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Abacavir

January 29, 2023

Abacavir, sold under the brand name Ziagen among others, is a medication used to treat HIV/AIDS.[2][3][4][5] Similar to other nucleoside analog reverse-transcriptase inhibitors (NRTIs), abacavir is used together with other HIV medications, and is not recommended by itself.[6] It is taken by mouth as a tablet or solution and may be used in children over the age of three months.[4][7]

Abacavir
Chemical structure of abacavir
Clinical data
Pronunciation/əˈbækəvɪər/ (listen)
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
CAS Number
  • 136470-78-5 Y
PubChem CID
  • 441300
DrugBank
  • DB01048 Y
ChemSpider
  • 390063 Y
UNII
  • WR2TIP26VS
KEGG
  • D07057 Y
ChEBI
  • CHEBI:421707 Y
ChEMBL
  • ChEMBL1380 Y
NIAID ChemDB
  • 028596
CompTox Dashboard (EPA)
  • DTXSID4046444
ECHA InfoCard100.149.341
Chemical and physical data
FormulaC14H18N6O
Molar mass286.339 g·mol−1
3D model (JSmol)
  • Interactive image
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 Y
  • Key:MCGSCOLBFJQGHM-SCZZXKLOSA-N Y
  (verify)

Abacavir is generally well tolerated.[7] Common side effects include vomiting, insomnia (trouble sleeping), fever, and feeling tired.[4] Other common side effects include loss of appetite, headache, nausea (feeling sick), diarrhea, rash, and lethargy (lack of energy).[3] More severe side effects include hypersensitivity, liver damage, and lactic acidosis.[4] Genetic testing can indicate whether a person is at higher risk of developing hypersensitivity.[4] Symptoms of hypersensitivity include rash, vomiting, and shortness of breath.[7] Abacavir is in the NRTI class of medications, which work by blocking reverse transcriptase, an enzyme needed for HIV virus replication.[8] Within the NRTI class, abacavir is a carbocyclic nucleoside.[4]

Abacavir was patented in 1988, and approved for use in the United States in 1998.[9][10] It is on the World Health Organization's List of Essential Medicines.[11] It is available as a generic medication.[4] Abacavir is used together with other HIV medications, such as abacavir/lamivudine/zidovudine, abacavir/dolutegravir/lamivudine, and abacavir/lamivudine.[7][8] The combination abacavir/lamivudine is an essential medicine.[11]

Medical uses

Abacavir, in combination with other antiretroviral agents, is indicated for the treatment of HIV-1 infection.[2][3] Abacavir should be used in combination with other antiretroviral agents.[2][3]

Contraindications

Abacavir is contraindicated for people who have the HLA‑B*5701 allele or who have moderate or severe liver disease (hepatic impairment).[2][3]

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.[12]<

Hypersensitivity syndrome

Hypersensitivity to abacavir is strongly associated with a specific allele at the human leukocyte antigen B locus namely HLA-B*5701.[13][14][15] The mechanism for this hypersensitivity reaction is due to abacavir binding in the antigen-binding cleft of HLA-B*57:01, allowing alternative peptides to bind, which appear as "non-self" when presented to T cells.[16] There is an association between the prevalence of HLA-B*5701 and ancestry. The prevalence of the allele is estimated to be 3.4 to 5.8 percent on average in populations of European ancestry, 17.6 percent in Indian Americans, 3.0 percent in Hispanic Americans, and 1.2 percent in Chinese Americans.[17][18] There is significant variability in the prevalence of HLA-B*5701 among African populations. In African Americans, the prevalence is estimated to be 1.0 percent on average, 0 percent in the Yoruba from Nigeria, 3.3 percent in the Luhya from Kenya, and 13.6 percent in the Masai from Kenya, although the average values are derived from highly variable frequencies within sample groups.[19]

Common symptoms of abacavir hypersensitivity syndrome include fever, malaise, nausea, and diarrhea. Some patients may also develop a skin rash.[20] Symptoms of AHS typically manifest within six weeks of treatment using abacavir, although they may be confused with symptoms of HIV, immune reconstitution syndrome, hypersensitivity syndromes associated with other drugs, or infection.[21] The U.S. Food and Drug Administration (FDA) released an alert concerning abacavir and abacavir-containing medications on 24 July 2008,[22] 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.[2] 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.[23][24]

