Hypersensitivity reactions to abacavir

Hetherington, S. et al., Genetic variations in HLA-B region and hypersensitivity reactions to abacavir, Lancet, 359, 1121, 2002. 

Following a hypersensitivity reaction to abacavir, never restart abacavir or any abacavir-containing product because more severe symptoms can occur within hours and may include life-threatening hypotension and death. 

Symonds W, CutreU A, Edwards M, Steel H, Spreen B, Powell G, McGuirk S, Hetherington S. Risk factor analysis of hypersensitivity reactions to abacavir. Clin Ther 2002 24(4) 565-73. 

Hetherington S, Hughes AR, Mosteller M, Shortino D, Baker KL, Spreen W, Lai E, Davies K, Handley A, Dow DJ, Fling ME, Stocum M, Bowman C, Thurmond LM, Roses AD. Genetic variations in HLA-B region and hypersensitivity reactions to abacavir. Lancet 2002 359(9312) 1121-2. 

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 Two patients had a suspected hypersensitivity reaction to abacavir and were withdrawn. 

Patients who carry the HLA-B 5701 allele are at high risk for experiencing a hypersensitivity reaction to abacavir. Prior to initiating therapy with abacavir, screening for the HIA-B 5701 allele Is recommended this approach has been found to decrease the risk of hypersensitivity reaction. Screening is also recommended prior to reinitiation of abacavir in patients of unknown HLA-B 5701 status who have previously tolerated abacavir. HLA-B 5707-negative patients may develop a suspected hypersensitivity reaction to abacavir however, this occurs significantly less frequently than in HLA-B 5707-positive patients. 

Nervous system The Parsonage-Tumer syndrome, an idiopathic brachial plexus neuritis, has been reported during a hypersensitivity reaction to abacavir in a 35-year-... 

Nevertheless, hypersensitivity reactions to abacavir can occur in individuals who are negative for HLA B 5701, as in the case of a 41-year-old Caucasian woman who developed a fever and a severe rash after taking abacavir for 10 weeks [102 ]. In one case even a patch test to abacavir was negative, in a 61-year-old man who took abacavir for 10 days before developing a fever over 40° C, muscle aches, watery diarrhea, a rash, and rhabdomyolysis the authors suggested that another genetic association may be waiting to be found [103 ]. 

Abacavir sulfate has been associated with fatal hypersensitivity reactions. Do not restart abacavir following a hypersensitivity reaction to any abacavir containing product (see Warnino box) hepatic impairment previously demonstrated hypersensitivity to any of the components of the product. 

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. 

Hypersensitivity reactions Serious and sometimes fatal hypersensitivity reactions have been associated with abacavir therapy. Hypersensitivity to abacavir is a multi-organ clinical syndrome usually characterized by a sign or symptom in 2 or more of the following groups ... 

Reintroduction of abacavir or any other abacavir-containing product, even in patients who have no identified history or unrecognized symptoms of hypersensitivity to abacavir therapy, can result in serious or fatal hypersensitivity reactions. Such reactions can occur within hours. 

Dispense a Medication Guide and Warning Card that provide information about recognition of hypersensitivity reactions with each new prescription or refill. To facilitate reporting hypersensitivity reactions and collection of information on each case, an Abacavir Hypersensitivity Registry has been established. Physicians should register patients by calling (800) 270-0425. 

Abacavir is associated in 5-10% of cases with severe hypersensitivity reactions combined with fever, headache, myalgia, gastrointestinal symptoms and rash. This hypersensitivity is related to the gene expression of HLA B57-01. Blood tests are being developed to monitor the presence of this gene before starting abacavir. If one has had a hypersensitivity... 

Abacavir is associated with side effects such as anorexia, nausea, vomiting, malaise, headache, and insomnia. A potentially fatal hypersensitivity reaction develops in approximately 5% of patients, usually early in the course of treatment. Fever and rash are the most common symptoms of this reaction malaise, respiratory symptoms, and gastrointestinal complaints may also occur. Resistance to abacavir may be associated with resistance to zidovudine, didanosine, and lamivudine. 

Abacavir NRTT1 300 mg bid Testing to rule out the presence of the HI A-B 5701 allele is recommended prior to the initiation of therapy Rash, hypersensitivity reaction, nausea. Possible increase in myocardial infarction Avoid alcohol... 

Other effects associated with NRTIs include pancreatitis, CNS toxicity (headache, irritability, insomnia), and gastrointestinal disturbances (nausea, diarrhea). Abacavir can cause an allergic (hypersensitivity) reaction that produces symptoms such as fever, joint and muscle pain, skin rashes, abdominal pain, nausea, diarrhea, and vomiting.32 In severe cases, this reaction can progress to anaphylactic shock and possibly death. 

Hypersensitivity reactions, occasionally fatal, have been reported in 2-5% of patients receiving abacavir. Symptoms, which generally occur within the first 6 weeks of therapy, involve multiple organ systems and include fever, malaise, and gastrointestinal complaints. Skin rash may or may not be present. Laboratory abnormalities such as mildly elevated serum aminotransferase or creatine kinase levels are not specific for this reaction. Although the syndrome tends to resolve quickly with discontinuation of medication, rechallenge with abacavir following discontinuation results in return... 

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. 

Genetic factors affecting the immune response to abacavir have been sought in patients who had taken abacavir for more than 6 weeks, 18 with hypersensitivity reactions and 167 without (16). HLA-B 5701 was present in 14 of the 18 patients with abacavir hypersensitivity, and in four of the 167 others (OR = 117 95% Cl = 29, 481). The combination of HLA-DR7 and... 

Escaut L, Liotier JY, Albengres E, Cheminot N, Vittecoq D. Abacavir rechallenge has to be avoided in case of hypersensitivity reaction. AIDS 1999 13(ll) 1419-20. 

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. 

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