Emtricitabine/tenofovir

This article is about the combination emtricitabine/tenofovir disoproxil. For the combination emtricitabine/tenofovir alafenamide, see Tenofovir alafenamide.

Emtricitabine/tenofovir
Combination of
EmtricitabineNucleoside reverse transcriptase inhibitor
Tenofovir disoproxilNucleotide analogue reverse transcriptase inhibitor
Names
Trade namesTruvada, Tenvir-EM, other
Other namesEmtricitabine/tenofovir disoproxil fumarate
Clinical data
WHO AWaReUnlinkedWikibase error: ⧼unlinkedwikibase-error-statements-entity-not-set⧽
Pregnancy
category
  • AU: B3[1]
  • US: N (Not classified yet)[1]
    Routes of
    use    		By mouth
    External links
    AHFS/Drugs.comMonograph
    MedlinePlusa612036
    Legal
    License data
    Legal status
    • AU: S4 (Prescription only)
    • CA: ℞-only
    • UK: POM (Prescription only)
    • US: ℞-only
    • In general: ℞ (Prescription only)

    Emtricitabine/tenofovir (FTC/TDF), sold under the brand name Truvada among others, is a fixed-dose combination medication used to treat and prevent HIV/AIDS.[2][3] It contains the antiretroviral medications emtricitabine and tenofovir disoproxil.[4] For treatment, it is used either alone or together with other antiretroviral medications.[4][5] For prevention before exposure, in those who are at high risk, it is recommended with safe sex practices.[4] It does not cure HIV/AIDS.[2] Emtricitabine/tenofovir is taken by mouth.[6]

    Common side effects include headache, tiredness, trouble sleeping, abdominal pain, weight loss, and rash.[2] Serious side effects may include high blood lactate levels and enlargement of the liver.[4] Use of this medication during pregnancy does not appear to harm the baby, but has not been well studied.[1]

    Emtricitabine/tenofovir was approved for medical use in the United States in 2004.[2] It is on the World Health Organization's List of Essential Medicines.[7] In the United States, emtricitabine/tenofovir is under patent until 2020, but is available as a generic in the rest of the world.[8] The 2015 wholesale cost in the developing world is about US$6 to US$8 per month.[6] In the United States, as of 2019, the wholesale cost is about US$1,710 per month.[9] In Australia, this amount costs about US$8.[8]

    Medical uses

    Emtricitabine/tenofovir is used both to treat and to prevent HIV/AIDS.[2] It is a tablet taken by mouth.[6] The U.S. National Institutes of Health (NIH) recommends antiretroviral therapy (ART) for all people with HIV/AIDS.[10]

    HIV prevention

    The Centers for Disease Control and Prevention (CDC) recommends the use of emtricitabine/tenofovir for pre-exposure prophylaxis (PrEP) for uninfected, HIV-1 negative individuals that may be at risk for HIV-1 infection.[11][4] A Cochrane review found that both tenofovir alone, as well as the tenofovir/emtricitabine combination, decreased the risk of contracting HIV by 51%.[12] It was approved for PrEP against HIV infection in the United States in 2012.[13]

    The CDC recommends PrEP be considered for the following high-risk groups:[14]

    • Individuals in an ongoing sexual relationship with an HIV-positive partner
    • Gay or bisexual men who either have had anal sex without a condom or been diagnosed with an STD in the past six months
    • Heterosexual men or women who do not regularly use condoms during sex with partners of unknown HIV status who are substantial risk
    • Injection of drugs in the last six months with sharing of equipment
    • Sero-discordant heterosexual and homosexual partners where one partner is HIV-positive and the other HIV-negative

    The consideration of utilizing emtricitabine/tenofovir as a reduction strategy involves discussion with a health professional who can help the patient navigate the benefits and risks. Patients are advised to discuss any history of bone issues, kidney issues, of hepatitis B infection with their health care provider.[15]

    People who start taking emtricitabine/tenofovir see HIV reduction benefit up to 72 hours after starting, but the medicine must be taken for thirty days after a high-risk sexual event to ensure HIV transmission levels are optimally reduced.[16][17] Effectiveness of PrEP for prevention of infection is reliant on an individual's ability to take the medication consistently.[18]

