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{{Short description|Combination drug for HIV}} |
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{{Drugbox |
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{{Use dmy dates|date=August 2021}} |
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| verifiedrevid = 419518321 |
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{{cs1 config|name-list-style=vanc|display-authors=6}} |
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{{Infobox drug |
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<!--Combo data--> |
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| verifiedrevid = 447573543 |
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| drug_name = Efavirenz/emtricitabine/tenofovir disoproxil |
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| type = combo |
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| type = combo |
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| image = Efavirenz, emtricitabine and tenofovir disoproxil.svg |
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| component1 = Tenofovir |
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| width = |
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| class1 = Nucleotide analogue ] |
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| alt = |
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| caption = |
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<!-- Combo data --> |
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| component1 = Efavirenz |
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| class1 = ] |
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| component2 = Emtricitabine |
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| component2 = Emtricitabine |
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| class2 = ] ] |
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| class2 = ] analog ] |
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| component3 = Efavirenz |
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| component3 = Tenofovir disoproxil |
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| class3 = ] |
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| class3 = ] analog ] |
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<!--Clinical data--> |
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<!-- Clinical data --> |
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| tradename = |
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| pronounce = |
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| tradename = Atripla, Viraday, others |
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| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X --> |
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| Drugs.com = {{drugs.com|ppa|efavirenz-emtricitabine-and-tenofovir-disoproxil-fumarate}} |
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| pregnancy_US = D |
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| MedlinePlus = |
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| pregnancy_category = |
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| DailyMedID = Atripla |
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| legal_AU = <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 --> |
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| pregnancy_AU = D |
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| legal_CA = <!-- / Schedule I, II, III, IV, V, VI, VII, VIII --> |
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| pregnancy_AU_comment = <ref name="AU Atripla TGA" /><ref name="Drugs.com pregnancy">{{cite web | title=Efavirenz / emtricitabine / tenofovir (Atripla) Use During Pregnancy | website=Drugs.com | date=27 July 2018 | url=https://www.drugs.com/pregnancy/efavirenz-emtricitabine-tenofovir.html | access-date=31 March 2020}}</ref> |
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| pregnancy_category = |
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| routes_of_administration = ] |
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| ATC_prefix = J05 |
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| ATC_suffix = AR06 |
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| ATC_supplemental = |
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<!-- Legal status --> |
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| legal_AU = S4 |
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| legal_AU_comment = <ref name="AU Atripla TGA">{{Cite web|url=https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-03881-3|title = TGA eBS - Product and Consumer Medicine Information Licence}}</ref> |
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| legal_BR = <!-- OTC, A1, A2, A3, B1, B2, C1, C2, C3, C4, C5, D1, D2, E, F--> |
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| legal_BR_comment = |
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| legal_CA = <!-- OTC, Rx-only, Schedule I, II, III, IV, V, VI, VII, VIII --> |
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| legal_CA_comment = |
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| legal_DE = <!-- Anlage I, II, III or Unscheduled--> |
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| legal_DE_comment = |
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| legal_NZ = <!-- Class A, B, C --> |
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| legal_NZ_comment = |
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| legal_UK = POM |
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| legal_UK = POM |