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.[25]

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.[26] A meta-analysis of 26 studies conducted by the FDA, however, did not find any association between abacavir use and heart attack[27][28]

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.[16]

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:

  • Protease inhibitors such as tipranavir or ritonovir may decrease the serum concentration of abacavir through induction of glucuronidation. Abacavir is metabolized by both alcohol dehydrogenase and glucuronidation.[29][30]
  • Ethanol may result in increased levels of abacavir through the inhibition of alcohol dehydrogenase. Abacavir is metabolized by both alcohol dehydrogenase and glucuronidation.[29][31]
  • Methadone may diminish the therapeutic effect of Abacavir. Abacavir may decrease the serum concentration of Methadone.[32][33]
  • 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.[34]
  • Cabozantinib: Drugs from the MRP2 inhibitor (Multidrug resistance-associated protein 2 inhibitors) family such as abacavir could increase the serum concentration of Cabozantinib.[35]

Mechanism of action

Abacavir is a nucleoside reverse transcriptase inhibitor that inhibits viral replication. It is a guanosine analogue that is phosphorylated to carbovir triphosphate (CBV-TP). CBV-TP competes with the viral molecules and is incorporated into the viral DNA. Once CBV-TP is integrated into the viral DNA, transcription and HIV reverse transcriptase is inhibited.[36]

Pharmacokinetics

Abacavir is given orally and is rapidly absorbed with a high bioavailability of 83%.[37] Solution and tablet have comparable concentrations and bioavailability. Abacavir can be taken with or without food.[38]

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%.[39]

Abacavir is eliminated via excretion in the urine (83%) and feces (16%).[40] It is unclear whether abacavir can be removed by hemodialysis or peritoneal dialysis.[36]

History

Robert Vince and Susan Daluge along with Mei Hua, a visiting scientist from China, developed the medication in the '80s.[41][42][43]

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.[44] Its patent expired in the United States on 26 December 2009.[citation needed]

Synthesis

 
Abacavir synthesis:[45]

References

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  3. ^ a b c d e f "Ziagen EPAR". European Medicines Agency. 17 September 2018. 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.
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  6. ^ "What Not to Use Adult and Adolescent ARV Guidelines". AIDSinfo. from the original on 9 November 2016. Retrieved 8 November 2016.
  7. ^ a b c d Yuen GJ, Weller S, Pakes GE (2008). "A review of the pharmacokinetics of abacavir". Clinical Pharmacokinetics. 47 (6): 351–371. doi:10.2165/00003088-200847060-00001. PMID 18479171. S2CID 31107341.
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  24. ^ Martin MA, Hoffman JM, Freimuth RR, Klein TE, Dong BJ, Pirmohamed M, et al. (May 2014). "Clinical Pharmacogenetics Implementation Consortium Guidelines for HLA-B Genotype and Abacavir Dosing: 2014 update". Clinical Pharmacology and Therapeutics. 95 (5): 499–500. doi:10.1038/clpt.2014.38. PMC 3994233. PMID 24561393.
  25. ^ Shear NH, Milpied B, Bruynzeel DP, Phillips EJ (May 2008). "A review of drug patch testing and implications for HIV clinicians". AIDS. 22 (9): 999–1007. doi:10.1097/qad.0b013e3282f7cb60. PMID 18520343. S2CID 2972984.
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  29. ^ a b Prescribing information. Ziagen (abacavir). Research Triangle Park, NC: GlaxoSmithKline, July 2002
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  40. ^ Yuen GJ, Weller S, Pakes GE (2008). "A review of the pharmacokinetics of abacavir". Clinical Pharmacokinetics. 47 (6): 351–71. doi:10.2165/00003088-200847060-00001. PMID 18479171. S2CID 31107341.
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Further reading

  • Dean L (April 2018). "Abacavir Therapy and HLA-B*57:01 Genotype". In Pratt VM, McLeod HL, Rubinstein WS, et al. (eds.). Medical Genetics Summaries. National Center for Biotechnology Information (NCBI). PMID 28520363. from the original on 26 October 2020. Retrieved 6 February 2020.

