New FDA Actions: Gilead Sciences, Inc's Truvada

Truvada (emtricitabine/tenofovir disoproxil fumarate) was approved for prophylaxis to reduce the risk of HIV-1 infection in adults.

The FDA approved Gilead Sciences, Inc’s Truvada (emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) in combination with safer sex practices for pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 in adults at high risk.

High-risk patients include those with a partner known to be infected with HIV-1 or those who engage in sexual activity within an area of high HIV-1 prevalence and have 1 or more of following characteristics: inconsistent or nonexistent condom use, diagnosis of sexually transmitted infections, exchange of sex for commodities (such as money, food, shelter, or drugs), use of illicit drugs or alcohol dependence, incarceration, or partner(s) of unknown HIV-1 status with any of the previous risk factors.¹

In 2004, Truvada was approved for treatment of HIV-1 infection in combination with other antiretroviral agents in patients 12 years and older. It is the first agent to be approved for PrEP.^2,3

Pharmacology and Pharmacokinetics

Emtricitabine and tenofovir are nucleoside analogue HIV-1 reverse transcriptase inhibitors. Race did not affect the pharmacokinetics of emtricitabine. Data are insufficient to determine impact of race on the pharmacokinetics of tenofovir disoproxil fumarate. Gender does not affect the pharmacokinetics of Truvada. Truvada should not be used in patients younger than 12 years or weighing less than 35 kg. The pharmacokinetics of patients older than 65 years has not been fully evaluated.¹

Dosage and Administration

When given to HIV-1 uninfected adults for the indication of PrEP, Truvada should be dosed as 1 tablet orally each day taken with or without food. Truvada should not be used in uninfected HIV-1 patients with a creatinine clearance (CrCl) below 60 mL/min. If CrCl decreases during treatment, potential causes should be evaluated and the risks and benefits of continued use should be reassessed.¹

Clinical Trials

The safety and efficacy of Truvada for PrEP was evaluated in 2 randomized, double-blind, placebo-controlled trials. The iPrEx trial evaluated Truvada in 2499 HIVnegative men or transgender women who had sex with men and evidence of other high-risk behavior. Compared with placebo, the study found that Truvada reduced the risk of HIV infection by 42% and that efficacy was strongly correlated to medication adherence.

The Partners PrEP trial evaluated 4758 heterosexual couples where one partner was HIV infected and the other was not. The study found Truvada reduced the risk of infection by 75% compared with placebo.³

Contraindications, Warnings, and Precautions

Truvada carries the following boxed warning:

• Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported during treatment with nucleoside analogues, including tenofovir.
• Truvada is not approved for the 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 Truvada. Hepatic function should be closely monitored in these patients, and in some cases, anti—hepatitis B treatment may be necessary.
• When used for PrEP, Truvada must be prescribed only to patients who are confirmed to be HIV-negative immediately prior to initiation of treatment and periodically throughout its use. If signs or symptoms of HIV-1 infection are present, treatment with Truvada should not be initiated until negative infection status is obtained.

The use of Truvada for PrEP is contraindicated in patients with an unknown or positive HIV-1 status. When used in HIV-infected patients, Truvada should only be used in combination with other antiretroviral agents.

New onset or worsening renal failure has been reported. Do not use Truvada with other agents that contain either emtricitabine or tenofovir. Bone mineral density should be monitored. Body fat may accumulate or be redistributed during treatment with Truvada. Immune reconstitution syndrome has been reported. When used for PrEP, Truvada should be used as only part of a comprehensive strategy that includes other prevention methods, such as safer sex practices, as Truvada alone is not always effective in preventing HIV-1 infection. All uninfected patients should be counseled regarding strict adherence to Truvada therapy.

Dr. Holmberg earned her PharmD from the University of Connecticut and completed an ambulatory care residency at the Phoenix VA Healthcare System. Her practice has also included pediatrics and inpatient mental health. She resides in Phoenix, Arizona.

References

• Truvada complete prescribing information. www.gilead.com/pdf/truvada_pi.pdf. Accessed October 2012.
• US Food and Drug Administration approves Gilead’s Truvada for reducing risk of acquiring HIV. www.gilead.com/pr_1715013. Accessed October 2012.
• FDA approves first drug for reducing the risk of sexually acquired HIV infection. www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm312210.htm. Accessed October 2012.