Key result
Thirty-one drug combinations, most commonly antipsychotics and antidepressants, were identified as potential drug-drug interactions that elevate the risk of drug-induced long QT syndrome.
Why the study?
Drug-drug interactions are risk factors for drug-induced long QT syndrome, but the specific drug combinations that increase this risk have not been extensively investigated.
Which drug-drug interactions increase the incidence of drug-induced long QT syndrome in a spontaneous reporting system?
Observational
Which drug-drug interactions increase the incidence of drug-induced long QT syndrome in a spontaneous reporting system?
This pharmacovigilance study identified 31 specific drug combinations, particularly antipsychotics and antidepressants, that significantly increase the risk of drug-induced long QT syndrome.
May warrant QTc monitoring with common psychotropic pairs; leaves open prospective validation of interaction severity.
What is known and objective Drug-induced long QT syndrome (diLQTS) is a rare but serious adverse drug reaction. Drug-drug interaction (DDI) is one of the risk factors for the development of diLQTS. However, the combinations of drugs that increase the risk of diLQTS have not been extensively investigated. This study was performed to analyse the potential DDIs that elevate the incidence of diLQTS using a spontaneous reporting system. Methods The Japanese Adverse Drug Event Report database from April 2004 to January 2020 was used to assess adverse event reports. We calculated the reporting odds ratio and 95% confidence interval for signal detection. Results and discussion Signals for concomitant use risk were detected in 31 drug combinations. Combinations of antipsychotics and antidepressants were the most common (olanzapine & fluvoxamine, olanzapine & trazodone, quetiapine & paroxetine, sulpiride & fluvoxamine, sulpiride & trazodone). Sixteen, 17 and 21 combinations were designated as requiring precaution for concomitant use in at least one of the package inserts in Japan, the United States and the United Kingdom, respectively, although no such precautions were described for the remaining combinations. On the contrary, a combination of bepridil & clarithromycin was categorized as “X (avoid combination)” and two combinations (chlorpromazine & haloperidol, amiodarone & metildigoxin) were classified as “D (modify regimen)” in the Lexicomp® risk rating. What is new and conclusion This study identified 31 combinations of drugs that may elevate the risk of diLQTS. The use of these drug combinations should be monitored more carefully in future.
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Matsuo et al. (2021) conducted an observational in Drug-induced long QT syndrome (diLQTS). Concomitant use of drugs (drug-drug interactions) was evaluated on Signal detection for drug-induced long QT syndrome using reporting odds ratio. Thirty-one drug combinations, most commonly antipsychotics and antidepressants, were identified as potential drug-drug interactions that elevate the risk of drug-induced long QT syndrome.
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