![]() | |
![]() Chemical structure of abacavir | |
Clinical data | |
---|---|
Pronunciation | /əˈbækəvɪər/ |
Trade names | Ziagen |
Other names | Abacavir sulfate (USAN US) |
AHFS/Drugs.com | Monograph |
MedlinePlus | a699012 |
License data | |
Pregnancy category |
|
Routes of administration | By mouth |
ATC code | |
Legal status | |
Legal status | |
Pharmacokinetic data | |
Bioavailability | 83% |
Metabolism | Liver |
Elimination half-life | 1.54 ± 0.63 h |
Excretion | Kidney (1.2% abacavir, 30% 5'-carboxylic acid metabolite, 36% 5'-glucuronide metabolite, 15% unidentified minor metabolites). Fecal (16%) |
Identifiers | |
| |
CAS Number | |
PubChem CID | |
DrugBank | |
ChemSpider | |
UNII | |
KEGG | |
ChEBI | |
ChEMBL | |
NIAID ChemDB | |
CompTox Dashboard (EPA) | |
ECHA InfoCard | 100.149.341 |
Chemical and physical data | |
Formula | C14H18N6O |
Molar mass | 286.339 g·mol−1 |
3D model (JSmol) | |
Melting point | 165 °C (329 °F) |
| |
| |
(verify) |
Abacavir, sold under the brand name Ziagen among others, is a medication used to treat HIV/AIDS. [3] [4] [5] [6] Similar to other nucleoside analog reverse-transcriptase inhibitors (NRTIs), abacavir is used together with other HIV medications, and is not recommended by itself. [7] It is taken by mouth as a tablet or solution and may be used in children over the age of three months. [5] [8]
Abacavir is generally well tolerated. [8] Common side effects include vomiting, insomnia (trouble sleeping), fever, and feeling tired. [5] Other common side effects include loss of appetite, headache, nausea (feeling sick), diarrhea, rash, and lethargy (lack of energy). [4] More severe side effects include hypersensitivity, liver damage, and lactic acidosis. [5] Genetic testing can indicate whether a person is at higher risk of developing hypersensitivity. [5] Symptoms of hypersensitivity include rash, vomiting, and shortness of breath. [8] Abacavir is in the NRTI class of medications, which work by blocking reverse transcriptase, an enzyme needed for HIV virus replication. [9] Within the NRTI class, abacavir is a carbocyclic nucleoside. [5]
Abacavir was patented in 1988, and approved for use in the United States in 1998. [10] [11] It is on the World Health Organization's List of Essential Medicines. [12] It is available as a generic medication. [5] Abacavir is used together with other HIV medications, such as abacavir/lamivudine/zidovudine, abacavir/dolutegravir/lamivudine, and abacavir/lamivudine. [8] [9] The combination abacavir/lamivudine is an essential medicine. [12]
Abacavir, in combination with other antiretroviral agents, is indicated for the treatment of HIV-1 infection. [3] [4] Abacavir should be used in combination with other antiretroviral agents. [3] [4]
Abacavir is contraindicated for people who have the HLA‑B*5701 allele or who have moderate or severe liver disease (hepatic impairment). [3] [4]
Common adverse reactions include nausea, headache, fatigue, vomiting, diarrhea, Anorexia (symptom) (loss of appetite), and insomnia (trouble sleeping). Rare but serious side effects include hypersensitivity reaction such as rash, elevated AST and ALT, depression, anxiety, fever/chills, URI, lactic acidosis, hypertriglyceridemia, and lipodystrophy. [13]
Hypersensitivity to abacavir is strongly associated with a specific allele at the human leukocyte antigen B locus namely HLA-B*5701. [14] [15] [16] The mechanism for this hypersensitivity reaction is due to abacavir binding in the antigen-binding cleft of HLA-B*57:01, allowing alternative peptides to bind, which appear as "non-self" when presented to T cells. [17] There is an association between the prevalence of HLA-B*5701 and ancestry. The prevalence of the allele is estimated to be 3.4 to 5.8 percent on average in populations of European ancestry, 17.6 percent in Indian Americans, 3.0 percent in Hispanic Americans, and 1.2 percent in Chinese Americans. [18] [19] There is significant variability in the prevalence of HLA-B*5701 among African populations. In African Americans, the prevalence is estimated to be 1.0 percent on average, 0 percent in the Yoruba from Nigeria, 3.3 percent in the Luhya from Kenya, and 13.6 percent in the Masai from Kenya, although the average values are derived from highly variable frequencies within sample groups. [20]
Common symptoms of abacavir hypersensitivity syndrome include fever, malaise, nausea, and diarrhea. Some patients may also develop a skin rash. [21] Symptoms of AHS typically manifest within six weeks of treatment using abacavir, although they may be confused with symptoms of HIV, immune reconstitution syndrome, hypersensitivity syndromes associated with other drugs, or infection. [22] The U.S. Food and Drug Administration (FDA) released an alert concerning abacavir and abacavir-containing medications on 24 July 2008, [23] and the FDA-approved drug label for abacavir recommends pre-therapy screening for the HLA-B*5701 allele and the use of alternative therapy in subjects with this allele. [3] Additionally, both the Clinical Pharmacogenetics Implementation Consortium and the Dutch Pharmacogenetics Working Group recommend use of an alternative therapy in individuals with the HLA-B*5701 allele. [24] [25]
