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
Pregnancy cat.	D (US)
Legal status	POM (UK) ℞-only (US)
Routes	Oral
Identifiers
CAS number	731772-50-2 Y
ATC code	J05AR06
NIAID ChemDB	026223
Y (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 Bristol-Myers Squibb'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. The drug retails in the United States for US$1,850 for a one-month supply. As of 2007, annual cost in India is US$1,344, and US$528 in Africa. It was approved by the U.S. FDA on July 12, 2006. In the UK, the drug cost to the NHS is GB£626.90 per month 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. 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 could be taken once daily and reduces the overall stress in an antiretroviral regimen. There is currently no generic version of Atripla available in the United States, but countries like Brazil and India are involved with compulsory licensing. The main advantage for these countries in producing a generic Atripla (Viraday) is they can sell it domestically at a radically lower cost than the price of the United States version. India is currently a signatory to TRIPS and consequently there will be a drop in the amount of generic HIV medicines available.

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 TFC doses according to the patient’s CrCl levels.

Mechanism of action

Efavirenz is a non-nucleoside reverse transcriptase inhibitor (NNRT) of HIV-1. Emtricitabine is a nucleoside reverse transcriptase inhibitor (NRTI) of HIV-1.Tenofovir is a nucleotide reverse transcriptase inhibitor of HIV-1, but it can be classified as a NRTI. These three drugs work in combination to target HIV at different point in its life cycle and it reduces the virus’s capacity to mutate.

Antiviral activity In combination studies there were synergistic antiviral effects observed between emtricitabine and efavirenz, efavirenz and tenofovir, and emtricitabine and tenofovir.

Side effects

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

Interactions

Medications that should not be taken with Atripla are "Hismanal (astemizole), Vascor (bepridil), Propulsid (cisapride), 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.

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.^[6]

External links

• Atripla.com managed by Gilead Sciences and Bristol-Myers Squibb
• Atripla article on The Body, an HIV reference site