Managing Multiple Myeloma in the Face of Drug-Induced Adverse Drug Reaction

Drug-induced liver injury has been reported to cause up to 10% of adverse drug reactions in the United States. Risk factors for druginduced liver injury include female gender, older age, interacting medications and drugs that are metabolized by the liver. This case report describes a patient who was newly initiated on tizanidine, an alpha2 adrenergic agonist used for muscle spasm and musculoskeletal pain, and bortezomib, a proteasome inhibitor used for multiple myeloma. Both medications are metabolized by cytochrome P450 isoenzyme 1A2. The medications were suspected of causing acute hepatitis based on the timing of their initiation and evidence to suggest that they can cause acute hepatitis. The Naranjo adverse drug reaction scale was scored as possible. In addition, the drugs' blood levels may have been increased by acyclovir and hydralazine, both inhibitors of cytochrome P450 isoenzyme 1A2. A dilemma for the team was how to best manage bortezomib. It is part of first line treatment for multiple myeloma when combined with lenalidomide and dexamethasone. Other proteasome inhibitors are available for multiple myeloma treatment. When starting chemotherapy, it is important to be aware of medications that cause a rise in liver enzymes, potential drug interactions, and how best to manage the clinical consequences.