Skin-patch testing may also be used to determine whether an individual will experience a hypersensitivity reaction to abacavir, although some patients susceptible to developing AHS may not react to the patch test. [26]
The development of suspected hypersensitivity reactions to abacavir requires immediate and permanent discontinuation of abacavir therapy in all patients, including patients who do not possess the HLA-B*5701 allele. On 1 March 2011, the FDA informed the public about an ongoing safety review of abacavir and a possible increased risk of heart attack associated with the drug. [27] A meta-analysis of 26 studies conducted by the FDA, however, did not find any association between abacavir use and heart attack [28] [29]
The mechanism underlying abacavir hypersensitivity syndrome is related to the change in the HLA-B*5701 protein product. Abacavir binds with high specificity to the HLA-B*5701 protein, changing the shape and chemistry of the antigen-binding cleft. This results in a change in immunological tolerance and the subsequent activation of abacavir-specific cytotoxic T cells, which produce a systemic reaction known as abacavir hypersensitivity syndrome. [17]
Abacavir, and in general NRTIs, do not undergo hepatic metabolism and therefore have very limited (to none) interaction with the CYP enzymes and drugs that effect these enzymes. That being said there are still few interactions that can affect the absorption or the availability of abacavir. Below are few of the common established drug and food interaction that can take place during abacavir co-administration:
Abacavir is a nucleoside reverse transcriptase inhibitor that inhibits viral replication. It is a guanosine analogue that is phosphorylated to carbovir triphosphate (CBV-TP). CBV-TP competes with the viral molecules and is incorporated into the viral DNA. Once CBV-TP is integrated into the viral DNA, transcription and HIV reverse transcriptase is inhibited. [37]
Abacavir is given orally and is rapidly absorbed with a high bioavailability of 83%. [38] Solution and tablet have comparable concentrations and bioavailability. Abacavir can be taken with or without food. [39]
Abacavir can cross the blood–brain barrier. Abacavir is metabolized primarily through the enzymes alcohol dehydrogenase and glucuronyl transferase to an inactive carboxylate and glucuronide metabolites. It has a half-life of approximately 1.5-2.0 hours. If a person has liver failure, abacavir's half life is increased by 58%. [40]
Abacavir is eliminated via excretion in the urine (83%) and feces (16%). [41] It is unclear whether abacavir can be removed by hemodialysis or peritoneal dialysis. [37]
Robert Vince and Susan Daluge along with Mei Hua, a visiting scientist from China, developed the medication in the '80s. [42] [43] [44]
Abacavir was approved by the U.S. Food and Drug Administration (FDA) on 18 December 1998, and is thus the fifteenth approved antiretroviral drug in the United States. [45]
Zidovudine (ZDV), also known as azidothymidine (AZT), was the first antiretroviral medication used to prevent and treat HIV/AIDS. It is generally recommended for use in combination with other antiretrovirals. It may be used to prevent mother-to-child spread during birth or after a needlestick injury or other potential exposure. It is sold both by itself and together as lamivudine/zidovudine and abacavir/lamivudine/zidovudine. It can be used by mouth or by slow injection into a vein.
The management of HIV/AIDS normally includes the use of multiple antiretroviral drugs as a strategy to control HIV infection. There are several classes of antiretroviral agents that act on different stages of the HIV life-cycle. The use of multiple drugs that act on different viral targets is known as highly active antiretroviral therapy (HAART). HAART decreases the patient's total burden of HIV, maintains function of the immune system, and prevents opportunistic infections that often lead to death. HAART also prevents the transmission of HIV between serodiscordant same-sex and opposite-sex partners so long as the HIV-positive partner maintains an undetectable viral load.
Reverse-transcriptase inhibitors (RTIs) are a class of antiretroviral drugs used to treat HIV infection or AIDS, and in some cases hepatitis B. RTIs inhibit activity of reverse transcriptase, a viral DNA polymerase that is required for replication of HIV and other retroviruses.
Zalcitabine, also called dideoxycytidine, is a nucleoside analog reverse-transcriptase inhibitor (NRTI) sold under the trade name Hivid. Zalcitabine was the third antiretroviral to be approved by the Food and Drug Administration (FDA) for the treatment of HIV/AIDS. It is used as part of a combination regimen.
Stavudine (d4T), sold under the brand name Zerit among others, is an antiretroviral medication used to prevent and treat HIV/AIDS. It is generally recommended for use with other antiretrovirals. It may be used for prevention after a needlestick injury or other potential exposure. However, it is not a first-line treatment. It is given by mouth.
