P&T Portfolio: Emtriva

September 15, 2003

New AIDS drug featured - Emtriva

 

HEALTH-SYSTEM EDITION

P & T PORTFOLIO

Generic name

Emtricitabine

Proprietary name/manufacturer

Emtriva/Gilead

FDA-approved indication

Emtricitabine is approved for use in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults.

Pharmacology

Emtricitabine is a synthetic nucleoside analog with activity against HIV-1 reverse transcriptase. It requires intracellular conversion to the 5'-triphosphate, which then inhibits the activity of the HIV-1 reverse transcriptase by competing with the natural substrate deoxycytidine 5'-triphosphate and by being incorporated into nascent viral DNA that results in chain termination. Emtricitabine differs only slightly in structure from lamivudine.

Efficacy

A limited number of controlled clinical trials have shown that emtricitabine given once daily in combination with other antiretroviral agents is effective in the treatment of HIV-1 infection in adults. Efficacy in these trials was based on analysis of plasma HIV-1 RNA levels and CD4 cell counts in both antiretroviral-naive and antiretroviral treatment-experienced patients who were virologically suppressed on an HIV treatment regimen. Emtricitabine once daily appears to be more effective than stavudine twice daily and similar in efficacy to lamivudine twice daily when each is given in combination with other antiretroviral agents for the treatment of HIV-1 infection. Emtricitabine resistance in HIV-infected patients and cross-resistance to lamivudine and zalcitabine have been reported.

Pharmacokinetics

Absolute bioavailability3%
Protein binding4%
MetabolismOxidation and conjugation in liver. CYP450 enzymes are not inhibited.
ExcretionUrine (86%) Feces (14%)
Half-life10 hours

 

Contraindications

• Hypersensitivity to any product component

Warnings

• Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analog alone or in combination, including emtricitabine and other antivirals.

• Exacerbations of hepatitis B have been reported in patients after the discontinuation of emtricitabine.

Precautions

• Dose reduction is required in patients with impaired renal function.

Adverse effects

The most common adverse effects of emtricitabine, occurring in 2% to 30% of patients, were rash (17%-30%), dizziness (4%-25%), diarrhea (23%), headache (13%-22%), rhinitis (12%-18%), nausea (13%-18%), insomnia (7%-16%), asthenia (12%-16%), increased cough (14%), abdominal pain (8%-14%), abnormal dreams (2%-11%), vomiting (9%), depressive disorders (6%-9%), dyspepsia (4%-8%), paresthesia (5%-6%), myalgia (4%-6%), arthralgia (3%-5%), and peripheral neuropathy (4%).

Conclusion/comments

Emtricitabine is a once-daily nucleoside reverse transcriptase inhibitor (NRTI) that has shown efficacy for the treatment of HIV-1 infection in adults when used in combination with other antiretroviral agents. It appears to be similar in effectiveness to lamivudine twice daily and more effective than stavudine twice daily when each is given in combination with other antiretroviral agents. However, clinical comparisons with additional NRTIs are not available. Emtricitabine has a long half-life, which allows once-daily dosing, and it has a low potential for CYP450-mediated drug interactions. The manufacturer of emtricitabine is developing a fixed-dose coformulation of tenofovir plus emtricitabine and is also designing a study to examine the efficacy of a regimen of emtricitabine, tenofovir, and efavirenz compared with a regimen of zidovudine/lamivudine, and efavirenz.

 

Published September 2003. Content based on medical literature and product information available at that time.

 

 

P&T Portfolio: Emtriva. Drug Topics Sep. 15, 2003;147:HSE12.