweight and obese patients with two or more comorbidities.
Sustained weight loss and discontinuation effects of lorcaserin were evaluated in the BLOOM
study in patients who were randomized to continue on therapy or receive placebo for an
additional year. Of the patients who received lorcaserin for one year and continued on
therapy for a second, 67.9 percent of the patients maintained a weight loss of 5 percent or
more of their body weight compared to 50.3 percent of patients who received lorcaserin for
one year and placebo for the second year.5 Sustained effects of phentermine/topiramate were
also evaluated in an extension study (SEQUEL) and showed continued weight loss in patients
on therapy up to a 108 week period.10
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Lorcaserin should be discontinued if the patient has not lost at least 5% of baseline body
weight at week 12, since it is unlikely that the patient will achieve and sustain clinically
meaningful weight loss with continued treatment.1 Phentermine/topiramate should be
discontinued if the patient has not lost at least 5% of baseline body weight at week 12 on
maximum doses, since it is unlikely that the patient will achieve and sustain clinically
meaningful weight loss with continued treatment.2
Naltrexone/bupropion (NB)
Four 56-week multicenter, double-blind, placebo-controlled obesity trials (Contrave Obesity
Research, or COR-I, COR-II, COR-BMOD, and COR-Diabetes) were conducted to evaluate the
effect of NB in conjunction with lifestyle modification in 4,536 patients randomized to NB or
placebo. The COR-I, COR-II, and COR-BMOD trials enrolled patients with obesity (BMI >30
kg/m2) or overweight (BMI >27 kg/m2) and >1 comorbidity (hypertension or dyslipidemia).
The COR-Diabetes trial enrolled patients with BMI >27 kg/m 2 with type 2 diabetes with or
without hypertension and/or dyslipidemia. 21
FDA guidance stipulates that a drug will be considered effective if >1 of the following criteria
is satisfied after one year of treatment: 1) The difference in mean weight loss between the
active-product and placebo-treated groups is >5% and the difference is statistically
significant or, 2) The proportion of patients who lose >5% of baseline body weight in the
active-product group is >35%, is approximately double the proportion in the placebo-treated
group, and the difference between groups is statistically significant. 1) Mean placebo
subtracted weight changes with NB from baseline in the four trials were: -4.8%, -4.2%, 4.6%, -3.3% (all p<0.001 vs placebo). Therefore NB did not satisfy the first FDA criterion for
efficacy. 2) In the four NB trials, proportions of patients who lost >5% of baseline body
weight (NB vs placebo) were: Trial 301 [COR-I] 48% vs 16%; 302 [COR-BMOD] 66% vs
43%; 303 [COR-II] 56% vs 18%; 304{COR-Diabetic] 45% vs 19%. All NB32 vs placebo
comparisons were considered of nominal statistical significance. Two of these trials (301
[COR-I] and 304 [COR-Diabetes]) did satisfy the second criterion for efficacy. 22
Naltrexone/buproprion should be discontinued if the patient has not lost at least 5% of
baseline body weight at week 12, since it is unlikely that the patient will achieve and sustain
clinically meaningful weight loss with continued treatment.21
Phentermine/topiramate
The effect of phentermine/topiramate on weight loss in conjunction with reduced caloric
intake and increased physical activity was studied in 2 randomized, double-blind, placebocontrolled studies in obese patients (Study 1) and in obese and overweight patients with two
or more significant co-morbidities (Study 2). Both studies had a 4-week titration period,
followed by 52 weeks of treatment. Study 1 showed a -1.6%, -5.1%, and -10.9% least
squares mean change from baseline body weight in placebo, 3.75 mg/23 mg
phentermine/topiramate, and 15 mg/92 mg phentermine/topiramate respectively. Study 2
showed a -1.2%, -7.8%, and -9.8% least squares mean change from baseline body weight in
placebo, 7.5 mg/46 mg phentermine/topiramate, and 15 mg/92 mg phentermine/topiramate
respectively. The differences in least square mean body weight for all strengths of
phentermine/topiramate compared to placebo were statistically significant. 2
Liraglutide 30
The efficacy of liraglutide for chronic weight management in conjunction with reduced caloric
intake and increased physical activity were studied in three 56-week, randomized, doubleblind, placebo-controlled trials. In all studies, Saxenda was titrated to 3 mg daily during a 4week period. All patients received instruction for a reduced calorie diet (approximately 500
kcal/day deficit) and exercise counseling (recommended increase in physical activity of
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minimum 150 mins/week) that began with the first dose of study medication or placebo and
continued throughout the trial.