    Truvada as PrEP should not be used for individuals that are positive for HIV-1.[4]

    HIV treatment

    Emtricitabine/tenofovir has been approved in the United States as part of antiretroviral combination therapy for the treatment of HIV-1.[4] The combination therapy is suggested as one of the options for adults who have not received any prior treatment for HIV infection.[19]

    Hepatitis B

    Both emtricitabine and tenofovir are indicated for the treatment of hepatitis B, with the added benefit that they can target HIV for those with co-infection.[20] Emtricitabine/tenofovir may also be considered for some antiviral resistant hepatitis B infections.[21]

    Pregnancy and breastfeeding

    In the United States, it is recommend that all pregnant HIV-infected women start antiretroviral therapy (ART) as early in pregnancy as possible to reduce risk of transmission. ART generally does not increase risk of birth defects with exception of dolutegravir, which is not recommended during first trimester of pregnancy only due to potential risk of neural tube defects.[22]

    Emtricitabine/tenofovir is secreted in breast milk.[23] In developed countries, HIV-infected mothers are generally recommended to not breastfeed due to slight risk of mother-to-children HIV transmission.[24][25] In developing countries, where avoiding breastfeeding may not be an option, the World Health Organization recommends a triple drug regimen of tenofovir, efavirenz, and either lamivudine or emtricitabine.[25]

    Side effects

    Emtricitabine/tenofovir is generally well tolerated. Some of its side effects include:[4]

    • Rare: lactic acidosis, liver dysfunction, worsening of hepatitis B infection
    • Common: headache, abdominal pain, decreased weight, nausea, diarrhea, and decreased bone density

    Fat redistribution and accumulation (lipodystrophy) has been observed in people receiving antiretroviral therapy, including fat reductions in the face, limbs, and buttocks and increases in visceral fat of the abdomen and accumulations in the upper back.[4] When used as pre-exposure prophylaxis (PrEP) this effect may not be present.[26] Weight changes have however been linked to the medication.[27]

    Drug interactions

    Drug-drug interactions[4]
    Drug-drug Interaction Coadministration
    Tenofovir Didanosine
    • May increase didanosine concentration and risk of didanosine toxicity (e.g. pancreatitis, neuropathy).
    • Discontinue didanosine if patient develops didanosine-associated adverse events.
    • For patients who weigh more than 60 kg, didanosine dose should be reduced to 250 mg; there is no available data to recommend didanosine dose adjustments in patients who weigh less than 60 kg.
    Atazanavir
    • May decrease atazanavir and increase tenofovir concentrations.
    • Atazanavir should only be taken together with emtricitabine/tenofovir with ritonavir.
    • Monitor for tenofovir toxicity.
    Lopinavir/ritonavir, atazanavir coadministered with ritonavir & darunavir coadministered with ritonavir
    • May increase tenofovir concentrations.
    Ledipasvir/sofosbuvir
    • May increase tenofovir concentrations.
    • Consider alternative Hepatitis C antiviral or antiretroviral therapy.
    • Monitor for tenofovir toxicity.
    Emtricitabine/tenofovir P-glycoprotein and breast cancer resistance protein (BCRP) transporters inhibitors
    • May increase absorption of emtricitabine/tenofovir.
    Drugs may decrease renal function (e.g. adefovir, acyclovir, adefovir, dipivoxil, cidofovir, ganciclovir, valacyclovir, valganciclovir, aminoglycosides, etc.)
    • May increase emtricitabine and/or tenofovir concentrations.
    High-dose or multiple NSAIDs
    Orlistat
    • May inhibit absorption of emtricitabine/tenofovir and result in loss of viral control.[28]
    • Monitor HIV viral load frequently while patient is taking orlistat.
    • Discontinue orlistat if HIV viral load increases.

