300 mg tablet
Approved indication: HIV infection
Australian Medicines Handbook section 5.4.3
Darunavir is a new protease inhibitor that can be used in combination with other antiretroviral drugs to treat patients infected with HIV.1
It works by selectively inhibiting the cleavage of viral polyproteins in infected cells, which prevents the formation of mature virus.
Darunavir is extensively metabolised by CYP3A. Ritonavir inhibits this enzyme and, when co-administered, increases the bioavailability of darunavir 14-fold. After an oral dose of 600 mg darunavir with 100 mg ritonavir, peak plasma concentrations are reached within 2.5–4 hours. The terminal half-life is around 15 hours and most of the drug is excreted in the faeces. This drug should be taken with ritonavir and food to increase its bioavailability.
The efficacy of darunavir (with ritonavir 100 mg) has been compared to other protease inhibitors in a phase II dose-finding trial. The 318 patients who were enrolled had previously been treated with antiretroviral drugs and many of them had HIV that was resistant to commercially available protease inhibitors. Before the patients were allocated to a treatment group, they were prescribed an optimised background regimen of two or more nucleoside analogue reverse transcriptase inhibitors with or without enfuvirtide. Patients were then randomised to receive darunavir or another protease inhibitor (lopinavir, saquinavir, fosamprenavir, atazanavir or indinavir) selected by the investigator. After 24 weeks of treatment, 53% (32) of patients taking 600 mg darunavir (twice daily) had less than 50 viral copies/mL of blood compared to 18% (11) of patients taking another protease inhibitor. Corresponding to this, mean CD4 cell counts increased by 124 cells/microlitre of blood in the darunavir group and 20 cells/microlitre in the comparator group.2
Viral resistance to darunavir has been noted in patients previously treated with other protease inhibitors. This is associated with amino acid substitutions in the viral proteases. HIV strains that are resistant to darunavir may also have decreased susceptibility to other protease inhibitors.
Headache and gastrointestinal symptoms are the most common adverse events associated with darunavir. Skin rashes have also been reported.
Darunavir interacts with many drugs as it is metabolised by CYP3A. It must not be prescribed with drugs that rely on this enzyme for their clearance such as ergot derivatives and midazolam and triazolam. Darunavir can also interact with complementary medicines such as St John's wort. Other antiretroviral drugs (lopinavir/ritonavir and saquinavir) also affect the bioavailability of darunavir.
Darunavir is indicated in combination with other antiretroviral drugs for the treatment of HIV in heavily pre-treated adults who already have resistance to multiple protease inhibitors. So far, it has only been tested in a limited number of patients. The effectiveness of this drug depends on the treatment history of the individual patient and the genotype of their HIV strain.
The Transparency Score ( ) is explained in New drugs: transparency', Vol 37 No 1, Aust Prescr 2014;37:27.
- Post JP, Kelly MD. New developments in antiretroviral therapy for HIV infection. Aust Prescr 2005;28:146-9.
- Katlama C, Esposito R, Gatell JM, Goffard JC, Grinsztejn B, Pozniak A, et al. Efficacy and safety of TMC114/ritonavir in treatment-experienced HIV patients: 24-week results of POWER 1. AIDS 2007;21:395-402.