Nirmatrelvir

in PAXLOVID

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What it isSARS-CoV-2 main protease inhibitor, given with ritonavir; early COVID-19 in those at risk of progression.

Why this oneSubstantial reduction in hospitalization when started within five days of symptom onset.

What limits itThe ritonavir booster is the problem: it is a strong CYP3A4 inhibitor, so statins, some anticoagulants and many other drugs must be held. Renally adjusted.

FDA-approved for

COVID-19 (2023)

FDA label

Read the full label on DailyMed ↗

BOXED WARNING Significant drug interactions — ritonavir is a strong CYP3A inhibitor and may raise levels of CYP3A substrates, causing severe, life-threatening, or fatal events; review all concomitant medications before prescribing.

FDA dosing	Population	Start	Target	Max
Mild-to-moderate COVID-19 at high risk of progression to severe disease	adult	300 mg nirmatrelvir + 100 mg ritonavir BID × 5 days	300 mg/100 mg BID × 5 days

Renal Moderate (eGFR 30–<60): 150 mg/100 mg BID; severe (<30, incl. hemodialysis): 300/100 once Day 1 then 150/100 QD Days 2–5; no adjustment if mild

Hepatic Not recommended in severe (Child-Pugh C); no adjustment for mild–moderate

Complete the full 5-day course

Instructions

Start as soon as possible after diagnosis and within 5 days of symptom onset
Take all 3 tablets together twice daily for 5 days, with or without food
Swallow whole; do not chew, break, or crush
Nirmatrelvir must always be co-administered with ritonavir
On hemodialysis days, dose after dialysis

Contraindications

History of clinically significant hypersensitivity (e.g., TEN, SJS) to nirmatrelvir, ritonavir, or components
Co-administration with CYP3A substrates where elevated levels cause serious/life-threatening reactions (e.g., alfuzosin, amiodarone, dronedarone, colchicine, lurasidone, pimozide, ergot derivatives, lovastatin/simvastatin, oral midazolam, triazolam, sildenafil for PAH)
Co-administration with strong CYP3A inducers (e.g., rifampin, carbamazepine, phenobarbital, phenytoin, St. John's Wort, apalutamide, enzalutamide)

Cautions

Serious/life-threatening reactions from drug interactions (e.g., calcineurin inhibitors, calcium channel blockers)
Hypersensitivity/anaphylaxis, SJS/TEN
Hepatotoxicity (ritonavir)
Risk of HIV-1 resistance in uncontrolled/undiagnosed HIV-1