Liverpool COVID-19 Interactions

Do Not Coadminister

Nirmatrelvir/ritonavir (extended administration; 10 days or longer)

Simvastatin

Quality of Evidence: Very Low

Summary:

Coadministration of simvastatin and potent CYP3A4 inhibitors, such as ritonavir, is contraindicated due to the large magnitude of the predicted drug-drug interaction (i.e., 100-fold) which increases the risk of severe toxicity including rhabdomyolysis. Discontinue simvastatin at least 12 hours prior to initiation of nirmatrelvir/ritonavir. Inhibition of CYP3A4 by ritonavir takes several days to resolve. Resume simvastatin treatment at least 3 days after the last dose of nirmatrelvir/ritonavir but preferably 5 days after completing nirmatrelvir/ritonavir treatment due to the large inter-individual variability in the disappearance of CYP3A4 inhibition. Note, the British and American product labels for Paxlovid (5 day administration) recommend to hold simvastatin treatment for 5 days after completing nirmatrelvir/ritonavir treatment. If a statin is needed when nirmatrelvir/ritonavir is used for an extended treatment duration (10 days or longer), use a statin that does not interact with nirmatrelvir/ritonavir (e.g. pravastatin, pitavastatin) during and up to 3 days post last dose of nirmatrelvir/ritonavir. Rosuvastatin can also be used up to a maximal daily dose of 10 mg.

Description:

Coadministration may increase simvastatin concentrations. Since increased concentrations of simvastatin may predispose patients to myopathies, including rhabdomyolysis, the combination of this medicinal product with ritonavir is contraindicated. Discontinue use of simvastatin at least 12 hours prior to initiation of Paxlovid, during the 5 days of Paxlovid treatment and for 5 days after completing Paxlovid.

Paxlovid GB Summary of Product Characteristics, Pfizer Ltd, December 2024.

Coadministration is contraindicated. HMG-CoA reductase inhibitors which are highly dependent on CYP3A metabolism, such as simvastatin, are expected to have markedly increased plasma concentrations when coadministered with ritonavir at high dose in accordance with its previous use as an antiretroviral agent or as a pharmacokinetic enhancer. Since increased concentrations of simvastatin may predispose patients to myopathies, including rhabdomyolysis, the combination of this medicinal product with ritonavir is contraindicated.

Paxlovid EU Summary of Product Characteristics, Pfizer, February 2025.

Co-administration may increase simvastatin concentrations. Co-administration contraindicated due to potential for myopathy including rhabdomyolysis. If treatment with Paxlovid is considered medically necessary, discontinue use of simvastatin at least 12 hours prior to initiation of Paxlovid, during the 5 days of Paxlovid treatment and for 5 days after completing Paxlovid.

Paxlovid US Prescribing Information, Pfizer Inc, February 2025.