Milurit - General Information:A xanthine oxidase inhibitor that decreases uric acid production. It also acts as an antimetabolite on some simpler organisms. [PubChem]
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Pharmacology:Milurit, a structural analog of the natural purine base hypoxanthine, is used to prevent gout and renal calculi due to either uric acid or calcium oxalate and to treat uric acid nephropathy, hyperuricemia, and some solid tumors.
Milurit for patients
Patients should be informed of the following:
- They should be cautioned to discontinue allopurinol and to consult their physician immediately at the first sign of a skin rash, painful urination, blood in the urine, irritation of the eyes, or swelling of the lips or mouth.
- They should be reminded to continue drug therapy prescribed for gouty attacks since optimal benefit of allopurinol may be delayed for two to six weeks.
- They should be encouraged to increase fluid intake during therapy to prevent renal stones.
- If a single dose of allopurinol is occasionally forgotten, there is no need to double the dose at the next scheduled time.
- There may be certain risks associated with the concomitant use of allopurinol and dicumarol, sulfinpyrazone, mercaptopurine, azathioprine, ampicillin, amoxicillin and thiazide diuretics, and they should follow the instructions of their physician.
- Due to the occasional occurrence of drowsiness, patients should take precautions when engaging in activities where alertness is mandatory.
- Patients may wish to take allopurinol after meals to minimize gastric irritation.
The following drug interactions were observed in some patients undergoing treatment with oral allopurinol. Although the pattern of use for oral allopurinol includes longer term therapy, particularly for gout and renal calculi, the experience gained may be relevant.
Mercaptopurine/Azathioprine: Allopurinol inhibits the enzymatic oxidation of mercaptopurine and azathioprine to 6-thiouric acid. This oxidation, which is catalyzed by xanthine oxidase, inactivates mercaptopurine. In patients receiving mercaptopurine (Purinethol) or azathioprine (Imuran), the concomitant administration of 300-600 mg of allopurinol per day will require a reduction in dose to approximately one-third to one-fourth of the usual dose of mercaptopurine or azathioprine. Subsequent adjustment of doses of mercaptopurine or azathioprine should be made on the basis of therapeutic response and the appearance of toxic effects.
Dicumarol: It has been reported that allopurinol prolongs the half-life of the anticoagulant, dicumarol. The clinical basis of this drug interaction has not been established but should be noted when allopurinol is given to patients already on dicumarol therapy. Consequently, prothrombin time should be reassessed periodically in patients receiving both drugs.
Uricosuric Agents: Since the excretion of oxipurinol is similar to that of urate, uricosuric agents, which increase the excretion of urate, are also likely to increase the excretion of oxipurinol and thus lower the degree of inhibition of xanthine oxidase. The concomitant administration of uricosuric agents and allopurinol has been associated with a decrease in the excretion of oxypurines (hypoxanthine and xanthine) and an increase in urinary uric acid excretion compared with that observed with allopurinol alone. Although clinical evidence to date has not demonstrated renal precipitation of oxypurines in patients either on allopurinol alone or in combination with uricosuric agents, the possibility should be kept in mind.
Thiazide Diuretics: The reports that the concomitant use of allopurinol and thiazide diuretics may contribute to the enhancement of allopurinol toxicity in some patients have been reviewed in an attempt to establish a cause-and-effect relationship and a mechanism of causation. Review of these case reports indicates that the patients were mainly receiving thiazide diuretics for hypertension and that tests to rule out decreased renal function secondary to hypertensive nephropathy were not often performed. In those patients in whom renal insufficiency was documented, however, the recommendation to lower the dose of allopurinol was not followed. Although a causal mechanism and a cause-and-effect relationship have not been established, current evidence suggests that renal function should be monitored in patients on thiazide diuretics and allopurinol even in the absence of renal failure, and dosage levels should be even more conservatively adjusted in those patients on such combined therapy if diminished renal function is detected..
Ampicillin/Amoxicillin: An increase in the frequency of skin rash has been reported among patients receiving ampicillin or amoxicillin concurrently with allopurinol compared to patients who are not receiving both drugs. The cause of the reported association has not been established.
