PREZISTA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PREZISTA (PREZISTA).
PREZISTA (darunavir) is an HIV-1 protease inhibitor that selectively inhibits the cleavage of HIV-encoded Gag-Pol polyproteins in infected cells, thereby preventing the formation of mature infectious virions. It is coadministered with low-dose ritonavir as a pharmacokinetic enhancer.
| Metabolism | Primarily metabolized by CYP3A4. Coadministration with ritonavir inhibits CYP3A4, increasing darunavir exposure. Darunavir is also a substrate of P-glycoprotein. |
| Excretion | Primarily hepatic metabolism via CYP3A4; fecal excretion: 81.8% (44.1% as unchanged drug), renal excretion: 13.9% (8.2% as unchanged drug). |
| Half-life | Terminal elimination half-life: approximately 15 hours (range 10.3–24.5 hours) when co-administered with ritonavir; supports twice-daily dosing. |
| Protein binding | Approximately 99% bound to plasma proteins, primarily alpha-1-acid glycoprotein and albumin. |
| Volume of Distribution | Apparent Vd: 23–28 L (0.33–0.40 L/kg); indicates extensive tissue distribution. |
| Bioavailability | Oral bioavailability is approximately 82% when co-administered with ritonavir; absorption increased with food (high-fat meal increases AUC by 30–40%). |
| Onset of Action | Oral: Peak plasma concentration achieved in 2.5–4 hours; clinical antiviral effect begins within days. |
| Duration of Action | Sustained plasma levels above IC50 for 12 hours with twice-daily dosing; trough concentrations remain inhibitory. |
800 mg orally once daily with food in combination with ritonavir 100 mg or cobicistat 150 mg, or 600 mg orally twice daily with food in combination with ritonavir 100 mg twice daily.
| Dosage form | SUSPENSION |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment; not studied in severe renal impairment or end-stage renal disease; use with caution and monitor for adverse effects. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: not recommended; Child-Pugh C: contraindicated. |
| Pediatric use | For children ≥3 years and ≥15 kg: weight-based dosing twice daily with ritonavir; e.g., 15-<30 kg: 375 mg twice daily; 30-<40 kg: 450 mg twice daily; ≥40 kg: 600 mg twice daily. For once-daily dosing: only in children ≥40 kg: 800 mg once daily with ritonavir or cobicistat. |
| Geriatric use | No specific dose adjustment; use standard adult dosing; monitor for renal function and potential comorbidities due to increased risk of adverse effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PREZISTA (PREZISTA).
| Breastfeeding | Darunavir is excreted in human breast milk at low concentrations. The estimated infant dose is approximately 0.1% of the maternal therapeutic dose, and the M/P ratio is not well characterized. Given the potential for HIV transmission via breastfeeding and unknown long-term effects, breastfeeding is not recommended in HIV-positive mothers in developed settings. |
| Teratogenic Risk | Darunavir (PREZISTA) is not associated with increased risk of major birth defects based on data from the Antiretroviral Pregnancy Registry. However, due to insufficient data in the first trimester, it should be used only if clearly needed. No specific fetal toxicities are documented in the second and third trimesters. |
■ FDA Black Box Warning
No FDA black box warning is specified for PREZISTA.
| Serious Effects |
Coadministration with drugs highly dependent on CYP3A4 for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events (e.g., alfuzosin, dihydroergotamine, ergonovine, ergotamine, methylergonovine, cisapride, pimozide, oral midazolam, triazolam, lomitapide, lovastatin, simvastatin, rifampin, St. John's wort, and sildenafil when used for pulmonary arterial hypertension). Also contraindicated in patients with severe hepatic impairment (Child-Pugh Class C).
| Precautions | Hepatotoxicity: cases of drug-induced hepatitis and hepatic injury reported; monitor liver function. Severe skin reactions: including Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug rash with eosinophilia and systemic symptoms. Pancreatitis: elevated serum lipase and amylase; discontinue if symptoms occur. Fat redistribution: accumulation of visceral fat, lipodystrophy. Immune reconstitution syndrome: inflammatory response to opportunistic infections. Hemophilia: spontaneous bleeding reported in patients with hemophilia A and B. Sulfonamide allergy: darunavir contains a sulfonamide moiety; use with caution. |
Loading safety data…
| Fetal Monitoring | Monitor maternal viral load, CD4 count, and liver function tests regularly. Fetal ultrasound for growth and anatomy is recommended due to potential concurrent conditions. In third trimester, monitor for gestational diabetes and preeclampsia as with all antiretroviral therapy. |
| Fertility Effects | No specific data on darunavir affecting fertility in humans. Animal studies showed no adverse effects on fertility. However, HIV disease itself may impair fertility, and antiretroviral therapy may improve overall reproductive health. |