Drug Interactions between rifapentine and selumetinib

Selumetinib should be taken on an empty stomach, at least one hour before or two hours after a meal. Do not consume grapefruit, grapefruit juice, or any supplements that contain grapefruit extract during treatment with selumetinib unless directed otherwise by your doctor. Grapefruit juice can increase the blood levels of selumetinib. This may increase the risk and/or severity of serious side effects such as diarrhea; colitis (inflammation of the colon); skin rashes; cardiomyopathy (a condition that affects the heart muscle and its ability to pump blood); rhabdomyolysis (a rare condition involving the breakdown of skeletal muscle tissue that can cause kidney damage and death); and eye problems that can lead to blindness. Talk to your doctor if you have any questions or concerns. You should seek prompt medical attention if you experience severe diarrhea; severe skin reactions (rash over a large area of the body, peeling skin, blisters); signs and symptoms of heart trouble (persistent coughing or wheezing, shortness of breath, swelling of ankles and feet, fatigue, increased heart rate); muscle problems (unexplained muscle pain, tenderness or weakness, especially with fever and/or dark colored urine); or vision problems (blurred vision, light sensitivity, dark spots or floaters, vision loss). 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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ADJUST DOSING INTERVAL: Administration with food may increase the oral bioavailability of rifapentine and reduce the incidence of gastrointestinal adverse events. Administration with a high fat meal typically increases rifapentine's maximum concentration (Cmax) and systemic exposure (AUC) by approximately 40% to 50% over that observed when rifapentine is administered under fasting conditions. Rifapentine is often prescribed in combination with isoniazid. When single doses of rifapentine (900 mg) and isoniazid (900 mg) were administered with a low fat, high carbohydrate breakfast, the Cmax and AUC of rifapentine increased by 47% and 51%, respectively. On the other hand, isoniazid's Cmax and AUC decreased by 46% and 23%, respectively.

MANAGEMENT: Products containing oral rifapentine as the sole ingredient recommend administration with a meal to increase bioavailability and reduce the occurrence of gastrointestinal upset, nausea, and/or vomiting. Consultation of product labeling for combination products and/or relevant guidelines may be helpful if rifapentine is combined with a medication that is typically taken on an empty stomach.