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===Hypersensitivity syndrome===
===Hypersensitivity syndrome===
[[Hypersensitivity]] to abacavir is strongly associated with a specific allele at the [[human leukocyte antigen]] B [[locus (genetics)|locus]] namely [[HLA-B57|HLA-B*5701]].<ref>{{cite journal |last=Mallal |first=S., Phillips, E., Carosi, G. |title=HLA-B*5701 screening for hypersensitivity to abacavir |journal=New England Journal of Medicine |year=2008 |volume=358 |issue=6 |pages=568–579 |doi=10.1056/nejmoa0706135 |pmid=18256392 |display-authors=et al.}}</ref><ref>{{cite journal |last=Rauch |first=A., Nolan, D., Martin, A. |title=Prospective genetic screening decreases the incidence of abacavir hypersensitivity reactions in the Western Australian HIV cohort study |journal=Clinical Infectious Diseases |year=2006 |volume=43 |issue=1 |pages=99–102 |doi=10.1086/504874 |pmid=16758424 |display-authors=et al.}}</ref> 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 American]]s, 3.0 percent in Hispanic Americans, and 1.2 percent in [[Chinese American]]s.<ref>{{cite journal |last=Heatherington |title=Genetic variations in HLA-B region and hypersensitivity reactions to abacavir |journal=Lancet |year=2002 |volume=359 |issue=9312 |pages=1121–1122 |doi=10.1016/s0140-6736(02)08158-8 |pmid=11943262 |display-authors=et al.}}</ref><ref>{{cite journal |last=Mallal |title=Association between presence of HLA*B5701, HLA-DR7, and HLA-DQ3 and hypersensitivity to HIV-1 reverse-transcriptase inhibitor abacavir |journal=Lancet |year=2002 |volume=359 |issue=9308 |pages=727–732 |doi=10.1016/s0140-6736(02)07873-x |pmid=11888582 |display-authors=et al.}}</ref> There is significant variability in the prevalence of HLA-B*5701 among African populations. In [[African American]]s, the prevalence is estimated to be 1.0 percent on average, 0 percent in the [[Yoruba people|Yoruba]] from [[Nigeria]], 3.3 percent in the [[Luhya people|Luhya]] from [[Kenya]], and 13.6 percent in the [[Masai people|Masai]] from Kenya, although the average values are derived from highly variable frequencies within sample groups.<ref>{{cite journal |last=Rotimi |first=C. N. |author2=Jorde, L. B. |title=Ancestry and disease in the age of genomic medicine |journal=New England Journal of Medicine |year=2010 |volume=363 |issue=16 |pages=1551–1558 |doi=10.1056/nejmra0911564 |pmid=20942671}}</ref>
[[Hypersensitivity]] to abacavir is strongly associated with a specific allele at the [[human leukocyte antigen]] B [[locus (genetics)|locus]] namely [[HLA-B57|HLA-B*5701]].<ref>{{cite journal |last=Mallal |first=S., Phillips, E., Carosi, G. |title=HLA-B*5701 screening for hypersensitivity to abacavir |journal=New England Journal of Medicine |year=2008 |volume=358 |issue=6 |pages=568–579 |doi=10.1056/nejmoa0706135 |pmid=18256392 |display-authors=et al.}}</ref><ref>{{cite journal |last=Rauch |first=A., Nolan, D., Martin, A. |title=Prospective genetic screening decreases the incidence of abacavir hypersensitivity reactions in the Western Australian HIV cohort study |journal=Clinical Infectious Diseases |year=2006 |volume=43 |issue=1 |pages=99–102 |doi=10.1086/504874 |pmid=16758424 |display-authors=et al.}}</ref> <ref>{{Citation|last=Dean|first=Laura|title=Abacavir Therapy and HLA-B*57:01 Genotype|date=2012|url=http://www.ncbi.nlm.nih.gov/books/NBK315783/|work=Medical Genetics Summaries|editor-last=Pratt|editor-first=Victoria|publisher=National Center for Biotechnology Information (US)|pmid=28520363|access-date=2019-01-14|editor2-last=McLeod|editor2-first=Howard|editor3-last=Rubinstein|editor3-first=Wendy|editor4-last=Dean|editor4-first=Laura}}</ref> 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 American]]s, 3.0 percent in Hispanic Americans, and 1.2 percent in [[Chinese American]]s.<ref>{{cite journal |last=Heatherington |title=Genetic variations in HLA-B region and hypersensitivity reactions to abacavir |journal=Lancet |year=2002 |volume=359 |issue=9312 |pages=1121–1122 |doi=10.1016/s0140-6736(02)08158-8 |pmid=11943262 |display-authors=et al.}}</ref><ref>{{cite journal |last=Mallal |title=Association between presence of HLA*B5701, HLA-DR7, and HLA-DQ3 and hypersensitivity to HIV-1 reverse-transcriptase inhibitor abacavir |journal=Lancet |year=2002 |volume=359 |issue=9308 |pages=727–732 |doi=10.1016/s0140-6736(02)07873-x |pmid=11888582 |display-authors=et al.}}</ref> There is significant variability in the prevalence of HLA-B*5701 among African populations. In [[African American]]s, the prevalence is estimated to be 1.0 percent on average, 0 percent in the [[Yoruba people|Yoruba]] from [[Nigeria]], 3.3 percent in the [[Luhya people|Luhya]] from [[Kenya]], and 13.6 percent in the [[Masai people|Masai]] from Kenya, although the average values are derived from highly variable frequencies within sample groups.<ref>{{cite journal |last=Rotimi |first=C. N. |author2=Jorde, L. B. |title=Ancestry and disease in the age of genomic medicine |journal=New England Journal of Medicine |year=2010 |volume=363 |issue=16 |pages=1551–1558 |doi=10.1056/nejmra0911564 |pmid=20942671}}</ref>


