Allopurinol (Zyloprim) Adverse Reactions
- abdominal pain
- acute generalized exanthematous pustulosis (AGEP)
- aplastic anemia
- azotemia
- cataracts
- cholestasis
- diarrhea
- dyspepsia
- elevated hepatic enzymes
- exfoliative dermatitis
- gastritis
- glomerulonephritis
- hepatic necrosis
- hepatitis
- interstitial nephritis
- jaundice
- leukopenia
- maculopapular rash
- nausea/vomiting
- nephrolithiasis
- neutropenia
- purpura
- Stevens-Johnson syndrome
- toxic epidermal necrolysis
- urticaria
- vasculitis
Allopurinol (Zyloprim) Adverse Reactions
The most common adverse effects during allopurinol therapy are dermatologic, which can be severe and sometimes fatal. Allopurinol (Zyloprim) should be discontinued at the first sign of a skin rash or other signs which may indicate a hypersensitivity reaction. A maculopapular rash is the most frequently reported effect, which is more likely to occur in patients with renal impairment or receiving ampicillin or amoxicillin in combination with allopurinol. More severe dermatologic complications include exfoliative dermatitis, urticaria, purpura, maculopapular rash, Stevens-Johnson syndrome, toxic epidermal necrolysis and vasculitis, which in some cases have lead to fatalities. Skin rashes reportedly have occurred as long as 2 years after initiation of treatment.
Adverse GI effects occurring in more than 1% of patients receiving allopurinol include nausea/vomiting, diarrhea, gastritis, dyspepsia, and intermittent abdominal pain.
In rare cases, adverse hematologic effects have been reported during allopurinol therapy. These effects include leukopenia, neutropenia, and aplastic anemia. The majority of cases of bone marrow depression occurred in patients who were receiving other myelosuppressive drugs concomitantly.
Administration of allopurinol has been associated with a potentially fatal toxicity syndrome. Although the mechanism is unclear, elevated oxipurinol concentrations appear to be associated with its onset. This syndrome usually develops 2-4 weeks after initiation of treatment and characteristically occurs when standard dosages (200-400 mg/day) are administered to patients with renal dysfunction. This complication can manifest as skin rash (92%), fever (87%), hepatitis (68%), leukocytosis (39%), eosinophilia (73%), progressive renal failure (85%), or death (21%). Carefully adjusting dosages in patients with renal impairment can reduce the incidence of this life-threatening complication (see Dosage).
Allopurinol (Zyloprim) has been associated with acute generalized exanthematous pustulosis (AGEP). The nonfollicular, pustular, erythematous rash starts suddenly, is associated with fever above 38 degrees C, and is distinct from pustular psoriasis, although biopsy results in each reveal spongiform subcorneal pustules. Drugs are the main cause of AGEP. A period of 2-3 weeks after an inciting drug exposure appears necessary for a first episode of AGEP. Unintentional reexposure may cause a second episode within 2 days. Clinical presentation is diverse with cutaneous lesions beyond erythema and pustules present in half of the cases. For example, bullous lesions, edema, purpura, pruritus, and mucosal erosions are possible. The mean duration of the pustules is 9.7 days followed by an annular desquamation, as long as the causative drug or factor is discontinued. The physiopathological mechanisms of AGEP have not been determined but the pathological criteria of edema, leukocytoclastic vasculitis, eosinophil exocytosis, and keratinocyte focal necrosis are distinctive. Pustule confluence or very small pustules may lead a clinician to make an incorrect diagnosis of TEN, of drug-induced erythroderma, or of staphylococcal scalded skin syndrome.
Azotemia, pyelonephritis, ureteral obstruction, and nephrolithiasis, (xanthine and oxypurinol stones) have occurred in patients with renal disease receiving allopurinol. In addition, renal failure (e.g., glomerulonephritis) has been reported in some patients with multiple myeloma or congestive myocardial disease receiving allopurinol for hyperuricemia secondary to neoplastic disease. Renal failure also has occurred frequently in patients with gouty nephropathy. Interstitial nephritis, a hypersensitivity reaction, has been reported and is associated with the coadministration of thiazide diuretics or in patients with pre-existing renal disease. Patients should maintain a urine output >= 2 L/day to attempt to avoid the formation of xanthine calculi under the influence of allopurinol therapy and to help prevent renal precipitation of urates in patients receiving concurrent uricosuric agents.
Adverse hepatic effects are rare; they occur in <1% of patients. Adverse effects include hepatomegaly, hepatic necrosis, hepatitis, and jaundice. Reversible elevated hepatic enzymes, such as alkaline phosphatase, urinary urobilinogen, SGOT, and SGPT, also have occurred. Cholestasis with or without jaundice can occur. Patients with preexisting hepatic disease and/or renal disease have an increased risk of developing these complications.
Cataracts have been reported with allopurinol therapy. No causal relationship has been proven, but Allopurinol (Zyloprim) has been found in lenses taken from patients on long-term therapy.
[ Last revised: 8/10/2004 12:35:00 PM ]
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