Weight Management Agents

Initial U.S. Approval:  2012

Mechanism of Action:

INDICATIONS AND USAGE:  BELVIQ is indicated as an 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 weight related comorbid condition (e.g., hypertension, dyslipidemia, type 2 diabetes)

[see Dosage and Administration (2)]

Limitations of Use:
The safety and efficacy of coadministration of BELVIQ with other products intended for weight loss including prescription drugs (e.g., phentermine), over-the-counter drugs, and herbal preparations have not been established
The effect of BELVIQ on cardiovascular morbidity and mortality has not been established

DOSAGE AND ADMINISTRATION
The recommended dose of BELVIQ is 10 mg administered orally twice daily. Do not exceed recommended dose [see Warnings and Precautions (5.4) and Patient Counseling Information (17)].

BELVIQ can be taken with or without food.

Response to therapy should be evaluated by week 12. If a patient has not lost at least 5% of baseline body weight, discontinue BELVIQ, as it is unlikely that the patient will achieve and sustain clinically meaningful weight loss with continued treatment [see Clinical Studies (14)].

BMI is calculated by dividing weight (in kg) by height (in meters) squared.

A BMI chart for height in inches and weight in pounds is provided below:

Table 1. BMI Conversion Chart

HOW SUPPLIED:
BELVIQ is provided as blue, film-coated, 10 mg tablets. The tablets are round, biconvex, debossed with "A" on one side and "10" on the other side.

Drug UPDATES:  BELVIQ XR ® (lorcaserin hydrochloride) extended - release tablets CIV
[Drug information ]     REVIEW PACKAGE INSERT FOR POSSIBLE UPDATES
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Initial U.S. Approval:  2016

INDICATIONS AND USAGE: BELVIQ XR is a serotonin 2C receptor agonist indicated as an 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) (1) or
27 kg/m2 or greater (overweight) in the presence of at least one weight-related comorbid condition, (e.g., hypertension, dyslipidemia, type 2 diabetes) (1)

Limitations of Use:

The safety and efficacy of coadministration with other products for weight loss have not been established (1)
The effect of BELVIQ XR on cardiovascular morbidity and mortality has not been established (1)

DOSAGE AND ADMINISTRATION:
One tablet of 20 mg once daily (2)
Discontinue if 5% weight loss is not achieved by week 12 (2)

HOW SUPPLIED:
20 mg film-coated tablet

30 kg/m2 or greater (obese) or
27 kg/m2 or greater (overweight) in the presence of at least one weight-related comorbidity such as hypertension, type 2 diabetes mellitus, or dyslipidemia.

Limitations of Use:
The effect of Qsymia on cardiovascular morbidity and mortality has not been established.
The safety and effectiveness of Qsymia in combination with other products intended for weight loss, including prescription and over-the-counter drugs, and herbal preparations, have not been established.

USE IN SPECIFIC POPULATIONS
Nursing Mothers: Discontinue drug or nursing.
Pediatric Use: Safety and effectiveness not established and use not recommended.

DOSAGE AND ADMINISTRATION:
Take once daily in morning. Avoid evening dose to prevent insomnia.

Recommended dose: Qsymia 3.75 mg/23 mg (phentermine 3.75 mg/topiramate 23 mg extended-release) daily for 14 days; then increase to 7.5 mg/46 mg daily .

Discontinue or escalate dose (as described) if 3% weight loss is not achieved after 12 weeks on 7.5 mg/46 mg dose.

Discontinue Qsymia if 5% weight loss is not achieved after 12 weeks on maximum daily dose of 15 mg/92 mg.

Discontinue 15 mg/92 mg dose gradually (as described) to prevent possible seizure.

Do not exceed 7.5 mg/46 mg dose for patients with moderate or severe renal impairment or patients with moderate hepatic impairment.

DOSAGE FORMS AND STRENGTHS:
Capsules: (phentermine mg/topiramate mg extended-release)
3.75 mg/23 mg
7.5 mg/46 mg
11.25 mg/69 mg
15 mg/92 mg

CONTRAINDICATIONS:
Pregnancy
Glaucoma
Hyperthyroidism
During or within 14 days of taking monoamine oxidase inhibitors
Known hypersensitivity or idiosyncrasy to sympathomimetic amines

WARNINGS AND PRECAUTIONS
Fetal Toxicity: Females of reproductive potential: Obtain negative pregnancy test before treatment and monthly thereafter; use effective contraception. Qsymia is available through a limited program under a Risk Evaluation and Mitigation Strategy (REMS).