Common symptoms of abacavir hypersensitivity syndrome include [[fever]], [[malaise]], [[nausea]], and [[diarrhea]]. Some patients may also develop a [[rash|skin rash]].<ref>{{cite journal |last=Phillips |first=E., Mallal, S. |title=Successful translation of pharmacogenetics into the clinic |journal=Molecular Diagnosis & Therapy |year=2009 |volume=13 |pages=1–9 |doi=10.1007/bf03256308}}</ref> 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.<ref>{{cite journal |last=Phillips |first=E., Mallal S. |title=Drug hypersensitivity in HIV |journal=Current Opinion in Allergy and Clinical Immunology |year=2007 |volume=7 |issue=4 |pages=324–330 |doi=10.1097/aci.0b013e32825ea68a |pmid=17620824}}</ref> The U.S. [[Food and Drug Administration]] (FDA) released an alert concerning abacavir and abacavir-containing medications on July 24, 2008,<ref>{{cite web|url=http://www.fda.gov/drugs/drugsafety/postmarketdrugsafetyinformationforpatientsandproviders/ucm123927.htm|title=Postmarket Drug Safety Information for Patients and Providers - Information for Healthcare Professionals: Abacavir (marketed as Ziagen) and Abacavir-Containing Medications|last=|first=|date=|website=Center for Drug Evaluation and Research at the US FDA|language=en|archive-url=https://web.archive.org/web/20131211024108/http://www.fda.gov/drugs/drugsafety/postmarketdrugsafetyinformationforpatientsandproviders/ucm123927.htm|archive-date=2013-12-11|dead-url=no|access-date=2013-11-29|df=}}</ref> 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.<ref>{{cite web |url=http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=ca73b519-015a-436d-aa3c-af53492825a1 |title=Archived copy |accessdate=2014-07-31 |deadurl=no |archiveurl=https://web.archive.org/web/20140808105100/http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=ca73b519-015a-436d-aa3c-af53492825a1 |archivedate=2014-08-08 |df=}}</ref> 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.<ref>{{cite journal |vauthors=Swen JJ, Nijenhuis M, de Boer A |title=Pharmacogenetics: from bench to byte--an update of guidelines |journal=Clin Pharmacol Ther |volume=89 |issue=5 |pages=662–73 |date=May 2011 |pmid=21412232 |doi=10.1038/clpt.2011.34 |display-authors=et al.}}</ref><ref>{{cite journal |vauthors=Martin MA, Hoffman JM, Freimuth RR |title=Clinical Pharmacogenetics Implementation Consortium Guidelines for HLA-B Genotype and Abacavir Dosing: 2014 update |journal=Clin Pharmacol Ther |volume=95 |issue=5 |pages=499–500 |date=May 2014 |pmid= 24561393 |pmc=3994233 |doi=10.1038/clpt.2014.38 |display-authors=etal}}</ref>
