Drug Interaction Report

MONITOR: Coadministration of beta interferons with other agents known to induce hepatotoxicity may potentiate the risk of liver injury. Use of beta interferons has been associated with rare cases of liver injury, including autoimmune hepatitis and severe liver damage leading to hepatic failure, some of which required transplantation. In some cases, these events have occurred in the presence of other drugs that have been associated with hepatic injury. Symptoms of liver dysfunction typically began from 1 to 6 months following the initiation of therapy. Asymptomatic elevation of hepatic transaminases (particularly SGPT) have also been reported but is common with interferon therapy.

MANAGEMENT: The risk of hepatic injury should be considered when beta interferons are used with other potentially hepatotoxic agents (e.g., acetaminophen; alcohol; androgens and anabolic steroids; antituberculous agents; azole antifungal agents; ACE inhibitors; cyclosporine (high dosages); disulfiram; endothelin receptor antagonists; other 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). Liver function tests should be monitored at regular intervals and the interferon dosage reduced if SGPT rises above 5 times the upper limit of normal. The dosage may be gradually re-escalated when enzyme levels return to normal. 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. If liver injury is suspected, interferon therapy should be promptly discontinued due to the potential for rapid progression to liver failure.

MONITOR: Concomitant use of statin medication with substantial quantities of alcohol may increase the risk of hepatic injury. Transient increases in serum transaminases have been reported with statin use and while these increases generally resolve or improve with continued therapy or a brief interruption in therapy, there have been rare postmarketing reports of fatal and non-fatal hepatic failure in patients taking statins. Patients who consume substantial quantities of alcohol and/or have a history of liver disease may be at increased risk for hepatic injury. Active liver disease or unexplained transaminase elevations are contraindications to statin use.

MANAGEMENT: Patients should be counseled to avoid substantial quantities of alcohol in combination with statin medications and clinicians should be aware of the increased risk for hepatotoxicity in these patients.