Increase in Heart Rate: Monitor heart rate in all patients, especially those with cardiac or cerebrovascular disease .

Suicidal Behavior and Ideation: Monitor for depression or suicidal thoughts. Discontinue Qsymia if symptoms develop.
Acute Myopia and Secondary Angle Closure Glaucoma: Discontinue Qsymia.
Mood and Sleep Disorders: Consider dose reduction or withdrawal for clinically significant or persistent symptoms.
Cognitive Impairment: May cause disturbances in attention or memory. Caution patients about operating automobiles or hazardous machinery when starting treatment.
Metabolic Acidosis: Measure electrolytes before/during treatment.
Elevated Creatinine: Measure creatinine before/during treatment.
Use of Antidiabetic Medications: Weight loss may cause hypoglycemia. Measure serum glucose before/during treatment.

ADVERSE REACTIONS
Most common adverse reactions (incidence greater than or equal to 5% and at a rate at least 1.5 times placebo) are: paraesthesia, dizziness, dysgeusia, insomnia, constipation, and dry mouth.

TTo report SUSPECTED ADVERSE REACTIONS, contact VIVUS Inc., at 1-888-998-4887 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS
Oral contraceptives: Altered exposure may cause irregular bleeding but not increased risk of pregnancy. Advise patients not to discontinue oral contraceptives if spotting occurs.
CNS depressants including alcohol: Potentiate CNS depressant effects. Avoid concomitant use of alcohol.
Non-potassium sparing diuretics: May potentiate hypokalemia. Measure potassium before/during treatment.

The limited usefulness of agents of this class, including Suprenza, should be measured against possible risk factors inherent in their use.

USE IN SPECIFIC POPULATIONS
Nursing mothers: Discontinue drug or nursing taking into consideration importance of drug to mother.
Pediatric use: Safety and effectiveness not established.
Geriatric use: Due to substantial renal excretion, use with caution.
Use caution when administering Suprenza to patients with renal impairment

DOSAGE AND ADMINISTRATION:
Dosage should be individualized to obtain an adequate response with the lowest effective dose.
Late evening administration should be avoided (risk of insomnia).
Suprenza can be taken with or without food.

DOSAGE FORMS AND STRENGTHS:
Orally disintegrating tablets containing 15 mg, 30 mg, or 37.5 mg phentermine hydrochloride.

CONTRAINDICATIONS:
-History of cardiovascular disease (e.g., coronary artery disease, stroke, arrhythmias, congestive heart failure, uncontrolled hypertension).
-During or within 14 days following the administration of monoamine oxidase inhibitors.
-Hyperthyroidism.
-Glaucoma.
-Agitated states.
-History of drug abuse.
-Pregnancy.
-Nursing.
-Known hypersensitivity, or idiosyncrasy to the sympathomimetic amines.

WARNINGS AND PRECAUTIONS
-Coadministration with other drugs for weight loss is not recommended (safety and efficacy of combination not established).
-Rare cases of primary pulmonary hypertension have been reported. Suprenza should be discontinued in case of new, unexplained symptoms of dyspnea, angina pectoris, syncope or lower extremity edema.
-Rare cases of serious regurgitant cardiac valvular disease have been reported.
-Tolerance to the anorectic effect usually develops within a few weeks. If this occurs, Suprenza should be discontinued. The recommended dose should not be exceeded.
-Suprenza may impair the ability of the patient to engage in potentially hazardous activities such as operating machinery or driving a motor vehicle.
-Risk of abuse and dependence. The least amount feasible should be prescribed or dispensed at one time in order to minimize the possibility of overdosage.
-Concomitant alcohol use may result in an adverse drug reaction.
-Use caution in patients with even mild hypertension (risk of increase in blood pressure).
-A reduction in dose of insulin or oral hypoglycemic medication may be required in some patients.
Contains FD&C Yellow No. 5 (tartrazine) as color additive.

