Once-Daily Triple HIV Drug Receives FDA Approval

Martha Kerr

August 10, 2011

August 10, 2011 (UPDATED September 11, 2011) — The US Food and Drug Administration (FDA) granted approval of Complera, a once-daily, 3-drug combination for treatment-naive HIV-infected patients.

Complera is a single tablet that contains rilpivirine (Edurant, Janssen Pharmaceuticals), a nonnucleoside reverse transcriptase inhibitor (NNRTI), and tenofovir (Viread, Gilead Sciences) and emtricitabine (Emtriva, Gilead Sciences), both nucleoside reverse transcriptase inhibitors (NRTIs).

Approval of the combination drug was based on previously conducted phase 3 randomized studies (ECHO and THRIVE) of rilpivirine, on which approval of that drug was based. No new studies were conducted for approval of Complera.

A bioequivalence study demonstrated that the triple-drug tablet achieved the same blood levels as each of the drugs administered individually.

The recommended dose of Complera is 1 tablet, containing emtricitabine 200 mg, rilpivirine 25 mg, and tenofovir 300 mg, once daily, to be taken with food.

Cautions, Adverse Reactions

FDA issued the following cautions in announcing the drug's approval:

  • More patients with HIV-1 RNA levels greater than 100,000 copies/mL at the start of therapy experienced virologic failure vs patients with lower HIV-1 RNA levels at the start of therapy with rilpivirine.

  • The virologic failure rate in rilpivirine-treated participants conferred a higher rate of overall treatment resistance and cross-resistance to the NNRTI class compared with efavirenz.

  • More patients treated with rilpivirine went on to have lamivudine/emtricitabine-associated resistance compared with efavirenz.

The most common grade 2 to 4 adverse drug reactions to rilpivirine, occurring in 2% or more of patients, are insomnia and headache. The most common adverse drug reactions to emtricitabine and tenofovir disoproxil fumarate, occurring in 10% or more of patients, are diarrhea, nausea, fatigue, headache, dizziness, depression, insomnia, abnormal dreams, and rash.

Emtricitabine/rilpivirine/tenofovir DF is contraindicated in patients taking the following drugs:

  • the anticonvulsants carbamazepine, oxcarbazepine, phenobarbital, and phenytoin

  • the antimycobacterials rifabutin, rifampin, and rifapentine

  • proton pump inhibitors, such as esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole

  • more than a single dose of systemic dexamethasone

  • St. John's wort (Hypericum perforatum)

These drugs may cause significant decreases in rilpivirine plasma concentrations and may result in a loss of virologic response and possible resistance to rilpivirine or to all NNRTIs.

Additional FDA warnings related to the drug indicate that caution is needed regarding prescribing Complera with drugs with a known risk for torsade de pointes, and that monitoring bone mineral density should be considered in patients with a history of pathologic fracture or other risk factors for osteoporosis or bone loss. Severe depressive disorders have been reported with Complera; if these occur, immediate medical evaluation is recommended for severe depressive disorders.

Use in Special Populations

The following should be considered regarding use of Complera in specific populations:

  • The drug is pregnancy Category B, meaning that it should be used during pregnancy only if the potential benefit justifies the potential risk. Because of the potential for HIV transmission, women infected with HIV should be instructed not to breast-feed.

  • Complera is not recommended for patients younger than 18 years, and clinical studies of the component drugs did not include enough participants 65 years and older to determine whether they respond differently than younger participants.

  • Dose selection for elderly patients should be cautious, considering the higher prevalence of hepatic, renal, or cardiac impairment, and concomitant disease or other drug therapy.

  • Because Complera is a fixed-dose combination, it should not be given to patients requiring dosage adjustment, such as those with moderate, severe, or end-stage renal impairment and creatinine clearance of less than 50 mL per minute.

  • No dosage adjustment of Complera is needed in patients with mild or moderate hepatic impairment, but it has not been studied in patients with severe hepatic impairment.

More information on Complera is available on the FDA Drug Web site.

Laurie Barclay, MD, contributed to the news brief.


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