Abacavir adverse effects

Lamivudine is the best-tolerated NRTI. Its most common adverse effects include headache, malaise, fatigue, and insomnia. Pancreatitis is rare. Gastrointestinal complaints are common with lamivudine-zidovudine therapy but are probably mainly due to the zidovudine component. Lamivudine resistance sometimes occurs early in treatment. Cross-resistance to zal-citabine, didanosine, and abacavir can occur simultaneously. Withdrawal of lamivudine in patients infected with both hepatitis B virus and HIV can cause a flare-up of hepatitis symptoms. 

Abacavir (t) 2 h) may be the most potent reverse transcriptase inhibitor. It is usually well-tolerated, but adverse effects may include hypersensitivity reactions especially during the first 6 weeks of therapy. 

Indinavir has been compared with abacavir in a randomized equivalence trial in 562 patients who were also taking lamivudine and zidovudine (10). The only significant difference in adverse effects was that there was hyperbilirubinemia in 8% of those taking indinavir and 2% of those taking abacavir. It has been postulated that indinavir-induced hyperbilirubinemia is due to inhibition of bilirubin UDP glucuronyl transferase activity, since it is more common in individuals with Gilbert s syndrome (11). 

The efficacy and safety of abacavir (NRTI) and efavirenz (NNRTI) plus background therapy have been retrospectively evaluated in 50 patients, who had previously been treated with HAART (3). There was some immunological benefit, albeit limited, in most of the patients. Adverse effects were not mentioned in detail, but the dropout rate during the first 4 weeks of treatment was high, owing to skin rashes and hypersensitivity reactions. 

In an open, 48-week, single-arm, multicenter phase II study in 99 patients abacavir 300 mg bd, amprenavir 1200 mg bd, and efavirenz 600 mg/day were associated with rashes in 50 patients, possibly because of abacavir hjrpersensitivity 17 permanently discontinued one or more drugs as a result (5). Other adverse effects included nausea (n = 41), diarrhea (n = 27), sleep disorders (n = 27), dizziness (n = 25), fatigue (n = 23), hypertriglyceridemia (n = 18), neutropenia (n = 8), hyperamylasemia (n = 4), leukopenia (n = 3), hypercholesterolemia (n = 2), raised alkaline phosphatase (n = 1), and raised aspartate transaminase (n = 1). 

In a 24-week open, single-arm trial, 108 antiretroviral therapy-naive, HIV-infected prisoners were given a combination tablet of lamivudine -I- zidovudine (150 mg/300 mg) and a tablet of abacavir 300 mg bd (2). The plasma HIV-1 RNA concentration remained at 400 copies/ml or less in 85% of the patients and at less than 50 copies/ml in 75%. Nausea was the most common adverse effect (n = 40). Four patients withdrew prematurely because of one or more of the following abdominal discomfort and pain abdominal distension neutropenia malaise or fatigue nausea and vomiting. Two patients had a suspected hypersensitivity reaction to abacavir and were withdrawn. 

The most important adverse effect of abacavir is a unique and potentially fatal hypersensitivity syndrome. This syndrome is characterized by fever, abdominal pain, and other gastrointestinal complaints a mild maculopapular rash and malaise or fatigue. Respiratory complaints (cough, pharyngitis, dyspnea), musculoskeletal complaints, headache, and paresthesias are reported less commonly. Abacavir is rapidly absorbed and is metabolized to inactivate metabolites by alcohol dehydrogenase and glucuronyl transferase. Alcohol decreases the elimination of abacavir and prolongs its half-life. 

The most common adverse effect with stavudine is peripheral neuropathy which occurs in -12% of patients. Combining stavudine with zidovudine leads to increased risk and severity of peripheral neuropathy and potentially fatal pancreatitis, and these drugs shorrld not be used together under most circumstances. Lactic acidosis and hepatic steatosis also have been seen and are more common with stavudine than with zidovudine or abacavir. Of aU the nucleoside analogs, stavudine is most strongly linked to the HIV lipodystrophy syndrome, perhaps due to toxic effects on adipocytes. 

Abacavir is a nucleoside reverse-transcriptase inhibitor with activity against the human immunodeficiency virus (HTV). The most important adverse effect... 

Educate the patient on common adverse drug effects and a few of the key signs and symptoms of severe toxicity (i.e., jaundice and abacavir hypersensitivity reaction). Tell them to call their provider immediately if any of those symptoms occur. Make sure they have the correct telephone number for the clinic. 

The effects of abacavir have been evaluated in a study in over 13 000 adults who no longer responded to commercially available treatment regimens (2). By month 2 of treatment with abacavir, plasma HIV-1 RNA concentrations fell by at least half a log unit in 31% of patients, and in 5.6% of the patients HIV-1 RNA concentrations fell to under 400 copies/ml. Serious drug-related adverse events were reported by 7.7% of patients. The most common were nausea, skin rash, diarrhea, malaise or fatigue, and fever. About 4.6% of patients had a hypersensitivity reaction that was possibly drug-related. 

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