How long should atorvastatin (Lipitor) be held after starting Paxlovid (nirmatrelvir/ritonavir)?

Atorvastatin Should Be Temporarily Discontinued During Paxlovid Treatment

Atorvastatin should be temporarily discontinued during the 5-day course of Paxlovid (nirmatrelvir/ritonavir) therapy and for 2 days after completing treatment due to significant drug-drug interactions. 1, 2

Drug Interaction Mechanism

• Ritonavir, a component of Paxlovid, is a strong CYP3A inhibitor that significantly affects the metabolism of atorvastatin 1
• When co-administered with ritonavir, atorvastatin exposure (AUC) increases approximately 4.76-fold and maximum concentration (Cmax) increases 3.78-fold 2
• This increased exposure significantly elevates the risk of statin-related adverse effects, particularly myopathy and rhabdomyolysis 1, 3

Management Options

Option 1: Temporary Discontinuation (Preferred)

• Temporarily discontinue atorvastatin during the 5-day course of Paxlovid and for 2 days after completing treatment 2
• Short-term statin interruption (7 days total) poses minimal cardiovascular risk while avoiding potentially serious adverse effects 4
• Resume normal atorvastatin dosing 2 days after completing Paxlovid treatment 2

Option 2: Dose Reduction (If discontinuation not possible)

• For patients on 20 mg atorvastatin: reduce to half the original dose (10 mg) during Paxlovid treatment 2
• For patients on 40 mg or higher: reduce to one-quarter of the original dose during Paxlovid treatment and for 2 days after 2
• This approach is less preferable as it still carries increased risk of adverse effects 1

Important Considerations

• The interaction risk extends beyond the 5-day Paxlovid treatment period due to ritonavir's prolonged effects on metabolism 1
• Pravastatin or fluvastatin may be considered as alternative statins during Paxlovid treatment if lipid-lowering therapy cannot be interrupted 4
• These alternative statins have minimal dependence on CYP3A4 metabolism 4
• Monitor for symptoms of myopathy (muscle pain, tenderness, or weakness) if any statin is continued during Paxlovid treatment 5

Clinical Monitoring

• If statin therapy must be continued during Paxlovid treatment, monitor for:
  • Muscle symptoms (pain, tenderness, weakness) 5
  • Signs of rhabdomyolysis (dark urine, severe muscle pain) 3
  • Liver function abnormalities 5

Resuming Therapy

• Resume normal atorvastatin dosing 2 days after completing the 5-day course of Paxlovid 2
• No special monitoring is required when resuming normal dosing if the patient was asymptomatic during the interruption 5