Single-tablet HIV regimen Pregnancy: eMC §4.6: pregnancy should be AVOIDED in women receiving this combination; women of childbearing potential should undergo pregnancy testing before initiation. Barrier contraception should always be used in combination with other methods of contraception (e.g. oral or other hormonal contraceptives) during therapy, and adequate contraception is recommended for 12 weeks after discontinuation because of the long half-life of efavirenz. Efavirenz: seven retrospective reports of findings consistent with neural tube defects (including meningomyelocele) in mothers exposed to efavirenz-containing regimens in the first trimester, plus two further cases with the fixed-dose combination; causality has not been established and the denominator is unknown. Emtricitabine and tenofovir disoproxil: a large amount of data (more than 1,000 pregnancy outcomes) indicates no malformations or foetal/neonatal toxicity. This combination should not be used during pregnancy unless the clinical condition of the woman requires it. Efavirenz, emtricitabine and tenofovir are excreted in human milk.

Efavirenz with emtricitabine and tenofovir disoproxil

Brand names: Atripla

A once-daily single-tablet antiretroviral regimen combining the non-nucleoside reverse transcriptase inhibitor efavirenz with the nucleos(t)ide analogues emtricitabine and tenofovir disoproxil, used as complete treatment for HIV-1 infection in adults.

Adult dose

Dose: One tablet (efavirenz 600 mg / emtricitabine 200 mg / tenofovir disoproxil 245 mg) once daily, on an empty stomach

Route: Oral - swallow the tablet whole with water

Frequency: Once daily, bedtime dosing recommended

eMC SPC §4.2 (Efavirenz/emtricitabine/tenofovir disoproxil 600 mg/200 mg/245 mg film-coated tablets). Therapy should be initiated by a physician experienced in the management of HIV infection. ADMINISTRATION: recommended to be taken on an empty stomach, since food may increase efavirenz exposure and lead to an increase in the frequency of adverse reactions; bedtime dosing is recommended to improve tolerability with respect to efavirenz nervous-system effects. Taking on an empty stomach is anticipated to give approximately 30% lower tenofovir exposure (AUC) than tenofovir disoproxil taken with food as a single component. MISSED DOSE: if missed within 12 hours of the usual time, take as soon as possible and resume the normal schedule; if missed by more than 12 hours and it is almost time for the next dose, skip it and resume the usual schedule. VOMITING: if the patient vomits within 1 hour of taking the tablet, another tablet should be taken; if more than 1 hour after, no extra tablet is needed. DOSE ADJUSTMENT: if co-administered with rifampicin in patients weighing 50 kg or more, an additional 200 mg/day of efavirenz (800 mg total) may be considered (§4.5). Where discontinuation or dose modification of one component is indicated, separate preparations of efavirenz, emtricitabine and tenofovir disoproxil are available. On discontinuation, consider the long half-life of efavirenz and the long intracellular half-lives of emtricitabine and tenofovir, and consult HIV treatment guidelines. ELDERLY: administer with caution. HEPATIC IMPAIRMENT: not studied in hepatic impairment; patients with mild liver disease (Child-Pugh-Turcotte Class A) may be treated with the normal recommended dose, with careful monitoring for adverse reactions especially efavirenz-related nervous system symptoms; contraindicated in severe hepatic impairment (CPT Class C). HBV CO-INFECTION: if discontinued in patients co-infected with HIV and HBV, monitor closely for exacerbation of hepatitis. PAEDIATRIC: safety and efficacy in children under 18 years have not been established - verify any under-18 use against a children's formulary. NOTE ON US LABELLING: the openFDA label in this bundle is a single-component efavirenz label and does not describe this fixed-dose triple combination; it was not used for the dose.

Dose adjustments

Renal

eMC §4.2: NOT recommended for patients with moderate or severe renal impairment (creatinine clearance < 50 mL/min). Such patients require dose interval adjustment of emtricitabine and tenofovir disoproxil that cannot be achieved with the fixed-dose combination tablet.