External links

 
Wikimedia Commons has media related to Abacavir.
  • "Abacavir". Drug Information Portal. U.S. National Library of Medicine.
  • "Abacavir sulfate". Drug Information Portal. U.S. National Library of Medicine.
  • Abacavir pathway on PharmGKB

January 29, 2023
abacavir, sold, under, brand, name, ziagen, among, others, medication, used, treat, aids, similar, other, nucleoside, analog, reverse, transcriptase, inhibitors, nrtis, abacavir, used, together, with, other, medications, recommended, itself, taken, mouth, tabl. Abacavir sold under the brand name Ziagen among others is a medication used to treat HIV AIDS 2 3 4 5 Similar to other nucleoside analog reverse transcriptase inhibitors NRTIs abacavir is used together with other HIV medications and is not recommended by itself 6 It is taken by mouth as a tablet or solution and may be used in children over the age of three months 4 7 AbacavirChemical structure of abacavirClinical dataPronunciation e ˈ b ae k e v ɪer listen Trade namesZiagenOther namesAbacavir sulfate USAN US AHFS Drugs comMonographMedlinePlusa699012License dataEU EMA by INN US DailyMed AbacavirPregnancycategoryAU B3Routes ofadministrationBy mouthATC codeJ05AF06 WHO Legal statusLegal statusAU S4 Prescription only 1 UK POM Prescription only US only 2 EU Rx only 3 Pharmacokinetic dataBioavailability83 MetabolismLiverElimination half life1 54 0 63 hExcretionKidney 1 2 abacavir 30 5 carboxylic acid metabolite 36 5 glucuronide metabolite 15 unidentified minor metabolites Fecal 16 IdentifiersIUPAC name 1S 4R 4 2 amino 6 cyclopropylamino 9H purin 9 yl cyclopent 2 en 1 yl methanolCAS Number136470 78 5 YPubChem CID441300DrugBankDB01048 YChemSpider390063 YUNIIWR2TIP26VSKEGGD07057 YChEBICHEBI 421707 YChEMBLChEMBL1380 YNIAID ChemDB028596CompTox Dashboard EPA DTXSID4046444ECHA InfoCard100 149 341Chemical and physical dataFormulaC 14H 18N 6OMolar mass286 339 g mol 13D model JSmol Interactive imageMelting point165 C 329 F SMILES n3c1c ncn1 C H 2 C C C H CO C2 c nc3N NC4CC4InChI 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 YKey MCGSCOLBFJQGHM SCZZXKLOSA N Y verify Abacavir is generally well tolerated 7 Common side effects include vomiting insomnia trouble sleeping fever and feeling tired 4 Other common side effects include loss of appetite headache nausea feeling sick diarrhea rash and lethargy lack of energy 3 More severe side effects include hypersensitivity liver damage and lactic acidosis 4 Genetic testing can indicate whether a person is at higher risk of developing hypersensitivity 4 Symptoms of hypersensitivity include rash vomiting and shortness of breath 7 Abacavir is in the NRTI class of medications which work by blocking reverse transcriptase an enzyme needed for HIV virus replication 8 Within the NRTI class abacavir is a carbocyclic nucleoside 4 Abacavir was patented in 1988 and approved for use in the United States in 1998 9 10 It is on the World Health Organization s List of Essential Medicines 11 It is available as a generic medication 4 Abacavir is used together with other HIV medications such as abacavir lamivudine zidovudine abacavir dolutegravir lamivudine and abacavir lamivudine 7 8 The combination abacavir lamivudine is an essential medicine 11 Contents 1 Medical uses 2 Contraindications 3 Side effects 3 1 Hypersensitivity syndrome 3 2 Immunopathogenesis 4 Interaction 5 Mechanism of action 6 Pharmacokinetics 7 History 8 Synthesis 9 References 10 Further reading 11 External linksMedical uses EditAbacavir in combination with other antiretroviral agents is indicated for the treatment of HIV 1 infection 2 3 Abacavir should be used in combination with other antiretroviral agents 2 3 Contraindications EditAbacavir is contraindicated for people who have the HLA B 5701 allele or who have moderate or severe liver disease hepatic impairment 2 3 Side effects EditCommon 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 12 lt Hypersensitivity syndrome Edit Hypersensitivity to abacavir is strongly associated with a specific allele at the human leukocyte antigen B locus namely HLA B 5701 