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Abacavir
Systematic (IUPAC) name
{(1S,4R)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]cyclopent-2-en-1-yl}methanol
Identifiers
CAS number 136470-78-5
ATC code J05AF06
PubChem 441300
DrugBank APRD00216
ChemSpider 390063
Chemical data
Formula C14H18N6O 
Mol. mass 286.332 g/mol
SMILES eMolecules & PubChem
Pharmacokinetic data
Bioavailability 83%
Metabolism Hepatic
Half life 1.54 ± 0.63 hours
Excretion Renal (1.2% abacavir, 30% 5'-carboxylic acid metabolite, 36% 5'-glucuronide metabolite, 15% unidentified minor metabolites). Fecal (16%)
Therapeutic considerations
Pregnancy cat. B3(AU) C(US)
Legal status POM (UK)
Routes Oral (solution or tablets)
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Abacavir (ABC) is a nucleoside analog reverse transcriptase inhibitor (NRTI) used to treat HIV and AIDS. It is available under the trade name Ziagen (GlaxoSmithKline) 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%.[1]

Two (2) Abacavir 300mg tablets

Viral strains that are resistant to zidovudine (AZT) or lamivudine (3TC) are generally sensitive to abacavir, whereas strains that are resistant to AZT and 3TC are not as sensitive to abacavir.

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.

Indication

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.

Mechanism of action

ABC is an analog of guanosine (a purine). Its target is the viral reverse transcriptase enzyme.

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 blood-brain barrier.

Adverse reactions

Fatal hypersensitivity reactions have been associated with therapy with abacavir. Symptoms of hypersensitivity include fever, skin rash, fatigue, gastrointestinal symptoms such as nausea, vomiting, diarrhea or abdominal pain and respiratory symptoms such as pharyngitis, dyspnea, or cough.

Hypersensitivity is strongly associated with HLA-B*5701[2][3][4] for which testing is now available in most western countries. There is a strong relationship with race: the prevalence of HLA-B*5701 in some Indian ethic groups is up to 10%, but is 0% in Japan; the prevalence is 5–7% in western Europe. Screening for the HLA-B*5701 has been convincingly shown to reduce the incidence of abacavir hypersensitivity reactions.[5][6]

A new FDA alert concerning abacavir and abacavir containing medications was issued on July 24, 2008. FDA informed that based on data from two studies they support a recommendation for pre-therapy screening for the presence of the HLA-B*5701 allele and the selection of alternative therapy in positive subjects. Genetic tests for HLA-B*5701 are available and all patients should be screened for the HLA-B*5701 allele before starting or restarting treatment with abacavir or abacavir containing medications. Development of clinically suspected abacavir HSR requires immediate and permanent discontinuation of abacavir therapy in all patients, including patients negative for HLA-B*5701.[7]

Cautions and Warnings

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 of the neck (buffalo hump).

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

Food Interactions

None known

Usual Dose

Adult (age 17 and over) :300 mg 2 times a day Child (age 3 months - 16 years) 3.6 mg per lb. of body weight twice a day, up to a maximum of 300 mg in each dose.

Overdosage

Little is known about the effects of Abacavir overdose. Overdose victims should be taken to a hospital emergency room for treatment and always bring the prescription bottle or container.

References

  1. ^ SFGate.com
  2. ^ Mallal S, Phillips E, Carosi G, et al. (February 2008). "HLA-B*5701 screening for hypersensitivity to abacavir". N. Engl. J. Med. 358 (6): 568–79. doi:10.1056/NEJMoa0706135. PMID 18256392. http://content.nejm.org/cgi/pmidlookup?view=short&pmid=18256392&promo=ONFLNS19. 
  3. ^ Mallal S, Nolan D, Witt C, et al. (2002). "Association between the presence of HLA-B*5701, HLA-DR7 and HLA-DQ3 and hypersensitivity to HIV-1 reverse transcriptase inhibitor abacavir". Lancet 359: 727–32. doi:10.1016/S0140-6736(02)07873-X. 
  4. ^ Hetherington S, Hughes AR, Mosteller M, et al. (2002). "Genetic variations in HLA-B region and hypersensitivity reactions to abacavir". Lancet 359: 1121–2. doi:10.1016/S0140-6736(02)08158-8. 
  5. ^ 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". Clin Infect Dis 43 (1): 99–102. doi:10.1086/504874. 
  6. ^ Zucman D, de Truchis P, Majerholc C, et al. (2007). "Prospective Screening for Human Leukocyte Antigen-B*5701 Avoids Abacavir Hypersensitivity Reaction in the Ethnically Mixed French HIV Population". J Acquir Immune Defic Syndr 45: 1. doi:10.1097/QAI.0b013e318046ea31. PMID 17356469. 
  7. ^ http://www.fda.gov/cder/drug/InfoSheets/HCP/abacavirHCP.htm FDA abacavir alert web access July 29, 2008

External links

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