Drug Interaction Report

Consumer information for this interaction is not currently available.

MONITOR: Coadministration with inhibitors of CYP450 1A2 or 2D6 may increase the plasma concentrations of fenfluramine. 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 50 mg once daily fluvoxamine (a potent CYP450 1A2 inhibitor) at steady state in healthy volunteers, fenfluramine peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 22% and 102%, respectively, while the Cmax and AUC of norfenfluramine decreased by 44% and 22%, respectively. Coadministration with 30 mg once daily paroxetine (a potent CYP450 2D6 inhibitor) at steady state in healthy volunteers increased the Cmax and AUC of fenfluramine by 13% and 81%, respectively, and decreased Cmax and AUC of norfenfluramine by 29% and 13%, respectively. Coadministration with repeated doses of cannabidiol (a weak CYP450 1A2 inhibitor with the potential to also inhibit CYP450 2B6, 2C8, 2C9, and 2C19 at clinically relevant concentrations) increased the Cmax and AUC of fenfluramine by 10% and 59%, respectively, and decreased Cmax and AUC of norfenfluramine by 33% and 22%, respectively. Elevated plasma levels of fenfluramine may increase the risk of serious adverse effects such as valvular heart disease, pulmonary arterial hypertension, blood pressure increases, and serotonin syndrome.

MANAGEMENT: Caution is advised when fenfluramine is used with CYP450 1A2 or 2D6 inhibitors. Patients should be monitored for increased adverse effects, and the dosage of fenfluramine adjusted as necessary.

Using fenfluramine with alcohol can increase the risk of cardiovascular side effects such as increased heart rate, chest pain, or blood pressure changes. In addition, you may also be more likely to experience nervous system side effects such as dizziness, drowsiness, depression, and difficulty concentrating. You should avoid or limit the use of alcohol while being treated with fenfluramine. Do not use more than the recommended dose of fenfluramine, and avoid activities requiring mental alertness such as driving or operating hazardous machinery until you know how the medication affects you. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medication without first talking to your doctor.

Grapefruit juice may increase the blood levels of certain medications such as imatinib. You should avoid consumption of grapefruit and grapefruit juice during treatment with imatinib. However, if you have been regularly consuming grapefruit or grapefruit juice with the medication, then it is advisable for you to talk with your doctor before changing the amounts of these products in your diet, as this may alter the effects of your medication. Contact your doctor if your condition changes or you experience increased side effects. Orange juice is not expected to interact.