    Other drugs with adverse reactions include dabigatran etexilate, lamivudine, and vincristine. Dabigatran etexilate used with p-glycoprotein inducers require monitoring of decreased levels and effects of dabigatran. Lamivudine may increase the adverse or toxic effect of emtricitabine. Vincristine used with P-glycoprotein/ABCB1 inducers can decrease the serum concentration of vincristine.[29]

    Society and culture

    Cost

    See also: Pre-exposure prophylaxis § Availability and pricing

    As of 2014, the median cost per tablet, in Namibia and South Africa, was US$0.20.[6] In Canada, emtricitabine/tenofovir cost between $800 - $1,100 per month in 2016.[30] Generic emtricitabine/tenofovir was approved by Health Canada in August 2017, with a wholesale cost of $400 per month.[31] The cost for emtricitabine/tenofovir PrEP in Ontario, Canada dropped significantly after approval in September 2017.[32]

    In the United States, as of 2016, the wholesale cost is about US$1,415.00 per month.[33] This increased in 2019 to about US$1,710.00 per month.[9] The price of emtricitabine/tenofovir in the United States has been criticized by activists, who argued in a 2018 The New York Times opinion piece that the high cost keeps the drug out of reach for millions, thus harming efforts to reduce new HIV infections.[34] The Gilead CEO defended the high price at a U.S. House of Representatives committee hearing.[35] Generic emtricitabine/tenofovir was approved in the United States in 2018,[36] and it is scheduled to be released by Teva in September 2020.[37]

    Emtricitabine/tenofovir can be dispensed by trained pharmacists in California, without a prescription, for a maximum of 60 days.[38][39][40]

    Patent status

    The patent for the combination is owned by Gilead Sciences in some regions. The European patent EP0915894B1[41] was due to expire in July 2017, however a case is due before the European Court of Justice seeking to extend the patent.[42] An Irish court rejected an injunction request to prevent the launch of generic Emtricitabine/tenofovir prior to the resolution of the case.[43]

    In 2019, Gilead Sciences challenged patents held by the United States for the drug combination.[44][45][46]

