Abacavir

Abacavir (ABC) is the most powerful nucleoside analog reverse transcriptase inhibitor (NARTI) used to treat HIV and AIDS. It is available under the trade name Ziagen™ (GlaxoSmithKline} and the combination drugs Trizivir™(abacavir, zidovudine and lamivudine) and Kivexa®/Epzicom™(abacavir and lamivudine) . It has been well tolerated; its main side effect being hypersensitivity reactions, which can be dangerous or even (in some rare cases) fatal. Fortunately, genetic testing can indicate beforehand whether an individual will be hypersensitive; over 90% of patients can safely take abacavir.

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, diarrhoea or abdominal pain and respiratory symptoms such as pharyngitis, dyspnea, or cough. Hypersensitivity is strongly associated with HLA-B

  • 5701 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 50–20%, 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.

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