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 adults and adolescents aged 12 years of age and older who weigh at least 40 kilograms (88 lb). [3] [4]

Adverse effects

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

See individual agents as well as other combination products for additional information.

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 ] Dolutegravir and abacavir were shown to be excreted in the milk of lactating rats.[ medical citation needed ] Lamivudine was shown to be excreted in human breast milk. [11]

History

Approval

The patent was filed on April 28, 2006, [12] and expires on October 5, 2027. [13] It was approved for use in the United States and in the European Union in 2014. [5] [4]

Major label changes

In August 2015, the Food and Drug Administration (FDA) sent a bulletin regarding label updates for dolutegravir and Triumeq regarding drug-drug information. [11]

Drug interactions was updated to include a statement that in vitro, dolutegravir was not a substrate of OATP1B1 or OATP1B3. [11] Furthermore, information regarding drug interactions with carbamazepine and metformin. [11]

Additionally, less common adverse reactions observed in clinical trials was updated to include suicidal ideation, attempt, behavior, or completion in order to be consistent with dolutegravir label. [14]

In September 2015, the FDA added a boxed warning of hypersensitivity reactions, lactic acidosis, and severe hepatomegaly in abacavir-containing products regarding HLA-B*507 allele. [15]

Boxed warning (9/2015)

Dosage and administration

Contraindications (9/2015)

Warnings and precautions, hypersensitivity reactions (9/2015)

Society and culture

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. [16]

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. [17]

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. [18] [19] 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%. [19] The trial has since progressed to Phase 3.[ citation needed ]

Related Research Articles

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 trade 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">Nevirapine</span> Chemical compound

Nevirapine (NVP), sold under the brand name Viramune among others, is a medication used to treat and prevent HIV/AIDS, specifically HIV-1. It is generally recommended for use with other antiretroviral medications. It may be used to prevent mother to child spread during birth but is not recommended following other exposures. It is taken by mouth.

<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">Emtricitabine/tenofovir</span> Drug combination for HIV/AIDS prophylaxis and treatment

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

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

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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

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

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

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Dolutegravir/lamivudine, sold under the brand name Dovato, is a fixed-dose combination antiretroviral medication for the treatment of HIV/AIDS. It contains dolutegravir, as the salt, an integrase strand transfer inhibitor (INSTI), and 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 "Triumeq- abacavir sulfate, dolutegravir sodium, lamivudine tablet, film coated". DailyMed. March 23, 2021. Retrieved April 1, 2022.
  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 3 4 5 "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. ↑ "Tivicay (dolutegravir) and Triumeq (abacavir/dolutegravir/lamivudine) product labeling was updated". U.S. Food & Drug Administration (FDA). Archived from the original on December 22, 2015. Retrieved December 15, 2015.
  15. ↑ "Safety Information - Ziagen (abacavir sulfate) Tablets and Oral Solution". www.fda.gov. Archived from the original on December 22, 2015. Retrieved December 15, 2015.
  16. ↑ Palmer E (July 2, 2015). "GSK's ViiV turns to Chinese company for cheap supply of Tivicay API". Fierce Pharma. Retrieved December 15, 2015.
  17. ↑ 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
  18. ↑ 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.
  19. 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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