    References

    1. 1 2 3 "Emtricitabine / tenofovir Pregnancy and Breastfeeding Warnings". Drugs.com. 1 August 2018. Archived from the original on 10 October 2019. Retrieved 10 October 2019.
    2. 1 2 3 4 5 "Truvada". Drugs.com. Archived from the original on 20 December 2016. Retrieved 12 December 2016.
    3. ↑ "UK label Truvada film-coated tablets". Electronic Medicines Compendium. August 2016. Archived from the original on 20 December 2016.
    4. 1 2 3 4 5 6 7 8 9 10 "Truvada- emtricitabine and tenofovir disoproxil fumarate tablet, film coated label". DailyMed. 18 May 2018. Archived from the original on 31 October 2019. Retrieved 31 October 2019.
    5. ↑ World Health Organization (2009). Stuart MC, Kouimtzi M, Hill SR (eds.). WHO Model Formulary 2008. World Health Organization. p. 160. hdl:10665/44053. ISBN 9789241547659.
    6. 1 2 3 4 "Tenofovir DF+Emtricitabine". International Drug Price Indicator Guide. Management Sciences for Health and World Health Organization. 2014. Archived from the original on 22 January 2018. Retrieved 1 August 2015.
    7. ↑ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
    8. 1 2 "AOC asks pharma CEO why $2,000 HIV drug costs just $8 in Australia". The Independent. 17 May 2019. Archived from the original on 15 November 2019. Retrieved 15 November 2019.
    9. 1 2 "NADAC as of 2019-11-13 | Data.Medicaid.gov". Centers for Medicare and Medicaid Services. Archived from the original on 15 November 2019. Retrieved 15 November 2019.
    10. ↑ "Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV" (PDF). AIDSinfo Clinical Guidelines. July 2019. Archived (PDF) from the original on 4 December 2016. Retrieved 30 October 2019.
    11. ↑ "PrEP". Centers for Disease Control and Prevention (CDC). 17 October 2019. Archived from the original on 31 October 2019. Retrieved 31 October 2019. Public Domain This article incorporates text from this source, which is in the public domain.
    12. ↑ Okwundu CI, Uthman OA, Okoromah CA (2012). "Antiretroviral pre-exposure prophylaxis (PrEP) for preventing HIV in high-risk individuals". Cochrane Database Syst Rev. 7 (7): CD007189. doi:10.1002/14651858.CD007189.pub3. PMID 22786505. S2CID 35672491.
    13. ↑ Perrone, Matthew (16 July 2012). "FDA approves first pill to help prevent HIV". The Seattle Times. Associated Press. Archived from the original on 19 July 2012.
    14. ↑ "Pre-Exposure Prophylaxis (PrEP)". Archived from the original on 5 June 2015. Retrieved 4 June 2015.{{cite web}}: CS1 maint: unfit URL (link)Public Domain This article incorporates text from this source, which is in the public domain.
    15. ↑ "Administration of pre-exposure prophylaxis against HIV infection". UpToDate. Archived from the original on 1 November 2019. Retrieved 31 October 2019.
    16. ↑ Panlilio AL, Cardo DM, Grohskopf LA, et al. (September 2005). "Updated U.S. Public Health Service guidelines for the management of occupational exposures to HIV and recommendations for postexposure prophylaxis" (PDF). MMWR Recomm Rep. 54 (RR-9): 1–17. PMID 16195697. Archived (PDF) from the original on 31 July 2020. Retrieved 10 October 2019.
    17. ↑ Kuhar DT, Henderson DK, Struble KA, et al. (September 2013). "Updated US Public Health Service guidelines for the management of occupational exposures to human immunodeficiency virus and recommendations for postexposure prophylaxis" (PDF). Infection Control and Hospital Epidemiology. 34 (9): 875–92. doi:10.1086/672271. PMID 23917901. 20711. Archived (PDF) from the original on 30 October 2019. Retrieved 30 October 2019.Public Domain This article incorporates text from this source, which is in the public domain.
    18. ↑ "Pre-exposure prophylaxis of HIV in adults at high risk: Truvada (emtricitabine/tenofovir disoproxil)". Archived from the original on 2 November 2019.
    19. ↑ "Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV" (PDF). Archived (PDF) from the original on 4 December 2016.
    20. ↑ "Update on Prevention, Diagnosis, and Treatment of Chronic Hepatitis B: AASLD 2018 Hepatitis B Guidance" (PDF). Archived (PDF) from the original on 25 January 2020.
    21. ↑ "Emtricitabine and Tenofovir Disoproxil Fumarate (Professional Patient Advice)". Drugs.com. Archived from the original on 31 July 2020. Retrieved 31 October 2019.
    22. ↑ "Brief What's New in the Guidelines Perinatal". AIDSinfo. Archived from the original on 23 October 2019. Retrieved 23 October 2019.
    23. ↑ "Recommendations for use of antiretroviral drugs in pregnant HIV-1-infected women for maternal health and interventions to reduce perinatal HIV transmission in the United States" (PDF). National Institutes of Health (NIH). Archived (PDF) from the original on 12 April 2014. Retrieved 21 October 2014.
