Influence of a Short Course of Ritonavir Used as Booster in Antiviral Therapies Against SARS-CoV-2 on the Exposure of Atorvastatin and Rosuvastatin
© 2023. The Author(s)..
PURPOSE: Early antiviral treatment with nirmatrelvir/ritonavir is recommended for SARS-CoV-2-infected patients at high risk for severe courses. Such patients are usually chronically ill and susceptible to adverse drug interactions caused by ritonavir. We investigated the interactions of short-term low-dose ritonavir therapy with atorvastatin and rosuvastatin, two statins commonly used in this population.
METHOD: We assessed exposure changes (area under the concentration-time curve (AUC∞) and maximum concentration (Cmax)) of a single dose of 10 mg atorvastatin and 10 mg rosuvastatin before and on the fifth day of ritonavir treatment (2 × 100 mg/day) in healthy volunteers and developed a semi-mechanistic pharmacokinetic model to estimate dose adjustment of atorvastatin during ritonavir treatment.
RESULTS: By the fifth day of ritonavir treatment, the AUC∞ of atorvastatin increased 4.76-fold and Cmax 3.78-fold, and concurrently, the concentration of atorvastatin metabolites decreased to values below the lower limit of quantification. Pharmacokinetic modelling indicated that a stepwise reduction in atorvastatin dose during ritonavir treatment with a stepwise increase up to 4 days after ritonavir discontinuation can keep atorvastatin exposure within safe and effective margins. Rosuvastatin pharmacokinetics were only mildly modified; ritonavir significantly increased the Cmax 1.94-fold, while AUC∞ was unchanged.
CONCLUSION: Atorvastatin doses should likely be adjusted during nirmatrelvir/ritonavir treatment. For patients on a 20-mg dose, we recommend half of the original dose. In patients taking 40 mg or more, a quarter of the dose should be taken until 2 days after discontinuation of nirmatrelvir/ritonavir. Patients receiving rosuvastatin do not need to change their treatment regimen.
TRIAL REGISTRATION: EudraCT number: 2021-006634-39. DRKS00027838.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2023 |
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| Enthalten in: |
Cardiovascular drugs and therapy - (2023) vom: 19. Dez. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Krohmer, Evelyn [VerfasserIn] |
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| Links: |
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| Themen: |
Atorvastatin |
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| Anmerkungen: |
Date Revised 19.12.2023 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1007/s10557-023-07538-w |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM366036297 |
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| 100 | 1 | |a Krohmer, Evelyn |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Influence of a Short Course of Ritonavir Used as Booster in Antiviral Therapies Against SARS-CoV-2 on the Exposure of Atorvastatin and Rosuvastatin |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Revised 19.12.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status Publisher | ||
| 520 | |a © 2023. The Author(s). | ||
| 520 | |a PURPOSE: Early antiviral treatment with nirmatrelvir/ritonavir is recommended for SARS-CoV-2-infected patients at high risk for severe courses. Such patients are usually chronically ill and susceptible to adverse drug interactions caused by ritonavir. We investigated the interactions of short-term low-dose ritonavir therapy with atorvastatin and rosuvastatin, two statins commonly used in this population | ||
| 520 | |a METHOD: We assessed exposure changes (area under the concentration-time curve (AUC∞) and maximum concentration (Cmax)) of a single dose of 10 mg atorvastatin and 10 mg rosuvastatin before and on the fifth day of ritonavir treatment (2 × 100 mg/day) in healthy volunteers and developed a semi-mechanistic pharmacokinetic model to estimate dose adjustment of atorvastatin during ritonavir treatment | ||
| 520 | |a RESULTS: By the fifth day of ritonavir treatment, the AUC∞ of atorvastatin increased 4.76-fold and Cmax 3.78-fold, and concurrently, the concentration of atorvastatin metabolites decreased to values below the lower limit of quantification. Pharmacokinetic modelling indicated that a stepwise reduction in atorvastatin dose during ritonavir treatment with a stepwise increase up to 4 days after ritonavir discontinuation can keep atorvastatin exposure within safe and effective margins. Rosuvastatin pharmacokinetics were only mildly modified; ritonavir significantly increased the Cmax 1.94-fold, while AUC∞ was unchanged | ||
| 520 | |a CONCLUSION: Atorvastatin doses should likely be adjusted during nirmatrelvir/ritonavir treatment. For patients on a 20-mg dose, we recommend half of the original dose. In patients taking 40 mg or more, a quarter of the dose should be taken until 2 days after discontinuation of nirmatrelvir/ritonavir. Patients receiving rosuvastatin do not need to change their treatment regimen | ||
| 520 | |a TRIAL REGISTRATION: EudraCT number: 2021-006634-39. DRKS00027838 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Atorvastatin | |
| 650 | 4 | |a Drug-drug interaction | |
| 650 | 4 | |a Healthy volunteers | |
| 650 | 4 | |a Nirmatrelvir-ritonavir | |
| 650 | 4 | |a Rosuvastatin | |
| 700 | 1 | |a Rohr, Brit Silja |e verfasserin |4 aut | |
| 700 | 1 | |a Stoll, Felicitas |e verfasserin |4 aut | |
| 700 | 1 | |a Gümüs, Katja S |e verfasserin |4 aut | |
| 700 | 1 | |a Bergamino, Mariano |e verfasserin |4 aut | |
| 700 | 1 | |a Mikus, Gerd |e verfasserin |4 aut | |
| 700 | 1 | |a Sauter, Max |e verfasserin |4 aut | |
| 700 | 1 | |a Burhenne, Jürgen |e verfasserin |4 aut | |
| 700 | 1 | |a Weiss, Johanna |e verfasserin |4 aut | |
| 700 | 1 | |a Meid, Andreas D |e verfasserin |4 aut | |
| 700 | 1 | |a Czock, David |e verfasserin |4 aut | |
| 700 | 1 | |a Blank, Antje |e verfasserin |4 aut | |
| 700 | 1 | |a Haefeli, Walter E |e verfasserin |4 aut | |
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