Abacavir/dolutegravir/lamivudine

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Abacavir/dolutegravir/lamivudine
Abacavir, dolutegravir and lamivudine.svg
Combination of
Abacavir nucleoside analog reverse transcriptase inhibitor
Dolutegravir integrase inhibitor
Lamivudine nucleoside analog reverse transcriptase inhibitor
Clinical data
Trade names Triumeq, Triumeq PD
AHFS/Drugs.com Monograph
MedlinePlus a617015
License data
Pregnancy
category
  • AU:B3
Routes of
administration 		By mouth
ATC code
Legal status
Legal status
Identifiers
CAS Number
PubChem CID
ChemSpider
  • none
KEGG

Abacavir/dolutegravir/lamivudine, sold under the brand name Triumeq among others, is a fixed-dose combination antiretroviral medication for the treatment of HIV/AIDS. [3] It is a combination of three medications with different and complementary mechanisms of action: abacavir (reverse transcriptase inhibitor), dolutegravir (integrase inhibitor) and lamivudine (nucleoside analog reverse transcriptase inhibitor). [3]

Contents

The medication was developed by ViiV Healthcare and was approved for use in the United States and in the European Union in 2014. [4] [5] [6]

Abacavir is a nucleotide reverse transcriptase inhibitor. [3] Specifically, abacavir is a guanosine analogue that interferes with HIV viral RNA-dependent DNA polymerase, ultimately resulting in inhibition of replication of HIV. Dolutegravir inhibits the HIV replication cycle by binding to the integrase active site and inhibiting the strand transfer step of HIV-1 DNA integration. Lamivudine is a cytosine analogue that inhibits HIV reverse transcription by terminating the viral DNA chain. [7]

Medical uses

Abacavir/dolutegravir/lamivudine is indicated for the treatment of HIV/AIDS in people aged twelve years of age and older who weigh at least 40 kilograms (88 lb). [3] [4]

Adverse effects

The US FDA label contains a boxed warning of hypersensitivity reactions and exacerbations of hepatitis B. [3]

The following adverse reactions were reported in <2% of patients: [3] [7]

Pregnancy

Abacavir/dolutegravir/lamivudine should only be used in pregnancy if the potential benefits outweigh the risks. [3] [8]

Breastfeeding

The US Centers for Disease Control and Prevention (CDC) recommends that HIV-infected mothers do not breastfeed their infants to avoid risking postnatal transmission of HIV. [9] [10] This recommendation is coupled with the potential for serious adverse reactions in nursing infants.[ medical citation needed ] Lamivudine was shown to be excreted in human breast milk. [11]

History

The patent was filed in April 2006, [12] and expires in October 2027. [13]

Society and culture

The combination was approved for use in the United States and in the European Union in 2014. [5] [4]

Economics

A year supply of abacavir/dolutegravir/lamivudine costs around US$33,000 as it is under patent and not available as a generic. [7]

In July 2015, ViiV Healthcare struck a deal with Shanghai-based Desano Pharmaceuticals for a cheaper supply of dolutegravir (Tivicay) with the goal of cutting the cost in China and other developing countries. After approval of dolutegravir (Tivicay) in 2014, it came with a retail cost of $14,000 per year in the United States. [14]

Research

Clinical trials

Efficacy of abacavir/dolutegravir/lamivudine was demonstrated in antiretroviral treatment-naive participants by SINGLE (ING114467), the randomized, controlled trial and other trials in treatment-naive subjects (see dolutegravir).[ citation needed ]

In the SINGLE trial, 414 participants received dolutegravir + abacavir/lamivudine once daily and 419 participants received efavirenz/emtricitabine/tenofovir once daily. dolutegravir + abacavir/lamivudine compared to efavirenz/emtricitabine/tenofovir showed a reduction in viral load of HIV-1 RNA <50 copies/mL in 80% of participants compared to 72% of participants, respectively. Furthermore, in participants with baseline plasma viral load of <100,000 and >100,000 copies/mL, dolutegravir + abacavir/lamivudine compared to efavirenz/emtricitabine/tenofovir showed a reduction to <50 copies/mL in 85% and 71% compared to 73% and 72%, respectively. [15]

Post-marketing experience

In addition to the adverse reactions reported in clinical trials, the following adverse reactions have been reported voluntarily from a population of unknown size. As such, it is not always possible to estimate frequency or establish a causal relationship to drug exposure. [11]

