Abacavir (ABC) is a nucleoside Nucleosides are glycosylamines consisting of a nucleobase bound to a ribose or deoxyribose sugar via a beta-glycosidic linkage. Examples of nucleosides include cytidine, uridine, adenosine, guanosine, thymidine and inosine analog 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 (NRTI) used to treat HIV Human immunodeficiency virus is a lentivirus (a member of the retrovirus family) that causes acquired immunodeficiency syndrome (AIDS), a condition in humans in which the immune system begins to fail, leading to life-threatening opportunistic infections. Infection with HIV occurs by the transfer of blood, semen, vaginal fluid, pre-ejaculate, or and AIDS Acquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the human immunodeficiency virus (HIV). This condition progressively reduces the effectiveness of the immune system and leaves individuals susceptible to opportunistic infections and tumors. HIV is transmitted through direct. It is available under the trade name Ziagen (GlaxoSmithKline GlaxoSmithKline plc is a British pharmaceutical, biological, and healthcare company. GSK is the world's fourth largest pharmaceutical company after Johnson & Johnson, Pfizer, and Roche respectively by revenue; and a research-based company with a wide portfolio of pharmaceutical products covering anti-infectives, central nervous system,) and in the combination formulations Trizivir (abacavir, zidovudine Zidovudine or azidothymidine (AZT) (also called ZDV) is a nucleoside analog reverse transcriptase inhibitor (NRTI), a type of antiretroviral drug used for the treatment of HIV/AIDs. It is an analog of thymidine and lamivudine Lamivudine is a potent nucleoside analog reverse transcriptase inhibitor (nRTI)) and Kivexa/Epzicom(abacavir and lamivudine) . It has been well tolerated: the main side effect is hypersensitivity Hypersensitivity refers to undesirable (damaging, discomfort-producing and sometimes fatal) reactions produced by the normal immune system. Hypersensitivity reactions require a pre-sensitized (immune) state of the host. The four-group classification was expounded by P. H. G. Gell and Robin Coombs in 1963, 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%.[1]

Two (2) Abacavir 300mg tablets

Viral strains that are resistant to zidovudine Zidovudine or azidothymidine (AZT) (also called ZDV) is a nucleoside analog reverse transcriptase inhibitor (NRTI), a type of antiretroviral drug used for the treatment of HIV/AIDs. It is an analog of thymidine (AZT) or lamivudine Lamivudine is a potent nucleoside analog reverse transcriptase inhibitor (nRTI) (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 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, responsible for protecting and promoting public health through the regulation and supervision of food safety, tobacco products, dietary supplements, prescription and over-the-counter (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 In chemistry, structural analogs , also known as chemical analogs or simply analogs, are compounds in which one or more atoms, functional groups, or substructures have been replaced with different atoms, groups, or substructures. Despite a high chemical similarity, structural analogs are not necessarily functional analogs and can have very of guanosine Guanosine is a nucleoside comprising guanine attached to a ribose ring via a β-N9-glycosidic bond (a 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 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 double-stranded DNA. It also helps in the formation of a double helix DNA once the RNA has been reverse transcribed into a single strand cDNA. Normal enzyme.

Pharmacokinetics

Abacavir is given orally and has a high bioavailability In pharmacology, bioavailability 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 intravenously, its bioavailability is 100%. However, when a medication is administered via (83%). It is metabolised primarily through alcohol dehydrogenase Alcohol dehydrogenases (EC 1.1.1.1) are a group of seven dehydrogenase enzymes that occur in many organisms and facilitate the interconversion between alcohols and aldehydes or ketones with the reduction of NAD+ to NADH. In humans and many other animals, they serve to break down alcohols which could otherwise be toxic; in yeast, plants and many or glucuronyl transferase. It is capable of crossing the blood-brain barrier The blood-brain barrier is a separation of circulating blood and cerebrospinal fluid (CSF) in the central nervous system (CNS). It occurs along all capillaries and consists of tight junctions around the capillaries that don't exist in normal circulation. Endothelial cells restrict the diffusion of microscopic objects (e.g. bacteria) and large or.

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 The human leukocyte antigen system is the name of the major histocompatibility complex (MHC) in humans. The superlocus 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 many other genes. The HLA genes are the human-B*5701[2][3][4] 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.[5][6]

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.[7]

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 Nucleosides are glycosylamines consisting of a nucleobase bound to a ribose or deoxyribose sugar via a beta-glycosidic linkage. Examples of nucleosides include cytidine, uridine, adenosine, guanosine, thymidine and inosine drugs such as abacavir can very rarely cause lactic acidosis Lactic acidosis is a physiological condition characterized by low pH in body tissues and blood accompanied by the buildup of lactate, and is considered a distinct form of metabolic acidosis. The condition typically occurs when cells receive too little oxygen (hypoxia), for example during vigorous exercise. In this situation, impaired cellular.

