[Pharmacokinetics and interactions of raltegravir]

Raltegravir is the first integrase inhibitor approved for the treatment of HIV-1 infection in pretreated adults with evidence of viral replication despite receiving antiretroviral therapy. Raltegravir is administered orally at a dose of 400 mg every 12 hours, with or without food. This drug is mainly eliminated through UGT1A1-mediated glucuronidation and is not an inhibitor or inducer of the main liver cytochrome P450 isoenzymes; consequently there is virtually no risk of pharmacological interactions with most commonly used drugs such as methadone, azole antifungal agents or drugs used to treat erectile dysfunction. Studies of interaction with other antiretroviral agents show that raltegravir can be used in combination with tenofovir, efavirenz, atazanavir, ritonavir or tipranavir/ritonavir without the need for dose adjustments. When combined with rifampicin, the dose of raltegravir should be increased to 800 mg/12 h. Proton pump inhibitors increase plasma levels of raltegravir (a 3-fold increase in exposure or AUC levels), and consequently their combined use should be avoided as far as posible. Raltegravir is well tolerated and does not require dose adjustments in patients with severe renal impairment or mild-to-moderate liver impairment. There are no studies in patients with severe liver impairment.