- DRUGS USED TO TREAT GOUT
- Pharmaceutical Form : Tablets
- Composition : Allopurinol 100 mg / Tab
- Active Substance : Allopurinol
MECHANISM OF ACTION:
Allopurinol is a xanthine-oxidase inhibitor. Allopurinol and its main metabolite oxipurinol lower the level of uric acid in plasma and urine by inhibition of xanthine oxidase, the enzyme catalyzing the oxidation of hypoxanthine to xanthine and xanthine to uric acid. In addition to the inhibition of purine catabolism in some patients.
Absorption: Allopurinol is rapidly absorbed from the upper gastrointestinal tract .The bioavailability vary from 67% to 90%.. Peak plasma levels of allopurinol generally occur approximately 1.5 hours after oral administration of the drug. Peak plasma levels of oxipurinol generally occur after 3-5 hours after oral administration of the drug.
Distribution: Allopurinol is negligibly bound by plasma proteins. The volume of distribution is approximately 1.6 L/kg
Metabolism: The main metabolite of the drug is oxipurinol.
Elimination: Approximately 20% of the ingested allopurinol is excreted in the faeces, and less than 10% of the unchanged drug excreted in the urine. Allopurinol has a plasma half-life of about 0.5 to 1.5 hours.
Pharmacokinetics in patients with renal impairment: Allopurinol and oxipurinol clearance is greatly reduced in patients with poor renal function resulting in higher plasma levels in chronic therapy.
This drug is indicated for reducing urate/uric acid formation in conditions where urate/uric acid deposition has already occurred (e.g. gouty arthritis, skin tophi, nephrolithiasis). idiopathic gout; uric acid lithiasis; acute uric acid nephropathy; neoplastic disease, myeloproliferative disease and certain enzyme disorders which lead to overproduction of urate. The drug is indicated for the management of renal stones related to deficient activity of adenine phosphoribosyl transferase. The drug is also indicated for the management of recurrent mixed calcium oxalate renal stones in the presence of hyperuricosuria.
The drug should not be administered to individuals known to be hypersensitive to allopurinol or to any of its components.
Common: rash, vomiting, nausea, hypersensetivity including skin reactions associated with exfoliation, fever, lymphadenopathy, pseudo lymphoma, arthralgia, leucopenia and/or eosinophilia.
Rare: hepatitis (including hepatic necrosis and granulomatous hepatitis), Stevens-Johnson syndrome/toxic epidermal necrolysis.
EFFECTS ON ABILITY TO DRIVE AND USE MACHINES:
Since adverse reactions such as somnolence, vertigo and ataxia have been reported in patients receiving allopurinol, patients should exercise caution before driving.
- When 6-mercaptopurine or azathioprine is given concurrently with this drug, only one-quarter of the usual dose of 6-mercaptopurine or azathioprine should be given because inhibition of xanthine oxidase will prolong their activity.
- Plasma half-life of vidarabine is increased in the presence of allopurinol. When the two products are used concomitantly extra vigilance is necessary, to recognise enhanced toxic effects.
- Large doses of salicylate may accelerate the excretion of oxipurinol (the major metabolite of allopurinol), this may decrease the therapeutic activity of the drug.
- When This drug is given concomitantly with chlorpropamide when renal function is poor, there may be an increased risk of prolonged hypoglycaemic activity because allopurinol and chlorpropamide may compete for excretion in the renal tubule.
- All patients receiving anticoagulants must be carefully monitored when co-administered with Allopurinol.
- Allopurinol may inhibit hepatic oxidation of phenytoin.
- Theophylline levels should be monitored in patients taking allopurinol.
- An increase in frequency of skin rash has been reported among patients receiving ampicillin or amoxicillin concurrently with allopurinol, . However, it is recommended an alternative to ampicillin or amoxicillin is used where available.
- The possibility of enhanced ciclosporin toxicity should be considered if the drugs are co-administered because the plasma concentration of ciclosporin may be increased.
- Co-administration with didanosine is generally not recommended. If concomitant use is unavoidable, a dose reduction of didanosine may be required, and patients should be closely monitored.
- An increased risk of hypersensitivity has been reported when allopurinol is given with diuretics, in particular thiazides,and with ACE inhibitors especially in renal impairment.
WARNINGS and PRECAUTIONS:
- Allopurinol should be withdrawn immediately when a skin rash or other evidence of sensitivity occurs as this could result in more serious hypersensitivity reactions, (including Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN)).
- Screening for HLA-B*58:01(The HLA-B*58:01 allele has been identified as a genetic risk factor for allopurinol associated SJS/TEN) should be considered before starting treatment with allopurinol.
- Patients with chronic renal impairment and concomitant diuretic use, in particular thiazides, may be at increased risk of developing hypersensitivity reactions.
- Reduced doses should be used in patients with hepatic or renal impairment or patients under treatment for hypertension or cardiac insufficiency.
- Allopurinol treatment should not be started until an acute attack of gout has completely subsided. If acute attacks develop in patients receiving allopurinol, treatment should continue at the same dosage while the acute attack is treated with a suitable anti-inflammatory agent.
- In conditions where the rate of urate formation is greatly increased, the concentration of xanthine in urine could, in rare cases, rise sufficiently to allow deposition in the urinary tract. This risk may be minimized by adequate hydration to achieve optimal urine dilution.
- Adequate therapy with this drug will lead to dissolution of large uric acid renal pelvic stones, with the remote possibility of impaction in the ureter.
- These tablets contain lactose and therefore should not be administered to patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.
DOSAGE and ADMINISTRATION:
Adults: 100 to 200 mg daily in mild conditions, 300 to 600 mg daily in moderately severe conditions,700 to 900 mg daily in severe conditions.
Children under 15 years: 10 to 20 mg/kg bodyweight/day up to a maximum of 400 mg daily.
Older people: the lowest dosage which produces satisfactory urate reduction should be used.
Patients with renal impairment: In severe renal insufficiency, it may be advisable to use less than 100 mg per day or to use single doses of 100 mg at longer intervals than one day.
Patients with hepatic impairment: Reduced doses should be used in patients with hepatic impairment. Dosage should be at the lower end of the recommended dosage schedule.
Symptoms: nausea, vomiting, diarrhoea and dizziness in a patient who ingested 20 g allopurinol.
Treatment: Adequate hydration to maintain optimum diuresis facilitates excretion of allopurinol and its metabolites also, haemodialysis may be used.
URIZOL 100: box of 50 tablets.
URIZOL 300: box of 30 tablets.
Keep in a cool and dry place below 25°C.