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| legal_UK_comment = <ref>{{cite web | title=Atripla 600 mg/200 mg/245 mg film coated tablets - Summary of Product Characteristics (SmPC) | website=(emc) | date=2 March 2020 | url=https://www.medicines.org.uk/emc/product/6173/smpc | access-date=31 March 2020 | archive-date=10 August 2020 | archive-url=https://web.archive.org/web/20200810164326/https://www.medicines.org.uk/emc/product/6173/smpc | url-status=dead }}</ref> |
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| legal_US = Rx-only |
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| legal_US = Rx-only |
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| legal_US_comment = <ref name="Atripla FDA label" /> |
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| legal_status = |
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| legal_EU = Rx-only |
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| routes_of_administration = Oral |
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| legal_EU_comment = <ref name="Atripla EPAR" /> |
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| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV--> |
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| legal_UN_comment = |
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| legal_status = Rx-only |
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<!--Identifiers--> |
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<!-- Identifiers --> |
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| CAS_number_Ref = {{cascite|correct|??}} |
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| CAS_number = 731772-50-2 |
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| CAS_number = 731772-50-2 |
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| ATC_prefix = J05 |
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| CAS_supplemental = |
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| ATC_suffix = AR06 |
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| PubChem = |
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| PubChem = |
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| IUPHAR_ligand = |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| DrugBank_Ref = {{drugbankcite|correct|drugbank}} |
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| DrugBank = |
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| DrugBank = |
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| ChemSpiderID = none |
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| UNII = |
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<!--Chemical data--> |
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| KEGG_Ref = {{keggcite|correct|kegg}} |
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| KEGG = D10851 |
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| ChEBI = |
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| ChEMBL = |
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| NIAID_ChemDB = |
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| PDB_ligand = |
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| synonyms = tenofovir disoproxil fumarate/emtricitabine/efavirenz |
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}} |
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}} |
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<!-- Definition and medication uses --> |
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'''Emtricitabine/tenofovir/efavirenz''' (], trade name '''Atripla''') is a ] drug for the treatment of ] infection. It combines ]'s ] and ] (already available in the anti-HIV combination ]) with ]'s ] into a fixed-dose pill. Combining the three drugs into a single, once-daily pill reduces ] and simplifies dosing schedules, and therefore has the potential to increase adherence to ] therapy. |
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'''Efavirenz/emtricitabine/tenofovir''', sold under the brand name '''Atripla''' among others, is a ] ] used to treat ].<ref name=WHO2008/><ref name="Atripla EPAR" /> It contains ], ], and ].<ref name=WHO2008/><ref name="Atripla EPAR" /> It can be used by itself or together with other ].<ref name=WHO2008/> It is taken ].<ref name="Atripla FDA label"/><ref name="Atripla EPAR" /><ref name=WHO2008>{{cite book | title = WHO Model Formulary 2008 | year = 2009 | isbn = 9789241547659 | vauthors = ((World Health Organization)) | veditors = Stuart MC, Kouimtzi M, Hill SR | hdl = 10665/44053 | author-link = World Health Organization | publisher = World Health Organization | hdl-access=free |page=160 }}</ref> |
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<!-- Side effects and mechanism --> |
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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.<ref>{{cite web | author= | title=Search for Tradename: Atripla | url=http://drugpatentwatch.com/ultimate/preview/tradename/index.php?query=Atripla | work=Drug Patent Watch | year=2010 | accessdate=2010-01-03}}</ref> 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. ] on July 12, 2006. In the UK, the drug cost to the NHS is {{GB£}}620 per month. |
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Common side effects include headache, trouble sleeping, sleepiness, and unsteadiness.<ref name="Atripla FDA label" /> Serious side effects may include ], psychiatric symptoms, and ].<ref name="Atripla FDA label" /> It should not be used in children.<ref name=WHO2008/> If used during the ] of ] harm to the baby may occur.<ref name="Atripla FDA label" /> |
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<!-- History and culture --> |
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Atripla is a fixed dose combination of 600 mg ], 300 mg ], and 200 mg ]. 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. |
