Paxlovid (Eua) (nirmatrelvir/ritonavir)

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Nirmatrelvir must be used with a pharmacokinetic enhancer (i.e., low-dose ritonavir), and drug interactions associated with both nirmatrelvir and ritonavir should be considered.

Ritonavir-boosted nirmatrelvir is a strong inhibitor of CYP3A, and an inhibitor of CYP2D6, P-gp, and OATP1B1. Co-administration of ritonavir-boosted nirmatrelvir with drugs that are primarily metabolized by CYP3A and CYP2D6 or are transported by P-gp or OATP1B1 may result in increased plasma concentrations of these drugs and increase the risk of adverse events. Co-administration of ritonavir-boosted nirmatrelvir with drugs highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events is contraindicated.

Nirmatrelvir and ritonavir are CYP3A substrates; therefore, drugs that induce CYP3A may decrease nirmatrelvir and ritonavir plasma concentrations and reduce therapeutic effect of ritonavir-boosted nirmatrelvir.

The following information is based on drug interactions that are known or may potentially occur with the combination of ritonavir and nirmatrelvir (ritonavir-boosted nirmatrelvir). The drug interactions described below are not considered a comprehensive list of all possible drugs that may interact with ritonavir-boosted nirmatrelvir. Other appropriate resources such as the prescribing information for the interacting drug should be consulted for comprehensive information on dosing or monitoring with concomitant use of a strong CYP3A inhibitor such as ritonavir.

There are no contraindication interactions for this drug.

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

*History of clinically significant hypersensitivity reactions (e.g., toxic epidermal necrolysis (TEN) or Stevens-Johnson syndrome) to nirmatrelvir, ritonavir, or any other ingredient in the preparation.

*Concomitant use of drugs that are highly dependent on cytochrome P-450 (CYP) isoenzyme 3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events; these drugs include, but are not limited to, alfuzosin, ranolazine, amiodarone, dronedarone, flecainide, propafenone, quinidine, colchicine (in patients with renal and/or hepatic impairment), lurasidone, pimozide, silodosin, eplerenone, ivabradine, dihydroergotamine, ergotamine, methylergonovine, lovastatin, simvastatin, voclosporin, lomitapide, eletriptan, ubrogepant, finerenone, suzetrigine, naloxegol, sildenafil (Revatio(R)) for treatment of pulmonary arterial hypertension, triazolam, oral midazolam, flibanserin, and tolvaptan.

*Concomitant use of potent CYP3A inducers that can significantly reduce nirmatrelvir or ritonavir plasma concentrations and result in potential loss of virologic response and possible resistance; these drugs include, but are not limited to, apalutamide, enzalutamide, carbamazepine, phenobarbital, primidone, phenytoin, lumacaftor/ivacaftor, rifampin, rifapentine, and St. John's wort (Hypericum perforatum). Do not start ritonavir-boosted nirmatrelvir immediately after discontinuation of any of these drugs due to the delayed offset of the recently discontinued CYP3A inducer.

There are no contraindication contraindications for this drug.

There are no severe contraindications for this drug.

There are no moderate contraindications for this drug.

Adverse effects reported in >=1% of patients receiving ritonavir-boosted nirmatrelvir for the treatment of COVID-19 and more frequently than placebo include dysgeusia and diarrhea.

There are no severe adverse reactions for this drug.

There are no less severe adverse reactions for this drug.

No enhanced messaging available.

The FDA EUA permits use of ritonavir-boosted nirmatrelvir for the treatment of COVID-19 in certain pediatric patients >=12 years of age weighing at least 40 kg. Use of ritonavir-boosted nirmatrelvir is not authorized for pediatric patients <12 years of age or those weighing less than 40 kg.

Safety and efficacy of ritonavir-boosted nirmatrelvir have not been established in pediatric patients.

The pharmacokinetics of ritonavir-boosted nirmatrelvir have not been evaluated in pediatric patients <18 years of age. The EUA-recommended dosage of ritonavir-boosted nirmatrelvir is expected to result in plasma concentrations of the drugs in patients >=12 years of age weighing at least 40 kg that are comparable to those observed in adults since adults with similar body weight were included in the EPIC-HR trial evaluating ritonavir-boosted nirmatrelvir for the treatment of COVID-19.

Nirmatrelvir: Data are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In an embryo-fetal development study, reduced fetal body weight following oral administration of nirmatrelvir to pregnant rabbits was observed at systemic exposures approximately 10 times higher than clinical exposure at the authorized human dose. No other adverse developmental outcomes were observed in animal reproduction studies with nirmatrelvir at systemic exposures 3 times or greater than clinical exposure at the authorized human dose.

Ritonavir: Published observational studies have not identified an increase in the risk of major birth defects when ritonavir was used in pregnant women. Published studies with ritonavir are insufficient to identify a drug-associated risk of miscarriage. In animal reproduction studies, no evidence of adverse developmental outcomes was observed following oral administration of ritonavir to pregnant rats and rabbits at doses (based on body surface area conversions) or systemic exposures 3 times or greater than clinical doses or exposure at the authorized human dose.

The estimated background risk of major birth defects and miscarriage in the indicated population is unknown. COVID-19 in pregnancy is associated with adverse maternal and fetal outcomes, including preeclampsia, eclampsia, preterm birth, premature rupture of membranes, venous thromboembolic disease, and fetal death.

Nirmatrelvir and ritonavir are present in human milk in small amounts (<2%). There are no data on the effects of nirmatrelvir and ritonavir on the breastfed infant or on milk production.

The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for ritonavir-boosted nirmatrelvir and any potential adverse effects on the breast-fed child from the drug or from the underlying maternal condition.

Females with COVID-19 who are breast-feeding should follow clinical guidelines to avoid exposing the infant to the virus.

The manufacturer makes no specific dosage recommendations.

In an integrated data set of 1,578 patients who received nirmatrelvir and ritonavir, 10% were >=65 years of age and 2% were >=75 years of age. No overall differences in safety were seen between elderly and younger subjects; however, greater sensitivity of some older individuals cannot be ruled out.