Darunavir

PREZISTA

What it isHIV protease inhibitor; treatment-experienced and first-line HIV.

Why this oneThe highest resistance barrier of the protease inhibitors, so it holds up against resistant virus.

What limits itIt requires ritonavir or cobicistat boosting, bringing CYP3A4 interactions. Rash; it is a sulfonamide.

FDA-approved for

FDA dosing	Population	Start	Target	Max
HIV-1 infection (with other antiretrovirals)	Adults & peds >=40 kg	800 mg/150 mg QD	800 mg/150 mg QD	800 mg/150 mg QD
HIV-1 infection (with other antiretrovirals)	Peds 25 to <40 kg	675 mg/150 mg QD	675 mg/150 mg QD	675 mg/150 mg QD
HIV-1 infection (with other antiretrovirals)	Peds >=3 yr, 15 to <25 kg	600 mg/90 mg QD (oral suspension tablet)	600 mg/90 mg QD	600 mg/90 mg QD

Renal Undefined

Hepatic Not recommended in severe hepatic impairment; not studied — no adjustment stated for mild-moderate.

Fixed-dose combination; do not co-administer with strong CYP3A inducers.

Take once daily with food.
Prezcobix Ped tablet for oral suspension: disperse in drinking water and take immediately with food.
HIV genotypic testing recommended in treatment-experienced patients; assess eGFR before starting.

Co-administration with drugs highly dependent on CYP3A for clearance with narrow therapeutic index (e.g., alfuzosin, ergot derivatives, lurasidone, pimozide, dronedarone, ivabradine, ranolazine, colchicine in renal/hepatic impairment)
Strong CYP3A inducers (e.g., carbamazepine, phenobarbital, phenytoin, rifampin, St. John's wort) — may reduce darunavir/cobicistat exposure

Hepatotoxicity — monitor LFTs
Severe skin reactions (including SJS, DRESS)
Effects on serum creatinine (cobicistat inhibits tubular secretion without affecting GFR)
New onset/worsening renal impairment with tenofovir DF
Immune reconstitution syndrome
Sulfonamide cross-sensitivity

Pregnancy Not recommended during pregnancy (substantially lower exposures in 2nd/3rd trimesters).

Lactation Breastfeeding not recommended (HIV transmission risk; drug present in animal milk).

NO BOXED WARNINGS

Principal riskBoosting brings CYP3A4 interactions; it is a sulfonamide

Cost, est. cash$10–$500/month

Generic entry2026

Therapeutic safety burden2 / 4

Overdose danger2 / 4

Weight-gain liability0 / 4

Sedation liability0 / 4

QT / Torsades0 / 4

Direct muscarinic antagonism0 / 4

Embryofetal risk2 / 4

Legacy pregnancy categoryUnknown / historical label unavailable

Defining liabilityAgent-specific renal, hepatic, hematologic, metabolic and drug-interaction toxicity.