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Efavirenz/emtricitabine/tenofovir was approved for medical use in the United States in 2006,<ref name="Atripla FDA label" /><ref>{{cite web | title=Drug Approval Package: Atripla (Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate) NDA #021937 | website=U.S. ] (FDA) | date=13 December 2006 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2006/021937TOC2.cfm | access-date=25 September 2021}}</ref> and in the European Union in 2007.<ref name="Atripla EPAR">{{cite web | title=Atripla EPAR | website=] (EMA) | date=7 July 2008 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/atripla | access-date=31 March 2020}}</ref> It is on the ].<ref name="WHO21st">{{cite book | vauthors = ((World Health Organization)) | title = World Health Organization model list of essential medicines: 21st list 2019 | year = 2019 | hdl = 10665/325771 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO | hdl-access=free }}</ref> Efavirenz/emtricitabine/tenofovir is available as a ].<ref>{{cite web | title=Office of Generic Drugs 2018 Annual Report | website=U.S. ] (FDA) | date=28 January 2021 | url=https://www.fda.gov/drugs/first-generic-drug-approvals/2018-first-generic-drug-approvals | access-date=25 September 2021}}</ref><ref>{{cite web | title=Efavirenz, Emtricitabine, and Tenofovir Disoproxil Fumarate: FDA-Approved Drugs | website=U.S. ] (FDA) | url=https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=203041 | access-date=25 September 2021}}</ref> |
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==Medical uses== |
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Atripla is a pink, capsule-shaped tablet with "123" impressed on one side. |
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Efavirenz/emtricitabine/tenofovir is indicated for the treatment of ].<ref name="Atripla FDA label"/><ref name="Atripla EPAR" /> |
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== Contraindications == |
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In North America and Europe, Atripla is marketed jointly by ] and ], but in much of the developing world, marketing and distribution is handled by ]<ref>{{cite web | author= | title=Merck To Register, Lower Cost Of Antiretroviral Atripla In Developing Countries | url=http://www.medicalnewstoday.com/articles/63612.php | work=Medical News Today | date=23 February 2007 | accessdate=2010-01-03}}</ref> ] released its own version of Atripla in India, called '''Viraday'''. In ], Atripla is marketed by Laboratorios Gador. |
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People who have shown strong hypersensitivity to efavirenz, should not take efavirenz/emtricitabine/tenofovir. Drugs that are contraindicated 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.<ref name="Atripla FDA label"/> |
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== Background == |
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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.<ref>{{cite web | author= | title=HIV Medication List - AIDS Drugs: | url=http://www.aidsdrugsonline.com/index.php?option=com_content&view=article&id=50&Itemid=27 | work=AIDS Drugs HIV Reference | publisher=aidsdrugsonline | year=2009 | accessdate=2010-01-03}} {{Dead link|date=October 2010|bot=H3llBot}}</ref> 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 ] and consequently there will be a drop in the amount of generic HIV medicines available. |
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== Side effects == |
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== Side effects == |
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Common side effects of Atripla are tiredness, dizziness, stomach and intestinal upset, and skin discoloration. More severe side effects are hallucinations, sleeplessness and depression.<ref name=side-effects>{{cite web | author= | title=Possible Side Effects of ATRIPLA | url=http://www.atripla.com/Content.aspx?bmscontentpg=atripla-side-effects | publisher=Bristol-Myers Squibb & Gilead Sciences, LLC | year=2008 | accessdate=2010-01-03}}</ref> |
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Common side effects of efavirenz/emtricitabine/tenofovir are tiredness, dizziness, gastrointestinal distress, and skin discoloration. More severe side effects are hallucinations, sleeplessness and depression.<ref name="side-effects">{{cite web | title=Possible Side Effects of Atripla | url=http://www.atripla.com/Content.aspx?bmscontentpg=atripla-side-effects | publisher=Bristol-Myers Squibb & Gilead Sciences, LLC | year=2008 | access-date=3 January 2010}}</ref> |
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Recommended dosage for efavirenz/emtricitabine/tenofovir is one tablet at or before bedtime. Side effects can be reduced if it is taken on an empty stomach. People with kidney or liver problems can take one tablet by mouth once a day. However, people 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.<ref>{{cite web|title=Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents.|url=http://aidsinfo.nih.gov/contentfiles/lvguidelines/adultandadolescentgl.pdf|access-date=19 October 2012|url-status=live|archive-url=https://web.archive.org/web/20161101202407/https://aidsinfo.nih.gov/contentfiles/lvguidelines/adultandadolescentgl.pdf|archive-date=1 November 2016}}</ref> |
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== Interactions == |
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== Interactions == |
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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.<ref>{{cite web | author= | title=Medicines You Should Not Take with ATRIPLA | url=http://www.atripla.com/Content.aspx?bmscontentpg=hiv-medications | publisher=Bristol-Myers Squibb & Gilead Sciences, LLC | year=2008 | accessdate=2010-01-03}}</ref> |
