Abacavir

1
Abacavir
Abacavir
Chemical structure of abacavir
Systematic (IUPAC) name
{(1S,4R)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]cyclopent-2-en-1-yl}methanol
Clinical data
Trade names Ziagen
AHFS/Drugs.com
monograph
[1]
MedlinePlus
a699012
[2]
Pregnancy cat. B3 (AU) C (US)
Legal status POM (UK) -only (US)
Routes Oral (solution or tablets)
Pharmacokinetic data
Bioavailability 83%
Metabolism Hepatic
Half-life 1.54 0.63 h
Excretion Renal (1.2% abacavir, 30% 5'-carboxylic acid metabolite, 36% 5'-glucuronide metabolite, 15% unidentified minor
metabolites). Fecal (16%)
Identifiers
CAS number
136470-78-5
[3]

ATC code
J05AF06
[4]
PubChem
CID 441300
[5]
DrugBank
DB01048
[6]
ChemSpider
390063
[7]

UNII
WR2TIP26VS
[8]

KEGG
D07057
[9]

Abacavir
2
ChEBI
CHEBI:421707
[10]

ChEMBL
CHEMBL1380
[11]

NIAID ChemDB
028596
[12]
Chemical data
Formula C
14
H
18
N
6
O
Mol. mass 286.332 g/mol
Physical data
Melt. point 165C (329F)
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[13]
Abacavir (ABC)
i
/.bk..vr/ is a nucleoside analog reverse transcriptase inhibitor (NRTI) used to treat HIV
and AIDS. It is available under the trade name Ziagen (ViiV Healthcare) and in the combination formulations
Trizivir (abacavir, zidovudine and lamivudine) and Kivexa/Epzicom (abacavir and lamivudine). It has been well
tolerated: the main side effect is hypersensitivity, which can be severe, and in rare cases, fatal. Genetic testing can
indicate whether an individual will be hypersensitive; over 90% of patients can safely take abacavir. However, in a
separate study, the risk of heart attack increased by nearly 90%.
[14]
Viral strains that are resistant to zidovudine (AZT) or lamivudine (3TC) are generally sensitive to abacavir (ABC),
whereas some strains that are resistant to AZT and 3TC are not as sensitive to abacavir.
It is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed
in a basic health system.
Two Abacavir 300mg tablets
Medical uses
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 reactions include nausea, headache, fatigue, vomiting,
hypersensitivity reaction, diarrhea, fever/chills, depression, rash,
anxiety, URI, ALT, AST elevated, hypertriglyceridemia, and
lipodystrophy.
[15]
Patients with liver disease should be cautious about using abacavir because of the possibility that it can aggravate the
condition. The use of nucleoside drugs such as abacavir can very rarely cause lactic acidosis. 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.
Redistribution or accumulation of body fat, lipodystrophy, may occur in people taking antiviral medications giving
rise to central obesity, facial, arm, leg, and/ or buttock wasting, breast enlargement, and fat accumulation at the base
Abacavir
3
of the neck (buffalo hump).
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 single-nucleotide polymorphism at the human leukocyte
antigen B*5701 locus. 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% on average in populations of European ancestry, 17.6% in Indian
Americans, 3.0% in Hispanic Americans, and 1.2% in Chinese Americans. 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% on average, 0% in the Yoruba from Nigeria, 3.3% in the Luhya from Kenya, and 13.6% in the Masai from
Kenya, although the average values are derived from highly variable frequencies within sample groups.
Common symptoms of abacavir hypersensitivity syndrome include fever, malaise, nausea, and diarrhea; some
patients may also develop a skin rash. Symptoms of AHS typically manifest within six weeks of treatment using
abacavir, although they may be confused with symptoms of HIV, immune restoration disease, hypersensitivity
syndromes associated with other drugs, or infection. The FDA released an alert concerning abacavir and
