Paxlovid (Eua)

FDA label

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Renal eGFR ≥60–<90: no adjustment. eGFR ≥30–<60: 150/100 mg BID x 5 days. eGFR <30 incl. hemodialysis: 300/100 mg once Day 1, then 150/100 mg QD Days 2–5; on dialysis days give after hemodialysis.

Hepatic Mild–moderate (Child-Pugh A/B): no adjustment. Severe (Child-Pugh C): not recommended (no PK/safety data).

Cannot be started immediately after discontinuing a strong CYP3A inducer (delayed inducer offset).

Instructions

• Start ASAP after COVID-19 diagnosis and within 5 days of symptom onset; complete full 5-day course
• Take the prescribed nirmatrelvir and ritonavir tablets together, with or without food, at ~same time each day; tablet count and frequency depend on renal function (eGFR ≥60: two 150 mg nirmatrelvir + one 100 mg ritonavir BID; eGFR ≥30–<60: one + one BID; eGFR <30 incl. hemodialysis: two + one once Day 1, then one + one QD Days 2–5)
• Swallow whole — do not chew, break, or crush
• Nirmatrelvir must be co-administered with ritonavir (alone → subtherapeutic levels)
• Missed dose ≤8 h: take ASAP; >8 h: skip, do not double
• If hospitalized for severe COVID after starting, complete the 5-day course per provider discretion

Available strengths

• tab 150/100 mg

Contraindications

• Drugs highly CYP3A-dependent where elevated levels are serious/life-threatening: alfuzosin, ranolazine, amiodarone, dronedarone, flecainide, propafenone, quinidine, colchicine (in renal/hepatic impairment), lurasidone, pimozide, silodosin, eplerenone, ivabradine, ergots (DHE, ergotamine, methylergonovine), lovastatin, simvastatin, voclosporin, lomitapide, eletriptan, ubrogepant, finerenone, suzetrigine, naloxegol, sildenafil-for-PAH, triazolam, oral midazolam, flibanserin, tolvaptan
• Strong CYP3A inducers (apalutamide, enzalutamide, carbamazepine, phenobarbital, primidone, phenytoin, rifampin, rifapentine, lumacaftor/ivacaftor, St. John's Wort) — loss of virologic response/resistance; do not start Paxlovid immediately after stopping one

Cautions

• Boxed: review all concomitant meds for CYP3A interactions (worst offenders: calcineurin inhibitors e.g. tacrolimus/cyclosporine, calcium channel blockers)
• Hypersensitivity: anaphylaxis, TEN, SJS reported — discontinue immediately
• Hepatotoxicity (ritonavir): transaminase elevations, hepatitis, jaundice — caution with pre-existing liver disease
• HIV-1 protease-inhibitor resistance risk in uncontrolled/undiagnosed HIV-1
• Ritonavir may reduce combined hormonal contraceptive efficacy — use alternative/barrier method

Adverse reactions

• Dysgeusia (5%)
• Diarrhea (3%)
• Post-EUA: anaphylaxis, TEN/SJS, headache, hypertension, abdominal pain, nausea, vomiting, malaise

Pregnancy Insufficient nirmatrelvir human data; ritonavir observational data show no increased birth-defect risk; untreated COVID-19 in pregnancy itself carries maternal/fetal risk.

Lactation Present in milk in small amounts (infant dose <2% of maternal weight-adjusted); no infant-effect data; weigh benefit vs need.