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Efavirenz with emtricitabine and tenofovir disoproxil oral


Oral formulations containing efavirenz, emtricitabine, and tenofovir disoproxil (as fumarate).

Drugs List

  • ATRIPLA tablets
  • efavirenz 600mg and emtricitabine 200mg and tenofovir disoproxil 245mg tablets
  • Therapeutic Indications


    Treatment of HIV infected adults

    Treatment of human immunodeficiency virus 1 (HIV-1) infected adults with virological suppression to HIV-1 RNA levels of less than 50 copies/ml on their current combination antiretroviral therapy for more than three months.

    Patients must not have experienced virological failure on any prior antiretroviral therapy and must not have harboured viral strains with mutations conferring significant resistance to any of the three components of this medicine.

    Benefit of the combination of efavirenz, emtricitabine and tenofovir disoproxil fumarate is primarily based on 48-week data from a clinical study in which patients with stable virological suppression on antiretroviral combination therapy changed to efavirenz with emtricitabine and tenofovir.

    There are no data available on the use of efavirenz with emtricitabine and tenofovir in treatment-naive or heavily pre-treated patients.

    There are no data available to support the use of efavirenz with emtricitabine and tenofovir in combination with other antiretroviral products.


    When one of the active substances needs to be discontinued or when dosage needs to be modified, separate preparations of efavirenz, emtricitabine and tenofovir disoproxil are available. For further information, refer to the individual summary of products characteristics of these medicinal products.


    One tablet daily.


    One tablet daily.

    Use with caution in elderly patients. The combination of efavirenz with emtricitabine and tenofovir has not been studied in patients over the age of 65.

    Patients with Renal Impairment

    Moderate to severe renal impairment (creatinine clearance less than 50 ml/minute)
    Contraindicated in these patients as appropriate dosage modifications of emtricitabine and tenofovir cannot be made with the combination tablet.

    Patients with Hepatic Impairment

    The pharmacokinetics of efavirenz with emtricitabine and tenofovir have not been studied in patients with hepatic impairment.

    Efavirenz is principally metabolised by the CYP450 system, therefore use with caution in patients with mild hepatic impairment. These patients should be monitored carefully for efavirenz related adverse effects, especially nervous system effects. Hepatic function tests should be performed at periodic intervals in these patients.

    Mild hepatic impairment (Child-Pugh grade A)
    One tablet daily.
    Patients should be monitored carefully for adverse effects, especially nervous system effects related to efavirenz.

    Moderate and severe hepatic impairment (Child-Pugh grade B and C)
    Contraindicated in these patients.

    Physicians should refer to current HIV treatment guidelines to determine the best treatment for patients co-infected with HIV and hepatitis.

    Patients with chronic hepatitis B or C who are treated with combination antiretroviral therapy have an increased risk of developing severe and potentially fatal hepatic adverse effects, and therefore should be closely monitored during treatment. The product literature relating to concurrent treatments for hepatitis B or C should be consulted.

    The safety and efficacy of efavirenz with emtricitabine and tenofovir has not been established for the treatment of chronic hepatitis B infection. Limited clinical experience suggests that emtricitabine and tenofovir are active against hepatitis B infection when used in antiretroviral combination therapy to control HIV infection.

    If efavirenz with emtricitabine and tenofovir is discontinued in patients co-infected with the hepatitis B virus, close monitoring with clinical and laboratory follow up for at least four months after discontinuation is necessary as the discontinuation of this product may result in an exacerbation of hepatitis. If appropriate, resumption of anti-hepatitis B therapy may be considered. In patients with advanced liver disease or cirrhosis, discontinuation of treatment is not recommended since post-treatment exacerbation may lead to hepatic decompensation.

    Additional Dosage Information

    Concurrent rifampicin
    If efavirenz with emtricitabine and tenofovir is administered concurrently with rifampicin, an additional 200 mg per day of efavirenz is recommended.


