Paxlovid Special Precautions

Risk of serious adverse reactions due to interactions with other medicinal products: Management of drug-drug interactions (DDIs) in high-risk COVID-19 patients receiving multiple concomitant medications can be complex and require a thorough understanding of the nature and magnitude of interaction with all concomitant medications. In certain patients, a multi-disciplinary approach (e.g., involving physicians and specialists in clinical pharmacology) should be considered for management of DDIs especially if concomitant medications are withheld, their dosage is reduced, or if monitoring of side effects is necessary.
Effects of Nirmatrelvir+Ritonavir (Paxlovid) on other medicinal products: Initiation of Nirmatrelvir+Ritonavir (Paxlovid), a CYP3A inhibitor, in patients receiving medicinal products metabolized by CYP3A or initiation of medicinal products metabolized by CYP3A in patients already receiving Nirmatrelvir+Ritonavir (Paxlovid), may increase plasma concentrations of medicinal products metabolized by CYP3A (see Interactions).
Coadministration 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).
Effects of other medicinal products on Nirmatrelvir+Ritonavir (Paxlovid): Initiation of medicinal products that inhibit or induce CYP3A may increase or decrease concentrations of Nirmatrelvir+Ritonavir (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 Nirmatrelvir+Ritonavir (Paxlovid).
Loss of therapeutic effect of Nirmatrelvir+Ritonavir (Paxlovid) and possible development of viral resistance.
See Tables 5a, 5b, 5c and 5d for medicinal products that are contraindicated for concomitant use with nirmatrelvir/ritonavir and for potentially significant interactions with other medicinal products (see Interactions). Potential for interactions should be considered with other medicinal products prior to and during Nirmatrelvir+Ritonavir (Paxlovid) therapy; concomitant medicinal products should be reviewed during Nirmatrelvir+Ritonavir (Paxlovid) therapy and the patient should be monitored for the adverse reactions associated with the concomitant medicinal products.
Hypersensitivity reactions: Anaphylaxis and other hypersensitivity reactions have been reported with Nirmatrelvir+Ritonavir (Paxlovid) (see Adverse Reactions). Cases of Toxic Epidermal Necrolysis and Stevens-Johnson syndrome have been reported with ritonavir, a component of Nirmatrelvir+Ritonavir (Paxlovid) (refer to ritonavir Product information). If signs and symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue Nirmatrelvir+Ritonavir (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 Nirmatrelvir+Ritonavir (Paxlovid) to patients with pre existing liver diseases, liver enzyme abnormalities or hepatitis.
Risk of HIV-1 resistance development: Because 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: Nirmatrelvir+Ritonavir (Paxlovid) is expected to have no influence on the ability to drive and use machines.
Severe renal impairment: No clinical data are available in patients with severe renal impairment (including patients with ESRD). Based on pharmacokinetic data (see Pharmacology: Pharmacokinetics under Actions), the use of Nirmatrelvir+Ritonavir (Paxlovid) in patients with severe renal impairment could lead to over-exposure with potential toxicity. No recommendation in terms of dose adjustment could be elaborated at this stage pending dedicated investigation. Therefore, Nirmatrelvir+Ritonavir (Paxlovid) should not be used in patients with severe renal impairment (eGFR <30 mL/min, including patients with ESRD under hemodialysis).
Severe hepatic impairment: No pharmacokinetic and clinical data are available in patients with severe hepatic impairment. Therefore, Nirmatrelvir+Ritonavir (Paxlovid) should not be used in patients with severe hepatic impairment.