The FDA approval of once-daily ISENTRESS HD (raltegravir) is supported by data from the pivotal Phase 3 ONCEMRK trial. At Week 48, 89 percent (N=531) of treatment-naïve HIV-1 infected patients receiving ISENTRESS HD 1200 mg (2 x 600 mg) once a day achieved viral suppression of HIV-1 RNA <40 copies/mL compared to 88 percent (N=266) of patients receiving ISENTRESS 400 mg twice a day, each in combination therapy with emtricitabine + tenofovir disoproxil fumarate, with a treatment difference of 0.5 percent, and a 95 percent confidence interval of -4.2, 5.2. This was consistent across demographic groups at initiation of therapy and a variety of patient populations, including those with high viral load (HIV-1 RNA >100,000 copies/mL).
In ONCEMRK, through 48 weeks, the rate of discontinuation of therapy due to adverse events was low (1 percent in patients receiving ISENTRESS HD 1200 mg once daily and 2 percent in patients receiving ISENTRESS 400 mg twice daily). There were no drug-related clinical adverse reactions of moderate to severe intensity occurring in ≥2 percent of patients in either treatment group. Clinical adverse reactions of all intensities (mild, moderate, and severe) occurring in ≥2 percent of patients on ISENTRESS HD or ISENTRESS included abdominal pain, diarrhea, vomiting, and decreased appetite. Treatment-emergent viral mutations leading to any drug resistance were detected in less than 1 percent (4/531) of those treated with ISENTRESS HD once daily.
ISENTRESS HD can be co-administered with a wide range of antiretroviral agents and non-antiretroviral agents. The potential for drug-drug interactions must be considered prior to and during therapy. The co-administration of ISENTRESS HD with aluminum and/or magnesium-containing antacids, calcium carbonate antacids, rifampin, tipranavir/ritonavir, etravirine, and other strong inducers of drug metabolizing enzymes (e.g., carbamazepine, phenobarbital, and phenytoin) is not recommended.
The most commonly reported (≥2 percent) drug-related clinical adverse reactions of moderate to severe intensity in treatment-naïve adult patients receiving ISENTRESS compared with efavirenz were headache (4 percent vs. 5 percent), insomnia (4 percent vs. 4 percent), nausea (3 percent vs. 4 percent), dizziness (2 percent vs. 6 percent), and fatigue (2 percent vs. 3 percent), respectively. The most commonly reported (≥2 percent) clinical adverse reactions of all intensities (Mild, Moderate, and Severe) in treatment-naïve adult patients receiving ISENTRESS HD compared with ISENTRESS through 48 weeks included abdominal pain, diarrhea, vomiting, and decreased appetite. Intensities were defined as follows: Mild (awareness of sign or symptom, but easily tolerated); Moderate (discomfort enough to cause interference with usual activity); or Severe (incapacitating with inability to work or do usual activity).
ISENTRESS and ISENTRESS HD do not cure HIV-1 infection or AIDS. Severe, potentially life-threatening and fatal skin reactions have been reported. This includes cases of Stevens-Johnson syndrome, hypersensitivity reaction, and toxic epidermal necrolysis. Immediately discontinue treatment with ISENTRESS or ISENTRESS HD and other suspect agents if severe hypersensitivity, severe rash, or rash with systemic symptoms or liver aminotransferase elevations develop and monitor clinical status, including liver aminotransferases closely. For more information, see “Selected Safety Information” below.
Immune reconstitution syndrome can occur, including the occurrence of autoimmune disorders with variable time to onset, which may necessitate further evaluation and treatment.
ISENTRESS chewable tablets contain phenylalanine, a component of aspartame, which may be harmful to patients with phenylketonuria.
Co-administration of ISENTRESS or ISENTRESS HD with drugs that induce uridine diphosphate glucuronosyltransferase (UGT) 1A1 may result in reduced plasma concentrations of raltegravir. Co-administration of ISENTRESS or ISENTRESS HD with drugs that inhibit UGT1A1 may increase plasma levels of raltegravir.
Grade 2–4 creatine kinase laboratory abnormalities were observed in subjects treated with ISENTRESS or ISENTRESS HD. Myopathy and rhabdomyolysis have been reported with ISENTRESS. Use with caution in patients at increased risk of myopathy or rhabdomyolysis, such as patients receiving concomitant medications known to cause these conditions and patients with a history of rhabdomyolysis, myopathy, or increased serum creatine kinase.
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ISENTRESS or ISENTRESS HD during pregnancy. Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263.
Women infected with HIV-1 should be instructed not to breastfeed if they are receiving ISENTRESS or ISENTRESS HD due to the potential for HIV transmission.
The price of ISENTRESS HD will be the same as ISENTRESS twice daily. Merck anticipates ISENTRESS HD to be available in pharmacies in approximately four weeks.
Read the full press release here.
Read the full drug label here.
Access the FDA drug database entry for ISENTRESS HD here.