Gilead Sciences, Inc's Complera

Gilead Sciences, Inc's Complera received approval from the FDA for use as a complete regimen for the treatment of HIV-1 infection in treatment-naïve adults.

Gilead Sciences, Inc’s Complera (emtricitabine 200 mg/ rilpivirine 25 mg/ tenofovir disoproxil fumarate [DF] 300 mg) has received approval from the FDA for use as a complete regimen for the treatment of HIV-1 infection in treatment naïve adult patients.¹ The drug carries a boxed warning (see Contraindications, Warnings, and Precautions). Complera is the second complete single-tablet, oncea- day HIV-1 medication regimen for treatment-naïve adults available on the US market.²

PHARMACOLOGY AND PHARMACOKINETICS

Emtricitabine and tenofovir DF are nucleoside analogue HIV-1 reverse transcriptase inhibitors. Rilpivirine is a nonnucleoside reverse transcriptase inhibitor (NNRTI).

Race did not affect the pharmacokinetics of emtricitabine or rilpivirine. Data are insufficient to determine impact of race on the pharmacokinetics of tenofovir DF. Gender does not affect the pharmacokinetics of any component of Complera. The pharmacokinetics of patients older than 65 years has not been evaluated.¹

DOSING AND ADMINISTRATION

The following should be considered prior to beginning therapy with Complera:

• More rilpivirine-treated patients whose HIV-1 RNA was greater than 100,000 copies/mL at the start of treatment experienced virologic failure compared with patients whose HIV-1 RNA was less than 100,000 copies/mL at the start of treatment.

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

• More patients who were treated with rilpivirine developed lamivudine-/ emtricitabine-associated resistance compared with efavirenz.

• Complera should not be used in patients younger than 18 years. Complera is dosed as 1 tablet once a day and should be taken with a meal. It should not be used in patients with a creatinine clearance less than 50 mL/min.¹

CLINICAL TRIALS

Complera was evaluated in two 48-week, double-blind, active-controlled, randomized trials (ECHO and THRIVE) to determine the safety and efficacy of rilpivirine compared with efavirenz in patients with HIV-1 who had not previously tried any antiretroviral regimens.

Both arms of each trial also received a background regimen: the patients in the ECHO trial used emtricitabine/tenofovir DF, whereas the patients in THRIVE used either emtricitabine/tenofovir DF, lamivudine/zidovudine, or abacavir/ lamivudine.^1,2 Pooled data from both ECHO and THRIVE showed noninferiority of rilpivirine to efavirenz (83% of patients using rilpivirine achieved viral load <50 copies per mL versus 81% of the efavirenz group).^1,3,4 Additionally, patients using rilpivirine experienced fewer adverse effects than patients using efavirenz.^3,4

CONTRAINDICATIONS, WARNINGS, AND PRECAUTIONS

Complera carries a boxed warning regarding reports of lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, during use of tenofovir DF, which is a component of Complera. The warning also stipulates that Complera is not approved for treatment of chronic hepatitis B virus (HBV) infection. Severe acute exacerbations of HBV have been reported in patients with both HIV-1 and HBV who have discontinued emtricitabine or tenofovir DF. Hepatic function should be closely monitored in these patients, and if appropriate, anti-hepatitis B treatment may be warranted.

Complera is contraindicated when coadministered with drugs where significant decreases in rilpivirine plasma concentrations may occur, which could lead to a loss of virologic response and possible resistance and cross-resistance.

New-onset or worsening renal impairment, depressive disorders, and immune reconstitution syndrome have been reported during treatment with Complera; appropriate monitoring for each is recommended. Use caution when prescribing Complera with drugs that may reduce the exposure of rilpivirine or with drugs with a risk of Torsade de Pointes. Bone mineral density monitoring may be required during treatment with Complera. Complera should not be used in conjunction with lamivudine or other medications that contain any components of Complera, including Atripla, Edurant, Emtriva, Truvada, and Viread. Do not administer concurrently with Hepsera (adefovir). Redistribution or accumulation of body fat has been reported during treatment with antiretrovirals. Complera is Pregnancy Category B. It should not be used during breast-feeding due to the potential for HIV transmission.

Complera is a complete regimen for HIV-1 and should not be coadministered with any other antiretroviral agents. Inducers or inhibitors of cytochrome P450 3A4 may affect plasma concentrations of rilpivirine. Medications that increase gastric pH may decrease plasma concentrations of rilpivirine.

Rilpivirine’s most common adverse reactions (incidence ≥2%) are insomnia and headache. Emtricitabine and tenofovir DF’s most common side effects (incidence ≥10%) are diarrhea, nausea, fatigue, headache, dizziness, depression, insomnia, abnormal dreams, and rash.¹

SPT

References:

1. Complera complete prescribing information. www.complera.com/Content/pdf/Complera_prescribing_information.pdf. Accessed February 2012.

2. U.S. Food and Drug Administration approves Gilead Sciences’ Complera, a new complete once-daily, single-tablet regimen for HIV-1 infection in treatment-naïve adults. www.gilead.com/pr_1595280. Accessed February 2012.

3. Molina J-M, Cahn P, Grinsztejn B, et al. Rilpivirine versus efavirenz with tenofovir and emtricitabine in treatment-naive adults infected with HIV-1 (ECHO): a phase 3 randomised double-blind active-controlled trial. Lancet. 2011;378(9787):238-246.

4. Cohen CJ, Andrade-Villanueva J, Clotet B, et al; THRIVE study group. Rilpivirine versus efavirenz with two background nucleoside or nucleotide reverse transcriptase inhibitors in treatment-naive adults infected with HIV-1 (THRIVE): a phase 3, randomised, non-inferiority trial. Lancet. 2011;378(9787):229-237.