Paxlovid Special Precautions

Risk of serious adverse reactions due to interactions with other medicinal products: Initiation of Paxlovid, a CYP3A inhibitor, in patients receiving medicinal products metabolised by CYP3A or initiation of medicinal products metabolised by CYP3A in patients already receiving Paxlovid, may increase plasma concentrations of medicinal products metabolised by CYP3A.
Initiation of medicinal products that inhibit or induce CYP3A may increase or decrease concentrations of Paxlovid, respectively.
These interactions may lead to: Clinically significant adverse reactions, potentially leading to severe, life-threatening or fatal events from greater exposures of concomitant medicinal products; Clinically significant adverse reactions from greater exposures of Paxlovid; Loss of therapeutic effect of Paxlovid and possible development of viral resistance.
See Table 8 for medicinal products that are contraindicated for concomitant use with nirmatrelvir/ritonavir (see Contraindications) and Table 10 for potentially significant interactions with other medicinal products (see Interactions). Potential for interactions should be considered with other medicinal products prior to and during Paxlovid therapy; concomitant medicinal products should be reviewed during Paxlovid therapy and the patient should be monitored for the adverse reactions associated with the concomitant medicinal products. The risk of interactions with concomitant medications during the 5-day treatment period for Paxlovid should be weighed against the risk of not receiving Paxlovid.
Co-administration of Paxlovid with calcineurin inhibitors and mTOR inhibitors: Consultation of a multidisciplinary group (e.g., involving physicians, specialists in immunosuppressive therapy, and/or specialists in clinical pharmacology) is required to handle the complexity of this coadministration by closely and regularly monitoring immunosuppressant serum concentrations and adjusting the dose of the immunosuppressant in accordance with the latest guidelines (see Interactions).
Hypersensitivity reactions: Anaphylaxis, other hypersensitivity reactions, and serious skin reactions (including toxic epidermal necrolysis and Stevens-Johnson syndrome) have been reported with Paxlovid (see Adverse Reactions). If signs and symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue Paxlovid and initiate appropriate medications and/or supportive care.
Hepatotoxicity: Hepatic transaminase elevations, clinical hepatitis and jaundice have occurred in patients receiving ritonavir. Therefore, caution should be exercised when administering Paxlovid to patients with pre-existing liver diseases, liver enzyme abnormalities or hepatitis.
Risk of HIV-1 resistance development: As nirmatrelvir is coadministered with ritonavir, there may be a risk of HIV-1 developing resistance to HIV protease inhibitors in individuals with uncontrolled or undiagnosed HIV-1 infection.
Excipients: Nirmatrelvir tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Nirmatrelvir and ritonavir tablets each contain less than 1 mmol sodium (23 mg) per dose, that is to say essentially 'sodium-free'.
Effects on ability to drive and use machines: There are no clinical studies that evaluated the effects of Paxlovid on ability to drive and use machines.