Dose independently re-sourced from UK Summary of Product Characteristics (SPC) via the eMC; US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — clinician-reviewed. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

Hypersensitivity to the active substances or to any of the excipients (eMC §4.3)
Severe hepatic impairment (Child-Pugh-Turcotte Class C)
Co-administration with terfenadine, astemizole, cisapride, midazolam, triazolam, pimozide, bepridil, or ergot alkaloids (e.g. ergotamine, dihydroergotamine, ergonovine, methylergonovine) - competition for CYP3A4 by efavirenz could inhibit their metabolism and cause serious and/or life-threatening reactions such as cardiac arrhythmias, prolonged sedation or respiratory depression
Co-administration with elbasvir/grazoprevir, with voriconazole (the efavirenz dose cannot be altered in this fixed-dose combination), or with herbal preparations containing St John's wort (Hypericum perforatum)
Patients with a family history of sudden death or of congenital QTc prolongation, or any other condition known to prolong the QTc interval; a history of symptomatic cardiac arrhythmias, clinically relevant bradycardia, or congestive cardiac failure with reduced left ventricular ejection fraction; or severe electrolyte disturbance such as hypokalaemia or hypomagnesaemia
Co-administration with drugs known to prolong the QTc interval (proarrhythmic), including class IA and III antiarrhythmics, neuroleptics, antidepressive agents, certain antibiotics (some macrolides, fluoroquinolones, imidazole and triazole antifungals), certain non-sedating antihistamines (terfenadine, astemizole), cisapride, flecainide, certain antimalarials and methadone

Side effects

Psychiatric disorders (16% of patients in study AI266073) - including severe depression, death by suicide and psychosis-like behaviour (eMC §4.8)
Nervous system disorders (13%) - efavirenz-related nervous system symptoms, and seizures have been reported
Gastrointestinal disorders (7%); anorexia common, with dry mouth, incoherent speech, increased appetite, decreased libido and myalgia uncommon
Severe skin reactions such as Stevens-Johnson syndrome and erythema multiforme have been reported
Severe hepatic events, pancreatitis and lactic acidosis (sometimes fatal); rare events of renal impairment and renal failure and uncommon events of proximal renal tubulopathy (including Fanconi syndrome) sometimes leading to bone abnormalities and infrequently contributing to fractures - renal function monitoring is recommended. Discontinuation in HIV/HBV co-infected patients may be associated with severe acute exacerbations of hepatitis

Interactions

CYP3A4 substrates with narrow safety margins (terfenadine, astemizole, cisapride, midazolam, triazolam, pimozide, bepridil, ergot alkaloids) - contraindicated (eMC §4.3)
Elbasvir/grazoprevir (significant decreases in plasma concentrations via CYP3A4/P-gp induction), voriconazole (mutual interaction and the efavirenz dose cannot be altered in a fixed-dose product), and St John's wort - contraindicated (eMC §4.3)
QTc-prolonging (proarrhythmic) medicines including class IA and III antiarrhythmics, neuroleptics, antidepressants, macrolides, fluoroquinolones, imidazole/triazole antifungals, cisapride, flecainide, certain antimalarials and methadone - contraindicated (eMC §4.3)
Rifampicin - in patients weighing 50 kg or more an additional 200 mg/day of efavirenz (800 mg total) may be considered (eMC §4.2)
Not to be given with other products containing emtricitabine or tenofovir disoproxil, with other cytidine analogues such as lamivudine, with adefovir dipivoxil or with tenofovir alafenamide-containing products; co-administration with didanosine, with sofosbuvir/velpatasvir or sofosbuvir/velpatasvir/voxilaprevir, and concomitant use of Ginkgo biloba extracts are not recommended. Barrier contraception must always be added to hormonal contraception (eMC §4.4/§4.6)

Clinical monograph

How it works

Efavirenz directly inhibits reverse transcriptase by binding a non-catalytic site, while emtricitabine and tenofovir disoproxil are phosphorylated and incorporated into viral DNA by reverse transcriptase, terminating chain elongation.

Prescribing in practice

Efavirenz commonly causes central nervous system effects including dizziness, abnormal dreams and mood disturbance, and has been associated with depression and suicidal ideation, so screen for psychiatric history.
Tenofovir disoproxil can cause renal tubular dysfunction and reduced bone mineral density, requiring caution in renal impairment and avoidance with other nephrotoxic drugs.
Efavirenz induces hepatic enzymes and can lower the efficacy of hormonal contraception and many co-medications.

Monitoring

Monitor HIV viral load and CD4 count, together with renal function, liver function and lipids during treatment.

Counselling the patient

Take once daily, ideally at bedtime and on an empty stomach, to reduce nervous-system side effects.
Tell your doctor about any low mood, anxiety or unusual dreams.
Use additional or non-hormonal contraception, as this medicine can reduce the pill's effectiveness.

Evidence & guidelines

Efficacy of efavirenz-based fixed-dose therapy is well established, though current BHIVA guidance generally favours integrase-inhibitor regimens as first line.

Reference: BHIVA HIV guidelines; EACS; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Curated clinical cross-links plus same-class fallbacks.

Calculators

Drugs

Emtricitabine with rilpivirine and tenofovir disoproxil · Single-tablet HIV regimen

Pathways