Paxlovid Drug Interactions

Paxlovid (nirmatrelvir/ritonavir) is an inhibitor of CYP3A and may increase plasma concentrations of medicinal products that are primarily metabolised by CYP3A. Medicinal products that are extensively metabolised by CYP3A and have high first pass metabolism appear to be the most susceptible to large increases in exposure when co-administered with nirmatrelvir/ritonavir. Thus, co-administration of nirmatrelvir/ritonavir with medicinal products highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events is contraindicated (see Table 5, Contraindications).
In vitro study results showed nirmatrelvir may be inducer of CYP3A4, CYP2B6, CYP2C8, and CYP2C9. The clinical relevance is unknown. Based on in vitro data, nirmatrelvir has a low potential to inhibit BCRP, MATE2K, OAT1, OAT3, OATP1B3 and OCT2. There is a potential for nirmatrelvir to inhibit MDR1, MATE1, OCT1 and OATP1B1 at clinically relevant concentrations.
Ritonavir has a high affinity for several cytochrome P450 (CYP) isoforms and may inhibit oxidation with the following ranked order: CYP3A4 > CYP2D6. Ritonavir also has a high affinity for P-glycoprotein (P-gp) and may inhibit this transporter. Ritonavir may induce glucuronidation and oxidation by CYP1A2, CYP2C8, CYP2C9 and CYP2C19 thereby increasing the biotransformation of some medicinal products metabolised by these pathways and may result in decreased systemic exposure to such medicinal products, which could decrease or shorten their therapeutic effect.
Co-administration of other CYP3A4 substrates that may lead to potentially significant interaction should be considered only if the benefits outweigh the risks (see Table 7).
Nirmatrelvir/ritonavir is a CYP3A substrate; therefore, medicinal products that induce CYP3A may decrease plasma concentrations of nirmatrelvir and ritonavir and reduce Paxlovid therapeutic effect.
Medicinal products listed in Table 5 (Contraindications) and Table 7 are a guide and not considered a comprehensive list of all possible medicinal products that may interact with nirmatrelvir/ritonavir. The healthcare provider should consult appropriate references for comprehensive information. (See Table 7.)

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