Common symptoms of abacavir hypersensitivity syndrome include [[fever]], [[malaise]], [[nausea]], and [[diarrhea]]. Some patients may also develop a [[rash|skin rash]].<ref>{{cite journal |last=Phillips |first=E., Mallal, S. |title=Successful translation of pharmacogenetics into the clinic |journal=Molecular Diagnosis & Therapy |year=2009 |volume=13 |pages=1–9 |doi=10.1007/bf03256308}}</ref> 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.<ref>{{cite journal |last=Phillips |first=E., Mallal S. |title=Drug hypersensitivity in HIV |journal=Current Opinion in Allergy and Clinical Immunology |year=2007 |volume=7 |issue=4 |pages=324–330 |doi=10.1097/aci.0b013e32825ea68a |pmid=17620824}}</ref> The U.S. [[Food and Drug Administration]] (FDA) released an alert concerning abacavir and abacavir-containing medications on July 24, 2008,<ref>{{cite web|url=http://www.fda.gov/drugs/drugsafety/postmarketdrugsafetyinformationforpatientsandproviders/ucm123927.htm|title=Postmarket Drug Safety Information for Patients and Providers - Information for Healthcare Professionals: Abacavir (marketed as Ziagen) and Abacavir-Containing Medications|last=|first=|date=|website=Center for Drug Evaluation and Research at the US FDA|language=en|archive-url=https://web.archive.org/web/20131211024108/http://www.fda.gov/drugs/drugsafety/postmarketdrugsafetyinformationforpatientsandproviders/ucm123927.htm|archive-date=2013-12-11|dead-url=no|access-date=2013-11-29|df=}}</ref> 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.<ref>{{cite web |url=http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=ca73b519-015a-436d-aa3c-af53492825a1 |title=Archived copy |accessdate=2014-07-31 |deadurl=no |archiveurl=https://web.archive.org/web/20140808105100/http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=ca73b519-015a-436d-aa3c-af53492825a1 |archivedate=2014-08-08 |df=}}</ref> 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.<ref>{{cite journal |vauthors=Swen JJ, Nijenhuis M, de Boer A |title=Pharmacogenetics: from bench to byte--an update of guidelines |journal=Clin Pharmacol Ther |volume=89 |issue=5 |pages=662–73 |date=May 2011 |pmid=21412232 |doi=10.1038/clpt.2011.34 |display-authors=et al.}}</ref><ref>{{cite journal |vauthors=Martin MA, Hoffman JM, Freimuth RR |title=Clinical Pharmacogenetics Implementation Consortium Guidelines for HLA-B Genotype and Abacavir Dosing: 2014 update |journal=Clin Pharmacol Ther |volume=95 |issue=5 |pages=499–500 |date=May 2014 |pmid= 24561393 |pmc=3994233 |doi=10.1038/clpt.2014.38 |display-authors=etal}}</ref>
Line 131: Line 131:
*[http://www.pharmgkb.org/guideline/PA166104997 Abacavir dosing guidelines from the Clinical Pharmacogenetics Implementation Consortium (CPIC)]
*[http://www.pharmgkb.org/guideline/PA166104997 Abacavir dosing guidelines from the Clinical Pharmacogenetics Implementation Consortium (CPIC)]
*[http://www.pharmgkb.org/guideline/PA166104991 Abacavir dosing guidelines from the Dutch Pharmacogenetics Working Group (DPWG)]
*[http://www.pharmgkb.org/guideline/PA166104991 Abacavir dosing guidelines from the Dutch Pharmacogenetics Working Group (DPWG)]
*[https://www.ncbi.nlm.nih.gov/books/NBK315783/ U.S. National Center for Biotechnology Information: Medical Genetics Summaries - Abacavir Therapy and HLA-B*57:01 Genotype]


