Important Interactions of Immunosuppressants With Experimental Therapies for Novel Coronavirus Disease (COVID-19): How to Act

Zijp, Tanja R; Toren-Wielema, Martha L; Panday, Prashant V Nannan; Kosterink, Jos G. W.; Berger, Stefan P.; Touw, Daan

doi:10.1097/ftd.0000000000000766

Cited by 7 publications

(4 citation statements)

References 10 publications

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Section: Nirmatrelvir/ritonavir With Mtoris: Everolimus and Sirolimusmentioning

confidence: 99%

“…From the day after the cessation of nirmatrelvir/ritonavir, the mTORi may be reintroduced in one-fifth of the original dose, and the dose may be increased by 20% each day or according to the measured mTORi trough concentrations. 37 The timing and selection of dose for reintroduction of the mTORi may also depend on which combination of other immunosuppressants are used and the importance of the contribution of mTORis in the immunosuppressive regimen. Alternatively, if it is considered important to avoid subtherapeutic mTORi concentrations, and given the low risk of immediate adverse drug reactions with these drugs, another strategy that can be considered is as follows: A microdose of one-eighth of the patient's initial daily dose should be given on days 1, 3, and 5 after starting nirmatrelvir/ritonavir, and the initial treatment dosage could be restarted on day 7 (Table 1).…”

Section: Recommendationsmentioning

confidence: 99%

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Therapeutic Drug Monitoring and Dosage Adjustments of Immunosuppressive Drugs When Combined With Nirmatrelvir/Ritonavir in Patients With COVID-19

Lemaître

Budde

Gelder

et al. 2023

Therapeutic Drug Monitoring

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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. Coadministration of nirmatrelvir/ritonavir with immunosuppressive 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. Although a decrease in the dosage of ISDs can prevent toxicity, an inappropriate dosage regimen may also result in insufficient exposure and a risk of rejec-tion. Here, we provide some general recommendations for therapeutic drug monitoring of ISDs and dosing recommendations when coadministered with nirmatrelvir/ritonavir. Particularly, tacrolimus should be discontinued, or patients should be given a microdose on day 1, whereas 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.

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Section: Nirmatrelvir/ritonavir With Mtoris: Everolimus and Sirolimusmentioning

confidence: 99%

Section: Recommendationsmentioning

confidence: 99%

Therapeutic Drug Monitoring and Dosage Adjustments of Immunosuppressive Drugs When Combined With Nirmatrelvir/Ritonavir in Patients With COVID-19

Lemaître

Budde

Gelder

et al. 2023

Therapeutic Drug Monitoring

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“…The mammalian target of rapamycin inhibitor sirolimus is also a CYP3A4 substrate leading to toxic levels when co-administered with NMVr. 48 …”

Section: Cardiovascular Drug Interactions With Nmvrmentioning

confidence: 99%

Cardiovascular Drug Interactions With Nirmatrelvir/Ritonavir in Patients With COVID-19

Abraham

Nohria

Neilan

et al. 2022

Journal of the American College of Cardiology

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“…Interactions between drugs used for immunosuppression, such as CNIs, may have significant drug interactions, which, if not paid attention to, can be deleterious. 89 We have listed the interactions between the drugs used for the management of COVID-19 and the drugs used in AIH in the table below ( Table 3 ). As to the optimal treatment and drugs for COVID-19, the data are still evolving; however, it is suggested to check the side effect profile and drug interactions of the drug being used.…”

Section: Management Of Aih In Covid-19 Patientsmentioning

confidence: 99%

Special Considerations in the Management of Autoimmune Hepatitis in COVID-19 Hotspots: A Review

Madhu¹,

Sharma²,

Agarwal³

et al. 2021

Journal of Clinical and Translational Hepatology

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The ongoing coronavirus disease-2019 (COVID-19) pandemic has necessitated special considerations in the management of diseases. The way presence of pre-existing diseases or treatment for it predisposes to, alters course of, and changes the management of COVID-19, is of relevance and is being extensively studied. Autoimmune hepatitis (AIH) is unique in that it is an autoimmune disease mandating treatment with immunosuppressive drugs, as well as a liver disease with potential for varying degrees of underlying fibrosis. The use of immunosuppressive drugs could alter the risk of acquiring COVID-19, the clinical course and severity of COVID-19 and the degree of underlying liver fibrosis could alter the clinical outcomes of patients with COVID-19. In this review, we try to summarize key areas relevant in understanding and improving the clinical care of patients with AIH in the current pandemic. Special considerations required in the management of patients with AIH in COVID-19 hotspots have been outlined based on the current evidence.

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Important Interactions of Immunosuppressants With Experimental Therapies for Novel Coronavirus Disease (COVID-19): How to Act

Cited by 7 publications

References 10 publications

Therapeutic Drug Monitoring and Dosage Adjustments of Immunosuppressive Drugs When Combined With Nirmatrelvir/Ritonavir in Patients With COVID-19

Therapeutic Drug Monitoring and Dosage Adjustments of Immunosuppressive Drugs When Combined With Nirmatrelvir/Ritonavir in Patients With COVID-19

Cardiovascular Drug Interactions With Nirmatrelvir/Ritonavir in Patients With COVID-19

Special Considerations in the Management of Autoimmune Hepatitis in COVID-19 Hotspots: A Review

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