Risk of digoxin intoxication caused by clarithromycin-digoxin interactions in heart failure patients: a population-based study.
OBJECTIVE
To quantify the effect of exposures to digoxin–clarithromycin interactions on the risk of digoxin toxicity requiring hospitalizations in a population-based manner in a Taiwanese population.


METHODS
This is a retrospective population-based nested case–control study. Data were retrieved from the National Health Insurance Research Database. Heart failure (HF) patients newly treated with digoxin between 1 January 2001 and 31 December 2004 were retrieved from the database as the study cohort. Case patients, admitted to the hospitals with the diagnosis of digoxin intoxication (ICD-9 code 972.1) were identified from the study cohort and compared with the matched controls for the receipt of clarithromycin.


RESULTS
A total of 154,058 patients were identified as the study cohort; from these, 595 cases and 27,020 matched controls were selected for study. The prescription of clarithromycin at 7, 14, and 30 days prior to the index date was associated with a 4.36- (95% CI 1.28–14.79), 5.07- (95% CI 2.36–10.89), and 2.98-fold (95% CI 1.59–5.63) increase in hospitalization for digoxin intoxication, respectively. The results of the dose–response relationship also indicated that clarithromycin prescribed with a prescribed daily dose (PDD)/defined daily dose (DDD) ratio >2 led to a 55.41-fold (95% CI 9.31–329.9) increase of the risk, which is significantly greater than that prescribed with a 1–2 PDD/DDD ratio (adjusted OR  4.81; 95% CI 1.88–12.30) or with a <1 PDD/DDD ratio (adjusted OR  0.78; 95% CI 0.19–3.20).


CONCLUSIONS
This study provides empirical evidence that digoxin–clarithromycin interactions do increase the risk of hospitalization for digoxin intoxication in HF patients and that this risk could reach as high as 55.4-fold. We strongly recommend that the combined use of digoxin with clarithromycin should be avoided and that digoxin concentrations should be monitored closely in situations where the combination can not be avoided.
Chan
Agnes L F
AL
Department of Pharmacy, Chi Mei Medical Center, Tinan, Taiwan.
Wang
Meng-Ting
MT
Su
Chen-Yi
CY
Tsai
Fu-Hsiung
FH
D000368:Aged; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use; D002316:Cardiotonic Agents / Q000009:adverse effects / Q000627:therapeutic use; D016022:Case-Control Studies; D017291:Clarithromycin / Q000009:adverse effects* / Q000627:therapeutic use; D015331:Cohort Studies; D004077:Digoxin / Q000009:adverse effects* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006333:Heart Failure / Q000139:chemically induced / Q000188:drug therapy*; D006760:Hospitalization; D006801:Humans; D008297:Male; D012189:Retrospective Studies
D000900:Anti-Bacterial Agents; D002316:Cardiotonic Agents; D004077:Digoxin; D017291:Clarithromycin