ADVERSE REACTIONS
Adverse events have been reported in the cardiovascular, central nervous, gastrointestinal, allergic, and endocrine systems.

To report SUSPECTED ADVERSE REACTIONS, contact Akrimax Pharmaceuticals, LLC at 1-888-383-1733 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS
Monoamine oxidase inhibitors: Risk of hypertensive crisis.
Alcohol: Consider potential interaction
Insulin and oral hypoglycemics: Requirements may be altered.
Adrenergic neuron blocking drugs: Hypotensive effect may be decreased by Suprenza.

Initial U.S. Approval:  2014

Mechanism of Action: Liraglutide is an acylated human glucagon-like peptide-1 (GLP-1) receptor agonist with 97% amino acid sequence homology to endogenous human GLP-1(7-37). Like endogenous GLP-1, liraglutide binds to and activates the GLP-1 receptor, a cell-surface receptor coupled to adenylyl cyclase activation through the stimulatory G-protein, Gs. Endogenous GLP-1 has a half-life of 1.5-2 minutes due to degradation by the ubiquitous endogenous enzymes, dipeptidyl peptidase 4 (DPP-4) and neutral endopeptidases (NEP). Unlike native GLP-1, liraglutide is stable against metabolic degradation by both peptidases and has a plasma half-life of 13 hours after subcutaneous administration. The pharmacokinetic profile of liraglutide, which makes it suitable for once-daily administration, is a result of self-association that delays absorption, plasma protein binding, and stability against metabolic degradation by DPP-4 and NEP.

GLP-1 is a physiological regulator of appetite and calorie intake, and the GLP-1 receptor is present in several areas of the brain involved in appetite regulation. In animal studies, peripheral administration of liraglutide resulted in the presence of liraglutide in specific brain regions regulating appetite, including the hypothalamus. Although liraglutide activated neurons in brain regions known to regulate appetite, specific brain regions mediating the effects of liraglutide on appetite were not identified in rats.

INDICATIONS AND USAGE: 
Saxenda is a glucagon-like peptide-1 (GLP-1) receptor agonist indicated as an 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/m 2 or greater (obese) ( 1) or
27 kg/m 2 or greater (overweight) in the presence of at least one weight-related comorbid condition (e.g. hypertension, type 2 diabetes mellitus, or dyslipidemia).

Limitations of Use:
Saxenda is not indicated for the treatment of type 2 diabetes.
Saxenda should not be used in combination with any other GLP-1 receptor agonist.
Saxenda should not be used with insulin ( 1, 5.4).
The effects of Saxenda on cardiovascular morbidity and mortality have not been established.
The safety and efficacy of coadministration with other products for weight loss have not been established.
Saxenda has not been studied in patients with a history of pancreatitis ( 1, 5.2).

HOW SUPPLIED: Solution for subcutaneous injection, pre-filled, multi-dose pen that delivers doses of 0.6 mg, 1.2 mg, 1.8 mg, 2.4 mg or 3 mg (6 mg/mL, 3 mL)

Initial U.S. Approval:  2014

Mechanism of Action: CONTRAVE has two components: naltrexone, an opioid antagonist, and bupropion, a relatively weak inhibitor of the neuronal reuptake of dopamine and norepinephrine. Nonclinical studies suggest that naltrexone and bupropion have effects on two separate areas of the brain involved in the regulation of food intake: the hypothalamus (appetite regulatory center) and the mesolimbic dopamine circuit (reward system). The exact neurochemical effects of CONTRAVE leading to weight loss are not fully understood.

INDICATIONS AND USAGE:
CONTRAVE is a combination of naltrexone, an opioid antagonist, and bupropion, an aminoketone antidepressant, indicated as an 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/m 2 or greater (obese) or
27 kg/m 2 or greater (overweight) in the presence of at least one weight-related comorbidity (e.g., hypertension, type 2 diabetes mellitus, or dyslipidemia).

Limitations of Use:
The effect of CONTRAVE on cardiovascular morbidity and mortality has not been established.
The safety and effectiveness of CONTRAVE in combination with other products intended for weight loss, including prescription and over-the-counter drugs, and herbal preparations, have not been established.

HOW SUPPLIED: Extended-Release Tablets: 8 mg naltrexone HCl /90 mg bupropion HCl