Abacavir
Encyclopedia
Abacavir 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.
_300mg.jpg)
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.
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.
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.
of guanosine
(a purine
). Its target is the viral reverse transcriptase
enzyme.
(83%). It is metabolised primarily through alcohol dehydrogenase
or glucuronyl transferase. It is capable of crossing the blood-brain barrier
.
(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.
Nucleoside
Nucleosides are glycosylamines consisting of a nucleobase bound to a ribose or deoxyribose sugar via a beta-glycosidic linkage...
analog reverse transcriptase inhibitor
Reverse transcriptase inhibitor
Reverse-transcriptase inhibitors are a class of antiretroviral drug used to treat HIV infection, tumors, and cancer. RTIs inhibit activity of reverse transcriptase, a viral DNA polymerase enzyme that retroviruses need to reproduce.-Mechanism:...
(NRTI) used to treat HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
and AIDS
AIDS
Acquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the human immunodeficiency virus...
. It is available under the trade name Ziagen (ViiV Healthcare
ViiV Healthcare
ViiV Healthcare is a pharmaceutical company specializing in the development of therapies for HIV that was created as a joint venture by Pfizer and GlaxoSmithKline in November 2009 with both companies transferring their HIV assets to the new company. 85% of the company is owned by GlaxoSmithKline...
) and in the combination formulations Trizivir (abacavir, zidovudine
Zidovudine
Zidovudine or azidothymidine is a nucleoside analog reverse-transcriptase inhibitor , a type of antiretroviral drug used for the treatment of HIV/AIDS. It is an analog of thymidine....
and lamivudine
Lamivudine
Lamivudine is a potent nucleoside analog reverse transcriptase inhibitor .It is marketed by GlaxoSmithKline with the brand names Zeffix, Heptovir, Epivir, and Epivir-HBV.Lamivudine has been used for treatment of chronic hepatitis B at a lower dose than for treatment of HIV...
) and Kivexa/Epzicom(abacavir and lamivudine) . It has been well tolerated: the main side effect is hypersensitivity
Hypersensitivity
Hypersensitivity refers to undesirable reactions produced by the normal immune system, including allergies and autoimmunity. These reactions may be damaging, uncomfortable, or occasionally fatal. Hypersensitivity reactions require a pre-sensitized state of the host. The four-group classification...
, 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
Zidovudine
Zidovudine or azidothymidine is a nucleoside analog reverse-transcriptase inhibitor , a type of antiretroviral drug used for the treatment of HIV/AIDS. It is an analog of thymidine....
(AZT) or lamivudine
Lamivudine
Lamivudine is a potent nucleoside analog reverse transcriptase inhibitor .It is marketed by GlaxoSmithKline with the brand names Zeffix, Heptovir, Epivir, and Epivir-HBV.Lamivudine has been used for treatment of chronic hepatitis B at a lower dose than for treatment of HIV...
(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
Human leukocyte antigen
The human leukocyte antigen system is the name of the major histocompatibility complex in humans. The super locus contains a large number of genes related to immune system function in humans. This group of genes resides on chromosome 6, and encodes cell-surface antigen-presenting proteins and...
-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
Nucleoside
Nucleosides are glycosylamines consisting of a nucleobase bound to a ribose or deoxyribose sugar via a beta-glycosidic linkage...
drugs such as abacavir can very rarely cause lactic acidosis
Lactic acidosis
Lactic acidosis is a physiological condition characterized by low pH in body tissues and blood accompanied by the buildup of lactate especially D-lactate, and is considered a distinct form of metabolic acidosis. The condition typically occurs when cells receive too little oxygen , for example...
.
Resistance to abacavir has developed in laboratory versions of HIV which are also resistant to other HIV-specific antiretrovirals such as lamivudine
Lamivudine
Lamivudine is a potent nucleoside analog reverse transcriptase inhibitor .It is marketed by GlaxoSmithKline with the brand names Zeffix, Heptovir, Epivir, and Epivir-HBV.Lamivudine has been used for treatment of chronic hepatitis B at a lower dose than for treatment of HIV...
, didanosine
Didanosine
Didanosine is sold under the trade names Videx and Videx EC. It is a reverse transcriptase inhibitor, effective against HIV and used in combination with other antiretroviral drug therapy as part of highly active antiretroviral therapy .-History:The related pro-drug of 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
Lipodystrophy
Lipodystrophy is a medical condition characterized by abnormal or degenerative conditions of the body's adipose tissue. A more specific term, lipoatrophy is used when describing the loss of fat from one area...
, 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.
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 analogAnalog (chemistry)
In chemistry, a structural analog , also known as chemical analog or simply analog, is a compound having a structure similar to that of another one, but differing from it in respect of a certain component. It can differ in one or more atoms, functional groups, or substructures, which are replaced...
of guanosine
Guanosine
Guanosine is a purine nucleoside comprising guanine attached to a ribose ring via a β-N9-glycosidic bond. Guanosine can be phosphorylated to become guanosine monophosphate , cyclic guanosine monophosphate , guanosine diphosphate , and guanosine triphosphate...
(a purine
Purine
A purine is a heterocyclic aromatic organic compound, consisting of a pyrimidine ring fused to an imidazole ring. Purines, including substituted purines and their tautomers, are the most widely distributed kind of nitrogen-containing heterocycle in nature....
). Its target is the viral reverse transcriptase
Reverse transcriptase
In the fields of molecular biology and biochemistry, a reverse transcriptase, also known as RNA-dependent DNA polymerase, is a DNA polymerase enzyme that transcribes single-stranded RNA into single-stranded DNA. It also helps in the formation of a double helix DNA once the RNA has been reverse...
enzyme.
Pharmacokinetics
Abacavir is given orally and has a high bioavailabilityBioavailability
In pharmacology, bioavailability is a subcategory of absorption and is used to describe the fraction of an administered dose of unchanged drug that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. By definition, when a medication is administered...
(83%). It is metabolised primarily through alcohol dehydrogenase
Alcohol dehydrogenase
Alcohol dehydrogenases are a group of dehydrogenase enzymes that occur in many organisms and facilitate the interconversion between alcohols and aldehydes or ketones with the reduction of nicotinamide adenine dinucleotide...
or glucuronyl transferase. It is capable of crossing the blood-brain barrier
Blood-brain barrier
The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...
.
History
Abacavir was approved by the Food and Drug AdministrationFood and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
(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.