Drug Interactions between fenfluramine and rifabutin

Consumer information for this interaction is not currently available.

GENERALLY AVOID: Coadministration of fenfluramine with potent inducers of CYP450 1A2, 2B6, or 3A4/5 may decrease exposure to fenfluramine and its major active metabolite, norfenfluramine. Over 75% of fenfluramine is metabolized to norfenfluramine prior to elimination, primarily by CYP450 1A2, 2B6 and 2D6, but also to a minor extent by CYP450 2C9, 2C19 and 3A4/5. When a single 0.35 mg/kg dose of fenfluramine oral solution was coadministered with 600 mg once daily rifampin (a weak CYP450 1A2, moderate CYP450 2B6, and potent CYP450 3A4/5 inducer) at steady state in healthy volunteers, fenfluramine peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 40% and 58%, respectively, compared to fenfluramine administered alone. The AUC of norfenfluramine also decreased by 50%, while the Cmax increased by 13%. Reduced efficacy of fenfluramine may occur.

MANAGEMENT: Concomitant use of fenfluramine with potent inducers of CYP450 1A2, 2B6, or 3A4/5 should be avoided when possible. If coadministration is required, monitor the patient for reduced efficacy and consider increasing the dosage of fenfluramine as needed in accordance with the product labeling, but not to exceed the recommended maximum daily dosage. If a potent inducer of CYP450 1A2, 2B6, or 3A4/5 is discontinued during maintenance treatment with fenfluramine, consider a gradual reduction to the fenfluramine dosage that was administered prior to initiating the inducer.