Efavirenz/emtricitabine/tenofovir disoproxil fumarate

Detailed information

This fixed-dose tablet combines 600mg efavirenz, 200mg emtricitabine (FTC), and 245mg tenofovir disoproxil fumarate (TDF).

Efavirenz is a non-nucleoside reverse transcriptase inhibitor (NNRTI), emtricitabine is a nucleoside reverse transcriptase inhibitor (NRTI), and tenofovir disoproxil fumarate is a nucleotide reverse transcriptase inhibitor (NtRTI). These drugs reduce the amount of HIV in the body and prevent the development of AIDS-defining illnesses.

The fixed-dose combination was first approved as Atripla in the United States in 2006 and in the European Union in late 2007. Numerous generic versions are also available. Branded Atripla will be discontinued at the end of 2021 due to lack of demand.

In the European Union and United Kingdom efavirenz/tenofovir (TDF)/emtricitabine is licensed for use in patients who have already achieved undetectable viral load on a combination in which the components are dosed separately as tenofovir (TDF)/emtricitabine and efavirenz. In the United States it can be used as initial therapy without the need for an induction phase using separate components. The European medicines licensing body has not issued an explanation of its divergent licensing decision.

Effectiveness

Atripla was licensed on the basis of data from Study 934, which compared efavirenz (Sustiva), emtricitabine (Emtriva) and tenofovir disoproxil fumarate (Viread) taken as separate drugs, to the combination of efavirenz and zidovudine (AZT) plus lamivudine (3TC) as Combivir. In this study, more patients in the emtricitabine and tenofovir arm achieved viral loads below 400 copies/ml after 48 weeks, largely due to fewer discontinuations due to drug side effects. (Gallant) A study in HIV-negative subjects revealed that the triple combination tablet produces blood levels equivalent to the three drugs taken separately.

Taking it

The standard dose of the efavirenz/tenofovir (TDF)/emtricitabine fixed-dose tablet is one tablet once a day. The manufacturers advise patients to take the tablet on an empty stomach before going to bed.

Side effects

The most common side effects of the efavirenz/tenofovir (TDF)/emtricitabine fixed-dose tablet  are rash, dizziness, headache, depression, anxiety, abnormal dreams, difficulty in sleeping, concentration problems, drowsiness, diarrhoea, nausea, vomiting, abdominal pain, itching, fatigue and weakness.

Increases in lipid levels, liver enzymes, pancreatic enzymes, blood glucose, phosphate and creatine kinase are common in people taking this combination.

The combination should not be taken by people with impaired kidney function (creatine clearance less than 50ml/min).

Drug interactions

Because of the efavirenz component in this fixed-dose combination, use of many drugs is contraindicated or may require dosing adjustment. See efavirenz for further details.

Glossary

resistance

A drug-resistant HIV strain is one which is less susceptible to the effects of one or more anti-HIV drugs because of an accumulation of HIV mutations in its genotype. Resistance can be the result of a poor adherence to treatment or of transmission of an already resistant virus.

reverse transcriptase

A retroviral enzyme which converts genetic material from RNA into DNA, an essential step in the lifecycle of HIV. Several classes of anti-HIV drugs interfere with this stage of HIV’s life cycle: nucleoside reverse transcriptase inhibitors and nucleotide reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). 

nucleoside

A precursor to a building block of DNA or RNA. Nucleosides must be chemically changed into nucleotides before they can be used to make DNA or RNA. 

non-nucleoside reverse transcriptase inhibitor (NNRTI)

Non-nucleoside reverse transcriptase inhibitor, the family of antiretrovirals which includes efavirenz, nevirapine, etravirine, doravirine and rilpivirine. Non-nucleoside reverse transcriptase inhibitors (NNRTIs) bind to and block HIV reverse transcriptase (an HIV enzyme), preventing HIV from replicating.

fixed-dose combination (FDC)

Two or more drugs contained in a single dosage form, such as a capsule or tablet. By reducing the number of pills a person must take each day, fixed-dose combination drugs may help improve adherence.

See also tenofovir disoproxil fumarate (TDF) and emtricitabine.

Resistance

Viral rebound or lack of viral suppression on the efavirenz/tenofovir (TDF)/emtricitabine combination most frequently leads to resistance to efavirenz and cross-resistance to other non-nucleoside reverse transcriptase inhibitors. Emtricitabine and TDF resistance were rare in people experiencing viral rebound on this combination in Study 934.

Pregnancy

See efavirenz for further details.

Children

The efavirenz/tenofovir (TDF)/emtricitabine combination tablet is not approved for use in children or adolescents under 18 years of age.

For more information on its component drugs, including drug interactions, side effects and resistance, see efavirenz, emtricitabine (Emtriva) and tenofovir disoproxil fumarate.

References

Gallant JE et al. Tenofovir DF, Emtricitabine, and Efavirenz vs. Zidovudine, Lamivudine, and Efavirenz for HIV. New England Journal of Medicine, 354:251-260, 2006.

 

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