tetano
Editor, Senior Moderator
Therapie
. 2022 Apr 20;S0040-5957(22)00065-8.
doi: 10.1016/j.therap.2022.03.005. Online ahead of print.
Management of drug-drug interactions with nirmatrelvir/ritonavir in patients treated for Covid-19: Guidelines from the French Society of Pharmacology and Therapeutics (SFPT)
Florian Lemaitre[SUP] 1 [/SUP], Matthieu Grégoire[SUP] 2 [/SUP], Caroline Monchaud[SUP] 3 [/SUP], Stéphane Bouchet[SUP] 4 [/SUP], Béatrice Saint-Salvi[SUP] 5 [/SUP], Elisabeth Polard[SUP] 6 [/SUP], SFPT Therapeutic Drug Monitoring and Treatment Personalization group (STP-PT) of the French Society of Pharmacology and Therapeutics (SFPT); French Pharmacovigilance Network (CRPV); ANRS-MIE AC-43 Clinical Pharmacology Committee, joint working group; SFPT Therapeutic Drug Monitoring and Treatment Personalization group (STP-PT) of the French Society of Pharmacology and Therapeutics (SFPT); French Pharmacovigilance Network (CRPV); ANRS-MIE AC-43 Clinical Pharmacology Committee, joint working group
Collaborators, Affiliations
Abstract
Objectives: Nirmatrelvir in association with ritonavir (PAXLOVID™, 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 recommendations and proposed modifications. The final draft was then validated by all 18 participants.
Results: Five distinct recommendations were issued: i) contra-indications, ii) "PAXLOVID™ not recommended with the comedication", iii) "PAXLOVID™ possible whether the comedication is discontinued", iv) "PAXLOVID™ possible only after an expert advice" and v) "PAXLOVID™ 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 nirmatrelvir/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.
Keywords: Antiviral; Drug monitoring; Paxlovid; Pharmacodynamics; Pharmacokinetics; Ritonavir.
. 2022 Apr 20;S0040-5957(22)00065-8.
doi: 10.1016/j.therap.2022.03.005. Online ahead of print.
Management of drug-drug interactions with nirmatrelvir/ritonavir in patients treated for Covid-19: Guidelines from the French Society of Pharmacology and Therapeutics (SFPT)
Florian Lemaitre[SUP] 1 [/SUP], Matthieu Grégoire[SUP] 2 [/SUP], Caroline Monchaud[SUP] 3 [/SUP], Stéphane Bouchet[SUP] 4 [/SUP], Béatrice Saint-Salvi[SUP] 5 [/SUP], Elisabeth Polard[SUP] 6 [/SUP], SFPT Therapeutic Drug Monitoring and Treatment Personalization group (STP-PT) of the French Society of Pharmacology and Therapeutics (SFPT); French Pharmacovigilance Network (CRPV); ANRS-MIE AC-43 Clinical Pharmacology Committee, joint working group; SFPT Therapeutic Drug Monitoring and Treatment Personalization group (STP-PT) of the French Society of Pharmacology and Therapeutics (SFPT); French Pharmacovigilance Network (CRPV); ANRS-MIE AC-43 Clinical Pharmacology Committee, joint working group
Collaborators, Affiliations
- PMID: 35618549
- DOI: 10.1016/j.therap.2022.03.005
Abstract
Objectives: Nirmatrelvir in association with ritonavir (PAXLOVID™, 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 recommendations and proposed modifications. The final draft was then validated by all 18 participants.
Results: Five distinct recommendations were issued: i) contra-indications, ii) "PAXLOVID™ not recommended with the comedication", iii) "PAXLOVID™ possible whether the comedication is discontinued", iv) "PAXLOVID™ possible only after an expert advice" and v) "PAXLOVID™ 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 nirmatrelvir/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.
Keywords: Antiviral; Drug monitoring; Paxlovid; Pharmacodynamics; Pharmacokinetics; Ritonavir.