Drug Interactions between garlic and nirmatrelvir / ritonavir

GENERALLY AVOID: Coadministration with garlic supplements may decrease the plasma concentrations of saquinavir and possibly other protease inhibitors (PIs). The exact mechanism is unknown but may involve induction of CYP450 3A4 metabolism and/or P-gycloprotein transport in the intestine by certain component(s) of garlic. In nine healthy, HIV-negative volunteers, investigators from the National Institutes of Health found that pretreatment with a garlic supplement (GarliPure Maximum Allicin Formula twice daily for 3 weeks) reduced the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of saquinavir (soft gelatin capsule 1200 mg 3 times daily for 10 doses during the last 4 days of garlic supplementation) by 54% and 51%, respectively, compared to baseline when saquinavir was administered alone. The effects appear to be sustained, since saquinavir Cmax and AUC returned to just 61% and 65% of baseline, respectively, after a 10-day washout period. Whether and how dietary garlic or other formulations of garlic supplement may affect saquinavir pharmacokinetics are currently unknown. It is also uncertain if and to what extent the interaction may occur with other PIs, which are also substrates of CYP450 3A4.

MANAGEMENT: Given the risk of reduced viral susceptibility and resistance development associated with subtherapeutic antiretroviral drug levels, garlic supplements should preferably be avoided in patients treated with PIs, particularly if they are using saquinavir as the sole PI in their antiretroviral regimen. Patients should be advised to consult with their caregivers before using any herbal or alternative medicines.