Adult: Treatment-naive or treatment-experienced patients w/o duranavir resistance associated mutations (DRV-RAMs): 800 mg once daily, given in combination w/ ritonavir 100 mg or cobicistat 150 mg. Treatment-experienced patients w/ ≥1 DRV-RAMs or if genotype testing is not possible: 600 mg bid, given in combination w/ ritonavir 100 mg. Child: 3-17 yr Treatment-naive or treatment-experienced patients w/o DRV-RAMs (given in combination w/ ritonavir 100 mg): ≥15-<30 kg: 600 mg once daily; ≥30-<40 kg: 675 mg once daily; ≥40 kg: 800 mg once daily. Treatment-experienced patients (given in combination w/ ritonavir 50 mg): ≥15-<30 kg: 375 mg bid; ≥30-<40 kg: 450 mg bid; ≥40 kg: 600 mg bid.
Special Patient Group
Pregnant patients: 600 mg bid, given in combination w/ ritonavir 100 mg.
Severe (Child-Pugh Class C): Contraindicated.
Should be taken with food.
Hypersensitivity to darunavir. Severe hepatic (Child-Pugh Class C) impairment. Lactation. Concomitant use w/ strong CYP3A4 enzyme inducers and narrow therapeutic index (NTI) drugs that are highly dependent on CYP3A4 enzyme for clearance.
Patient w/ advanced HIV infection, immune reconstitution syndrome, sulfonamide allergy, chronic active hepatitis B or C, cirrhosis, haemophilia A and B, DM, history of pancreatitis, elevated triglycerides. Patient on multiple medications. Mild to moderate hepatic impairment. Pregnancy.
Perform LFTs prior to and during therapy. Perform baseline genotypic and phenotypic testing in treatment-experienced patients if possible. Monitor viral load, CD4, transaminase, triglyceride, and cholesterol levels prior to and during therapy.
Enhanced systemic exposure w/ ritonavir and cobicistat. Increased plasma concentration w/ CYP3A4 enzyme inhibitors (e.g. ketoconazole, clotrimazole, indinavir). Potentially Fatal: Strong CYP3A4 enzyme inducers (e.g. rifampicin, lopinavir, carbamazepine, phenobarbital, phenytoin) may reduce plasma concentration of darunavir leading to loss of therapeutic effect and development of resistance. May inhibit elimination and increase exposure of NTI drugs that are highly dependent on CYP3A4 enzyme for clearance (e.g. sildenafil [when used for pulmonary HTN], salmeterol, alfuzosin, amiodarone, bepridil, systemic lidocaine, quinidine, terfenadine, astemizole, sertindole, pimozide, ergot derivatives, cisapride, oral midazolam, triazolam, simvastatin, lovastatin) leading to serious or life-threatening events.
Absorption and bioavailability are increased w/ food. Concomitant use w/ St. John’s wort is not recommended since it may reduce plasma concentration of darunavir leading to loss of therapeutic effect and development of resistance.
Description: Darunavir is a sulfonamide derivative that inhibits HIV-1 replication. It selectively blocks viral protease, inhibiting the cleavage of Gag-Pol polypeptides into infectious viral proteins, thereby forming non-functional, immature, and non-infectious virions. Pharmacokinetics: Absorption: Rapidly absorbed. Bioavailability: 82%. Increased absorption and bioavailability w/ food. Time to peak plasma concentration: W/in 2.5-4 hr. Distribution: Plasma protein binding: Approx 95%, mainly to α1-acid glycoprotein. Metabolism: Metabolised in the liver via oxidation, mainly by CYP3A4 enzyme to at least 3 active metabolites. Excretion: Via faeces (approx 80%, 41.2% as unchanged drug) and urine (approx 14%, 7.7% as unchanged drug). Terminal elimination half-life: Approx 15 hr.
Store at 25°C. Oral susp: Do not refrigerate, freeze, or expose to excessive heat.
J05AE10 - darunavir ; Belongs to the class of protease inhibitors. Used in the systemic treatment of viral infections.
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