PREZCOBIX PED
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PREZCOBIX PED (PREZCOBIX PED).
Darumavir is an HIV-1 protease inhibitor that inhibits the cleavage of HIV-1 Gag-Pol polyproteins, resulting in non-infectious immature viral particles. Cobicistat is a CYP3A inhibitor that boosts darunavir exposure without contributing to antiviral activity.
| Metabolism | Darumavir is extensively metabolized by CYP3A; cobicistat is a mechanism-based inhibitor of CYP3A and is metabolized by CYP3A and to a minor extent by CYP2D6. |
| Excretion | Darunavir: ~80% fecal (mostly as parent), ~14% renal (3% unchanged). Cobicistat: ~86% fecal, ~8% renal. |
| Half-life | Darunavir: ~15 hours (with cobicistat). Cobicistat: ~3-4 hours. |
| Protein binding | Darunavir: ~95% bound to alpha-1-acid glycoprotein (AAG). Cobicistat: ~97-98% bound to plasma proteins. |
| Volume of Distribution | Darunavir: Vd ~88 L (1.3 L/kg for 70 kg adult). Cobicistat: Vd ~144 L (2.1 L/kg for 70 kg adult). |
| Bioavailability | Darunavir: ~82% (with cobicistat, relative to ritonavir-boosted). Cobicistat: ~70%. |
| Onset of Action | Oral: Therapeutic effect typically within 1-2 weeks of consistent dosing, achieving virologic suppression. |
| Duration of Action | Darunavir: Approximately 24 hours with once-daily dosing. Cobicistat: CYP3A inhibition lasts ~24 hours. |
PREZCOBIX PED is a pediatric formulation; adult dosing is not applicable. For adults, the equivalent product is PREZCOBIX (darunavir/cobicistat) fixed-dose combination: 800 mg/150 mg orally once daily with food.
| Dosage form | TABLET, FOR SUSPENSION |
| Renal impairment | For darunavir/cobicistat: not recommended in patients with CrCl <70 mL/min due to cobicistat component. No dose adjustment required for CrCl ≥70 mL/min. |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh Class C). Not recommended in moderate impairment (Child-Pugh Class B) due to lack of data. Use with caution in mild impairment (Child-Pugh Class A); no dose adjustment required. |
| Pediatric use | Pediatric dosing for PREZCOBIX PED (darunavir/cobicistat) is weight-based: for body weight ≥40 kg: 800 mg/150 mg orally once daily with food. For weight 30 to <40 kg: 675 mg/150 mg orally once daily with food. For weight 15 to <30 kg: 600 mg/150 mg orally once daily with food. For weight <15 kg: not recommended. |
| Geriatric use | No specific dose adjustment for elderly patients; use standard dosing. Monitor renal function, as age-related decline may affect clearance of cobicistat component. Consider alternative regimen if CrCl <70 mL/min. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PREZCOBIX PED (PREZCOBIX PED).
| Breastfeeding | Breastfeeding is not recommended for HIV-infected mothers to avoid HIV transmission. Darunavir is excreted in human milk at low concentrations; cobicistat is likely excreted. M/P ratio not established. |
| Teratogenic Risk | PREZCOBIX PED (darunavir/cobicistat) is contraindicated in pregnancy due to the risk of preterm delivery, low birth weight, and potential for neural tube defects based on animal studies. First trimester exposure associated with increased risk of congenital anomalies; second and third trimester exposure linked to fetal growth restriction and metabolic disturbances. |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to darunavir, cobicistat, or any component of the formulation","Co-administration with drugs highly dependent on CYP3A for clearance (e.g., alfuzosin, amiodarone, colchicine in renal/hepatic impairment, ergot derivatives, lomitapide, lovastatin, oral midazolam, sildenafil for pulmonary arterial hypertension, simvastatin, triazolam)","Co-administration with St. John's Wort","Severe hepatic impairment (Child-Pugh Class C)"]
| Precautions | ["Hepatotoxicity: monitor hepatic function; discontinue if signs of hepatitis or elevated transaminases with rash or systemic symptoms occur","Severe skin reactions: including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS); discontinue if severe rash develops","Sulfonamide allergy: darunavir contains a sulfonamide moiety; use with caution in patients with known sulfonamide allergy","Drug interactions: cobicistat is a CYP3A inhibitor; contraindicated with drugs highly dependent on CYP3A for clearance","Diabetes mellitus: new onset or exacerbation may occur","Hemophilia: increased bleeding risk in patients with hemophilia A or B","Fat redistribution and immune reconstitution syndrome"] |
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| Fetal Monitoring | Monitor maternal HIV viral load and CD4 count monthly. Perform fetal ultrasound for growth and anatomy at 18-20 weeks and again at 32-36 weeks. Assess for preterm labor. Monitor neonatal HIV status. |
| Fertility Effects | No evidence of impaired fertility in animal studies. In humans, darunavir/cobicistat does not appear to affect spermatogenesis or oogenesis. However, effective HIV suppression improves reproductive health. |