PREZISTA

What it is

Darunavir is an HIV protease inhibitor medicine supplied as film-coated tablets containing 400 mg, 600 mg or 800 mg of darunavir . Darunavir must always be given with low dose ritonavir as a pharmacokinetic enhancer and in combination with other antiretroviral medicinal products .

Approved indications

— Adults: treatment of human immunodeficiency virus-1 (HIV-1) infection in combination with other antiretroviral agents . — Treatment-experienced paediatric patients aged 6 years and older, weighing at least 20 kg: treatment of human immunodeficiency virus (HIV) infection in combination with other antiretroviral agents .

Dosing overview

The recommended dose for adults is 800 mg once daily with ritonavir 100 mg once daily taken with food . The recommended dose is 600 mg twice daily taken with ritonavir 100 mg twice daily taken with food for certain treatment-experienced patients with at least one darunavir resistance associated mutation, HIV protease inhibitor treatment-experienced patients, or treatment-experienced patients with plasma HIV-1 RNA ≥100,000 copies/ml .

Darunavir with ritonavir should be taken with food, although the type of food does not affect the exposure to darunavir .

Key safety warnings

Drug-induced hepatitis (such as acute hepatitis or cytolytic hepatitis) has been reported with darunavir/ritonavir, occurring in 0.5% of patients receiving combination therapy during the clinical development program . Patients with pre-existing liver dysfunction, including chronic active hepatitis B or C, have an increased risk for liver function abnormalities including severe hepatic adverse events . Appropriate laboratory testing should be conducted prior to initiating therapy and increased AST/ALT monitoring should be considered in patients with underlying chronic hepatitis, cirrhosis, or pre-treatment elevations of transaminases, especially during the first several months of treatment . Severe skin reactions have been reported in 0.4% of patients during clinical development; Stevens-Johnson Syndrome has been rarely reported, and toxic epidermal necrolysis, Drug Rash with Eosinophilia and Systemic Symptoms (DRESS), and acute generalised exanthematous pustulosis have been reported very rarely . Darunavir should be discontinued immediately if signs or symptoms of severe skin reactions develop, which can include severe rash or rash accompanied with fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, hepatitis and/or eosinophilia . Darunavir contains a sulfonamide moiety and should be used with caution in patients with a known sulfonamide allergy . New onset diabetes mellitus, hyperglycaemia, or exacerbation of existing diabetes mellitus has been reported in patients receiving antiretroviral therapy, including HIV protease inhibitors; in some patients the hyperglycaemia was severe and in some cases associated with ketoacidosis .

Contraindications

Hypersensitivity to darunavir or to any of the excipients . Darunavir should not be co-administered with medicinal products that are highly dependent on CYP3A for clearance and for which increased plasma concentrations are associated with serious and/or life-threatening events, including astemizole, apixaban, alfuzosin, sildenafil (when used for treatment of pulmonary arterial hypertension), terfenadine, midazolam (oral), triazolam, cisapride, colchicine (in patients with renal and/or hepatic impairment), dapoxetine, dronedarone, elbasvir/grazoprevir, pimozide, ranolazine, the ergot alkaloids, lomitapide, ivabradine, lovastatin, lurasidone, naloxegol, simvastatin and antiarrhythmic drugs . Products containing potent CYP3A inducers such as rifampicin or St. John's Wort should not be used with darunavir as co-administration may result in reduced plasma concentrations of darunavir, potentially resulting in loss of therapeutic effect and development of resistance .

PBS listing

The 600 mg tablet (as ethanolate) is listed on the PBS with streamlined restriction at an ex-manufacturer price of A$662.53, and the 800 mg tablet (as ethanolate) is listed with streamlined restriction at an ex-manufacturer price of A$385.23 .

Regulatory history

Darunavir 400 mg and 600 mg tablets were first listed on the ARTG on 30 July 2009, the 75 mg tablets on 4 February 2010, and the 800 mg tablets on 8 April 2013 . In November 2017, the PBAC recommended an amendment to the current PBS listing to expand the eligibility criteria for darunavir to include patients with HIV-1 infection who are initiating antiretroviral therapy .