Resistance to abacavir has developed in laboratory versions of HIV which are also resistant to other HIV-specific antiretrovirals such as lamivudine Lamivudine is a potent nucleoside analog reverse transcriptase inhibitor (nRTI), didanosine and zalcitabine. HIV strains that are resistant to protease inhibitors Protease inhibitors are a class of drugs used to treat or prevent infection by viruses, including HIV and Hepatitis C. PIs prevent viral replication by inhibiting the activity of HIV-1 protease, an enzyme used by the viruses to cleave nascent proteins for final assembly of new virons are not likely to be resistant to abacavir.

Redistribution or accumulation of body fat, 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 (usually the face). This condition is also characterized by a lack of circulating leptin which may lead to osteosclerosis, 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 day Child (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.

References

  1. ^ SFGate.com
  2. ^ Mallal S, Phillips E, Carosi G, et al. (February 2008). "HLA-B*5701 screening for hypersensitivity to abacavir". N. Engl. J. Med. 358 (6): 568–79. doi A digital object identifier is a character string used to uniquely identify an electronic document or other object. Metadata about the object is stored in association with the DOI name and this metadata may include a location, such as a URL, where the object can be found. The DOI for a document is permanent, whereas its location and other metadata:10.1056/NEJMoa0706135. PMID A PMID is a unique number assigned to each PubMed citation of life sciences and biomedical scientific journal articles. The related Pubmed Central archive may additionally assign a separate number, a PMCID (PubMed Central Identifier), normally written with a PMC prefix 18256392. http://content.nejm.org/cgi/pmidlookup?view=short&pmid=18256392&promo=ONFLNS19.
  3. ^ Mallal S, Nolan D, Witt C, et al. (2002). "Association between the presence of HLA-B*5701, HLA-DR7 and HLA-DQ3 and hypersensitivity to HIV-1 reverse transcriptase inhibitor abacavir". Lancet 359 (9308): 727–32. doi A digital object identifier is a character string used to uniquely identify an electronic document or other object. Metadata about the object is stored in association with the DOI name and this metadata may include a location, such as a URL, where the object can be found. The DOI for a document is permanent, whereas its location and other metadata:10.1016/S0140-6736(02)07873-X. PMID A PMID is a unique number assigned to each PubMed citation of life sciences and biomedical scientific journal articles. The related Pubmed Central archive may additionally assign a separate number, a PMCID (PubMed Central Identifier), normally written with a PMC prefix 11888582.
  4. ^ Hetherington S, Hughes AR, Mosteller M, et al. (2002). "Genetic variations in HLA-B region and hypersensitivity reactions to abacavir". Lancet 359 (9312): 1121–2. doi A digital object identifier is a character string used to uniquely identify an electronic document or other object. Metadata about the object is stored in association with the DOI name and this metadata may include a location, such as a URL, where the object can be found. The DOI for a document is permanent, whereas its location and other metadata:10.1016/S0140-6736(02)08158-8. PMID A PMID is a unique number assigned to each PubMed citation of life sciences and biomedical scientific journal articles. The related Pubmed Central archive may additionally assign a separate number, a PMCID (PubMed Central Identifier), normally written with a PMC prefix 11943262.
  5. ^ Rauch A, Nolan D, Martin A, et al. (2006). "Prospective genetic screening decreases the incidence of abacavir hypersensitivity reactions in the Western Australian HIV cohort study". Clin Infect Dis 43 (1): 99–102. doi A digital object identifier is a character string used to uniquely identify an electronic document or other object. Metadata about the object is stored in association with the DOI name and this metadata may include a location, such as a URL, where the object can be found. The DOI for a document is permanent, whereas its location and other metadata:10.1086/504874. PMID A PMID is a unique number assigned to each PubMed citation of life sciences and biomedical scientific journal articles. The related Pubmed Central archive may additionally assign a separate number, a PMCID (PubMed Central Identifier), normally written with a PMC prefix 16758424.
  6. ^ Zucman D, de Truchis P, Majerholc C, et al. (2007). "Prospective Screening for Human Leukocyte Antigen-B*5701 Avoids Abacavir Hypersensitivity Reaction in the Ethnically Mixed French HIV Population". J Acquir Immune Defic Syndr 45 (1): 1. doi A digital object identifier is a character string used to uniquely identify an electronic document or other object. Metadata about the object is stored in association with the DOI name and this metadata may include a location, such as a URL, where the object can be found. The DOI for a document is permanent, whereas its location and other metadata:10.1097/QAI.0b013e318046ea31. PMID A PMID is a unique number assigned to each PubMed citation of life sciences and biomedical scientific journal articles. The related Pubmed Central archive may additionally assign a separate number, a PMCID (PubMed Central Identifier), normally written with a PMC prefix 17356469.
  7. ^ http://www.fda.gov/cder/drug/InfoSheets/HCP/abacavirHCP.htm FDA abacavir alert web access July 29, 2008

