Liverpool COVID-19 Interactions

Potential Interaction

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

Clarithromycin

Quality of Evidence: Very Low

Summary:

Coadministration with nirmatrelvir/ritonavir has not been studied. Coadministration with ritonavir increased clarithromycin AUC and Cmax by 77% and 31%; AUC and Cmax of 14-OH clarithromycin decreased by 100% and 99%. Due to the large therapeutic window of clarithromycin no dose reduction should be necessary in patients with normal renal function. Clarithromycin doses greater than 1 g per day should not be coadministered with ritonavir dosed as a pharmacokinetic enhancer. Product labels recommend a dose reduction of clarithromycin for patients with impaired renal function (Clcr 30-60 mL/min, dose reduce clarithromycin by 50%; CLcr less than 30 mL/min, dose reduce clarithromycin by 75%). After stopping nirmatrelvir/ritonavir, the CYP3A4 inhibitory effect of nirmatrelvir/ritonavir is predicted to mostly disappear after 3 days.

Description:

Coadministration with ritonavir increased clarithromycin AUC and Cmax by 77% and 31%; AUC and Cmax of 14-OH clarithromycin decreased by 100% and 99%. Due to the large therapeutic window of clarithromycin no dose reduction should be necessary in patients with normal renal function. Clarithromycin doses greater than 1 g per day should not be coadministered with ritonavir dosed as a pharmacokinetic enhancer. For patients with moderate renal impairment, the dose should be reduced by 50%. Paxlovid is contraindicated in patients with severe renal impairment.

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

Coadministration with ritonavir increased clarithromycin AUC and Cmax by 77% and 31%; AUC and Cmax of 14-OH clarithromycin decreased by 100% and 99%. Due to the large therapeutic window of clarithromycin no dose reduction should be necessary in patients with normal renal function. Clarithromycin doses greater than 1 g per day should not be coadministered with ritonavir dosed as a pharmacokinetic enhancer. For patients with renal impairment, a clarithromycin dose reduction should be considered: for patients with creatinine clearance of 30 to 60 mL/min the dose should be reduced by 50%.

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

Co-administration may increase clarithromycin concentrations. Refer to the clarithromycin prescribing information for anti-infective dose adjustment.

Paxlovid US Prescribing Information, Pfizer Inc, February 2025.