Uses and Administration of Allopurinol in Kenya
Allopurinol is used to treat hyperuricaemia associated with chronic gout, acute uric acid nephropathy, recurrent uric acid stone formation, enzyme disorders, or cancer and its treatment (see Tumour Lysis Syndrome. It is not used for asymptomatic hyperuricaemia. Allopurinol is also used in the management of renal calculi caused by the deposition of calcium oxalate (in the presence of hyperuricosuria) and of 2,8-dihydroxyadenine. It may have the potential to reduce oxidative stress by blocking the production of free radicals and is an ingredient of kidney preservation solutions. In addition allopurinol has antiprotozoal activity and has been used in leishmaniasis and American trypanosomiasis.
Allopurinol is used in gout and hyperuricaemia to inhibit the enzyme xanthine oxidase, thus preventing the oxidation of hypoxanthine to xanthine and xanthine to uric acid. The urinary purine load, normally almost entirely uric acid, is thereby divided between hypoxanthine, xanthine, and uric acid, each with its independent solubility. This results in the reduction of urate and uric acid concentrations in plasma and urine, ideally to such an extent that deposits of monosodium urate monohydrate or uric acid are dissolved or prevented from forming. At low concentrations allopurinol acts as a competitive inhibitor of xanthine oxidase and at higher concentrations as a non-competitive inhibitor. However, most of its activity is due to the metabolite oxipurinol which is a non-competitive inhibitor of xanthine oxidase.
Allopurinol in Kenya is used in chronic gout to correct hyperuricaemia, reduce the likelihood of acute attacks, and prevent the sequelae of chronic gout. Initially, it may increase plasma-concentrations of urate and uric acid by dissolving deposits. This can trigger or exacerbate acute attacks, hence allopurinol should not be started until an acute attack has completely subsided, and treatment should be started with a low dose increased gradually; an NSAID or colchicine should also be given during the first few months.
A suggested starting dose of allopurinol is 100 mg daily by mouth, gradually increased by 100 mg for example at weekly intervals until the concentration of urate in plasma is reduced to 0.36 mmol/litre (6 mg per 100 mL) or less. A daily dose range of 100 to 300 mg may be adequate for those with mild gout and up to 600 mg for those with moderately severe tophaceous gout. The maximum recommended daily dose is 800 mg in the USA and 900 mg in the UK. Up to 300 mg may be taken as a single daily dose; larger amounts should be taken in divided doses to reduce the risk of gastric irritation. Taking allopurinol after food will also minimise gastric irritation. Patients should maintain an adequate fluid intake to prevent renal xanthine deposition.
When used for the prevention of uric acid nephropathy associated with cancer therapy 600 to 800 mg may be given daily generally for 2 or 3 days before starting the cancer treatment. A high fluid intake is essential. In hyperuricaemia secondary to cancer or cancer chemotherapy, maintenance doses of allopurinol are similar to those used in gout and are given according to the response.
The main use of allopurinol in children is for hyperuricaemia associated with cancer or cancer chemotherapy or with enzyme disorders. The dosage used may vary: in the UK a dose of 10 to 20 mg/kg daily up to a maximum of 400 mg daily is recommended for children under 15 years of age, while in the USA the dose is 150 mg daily for children under 6 years of age and 300 mg daily for those aged 6 to 10 years, adjusted if necessary after 48 hours.
Allopurinol sodium has been given by intravenous infusion in sodium chloride 0.9% or glucose 5% to patients (usually cancer patients) unable to take allopurinol by mouth. The recommended dose in adults is the equivalent of allopurinol 200 to 400 mg/m2 daily up to a maximum of 600 mg daily. Allopurinol sodium 116.2 mg is equivalent to 100 mg of allopurinol.