    24. ↑ "Emtricitabine / tenofovir Use During Pregnancy". Drugs.com. Archived from the original on 10 October 2019. Retrieved 23 October 2019.
    25. 1 2 "Tenofovir". Drugs and Lactation Database (LactMed). National Library of Medicine (US). 2006. Archived from the original on 26 February 2021. Retrieved 23 October 2019.
    26. ↑ "PrEP does not raise lipids or alter body fat, safety study finds". Archived from the original on 17 February 2018. Retrieved 16 February 2018.
    27. ↑ Glidden DV, Mulligan K, McMahan V, et al. (July 2018). "Metabolic Effects of Preexposure Prophylaxis With Coformulated Tenofovir Disoproxil Fumarate and Emtricitabine". Clin. Infect. Dis. 67 (3): 411–419. doi:10.1093/cid/ciy083. PMC 6051460. PMID 29415175.
    28. ↑ "DailyMed - XENICAL- orlistat capsule". dailymed.nlm.nih.gov. Archived from the original on 27 February 2019. Retrieved 30 October 2019.
    29. ↑ Ramanathan S, Shen G, Cheng A, et al. (July 2007). "Pharmacokinetics of emtricitabine, tenofovir, and GS-9137 following coadministration of emtricitabine/tenofovir disoproxil fumarate and ritonavir-boosted GS-9137". J. Acquir. Immune Defic. Syndr. 45 (3): 274–9. doi:10.1097/QAI.0b013e318050d88c. PMID 17414929.
    30. ↑ "Pre-Exposure Prophylaxis (PrEP) as a form of HIV prevention". AIDS Committee of Toronto. Archived from the original on 4 November 2016. Retrieved 1 November 2016.
    31. ↑ "Generic tenofovir + FTC coming to Canada". www.catie.ca. Archived from the original on 30 August 2017. Retrieved 30 August 2017.
    32. ↑ "PrEP in Ontario" (PDF). AIDS Committee of Toronto. 28 September 2017. Archived (PDF) from the original on 31 October 2019. Retrieved 31 October 2019.
    33. ↑ "NADAC as of 2016-12-07". Centers for Medicare and Medicaid Services (CMS). Archived from the original on 21 December 2016. Retrieved 12 December 2016.
    34. ↑ Krellenstein, James; Lord, Aaron; Staley, Peter (16 July 2018). "Why Don't More Americans Use PrEP?". The New York Times. Archived from the original on 30 July 2018. Retrieved 30 July 2018.
    35. ↑ Grover, Natalie (17 May 2019). "Under fire for Truvada US pricing at House hearing, Gilead chief O'Day touts R&D costs, asserts governments patents are void". Endpoints News. Archived from the original on 1 November 2019. Retrieved 31 October 2019.
    36. ↑ "2018 First Generic Drug Approvals". U.S. Food and Drug Administration (FDA). 1 November 2019. Archived from the original on 30 October 2019. Retrieved 29 October 2019.Public Domain This article incorporates text from this source, which is in the public domain.
    37. ↑ "Gilead Sciences Form 10-Q Quarterly Filing". Gilead Sciences. 31 March 2019. Archived from the original on 30 October 2019. Retrieved 29 October 2019.
    38. ↑ Metz, Sam (7 October 2019). "Newsom signs bill allowing California pharmacists to give PrEP and PEP for HIV prevention". The Desert Sun. Archived from the original on 8 October 2019. Retrieved 9 October 2019.
    39. ↑ Zraick, Karen; Garcia, Sandra E. (9 October 2019). "California Makes H.I.V.-Prevention Drugs Available Without a Prescription". The New York Times. Archived from the original on 9 October 2019. Retrieved 9 October 2019.
    40. ↑ "Senate Bill No. 159 HIV: preexposure and postexposure prophylaxis". California Legislative Information. 8 October 2019. Archived from the original on 10 October 2019. Retrieved 9 October 2019.
    41. ↑ "EP0915894B1 - NUCLEOTIDE ANALOGS". Espacenet. Archived from the original on 30 January 2019. Retrieved 13 December 2017.
    42. ↑ "Gilead in row with generics manufacturers over HIV drug in Ireland". The Irish Times. Archived from the original on 7 November 2017. Retrieved 30 October 2017.
    43. ↑ "Gilead loss of generic HIV drug battle a boost for gay community". The Irish Times. Archived from the original on 18 May 2018. Retrieved 18 May 2018.
    44. ↑ Rowland, Christopher (24 April 2019). "Gilead defied a government HIV patent. The Justice Department has opened a review". The Washington Post. Archived from the original on 31 October 2019. Retrieved 31 October 2019.
    45. ↑ Rowland, Christopher (21 August 2019). "Gilead files challenge to government patents for HIV prevention pill". The Washington Post. Archived from the original on 31 October 2019. Retrieved 29 October 2019.
    46. ↑ "Petitions to US Patent and Trademark Office on HIV PrEP Patents". Gilead Sciences (Press release). 21 August 2019. Archived from the original on 30 October 2019. Retrieved 29 October 2019.
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