Potential clinically significant drug-drug interactions of hydroxychloroquine used in the treatment of COVID-19.

AIMS: Hydroxychloroquine (HCQ) is using as a repurposed drug in considerable proportion of COVID-19 patients. However, being a substrate of cytochrome P450 (CYP) enzymes of CYP3A4/5, CYP2C8 and CYP2D6, the safety and efficacy of this drug may be affected by the coadministration of respective CYP inhibitors, substrates or inducer drugs. It was aimed to identify potential clinically significant drug-drug interaction (DDI) pairs of HCQ. METHODS: Inhibitors, substrates and inducer drugs lists of CYP enzymes of interest from international well-recognised evidence-based drug interaction resources were used to identify potential clinically significant pharmacokinetic DDI pairs of HCQ. RESULTS: Among 329 identified interacting drugs that predicted to cause clinically significant DDIs of HCQ, 45 (13.7%), 43 (13.1%) and 123 (37.4%) unique DDI pairs were identified from the FDA, Stockley's and Flockhart lists, respectively. Of interest, 55 (16.7%) DDI pairs were recognised by all three resources. At least, 29 (8.8%) severe DDI pairs were identified predicted to cause severe toxicity of HCQ in patients with COVID-19. When comparing these interactions with Liverpool DDI lists, it was found that out of 423 total interactions, 238 (56.3%) and 94 (22.2%) unique DDI pairs were identified from all three resources and Liverpool DDI lists, respectively. Of interest, only three (0.7%) DDI pairs were recognised by both the three international resources and Liverpool DDI lists of HCQ. CONCLUSION: Using HCQ has clinical debate whether it should or should not continue in COVID-19 patients, however, potential clinically significant DDIs identified in this study may optimise safety or efficacy of HCQ in considerable proportion of patients.