Abacavir

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Abacavir
Chemical structure of abacavir
Clinical data
Pronunciation/əˈbækəvɪər/ ⓘ
Trade namesZiagen
Other namesAbacavir sulfate (USAN US)
AHFS/Drugs.comMonograph
MedlinePlusa699012
License data
Pregnancy
category
  • AU: B3
Routes of
administration		By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability83%
MetabolismLiver
Elimination half-life1.54 ± 0.63 h
ExcretionKidney (1.2% abacavir, 30% 5'-carboxylic acid metabolite, 36% 5'-glucuronide metabolite, 15% unidentified minor metabolites). Fecal (16%)
Identifiers
  • {(1S,4R)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]cyclopent-2-en-1-yl}methanol
JSmol)
Melting point165 °C (329 °F)
  • n3c1c(ncn1[C@H]2/C=C\[C@@H](CO)C2)c(nc3N)NC4CC4
  • InChI=1S/C14H18N6O/c15-14-18-12(17-9-2-3-9)11-13(19-14)20(7-16-11)10-4-1-8(5-10)6-21/h1,4,7-10,21H,2-3,5-6H2,(H3,15,17,18,19)/t8-,10+/m1/s1 checkY
  • Key:MCGSCOLBFJQGHM-SCZZXKLOSA-N checkY
  (verify)

Abacavir, sold under the brand name Ziagen among others, is a

HIV medications, and is not recommended by itself.[7] It is taken by mouth as a tablet or solution and may be used in children over the age of three months.[5][8]

Abacavir is generally well tolerated.

HIV virus replication.[9] Within the NRTI class, abacavir is a carbocyclic nucleoside.[5]

Abacavir was patented in 1988, and approved for use in the United States in 1998.

generic medication.[5] Abacavir is used together with other HIV medications, such as abacavir/lamivudine/zidovudine, abacavir/dolutegravir/lamivudine, and abacavir/lamivudine.[8][9] The combination abacavir/lamivudine is an essential medicine.[12]

Medical uses

Abacavir, in combination with other antiretroviral agents, is

indicated for the treatment of HIV-1 infection.[3][4] Abacavir should be used in combination with other antiretroviral agents.[3][4]

Contraindications

Abacavir is contraindicated for people who have the HLA‑B*5701 allele or who have moderate or severe liver disease (hepatic impairment).[3][4]

Side effects

Common adverse reactions include nausea, headache, fatigue, vomiting, diarrhea, Anorexia (symptom) (loss of appetite), and insomnia (trouble sleeping). Rare but serious side effects include hypersensitivity reaction such as rash, elevated AST and ALT, depression, anxiety, fever/chills, URI, lactic acidosis, hypertriglyceridemia, and lipodystrophy.[13]

Hypersensitivity syndrome

Masai from Kenya, although the average values are derived from highly variable frequencies within sample groups.[20]

Common symptoms of abacavir hypersensitivity syndrome include

immune reconstitution syndrome, hypersensitivity syndromes associated with other drugs, or infection.[22] The U.S. Food and Drug Administration (FDA) released an alert concerning abacavir and abacavir-containing medications on 24 July 2008,[23] and the FDA-approved drug label for abacavir recommends pre-therapy screening for the HLA-B*5701 allele and the use of alternative therapy in subjects with this allele.[3] Additionally, both the Clinical Pharmacogenetics Implementation Consortium and the Dutch Pharmacogenetics Working Group recommend use of an alternative therapy in individuals with the HLA-B*5701 allele.[24][25]

Patch test

Skin-patch testing may also be used to determine whether an individual will experience a hypersensitivity reaction to abacavir, although some patients susceptible to developing AHS may not react to the patch test.[26]

The development of suspected hypersensitivity reactions to abacavir requires immediate and permanent discontinuation of abacavir therapy in all patients, including patients who do not possess the HLA-B*5701 allele. On 1 March 2011, the FDA informed the public about an ongoing safety review of abacavir and a possible increased risk of heart attack associated with the drug.[27] A meta-analysis of 26 studies conducted by the FDA, however, did not find any association between abacavir use and heart attack[28][29]

Immunopathogenesis

The mechanism underlying abacavir hypersensitivity syndrome is related to the change in the HLA-B*5701 protein product. Abacavir binds with high specificity to the HLA-B*5701 protein, changing the shape and chemistry of the antigen-binding cleft. This results in a change in immunological tolerance and the subsequent activation of abacavir-specific cytotoxic T cells, which produce a systemic reaction known as abacavir hypersensitivity syndrome.[17]

Interaction

Abacavir, and in general NRTIs, do not undergo hepatic metabolism and therefore have very limited (to none) interaction with the CYP enzymes and drugs that effect these enzymes. That being said there are still few interactions that can affect the absorption or the availability of abacavir. Below are few of the common established drug and food interaction that can take place during abacavir co-administration:

