Abacavir is an anti-viral agent and belongs to the class of nucleoside reverse transcriptase inhibitors. It is available under the trade names Ziagen ,Abmune ,Abavir ,Abcavir and in combinations like Trizivir(Abacavir , Zidovudine , Lamivudine). Abacavir is used for treating HIV -1 in combination with other antiretroviral agents. It was approved by the US food and drug administration in 1998. The recommended dosing for adults, adolescents and children weighing more than 25 kg is 600mg daily.in children up to 12 years , the dose is administered as 300mg twice daily. In patients older than 12 years it may be administered as 300mg twice daily or 600mg once a day. For children weighing less than 25 kg, oral solutions are available. Abacavir is the only approved antiviral that is active as a guanosine analog. Adenosine phosphotransferase monophosphorylates abacavir. This monophosphate is then converted to carbovir 3́- monophosphate which in turn gets phosphorylated to di and triphosphates by cellular kinases. The elongation chain of proviral DNA is terminated due to the incorporation of carbovir 5’- triphosphate during the reverse transcription process. Abacavir has a bioavailability of 83% and is well absorbed; hence it can be taken without regard to food.
The side effects for the drug include
Idiosyncratic Hypersensitivity reactions are a primary concern with prescribing abacavir. It usually occurs in the first week of the therapy. it is a multi organ syndrome with manifestations that include maculopapular rash, fever, lymphadenopathy ,pneumonitis , myocarditis ,nausea, vomiting , abdominal pain, diarrhea, dyspnea ,hepatitis ,interstitial nephritis and hematologic effects like eosinophilia. A weakened immune system and unusual drug metabolism are the causes of hypersensitivity reactions. It is believed that in some individuals, an unknown chemically active metabolite is formed that rises to the liver and is transported to other tissues where the immune mediated effects take place. It is also believed that haptens are produced by the active metabolite that binds to host protein amino acids and trigger an immune response. Supportive therapy with intravenous hydration and discontinuation of abacavir are the goals of managing hypersensitivity reactions.to prevent such reactions; patients must be informed about the hypersensitivity reactions and the need to report it immediately. Once hypersensitivity reaction occurs, abacavir must not be restarted. Laboratory test for determining the inheritance of gene HLA-B*5701 or a patch test must be done before initiating abacavir therapy to prevent hypersensitivity reactions. Hypersensitivity reactions occur in the first 6 weeks of starting the therapy, hence patient must be called for follow up and evaluated every two weeks for the first two months.
Central nervous system
The penetration of abacavir in CNS is high leading to headache, fever, malaise, insomnia, vertigo, peripheral neuropathy, and paresthesias.
Gastro intestinal system
The effects on gastro intestinal system are usually caused due to the hypersensitivity reactions. The gastro intestinal side effects observed are nausea, vomiting, diarrhea, anorexia, cramps, abdominal pain, increased ALT, AST, and hepatotoxicity. The symptoms of hepatotoxicity are anorexia, nausea, vomiting, jaundice, hepatomegaly, splenomegaly, elevated bilirubin, elevated GGT, alkaline phosphatase, and increased PT. Some of the gastro intestinal side effects like abdominal cramps and diarrhea occur due to the presence of sorbitol in abacavir solution. These symptoms are generally mild and resolve spontaneously after the first week of medicine intake. Hepatotoxicity occurs in about 2-14% of the population treated with abacavir or its combination drugs. Liver toxicity may be because of the hypersensitivity reaction that affects multiple organs or may be due to abacavir binding to the antigen binding cleft of he HLA-B*5701 molecule and altering its peptide binding repertoire. Hepatic studies must be done before and during the therapy to identify hepatotoxicity. It is important that patients are informed about the necessity of routine liver function tests to ensure their adherence to follow up and prevention of hepatic liver toxicity. Discontinue the drug if hepatotoxicity occurs. The patient must be advised to refrain from alcohol use because alcohol may compete with abacavir for metabolism by alcohol dehydrogenase, thereby increasing the plasma levels of abacavir about 40%, leading to increase in the severity of side effects.
Long term therapy with abacavir is believed to cause bone marrow suppression and variable degrees of mitochondrial dysfunction resulting in side effects of hematologic system that includes granulocytopenia, anemia, and lymphopenia. Blood counts must be assessed every 2 week. If the hemoglobin falls too low, abacavir therapy may have to be discontinued and the patient may have to be given blood transfusions.
Studies have shown that Abacavir is associated with a risk for myocardial infarction but the FDA has found no significant association between abacavir and myocardial infarction.
Acute neutrophilic dermatosis (Sweet’s syndrome) has been associated with abacavir. Sweet’s syndrome is characterized by painful erythematous papules, plaques, pustules and nodules appearing mainly on the back, neck arms and face, fever and leukocytosis. eryhthema multiforme , Stevens – Johnson syndrome and toxic epidermal necrolysis are also observed in patients on abacavir or abacavir combination therapies. The other minor dermatologic side effects include rashes, urticaria , alopecia.
Hyperglycemia is associated with the use of abacavir. However the exact mechanism is unknown. It is recommended that clinicians monitor the blood glucose levels of patients on abacavir. Lactic acidosis with hepatic steatosis is another serious side effect and is characterized by myalgias, dyspnea, tingling sensation in the hands and legs, abdominal cramps, nausea, vomiting ,tachycardia, dizziness , loss of consciousness. Emergency management to reverse lactic acidosis must be initiated. To prevent serious complications, the patient must be informed about the signs and symptoms of lactic acidosis and must be advised to contact the health care provider as soon as they appear. The incidence of lactic acidosis appears to be increased when abacavir is used during pregnancy; hence it is advisable to avoid the use of abacavir in pregnant women. Elevation in triglyceride levels and accumulation/redistribution of body fat including peripheral muscle wasting , dorsocervical fat deposition with ‘cushingoid’ appearance, breast enlargement have been observed in patients taking abacavir or its combination drugs.
Abacavir may cause dyspnea secondary to the hypersensitivity reaction.
Some psychiatric symptoms are also associated with abacavir; these include depression, anxiety, mood swings, and abnormal dreams.
Studies have shown that abacavir and its combination drugs resulted in rhabdomylosis , CPK elevation , muscle weakness and elevated CPK.