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.

The revised label will be available on the FDA web site:

or through the National Library of Medicine’s DailyMed site:

Source: FDA listserve (09 July 2009)

Links to other websites are current at date of posting but not maintained.