    Children under 18 years
    Acute porphyria
    Long QT syndrome
    Moderate hepatic impairment
    Renal impairment - creatinine clearance below 50ml/minute
    Torsade de pointes

    Precautions and Warnings

    Family history of long QT syndrome
    Congestive cardiac failure with reduced left ventricular ejection fraction
    Electrolyte imbalance
    Hepatitis B
    Hepatitis C
    History of cardiac arrhythmias
    History of depression
    History of psychiatric disorder
    History of seizures
    History of torsade de pointes
    Mild hepatic impairment
    Renal impairment

    Contains more than 1 mmol (23 mg) sodium per dose
    Correct electrolyte disorders before treatment
    Therapy cessation not recommended in decompensated liver disease/cirrhosis
    Treatment does not prevent risk of transmission of HIV
    Advise ability to drive/operate machinery may be affected by side effects
    Consider prophylactic antihistamines for high risk patients
    Perform viral resistance testing before initiating therapy
    Treatment should be initiated by doctor experienced in HIV management
    Exclude pregnancy prior to initiation of treatment
    Monitor renal function prior to initiating treatment
    Autoimmune disorders can occur many months after initiation of treatment
    Blood lipid and glucose levels may increase requiring treatment
    Consider monitoring ECG in patients at risk of QT prolongation
    Monitor for depressive disorders/suicidal ideation-consider discontinuation
    Monitor hepatic enzymes
    Monitor patients with hepatic impairment
    Monitor renal function every 4 weeks during first year, then every 3 months
    Monitor serum electrolytes
    On discontinuation, may cause recurrence of hepatitis B
    Advise patient to report any new or worsening depression/suicidal ideation
    Advise patient to seek medical advice if joint aches or pain occur
    Advise patient to seek medical advice if movement becomes difficult
    Autoimmune diseases may occur during treatment
    Inflammatory symptoms should be evaluated and treated appropriately
    May cause loss of bone mineral density
    Neonate exposed in utero: Risk of mitochondrial dysfunction
    Risk of developing opportunistic infections
    May affect results of some laboratory tests
    Discontinue if hepatic function deteriorates in pts with hepatic impairment
    Discontinue if severe skin reaction occurs
    Discontinue if symptomatic hyperlactataemia occurs
    Interrupt therapy if hepatic transaminases > 5 times upper limit of normal
    Interrupt treatment if creatinine clearance below 50 ml/minute
    Interrupt treatment if serum phosphate decreases to below 1 mg/dL
    Advise patient not to take ginkgo unless advised by clinician
    Advise patient not to take NSAIDs unless advised by clinician
    Advise patient not to take St John's wort concurrently
    Advise patient grapefruit products may increase plasma level
    Female: Two reliable methods of contraception should be used simultaneously
    Male & female: Contraception required during & for 3 months after treatment
    Take another dose if vomiting occurs within one hour

    When one of the active substances needs to be discontinued or when dosage needs to be modified, separate preparations of efavirenz, emtricitabine and tenofovir disoproxil are available. For further information, refer to the individual summary of products characteristics of these medicinal products.

    If therapy is discontinued, consideration should be given to the long half-life of efavirenz and the long intracellular half-lives of emtricitabine and tenofovir.

    Patients who are on a protease-inhibitor based antiretroviral regimen may experience a reduction in response to therapy upon switching to efavirenz with emtricitabine and tenofovir. Monitor these patients for rises in viral load and adverse reactions.

    Creatinine clearance should be calculated in all patients prior to initiating therapy. Renal function tests (including serum creatinine and serum phosphate) should be taken before treatment begins and at four-weekly intervals during the first year and every three months thereafter. If deemed necessary, this monitoring should be more frequent in patients with a history of renal impairment or those at risk of renal impairment.
    If serum phosphate levels decrease to less than 1.5 mg/dl or creatinine clearance decreases to less than 50 ml/minute, renal function should be re-evaluated within one week (including measurements of blood glucose, blood potassium and urinary glucose levels). Interrupt therapy in patients with creatinine clearance less than 50 ml/minute or serum phosphate less than 1mg/dl. Interrupting treatment should also be considered in case of progressive decline of renal function when no other cause has been identified.

