Drug reference

nirmatrelvir

SARS-CoV-2 main protease (3CLpro/Mpro) inhibitor antiviral · Antiviral

START

300 mg + ritonavir 100 mg PO q12h ×5 days (≤5 d onset)

TYPICAL MAX

300 mg twice daily (150 mg if eGFR 30–59)

STOP IF

Severe hypersensitivity or significant hepatotoxicity

WATCH

Full drug-interaction review (ritonavir), renal function, BP

CDSCO approvedATC J05AE30

Dose laddermg/d

Renal dose adjustmenteGFR mL/min/1.73m²

KDIGO 2024 + manufacturer label

Pharmacokineticsplasma · t hours

ONSET: 1h · absorption
PEAK: 3h · Tmax
t½: 6h · t½ (boosted)
DURATION: 12h · q12h

EXCRETION

Renal (boosted, unchanged) and faecal

route + CYP

INTERACTIONS

5 major

incl. contraindicated

PREGNANCY

Limited data; individualised use considering risk of severe COVID-19.

FDA category + note

Top interactionssee all 8 →

AmiodaroneContraindicatedDatabaseKimi deep-research + Cla
Ergot AlkaloidsContraindicatedDatabaseKimi deep-research + Cla
SimvastatinContraindicatedDatabaseKimi deep-research + Cla
Drugs Highly Dependent On Cyp3aSevereTextbookHarrison 22e · unknown

Mechanism

Peptidomimetic inhibitor of the SARS-CoV-2 3CL main protease, blocking viral polyprotein processing and replication; co-administered with ritonavir as a pharmacokinetic booster (CYP3A4 inhibition).

Indications

Mild-to-moderate COVID-19 in patients at high risk of progression (with ritonavir, within 5 days of symptoms)

Dosing

Adult: 300 mg nirmatrelvir + 100 mg ritonavir PO every 12 h for 5 days; start within 5 days of symptom onset.
Pediatric: ≥12 y and ≥40 kg: adult dose.
Renal adjustment: eGFR 30–59: reduce to 150 mg nirmatrelvir + 100 mg ritonavir q12h. eGFR <30: not recommended.
Hepatic adjustment: Mild–moderate: no adjustment; severe (Child-Pugh C): not recommended.
Geriatric: No specific adjustment (assess renal function).
Max dose: 300 mg nirmatrelvir twice daily (with ritonavir 100 mg)

Pharmacokinetics

Onset

Antiviral effect within days

Peak effect

~3 h (Tmax, boosted)

Duration

~12 h (twice-daily)

Half-life

~6 h (ritonavir-boosted)

Bioavailability

Enhanced by ritonavir (CYP3A4 inhibition)

Protein binding

~69%

Metabolism

CYP3A4 (inhibited by co-dosed ritonavir)

Excretion

Renal (boosted, largely unchanged) and faecal

Contraindications

Co-administered ritonavir contraindications: drugs highly CYP3A4-dependent with serious toxicity (e.g., certain antiarrhythmics, ergot alkaloids, lovastatin/simvastatin, some sedatives)
Severe hypersensitivity
Severe hepatic impairment

Side effects

Common

Dysgeusia (metallic taste)DiarrhoeaHypertensionMyalgiaNausea

Serious

Hepatotoxicity
Severe hypersensitivity/anaphylaxis
Serious interactions via ritonavir CYP3A4 inhibition
COVID-19 rebound (generally mild)

Pregnancy & lactation

Pregnancy

Limited data; individualised use considering risk of severe COVID-19.

Lactation

Limited data; consider temporary interruption or monitoring.

Drug interactions

Amiodarone

Contraindicated

Database

Increased antiarrhythmic levels

Contraindicated; choose alternative COVID therapy

Source: Kimi deep-research + Cla

Ergot Alkaloids

Contraindicated

Database

CYP3A4 inhibition

Contraindicated

Source: Kimi deep-research + Cla

Simvastatin

Contraindicated

Database

Ritonavir CYP3A4 inhibition

Withhold statin during and 5 days after course

Source: Kimi deep-research + Cla

Drugs Highly Dependent On Cyp3a

Severe

Textbook

Severe reactions due to elevated levels of co-administered drugs.

Nirmatrelvir/ritonavir should not be given with drugs highly dependent on CYP3A. Examples include statins, sirolimus, tacrolimus, colchicine, and many others.

Source: Harrison 22e · unknown

Direct Oral Anticoagulants

Severe

Database

CYP3A4 inhibition

Dose-adjust or interrupt; specialist input

Source: Kimi deep-research + Cla

Cyp3a Inducers

Moderate

Textbook

Reduced plasma levels and potential loss of effectiveness of nirmatrelvir.

Avoid co-administration with strong CYP3A inducers.