Potential for XOCOVA to affect other drugs1

XOCOVA is a strong inhibitor of CYP3A and an inhibitor of P-gp and BCRP. Co-administration of XOCOVA with drugs that are primarily metabolized by CYP3A or are transported by P-gp or BCRP may result in increased plasma concentrations of such drugs and increase the risk of adverse events. For drugs that are CYP3A substrates and contraindicated with XOCOVA, initiation of XOCOVA should be considered only after careful evaluation of relevant clinical and pharmacokinetic factors related to the concomitant medication. In addition, re‑initiation of contraindicated CYP3A substrates should be considered based on an assessment of the duration of CYP3A inhibition and patient‑specific considerations. Refer to individual drug prescribing information for additional information.

Potential for other drugs to affect XOCOVA1

XOCOVA is a CYP3A substrate; therefore, drugs that induce CYP3A may decrease ensitrelvir plasma concentrations and reduce XOCOVA therapeutic effect. Therefore, use of XOCOVA with strong CYP3A4 inducers is contraindicated. No dose adjustment is recommended when XOCOVA is used concomitantly with moderate or weak CYP3A inducers. Refer to individual drug prescribing information for additional information.

Established and other potentially significant drug interactions1

The table below provides examples of drugs that are contraindicated with XOCOVA. It is provided as a guide consistent with Section 7 of the XOCOVA Prescribing Information. It is not a comprehensive list of all possible drugs that may interact with XOCOVA. The healthcare provider should consult other appropriate resources, such as the prescribing information for the interacting drug, for comprehensive information on dosing and monitoring with concomitant use of a strong CYP3A inhibitor, like XOCOVA.

Drugs Contraindicated with XOCOVA due to Risk of Potentially Serious or Fatal Interaction1

↑ = increase in effect on drug concentration↓ = decrease in effect on drug concentration

*Strong CYP3A4 inducers: Co-administration with the strong CYP3A inducer carbamazepine (titrated from 100 mg twice daily to 300 mg twice daily over 1 week and then maintained at a 300-mg twice-daily dose for 11 days, with some subjects requiring dose reduction) decreased the AUC of ensitrelvir by approximately 40-45%.1

AUC=area under curve.

Review XOCOVA once-daily dosing

INDICATION & IMPORTANT SAFETY INFORMATION

INDICATION

XOCOVA (ensitrelvir) is indicated for post-exposure prophylaxis (PEP) of coronavirus disease 2019 (COVID-19) in adults and adolescents 12 years of age and older following contact with an individual who has COVID-19.

IMPORTANT SAFETY INFORMATION

Contraindications

XOCOVA is contraindicated in patients with a history of clinically significant hypersensitivity reactions to XOCOVA or any of its components. XOCOVA is also contraindicated when administered with drugs primarily metabolized by CYP3A for which elevated concentrations may be associated with serious and/or life-threatening reactions or when administered with strong CYP3A inducers because they may significantly reduce XOCOVA plasma concentrations leading to potential loss of virologic response.

Embryofetal Toxicity

Based on animal data, XOCOVA may cause fetal harm when administered to a pregnant woman. Advise pregnant women and females of reproductive potential that XOCOVA may cause fetal harm. Verify pregnancy status of females of reproductive potential before initiating XOCOVA and advise using effective contraception during XOCOVA use and for 2 weeks after the final dose.

Risk of Serious Adverse Reactions Due to Drug Interactions

XOCOVA is a strong CYP3A inhibitor and an inhibitor of P-gp and BCRP. In patients receiving or initiating medications metabolized by CYP3A or transported by P-gp or BCRP, XOCOVA may increase plasma concentrations of those medications and may potentially lead to severe, life-threatening, or fatal events from increased exposure. CYP3A inducers may decrease concentrations of XOCOVA, leading to loss of therapeutic effect.

Before prescribing XOCOVA, review all concomitant medications to assess potential drug-drug interactions and determine if those medications require a dose adjustment, interruption, and/or additional monitoring. Consider the benefit of XOCOVA and whether risk of potential drug-drug interactions can be managed.

Hypersensitivity Reactions Including Anaphylaxis

Hypersensitivity reactions, including anaphylaxis, anaphylactic shock, and angioedema have been reported. If signs and symptoms of a clinically significant hypersensitivity reaction occur, immediately discontinue XOCOVA and initiate appropriate treatment.

Lactation

There are no data on the presence of XOCOVA in human milk, effects on breastfed infants, or effects on milk production. XOCOVA was present in the milk of lactating rats. Advise women not to breastfeed while on XOCOVA and for 2 weeks after the final dose.

Adverse Reactions

The most common adverse events occurring in ≥1% of XOCOVA patients and at greater frequency than placebo, respectively, were headache (2.9% vs 2.6%), diarrhea (1.7% vs 1.3%), and cough (1.1% vs 0.6%).

Laboratory Abnormalities

Asymptomatic hemoglobin declines from baseline of >2 g/dL occurred in XOCOVA and placebo patients (3% vs 1%, respectively).

Please see full Prescribing Information.

Reference: 1. XOCOVA [package insert]. Florham Park, NJ: Shionogi Inc.