nirmatrelvir and ritonavir

J05AE30

Forms & Strengths

Nirmatrelvir 150 mg tablets; Ritonavir 100 mg tablets
Co-packaged blister cards: 2 nirmatrelvir tablets (150 mg each) and 1 ritonavir tablet (100 mg) per dose

Adult Dosing

Mild-to-moderate COVID-19: 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet) taken together orally twice daily for 5 days
Initiate as soon as possible after COVID-19 diagnosis and within 5 days of symptom onset
Renal impairment (eGFR 30 to <60 mL/min): 150 mg nirmatrelvir with 100 mg ritonavir twice daily for 5 days
Renal impairment (eGFR <30 mL/min): Not recommended

Pediatric Dosing

Pediatric patients (<12 years or weighing <40 kg): Safety and efficacy have not been established
Pediatric patients (≥12 years and weighing ≥40 kg): 300 mg nirmatrelvir and 100 mg ritonavir twice daily for 5 days

Indications

Treatment of mild-to-moderate coronavirus disease 2019 (COVID-19) in adults and pediatric patients (≥12 years of age weighing ≥40 kg) with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progression to severe COVID-19

Mechanism of Action

Nirmatrelvir is a peptidomimetic inhibitor of the SARS-CoV-2 main protease (Mpro, also known as 3CLpro), preventing viral replication
Ritonavir inhibits the CYP3A-mediated metabolism of nirmatrelvir, resulting in increased systemic concentrations and sustained therapeutic levels of nirmatrelvir

Contraindications

History of clinically significant hypersensitivity reactions to active substances or any excipients
Co-administration with drugs highly dependent on CYP3A for clearance and for which elevated concentrations are associated with serious/life-threatening reactions (e.g., alfuzosin, meperidine, piroxicam, propafenone, amiodarone, dronedarone, colchicine, sildenafil when used for PAH)
Co-administration with potent CYP3A inducers where significantly reduced nirmatrelvir/ritonavir plasma concentrations may be associated with potential for loss of virologic response and possible resistance (e.g., rifampin, carbamazepine, phenobarbital, St. John's wort)

Adverse Reactions

Drug Interactions

Contraindicated with potent CYP3A inducers (e.g., rifampin, carbamazepine, St. John's wort)
Contraindicated with drugs heavily reliant on CYP3A for clearance leading to toxicity (e.g., statins like simvastatin and lovastatin, oral midazolam, triazolam)
Co-administration with antiplatelets/anticoagulants (e.g., apixaban, rivaroxaban, clopidogrel) may significantly increase bleeding risk
Potential interactions with immunosuppressants (e.g., tacrolimus, cyclosporine) requiring rigorous therapeutic drug monitoring

Curated Content: Needs Vetting Before Put to Clinical Use