Drug Interaction Report

GENERALLY AVOID: Coadministration of bedaquiline with other agents known to induce hepatotoxicity may potentiate the risk of liver injury. In clinical trials, hepatic adverse drug reactions developed in more bedaquiline-treated patients than in those who received other drugs used to treat tuberculosis. In patients receiving bedaquiline or placebo in combination with other drugs used to treat multidrug-resistant tuberculosis, reversible aminotransferase elevations of at least 3 times the upper limit of normal (ULN) developed more frequently in the bedaquiline treatment group [10.8%] than in the placebo group [5.7%].

MANAGEMENT: The use of bedaquiline with other potentially hepatotoxic agents should be avoided whenever possible (e.g., acetaminophen; alcohol; androgens and anabolic steroids; other antituberculous agents; azole antifungal agents; ACE inhibitors; disulfiram; endothelin receptor antagonists; ketolide and macrolide antibiotics; interferons; kinase inhibitors; minocycline; nonsteroidal anti-inflammatory agents; nucleoside reverse transcriptase inhibitors; proteasome inhibitors; retinoids; sulfonamides; tamoxifen; thiazolidinediones; tolvaptan; vincristine; zileuton; anticonvulsants such as carbamazepine, hydantoins, felbamate, and valproic acid; lipid-lowering medications such as fenofibrate, lomitapide, mipomersen, niacin, and statins; herbals and nutritional supplements such as black cohosh, chaparral, comfrey, DHEA, kava, pennyroyal oil, and red yeast rice), especially in patients with diminished hepatic reserve. Patients treated with bedaquiline should have serum ALT, AST, alkaline phosphatase, and bilirubin monitored at baseline and monthly during treatment, or as often as needed. An increase of serum aminotransferases to greater than 3 times ULN should be followed by repeat testing within 48 hours. Patients should be advised to seek medical attention if they experience potential signs and symptoms of hepatotoxicity such as fever, rash, itching, anorexia, nausea, vomiting, fatigue, malaise, right upper quadrant pain, dark urine, pale stools, and jaundice. Discontinue bedaquiline if aminotransferase elevations are accompanied by total bilirubin elevation greater than 2 times ULN, aminotransferase elevations are greater than 8 times ULN, or aminotransferase elevations persist beyond 2 weeks.

GENERALLY AVOID: Use of duloxetine in conjunction with chronic alcohol consumption may potentiate the risk of liver injury. Duloxetine alone can increase serum transaminase levels. In clinical trials, 0.3% of patients discontinued duloxetine due to liver transaminase elevations. The median time to detection was about two months. Three duloxetine-treated patients had liver injury as manifested by transaminase and bilirubin elevations, with evidence of obstruction. Substantial intercurrent ethanol use was present in each of these cases, which may have contributed to the abnormalities observed. Duloxetine does not appear to enhance the central nervous system effects of alcohol. When duloxetine and ethanol were administered several hours apart so that peak concentrations of each would coincide, duloxetine did not increase the impairment of mental and motor skills caused by alcohol.

MANAGEMENT: Due to the risk of liver injury, patients prescribed duloxetine should be counseled to avoid excessive use of alcohol. Duloxetine should generally not be prescribed to patients with substantial alcohol use.

ADJUST DOSING INTERVAL: Food enhances the oral bioavailability of bedaquiline. When administered with a standard meal containing approximately 22 grams of fat (558 total Kcal), the relative bioavailability of bedaquiline increased by approximately 2-fold compared to administration under fasted conditions.

GENERALLY AVOID: Coadministration with alcohol may increase the risk of hepatotoxicity associated with the use of bedaquiline. In clinical trials, hepatic adverse drug reactions developed in more bedaquiline-treated patients than in those who received other drugs used to treat tuberculosis. In patients receiving bedaquiline or placebo in combination with other drugs used to treat multidrug-resistant tuberculosis, reversible aminotransferase elevations of at least 3 times the upper limit of normal developed more frequently in the bedaquiline treatment group [10.8%] than in the placebo group [5.7%].

MANAGEMENT: To ensure maximal oral absorption, bedaquiline should be taken with food. Patients should avoid alcohol use during treatment.