Raltegravir approved in the US for treatment-naive patients: paranoia and anxiety added as side effects

On 8 July 2009, the US FDA granted approval for raltegravir (Isentress), to be used in treatment-naive patients. The recommended dose for raltegravir is 400 mg twice daily, with or without food.

This expanded use in treatment-naive patients is based on 48-week results of a randomised, double-blind trial comparing raltegravir to efavirenz, both with tenofovir+FTC backgroung nucleosides. Viral load was reduced to <50 copies/mL in 87% of the raltegravir group compared to 82% of the efavirenz group (difference 4.7% 95% CI -1.3%, 10.6%).

Other changes were made to the US package insert included new reference to paranoia and anxiety as newly repirted side effects.

DRUG INTERACTIONS Together with a warning about use with UGT (UDP-glucuronosyltransferases) inducers other than rifampin, specifically, Coadministration of raltegravir with drugs that are strong inducers of UGT1A1 may result in reduced plasma concentrations of raltegravir

SIDE EFFECTS Section 6.2: Postmarketing experience: the addition of paranoia and anxiety.

DRUG INTERACTIONS Section 7.1 Effect of raltegravir on the pharmacokinetics of other agents adds information for CYP1A2, CYP2B6 and methadone.

RESISTANCE: Treatment-naive subjects: By Week 48 in the STARTMRK trial, the primary raltegravir resistance-associated substitutions were observed in 3 (1 with Y143R and 2 with Q148H/R) of the 6 virologic failure subjects with evaluable paired genotypic data.

Minor editorial changes were made to the patient package insert for consistency with other antiretrovirals.