Abacavir and/or Lamivudine

Amyotrophic lateral sclerosis

The safety and tolerability of Triumeq was evaluated for amyotrophic lateral sclerosis (ALS) patients as part of the Lighthouse trial, an open-label, phase 2a study, conducted in Australia beginning in late 2016 over 24 weeks. [16] [17] The study premise was human endogenous retroviruses, specifically human endogenous retrovirus K (HERV-K) may be a trigger or cause of ALS. Research has linked HERV-K to ALS based on increased nonspecific reverse transcriptase activity in the cerebrospinal fluid and blood of ALS patients, as well as HERV-K being found in the motor neurons of ALS patients. Triumeq was chosen as all three component drugs have good penetration of the central nervous system, particularly dolutegravir, which has high clearance rates for CNS HIV. The study found a significant decrease in HERV-K DNA in serum among study participants and showed a decrease in the slope of clinical progression based on the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) of roughly 30%. [17] The trial has since progressed to Phase 3.[ citation needed ]

Related Research Articles

The management of HIV/AIDS normally includes the use of multiple antiretroviral drugs as a strategy to control HIV infection. There are several classes of antiretroviral agents that act on different stages of the HIV life-cycle. The use of multiple drugs that act on different viral targets is known as highly active antiretroviral therapy (HAART). HAART decreases the patient's total burden of HIV, maintains function of the immune system, and prevents opportunistic infections that often lead to death. HAART also prevents the transmission of HIV between serodiscordant same-sex and opposite-sex partners so long as the HIV-positive partner maintains an undetectable viral load.

Reverse-transcriptase inhibitors (RTIs) are a class of antiretroviral drugs used to treat HIV infection or AIDS, and in some cases hepatitis B. RTIs inhibit activity of reverse transcriptase, a viral DNA polymerase that is required for replication of HIV and other retroviruses.

<span class="mw-page-title-main">Lamivudine</span> Chemical compound

Lamivudine, commonly called 3TC, is an antiretroviral medication used to prevent and treat HIV/AIDS. It is also used to treat chronic hepatitis B when other options are not possible. It is effective against both HIV-1 and HIV-2. It is typically used in combination with other antiretrovirals such as zidovudine, dolutegravir, and abacavir. Lamivudine may be included as part of post-exposure prevention in those who have been potentially exposed to HIV. Lamivudine is taken by mouth as a liquid or tablet.

<span class="mw-page-title-main">Abacavir</span> Chemical compound

Abacavir, sold under the brand name Ziagen among others, is a medication used to treat HIV/AIDS. Similar to other nucleoside analog reverse-transcriptase inhibitors (NRTIs), abacavir is used together with other HIV medications, and is not recommended by itself. It is taken by mouth as a tablet or solution and may be used in children over the age of three months.

<span class="mw-page-title-main">Emtricitabine</span> Antiretroviral drug used to treat HIV infection

Emtricitabine, with trade name Emtriva, is a nucleoside reverse-transcriptase inhibitor (NRTI) for the prevention and treatment of HIV infection in adults and children. In 2019, it was the 494th most commonly prescribed medication in the United States, with more than 3 thousand prescriptions.

ATC code J05Antivirals for systemic use is a therapeutic subgroup of the Anatomical Therapeutic Chemical Classification System, a system of alphanumeric codes developed by the World Health Organization (WHO) for the classification of drugs and other medical products. Subgroup J05 is part of the anatomical group J Antiinfectives for systemic use.

<span class="mw-page-title-main">Tenofovir disoproxil</span> Antiviral drug used to treat or prevent HIV and hepatitis infections

Tenofovir disoproxil, sold under the brand name Viread among others, is a medication used to treat chronic hepatitis B and to prevent and treat HIV/AIDS. It is generally recommended for use with other antiretrovirals. It may be used for prevention of HIV/AIDS among those at high risk before exposure, and after a needlestick injury or other potential exposure. It is sold both by itself and together in combinations such as emtricitabine/tenofovir, efavirenz/emtricitabine/tenofovir, and elvitegravir/cobicistat/emtricitabine/tenofovir. It does not cure HIV/AIDS or hepatitis B. It is available by mouth as a tablet or powder.

<span class="mw-page-title-main">Efavirenz</span> Antiretroviral medication

Efavirenz (EFV), sold under the brand names Sustiva among others, is an antiretroviral medication used to treat and prevent HIV/AIDS. It is generally recommended for use with other antiretrovirals. It may be used for prevention after a needlestick injury or other potential exposure. It is sold both by itself and in combination as efavirenz/emtricitabine/tenofovir. It is taken by mouth.