Incompatibilities of Allopurinol with other drugs
Allopurinol sodium as a 3 mg/mL solution in 0.9% sodium chloride was visually incompatible with amikacin sulfate, amphotericin B, carmustine, cefotaxime sodium, chlormethine hydrochloride, chlorpromazine hydrochloride, cimetidine hydrochloride, clindamycin phosphate, cytarabine, dacarbazine, daunorubicin hydrochloride, diphenhydramine hydrochloride, doxorubicin hydrochloride, doxycycline hyclate, droperidol, floxuridine, gentamicin sulfate, haloperidol lactate, hydroxyzine hydrochloride, idarubicin hydrochloride, imipenem with cilastatin sodium, methylprednisolone sodium succinate, metoclopramide hydrochloride, minocycline hydrochloride, nalbuphine hydrochloride, netilmicin sulfate, ondansetron hydrochloride, pethidine hydrochloride, prochlorperazine edisilate, promethazine hydrochloride, sodium bicarbonate, streptozocin, tobramycin sulfate, and vinorelbine tartrate.1
- 1. Trissel LA, Martinez JF. Compatibility of allopurinol sodium with selected drugs during simulated Y-site administration. Am J Hosp Pharm 1994; 51: 17929. PubMed
Adverse Effects & Side Effects of Allopurinol
The most common side-effect of allopurinol is skin rash. Rashes are generally maculopapular or pruritic, sometimes purpuric, but more serious hypersensitivity reactions may occur and include exfoliative rashes, the Stevens-Johnson syndrome, and toxic epidermal necrolysis. It is therefore recommended that allopurinol be withdrawn immediately if a rash occurs. Further symptoms of hypersensitivity include fever and chills, lymphadenopathy, leucopenia or leucocytosis, eosinophilia, arthralgia, and vasculitis leading to renal and hepatic damage and, very rarely, seizures. These hypersensitivity reactions may be severe, even fatal, and patients with hepatic or renal impairment are at special risk.
Hepatotoxicity and signs of altered liver function may also be found in patients not exhibiting hypersensitivity. Haematological effects include thrombocytopenia, aplastic anaemia, agranulocytosis, and haemolytic anaemia.
Many other side-effects have been noted rarely and include paraesthesia, peripheral neuropathy, alopecia, gynaecomastia, hypertension, taste disturbances, nausea, vomiting, abdominal pain, diarrhoea, headache, malaise, drowsiness, vertigo, and visual disturbances.
Patients with gout may experience an increase in acute attacks on beginning treatment with allopurinol, although attacks usually subside after several months.
Allopurinol should not be used for the treatment of an acute attack of gout; additionally, allopurinol therapy should not be initiated for any purpose during an acute attack. However, allopurinol is continued when acute attacks occur in patients already receiving the drug, and the acute attack is treated separately.
Treatment should be stopped immediately if any skin reactions or other signs of hypersensitivity develop. A cautious reintroduction at a low dose may be attempted when mild skin reactions have cleared; allopurinol should not be reintroduced in those patients who have experienced other forms of hypersensitivity reaction. Dosage should be reduced in renal impairment and in hepatic impairment. Care is advised in patients being treated for hypertension or cardiac insufficiency, who may have concomitant renal impairment.
To reduce the risk of renal xanthine deposition an adequate fluid intake (2 to 3 litres daily) is required. In addition, a neutral or slightly alkaline urine may be desirable.
Allopurinol and its metabolite, oxipurinol, are distributed into breast milk, and the manufacturers recommend that allopurinol should be given with caution to breast feeding women. Although oxipurinol was detected in the plasma of a breast-fed infant, no adverse effects were noted in the infant during 6 weeks of maternal treatment with allopurinol.1 The American Academy of Pediatrics noted that there had been no documented problems with allopurinol and considered its use to be usually compatible with breast feeding.2
- 1. Kamilli I, Gresser U. Allopurinol and oxypurinol in human breast milk. Clin Investig 1993; 71: 1614. PubMed
- 2. American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 2001; 108: 77689. PubMed Correction. ibid.; 1029. Also available at: online (accessed 26/05/04)