Abacavir

Oral
HIV infection

Pharmacogenomics

Human leukocyte antigen B (HLA-B) plays a critical role in immune recognition of pathogens. A variant allele HLA-B*57:01 is associated with increased risk of life-threatening hypersensitivity reactions to abacavir. The prevalence of this variant allele is estimated in 11% of Southwest Asians, 6.8 % of Europeans, 2.6% of South Americans, 2.5% of Middle Easterners, 2.2% of Mexicans, 1.6% of Asians, and 1% of Africans.

Patients who are positive to HLA-B*57:01 allele have higher risk of developing hypersensitivity reactions with abacavir. CPIC does not recommend use of abacavir for these patients. Genetic screening is recommended prior to initiation of treatment. However, a negative test result for HLA-B*57:01 does not absolutely rule out the possibility of developing hypersensitivity reactions.

ESRD: Not recommended.

Mild (Child-Pugh score 5-6): 200 mg bid. Moderate to severe: Contraindicated.

May be taken with or without food.

Hypersensitivity to abacavir. Patients who are positive for HLA-B*57:01 allele. Moderate to severe hepatic impairment. Lactation.

Patient w/ risk factors for liver disease (e.g. obesity) and those w/ risk factors for coronary heart disease (e.g. HTN, DM, smoking). Renal or mild hepatic impairment. Pregnancy.

Fever, rash, cough, dyspnoea, lethargy, malaise, headache, myalgia, GI disturbances, particularly nausea, vomiting, diarrhoea and abdominal pain; pancreatitis and elevated liver enzyme values, osteonecrosis, immune reconstitution syndrome, MI, lipodystrophy syndrome. Rarely, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis.
Potentially Fatal: Serious and fatal hypersensitivity reactions w/ multiple organ involvement, lactic acidosis and severe hepatomegaly w/ steatosis.

PO: C

Monitor blood lipids and glucose reference.

Decreased serum concentrations of methadone. Slightly decreased plasma concentration w/ potent enzymatic inducers (e.g. rifampicin, phenobarbital, phenytoin). Ribavirin may enhance the hepatotoxic effect of nucleoside reverse transcriptase inhibitors.

Description:
Mechanism of Action: Abacavir competitively inhibits the reverse transcriptase of retroviruses, interfering w/ HIV viral RNA-dependent DNA polymerase resulting in inhibition of viral replication.
Pharmacokinetics:
Absorption: Rapidly absorbed from the GI tract. Absorption slightly delayed by food. Bioavailability: Approx 80%. Time to peak plasma concentration: 0.7-1.7 hr.
Distribution: Distributed into CSF. Crosses the placenta and blood brain barrier. Volume of distribution: 0.86 ± 0.15 L/kg. Plasma protein binding: Approx 50%.
Metabolism: Undergoes intracellular metabolism to carbovir triphosphate (active metabolite); hepatic metabolism via alcohol dehydrogenase and glucuronidation to inactive carboxylate and glucuronide metabolites.
Excretion: Mainly via urine. Elimination half-life: About 1.5 hr.

Source: National Center for Biotechnology Information. PubChem Database. Abacavir, CID=441300, https://pubchem.ncbi.nlm.nih.gov/compound/Abacavir (accessed on Jan. 20, 2020)

Store between 20-25°C. Oral soln may be refrigerated, do not freeze.

Antivirals

J05AF06 - abacavir ; Belongs to the class of nucleoside and nucleotide reverse transcriptase inhibitors. Used in the systemic treatment of viral infections.

Dean, L. Abacavir Therapy and HLA-B*57:01 Genotype. Medical Genetics Summaries [Internet]. Bethesda (MD): National Center for Biotechnology Information (US). Accessed 11/09/2018. PMID: 28520363

Martin M, Hoffman J, Freimuth et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for HLA-B Genotype and Abacavir Dosing: 2014 Update. Clinical Pharmacogenetics Implementation Consortium. Accessed 17/10/2018

Martin MA, Klein TE, Dong BJ, et al. Clinical Pharmacogenetics Implementation Consortium Guidelines for HLA-B Genotype and Abacavir Dosing. Nature Publishing Group. 91. doi: 10.1038/clpt.2011.355. Accessed 17/10/2018

Abacavir Overview. Pharmacogenomics Knowledgebase (PharmGKB). https://www.pharmgkb.org/. Accessed 11/09/2018.

Abacavir Sulfate Tablet, Film Coated (Apotex Corp). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 18/08/2016.

Anon. Abacavir. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 15/02/2016.

Buckingham R (ed). Abacavir. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 15/02/2016.

Clinical Pharmacogenetics Implementation Consortium Guidelines for HLA-B Genotype and Abacavir Dosing. Clinical Pharmacogenetics Implementation Consortium (CPIC). https://cpicpgx.org/. Accessed 17/10/2018.

Joint Formulary Committee. Abacavir. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. Accessed 15/02/2016.

McEvoy GK, Snow EK, Miller J et al (eds). Abacavir Sulfate. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 15/02/2016.

Supplemental Material CPIC Guidelines for HLA-B Genotype and Abacavir Dosing: 2014 Update. Clinical Pharmacogenetics Implementation Consortium (CPIC). https://cpicpgx.org/. Accessed 17/10/2018.