Drug Interactions between chlorzoxazone and naltrexone

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents such as chlorzoxazone. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills. In addition, in one small study, watercress was reported to increase chlorzoxazone peak concentrations, AUC, and half-life. The proposed mechanism is inhibition of CYP450 2E1 metabolism. The clinical significance is unknown.

MANAGEMENT: Patients receiving chlorzoxazone should be advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how chlorzoxazone affects them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities. Watercress should be avoided if an interaction is suspected; e.g., excess sedation, nausea, or headache occurs.

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.