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. |
| Molecular Weight | Darumavir: 547.7 Da; Cobicistat: 776.0 Da |
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 | Insufficient human data; animal studies show no teratogenicity at clinically relevant doses; use only if benefit outweighs risk. |
| 2nd trimester | Limited human data; no evidence of fetal harm in small studies; avoid unless necessary. |
| 3rd trimester | No specific adverse fetal outcomes reported; monitor for neonatal hyperbilirubinemia if used near term. |
Clinical note
Comprehensive clinical and safety monograph for PREZCOBIX PED (PREZCOBIX PED).
| Placental transfer | Darumavir crosses placenta with cord blood concentrations approximately 50% of maternal levels; cobicistat minimal transfer. |
| Breastfeeding | Darumavir and cobicistat are excreted in human milk at low levels; potential for HIV transmission and adverse effects in infant; generally not recommended. |
■ FDA Black Box Warning
None
| Serious Effects |
Severe hepatic impairment (Child-Pugh Class C)Coadministration with drugs highly dependent on CYP3A4 clearance (e.g., alfuzosin, sildenafil for PAH, triazolam, midazolam oral)
| 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 |
| Food/Dietary | Administer with food to enhance absorption. No specific dietary restrictions, but avoid grapefruit juice as it may alter drug levels. Do not take with St. John's wort (herbal supplement). Avoid alcohol in patients with liver disease. |
Loading safety data…
| Lactation Rating |
| L5 |
| 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. |
| 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. |
| Clinical Pearls | Prezcobix PED is a fixed-dose combination of darunavir (protease inhibitor) and cobicistat (pharmacokinetic enhancer) for pediatric patients. Do not use in patients with severe hepatic impairment (Child-Pugh Class C). Monitor for hepatotoxicity, especially in patients with HBV/HCV coinfection. Renal impairment: cobicistat decreases creatinine secretion, leading to increased serum creatinine without affecting GFR; no dose adjustment needed but monitor renal function. Contraindicated with drugs that are strong CYP3A inducers (e.g., rifampin, St. John's wort) or substrates with narrow therapeutic index (e.g., alfuzosin, ergot derivatives). Administer with food to enhance absorption. |
| Patient Advice | Take exactly as prescribed; do not skip doses to reduce risk of resistance. · Must be taken with food to ensure adequate absorption. · Inform your doctor of all medications, including over-the-counter drugs and herbal supplements, due to potential interactions. · This medicine does not cure HIV; it reduces viral load and can still transmit HIV to others. Use condoms and avoid sharing needles. · Report any signs of liver problems: yellowing of skin/eyes, dark urine, right upper quadrant pain, or unusual fatigue. · Do not use with St. John's wort, rifampin, or certain other drugs; ensure your doctor knows your full medication list. · If you have hemophilia, note that protease inhibitors may increase bleeding risk. · Store at room temperature, away from moisture and heat. |