Drug Interaction Report

MONITOR: Concomitant use of ashwagandha with other agents that are known to induce hepatotoxicity may theoretically increase the risk of hepatotoxicity. There are case reports of adverse effects on liver functions associated with ashwagandha use. In a case report, a 20-year-old man in Japan developed liver dysfunction and hyperbilirubinemia after using ashwagandha in combination with multiple antianxiety drugs. In additional case reports, three men and two women, age range 21 to 62 years who reportedly took supplements containing 450 to 1,350 mg ashwagandha daily over the course of one week to four months when signs of liver injury, such as jaundice, pruritus, nausea, lethargy, abdominal discomfort, and hyperbilirubinemia, appeared.

MANAGEMENT: Liver function tests should be monitored, and patients should be advised to report any symptoms such as abdominal pain, jaundice, dark urine, light stools, fever, or unusual fatigue.

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.