<span class="mw-page-title-main">Abacavir/lamivudine/zidovudine</span> Mixture of chemical compounds

Abacavir/lamivudine/zidovudine, sold under the brand name Trizivir, is a fixed-dose combination antiretroviral medication for the treatment of HIV/AIDS. It contains three reverse transcriptase inhibitors patented by GlaxoSmithKline and marketed by a joint venture with Pfizer, ViiV Healthcare:

<span class="mw-page-title-main">Efavirenz/emtricitabine/tenofovir</span> Combination drug for HIV

Efavirenz/emtricitabine/tenofovir, sold under the brand name Atripla among others, is a fixed-dose combination antiretroviral medication used to treat HIV/AIDS. It contains efavirenz, emtricitabine, and tenofovir disoproxil. It can be used by itself or together with other antiretroviral medications. It is taken by mouth.

<span class="mw-page-title-main">Raltegravir</span> Chemical compound

Raltegravir, sold under the brand name Isentress, is an antiretroviral medication used, together with other medication, to treat HIV/AIDS. It may also be used, as part of post exposure prophylaxis, to prevent HIV infection following potential exposure. It is taken by mouth.

Integrase inhibitors (INIs) are a class of antiretroviral drug designed to block the action of integrase, a viral enzyme that inserts the viral genome into the DNA of the host cell. Since integration is a vital step in retroviral replication, blocking it can halt further spread of the virus. Integrase inhibitors were initially developed for the treatment of HIV infection, but have been applied to other retroviruses. The class of integrase inhibitors called integrase strand transfer inhibitors (INSTIs) are in established medical use. Other classes, such as allosteric integrase inhibitors (ALLINIs) or integrase binding inhibitors (INBIs), are still experimental.

<span class="mw-page-title-main">Abacavir/lamivudine</span> Combination drug for HIV

Abacavir/lamivudine, sold under the brand name Kivexa among others, is a fixed-dose combination antiretroviral medication used to treat HIV/AIDS. It contains abacavir and lamivudine. It is generally recommended for use with other antiretrovirals. It is commonly used as part of the preferred treatment in children. It is taken by mouth as a tablet.

<span class="mw-page-title-main">Rilpivirine</span> HIV treatment

Rilpivirine, sold under the brand names Edurant and Rekambys, is a medication, developed by Tibotec, used for the treatment of HIV/AIDS. It is a second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) with higher potency, longer half-life and reduced side-effect profile compared with older NNRTIs such as efavirenz.

Discovery and development of nucleoside and nucleotide reverse-transcriptase inhibitors began in the 1980s when the AIDS epidemic hit Western societies. NRTIs inhibit the reverse transcriptase (RT), an enzyme that controls the replication of the genetic material of the human immunodeficiency virus (HIV). The first NRTI was zidovudine, approved by the U.S. Food and Drug Administration (FDA) in 1987, which was the first step towards treatment of HIV. Six NRTI agents and one NtRTI have followed. The NRTIs and the NtRTI are analogues of endogenous 2´-deoxy-nucleoside and nucleotide. Drug-resistant viruses are an inevitable consequence of prolonged exposure of HIV-1 to anti-HIV drugs.

<span class="mw-page-title-main">Dolutegravir</span> Chemical compound

Dolutegravir (DTG), sold under the brand name Tivicay, is an antiretroviral medication used, together with other medication, to treat HIV/AIDS. It may also be used, as part of post exposure prophylaxis, to prevent HIV infection following potential exposure. It is taken by mouth.

<span class="mw-page-title-main">Tenofovir alafenamide</span> Chemical compound

Tenofovir alafenamide, sold under the brand name Vemlidy, is an antiviral medication used against hepatitis B and HIV. It is used for the treatment of chronic hepatitis B virus (HBV) infection in adults with compensated liver disease and is given in combination with other medications for the prevention and treatment of HIV. It is taken by mouth.

Elvitegravir/cobicistat/emtricitabine/tenofovir, sold under the brand name Stribild, also known as the Quadpill, is a fixed-dose combination antiretroviral medication for the treatment of HIV/AIDS. Elvitegravir, emtricitabine and tenofovir disoproxil directly suppress viral reproduction. Cobicistat increases the effectiveness of the combination by inhibiting the liver and gut wall enzymes that metabolize elvitegravir. It is taken by mouth.