{{Antiretroviral drug}}
{{Antiretroviral drug}}

Revision as of 11:02, 14 January 2019

Abacavir
Chemical structure of abacavir
Clinical data
Pronunciation/əˈbækəvɪər/ ⓘ
Trade namesZiagen, others[1]
AHFS/Drugs.comMonograph
MedlinePlusa699012
License data
Pregnancy
category
  • AU: B3
Routes of
administration		By mouth (solution or tablets)
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
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
NIAID ChemDB
CompTox Dashboard (EPA)
ECHA InfoCard100.149.341 Edit this at Wikidata
Chemical and physical data
FormulaC14H18N6O
Molar mass286.332 g/mol g·mol−1
3D model (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 (ABC) is a medication used to prevent and treat HIV/AIDS.[1][3] Similar to other nucleoside analog reverse-transcriptase inhibitors (NRTIs), abacavir is used together with other HIV medications, and is not recommended by itself.[4] It is taken by mouth as a tablet or solution and may be used in children over the age of three months.[1][5]

Abacavir is generally well tolerated.[5] Common side effects include vomiting, trouble sleeping, fever, and feeling tired.[1] More severe side effects include hypersensitivity, liver damage, and lactic acidosis.[1] Genetic testing can indicate whether a person is at higher risk of developing hypersensitivity.[1] Symptoms of hypersensitivity include rash, vomiting, and shortness of breath.[5] Abacavir is in the NRTI class of medications, which work by blocking reverse transcriptase, an enzyme needed for HIV virus replication.[6] Within the NRTI class, abacavir is a carbocyclic nucleoside.[1]

Abacavir was patented in 1988 and approved for use in the United States in 1998.[7][8] It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system.[9] It is available as a generic medication.[1] The wholesale cost in the developing world as of 2014 is between 0.36 and 0.83 USD per day.[10] As of 2016 the wholesale cost for a typical month of medication in the United States is 70.50 USD.[11] Commonly, abacavir is sold together with other HIV medications, such as abacavir/lamivudine/zidovudine, abacavir/dolutegravir/lamivudine, and abacavir/lamivudine.[5][6]

Medical uses

Two Abacavir 300mg tablets

Abacavir tablets and oral solution, in combination with other antiretroviral agents, are indicated for the treatment of HIV-1 infection.

Abacavir should always be used in combination with other antiretroviral agents. Abacavir should not be added as a single agent when antiretroviral regimens are changed due to loss of virologic response.

Side effects

Common adverse reactions include nausea, headache, fatigue, vomiting, diarrhea, loss of appetite and trouble sleeping. Rare but serious side effects include hypersensitivity reaction or rash, elevated AST and ALT, depression, anxiety, fever/chills, URI, lactic acidosis, hypertriglyceridemia, and lipodystrophy.[12]

People with liver disease should be cautious about using abacavir because it can aggravate the condition. Signs of liver problems include nausea and vomiting, abdominal pain, dark-colored urine and yellowing of the skin or whites of the eyes. The use of nucleoside drugs such as abacavir can very rarely cause lactic acidosis. Signs of lactic acidosis include fast or irregular heartbeat, unusual muscle pain, fatigue, difficulty breathing and stomach pain with nausea and vomiting.[13] Abacavir can also lead to immune reconstitution inflammatory syndrome, a change in body fat as well as an increased risk of heart attack.

Resistance to abacavir has developed in laboratory versions of HIV which are also resistant to other HIV-specific antiretrovirals such as lamivudine, didanosine, and zalcitabine. HIV strains that are resistant to protease inhibitors are not likely to be resistant to abacavir.

Abacavir is contraindicated for use in infants under 3 months of age.

Little is known about the effects of Abacavir overdose. Overdose victims should be taken to a hospital emergency room for treatment.

Hypersensitivity syndrome

Hypersensitivity to abacavir is strongly associated with a specific allele at the human leukocyte antigen B locus namely HLA-B*5701.[14][15] [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 July 24, 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.[23] 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 March 1, 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. 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.[29]

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.[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 MPR2 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 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.[37]

Pharmacokinetics

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

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%.

Abacavir is eliminated via excretion in the urine (83%) and feces (16%). 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.[38][39][40]

Abacavir was approved by the Food and Drug Administration (FDA) on December 18, 1998, and is thus the fifteenth approved antiretroviral drug in the United States. Its patent expired in the United States on 2009-12-26.