External links

Antiviral drugs Antiviral drugs are a class of medication used specifically for treating viral infections. Like antibiotics for bacteria, specific antivirals are used for specific viruses. Unlike most antibiotics, antiviral drugs do not destroy their target pathogen; instead they inhibit their development: antiretroviral drugs Antiretroviral drugs are medications for the treatment of infection by retroviruses, primarily HIV. When several such drugs, typically three or four, are taken in combination, the approach is known as highly active antiretroviral therapy, or HAART. The American National Institutes of Health and other organizations recommend offering antiretroviral used against HIV Human immunodeficiency virus is a lentivirus (a member of the retrovirus family) that causes acquired immunodeficiency syndrome (AIDS), a condition in humans in which the immune system begins to fail, leading to life-threatening opportunistic infections. Infection with HIV occurs by the transfer of blood, semen, vaginal fluid, pre-ejaculate, or (primarily J05)
Entry/fusion inhibitors (Discovery & development) gp41 (Enfuvirtide) · CCR5 C-C chemokine receptor type 5 also known as CCR5 is a protein that in humans is encoded by the CCR5 gene. CCR5 is a member of the beta chemokine receptors family of integral membrane proteins (Maraviroc, Vicriviroc†, PRO 140†) · CD4 CD4 is a glycoprotein expressed on the surface of T helper cells, regulatory T cells, monocytes, macrophages, and dendritic cells. It was discovered in the late 1970s and was originally known as leu-3 and T4 (after the OKT4 monoclonal antibody that reacted with it) before being named CD4 in 1984. In humans, the CD4 protein is encoded by the CD4 (Ibalizumab†)
Reverse transcriptase inhibitors (RTIs)
Nucleoside & Nucleotide (NRTI)

Nucleoside analogues/NARTIs 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: Abacavir (ABC)°# · Emtricitabine (FTC)°# · Lamivudine (3TC) Lamivudine is a potent nucleoside analog reverse transcriptase inhibitor (nRTI)°# · Didanosine (ddI)# · Zidovudine (AZT) Zidovudine or azidothymidine (AZT) (also called ZDV) is a nucleoside analog reverse transcriptase inhibitor (NRTI), a type of antiretroviral drug used for the treatment of HIV/AIDs. It is an analog of thymidine# · Apricitabine† · Stampidine† · Elvucitabine† · Racivir† · Amdoxovir† · Stavudine (d4T) Stavudine is a nucleoside analog reverse transcriptase inhibitor (NARTI) active against HIV# · Zalcitabine (ddC)◊

Nucleotide analogues/NtRTIs 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: Tenofovir Tenofovir disoproxil fumarate , marketed by Gilead Sciences under the trade name Viread, belongs to a class of antiretroviral drugs known as nucleotide analogue reverse transcriptase inhibitors (nRTIs), which block reverse transcriptase, an enzyme crucial to viral production in HIV-infected people°#
Non-Nucleoside (NNRTI) 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 (Discovery & development) (1st gen) Efavirenz Efavirenz is a non-nucleoside reverse transcriptase inhibitor (NNRTI) and is used as part of highly active antiretroviral therapy (HAART) for the treatment of a human immunodeficiency virus (HIV) type 1°# · Nevirapine# · Loviride◊ · Delavirdine Delavirdine (brand name Rescriptor) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) marketed by Pfizer. It is used as part of highly active antiretroviral therapy (HAART) for the treatment of human immunodeficiency virus (HIV) type 1. It is presented as the mesylate. The recommended dosage is 400 mg, three times a day◊ · (2nd gen) diarylpyrimidines (Etravirine, Rilpivirine†) · Lersivirine†
Integrase inhibitors Integrase inhibitors are a class of antiretroviral drug designed to block the action of integrase, a viral enzyme that inserts the viral genome into the DNA of the host cell. Since integration is a vital step in retroviral replication, blocking it can halt further spread of the virus. Integrase inhibitors were initially developed for the treatment Raltegravir · Elvitegravir† · Globoidnan A (experimental) · MK-2048† · GSK-572†
Maturation inhibitors Bevirimat† · Vivecon†
Protease Inhibitors (PI) Protease inhibitors are a class of medications used to treat or prevent infection by viruses, including HIV and Hepatitis C. PIs prevent viral replication by inhibiting the activity of HIV-1 protease, an enzyme used by the viruses to cleave nascent proteins for final assembly of new virons (Discovery and development) Atazanavir° · Fosamprenavir° · Lopinavir°# · Darunavir · Nelfinavir# · Ritonavir# · Saquinavir# · Tipranavir · Amprenavir◊ · Indinavir◊#
Combined formulations Combivir · Atripla · Trizivir · Truvada · Kaletra · Epzicom
Experimental agents
Uncoating inhibitors TRIM5alpha (gene)
Transcription inhibitors Tat antagonists
Translation inhibitors Trichosanthin
Other Abzyme · Calanolide A · Ceragenin · Cyanovirin-N · Diarylpyrimidines · Epigallocatechin gallate (EGCG) · Foscarnet · Griffithsin · Hydroxycarbamide · Miltefosine · Portmanteau inhibitors · Seliciclib† · Synergistic enhancers · Tre recombinase · Zinc finger protein transcription factor · KP-1461†
Failed agents Dexelvucitabine · Capravirine · Emivirine · Lodenosine · Atevirdine · Brecanavir · Aplaviroc
#WHO-EM. ‡Withdrawn from market. CLINICAL TRIALS: †Phase III. §Never to phase III °DHHS preferred first-line agent. ◊Formerly or rarely used agent.

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