13 14 15 The mechanism for this hypersensitivity reaction is due to abacavir binding in the antigen binding cleft of HLA B 57 01 allowing alternative peptides to bind which appear as non self when presented to T cells 16 There is an association between the prevalence of HLA B 5701 and ancestry The prevalence of the allele is estimated to be 3 4 to 5 8 percent on average in populations of European ancestry 17 6 percent in Indian Americans 3 0 percent in Hispanic Americans and 1 2 percent in Chinese Americans 17 18 There is significant variability in the prevalence of HLA B 5701 among African populations In African Americans the prevalence is estimated to be 1 0 percent on average 0 percent in the Yoruba from Nigeria 3 3 percent in the Luhya from Kenya and 13 6 percent in the Masai from Kenya although the average values are derived from highly variable frequencies within sample groups 19 Common symptoms of abacavir hypersensitivity syndrome include fever malaise nausea and diarrhea Some patients may also develop a skin rash 20 Symptoms of AHS typically manifest within six weeks of treatment using abacavir although they may be confused with symptoms of HIV immune reconstitution syndrome hypersensitivity syndromes associated with other drugs or infection 21 The U S Food and Drug Administration FDA released an alert concerning abacavir and abacavir containing medications on 24 July 2008 22 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 2 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 23 24 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 25 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 26 A meta analysis of 26 studies conducted by the FDA however did not find any association between abacavir use and heart attack 27 28 Immunopathogenesis Edit 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 16 Interaction EditAbacavir 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 Protease inhibitors such as tipranavir or ritonovir may decrease the serum concentration of abacavir through induction of glucuronidation Abacavir is metabolized by both alcohol dehydrogenase and glucuronidation 29 30 Ethanol may result in increased levels of abacavir through the inhibition of alcohol dehydrogenase Abacavir is metabolized by both alcohol dehydrogenase and glucuronidation 29 31 Methadone may diminish the therapeutic effect of Abacavir Abacavir may decrease the serum concentration of Methadone 32 33 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 34 Cabozantinib Drugs from the MRP2 inhibitor Multidrug resistance associated protein 2 inhibitors family such as abacavir could increase the serum concentration of Cabozantinib 35 Mechanism of action EditAbacavir is a nucleoside reverse transcriptase inhibitor that inhibits viral replication It is a guanosine analogue that is phosphorylated to carbovir triphosphate CBV TP CBV TP competes with the viral molecules and is incorporated into the viral DNA Once CBV TP is integrated into the viral DNA transcription and HIV reverse transcriptase is inhibited 36 Pharmacokinetics EditAbacavir is given orally and is rapidly absorbed with a high bioavailability of 83 37 Solution and tablet have comparable concentrations and bioavailability Abacavir can be taken with or without food 38 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 39 Abacavir is eliminated via excretion in the urine 83 and feces 16 40 It is unclear whether abacavir can be removed by hemodialysis or peritoneal dialysis 36 History EditRobert Vince and Susan Daluge along with Mei Hua a visiting scientist from China developed the medication in the 80s 41 42 43 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 44 Its patent expired in the United States on 26 December 2009 citation needed Synthesis Edit Abacavir synthesis 45 References Edit TGA eBS Product and Consumer Medicine Information Licence Archived from the original on 24 March 2022 Retrieved 23 August 2022 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 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 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 