Sub‐therapeutic colchicine levels in a patient treated for acute pericarditis in the setting of carbamazepine use: A case report

Abstract

What is known and objective Colchicine is a standard therapy for the treatment of acute pericarditis. It is metabolized by cytochrome P‐450 3A4 (CYP3A4) and is subject to potential drug interactions. Multiple case reports describe accumulation of colchicine with CYP3A4 inhibitors, but limited data exist for increased colchicine clearance with CYP3A4 inducers. We describe a case of idiopathic haemorrhagic pericarditis treated with colchicine but rendered ineffective given potential drug interaction with carbamazepine. Case summary A 61‐year‐old man with a history of seizures presented to the emergency department with severe chest pain radiating to the back and was found to have a large pericardial effusion. The patient underwent pericardiocentesis, which demonstrated a haemorrhagic pericardial effusion. After an extensive workup, he was treated for idiopathic pericarditis with anti‐inflammatories and colchicine but failed to improve despite adequate colchicine loading and maintenance dosing. A serum colchicine level was checked given a potential CYP3A4 drug interaction in the setting of chronic carbamazepine use and was found to be sub‐therapeutic. Concomitant use of CYP3A4 inducers in the setting of colchicine use can render anti‐inflammatory strategies ineffective and may result in treatment failure. What is new and conclusion Due to its hepatic and intestinal metabolism by CYP3A4 enzymes, colchicine is susceptible to drug‐drug interactions resulting in either toxicities or rendering it ineffective with concomitant CYP3A4 inhibitors or inducers, respectively. Carbamazepine, a common anti‐epileptic medication and known inducer of the CYP3A4 enzyme, may reduce levels of colchicine in the blood resulting in treatment failure. Further study is required to determine if dose adjustments may overcome this drug interaction.

Colchicine Drug Interaction Errors and Misunderstandings: Recommendations for Improved Evidence-Based Management

“…Enzyme inducers such as rifampin, barbiturates, carbamazepine, efavirenz, lumacaftor, phenytoin, primidone, and St. John’s wort increase CYP3A4/P-gp activity, and would be expected to reduce colchicine AUC. Case reports suggest that both rifampin and carbamazepine can substantially reduce colchicine concentrations [ 31 , 32 ]. (See case report details in the online Supplemental Table in the ESM).…”