Drug Interactions between fenfluramine and phentermine / topiramate

CONTRAINDICATED: The efficacy of centrally-acting appetite suppressants in combination with other anorectic agents has not been studied, but available data suggest that combined use may have the potential for serious cardiac problems. In a case-control epidemiological study, the use of anorectic agents was associated with an increased risk of pulmonary hypertension, a rare but often fatal disorder, and use for longer than three months was associated with a 23-fold increase in risk. Increased risk of pulmonary hypertension with repeated courses of therapy cannot be excluded. The use of some anorectic agents such as fenfluramine and dexfenfluramine has been associated with valvular heart disease. Possible contributing factors include use for extended periods of time, higher than recommended dosages, and/or use in combination with other anorectic drugs.

MANAGEMENT: Centrally--acting appetite suppressants should not be used in combination with other anorectic agents, including prescription, over-the-counter, and herbal preparations. In addition, they are not recommended for patients who have used any anorectic agents within the prior year. The potential risk of possible serious adverse effects such as valvular heart disease and pulmonary hypertension should be assessed carefully against the benefit of weight loss, and baseline cardiac evaluation should be considered to detect preexisting valvular heart diseases or pulmonary hypertension prior to initiating treatment. These agents are not recommended for use in patients with known heart murmur or valvular heart disease, severe hypertension, or symptomatic cardiovascular disease including arrhythmias. Patients should be advised to immediately discontinue the medication and contact their physician if they experience potential signs and symptoms of pulmonary hypertension such as new onset or aggravation of exertional dyspnea, chest pain or tightness, syncope, and lower extremity edema.

MONITOR: Coadministration with topiramate may increase the plasma concentrations of phentermine. The exact mechanism of interaction has not been established. When a single 15 mg dose of phentermine was administered with a 92 mg dose of topiramate, phentermine peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 13% and 42%, respectively, compared to phentermine administered alone. No significant changes were observed in the pharmacokinetics of topiramate.

MANAGEMENT: Caution is advised when phentermine is used in combination with topiramate. Patients should be monitored for potentially increased adverse effects of phentermine such as dizziness, restlessness, insomnia, tremor, headache, euphoria, dysphoria, palpitation, tachycardia, and blood pressure elevation.

MONITOR: Central nervous system- and/or respiratory-depressant effects may be additively or synergistically increased in patients taking multiple drugs that cause these effects, especially in elderly or debilitated patients. Sedation and impairment of attention, judgment, thinking, and psychomotor skills may increase.

MANAGEMENT: During concomitant use of these drugs, patients should be monitored for potentially excessive or prolonged CNS and respiratory depression. Cautious dosage titration may be required, particularly at treatment initiation. Ambulatory patients should be counseled to avoid hazardous activities requiring mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.