1 INDICATIONS AND USAGE ADIPEX-P® 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/m2, or ≥ 27 kg/m2 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 x 0.0254 = meters. The limited usefulness of agents of this class, including ADIPEX-P®, [see Clinical Pharmacology (12.1, 12.2)] should be measured against possible risk factors inherent in their use such as those described below. ADIPEX-P® 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/m2, or ≥ 27 kg/m2 in the presence of other risk factors (e.g., controlled hypertension, diabetes, hyperlipidemia). (1) The limited usefulness of agents of this class, including ADIPEX-P®, should be measured against possible risk factors inherent in their use. (1) Figure 1
3 DOSAGE FORMS AND STRENGTHS Capsules containing 37.5 mg phentermine hydrochloride (equivalent to 30 mg phentermine base). Tablets containing 37.5 mg phentermine hydrochloride (equivalent to 30 mg phentermine base). •Capsules containing 37.5 mg phentermine hydrochloride. (3) •Tablets containing 37.5 mg phentermine hydrochloride. (3)
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)
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. ADIPEX-P® 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, ADIPEX-P® should be discontinued. The recommended dose should not be exceeded. (5.4) •ADIPEX-P® 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 ADIPEX-P® is indicated only as short-term (a few weeks) monotherapy for the management of exogenous obesity. The safety and efficacy of combination therapy with ADIPEX-P® 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 ADIPEX-P® 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 ADIPEX-P® 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 ADIPEX-P® 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 ADIPEX-P® 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 ADIPEX-P® is related chemically and pharmacologically to amphetamine (d- and dll-amphetamine) and other related stimulant drugs that have been extensively abused. The possibility of abuse of ADIPEX-P® should be kept in mind when evaluating the desirability of including a drug as part of a weight reduction program. See Drug Abuse and Dependence (9) and Overdosage (10). The least amount feasible should be prescribed or dispensed at one time in order to minimize the possibility of overdosage. 5.7 Usage With Alcohol Concomitant use of alcohol with ADIPEX-P® may result in an adverse drug reaction. 5.8 Use in Patients With Hypertension Use caution in prescribing ADIPEX-P® for patients with even mild hypertension (risk of increase in blood pressure). 5.9 Use in Patients on Insulin or Oral Hypoglycemic Medications for Diabetes Mellitus A reduction in insulin or oral hypoglycemic medications in patients with diabetes mellitus may be required.
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 TEVA USA, PHARMACOVIGILANCE at 1-866-832-8537 or email@example.com; 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 ADIPEX-P®. (7.4) 7.1 Monoamine Oxidase Inhibitors Use of ADIPEX-P® 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 ADIPEX-P® 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 ADIPEX-P® may decrease the hypotensive effect of adrenergic neuron blocking drugs.
8 USE IN SPECIFIC POPULATIONS •Nursing mothers: Discontinue drug or nursing taking into consideration importance of drug to mother. (4, 8.3) •Pediatric use: Safety and effectiveness not established. (8.4) •Geriatric use: Due to substantial renal excretion, use with caution. (8.5) •Use caution when administering ADIPEX-P® to patients with renal impairment (8.6) 8.1 Pregnancy Teratogenic Effects Pregnancy category X ADIPEX-P® 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 ADIPEX-P® 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. 8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established. Because pediatric obesity is a chronic condition requiring long-term treatment, the use of this product, approved for short-term therapy, is not recommended. 8.5 Geriatric Use In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. 8.6 Renal Impairment ADIPEX-P® was not studied in patients with renal impairment. Based on the reported excretion of phentermine in urine, exposure increases can be expected in patients with renal impairment. Use caution when administering ADIPEX-P® to patients with renal impairment [see Clinical Pharmacology (12.3)].