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Coadministration of Nirmatrelvir+Ritonavir (Paxlovid) with medicinal products that induce CYP3A may decrease nirmatrelvir and ritonavir plasma concentrations and reduce Nirmatrelvir+Ritonavir (Paxlovid) therapeutic effect.
Coadministration of Nirmatrelvir+Ritonavir (Paxlovid) with medicinal product that inhibits CYP3A4 may increase nirmatrelvir and ritonavir plasma concentrations.
Effects of Nirmatrelvir+Ritonavir (Paxlovid) on other medicinal products: Medicinal products CYP3A4 substrates: Nirmatrelvir+Ritonavir (Paxlovid) is a strong inhibitor of CYP3A and increases plasma concentrations of medicinal products that are primarily metabolized by CYP3A. Thus, coadministration 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 Tables 5a, 5b, 5c and 5d). Coadministration of other CYP3A4 substrates that may lead to potentially significant interaction (see Tables 5a, 5b, 5c and 5d) should be considered only if the benefits outweigh the risks.
Medicinal products CYP2D6 substrates: Based on in vitro studies, ritonavir has a high affinity for several cytochrome P450 (CYP) isoforms and may inhibit oxidation with the following ranked order: CYP3A4 > CYP2D6. Coadministration of Nirmatrelvir+Ritonavir (Paxlovid) with drug substrates of CYP2D6 may increase the CYP2D6 substrate concentration.
Medicinal products P-glycoprotein substrates: Nirmatrelvir+Ritonavir (Paxlovid) also has a high affinity for P glycoprotein (P gp) and inhibits this transporter; caution should thus be exercised in case of concomitant treatment. Close drug monitoring for safety and efficacy should be performed, and dose reduction may be adjusted accordingly, or avoid concomitant use.
Nirmatrelvir+Ritonavir (Paxlovid) may induce glucuronidation and oxidation by CYP1A2, CYP2C8, CYP2C9 and CYP2C19 thereby increasing the biotransformation of some medicinal products metabolized by these pathways and may result in decreased systemic exposure to such medicinal products, which could decrease or shorten their therapeutic effect.
Based on in vitro studies there is a potential for nirmatrelvir to inhibit MDR1, MATE1, OCT1 and OATP1B1 at clinically relevant concentrations.
Dedicated drug-drug interactions studies conducted with Nirmatrelvir+Ritonavir (Paxlovid) indicate that the drug interactions are primarily due to ritonavir. Hence, drug interactions pertaining to ritonavir are applicable for Nirmatrelvir+Ritonavir (Paxlovid).
Medicinal products listed in Tables 5a, 5b, 5c and 5d are a guide and not considered a comprehensive list of all possible medicinal products that are contraindicated or may interact with nirmatrelvir/ritonavir. (See Tables 5a, 5b, 5c and 5d.)
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