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Abacavir



Abacavir
Systematic (IUPAC) name
[(1R)-4-[2-amino-6-(cyclopropylamino)purin-9-yl]-
1-cyclopent-2-enyl]methanol
Identifiers
CAS number ?
ATC code J05AF06
PubChem 441300
DrugBank APRD00216
Chemical data
Formula C14H18N6O 
Mol. mass 286.333 g/mol
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)

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, rarely, fatal. Genetic testing can indicate whether an individual will be hypersensitive; over 90% of patients can safely take abacavir.

Additional recommended knowledge

 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 will expire 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 gluconyl 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[1][2] for which testing is now available in most western countries. There is a strong relationship with race: the prevalence of HLA-B*5701 in India is 20–50%, 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.[3][4]

Cautions and Warnings

Stop taking this drug at the first sign of drug allergy or sensitivity. People have died from abacavir sensitivity. People with liver disease should be cautious about using this drug because of the possibility that it can aggravate the condition. Some people have died from liver damage associated with abacavir. The use of nucleoside drugs such as abacavir can very rarely cause lactic acidosis, a fatal metabolic disturbance. Resistance to abacavir has developed in laboratort versions of HIV also resistant to lamivudine, didanosine and zalcitabine. HIV that is resistant to protease inhibitors is not likely to be resistant to abacavir. Redistribution or accumulation of body fat may occur in people taking antiviral medications including: central obesity; facial arm, leg, and/ or buttock wasting; breast enlargement; and fat accumulation at the base of the neck (buffalo hump). Abacavir cannot be used in infants under age 3 months.

Food Interactions

None known

Usual Dose

Adult (age 17 and over) :300mg 2 times a day Child (age 3 months - 16 years) 3.6mg per lb. of body weight twice a day, up to a maximun of 300mg 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. ALWAYS brings the prescription bottle or container.

References

  • Antiretroviral Therapy-Investigational NRTIs: HIV Clinical Management Vol. 3. Medscape Inc, 1998
  • HIV Insite Antiretroviral Drug Database; UC Regents, 1999
  1. ^ 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.
  2. ^ Hetherington S, Hughes AR, Mosteller M, et al. (2002). "Genetic variations in HLA-B region and hypersensitivity reactions to abacavir". Lancet 359: 1121–2.
  3. ^ 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.
  4. ^ 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. PMID 17356469.
 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Abacavir". A list of authors is available in Wikipedia.
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