Classes
DEA Class; Rx
Common Brand Names; Prezcobix
- HIV, ART Combos
Description
Fixed-dose combination product containing a protease inhibitor and a pharmacokinetic enhancer
Used with other antiretrovirals to treat HIV-1 infection in treatment-naive and experienced adults and pediatric patients weighing 40 kg or more without darunavir resistance-associated substitutions
Genotypic testing is recommended prior to initiating treatment
Indications
Indicated in combination with other antiretroviral agents in naïve and treatment-experienced patients without darunavir resistance-associated mutations
Contraindications
Coadministration iwth alfuzosin, dronedarone, ivabradine, ranolazine, naloxegol
CYP inducers (rifampin, St. John’s wort), cisapride, pimozide, lurasidone, ergot derivatives (dihydroergotamine, ergotamine, methylergonovine)
HMG-CoA reductase inhibitors (lomitapide, lovastatin, simvastatin)
PDE5 inhibitors (long-term administration [eg, sildenafil as Revatio for PAH]), triazolam, midazolam, anticonvulsants (carbamazepine, phenobarbital, phenytoin)
Hepatitis C direct-acting antiviral (elbasvir/grazoprevir)
Colchicine (in patients with renal/and or hepatic impairment)
CYP3A4 substrates with narrow therapeutic index
Adverse Effects
- Increased total cholesterol (10-25%)
- Total bilirubin, >2.5 x ULN (65%)
- Ocular icterus, all grades (15%)
- Jaundice, all grades (13%)
- Nausea, all grades (12%)
- Increased triglycerides (3-10%)
- Diarrhea (9%)
- Headache (7%)
- Rash (6%)
- Abdominal pain (6%)
- Nausea (4%)
- Vomiting (2%)
- Anorexia (2%)
Warnings
Hepatotoxicity reported; monitor liver enzymes at baseline and during treatment; consider interrupting or discontinuing treatment with evidence of new or worsening liver dysfunction (including clinically significant elevation of liver enzymes and/or symptoms [eg, fatigue, anorexia, nausea, jaundice, dark urine, liver tenderness, hepatomegaly])
Severe skin reactions accompanied by fever and/or elevations of transaminases; Stevens-Johnson syndrome rarely; mild-to-moderate rash reported to occur within first 4 weeks of treatment and resolved with continued dosing
Assess eCrCl before initiating therapy; cobicistat decreases estimated creatinine clearance without affecting actual renal glomerular function by inhibiting tubular secretion of creatinine
Sulfa allergy: Darunavir contains a sulfa moiety; monitor patients with a known sulfonamide allergy
New-onset diabetes mellitus, exacerbation of pre-existing diabetes mellitus, and hyperglycemia reported during postmarketing surveillance in HIV-infected patients receiving protease inhibitors
Redistribution/accumulation of body fat, including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and cushingoid appearance have been observed in patients receiving ARTs
Increased bleeding, including spontaneous skin hematomas and hemarthrosis, reported in patients with hemophilia type A and B treated with HIV protease inhibitors
Not recommended for use in pregnant women because of substantially lower exposures of darunavir and cobicistat during pregnancy
Pregnancy and Lactation
Not recommended for use in pregnant women because of substantially lower exposures of darunavir and cobicistat during pregnancy
There are no data on presence of darunavir or cobicistat in human milk, effects on breastfed infant, or on milk production
Maximum Dosage
800 mg/150 mg PO daily.
800 mg/150 mg PO daily.
weighing 40 kg or more: 800 mg/150 mg PO daily.
weighing less than 40 kg: Safety and efficacy have not been established.
weighing 40 kg or more: 800 mg/150 mg PO daily.
weighing less than 40 kg: Safety and efficacy have not been established.
Safety and efficacy have not been established.
Safety and efficacy have not been established.
How supplied
Darunavir/cobicistat
tablet
- 800mg/150mg
