Allopurinol

Comparisons with antimonials in leishmaniasis

Allopurinol has an antileishmanial effect in vitro and in animals, its effect being increased by the addition of antimonial compounds. Allopurinol alone and in combination with meglumine antimoniate has been used in clinical studies. In a small study in patients with leishmaniasis and HIV infection, clinical and parasitological cure was achieved in four of five cases treated for 4 weeks, but in only one of the six treated for 3 weeks [ ].

Allopurinol + meglumine antimoniate (Glucantime) has been evaluated in a randomized controlled trial in 150 patients with cutaneous leishmaniasis [ ]. They received oral allopurinol (15 mg/kg/day) for 3 weeks or intramuscular meglumine antimoniate (30 mg/kg/day, corresponding to 8 mg/kg/day of pentavalent antimony, for 2 weeks), or combined therapy. There were a few adverse effects and reactions in those who used allopurinol: nausea, heartburn (n = 3), and mild increases in aminotransferases (n = 2); these subsided on drug withdrawal.

In an open study, 72 patients each received meglumine antimoniate (60 mg/kg/day) or allopurinol (20 mg/kg/day) plus low-dose meglumine antimoniate (30 mg/kg/day) for 20 days, and each was followed for 30 days after the end of treatment [ ]. Only six patients in the combined treatment group complained of mild abdominal pain and nausea; however, one patient who received meglumine antimoniate developed a skin eruption. Generalized muscle pain and weakness occurred in four patients.

Nervous system

Apart from headache and vertigo, adverse effects of allopurinol involving the nervous system are rare. Transient peripheral neuropathy has been reported [ ].

Seizures, which were unresponsive to standard anticonvulsive therapy, disappeared when allopurinol was withdrawn in a patient with a primary neurological disorder [ ].

In contrast, occasional reports that allopurinol may have an anticonvulsive effect prompted its use in therapy-resistant epileptic patients. Withdrawal in one of these patients precipitated convulsive status epilepticus [ ].

• A 60-year-old man developed aseptic meningitis after taking allopurinol on two separate occasions [ ].

Sensory systems

Allopurinol can reportedly cause cataracts [ ], but in one study there was no evidence to confirm this risk [ ].

Hematologic

Eosinophilia and leukocytosis are part of a general hypersensitivity reaction to allopurinol. Leukopenia and neutropenia are sometimes associated with allopurinol. Patients taking cytostatic therapy are more susceptible to bone marrow depression if they take allopurinol as well [ ]; however, this has not been confirmed in other reports [ ]. Agranulocytosis is extremely rare.

Cases of aplastic anemia, some in patients with renal insufficiency, have been reported [ ], confirming the need to reduce the dose of allopurinol in patients with renal insufficiency and to monitor toxicity [ ].

• Pure red cell aplasia occurred in a 79-year-old man taking allopurinol (dosage not stated) [ ]. The anemia promptly resolved after withdrawal, strongly supporting a drug effect.

Liver

Hepatitis can be part of a generalized hypersensitivity reaction. Hepatotoxicity ranges from mild granulomatous hepatitis to severe hepatocellular necrosis [ ]. Renal impairment seems to be a prerequisite for a severe hepatic reaction.