abacavir-containing medications on July 24, 2008.
[16]
It recommends pre-therapy screening for the HLA-B*5701
allele, and the use of alternative therapy in subjects with this allele. Genetic testing for the HLA-B*5701 allele is
recommended before starting or restarting treatment with abacavir or abacavir-containing medications.
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.
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.
[17]
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.
[18]
Mechanism of action
ABC is an analog of guanosine (a purine). Its target is the viral reverse transcriptase enzyme.
Abacavir
4
Pharmacokinetics
Abacavir is given orally and has a high bioavailability (83%). It is metabolised primarily through alcohol
dehydrogenase or glucuronyl transferase. It is capable of crossing the bloodbrain barrier.
History
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.
References
[1] http:/ / www. drugs. com/ monograph/ abacavir-sulfate.html
[2] http:/ / www. nlm. nih.gov/ medlineplus/ druginfo/ meds/ a699012. html
[3] http:/ / www. nlm. nih.gov/ cgi/ mesh/ 2009/ MB_cgi?term=136470-78-5& rn=1
[4] http:/ / www. whocc.no/ atc_ddd_index/ ?code=J05AF06
[5] http:/ / pubchem. ncbi. nlm.nih. gov/ summary/ summary. cgi?cid=441300
[6] http:/ / www. drugbank. ca/ drugs/ DB01048
[7] http:/ / www. chemspider.com/ Chemical-Structure.390063. html
[8] http:/ / fdasis.nlm. nih. gov/ srs/ srsdirect. jsp?regno=WR2TIP26VS
[9] http:/ / www. kegg. jp/ entry/ D07057
[10] https:/ / www.ebi.ac. uk/ chebi/ searchId.do?chebiId=CHEBI:421707
[11] https:/ / www.ebi.ac. uk/ chembldb/ index.php/ compound/ inspect/ CHEMBL1380
[12] http:/ / chemdb. niaid. nih.gov/ CompoundDetails. aspx?AIDSNO=028596
[13] http:/ / en. wikipedia. org/ w/ index. php?title=Special:ComparePages& rev1=477236809& page2=Abacavir
[14] SFGate.com (http:/ / www. sfgate. com/ cgi-bin/ article. cgi?f=/ c/ a/ 2008/ 04/ 02/ MNE2VU4TF. DTL)
[15] https:/ / online. epocrates.com/ noFrame/ showPage. do?method=drugs& MonographId=2043& ActiveSectionId=5
[16] http:/ / www.fda. gov/ drugs/ drugsafety/ postmarketdrugsafetyinformationforpatientsandproviders/ ucm123927. htm Accessed November
29, 2013.
[17] http:/ / www.drugs.com/ fda/ abacavir-ongoing-safety-review-possible-increased-risk-heart-attack-12914. html Accessed November 29,
2013.
[18] [18] Illing PT et al. 2012, Nature, doi:10.1038/nature11147
External links
Full Prescribing Information (http:/ / us. gsk. com/ products/ assets/ us_ziagen. pdf)
Article Sources and Contributors
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Article Sources and Contributors
Abacavir Source: http://en.wikipedia.org/w/index.php?oldid=608933285 Contributors: A.leatherd, Abidparakkal, Arcadian, Argus123, Averak, Bastique, Beetstra, BorisTM, Caknuck, Carlo
Banez, Ceyockey, ChemNerd, Chowbok, Circeus, CliffC, Cybercobra, DMacks, Daevatgl, Deflective, Deli nk, DragonflySixtyseven, Edgar181, Epeefleche, Epolk, Eras-mus, Espresso Addict,
Eumeng.chong, Fuzzform, Fvasconcellos, G716, Gak, Gary Battle, Giorgiogp2, Giraffedata, Hazard-SJ, Hoffmeier, Hopping, Hu12, Igno2, Jmh649, JovanCormac, J, KBlott,
Kajasudhakarababu, Kbh3rd, Keepcalmandcarryon, Khoikhoi, Kittenono, Kpjas, Kupirijo, Lightmouse, Louisajb, MattKingston, Meewam, Mercenario97, Michael Bailes, Micha Sobkowski,
Middayexpress, Mort459, Mykhal, Mysid, New matt, Nikkimaria, P Ingerson, Pashihiko, Pdeitiker, Plwha, Rich Farmbrough, Rjwilmsi, Rodasmith, Sedmic, TAnthony, Terrypoon, Thricecube,
ToastieIL, TorbenBarington, Travis.Thurston, Tremello, Trezatium, Urania3, Wikipediatastic, Williadb, Yikrazuul, 36 anonymous edits
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