<span class="mw-page-title-main">Cabotegravir</span> Medication for HIV/AIDS

Cabotegravir, sold under the brand name Vocabria among others, is a antiretroviral medication used for the treatment of HIV/AIDS. It is available in the form of tablets and as an intramuscular injection, as well as in an injectable combination with rilpivirine under the brand name Cabenuva.

Dolutegravir/lamivudine, sold under the brand name Dovato, is a fixed-dose combination antiretroviral medication for the treatment of HIV/AIDS. each pill contains 50 mg dolutegravir, as the salt, an integrase strand transfer inhibitor (INSTI), and 300 mg lamivudine, a nucleoside analogue reverse transcriptase inhibitor (NRTI). It is taken by mouth.

References

  1. ↑ "Drug and medical device highlights 2018: Helping you maintain and improve your health". Health Canada . October 14, 2020. Retrieved April 17, 2024.
  2. ↑ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA . Retrieved October 22, 2023.
  3. 1 2 3 4 5 6 7 8 "Triumeq - abacavir sulfate, dolutegravir sodium, lamivudine tablet, film coated; Triumeq PD - abacavir sulfate, dolutegravir sodium, lamivudine kit". DailyMed. April 18, 2024. Retrieved June 21, 2024.
  4. 1 2 3 4 "Triumeq EPAR". European Medicines Agency (EMA). Retrieved April 7, 2020.
  5. 1 2 "Triumeq (abacavir sulfate, dolutegravir, and lamivudine), Fixed-Dose Combination Tablets". U.S. Food and Drug Administration (FDA). August 11, 2015. Retrieved April 7, 2020.
  6. ↑ "FDA Approves Triumeq". drugs.com. August 22, 2014.
  7. 1 2 3 "Login" . Lexicomp. Retrieved December 10, 2015.
  8. ↑ "FDA: Potential Risk of Neural Tube Birth Defects". Food and Drug Administration . Archived from the original on July 24, 2018. Retrieved May 19, 2018.
  9. ↑ "Human immunodeficiency virus (HIV)". U.S. Centers for Disease Control and Prevention (CDC). March 2, 2022. Retrieved April 1, 2022.
  10. ↑ "HIV and Pregnant Women, Infants, and Children". U.S. Centers for Disease Control and Prevention (CDC). March 7, 2022. Retrieved April 1, 2022.
  11. 1 2 "Triumeq". ViiV Healthcare. Archived from the original on December 22, 2015. Retrieved December 15, 2015.
  12. ↑ US 8129385,Johns BA, Kawasuji T, Taishi T, Taoda Y,"Substituted 5-hydroxy-3,4,6,9,9a, 10-hexanhydro-2h-1-oxa04a,8a-diaza-anthracene-6,10-dioness",issued 6 March 2012, assigned to Shionogi & Co., Ltd. (Osaka, JP)and GlaxoSmithKline LLC (Philadelphia, PA)[ permanent dead link ]
  13. ↑ "Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations". U.S. Food and Drug Administration (FDA). Retrieved December 10, 2015.
  14. ↑ Palmer E (July 2, 2015). "GSK's ViiV turns to Chinese company for cheap supply of Tivicay API". Fierce Pharma. Retrieved December 15, 2015.
  15. ↑ Clinical trial number NCT01263015 for "A Trial Comparing GSK1349572 50mg Plus Abacavir/Lamivudine Once Daily to Atripla (Also Called The SINGLE Trial" at ClinicalTrials.gov
  16. ↑ Gold J, Rowe DB, Kiernan MC, Vucic S, Mathers S, van Eijk RP, et al. (November 2019). "Safety and tolerability of Triumeq in amyotrophic lateral sclerosis: the Lighthouse trial". Amyotrophic Lateral Sclerosis & Frontotemporal Degeneration. 20 (7–8): 595–604. doi: 10.1080/21678421.2019.1632899 . PMID   31284774. S2CID   195843560.{{cite journal}}: CS1 maint: overridden setting (link)
  17. 1 2 Pridmore W (February 19, 2021). "Updates from the fray: rational off-label and over-the-counter prescribing in amyotrophic lateral sclerosis". RRNMF Neuromuscular Journal. 2 (1). doi: 10.17161/rrnmf.v2i1.14789 . ISSN   2692-3092. S2CID   234923415.
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