darunavir
Brand: Prezista, Prezcobix (with cobicistat), Symtuza (combination)
Prototype: atazanavir
Drug Class: HIV protease inhibitor (PI)
Drug Family: antiretroviral
Subclass: second-generation HIV protease inhibitor
Organ Systems: infectious-disease
Mechanism of Action
Binds the active site of HIV-1 protease, preventing cleavage of gag-pol polyprotein precursors into functional viral proteins; produces immature, non-infectious viral particles; requires pharmacokinetic boosting with ritonavir or cobicistat.
HIV-1 protease
Indications
- HIV-1 infection (treatment-naïve and treatment-experienced patients) — must be given with ritonavir or cobicistat boosting
Contraindications
- darunavir/ritonavir hypersensitivity
- concurrent drugs highly dependent on CYP3A4 for clearance (alfuzosin, rifampin, ergotamine, pimozide, simvastatin, lovastatin, oral midazolam, triazolam)
Adverse Effects
Common
- diarrhea
- nausea
- headache
- rash
- elevated lipids
Serious
- hepatotoxicity
- hyperglycemia/diabetes
- fat redistribution/lipodystrophy
- hypersensitivity (sulfonamide component)
- drug interactions via CYP3A4 inhibition by ritonavir/cobicistat booster
Pharmacokinetics (ADME)
| Absorption | 82% (with food); must always be taken with food |
| Distribution | widely distributed; extensively protein-bound |
| Metabolism | hepatic CYP3A4; boosting with ritonavir or cobicistat (CYP3A4 inhibitors) increases darunavir AUC ~14-fold |
| Excretion | fecal (79.5%) and renal (13.9%) |
| Half-life | 15 hours (boosted) |
| Onset | 2.5–4 hours |
| Peak | 2.5–4 hours |
| Duration | 24 hours (boosted once-daily for treatment-naïve) |
| Protein Binding | 95% |
| Vd | moderate-large |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| statins (simvastatin, lovastatin) | ritonavir/cobicistat booster markedly increases statin levels; rhabdomyolysis — contraindicated | major |
| rifampin | potent CYP3A4 induction reduces darunavir to subtherapeutic levels; contraindicated | major |
| midazolam/triazolam | CYP3A4 inhibition by booster causes extreme sedation; IV midazolam requires caution, oral is contraindicated | major |
Nursing Considerations
- Always administer darunavir with food (any food); check whether patient is receiving ritonavir 100 mg or cobicistat as the pharmacokinetic booster.
- Extensively review drug interactions before prescribing; ritonavir/cobicistat as pharmacokinetic booster dramatically alters levels of many co-administered drugs.
- Monitor lipid panel, blood glucose, and LFTs at baseline and every 3–6 months.
- Darunavir contains a sulfonamide moiety; assess history of sulfonamide allergy before prescribing.
Clinical Pearls
- Darunavir is the preferred protease inhibitor in current HIV treatment guidelines due to its high genetic barrier to resistance — resistance requires accumulation of multiple specific mutations that rarely develop during therapy.
- Pharmacokinetic boosting with ritonavir or cobicistat is required: these agents inhibit CYP3A4 and increase darunavir bioavailability by preventing its rapid presystemic metabolism, achieving therapeutically adequate plasma levels.
Safety Profile
Pregnancy safe
Lactation avoid
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Not required
Concordance Terms
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