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Ther Drug Monit ; 2022 Aug 09.
Article in English | MEDLINE | ID: covidwho-1985145


ABSTRACT: Nirmatrelvir/ritonavir (Paxlovid®) consists of a peptidomimetic inhibitor (Nirmatrelvir) of the SARS-CoV-2 main protease and a pharmacokinetic enhancer (Ritonavir). It is approved for the treatment of mild-to-moderate COVID-19. This combination of nirmatrelvir and ritonavir can mediate significant and complex drug-drug interactions (DDIs), primarily due to the ritonavir component. Indeed, ritonavir inhibits the metabolism of nirmatrelvir through cytochrome P450 3A (CYP3A) leading to higher plasma concentrations and a longer half-life of nirmatrelvir. Co-administration of nirmatrelvir/ritonavir with immunosuppressant drugs (ISDs) is particularly challenging given the major involvement of CYP3A in the metabolism of most of these drugs and their narrow therapeutic ranges. Exposure of ISDs will be drastically increased through the potent ritonavir-mediated inhibition of CYP3A, resulting in an increased risk of adverse drug reactions. While a decrease in the dosage of ISDs can prevent toxicity, an inappropriate dosage regimen may also result in insufficient exposure and a risk of rejection. Here we provide some general recommendations for therapeutic drug monitoring (TDM) of ISDs and dosing recommendations when co-administered with nirmatrelvir/ritonavir. Particularly, tacrolimus should be discontinued, or patients should be given a microdose on day-1, while cyclosporine dosage should be reduced to 20% of the initial dosage during the antiviral treatment. Dosages of mammalian target of rapamycin inhibitors (m-TORis) should also be adjusted while dosages of mycophenolic acid and corticosteroids are expected to be less impacted.

Emerg Infect Dis ; 26(10): 2513-2515, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-623269


Because of in vitro studies, hydroxychloroquine has been evaluated as a preexposure or postexposure prophylaxis for coronavirus disease (COVID-19) and as a possible COVID-19 curative treatment. We report a case of COVID-19 in a patient with sarcoidosis who was receiving long-term hydroxychloroquine treatment and contracted COVID-19 despite adequate plasma concentrations.

Antimalarials/therapeutic use , Coronavirus Infections/complications , Hydroxychloroquine/therapeutic use , Pneumonia, Viral/complications , Sarcoidosis, Pulmonary/complications , Sarcoidosis, Pulmonary/drug therapy , Adult , Antimalarials/blood , COVID-19 , Coronavirus Infections/diagnosis , France , Humans , Hydroxychloroquine/blood , Male , Pandemics , Pneumonia, Viral/diagnosis , Time Factors , Tomography, X-Ray Computed
Fundam Clin Pharmacol ; 34(5): 530-547, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-626969


Patients with COVID-19 are sometimes already being treated for one or more other chronic conditions, especially if they are elderly. Introducing a treatment against COVID-19, either on an outpatient basis or during hospitalization for more severe cases, raises the question of potential drug-drug interactions. Here, we analyzed the potential or proven risk of the co-administration of drugs used for the most common chronic diseases and those currently offered as treatment or undergoing therapeutic trials for COVID-19. Practical recommendations are offered, where possible.

Coronavirus Infections/drug therapy , Pneumonia, Viral/drug therapy , Prescription Drugs/pharmacology , Analgesics/pharmacology , Anti-Asthmatic Agents/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Inflammatory Agents/pharmacology , Anticoagulants/pharmacology , Antineoplastic Agents/pharmacology , Antitubercular Agents/pharmacology , Antiviral Agents/pharmacology , Betacoronavirus , COVID-19 , Cardiovascular Agents/pharmacology , Drug Interactions , Humans , Hydroxychloroquine/pharmacology , Hypoglycemic Agents/pharmacology , Hypolipidemic Agents/pharmacology , Interferon beta-1b/pharmacology , Pandemics , Prescription Drugs/pharmacokinetics , Psychotropic Drugs/pharmacology , Receptors, Interleukin/antagonists & inhibitors , Risk Assessment , SARS-CoV-2 , Thyroid Hormones/pharmacology , COVID-19 Drug Treatment