Antiretroviral (HIV-1 integrase strand transfer inhibitor)
Raltegravir (as potassium) 400 mg; tabs.
HIV-1 infection, in combination with other antiretrovirals, in treatment-experienced adults with evidence of viral replication and HIV-1 strains resistant to multiple antiretrovirals.
Raltegravir works by inhibiting the activity of HIV-1 integrase, an enzyme needed for viral replication. Inhibiting this enzyme prevents the integration of linear HIV-1 DNA into the host-cell genome, thus preventing the formation of HIV-1 provirus and preventing the propagation of the virus.
Raltegravir may be taken without regard to food. It is metabolized chiefly by uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) in the liver; a small percentage is excreted unchanged by the kidneys. No dosage adjustment is necessary in patients with renal or hepatic impairment; however, theeffect of severe hepatic impairment on the pharmacokinetics of raltegravir has not been studied.
Analyses of 24-week data from two ongoing, randomized, double-blind, placebo-controlled studies provided evidence for the efficacy of raltegravir. These studies are being conducted in HIV-1-infected, antiretroviral treatment-experienced adults whose infection is resistant to at least one drug in each of the three major classes of antiretroviral agents: non-nucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors, and protease inhibitors. Patients were given either optimized background therapy (OBT) plus raltegravir or OBT plus placebo. Based on the responses of 436 subjects from the pooled studies who had completed 24 weeks of therapy, 75.5% of those given raltegravir had a viral load of <400 copies/mL, compared with 39.3% of those given placebo, and 62.6% of the raltegravir-treated subjects had a viral load of <50 copies/mL, compared with 33.3% of those given placebo. Based on 699 subjects who were randomized and treated (including those without 24-week data), 2.8% were deemed nonresponders in the raltegravir-treated group compared with 32.9% in the placebo group. The mean increase in CD4+ cell counts was higher in the groups given raltegravir compared with those in the control groups (89 cells/µL compared with 35 cells/µL).The safety and efficacy of raltegravir have not been established in treatment-naïve adult patients or pediatric patients.
>16 years: 400 mg twice daily. Avoid dosing before dialysis sessions.
<16 years: not recommended.
Severe hepatic impairment. Monitor for immune reconstitution syndrome (especially during initial therapy), myopathy, rhabdomyolysis. Pregnancy (Cat. C). Nursing mothers: not recommended.
Antagonized by rifampin, possibly other strong UGT1A1 inducers. May be potentiated by UGT1A1 inhibitors.Caution with other drugs that can cause myopathy (e.g., statins).
Nausea, headache, diarrhea, pyrexia; others (see literature).
Register pregnant patients exposed to raltegravir by calling 800.258.4263.
For more information, call800.622.4477 or visit www.Isentress.com