title: Colchicine-antimicrobial drug interactions: what pharmacists need to know in treating gout.
abstract: OBJECTIVE
  Review the magnitude and clinical relevance of drug-drug interactions between a new formulation of colchicine, used to treat gout, and antibiotics. SETTING AND PRACTICE DESCRIPTION: Relevant to community and institutional pharmacists servicing patients with gout.
  
  
  METHODS
  Pharmacists have clear roles for the identification of drug-drug interactions, providing recommendations for alternative therapy or dose adjustments/modifications, and monitoring for interactionrelated adverse events.
  
  
  METHODS
  Colchicine is metabolized via cytochrome P450 3A4 (CYP3A4); therefore, coadministration with agents that inhibit this isoenzyme can produce elevated colchicine plasma concentrations, resulting in severe and sometimes fatal adverse events. Knowledge of the potential for drug-drug interactions involving antibiotics (e.g., macrolide antibiotics, azole antifungals) allows pharmacists to help patients avoid serious adverse events.
  
  
  RESULTS
  Pharmacokinetic studies have demonstrated that the maximum plasma concentration (C(max)) and drug exposure (as assessed by area under the plasma concentration time curve [AUC]) of colchicine are increased by 277% and 282%, respectively, after coadministration with clarithromycin. Similarly, coadministration with ketoconazole increases colchicine C(max) and AUC by 102% and 212%, respectively. Other antibiotics that are strong CYP3A4 inhibitors include itraconazole and telithromycin, whereas erythromycin and fluconazole are moderate inhibitors of the isoenzyme CYP3A4. Coadministration of CYP3A4 inhibitors (particularly clarithromycin) and colchicine has resulted in acute colchicine toxicity manifested by severe gastrointestional toxicity, bone marrow suppression, multiorgan failure, and death.
  
  
  CONCLUSIONS
  Pharmacist awareness of potentially clinically significant interactions between colchicine and antibiotics that inhibit CYP3A4 can help to ensure the efficacy of colchicine is realized while mitigating serious toxicities and minimizing the risk of adverse events.
authors: Mutual Pharmaceutical Company, Inc, Philadelphia, PA 19111, USA.
authors: Matthew W
authors: MW
authors: Davis
authors: Suman
authors: S
authors: Wason
authors: Jennifer L
authors: JL
authors: Digiacinto
mesh_terms: D000890:Anti-Infective Agents / Q000009:adverse effects*; D019540:Area Under Curve; D001711:Biotransformation; D003078:Colchicine / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics; D015897:Comorbidity; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D065692:Cytochrome P-450 CYP3A Inhibitors; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000009:adverse effects*; D006073:Gout / Q000188:drug therapy*; D006074:Gout Suppressants / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics; D006801:Humans; D010595:Pharmacists; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D000890:Anti-Infective Agents; D065692:Cytochrome P-450 CYP3A Inhibitors; D004791:Enzyme Inhibitors; D006074:Gout Suppressants; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D003078:Colchicine