    Mild to moderate rash has been reported with the individual components of this medicine. Rash associated with efavirenz usually resolves with continued therapy. Antihistamines and/or corticosteroids may improve tolerability and hasten the resolution of rash. Treatment should be discontinued in patients who develop severe rash associated with blistering, desquamation, mucosal involvement or fever. Efavirenz with emtricitabine and tenofovir is not recommended for patients who have had a life-threatening cutaneous reaction (e.g. Stevens-Johnson syndrome) while taking non-nucleoside reverse transcriptase inhibitors as experience with efavirenz in patients who discontinued other antiretroviral agents of this class is limited.

    Treatment regimens containing nucleoside or nucleotide analogues have been reported to cause mitochondrial dysfunction in HIV-negative infants exposed in utero and/or post-natally. Adverse reactions such as haematological (anaemia, neutropenia), metabolic (hyperlactataemia, hyperlipasemia) and neurological (hypertonia, convulsions, abnormal behaviour) have been reported. Consider in children exposed to nucleoside or nucleotide analogues in utero (including HIV-negative infants) and who present with neurological symptoms or severe clinical findings of unknown cause.

    When combination antiretroviral therapy is initiated in HIV-infected patients with severe immune deficiency, an inflammatory reaction to asymptomatic or residual opportunist pathogens may arise. This can lead to the aggravation of symptoms or other serious clinical conditions such as cytomegalovirus retinitis, mycobacterial infections or Pneumocystis jiroveci pneumonia. These reactions are usually observed within the first few weeks or months after treatment initiation. Any inflammatory symptoms should be evaluated and treated appropriately.

    Clinical trials have indicated that tenofovir disoproxil fumarate may be associated with a decrease in bone mineral density of the hip and spine. If bone abnormalities (which may be associated with proximal renal tubulopathy) are suspected in patients taking efavirenz with emtricitabine and tenofovir, appropriate consultation should be obtained.

    Blood lipid and glucose levels may increase during antiretroviral therapy. This may be linked to disease control and lifestyle. Refer to established HIV treatment guidelines for monitoring and manage lipid and glucose level disorders as appropriate.

    Pregnancy and Lactation


    Use efavirenz with emtricitabine and tenofovir with caution during pregnancy.

    The manufacturer suggests efavirenz with emtricitabine and tenofovir should not be used during pregnancy unless the condition of the pregnant woman requires treatment with this combination.

    At the time of writing, there are limited data on the use of efavirenz with emtricitabine and tenofovir during human pregnancy.

    Animal data suggests a risk of decreased growth for treatment with tenofovir. Also animal data suggests that the risk from emtricitabine is low. Efavirenz has shown teratogenic effects during studies in primates and embryotoxicity has been observed in rats, suggesting a potential for risk in humans.

    The little data available on the use of tenofovir and emtricitabine during pregnancy suggest a low risk. However, a small number of cases of neural tube defects, including meningomyelocele, have been reported with the use of efavirenz but causality has not been established. It is not known whether tenofovir, emtricitabine, or efavirenz will cross the placenta, animal studies and the relatively low molecular weights of all the drugs in this preparation suggest that they will cross the placenta to the foetus.

    In the incidence of pregnancy occurring during therapy for HIV-1, combined antiretroviral therapy should continue. Withdrawal or interruption of therapy may increase the emergence of resistant viral strains. Treatment of the pregnant mother with monotherapy is considered inadequate.

    Guidelines recommend avoiding treatment with efavirenz due to animal data and reports of central nervous system defects in infants born of efavirenz exposed pregnancies. Therefore, administration of tenofovir and emtricitabine with efavirenz is not recommended.

    Pregnancy should be avoided during treatment with efavirenz. If pregnancy arises during treatment, the patient should be notified of the potential risk of efavirenz to the foetus. Briggs suggests the use of zidovudine during the intrapartum period regardless of current regimen, as this may prevent vertical transmission of HIV to the newborn.

    The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( ) or if this is unavailable at the backup site ( ).


    Efavirenz with emtricitabine and tenofovir is contraindicated in breastfeeding.

    It is recommend that HIV infected women do not breastfeed their infants under any circumstances in order to avoid transmission of HIV.

    There are insufficient data, at the time of writing, available on the use of efavirenz with emtricitabine and tenofovir during breastfeeding. Due to the low molecular weight all three drugs, excretion in breast milk is considered likely.

    Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
    Specialist advice is available from the UK Drugs in Lactation Advisory Service at


    Advise patients, tablets should be swallowed whole and taken on an empty stomach. Food may increase efavirenz exposure and increase the frequency of adverse events.

    Advise patients, bedtime dosing is recommended to improve the tolerability to efavirenz with respect to nervous system adverse effects.

    Advise patients that it is important to take efavirenz with emtricitabine and tenofovir on a regular dosing schedule to avoid missed doses. If patients forget to take the tablet at the correct time, they should be advised to take the tablet as soon as possible, unless it is less than 12 hours until the next scheduled dose. If this is the case, patients should be advised not to take the missed dose and take the next tablet at the normal time.

    Advise patients if the patient vomits within 1 hour of taking the tablet, another tablet should be taken. If the patient vomits more than 1 hour after taking the tablet they do not need to take another dose.

    Advise patients that treatment is not a cure for HIV infection and they may still develop opportunistic infections and other complications of HIV infection.

    Advise patients that treatment does not prevent the risk of HIV transmission through sexual contact or blood contamination and that appropriate precautions should be continued.

    Advise patient not to take NSAIDs unless advised by clinician.

    Advise patients not to use St. John's Wort or ginkgo biloba whilst being treated.

    Advise patients that if they experience symptoms such as severe depression, psychosis or suicidal ideation, they should consult their doctor immediately.

    Advise patients that nervous system symptoms, including dizziness, insomnia, somnolence, impaired concentration and abnormal dreaming, are likely to improve with continued treatment and are not predictive of subsequent onset of any of the less frequent psychiatric symptoms.

    Advise patients to seek medical advice if they experience joint aches or pains, joint stiffness or difficulty in movement.

    Advise patients to use barrier contraception in addition to oral or other hormonal contraception. Because of the long half life of efavirenz, use of adequate contraceptive measures for 12 weeks after discontinuing the product in recommended.

    Advise patients ability to drive or operate machinery may be affected by side effects.

    Side Effects

    Abdominal distension
    Abdominal pain
    Abnormal thinking
    Acute interstitial nephritis
    Acute tubular necrosis
    Allergic reaction
    Attention disturbances
    Autoimmune hepatitis
    Behavioural disturbances
    Blurred vision
    Cerebellar dysfunction
    Creatine kinase increased
    Diabetes insipidus
    Disturbances of appetite
    Dream abnormalities
    Dry mouth
    Elevated amylase levels
    Elevated serum lipase
    Emotional lability
    Erythema multiforme
    Fanconi syndrome
    Graves' disease
    Hepatic failure
    Hepatic steatosis
    Hot flushes
    Hyperpigmentation of skin
    Hypersensitivity reactions
    Immune Reactivation/Reconstitution Syndrome
    Impaired co-ordination
    Increase in serum ALT/AST
    Increase in serum transaminases
    Lactic acidosis
    Maculopapular rash
    Metabolic disorders
    Photoallergic reactions
    Proximal tubulopathy
    Pustular rash
    Reduced libido
    Renal failure
    Serum creatinine increased
    Sleep disturbances
    Stevens-Johnson syndrome
    Suicidal tendencies
    Vesiculo-bullous reactions

    Effects on Laboratory Tests

    Cannabinoid test interaction
    Efavirenz does not bind to cannabinoid receptors. False-positive urine cannabinoid test results have been reported with some screening assays in uninfected and HIV-infected volunteers who received efavirenz. The manufacturers suggest confirmatory testing by a more specific method such as gas chromatography/mass spectrometry should be used in such cases.


    It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

    The following number will direct the caller to the relevant local centre (0844) 892 0111

    Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( ) or if this is unavailable at the backup site ( ).

    Further Information

    Last Full Review Date: July 2014

    Reference Sources

    Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

    Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

    Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press [Accessed on June 22, 2014]

    Summary of Product Characteristics: Atripla 600 mg/200 mg/245 mg film-coated tablets. Gilead Sciences Ltd. Revised November 2018

    The Norwegian Porphyria Centre (NAPOS).
    Available at:
    Last revised: April 17, 2013
    Last accessed: June 22, 2014

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