Drug Interactions between fenfluramine and fluticasone / salmeterol

MONITOR: Coadministration with fenfluramine may decrease the plasma concentrations and therapeutic efficacy of drugs that are substrates of the CYP450 2B6 and/or CPY3A4 isoenzymes. The proposed mechanism, based on in vitro data, might be increased clearance due to induction of CYP450 2B6 and intestinal CYP450 3A4.

MANAGEMENT: Caution and monitoring are recommended if fenfluramine is used concomitantly with drugs that are substrates of CYP450 2B6 and/or CYP450 3A4, particularly sensitive substrates or those with a narrow therapeutic range. Monitoring for potential loss of therapeutic efficacy is recommended. The prescribing information for concomitant medications may be consulted to assess the benefits versus risks of coadministration, as well as any dosage adjustments that may be required during coadministration and/or following the discontinuation of a CYP450 2B6 and/or CYP450 3A4 inducer.

MONITOR: Coadministration of two or more sympathomimetic agents may increase the risk of adverse effects such as nervousness, irritability, and increased heart rate. Central nervous system (CNS) stimulants, particularly amphetamines, can potentiate the adrenergic response to vasopressors and other sympathomimetic agents. Additive increases in blood pressure and heart rate may occur due to enhanced peripheral sympathetic activity.

MANAGEMENT: Caution is advised if two or more sympathomimetic agents are coadministered. Pulse and blood pressure should be closely monitored.

Although they are often combined in clinical practice, the concomitant use of beta-2 adrenergic agonists and corticosteroids may result in additive hypokalemic effects. Since beta-2 agonists can sometimes cause QT interval prolongation, the development of hypokalemia may potentiate the risk of ventricular arrhythmias including torsade de pointes. However, clinical data are limited, and the potential significance is unknown. Patients who are receiving systemic or nebulized formulations of beta-2 agonists, high dosages of inhaled beta-2 agonists, or systemic corticosteroid therapy may be at a greater risk of developing hypokalemia.