Phentermine Hydrochloride

1 INDICATIONS AND USAGE Phentermine hydrochloride capsules are 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 Height (feet, inches) Weight (pounds) 5'0" 5'3" 5'6" 5'9" 6'0" 6'3" 140 27 25 23 21 19 18 150 29 27 24 22 20 19 160 31 28 26 24 22 20 170 33 30 28 25 23 21 180 35 32 29 27 25 23 190 37 34 31 28 26 24 200 39 36 32 30 27 25 210 41 37 34 31 29 26 220 43 39 36 33 30 28 230 45 41 37 34 31 29 240 47 43 39 36 33 30 250 49 44 40 37 34 31 The limited usefulness of agents of this class, including phentermine, [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 )

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 capsules 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 15 mg to 30 mg as prescribed by the physician, at approximately 2 hours after breakfast for appetite control. Administration of one 30 mg capsule daily has been found to be adequate in depression of the appetite for 12 to 14 hours. Phentermine 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 is 15 mg daily for patients with severe renal impairment (eGFR 15 to 29 mL/min/1.73m 2 ). Avoid use of phentermine 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) ].

5 WARNINGS AND PRECAUTIONS Coadministration with other drugs for weight loss is not recommended (safety and efficacy of combination not established). ( 5.1 ) Rare cases of primary pulmonary hypertension have been reported. Phentermine should be discontinued in case of new, unexplained symptoms of dyspnea, angina pectoris, syncope or lower extremity edema. ( 5.2 ) Rare cases of serious regurgitant cardiac valvular disease have been reported. ( 5.3 ) Tolerance to the anorectic effect usually develops within a few weeks. If this occurs, phentermine should be discontinued. The recommended dose should not be exceeded. ( 5.4 ) Phentermine may impair the ability of the patient to engage in potentially hazardous activities such as operating machinery or driving a motor vehicle. ( 5.5 ) 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. ( 5.6 ) Concomitant alcohol use may result in an adverse drug reaction. ( 5.7 ) Use caution in patients with even mild hypertension (risk of increase in blood pressure). ( 5.8 ) A reduction in dose of insulin or oral hypoglycemic medication may be required in some patients. ( 5.9 ) 5.1 Coadministration with Other Drug Products for Weight Loss Phentermine hydrochloride capsules are indicated only as short-term (a few weeks) monotherapy for the management of exogenous obesity. The safety and efficacy of combination therapy with phentermine and any other drug products for weight loss including prescribed drugs, over-the-counter preparations, and herbal products, or serotonergic agents such as selective serotonin reuptake inhibitors (e.g., fluoxetine, sertraline, fluvoxamine, paroxetine), have not been established. Therefore, coadministration of phentermine and these drug products is not recommended. 5.2 Primary Pulmonary Hypertension Primary Pulmonary Hypertension (PPH) - a rare, frequently fatal disease of the lungs - has been reported to occur in patients receiving a combination of phentermine with fenfluramine or dexfenfluramine. The possibility of an association between PPH and the use of phentermine alone cannot be ruled out; there have been rare cases of PPH in patients who reportedly have taken phentermine alone. The initial symptom of PPH is usually dyspnea. Other initial symptoms may include angina pectoris, syncope or lower extremity edema. Patients should be advised to report immediately any deterioration in exercise tolerance. Treatment should be discontinued in patients who develop new, unexplained symptoms of dyspnea, angina pectoris, syncope or lower extremity edema, and patients should be evaluated for the possible presence of pulmonary hypertension. 5.3 Valvular Heart Disease Serious regurgitant cardiac valvular disease, primarily affecting the mitral, aortic and/or tricuspid valves, has been reported in otherwise healthy persons who had taken a combination of phentermine with fenfluramine or dexfenfluramine for weight loss. The possible role of phentermine in the etiology of these valvulopathies has not been established and their course in individuals after the drugs are stopped is not known. The possibility of an association between valvular heart disease and the use of phentermine alone cannot be ruled out; there have been rare cases of valvular heart disease in patients who reportedly have taken phentermine alone. 5.4 Development of Tolerance, Discontinuation in Case of Tolerance When tolerance to the anorectant effect develops, the recommended dose should not be exceeded in an attempt to increase the effect; rather, the drug should be discontinued. 5.5 Effect on the Ability to Engage in Potentially Hazardous Tasks Phentermine may impair the ability of the patient to engage in potentially hazardous activities such as operating machinery or driving a motor vehicle; the patient should therefore be cautioned accordingly. 5.6 Risk of Abuse and Dependence Phentermine is related chemically …

4 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 [see Use in Specific Populations (8.1) ] Nursing [see Use in Specific Populations (8.3) ] Known hypersensitivity, or idiosyncrasy to the sympathomimetic amines History of cardiovascular disease (e.g., coronary artery disease, stroke, arrhythmias, congestive heart failure, uncontrolled hypertension) ( 4 ) During or within 14 days following the administration of monoamine oxidase inhibitors ( 4 ) Hyperthyroidism ( 4 ) Glaucoma ( 4 ) Agitated states ( 4 ) History of drug abuse ( 4 ) Pregnancy ( 4 , 8.1 ) Nursing ( 4 , 8.3 ) Known hypersensitivity, or idiosyncrasy to the sympathomimetic amines ( 4 )

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.

8.1 Pregnancy Pregnancy Category X Phentermine is contraindicated during pregnancy because weight loss offers no potential benefit to a pregnant woman and may result in fetal harm. A minimum weight gain, and no weight loss, is currently recommended for all pregnant women, including those who are already overweight or obese, due to obligatory weight gain that occurs in maternal tissues during pregnancy. Phentermine has pharmacologic activity similar to amphetamine (d- and dll-amphetamine) [see Clinical Pharmacology (12.1) ]. Animal reproduction studies have not been conducted with phentermine. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.

8.3 Nursing Mothers It is not known if phentermine is excreted in human milk; however, other amphetamines are present in human milk. Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

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: Adverse events have been reported in the cardiovascular, central nervous, gastrointestinal, allergic, and endocrine systems. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Elite Laboratories, Inc. at 1-888-852-6657 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 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.