Liraglutide is not indicated for the treatment of type 2 diabetes. Liraglutide should not be
used in combination with any GLP-1 receptor agonist or insulin. The effects of liraglutide on
cardiovascular morbidity and mortality have not been established. The safety and efficacy of
liraglutide co-administered with other products for weight loss have not been established.
Liraglutide has not been studied in patients with a history of pancreatitis.
Safety
Phentermine, benzphetamine, phendimetrazine, diethylpropion
These drugs should not be used in advanced arteriosclerosis; symptomatic cardiovascular
disease; moderate-to-severe hypertension; hyperthyroidism; known hypersensitivity or
idiosyncrasy to sympathomimetic amines; glaucoma; highly nervous or agitated states;
history of drug abuse; during or within 14 days following the administration of MAO inhibitors
(hypertensive crises may result); or for co-administration with other CNS stimulants.
Tolerance to the anorectic effects may develop within a few weeks. The recommended dose
should not be exceeded in an attempt to increase the effect; rather, the drug should be
discontinued.11
Abrupt discontinuation may result in depression or extreme fatigue; sleep EEG changes have
been noted. Gradual withdrawal of therapy is recommended. These drugs are related to
amphetamines, and have abuse potential. Psychological dependence may occur. Phentermine
is Drug Enforcement Agency (DEA) Schedule IV. Benzphetamine and phendimetrazine are
DEA schedule III; diethylpropion is DEA schedule IV.11 To what degree phentermine used
longer term for weight loss actually increases risk of abuse or results in significant
cardiovascular adverse effects has been debated in clinical practice.15,16 Although
phentermine is only approved for short-term use (usually interpreted as 12 weeks), some
clinicians use the drug on a long-term basis. A well conducted observational study did not
show significant increases in blood pressure or pulse among patients receiving phentermine
for 1 year vs control group with similar weight loss.18
These agents should not be used in combination with other anorectic agents, including
prescribed drugs, OTC preparations, and herbal products. There are additional potential
adverse interactions with alcohol. Convulsions may be increased in some epileptics receiving
diethylpropion. Dose titration or drug discontinuance may be necessary. 11 Data on adverse
events in weight-loss trials that used sympathomimetic amines are limited, but include
increased heart rate and blood pressure, dry mouth, nervousness, insomnia and
constipation.17
Lorcaserin
In the lorcaserin placebo-controlled trials, 3451 patients aged 18 to 66 years were exposed to
the drug for a minimum duration of one year. The most commonly reported adverse reactions
were headache, dizziness, fatigue, nausea, dry mouth, and constipation. Other clinically
important adverse reactions reported included hypoglycemia in patients with type 2 diabetes
mellitus (1.6% vs. 0.4%), cognitive impairment (2.3% vs. 0.7%), psychiatric disorders
leading to hospitalization or drug withdrawal (2.2% vs. 1.1%), euphoria (0.17% vs. 0.03%),
depression (2.6% vs. 2.4%), and suicidal ideation (0.6% vs. 0.4%), eye disorders (without
diabetes: 4.5% vs. 3.0%, with type 2 diabetes: 6.3% vs. 1.6%), and possible occurrence of
regurgitant cardiac valve disease (2.4% vs. 2.0%) and serotonin associated adverse
reactions. Lorcaserin carries warnings for serotonin syndrome or neuroleptic malignant
syndrome like reactions, valvular heart disease, cognitive impairment, psychiatric disorders,
depression and suicidal thoughts, use of antidiabetic medications, and priaprism. Lab
abnormalities reported included lymphocyte counts below lower limit of normal (LLN) was
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seen in 12.2% vs. 9.0%, low neutrophil counts (5.6% vs. 4.3%), hemoglobin below LLN
(10.4% vs. 9.3%), prolactin levels greater than the upper limit of normal (ULN).1
Phentermine/topiramate
The safety of phentermine/topiramate was evaluated in 2 phase III trials and 2 phase II
supportive trials in 2318 patients. The most commonly reported adverse reactions were
paresthesia, dizziness, dysgeusia, insomnia, constipation, and dry mouth. Other clinically
important adverse reactions reported included paresthesias (4.2% to 19.9% depending on
the dose vs. 1.9%), dysgeusia (1.3% to 9.4% depending on dose vs. 1.1%), mood and sleep
disorders (14.5% to 20.6% depending on dose vs. 10.3%), cognitive disorders (2.1% to
7.6% depending on dose vs. 1.5%), and nephrolithiasis (0.4% to 1.2% depending on dose
vs. 0.3%). Phentermine/topiramate carries warnings for fetal toxicity, increased heart rate,
suicidal behavior and ideation, acute myopia and secondary angle closure glaucoma, mood
and sleep disorders, cognitive impairment, metabolic acidosis, elevated creatinine, and use of
antidiabetic medications. Lab abnormalities reported included minor decreases in serum
bicarbonate levels, hypokalemia, dose related increases of serum creatinine from baseline. 2
Naltrexone/bupropion (NB)
Prescribing information for NB contains contraindications and precautions/warnings similar
with those for bupropion and naltrexone products. There is a boxed warning on suicidal
thoughts and behavior and neuropsychiatric reactions, and a dose related seizure risk. NB
should not be administered to patients receiving chronic opioids, due to the naltrexone
component. If chronic opiate therapy is required, NB treatment should be stopped. Patients
may be more sensitive to opioids, even at lower doses, after NB treatment is discontinued.
