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 expired 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 glucuronyl 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 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 medicationswas 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.

Cautions and 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

Usual Dose

Adult (age 17 and over) :300 mg 2 times a dayChild (age 3 months - 16 years) 3. 6 mg per lb. of body weight twice a day, up to a maximum of 300 mg 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 and always bring the prescription bottle or container.