Raltegravir

Indications

Raltegravir is used for: HIV-1 infection

Adult Dose

Oral HIV-1 infection Adult: In combination w/ other antiretroviral agents: As film-coated tab: 400 mg bid.

Child Dose

Oral HIV-1 infection Child: As susp: >4 wk 3-<4 kg: 25 mg bid; 4-<6 kg: 30 mg bid; 6-<8 kg: 40 mg bid; 8-<11 kg: 60 mg bid; 11-<14 kg: 80 mg bid; 14-<20 kg: 100 mg bid. As chewable tab: 11-<14 kg: 75 mg bid; 14-<20 kg: 100 mg bid; 20-<28 kg: 150 mg bid; 28-<40 kg: 200 mg bid; ?40 kg: 300 mg bid. As film-coated tab: >25 kg: Same as adult dose.

Renal Dose

Renal impairment No dosage adjustment required for any degree of renal impairment Dialysis: Unknown if drug is removed by dialysis; avoid dosing before dialysis session

Administration

May be taken with or without food. Granules for susp: Mix the contents of a single-use packet labelled as containing 100 mg in 5 mL of water to provide a soln containing 20 mg/mL.

Contra Indications

Hypersensitivity to raltegravir. Lactation.

Precautions

Patient w/ history of myopathy, rhabdomyolysis, depression, psychiatric illness. Patients taking concomitant rifampicin. Severe hepatic impairment (e.g. chronic hepatitis B or C). Childn. Pregnancy.

Pregnancy-Lactation

Pregnancy Available data from APR show no difference in rate of overall birth defects for raltegravir compared to background rate for major birth defects of 2.7% in U.S. reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP); the rate of miscarriage is not reported in the APR; the MACDP population is not disease-specific, evaluates women and infants from a limited geographic area, and does not include outcomes for births that occurred at <20 weeks gestation In animal reproduction studies in rats and rabbits, no evidence of adverse developmental outcomes observed with oral administration during organogenesis at doses that produced exposures up to approximately 4 times maximal recommended human dose (MRHD) of 1200 mg Lactation The Centers for Disease Control and Prevention recommend that HIV-1 infected mothers in United States not breastfeed infants to avoid risking postnatal transmission of HIV-1 infection No data are available on presence of raltegravir in human milk, effects on breastfed infant, or on milk production; when administered to lactating rats, raltegravir was present in milk Owing to the potential for HIV transmission (in HIV-negative infants), developing viral resistance (in HIV- positive infants), and adverse reactions in a breastfed infant, instruct mothers not to breastfeed if they are receiving therapy

Interactions

Reduced plasma concentration w/ rifampicin, Al- and Mg-containing antacids.

Adverse Effects

Side effects of Raltegravir : >10% (STARMARK trial) Serum alanine aminotransferase, Grade 2-4 (2-11%) Serum aspartate aminotransferase, Grade 2-4 (1-8%) 1-10% (STARTMRK trial) Fasting serum glucose test, Grade 2-4 (7%) Total serum bilirubin, Grade 2-4 (≤5%) Headache (4%) Insomnia (4%) Nausea (3%) ANC, Grade 2-4 (1-3%) Serum alkaline phosphate, Grade 2-4 (≤3%) Dizziness (2%) Fatigue (2%) Creatinine (≤1%) Hemoglobin, Grade 2-4 (≤1%) Platelet count, Grade 2-3 (≤1%) 1-10% (ONCEMRK trial) Lipase, Grade 2-4 (≤2-7%) Creatine kinase, Grade 2-4 (≤2-4%) Serum aspartate aminotransferase, Grade 2-4 (≤5%) Serum alanine aminotransferase, Grade 2-4 (≤4%) Serum alkaline phosphate, Grade 2-4 (≤1%) ANC, Grade 2-4 (≤2%) Platelet count, Grade 2-3 (≤1%) Total serum bilirubin, Grade 2-4 (≤3%) Headache (1%)

Mechanism of Action

Raltegravir is an inhibitor of HIV integrase, an enzyme essential for insertion of viral DNA into the host cell genome, thereby preventing viral gene expression and replication. It is active against HIV-1 and also has some in vitro activity against HIV-2.