|Chemical structure of abacavir|
|Systematic (IUPAC) name|
|Pregnancy cat.||B3 (AU) C (US)|
|Legal status||POM (UK) ℞-only (US)|
|Routes||Oral (solution or tablets)|
|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%)|
|Mol. mass||286.332 g/mol|
|Melt. point||165 °C (329 °F)|
| (what is this?)
Abacavir (ABC) i// 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%.
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.
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.
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*57:01 for which testing is now available in most western countries. There is a strong relationship with race: the prevalence of HLA-B*57:01 in some Indian ethnic groups is up to 10%, but is 0% in Japan; the prevalence is 5–7% in western Europe. Screening for the HLA-B*57:01 has been convincingly shown to reduce the incidence of abacavir hypersensitivity reactions. Abacavir binds specificially to the peptide-binding groove of HLA-B*57:01 and thereby alters the spectrum of peptides that bind to this molecule. This in turn leads to aberrant CD8 T-cell responses to self-antigens, which probably explains the side effect.
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*57:01 allele and the selection of alternative therapy in positive subjects. Genetic tests for HLA-B*57:01 are available and all patients should be screened for the HLA-B*57:01 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*57:01. On March 1, 2011 the FDA updated the public about an ongoing safety review of abacavir and a possible increased risk of heart attack.
Adverse drug reactions
Serious reactions include hypersensitivity rxn, severe anaphylaxis, Stevens Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, MI, lactic acidosis, hepatomegaly w/ steatosis, pancreatitis, immune reconstitution syndrome, and autoimmune disorders.
Common reactions include nausea, headache, fatigue, vomiting, hypersensitivity reaction, diarrhea, fever/chills, depression, rash, anxiety, URI, ALT, AST elevated, hypertriglyceridemia, and lipodystrophy.
Patients with liver disease should be cautious about using abacavir because of the possibility that it can aggravate the condition.
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.
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.
Mechanism of action
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.
- 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.
- 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 (9308): 727–32. doi:10.1016/S0140-6736(02)07873-X. PMID 11888582.
- Hetherington S, Hughes AR, Mosteller M et al. (2002). "Genetic variations in HLA-B region and hypersensitivity reactions to abacavir". Lancet 359 (9312): 1121–2. doi:10.1016/S0140-6736(02)08158-8. PMID 11943262.
- 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. PMID 16758424.
- 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): 1–3. doi:10.1097/QAI.0b013e318046ea31. PMID 17356469.
- Illing PT et al. 2012, Nature, doi:10.1038/nature11147
- Ostrov DA et al. 2012, PNAS, doi/10.1073/pnas.1207934109
- http://www.fda.gov/cder/drug/InfoSheets/HCP/abacavirHCP.htm FDA abacavir alert web access July 29, 2008.