Drug Name Abbreviations Adult and Adolescent ARV Guidelines AIDSinfo Archived from the original on 9 November 2016 Retrieved 8 November 2016 What Not to Use Adult and Adolescent ARV Guidelines AIDSinfo Archived from the original on 9 November 2016 Retrieved 8 November 2016 a b c d Yuen GJ Weller S Pakes GE 2008 A review of the pharmacokinetics of abacavir Clinical Pharmacokinetics 47 6 351 371 doi 10 2165 00003088 200847060 00001 PMID 18479171 S2CID 31107341 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 Fischer J Ganellin CR 2006 Analogue based Drug Discovery John Wiley amp Sons p 505 ISBN 9783527607495 Archived from the original on 8 September 2017 Kane BM 2008 HIV AIDS Treatment Drugs Infobase Publishing p 56 ISBN 9781438102078 Archived from the original on 8 September 2017 a b 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 Abacavir Adverse Reactions Epocrates Online Archived from the original on 23 August 2021 Retrieved 9 November 2012 Mallal S Phillips E Carosi G Molina JM Workman C Tomazic J et al February 2008 HLA B 5701 screening for hypersensitivity to abacavir The New England Journal of Medicine 358 6 568 579 doi 10 1056 nejmoa0706135 PMID 18256392 Archived from the original on 22 January 2021 Retrieved 9 July 2019 Rauch A Nolan D Martin A McKinnon E Almeida C Mallal S July 2006 Prospective genetic screening decreases the incidence of abacavir hypersensitivity reactions in the Western Australian HIV cohort study Clinical Infectious Diseases 43 1 99 102 doi 10 1086 504874 PMID 16758424 Dean L 2015 Abacavir Therapy and HLA B 57 01 Genotype In Pratt VM McLeod HL Rubinstein WS et al eds Medical Genetics Summaries National Center for Biotechnology Information NCBI PMID 28520363 Bookshelf ID NBK315783 Archived from the original on 26 October 2020 Retrieved 14 January 2019 a b Illing PT Vivian JP Dudek NL Kostenko L Chen Z Bharadwaj M et al June 2012 Immune self reactivity triggered by drug modified HLA peptide repertoire Nature 486 7404 554 558 Bibcode 2012Natur 486 554I doi 10 1038 nature11147 PMID 22722860 S2CID 4408811 Hetherington S Hughes AR Mosteller M Shortino D Baker KL Spreen W et al March 2002 Genetic variations in HLA B region and hypersensitivity reactions to abacavir Lancet 359 9312 1121 1122 doi 10 1016 s0140 6736 02 08158 8 PMID 11943262 S2CID 9434238 Mallal S Nolan D Witt C Masel G Martin AM Moore C et al March 2002 Association between presence of HLA B 5701 HLA DR7 and HLA DQ3 and hypersensitivity to HIV 1 reverse transcriptase inhibitor abacavir Lancet 359 9308 727 732 doi 10 1016 s0140 6736 02 07873 x PMID 11888582 S2CID 12923232 Rotimi CN Jorde LB October 2010 Ancestry and disease in the age of genomic medicine The New England Journal of Medicine 363 16 1551 1558 doi 10 1056 nejmra0911564 PMID 20942671 Phillips E Mallal S 2009 Successful translation of pharmacogenetics into the clinic the abacavir example Molecular Diagnosis amp Therapy 13 1 1 9 doi 10 1007 bf03256308 PMID 19351209 S2CID 45896364 Phillips E Mallal S August 2007 Drug hypersensitivity in HIV Current Opinion in Allergy and Clinical Immunology 7 4 324 330 doi 10 1097 aci 0b013e32825ea68a PMID 17620824 S2CID 37549824 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 Swen JJ Nijenhuis M de Boer A Grandia L Maitland van der Zee AH Mulder H et al May 2011 Pharmacogenetics from bench to byte an update of guidelines Clinical Pharmacology and Therapeutics 89 5 662 673 doi 10 1038 clpt 2011 34 PMID 21412232 S2CID 2475005 Martin MA Hoffman JM Freimuth RR Klein TE Dong BJ Pirmohamed M et al May 2014 Clinical Pharmacogenetics Implementation Consortium Guidelines for HLA B Genotype and Abacavir Dosing 2014 update Clinical Pharmacology and Therapeutics 95 5 499 500 doi 10 1038 clpt 2014 38 PMC 3994233 PMID 24561393 Shear NH Milpied B Bruynzeel DP Phillips EJ May 2008 A review of drug patch testing and implications for HIV clinicians AIDS 22 9 999 1007 doi 10 1097 qad 0b013e3282f7cb60 PMID 18520343 S2CID 2972984 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 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 