Ritonavir

NORVIR

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What it isHIV protease inhibitor now used almost entirely as a pharmacokinetic booster; HIV regimens and nirmatrelvir.

Why this oneIts potent CYP3A4 inhibition is exploited deliberately to raise partner drug levels, allowing lower doses.

What limits itThat same inhibition causes the interactions — every co-prescription must be checked. It also induces some enzymes, which complicates prediction.

FDA-approved for

HIV infection (1996)
pharmacokinetic booster (1996)

FDA label

Read the full label on DailyMed ↗

BOXED WARNING Drug-drug interactions may cause potentially serious and/or life-threatening reactions (via CYP3A inhibition); review concomitant medications.

FDA dosing	Population	Start	Target	Max
HIV-1 infection (with other antiretrovirals)	Adults	300 mg BID, titrate up by 100 mg BID q2-3 days	600 mg BID	600 mg BID
HIV-1 infection (with other antiretrovirals)	Pediatric >1 month	250 mg/m2 BID, titrate up by 50 mg/m2 BID q2-3 days	350-400 mg/m2 BID	600 mg BID

Titration Increase at 2-3 day intervals

Renal Undefined

Hepatic Mild-moderate (Child-Pugh A/B): no adjustment; severe (Child-Pugh C): not recommended

Instructions

Take with meals
Swallow tablets whole; do not chew, break, or crush
Reduce ritonavir dose when used to boost other protease inhibitors (atazanavir, darunavir, fosamprenavir, saquinavir, tipranavir)
Must be used in combination with other antiretroviral agents

Contraindications

Drugs highly dependent on CYP3A for clearance with serious/life-threatening toxicity at elevated levels: alfuzosin; ranolazine; antiarrhythmics (amiodarone, dronedarone, flecainide, propafenone, quinidine); voriconazole; colchicine; lurasidone; pimozide; ergot derivatives (dihydroergotamine, ergotamine, methylergonovine); cisapride; lovastatin, simvastatin; lomitapide; suzetrigine; sildenafil (Revatio) for PAH; triazolam, oral midazolam
Potent CYP3A inducers that markedly reduce ritonavir levels: apalutamide, St. John's Wort

Cautions

Hepatotoxicity - fatalities have occurred; monitor liver function
Pancreatitis - fatalities have occurred
Allergic reactions/hypersensitivity (anaphylaxis, TEN, SJS, angioedema, bronchospasm)
PR interval prolongation; second/third degree AV block
Elevated total cholesterol and triglycerides
New-onset or worsening diabetes/hyperglycemia
Immune reconstitution syndrome
Fat redistribution/accumulation
Increased bleeding in patients with hemophilia