Allopurinol precautions

List of precautions
Acute attacks of gout Fluid intake Pre-existing renal disease/poor urate clearance Renal failure Decreased renal function Bone marrow depression Lab tests Pregnancy Nursing mothers Pediatric use

Acute attacks of gout
An increase in acute attacks of gout has been reported during the early stages of Allopurinol administration, even when normal or subnormal serum uric acid levels have been attained. Accordingly, maintenance doses of colchicine generally should be given prophylactically when Allopurinol is begun. In addition, it is recommended that the patient start with a low dose of Allopurinol (100 mg daily) and increase at weekly intervals by 100 mg until a serum uric acid level of 6 mg/dL or less is attained but without exceeding the maximum recommended dose (800 mg per day). The use of colchicine or anti-inflammatory agents may be required to suppress gouty attacks in some cases. The attacks usually become shorter and less severe after several months of therapy. The mobilization of urates from tissue deposits which cause fluctuations in the serum uric acid levels may be a possible explanation for these episodes. Even with adequate Allopurinol therapy, it may require several months to deplete the uric acid pool sufficiently to achieve control of the acute attacks. Return to top

Fluid intake
A fluid intake sufficient to yield a daily urinary output of at least 2 liters and the maintenance of a neutral or, preferably, slightly alkaline urine are desirable to (1) avoid the theoretical possibility of formation of xanthine calculi under the influence of Allopurinol therapy and (2) help prevent renal precipitation of urates in patients receiving concomitant uricosuric agents. Return to top

Pre-existing renal disease/poor urate clearance
Some patients with pre-existing renal disease or poor urate clearance have shown a rise in BUN during Allopurinol administration. Although the mechanism responsible for this has not been established, patients with impaired renal function should be carefully observed during the early stages of Allopurinol administration and the dosage decreased or the drug withdrawn if increased abnormalities in renal function appear and persist. Return to top

Renal failure
Renal failure in association with Allopurinol administration has been observed among patients with hyperuricemia secondary to neoplastic diseases. Concurrent conditions such as multiple myeloma and congestive myocardial disease were present among those patients whose renal dysfunction increased after Allopurinol was begun. Renal failure is also frequently associated with gouty nephropathy and rarely with hypersensitivity reactions associated with Allopurinol. Albuminuria has been observed among patients who developed clinical gout following chronic glomerulonephritis and chronic pyelonephritis. Return to top

Decreased renal function
Patients with decreased renal function require lower doses of Allopurinol than those with normal renal function. Lower than recommended doses should be used to initiate therapy in any patients with decreased renal function and they should be observed closely during the early stages of Allopurinol administration. In patients with severely impaired renal function or decreased urate clearance, the half-life of oxipurinol in the plasma is greatly prolonged. Therefore, a dose of 100 mg per day or 300 mg twice a week, or perhaps less, may be sufficient to maintain adequate xanthine oxidase inhibition to reduce serum urate levels. Return to top

Bone marrow depression
Bone marrow depression has been reported in patients receiving Allopurinol, most of whom received concomitant drugs with the potential for causing this reaction. This has occurred as early as six weeks to as long as six years after the initiation of Allopurinol therapy. Rarely a patient may develop varying degrees of bone marrow depression, affecting one or more cell lines, while receiving Allopurinol alone. Return to top

Lab tests
The correct dosage and schedule for maintaining the serum uric acid within the normal range is best determined by using the serum uric acid level as an index. In patients with pre-existing liver disease, periodic liver function tests are recommended during the early stages of therapy. Allopurinol and its primary active metabolite oxipurinol are eliminated by the kidneys; therefore, changes in renal function have a profound effect on dosage. In patients with decreased renal function or who have concurrent illnesses which can affect renal function such as hypertension and diabetes mellitus, periodic laboratory parameters of renal function, particularly BUN and serum creatinine or creatinine clearance, should be performed and the patient’s Allopurinol dosage reassessed. The prothrombin time should be reassessed periodically in the patients receiving dicumarol who are given Allopurinol. Return to top

Pregnancy
Pregnancy Category C Teratogenic Effects Reproductive studies have been performed in rats and rabbits at doses up to twenty times the usual human dose (5 mg/kg/day), and it was concluded that there was no impaired fertility or harm to the fetus due to Allopurinol. There is a published report of a study in pregnant mice given 50 or 100 mg/kg Allopurinol intraperitoneally on gestation days 10 or 13. There were increased numbers of dead fetuses in dams given 100 mg/kg Allopurinol but not in those given 50 mg/kg. There were increased numbers of external malformations in fetuses at both doses of Allopurinol on gestation day 10 and increased numbers of skeletal malformations in fetuses at both doses on gestation day 13. It cannot be determined whether this represented a fetal effect or an effect secondary to maternal toxicity. There are, however, no adequate or well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Experience with Allopurinol during human pregnancy has been limited partly because women of reproductive age rarely require treatment with Allopurinol. There are two unpublished reports and one published paper of women giving birth to normal offspring after receiving Allopurinol during pregnancy. Return to top

Nursing mothers
Allopurinol and oxipurinol have been found in the milk of a mother who was receiving Allopurinol. Since the effect of Allopurinol on the nursing infant is unknown, caution should be exercised when Allopurinol is administered to a nursing woman. Return to top

Pediatric use
Allopurinol is rarely indicated for use in children with the exception of those with hyperuricemia secondary to malignancy or to certain rare inborn errors of purine metabolism. Return to top