Ding X Andraca Carrera E Cooper C Miele P Kornegay C Soukup M Marcus KA December 2012 No association of abacavir use with myocardial infarction findings of an FDA meta analysis Journal of Acquired Immune Deficiency Syndromes 61 4 441 447 doi 10 1097 QAI 0b013e31826f993c PMID 22932321 S2CID 7997822 a b Prescribing information Ziagen abacavir Research Triangle Park NC GlaxoSmithKline July 2002 Vourvahis M Kashuba AD June 2007 Mechanisms of pharmacokinetic and pharmacodynamic drug interactions associated with ritonavir enhanced tipranavir Pharmacotherapy 27 6 888 909 doi 10 1592 phco 27 6 888 PMID 17542771 S2CID 23591048 McDowell JA Chittick GE Stevens CP Edwards KD Stein DS June 2000 Pharmacokinetic interaction of abacavir 1592U89 and ethanol in human immunodeficiency virus infected adults Antimicrobial Agents and Chemotherapy 44 6 1686 1690 doi 10 1128 aac 44 6 1686 1690 2000 PMC 89933 PMID 10817729 Berenguer J Perez Elias MJ Bellon JM Knobel H Rivas Gonzalez P Gatell JM et al February 2006 Effectiveness and safety of abacavir lamivudine and zidovudine in antiretroviral therapy naive HIV infected patients results from a large multicenter observational cohort Journal of Acquired Immune Deficiency Syndromes 41 2 154 159 doi 10 1097 01 qai 0000194231 08207 8a PMID 16394846 S2CID 17609676 Dolophine methadone prescribing information Columbus OH Roxane Laboratories Inc March 2015 Gervasoni C Cattaneo D Di Cristo V Castoldi S Gervasi E Clementi E Riva A June 2016 Orlistat weight lost at cost of HIV rebound The Journal of Antimicrobial Chemotherapy 71 6 1739 1741 doi 10 1093 jac dkw033 PMID 26945709 Cometriq cabozantinib prescribing information South San Francisco CA Exelixis Inc May 2016 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 Chittick GE Gillotin C McDowell JA Lou Y Edwards KD Prince WT Stein DS August 1999 Abacavir absolute bioavailability bioequivalence of three oral formulations and effect of food Pharmacotherapy 19 8 932 942 doi 10 1592 phco 19 11 932 31568 PMID 10453964 S2CID 20131476 Jones A May 2019 Food requirements for anti HIV medications aidsmap com Archived from the original on 25 April 2021 Retrieved 21 December 2020 Wyles DL Gerber JG March 2005 Abacavir pharmacokinetics in hepatic dysfunction Clinical Infectious Diseases 40 6 909 910 doi 10 1086 429247 PMID 15736035 Yuen GJ Weller S Pakes GE 2008 A review of the pharmacokinetics of abacavir Clinical Pharmacokinetics 47 6 351 71 doi 10 2165 00003088 200847060 00001 PMID 18479171 S2CID 31107341 Dr Robert Vince 2010 Inductee Minnesota Inventors Hall of Fame Archived from the original on 15 February 2016 Retrieved 10 February 2016 Robert Vince PhD faculty listing University of Minnesota Archived from the original on 17 February 2016 Daluge SM Good SS Faletto MB Miller WH St Clair MH Boone LR et al May 1997 1592U89 a novel carbocyclic nucleoside analog with potent selective anti human immunodeficiency virus activity Antimicrobial Agents and Chemotherapy 41 5 1082 1093 doi 10 1128 AAC 41 5 1082 PMC 163855 PMID 9145874 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 Crimmins MT King BW June 1996 An Efficient Asymmetric Approach to Carbocyclic Nucleosides Asymmetric Synthesis of 1592U89 a Potent Inhibitor of HIV Reverse Transcriptase The Journal of Organic Chemistry 61 13 4192 4193 doi 10 1021 jo960708p PMID 11667311 Further reading EditDean L April 2018 Abacavir Therapy and HLA B 57 01 Genotype In Pratt VM McLeod HL Rubinstein WS et al eds Medical Genetics Summaries National Center for Biotechnology Information NCBI PMID 28520363 Archived from the original on 26 October 2020 Retrieved 6 February 2020 External links Edit Wikimedia Commons has media related to Abacavir Abacavir Drug Information Portal U S National Library of Medicine Abacavir sulfate Drug Information Portal U S National Library of Medicine Abacavir pathway on PharmGKB Portals Medicine Viruses Retrieved from https en wikipedia org w index php title Abacavir amp oldid 1136169574, wikipedia, wiki, book, books, library,

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