Abacavir

Abacavir (ABC) 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, whereas some strains that are resistant to AZT and 3TC are not as sensitive to abacavir.



Clinical indications
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.

Side effects
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 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

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. On March 1, 2011 the FDA updated the public about an ongoing safety review of abacavir and a possible increased risk of heart attack.

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

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.

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.

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.