Side-effects

A caution has been issued by the European Medicines Agency and the US FDA regarding hepatic issues concerning darunavir. About 0.5% of patients taking darunavir/ritonavir during its clinical development were diagnosed with drug-induced hepatitis. Patients with pre-existing liver problems, including hepatitis B or hepatitis C infection, had a greater risk of developing such a complication. No adjustment in the dose of DRV/r is recommended for patients with mild or moderate liver problems, but the US product label now notes that the drug is not recommended for patients with severe liver problems.

Liver function should be monitored in all patients before treatment with darunavir/ritonavir is started, and monitoring of ALT/AST levels should be increased in patients with pre-existing liver problems during the first few months of therapy with the drug. If a patients experiences a worsening of their liver function, or if they develop symptoms suggestive of drug-induced hepatitis (tiredness, weight loss, nausea, yellowing of the skin, dark urine, pain in the liver, or an enlarged liver) doctors are recommended to consider either interrupting or stopping treatment with the DRV/r.

In the POWER studies, side-effects were mild to moderate, and were similar across all doses of darunavir. The commonest side-effects were diarrhoea, nausea, and headache, but these were less common in the darunavir arms than in patients taking the comparator protease inhibitor.^[1][2] Around 7% of patients also experienced skin rash, which was serious in a few cases.