Fatal interaction between clarithromycin and colchicine in patients with renal insufficiency: a retrospective study

Clin Infect Dis. 2005 Aug 1;41(3):291-300. doi: 10.1086/431592. Epub 2005 Jun 23.

Abstract

Background: Clarithromycin is frequently used to treat community-acquired pneumonia in elderly persons. Like erythromycin, it may interact with other drugs by interfering with metabolism by cytochrome P450 enzymes and with the P-glycoprotein transporter system. Colchicine, used for treatment of acute gout and for prophylaxis, may cause bone marrow toxicity. It is metabolized by CYP3A4 and is transported by P-glycoprotein. Initial case reports suggested potentially fatal interactions between clarithromycin and colchicine.

Methods: A retrospective study was conducted with 116 patients who were prescribed clarithromycin and colchicine during the same clinical admission. Case-control comparisons were made between patients who received concomitant therapy with the 2 drugs and patients who received sequential therapy. We assessed the clinical presentations and outcomes of the 2 patient groups and analyzed the risk factors associated with fatal outcomes.

Results: Nine (10.2%) of the 88 patients who received the 2 drugs concomitantly died. Only 1 (3.6%) of the 28 patients who received the drugs sequentially died. Multivariate analysis of the 88 patients who received concomitant therapy showed that longer overlapped therapy (relative risk [RR], 2.16; 95% confidence interval [CI], 1.41-3.31; P< or =.01), the presence of baseline renal impairment (RR, 9.1; 95% CI, 1.75-47.06; P<.001), and the development of pancytopenia (RR, 23.4; 95% CI, 4.48-122.7; P<.001) were independently associated with death.

Conclusions: Clarithromycin increases the risk of fatal colchicine toxicity, especially for patients with renal insufficiency. Since there are other drugs for treatment of pneumonia and gout, these 2 drugs should not be coprescribed, because of the risk of fatality.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / adverse effects
  • Clarithromycin / adverse effects*
  • Colchicine / adverse effects*
  • Contraindications
  • Drug Interactions*
  • Female
  • Gout Suppressants / adverse effects
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Renal Insufficiency / complications*
  • Retrospective Studies
  • Risk Factors
  • Survival Rate

Substances

  • Anti-Bacterial Agents
  • Gout Suppressants
  • Clarithromycin
  • Colchicine