Patients should be opioid-free before starting NB treatment. Other safety precautions include
risk of increased blood pressure and heart rate, allergic reactions, hepatotoxicity, mania,
angle closure glaucoma, and drug interactions with drugs metabolized by CYP2D6 or CYP2B6,
drugs that lower seizure threshold, dopaminergic drugs or alcohol. 21
Liraglutide
The safety of liraglutide for chronic weight management in conjunction with reduced caloric
intake and increased physical activity were studied in three 56-week, randomized, doubleblind, placebo-controlled trials. Liraglutide is contraindicated in those with a personal or
family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type
2; hypersensitivity to liraglutide or any product components; and in pregnancy. Liraglutide is
not indicated for the treatment of type 2 diabetes. Liraglutide should not be used with
another GLP-1 receptor agonist agent, including another liraglutide agent. Saxenda should
not be used with insulin. Liraglutide should be discontinued if the patient has not lost at least
4% of baseline body weight at week 16, since it is unlikely that the patient will achieve and
sustain clinically meaningful weight loss with continued treatment. 30
Co-Administration
None of the FDA approved weight loss agents have approval for co-administration with
another weight loss agent. New guidelines do not support the use of co-administration of
weight loss pharmacological agents.32,33 The prescribing information for benzphetamine,
lorcaserin, naltrexone/bupropion, and phentermine/ topiramate states that the safety and
efficacy of co-administration with other products for weight loss have not been
established.1,2,21 Diethylpropion lists co-administration with other anorectic agents as a
contraindication.34 Use of non-approved drug combinations for obesity treatment should be
limited to clinical trials, and patients should be informed when drugs are being used off label
alone or in combination.31
For additional clinical information see Prime Therapeutics Formulary Chapter 9.5B: Weight
Loss Agents.
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REFERENCES:
1.
Belviq (lorcaserin) Prescribing Information. Arena. December 2014.
2.
Qsymia (phentermine/topiramate) Prescribing Information. Vivus. September 2014.
3.
Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of obesity in the United States,
2009–2010. NCHS data brief, no 82. Hyattsville, MD: National Center for Health
Statistics. January 2012. Accessed on July 13, 2012 @
http://www.cdc.gov/nchs/data/databriefs/db82.pdf
4.
Department of Veteran’s Affairs. Department of Defense. Management of overweight
and obesity. 2014. Accessed 10.9.2015 at:
http://www.healthquality.va.gov/guidelines/CD/obesity/CPGManagementOfOverweight
AndObesityFINAL041315.pdf.
5.
Smith SR, Weissman NJ, Anderson CM, et al. Multicenter, Placebo-Controlled Trial of
Lorcaserin for Weight Management. NEJM. 2010;363:245-56. [BLOOM]
6.
Fiddler MC, Sanchez M, Raether B, et al. A One-Year Randomized Trial of Lorcaserin
for Weight Loss in Obese and Overweight Adults: The BLOSSOM Trial. J Clin Endocrinol
Metab. 2011:96(10):3067-3077.
7.
O’Neil PM, Smith SR, Weissman NJ, et al. Randomized Placebo-Controlled Clinical Trial
of Lorcaserin for Weight Loss in Type 2 Diabetes Mellitus: The BLOOM-DM Study.
Obesity Journal. 2012:20(7):1426-1436.
8.
Allison DB, Gadde KM, Garvey WT, et al. Controlled-Release Phentermine/Topiramate
in Severely Obese Adults: A Randomized Controlled Trial (EQUIP). Obesity Journal.
2012:20(2):330-342.
9.
Gadde KM, Allison DB, Ryan DH, et al. Effect of low-dose, controlled-release,
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overweight and obese adults (CONQUER): a randomized, placebo-controlled, phase 3
trial. The Lancet. 2011;377:1341-1352.
