Emtricitabine/tenofovir/efavirenz

Emtricitabine/tenofovir/efavirenz
Combination of
emtricitabine nucleoside reverse transcriptase inhibitor
tenofovir disoproxil fumarate nucleotide analogue reverse transcriptase inhibitor
efavirenz non-nucleoside reverse transcriptase inhibitor
Clinical data
  • US: D (Evidence of risk)
Oral
Identifiers
731772-50-2 Yes
J05AR06
NIAID ChemDB 026223
 Yes (what is this?)  (verify)

Emtricitabine/tenofovir/efavirenz (INNs, trade names Atripla, Viraday) is a fixed-dose combination drug for the treatment of HIV infection. It combines Gilead Sciences's tenofovir and emtricitabine (already available in the anti-HIV combination Truvada) with Merck & Co's efavirenz into a fixed-dose pill. Combining the three drugs into a single, once-daily pill reduces pill burden and simplifies dosing schedules, and therefore has the potential to increase adherence to antiretroviral therapy.

Atripla is the first multi-class antiretroviral drug available in the United States and represents the first collaboration between two U.S. pharmaceutical companies to combine their patented anti-HIV drugs into one product.[1] The drug retails in the United States for US$1,850 for a one-month supply. An equivalent two pill regimen is available in developing countries at a price of about US$1.00 per day, as Gilead Sciences has licensed the patents covering emtricitabine/tenofovir to the Medicines Patent Pool[2] and Merck and Co makes efavirenz available in developing countries at a reduced price.[3] It was approved by the U.S. FDA on July 12, 2006. In the UK, the drug cost to the NHS is £626.90 per month[4] as of March 2012.

Atripla is a fixed dose combination of 600 mg efavirenz, 300 mg tenofovir, and 200 mg emtricitabine. In adults, it is taken once daily on an empty stomach. Dosing at bedtime is recommended to improve tolerability of nervous system symptoms. Atripla is not recommended for patients under 18 years of age.

Atripla is a pink, film-coated tablet with "123" impressed on one side.

In North America and Europe, Atripla is marketed jointly by Gilead Sciences and Bristol-Myers Squibb, but in much of the developing world, marketing and distribution is handled by Merck & Co.[5] Cipla released its own version of Atripla in India, called Viraday. In Argentina, Atripla is marketed by Laboratorios Gador.

In South Africa, the National Minister of Health, Doctor Aaron Motsoaledi, administered to the first state patient a fixed dose combination (FDC) tablet of Emtricitabine/Tenofovir/Efavirenz on 9 April 2013 in GaRankuwa.

Background

Atripla was approved as a once daily tablet to treat HIV in 2006. The main advantage of the new drug Atripla was that it could be taken once daily and reduces the overall stress in an antiretroviral regimen.[6] There is currently no generic version of Atripla available in the United States. An equivalent two pill regimen is available in developing countries at a price of about US$1.00 per day, as Gilead Sciences has licensed the patents covering emtricitabine/tenofovir to the Medicines Patent Pool[7] and Merck and Co makes efavirenz available in developing countries at a reduced price.[8]

Dosage

Recommended dosage for Atripla is 1 tablet at or before bedtime. Side effects can be reduced if Atripla is taken on an empty stomach. For patients with renal or hepatic insufficiency, patient can take 1 tablet by mouth once a day. However, patients whose CrCl levels are less than 50ml/min should not follow this dosage. Instead, patients should be prescribed drug components of the fixed-dose combinations while adjusting TDF and FTC doses according to the patient’s CrCl levels.[9]

Mechanism of action

Efavirenz is a non-nucleoside reverse transcriptase inhibitor (NNRTI) of HIV-1. Emtricitabine is a nucleoside reverse transcriptase inhibitor (NRTI) of HIV-1.Tenofovir is a nucleotide reverse transcriptase inhibitor of HIV-1, and it can be classified as an NtRTI. These three drugs work in combination to target the HIV reverse transcriptase protein in three ways, which reduces the virus’s capacity to mutate.[10]

In combination studies there were synergistic antiviral effects observed between emtricitabine and efavirenz, efavirenz and tenofovir, and emtricitabine and tenofovir.[10]

Side effects

Common side effects of Atripla are tiredness, dizziness, gastrointestinal distress, and skin discoloration. More severe side effects are hallucinations, sleeplessness and depression.[11]

Interactions

Medications that should not be taken with Atripla are Vascor (bepridil), Versed (midazolam), Orap (pimozide), Halcion (triazolam), or ergot derivatives (for example, Wigraine and Cafergot)." Discuss any other HIV or hepatitis medications you are taking with your doctor to avoid complications. Additionally, St. John's wort is known to reduce the effectiveness of Atripla, resulting in increased viral load and possible resistance to Atripla.[12]

Contraindications

Patients who have shown strong hypersensitivity to efavirenz, a constituent of Atripla, should not take Atripla. Drugs that are contraindicated in the intake of Atripla are: voriconazole, ergot derivative drugs, benzodiazepines midazolam and triazolam, calcium channel blocker bepridil, cisapride, pimozide and St. John’s wort (Hypericum perforatum). Breastfeeding is also contraindicated.[10]

References

External links