Drug Interactions between Fareston and gepirone

You should avoid drinking grapefruit juice during treatment with toremifene. Grapefruit juice may increase the blood levels of toremifene. This can make you more likely to develop side effects such as vaginal bleeding, blood clots, or an irregular heart rhythm that may be serious or life-threatening. Contact your doctor if you experience potential signs and symptoms of blood clots such as chest pain, shortness of breath, sudden loss of vision, and pain, redness or swelling your arms or legs. You should also seek immediate medical attention if you develop sudden dizziness, lightheadedness, fainting, or fast or pounding heartbeats during treatment with toremifene.

Talk to your doctor before using toremifene with soy products. There is some evidence that substances present in soy may stimulate breast tumor growth and interfere with the action of toremifene, although this has not been proven. Whether soy products are effective for hot flashes is also uncertain. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

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GENERALLY AVOID: Grapefruit and/or grapefruit juice may increase the plasma concentrations and effects of gepirone. The proposed mechanism is inhibition of CYP450 3A4 mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit juice, but has been reported for other CYP450 3A4 inhibitors. For example, when subjects who were at steady state on the strong CYP450 3A4 inhibitor ketoconazole (200 mg twice daily) received a single dose of gepirone (36.3 mg), the maximum plasma concentration (Cmax) and systemic exposure (AUC) of gepirone increased by approximately 5-fold. Similarly, when subjects who were at steady state on the moderate CYP450 3A4 inhibitor verapamil (80 mg three times daily) received a single dose of gepirone (18.2 mg), the maximum plasma concentration (Cmax) and systemic exposure (AUC) of gepirone increased by approximately 2.6-fold. In general, the effects of grapefruit products are concentration-, dose-, and preparation-dependent and can vary widely among both brands and individual patients. Some preparations have demonstrated strong CYP450 3A4 inhibition, while others have demonstrated moderate inhibition.

ADJUST DOSING INTERVAL: Food enhances the bioavailability of gepirone and its major active metabolites (3'-OH-gepirone and 1-PP). The magnitude of the effect is dependent on the fat content of the meal, but the systemic exposure of gepirone and its major metabolites was consistently higher under fed conditions as compared to the fasted state. The peak plasma concentration (Cmax) of gepirone after intake of a low-fat (about 200 calorie) breakfast was 27% higher, after a medium-fat (about 500 calorie) breakfast was 55% higher, and after a high-fat (about 850 calorie) breakfast was 62% higher than the Cmax achieved in the fasted state. Likewise, the systemic exposure (AUC) of gepirone was about 14% higher after a low-fat breakfast, 22% higher after a medium-fat breakfast, and 32% to 37% higher after a high-fat breakfast when compared to the AUC achieved in the fasted state. The effect of varying amounts of fat on the AUC and Cmax of 3'-OH-gepirone and 1-PP were similar to that of gepirone.

MANAGEMENT: Coadministration of gepirone with grapefruit products should be avoided. If grapefruit juice is consumed, monitoring for adverse effects (e.g., QT prolongation, serotonin syndrome, dizziness, nausea, insomnia, abdominal pain, and/or dyspepsia) should be considered. Gepirone should be taken orally with food at the approximately the same time each day. Tablets should be swallowed whole.