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

J Clin Pharm Ther. 2022 Apr;47(4):559-561. doi: 10.1111/jcpt.13549. Epub 2021 Oct 21.

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.

Publication types

  • Case Reports

MeSH terms

  • Anti-Inflammatory Agents / therapeutic use
  • Carbamazepine / adverse effects
  • Colchicine / therapeutic use
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 CYP3A Inducers / therapeutic use
  • Cytochrome P-450 CYP3A Inhibitors
  • Humans
  • Male
  • Middle Aged
  • Pericardial Effusion*
  • Pericarditis* / drug therapy

Substances

  • Anti-Inflammatory Agents
  • Cytochrome P-450 CYP3A Inducers
  • Cytochrome P-450 CYP3A Inhibitors
  • Carbamazepine
  • Cytochrome P-450 CYP3A
  • Colchicine