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Approval of new fixed dose combination, Stribild (elvitegravir, cobicistat, emtricitabine, tenofovir disoproxil fumarate)
On August 27, 2012, FDA approved Stribild (elvitegravir, cobicistat, emtricitabine, tenofovir disoproxil fumarate), a new once-a-day fixed-dose combination pill to treat HIV-1 infection in adults who have never been treated for HIV infection (antiretroviral treatment-naïve).
In addition to the combination of emtricitabine and tenofovir disoproxil fumarate, approved in 2004 and marketed as Truvada, which blocks the action HIV-1 reverse transcriptase, an enzyme that HIV needs to replicate in the body, Stribild contains two new drugs:
- Elvitegravir is an HIV integrase strand transfer inhibitor, a drug that interferes with one of the enzymes that HIV needs to multiply.
- Cobicistat, a pharmacokinetic enhancer, inhibits an enzyme that metabolizes certain HIV drugs and is used to prolong the effect of elvitegravir.
Together, these drugs provide a complete treatment regimen for HIV infection. The recommended dose is one tablet taken once daily with food.
The safety and effectiveness of Stribild was evaluated in 1,408 adult patients who were not previously treated for HIV in two double-blind clinical trials. Patients were randomly assigned to receive Stribild or Atripla, an HIV drug that contains Truvada (emtricitabine and tenofovir disoproxil fumarate) and efavirenz, once daily in the first trial; and Stribild or Truvada plus atazanavir and ritonavir once daily in the second trial.
The studies were designed to measure the percentage of patients who had an undetectable amount of HIV in their blood at 48 weeks. Results showed between 88 percent and 90 percent of patients treated with Stribild had an undetectable amount of HIV in their blood, compared with 84 percent treated with Atripla and 87 percent treated with Truvada plus atazanavir and ritonavir.
Like labels of many other drugs used to treat HIV, Stribild’s label carries a Boxed Warning alerting patients and health care professionals that the drug can cause a build up of lactic acid in the blood and severe liver problems, both of which can be fatal. The Boxed Warning also states that Stribild is not approved to treat chronic hepatitis B virus infection.
Common side effects observed in clinical trials include nausea and diarrhea. Serious side effects include new or worsening kidney problems, decreased bone mineral density, fat redistribution and changes in the immune system (immune reconstitution syndrome). Stribild’s label gives advice to health care providers on how to monitor patients for kidney or bone side effects.
Dosing in renal impairment: STRIBILD should not be initiated in patients with estimated creatinine clearance below 70 mL per minute. Discontinue in patients with estimated creatinine clearance below 50 mL per minute.
Stribild is contraindicated with drugs that:
- are highly dependaent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening adverse events. (4)
- strongly induce CYP3A which may lead to lower exposure of one or more components and loss of efficacy of STRIBILD which may result in loss of virologic response and possible resistance.
Labeled WARNINGS AND PRECAUTIONS include:
- New onset or worsening renal impairment: Can include acute renal failure and Fanconi syndrome. Assess creatinine clearance (CLcr), urine glucose and urine protein before initiating treatment with STRIBILD. Monitor CLcr, urine glucose, and urine protein in all patients. Monitor serum phosphorus in patients at risk for renal impairment. Avoid administering STRIBILD with concurrent or recent use of nephrotoxic drugs.
- Coadministration with other products: Do not use with drugs containing emtricitabine or tenofovir disoproxil fumarate including ATRIPLA, COMPLERA, EMTRIVA, TRUVADA, or VIREAD; with drugs containing lamivudine; or with drugs or regimens containing ritonavir. Do not administer in combination with HEPSERA.
- Decreases in bone mineral density (BMD): Consider monitoring BMD in patients with a history of pathologic fracture or other risk factors of osteoporosis or bone loss.
- Redistribution/accumulation of body fat: Observed in patients receiving antiretroviral therapy.
- Immune reconstitution syndrome: May necessitate further evaluation and treatment. /li>
Gilead Sciences, Stribild’s manufacturer, is required to conduct additional studies to help further characterize the drug’s safety in women and children, how resistance develops to Stribild, and the possibility of interactions between Stribild and other drugs.
The complete Stribild label may be viewed at Drugs@FDA
Gilead Sciences is based in Foster City, Calif.
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Food and Drug Administration
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Food and Drug Administration