Lamivudine, commonly called 3TC, is an antiretroviral medication used to prevent and treat HIV/AIDS. It is also used to treat chronic hepatitis B when other options are not possible. It is effective against both HIV-1 and HIV-2. It is typically used in combination with other antiretrovirals such as zidovudine, dolutegravir, and abacavir. Lamivudine may be included as part of post-exposure prevention in those who have been potentially exposed to HIV. Lamivudine is taken by mouth as a liquid or tablet.
Nevirapine (NVP), sold under the brand name Viramune among others, is a medication used to treat and prevent HIV/AIDS, specifically HIV-1. It is generally recommended for use with other antiretroviral medications. It may be used to prevent mother to child spread during birth but is not recommended following other exposures. It is taken by mouth.
Entecavir, sold under the brand name Baraclude, is an antiviral medication used in the treatment of hepatitis B virus infection. In those with both HIV/AIDS and hepatitis B virus antiretroviral medication should also be used. Entecavir is taken by mouth as a tablet or solution.
Abacavir/lamivudine/zidovudine, sold under the brand name Trizivir, is a fixed-dose combination antiretroviral medication for the treatment of HIV/AIDS. It contains three reverse transcriptase inhibitors patented by GlaxoSmithKline and marketed by a joint venture with Pfizer, ViiV Healthcare:
Lamivudine/zidovudine, sold under the brand name Combivir among others, is a fixed-dose combination antiretroviral medication used to treat HIV/AIDS. It contains two antiretroviral medications, lamivudine and zidovudine. It is used together with other antiretrovirals. It is taken by mouth twice a day.
Raltegravir, sold under the brand name Isentress, is an antiretroviral medication used, together with other medication, to treat HIV/AIDS. It may also be used, as part of post exposure prophylaxis, to prevent HIV infection following potential exposure. It is taken by mouth.
Abacavir/lamivudine, sold under the brand name Kivexa among others, is a fixed-dose combination antiretroviral medication used to treat HIV/AIDS. It contains abacavir and lamivudine. It is generally recommended for use with other antiretrovirals. It is commonly used as part of the preferred treatment in children. It is taken by mouth as a tablet.
Rilpivirine, sold under the brand names Edurant and Rekambys, is a medication, developed by Tibotec, used for the treatment of HIV/AIDS. It is a second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) with higher potency, longer half-life and reduced side-effect profile compared with older NNRTIs such as efavirenz.
Elvucitabine is an experimental nucleoside reverse transcriptase inhibitor (NRTI), developed by Achillion Pharmaceuticals, Inc. for the treatment of HIV infection.
HLA-B57 (B57) is an HLA-B serotype. B57 is a split antigen from the B17 broad antigen, the sister serotype being B58. The serotype identifies the more common HLA-B*57 gene products. Like B58, B57 is involved in drug-induced inflammatory skin disorders.
HIV disease–related drug reaction is an adverse drug reaction caused by drugs used for the treatment of HIV/AIDS.
ViiV Healthcare is a British multinational pharmaceutical company specializing in the research and development of medicines to treat and prevent HIV/AIDS. Its global headquarters is located in London. The company was created as a joint venture by GSK and Pfizer in November 2009, with both companies transferring their HIV assets to the new company. In 2012, Shionogi joined the company. As of December 2023, 76.5% of the company is owned by GSK, 13.5% by Pfizer and 10% by Shionogi. According to The Financial Times, the company's co-ownership structure may change depending on the achievement of certain milestones.
Discovery and development of nucleoside and nucleotide reverse-transcriptase inhibitors began in the 1980s when the AIDS epidemic hit Western societies. NRTIs inhibit the reverse transcriptase (RT), an enzyme that controls the replication of the genetic material of the human immunodeficiency virus (HIV). The first NRTI was zidovudine, approved by the U.S. Food and Drug Administration (FDA) in 1987, which was the first step towards treatment of HIV. Six NRTI agents and one NtRTI have followed. The NRTIs and the NtRTI are analogues of endogenous 2´-deoxy-nucleoside and nucleotide. Drug-resistant viruses are an inevitable consequence of prolonged exposure of HIV-1 to anti-HIV drugs.
Abacavir/dolutegravir/lamivudine, sold under the brand name Triumeq among others, is a fixed-dose combination antiretroviral medication for the treatment of HIV/AIDS. It is a combination of three medications with different and complementary mechanisms of action: abacavir, dolutegravir and lamivudine.
Bictegravir/emtricitabine/tenofovir alafenamide, sold under the brand name Biktarvy, is a fixed-dose combination antiretroviral medication for the treatment of HIV/AIDS. It contains bictegravir, a human immunodeficiency virus type 1 (HIV-1) integrase strand transfer inhibitor; emtricitabine, an HIV-1 nucleoside analog reverse transcriptase inhibitor; and tenofovir alafenamide, an HIV-1 nucleoside analog reverse transcriptase inhibitor.