Drug Interactions between milnacipran and naltrexone

GENERALLY AVOID: Use of milnacipran in conjunction with chronic alcohol consumption may potentiate the risk of liver injury. Milnacipran alone can increase serum transaminase levels. In placebo-controlled fibromyalgia trials, increases in ALT were more frequently observed in patients treated with milnacipran 100 mg/day (6%) and 200 mg/day (7%) compared to patients treated with placebo (3%). One patient receiving milnacipran 100 mg/day (0.2%) had an increase in ALT greater than 5 times the upper limit of normal (ULN) but did not exceed 10 times the ULN. Increases in AST were also more frequently observed in patients treated with milnacipran 100 mg/day (3%) and 200 mg/day (5%) than in patients treated with placebo (2%). There have been reported cases of increased liver enzymes and severe liver injury, including fulminant hepatitis, from foreign postmarketing experience with milnacipran. Significant underlying clinical conditions and/or use of multiple concomitant medications were present in the cases of severe liver injury.

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

GENERALLY AVOID: Coadministration of naltrexone with other agents known to induce hepatotoxicity may potentiate the risk of liver injury. Naltrexone, especially in larger than recommended doses (more than 50 mg/day), has been associated with hepatocellular injury, hepatitis, and elevations in liver transaminases and bilirubin. Other potential causative or contributory etiologies identified include preexisting alcoholic liver disease, hepatitis B and/or C infection, and concomitant usage of other hepatotoxic drugs.

MANAGEMENT: The use of naltrexone with other potentially hepatotoxic agents should be avoided whenever possible (e.g., acetaminophen; alcohol; androgens and anabolic steroids; antituberculous agents; azole antifungal agents; ACE inhibitors; cyclosporine (high dosages); disulfiram; endothelin receptor antagonists; interferons; ketolide and macrolide antibiotics; 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). 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. Periodic monitoring of hepatic function is advisable.