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Medications that should not be taken with efavirenz/emtricitabine/tenofovir include bepridil, midazolam, pimozide, triazolam, or ergot derivatives. Additionally, St. John's wort is known to reduce the effectiveness of efavirenz/emtricitabine/tenofovir, resulting in increased viral load and possible resistance to efavirenz/emtricitabine/tenofovir.<ref>{{cite web | title=Medicines You Should Not Take with Atripla | url=http://www.atripla.com/Content.aspx?bmscontentpg=hiv-medications | publisher=Bristol-Myers Squibb & Gilead Sciences, LLC | year=2008 | access-date=3 January 2010 | archive-url=https://web.archive.org/web/20100425050127/http://www.atripla.com/Content.aspx?bmscontentpg=hiv-medications | archive-date=25 April 2010 | url-status=dead }}</ref> |
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== References == |
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== Mechanism of action == |
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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.<ref name="Atripla FDA label">{{cite web | title=Atripla- efavirenz, emtricitabine, and tenofovir disoproxil fumarate tablet, film coated | website=DailyMed | date=5 November 2019 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2e97aa6d-09f7-46df-9499-63db7e9bac35 | access-date=3 February 2020}}</ref> |
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{{Reflist|2}} |
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In combination studies there were synergistic antiviral effects observed between emtricitabine and efavirenz, efavirenz and tenofovir, and emtricitabine and tenofovir.<ref name="Atripla FDA label"/> |
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==External links== |
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* managed by ] and ] |
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* article on The Body, an HIV reference site |
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== History == |
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{{HIVpharm|state=collapsed}} |
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Efavirenz/emtricitabine/tenofovir was approved in the United States to treat HIV in 2006. The main advantage of the new drug was that it could be taken once daily and reduce the overall stress in an antiretroviral regimen.<ref>{{cite web|title=HIV Medication List - AIDS Drugs |url=http://www.aidsdrugsonline.com/index.php?option=com_content&view=article&id=50&Itemid=27 |work=AIDS Drugs HIV Reference |publisher=aidsdrugsonline |year=2009 |access-date=3 January 2010 |url-status=dead |archive-url=https://web.archive.org/web/20081226083124/http://www.aidsdrugsonline.com/index.php?option=com_content&view=article&id=50&Itemid=27 |archive-date=26 December 2008 }}</ref> 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 ]<ref>{{cite web|url=http://www.unitaid.eu/en/resources/news/348-medicines-patent-pool-signs-licence-agreement-with-gilead-to-increase-access-to-hivaids-medicines|title=Medicines Patent Pool Signs Licence Agreement with Gilead to Increase Access to HIV/AIDS Medicines|url-status=dead|archive-url=https://web.archive.org/web/20140219024509/http://www.unitaid.eu/en/resources/news/348-medicines-patent-pool-signs-licence-agreement-with-gilead-to-increase-access-to-hivaids-medicines|archive-date=19 February 2014}}</ref> and Merck and Co makes efavirenz available in developing countries at a reduced price.<ref>{{cite web|url=http://www.aidsmap.com/Merck-cuts-price-of-efavirenz-for-developing-countries-again/page/1426314/|title=HIV & AIDS Information :: Merck cuts price of efavirenz for developing countries again|date=16 February 2007 |url-status=live|archive-url=https://web.archive.org/web/20140219082823/http://www.aidsmap.com/Merck-cuts-price-of-efavirenz-for-developing-countries-again/page/1426314/|archive-date=19 February 2014}}</ref> |
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==Society and culture== |
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{{DEFAULTSORT:Emtricitabine/Tenofovir/Efavirenz}} |
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It 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.<ref>{{cite web | title=Search for Tradename: Atripla | url=http://drugpatentwatch.com/ultimate/preview/tradename/index.php?query=Atripla | work=Drug Patent Watch | year=2010 | access-date=3 January 2010 | url-status=live | archive-url=https://web.archive.org/web/20110815065957/http://drugpatentwatch.com/ultimate/preview/tradename/index.php?query=Atripla | archive-date=15 August 2011 }}</ref> |
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In much of the developing world marketing and distribution is handled by ]<ref>{{cite web |title=Merck To Register, Lower Cost Of Antiretroviral Atripla In Developing Countries |url=http://www.medicalnewstoday.com/articles/63612.php |work=Medical News Today |date=23 February 2007 |access-date=3 January 2010 |url-status=dead |archive-url=https://web.archive.org/web/20100703142822/http://www.medicalnewstoday.com/articles/63612.php |archive-date=3 July 2010 }}</ref> |
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== References == |
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{{Reflist}} |
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{{Antiretroviral drug}} |
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{{Portal bar | Medicine | Viruses }} |
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{{DEFAULTSORT:Efavirenz Emtricitabine Tenofovir Disoproxil}} |
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