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benefits with controlled-release phentermine/topiramate in obese and overweight
adults (SEQUEL): a randomized, placebo-controlled, phase 3 extension study. Am J
Clin Nutr. 2012;95:297-308.
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2014.
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Antiobesity Agents Formulary Exception Criteria
OBJECTIVE
The criteria defined in the Antiobesity Formulary Exception Criteria will be applied when the
included medications are prescribed for any patient. The intent of the criteria is to limit
prescribing to those patients whose initial body mass index (BMI) is > 30 kg/m2 or > 27
kg/m2 in the presence of other risk factors (e.g., hypertension, coronary heart disease, type
2 diabetes, dyslipidemia, sleep apnea). Initial criteria also include medical evaluation ruling
out organic causes of obesity, determination of obesity-related risk factors, and involvement
in a weight loss program including a reduced-calorie diet and/or exercise, and/or behavioral
modification. These medications will not be approved for patients receiving monoamine
oxidase inhibitors. In addition, the criteria will require use of an orlistat product (prescription
Xenical or nonprescription Alli) prior to a stimulant. If the initial criteria are met, Xenical will
be approved for 12 months; stimulant medications for 3 months. Clinical literature supports a
reasonable and medically significant outcome for many patients is to lose 10% of body weight
in the first 6 months of treatment.3 If the patient loses 5% or more of his/her initial BMI or
body weight, the patient will receive an approval for 12 months for Xenical or for 3 months
for the stimulants.
TARGET DRUG
Adipex-P (phentermine)a
Belviq (lorcaserin)
Bontril Slow Release (phendimetrazine)a
Bontril PDM (phendimetrazine)a
Contrave® (naltrexone/bupropion)
Didrex (benzphetamine)a
Diethylpropion
Qsymia™ (phentermine/topiramate)
Regimex™ (benzphetamine)
Saxenda® (liraglutide)
Suprenza™ (phentermine)
Xenical (orlistat)
a - Indicates generic availability
b – brand name product no longer available in U.S. market
FORMULARY EXCEPTION CRITERIA FOR APPROVAL
Initial Evaluation - FlexRX formulary
Antiobesity Agents will be approved when ALL of the following are met:
1. Requested medication is not excluded under the patient’s current benefit plan AND
2. The patient has received a complete medication evaluation ruling out organic causes
of obesity (e.g., hypothyroidism) and including a determination of BMI and other
obesity-related risk factors (e.g., hypertension, coronary heart disease, type 2
diabetes, dyslipidemia, sleep apnea) AND
3. The patient has a BMI > 30 kg/m2 OR BMI > 27 kg/m2 (or high waist circumference)
and the presence of at least one obesity-related risk factor listed above AND
4. The patient will be concurrently involved in a weight loss program including a reducedcalorie diet and/or exercise, and/or behavioral modification AND
5. The patient is not currently taking a monoamine oxidase inhibitor or hasn’t taken one
in the past 14 days AND
6. ONE of the following:
a. The patient has tried and failed both Xenical AND generic phentermine
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OR
b. Patient has a documented intolerance, FDA labeled contraindication, or
hypersensitivity to both Xenical and phentermine
Length of approval: 3 months
Initial Evaluation - GenRx Formulary
Antiobesity Agents will be approved when ALL of the following are met:
1. Requested medication is not excluded under the patient’s current benefit plan AND
2. The patient has received a complete medication evaluation ruling out organic causes
of obesity (e.g., hypothyroidism) and including a determination of BMI and other
obesity-related risk factors (e.g., hypertension, coronary heart disease, type 2
diabetes, dyslipidemia, sleep apnea) AND
3. The patient has a BMI > 30 kg/m2 OR BMI > 27 kg/m2 (or high waist circumference)
and the presence of at least one obesity-related risk factor listed above AND
4. The patient will be concurrently involved in a weight loss program including a reducedcalorie diet and/or exercise, and/or behavioral modification AND
5. The patient is not currently taking a monoamine oxidase inhibitor or hasn’t taken one
in the past 14 days
AND
6. ONE of the following:
a. The patient has tried and failed generic phentermine
OR
b. Patient has a documented intolerance, FDA labeled contraindication, or
hypersensitivity to phentermine
Length of approval: 3 months
Renewal Evaluation – GenRx Formulary and FlexRx Formulary
Antiobesity Agents will be approved when the following is met:
1. The patient has lost 5% or more of his/her initial BMI or weight
Length of approval:
3 months for stimulants
12 months for non-stimulants
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