Phentermine Hydrochloride

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 is 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 and pharmacologically to amphetamine (d- and d/l-amphetamine) and to other related stimulant drugs have been extensively abused. The possibility of abuse of phentermine 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 phentermine may result in an adverse drug reaction. 5.8 Use in Patients With Hypertension Use caution in prescribing phentermine 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. 8 USE IN SPECIFIC POPULATIONS Nursing mother: 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 ) Renal Impairment: Avoid use in patients with eGFR less than 15 mL/min/m2 or end-stage renal disease requiring dialysis ( 8.6 ) 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 d/l-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. 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 Based on the reported excretion of Phentermine in urine, exposure increases can be expected in patients with renal impairment [see Clinical Pharmacology ( 12.3 )]. Use caution when administering phentermine hydrochloride to patients with renal impairment. In patients with severe renal impairment (eGFR 15 to 29 mL/min/1.73 m2), limit the dosage of phentermine hydrochloride to 15 mg daily [see Dosage and Administration ( 2.2 )]. Phentermine hydrochloride has not been studied in patients with eGFR less than 15 mL/min/1.73 m2, including end-stage renal disease requiring dialysis; avoid use in these populations.