Darunavir


Concise Prescribing Info
Indications/Uses
HIV-1 infection.
Dosage/Direction for Use
Adult : PO Treatment-naive or treatment-experienced patients w/o DRV-RAMs: 800 mg once daily, w/ ritonavir or cobicistat. Treatment-experienced patients w/ ≥1 DRV-RAMs or if genotype testing is not possible: 600 mg bid, w/ ritonavir.
Dosage Details
Oral
HIV-1 infection
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.
Hepatic Impairment
Severe (Child-Pugh Class C): Contraindicated.
Administration
Should be taken with food.
Contraindications
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.
Special Precautions
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.
Adverse Reactions
Significant: Fat redistribution (e.g. Cushingoid appearance, buffalo hump, peripheral and facial wasting, breast enlargement), mild to moderate rash, immune reconstitution syndrome, bleeding, hyperglycaemia, hypertriglyceridaemia, hypercholesterolaemia, pancreatitis, new onset or exacerbation of DM, hypersensitivity reactions (e.g. angioedema, erythema multiforme, toxic epidermal necrolysis, bronchospasm, rarely, drug rash w/ eosinophilia and systemic symptoms (DRESS) and Stevens-Johnson syndrome).
Nervous: Asthenia, dizziness, insomnia, headache, somnolence, vertigo, peripheral neuropathy.
CV: MI, tachycardia, TIA.
GI: Abdominal pain, diarrhoea, nausea, vomiting.
Resp: Nasopharyngitis.
Genitourinary: Polyuria.
Endocrine: Insulin resistance, hyperlactataemia, wt gain.
Haematologic: Anaemia, thrombocytopenia, neutropenia.
Musculoskeletal: Osteonecrosis, osteopenia, osteoporosis, myalgia, myositis.
Dermatologic: Folliculitis.
Others: Fatigue.
Potentially Fatal: Drug-induced hepatitis (e.g. acute hepatitis, cytolytic hepatitis).
MonitoringParameters
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.
Drug Interactions
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.
Food Interaction
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.
Action
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.
Chemical Structure

Click on icon to see table/diagram/image
Storage
Store at 25°C. Oral susp: Do not refrigerate, freeze, or expose to excessive heat.
MIMS Class
ATC Classification
J05AE10 - darunavir ; Belongs to the class of protease inhibitors. Used in the systemic treatment of viral infections.
Disclaimer: This information is independently developed by MIMS based on Darunavir from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
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