Synthesis

Abacavir synthesis:[41]

References

  1. ^ a b c d e f g h Lua error in Module:Citation/CS1/Date_validation at line 986: bad argument #3 to 'format' (string expected, got nil).
  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 22 Oct 2023.
  3. ^ "Drug Name Abbreviations Adult and Adolescent ARV Guidelines". AIDSinfo. Archived from the original on 2016-11-09. Retrieved 2016-11-08. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  4. ^ "What Not to Use Adult and Adolescent ARV Guidelines". AIDSinfo. Archived from the original on 2016-11-09. Retrieved 2016-11-08. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  5. ^ a b c d 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.
  6. ^ a b "Nucleoside reverse transcriptase inhibitors (NRTIs or 'nukes') - HIV/AIDS". www.hiv.va.gov. Archived from the original on 2016-11-09. Retrieved 2016-11-08. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  7. ^ Fischer, Janos; Ganellin, C. Robin (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 505. ISBN 9783527607495. Archived from the original on 2017-09-08. {{cite book}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  8. ^ Kane, Brigid M. (2008). HIV/AIDS Treatment Drugs. Infobase Publishing. p. 56. ISBN 9781438102078. Archived from the original on 2017-09-08. {{cite book}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  9. ^ "WHO Model List of Essential Medicines (19th List)" (PDF). World Health Organization. April 2015. Archived from the original (PDF) on 13 December 2016. Retrieved 8 December 2016. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  10. ^ "International Drug Price Indicator Guide". ERC. Retrieved 20 November 2016.
  11. ^ "NADAC as of 2016-12-07 | Data.Medicaid.gov". Centers for Medicare and Medicaid Services. Archived from the original on 21 December 2016. Retrieved 12 December 2016. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  12. ^ "Abacavir Adverse Reactions". Epocrates Online. {{cite web}}: Cite has empty unknown parameter: |dead-url= (help)
  13. ^ "Abacavir | Dosage, Side Effects | AIDSinfo". AIDSinfo. Archived from the original on 2017-03-06. Retrieved 2016-11-08. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
  14. ^ Mallal, S., Phillips, E., Carosi, G.; et al. (2008). "HLA-B*5701 screening for hypersensitivity to abacavir". New England Journal of Medicine. 358 (6): 568–579. doi:10.1056/nejmoa0706135. PMID 18256392.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  15. ^ Rauch, A., Nolan, D., Martin, A.; et al. (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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  16. ^ Dean, Laura (2012), Pratt, Victoria; McLeod, Howard; Rubinstein, Wendy; Dean, Laura (eds.), "Abacavir Therapy and HLA-B*57:01 Genotype", Medical Genetics Summaries, National Center for Biotechnology Information (US), PMID 28520363, retrieved 2019-01-14
  17. ^ Heatherington; et al. (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.
  18. ^ Mallal; et al. (2002). "Association between presence of HLA*B5701, 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.
  19. ^ Rotimi, C. N.; Jorde, L. B. (2010). "Ancestry and disease in the age of genomic medicine". New England Journal of Medicine. 363 (16): 1551–1558. doi:10.1056/nejmra0911564. PMID 20942671.
  20. ^ Phillips, E., Mallal, S. (2009). "Successful translation of pharmacogenetics into the clinic". Molecular Diagnosis & Therapy. 13: 1–9. doi:10.1007/bf03256308.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  21. ^ Phillips, E., Mallal S. (2007). "Drug hypersensitivity in HIV". Current Opinion in Allergy and Clinical Immunology. 7 (4): 324–330. doi:10.1097/aci.0b013e32825ea68a. PMID 17620824.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  22. ^ "Postmarket Drug Safety Information for Patients and Providers - Information for Healthcare Professionals: Abacavir (marketed as Ziagen) and Abacavir-Containing Medications". Center for Drug Evaluation and Research at the US FDA. Archived from the original on 2013-12-11. Retrieved 2013-11-29. {{cite web}}: Unknown parameter |dead-url= ignored (|url-status= suggested) (help)
  23. ^ "Archived copy". Archived from the original on 2014-08-08. Retrieved 2014-07-31. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)CS1 maint: archived copy as title (link)
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