(and dosage form):
150 mg Allopurinol per capsule
A 3.3 Antigout preparations.
Allopurinol inhibits xanthine oxidase (XO), the enzyme which catalyses the conversion of hypoxanthine and xanthine to urate.
Allopurinol is indicated for the treatment of gout and hyperuricaemia associated with other conditions.
Known intolerance to allopurinol, severe hepatic or renal disorder. Children or nursing mothers (except those with malignancy).
DOSAGE AND DIRECTIONS FOR USE:
Daily oral dose:
100 - 200 mg in mild conditions
300 - 600 mg in moderately severe conditions or 2 to 10 mg/kg body mass/day
700 - 900 mg in severe conditions
Children under 15 years:
Daily oral dose:
8 to 20 mg/kg body mass/day.
(A 150 mg dosage form may not always be suitable as a single dose or twice a day after meals).
The dose should be titrated against the serum urate/uric acid and or urinary uric acid levels at appropriate intervals.
Dose precautions in renal disorder:
Since allopurinol and its metabolites are excreted by the kidney, renal failure may lead to the retention of the drug and its metabolites with consequent prolongation of plasma half-lives.
To reduce attendant risks, the amount and frequency of the dosage may require reduction.
The following schedule is provided for guidance in adults:
If creatinine clearance exceeds 20 mL/minute - give standard does.
If creatinine clearance is between 20 and 10 mL/minute - give 100 to 200 mg/day.
If creatinine clearance is less than 10 mL/minute - give 100 mg/day or at longer intervals.
A 150 mg dosage form may not always be suitable.
Dose precautions in renal dialysis
Allopurinol and its metabolites are removed by the renal dialysis. If dialysis is required two or three times a week, consideration should be given to an alternative dosage schedule of 300 to 400 mg allopurinol immediately after each dialysis, with none in the interim.
(A 150 mg dosage form may not always be suitable.)
SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Acute attacks of gouty arthritis may be precipitated early during treatment with allopurinol. The incidence is higher in the presence of renal and /or hepatic disorder. Skin reactions are the most common and may occur anytime during treatment. They may be pruritic, maculopapular, sometimes scaly, sometimes purpuric and rarely exfoliative. Allopurinol should be withdrawn immediately should such reaction occur. Skin reactions associated with exfoliation, fever, lymphadenopathy, arthralgia and/or eosinophilia occur rarely. If they do occur, it may be at any time during treatment. Allopurinol should be withdrawn immediately and permanently. Corticosteroids may be beneficial in overcoming such reactions. When generalised hypersensitivity reactions have occurred, renal and/or hepatic disorder has usually been present. Nausea and vomiting may occur.
There have been reports of reduction in the number of circulating blood cells usually in association with renal and/or hepatic disorder. Fever, general malaise, muscle pain, headache, vertigo, somnolence, taste perversion, hepatic necrosis, granulomatous hepatitis, abnormal liver function tests, hyperlipaemia, visual disorder, cataracts, macular changes, neuropathy, impotence, diabetes mellitus, furunculosis, alopecia, haematuria, oedema. have been reported.
Xanthine deposition: In conditions where the body's miscible urate pool is greatly increased (e.g. malignant disease and its treatment; Lesch-Nyhan syndrome), the reduction of urate formation by allopurinol is accompanied by a relative rise in the xanthine and hypoxanthine fractions. In these circumstances, the absolute concentration of xanthine could rise to a level at which deposition in the urinary tract may occur. The risk may be minimised by adequate hydration to achieve maximum diuresis.
Alkalinisation of considerable benefit in relation to urate stones, may be less so in relation to xanthine stones. Xanthine crystals have been seen on muscle tissue of patients receiving allopurinol but this appears to have no clinical significance.
6- Mercaptopurine and azathioprine are inactivated by the action of xanthine oxidase. Hence inhibition of xanthine oxidase may prolong the action of these drugs.
Salicylates and Uricosuric drugs:
Oxypurinol, the major metabolite of allopurinol and itself therapeutically active, is excreted by the kidney in a very similar way to urate. Hence drugs causing uricosuria (e.g. probenecid, large doses of salicylate) may also accelerate the excretion of oxypurinol. This may lead to partial loss of therapeutic activity of allopurinol.
In the presence of allopurinol, there may be competition in the renal tubule for excretion of chlorpropamide. When renal function is poor, the hypoglycaemic activity of chlorpropamide may be increased by allopurinol.
Treatment of neoplasia:
Before instituting cytotoxic therapy it is advisable to assess existing serum urate and urinary uric acid levels. When hyperuricaemia and/or hyperuricousuria are present, they should be corrected prior to starting treatment. Adequate hydration, to maintain maximum diuresis throughout, is important.
See under dosage and directions for use.
Acute gouty attacks and initiation of therapy with Allopurinol:
Mobilisation of urate deposition may result in exacerbation of attacks of acute gouty arthritis. Hence when starting allopurinol, as with uricosuric agents, it is advisable to give colchicine (0,5 mg thrice daily) or some other anti-inflammatory agent effective in treatment of acute gouty arthritis, for at least one month. It has been suggested, but not confirmed that this effect can be avoided by using a small initial dose (100 mg per day) of allopurinol, gradually increasing the dose at intervals.
Pregnancy and Lactation:
The safety of allopurinol in pregnancy and lactation has not been established.
KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
The most likely reaction would be gastro-intestinal intolerance.
Massive absorption of allopurinol may lead to considerable inhibition of xanthine oxidase activity which should have no untoward effects unless 6-mercaptopurine and/or azathioprine is being taken concomitantly. In this case, the rise of incidence activity of these drugs must be recognised. Adequate hydration to maintain maximum diuresis facilitates excretion of allopurinol and its metabolites. Dialysis may be resorted to if considered necessary.
CONDITIONS OF REGISTRATION:
Advertising to the professions only.
Yellow and white imprinted capsules.
Plastic containers of 30, 100 & 1000 capsules.
Keep well closed in a cool place (below 25° C).
Keep out of reach of children.
NAME AND BUSINESS ADDRESS OF THE APPLICANT:
GEO SCHWULST LABS. LIMITED
1 Manchester Road
DATE OF PUBLICATION OF THIS PACKAGE INSERT:
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