Management of drug-drug interactions with nirmatrelvir/ritonavir in patients treated for Covid-19: Guidelines from the French Society of Pharmacology and Therapeutics (SFPT)

Objectives. - Nirmatrelvir in association with ritonavir (PAXLOVID (TM), Pfizer) is an antiviral agent targeting the 3-chymotrypsin-like cysteine protease enzyme (3C-like protease or Mpro) which is a key enzyme of the viral cycle of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This combination with a well-known pharmacokinetic enhancer leads to a high risk for drug-drug interactions in a polymedicated elected population for treatment. The aim of this work was to provide recommendations on behalf of the national French society of pharmacology (French Society of Pharmacology and Therapeutics; SFPT), by suggesting optimal and pragmatic therapeutic strategies if nirmatrelvir/ritonavir is to be given together with drugs commonly used, in order to ensure secured physicians' prescription. Methods. - Six clinical pharmacologists search the scientific literature to provide a first draft of recommendations. Thereafter, twelve other clinical pharmacologists verified the recommen-dations and proposed modifications. The final draft was then validated by all 18 participants. Results. - Five distinct recommendations were issued: i) contra-indications, ii) PAXLOVID (TM) not recommended with the comedication, iii) PAXLOVID (TM) possible whether the comed-ication is discontinued, iv) PAXLOVID (TM) possible only after an expert advice and v) PAXLOVID (TM) possible without modification of the associated treatment. The final document comprises recommendations for 171 drugs/therapeutic classes aiming to secure prescription. In complex situations, clinicians are advised to contact their pharmacology department to obtain specific recommendations on the management of drug-drug interactions with nirma-trelvir/ritonavir. Conclusion. - These recommendations intend to be a help for clinicians willing to prescribe nirmatrelvir/ritonavir and to prevent drug-drug interactions leading to adverse drug reactions or loss of efficacy. They constitute a guideline for primary care situations. Of course, some complex situations may require expert advices and here, again, clinical pharmacologists are at the forefront in providing therapeutic advice. (c) 2022 Societe francaise de pharmacologie et de therapeutique. Published by Elsevier Masson SAS. All rights reserved.

Automated summary

This study provides recommendations for the safe prescription of nirmatrelvir/ritonavir, aiming to prevent drug-drug interactions and ensure the efficacy of the treatment.