  • ritonovir may decrease the serum concentration of abacavir through induction of glucuronidation. Abacavir is metabolized by both alcohol dehydrogenase and glucuronidation.[30][31]
  • Ethanol may result in increased levels of abacavir through the inhibition of alcohol dehydrogenase. Abacavir is metabolized by both alcohol dehydrogenase and glucuronidation.[30][32]
  • Methadone may diminish the therapeutic effect of Abacavir. Abacavir may decrease the serum concentration of Methadone.[33][34]
  • Orlistat may decrease the serum concentration of antiretroviral drugs. The mechanism of this interaction is not fully established but it is suspected that it is due to the decreased absorption of abacavir by orlistat.[35]
  • Cabozantinib: Drugs from the MRP2 inhibitor (Multidrug resistance-associated protein 2 inhibitors) family such as abacavir could increase the serum concentration of Cabozantinib.[36]

Mechanism of action

Abacavir is a

transcription and HIV reverse transcriptase is inhibited.[37]

Pharmacokinetics

Abacavir is given orally and is rapidly absorbed with a high bioavailability of 83%.[38] Solution and tablet have comparable concentrations and bioavailability. Abacavir can be taken with or without food.[39]

Abacavir can cross the blood–brain barrier. Abacavir is metabolized primarily through the enzymes alcohol dehydrogenase and glucuronyl transferase to an inactive carboxylate and glucuronide metabolites. It has a half-life of approximately 1.5-2.0 hours. If a person has liver failure, abacavir's half life is increased by 58%.[40]

Abacavir is eliminated via excretion in the urine (83%) and feces (16%).[41] It is unclear whether abacavir can be removed by hemodialysis or peritoneal dialysis.[37]

History

Robert Vince and Susan Daluge along with Mei Hua, a visiting scientist from China, developed the medication in the '80s.[42][43][44]

Abacavir was approved by the U.S. Food and Drug Administration (FDA) on 18 December 1998, and is thus the fifteenth approved antiretroviral drug in the United States.[45] Its patent expired in the United States on 26 December 2009.[citation needed]

Synthesis

Abacavir synthesis:[46]

References

  1. FDA
    . Retrieved 22 October 2023.
  2. ^ "TGA eBS - Product and Consumer Medicine Information Licence". Archived from the original on 24 March 2022. Retrieved 23 August 2022.
  3. ^ a b c d e f "Ziagen- abacavir sulfate tablet, film coated label". DailyMed. 30 September 2015. Archived from the original on 11 January 2017. Retrieved 9 September 2019.
  4. ^ a b c d e f "Ziagen EPAR". European Medicines Agency. 17 September 2018. Archived from the original on 30 July 2022. Retrieved 22 August 2022. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  5. ^ a b c d e f g "Abacavir Sulfate". The American Society of Health-System Pharmacists. Archived from the original on 21 August 2017. Retrieved 31 July 2015.
  6. ^ "Drug Name Abbreviations Adult and Adolescent ARV Guidelines". AIDSinfo. Archived from the original on 9 November 2016. Retrieved 8 November 2016.
  7. ^ "What Not to Use Adult and Adolescent ARV Guidelines". AIDSinfo. Archived from the original on 9 November 2016. Retrieved 8 November 2016.
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  9. ^ a b "Nucleoside reverse transcriptase inhibitors (NRTIs or 'nukes') - HIV/AIDS". www.hiv.va.gov. Archived from the original on 9 November 2016. Retrieved 8 November 2016.
  10. ISBN 9783527607495. Archived
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  11. ISBN 9781438102078. Archived
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  12. ^
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    . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  13. ^ "Abacavir Adverse Reactions". Epocrates Online. Archived from the original on 23 August 2021. Retrieved 9 November 2012.
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  23. ^ "Information for Healthcare Professionals: Abacavir (marketed as Ziagen) and Abacavir-Containing Medications". Food and Drug Administration (FDA). 24 July 2008. Archived from the original on 11 December 2013. Retrieved 29 November 2013.
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  27. ^ "FDA Drug Safety Communication: Safety Review update of Abacavir and possible increased risk of heart attack". Food and Drug Administration (FDA). 1 March 2011. Archived from the original on 13 December 2019. Retrieved 9 September 2019.
  28. ^ "FDA Alert: Abacavir - Ongoing Safety Review: Possible Increased Risk of Heart Attack". Drugs.com. Archived from the original on 10 December 2013. Retrieved 29 November 2013.
  29. S2CID 7997822
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  30. ^ a b Prescribing information. Ziagen (abacavir). Research Triangle Park, NC: GlaxoSmithKline, July 2002
  31. S2CID 23591048
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  36. ^ Cometriq (cabozantinib) [prescribing information]. South San Francisco, CA: Exelixis, Inc.; May 2016.
  37. ^ a b Product Information: ZIAGEN(R) oral tablets, oral solution, abacavir sulfate oral tablets, oral solution. ViiV Healthcare (per Manufacturer), Research Triangle Park, NC, 2015.
  38. S2CID 20131476
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  39. ^ Jones A (May 2019). "Food requirements for anti-HIV medications". aidsmap.com. Archived from the original on 25 April 2021. Retrieved 21 December 2020.
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  45. ^ Mary Annette Banach. "How HIV Clinicians Acquire Representational Fluency: A Case Study of the HIV Resistance Preceptorship Archived 23 August 2022 at the Wayback Machine", University of California, Berkeley, 2003.
  46. PMID 11667311
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Further reading

External links

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