darunavir and cobicistat
Regulatory sources consulted
Approved indications
- Combination treatment of HIV-1 in adults and adolescents aged at least 12 years and weighing at least 40 kg without relevant darunavir resistance mutations.
Contraindications
Absolute
- Hypersensitivity to darunavir, cobicistat, or excipients.
- Child-Pugh C hepatic impairment.
- Concomitant carbamazepine, phenobarbital, phenytoin, rifampicin, lopinavir/ritonavir, or St John’s wort.
- Concomitant alfuzosin; contraindicated antiarrhythmics or antianginals such as amiodarone, dronedarone, ivabradine, quinidine, or ranolazine; ergot derivatives; cisapride; lurasidone, pimozide, or quetiapine; elbasvir/grazoprevir; oral midazolam or triazolam; sildenafil for PAH or avanafil; simvastatin, lovastatin, or lomitapide; dabigatran or ticagrelor.
- Colchicine in patients with renal or hepatic impairment.
Clinical warnings
- It may cause severe hepatotoxicity and severe skin reactions including DRESS/SJS/TEN. — CIMA/AEMPS, ficha técnica 114967001
- Major warning · Cobicistat raises creatinine by inhibiting tubular secretion; assess renal function and concomitant nephrotoxicity. — CIMA/AEMPS, ficha técnica 114967001
- Major warning · If genotype is unavailable or HIV-1 RNA <100,000 copies/mL and CD4 ≥100 cells/mm³ criteria are not met in treatment-experienced people, this fixed combination is unsuitable. — CIMA/AEMPS, ficha técnica 114967001
Drug interactions
- ModerateNarrow-therapeutic-index CYP3A substrates and strong inducers
Mechanism: Cobicistat may increase severe toxicity or inducers may cause failure.
Recommendation: Do not combine contraindicated drugs.
CIMA/AEMPS, ficha técnica 114967001
Adverse events
Common (≥1%)
Diarrhea, nausea, rash, and headache
Rare but serious
Liver failure, DRESS, Stevens-Johnson syndrome, and toxic epidermal necrolysis
Pregnancy and lactation
It is not recommended during pregnancy because of insufficient exposure; switch to an alternative regimen. Do not breastfeed during HIV treatment.