Cytotoxic Agents: Enhanced bone marrow suppression by cyclophosphamide and other cytotoxic agents has been reported among patients with neoplastic disease, except leukemia, in the presence of allopurinol. However, in a well-controlled study of patients with lymphoma on combination therapy, allopurinol did not increase the marrow toxicity of patients treated with cyclophosphamide, doxorubicin, bleomycin, procarbazine and/or mechlorethamine.
Chlorpropamide: Chlorpropamide's plasma half-life may be prolonged by allopurinol, since allopurinol and chlorpropamide may compete for excretion in the renal tubule. The risk of hypoglycemia secondary to this mechanism may be increased if allopurinol and chlorpropamide are given concomitantly in the presence of renal insufficiency.
Cyclosporin: Reports indicate that cyclosporine levels may be increased during concomitant treatment with allopurinol sodium for injection. Monitoring of cyclosporine levels and possible adjustment of cyclosporine dosage should be considered when these drugs are co-administered.
Tolbutamide's conversion to inactive metabolites has been shown to be catalyzed by xanthine oxidase from rat liver. The clinical significance, if any, of these observations is unknown.
Patients who have developed a severe reaction to allopurinol should not be restarted on the drug.
Additional information about MiluritMilurit Indication: For the treatment of hyperuricemia associated with primary or secondary gout.
Mechanism Of Action: Milurit inhibits the enzyme xanthine oxidase, blocking the conversion of the oxypurines hypoxanthine and xanthine to uric acid. Elevated concentrations of oxypurine and oxypurine inhibition of xanthine oxidase through negative feedback results in a decrease in the concentrations of uric acid in the blood and urine. Milurit also facilitates the incorporation of hypoxanthine and xanthine into DNA and RNA, resulting in further reductions of serum uric acid concentrations.
Drug Interactions: Anisindione Milurit increases the anticoagulant effect
Azathioprine Milurit increases the effect of thiopurine
Cyclosporine Milurit increases the effect and toxicity of cyclosporine
Dicumarol Milurit increases the anticoagulant effect
Warfarin Milurit increases the anticoagulant effect
Mercaptopurine Milurit increases the effect of thiopurine
Acenocoumarol Increases the anticoagulant effect
Food Interactions: Take with a full glass of water.
Take with food.
Generic Name: Allopurinol
Synonyms: Allopurinolum [Inn-Latin]; Allopurinol Sodium; Alopurinol [Inn-Spanish]
Drug Category: Free Radical Scavengers; Enzyme Inhibitors Antimetabolites; Gout Suppressants
Drug Type: Small Molecule; Approved
Other Brand Names containing Allopurinol: 7HP; Adenock; Ailural; Allo-Puren; Allopur; Allozym; Allural; Aloprim; Aloral; Alositol; Aluline; Anoprolin; Anzief; Apo-Allopurinol; Apulonga; Apurin; Apurol; Atisuril; Bleminol; Bloxanth; Caplenal; Cellidrin; Cosuric; Dabrosin; Dabroson; Dura Al; Embarin; Epidropal; Epuric; Foligan; Geapur; Gichtex; Gotax; HPP; Hamarin; Hexanuret; Ketanrift; Ketobun-A; Ledopur; Lopurin; Lysuron; Milurit; Miniplanor; Monarch; Nektrohan; Progout; Purinol; Remid; Riball; Sigapurol; Suspendol; Takanarumin; Urbol; Uricemil; Uriprim; Uripurinol; Uritas; Urobenyl; Urolit; Urosin; Urtias; Urtias 100; Xanturat; Zyloprim; Zyloric; Allohexal;
Absorption: Approximately 90% absorbed from the gastrointestinal tract.
Toxicity (Overdose): LD50=214 mg/kg (in mice)
Protein Binding: Negligible
Half Life: 1-2 hours
Dosage Forms of Milurit: Tablet Oral
Chemical IUPAC Name: 1,2-dihydropyrazolo[4,3-e]pyrimidin-4-one
Chemical Formula: C5H4N4O
Allopurinol on Wikipedia: http://en.wikipedia.org/wiki/Allopurinol
Organisms Affected: Humans and other mammals
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