Phentermine

12.1 Mechanism of Action Phentermine is a sympathomimetic amine with pharmacologic activity similar to the prototype drugs of this class used in obesity, amphetamine (d- and d / l-amphetamine). Drugs of this class used in obesity are commonly known as "anorectics" or "anorexigenics." It has not been established that the primary action of such drugs in treating obesity is one of appetite suppression since other central nervous system actions, or metabolic effects, may also be involved.

1 INDICATIONS AND USAGE Phentermine hydrochloride is indicated as a 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/m 2 , or ≥ 27 kg/m 2 in the presence of other risk factors (e.g., controlled hypertension, diabetes, hyperlipidemia). Below is a chart of body mass index (BMI) based on various heights and weights. BMI is calculated by taking the patient's weight, in kilograms (kg), divided by the patient's height, in meters (m), squared. Metric conversions are as follows: pounds ÷ 2.2 = kg; inches × 0.0254 = meters. BODY MASS INDEX (BMI), kg/m 2 The limited usefulness of agents of this class, including phentermine hydrochloride tablets, [ see Clinical Pharmacology (12.1 , 12.2) ] should be measured against possible risk factors inherent in their use such as those described below. Phentermine hydrochloride is a sympathomimetic amine anorectic indicated as a short-term adjunct (a few weeks) 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/m 2 , or ≥ 27 kg/m 2 in the presence of other risk factors (e.g., controlled hypertension, diabetes, hyperlipidemia). ( 1 ) The limited usefulness of agents of this class, including phentermine hydrochloride, should be measured against possible risk factors inherent in their use. ( 1 ) Figure

2 DOSAGE AND ADMINISTRATION Dosage should be individualized to obtain an adequate response with the lowest effective dose. (2.1) Late evening administration should be avoided (risk of insomnia). (2.1) Phentermine hydrochloride tablets can be taken with or without food. (2.1) Limit the dosage to 15 mg daily for patients with severe renal impairment (eGFR 15 to 29 mL/min/1.73 m 2 ) (2.2) 2.1 Exogenous Obesity Dosage should be individualized to obtain an adequate response with the lowest effective dose. The usual adult dose is one tablet (37.5 mg) daily, as prescribed by the physician, administered before breakfast or 1 to 2 hours after breakfast. The dosage may be adjusted to the patient’s need. For some patients, half tablet (18.75 mg) daily may be adequate, while in some cases it may be desirable to give half tablets (18.75 mg) two times a day. Phentermine hydrochloride is not recommended for use in pediatric patients ≤ 16 years of age. Late evening medication should be avoided because of the possibility of resulting insomnia. 2.2 Dosage in Patients With Renal Impairment The recommended maximum dosage of phentermine hydrochloride are 15 mg daily for patients with severe renal impairment (eGFR 15 to 29 mL min/1.73m 2 ). Avoid use of phentermine hydrochloride in patients with eGFR less than 15 mL/min/1.73m 2 or end-stage renal disease requiring dialysis [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].

6 ADVERSE REACTIONS The following adverse reactions are described, or described in greater detail, in other sections: Primary pulmonary hypertension [ see Warnings and Precautions (5.2) ] Valvular heart disease [ see Warnings and Precautions (5.3) ] Effect on the ability to engage in potentially hazardous tasks [ see Warnings and Precautions (5.5) ] Withdrawal effects following prolonged high dosage administration [ see Drug Abuse and Dependence (9.3) ] The following adverse reactions to phentermine have been identified: Cardiovascular Primary pulmonary hypertension and/or regurgitant cardiac valvular disease, palpitation, tachycardia, elevation of blood pressure, ischemic events. Central Nervous System Overstimulation, restlessness, dizziness, insomnia, euphoria, dysphoria, tremor, headache, psychosis. Gastrointestinal Dryness of the mouth, unpleasant taste, diarrhea, constipation, other gastrointestinal disturbances. Allergic Urticaria. Endocrine Impotence, changes in libido. Adverse events have been reported in the cardiovascular, central nervous, gastrointestinal, allergic, and endocrine systems. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Sun Pharmaceutical Industries, Inc. at 1-800-406-7984 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

7 DRUG INTERACTIONS Monoamine oxidase inhibitors: Risk of hypertensive crisis. ( 4 , 7.1 ) Alcohol: Consider potential interaction. ( 7.2 ) Insulin and oral hypoglycemics: Requirements may be altered. ( 7.3 ) Adrenergic neuron blocking drugs: Hypotensive effect may be decreased by phentermine. ( 7.4 ) 7.1 Monoamine Oxidase Inhibitors Use of phentermine is contraindicated during or within 14 days following the administration of monoamine oxidase inhibitors because of the risk of hypertensive crisis . 7.2 Alcohol Concomitant use of alcohol with phentermine may result in an adverse drug reaction . 7.3 Insulin and Oral Hypoglycemic Medications Requirements may be altered [ see Warnings and Precautions (5.9) ]. 7.4 Adrenergic Neuron Blocking Drugs Phentermine may decrease the hypotensive effect of adrenergic neuron blocking drugs.