Indicated for mild-to-moderate COVID-19 positive adult and pediatric patients (12 years of age and older weighing at least 40 kg), who are at high risk for progression to severe COVID-19, including hospitalization or death.

Each combipack contains

• 4 Nirmatrelvir Tablets (each tablet contains Nirmatrelvir INN 150 mg)
• and 2 Ritonavir Tablets (each tablet contains Ritonavir USP 100 mg).

This inhibits the main protease (Mpro) of SARS-CoV-2, also known as 3C-like protease (3CLpro) or nsp5 protease. This inhibition of Mpro disrupts the viral replication process of SARS-CoV-2. Ritonavir is an HIV-1 protease inhibitor but is not active against SARS-CoV-2 Mpro. It inhibits CYP3A-mediated metabolism of Nirmatrelvir, resulting in increased plasma concentration of Nirmatrelvir.

Nirmatrelvir must be co-administered with Ritonavir. Initiate this treatment as soon as possible after diagnosis of COVID-19 and within 3-5 days of symptom onset. Administer orally with or without food.

Dosage: 300 mg Nirmatrelvir (two 150 mg tablets) with 100 mg Ritonavir (one 100 mg tablet), with all three tablets taken together twice daily for 5 days.

Missed Dose: If the patient misses a dose of this within 8 hours of the time it is usually taken, the patient should take it as soon as possible and resume the normal dosing schedule. If the patient misses a dose by more than 8 hours, the patient should not take the missed dose and instead take the next dose at the regularly scheduled time. The patient should not double the dose to make up for a missed dose.

Co-administration of this tablet with drugs highly dependent on CYP3A for clearance and for which increased plasma concentrations are associated with serious and/or life-threatening events is contraindicated. Co-administration with other CYP3A substrates may require dose adjustment or additional monitoring. Nirmatrelvir and Ritonavir are CYP3A substrates; therefore, drugs that induce CYP3A may reduce plasma concentrations of Nirmatrelvir and Ritonavir and decrease the therapeutic effect of this tablet.

• History of clinically significant hypersensitivity reactions to Nirmatrelvir, Ritonavir, or any of the components.
• Co-administration with drugs highly dependent on CYP3A for clearance and associated with serious or life-threatening reactions.
• Co-administration with potent CYP3A inducers that may significantly reduce Nirmatrelvir or Ritonavir plasma levels, leading to loss of virologic response or resistance.

Common adverse events (incidence >1%) include dysgeusia, diarrhea, hypertension, and myalgia.

This tablet is not recommended during pregnancy or in individuals who may become pregnant and are not using contraception. Breastfeeding should be interrupted during treatment. Animal studies suggest high doses may affect fetal growth. It should be used in pregnancy only if clearly needed and benefits outweigh risks. Oral solution is not recommended.

Concomitant use with certain drugs may cause significant drug interactions.

epatotoxicity including elevated liver enzymes, hepatitis, and jaundice has been reported with Ritonavir.

Use may lead to HIV-1 resistance in individuals with undiagnosed or uncontrolled HIV infection.

Pediatric Use: Not authorized for patients younger than 12 years or weighing less than 40 kg. Safety and efficacy not established.

Geriatric Use: Data from patients ≥65 years contribute to overall safety and efficacy assessment.

Renal Impairment: No adjustment in mild impairment. In moderate impairment (eGFR >30 to <60 mL/min), dose reduction is required. Not recommended in severe impairment (eGFR <30 mL/min).

Hepatic Impairment: No adjustment in mild or moderate impairment. Not recommended in severe hepatic impairment (Child-Pugh C).

Management of overdose includes supportive care, monitoring vital signs, and clinical observation. No specific antidote is available.

Antiviral drugs

Do not store above 30°C. Keep in a dry place. Protect from light and keep out of reach of children.