Allopurinol
(NSAIDs and Antigout Preparations)
Drugs utilized in Gout
Pharmacology:
Allopurinol may be a xanthine oxidase inhibitor which is run orally. It acts on purine catabolism without disrupting the biosynthesis of purines. It reduces the assembly of acid by inhibiting the biochemical reactions immediately preceding its formation. Allopurinol may be a structural analogue of the natural purine base, hypoxanthine. it's an inhibitor of xanthine oxidase, the enzyme liable for the conversion of hypoxanthine to xanthine and xanthine to acid, the top product of purine metabolism. Allopurinol is approximately 90% absorbed from the alimentary canal. Peak plasma levels generally occur at 1.5 hours to 4.5 hours. it's a plasma half lifetime of about 1 to 2 hours. Approximately 20% of the ingested Allopurinol is excreted within the feces.
Indications:
Allopurinol is indicated for reducing urate/uric acid formation in conditions where urate/uric acid deposition has already occurred (e.g. gout, skin tophi, nephrolithiasis). Allopurinol is indicated for the management of two,8-dihydroxyadenine (2,8-DHA) renal stones associated with deficient activity of adenine phosphoribosyltransferase. Allopurinol is indicated for the management of recurrent mixed calcium oxalate renal stones within the presence of hyperuricosuria, when fluid, dietary, and similar measures have failed.
Dosage & Administration:
Adults: Allopurinol should be introduced at low dosage e.g. 100mg/day to scale back the danger of adverse reactions and increased as long as the serum urate response is unsatisfactory. Extra caution should be exercised if renal function is poor. the subsequent dosage schedules are suggested: 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: Children under 15 years: 10 to twenty mg/kg body weight/day up to a maximum of 400 mg daily. Use in children is never indicated, except in malignant conditions (especially leukaemia) and certain enzyme disorders like Lesch-Nyhan syndrome.
Elderly: within the absence of specific data, rock bottom dosage which produces satisfactory urate reduction should be used.
Dosage in renal impairment: In severe insufficiency , it's going to be advisable to use but 100 mg per day or to use single doses of 100mg at longer intervals than at some point .
Interaction:
When 6-mercaptopurine or azathioprine is given concurrently with Allopurinol, only one-quarter of the standard dose of 6- mercaptopurine or azathioprine should tend because inhibition of xanthine oxidase will prolong their activity. Evidence suggests that the plasma half-life of vidarabine is increased within the presence of allopurinol. When the 2 products are used concomitantly extra vigilance is important , to recognise enhanced toxic effects. Theophylline levels should be monitored in patients starting or increasing allopurinol therapy. a rise in frequency of rash has been reported among patients receiving ampicillin or amoxicillin concurrently with allopurinol compared to patients who aren't receiving both drugs. Reports suggest that the plasma concentration of ciclosporin could also be increased during concomitant treatment with allopurinol.
Contraindications:
Allopurinol tablet is contra-indicated in patients with known hypersensitive to allopurinol.
Side Effects:
Rashes, gastro intestinal disorder’s, rearly malaise, headache, vertigo, drowsiness, visual and test disturbances, hypertension, alopecia, hepatotoxicity, neuropathy, gynaeconastia and blood disorders.
Pregnancy & Lactation:
There is inadequate evidence of safety of Allopurinol in human pregnancy. Use in pregnancy only there's no safer alternative and when the disease itself carries risk for the mother or unborn child. There are not any data concerning the consequences of allopurinol or its metabolites on the breast-feed baby.
Precautions & Warnings:
Allopurinol should be withdrawn immediately when a rash or other evidence of sensitivity occurs. Reduced doses should be utilized in patients with hepatic or renal impairment. Patients under treatment for hypertension or coronary insufficiency may have some concomitant impairment of renal function and allopurinol should be used with care during this group.
Overdose Effects:
Ingestion of up to 22.5 g allopurinol without adverse effect has been reported. Symptoms and signs including nausea, vomiting, diarrhoea and dizziness are reported during a patient who ingested 20 gm allopurinol. Adequate hydration to take care of optimum diuresis facilitates excretion of allopurinol and its metabolites. If needed haemodialysis could also be used.
Storage:
Store during a cool and dry place, shielded from light.