Xanthine Oxidase Inhibitor

Lopurin

Approved 2 Apr 1987OralTablet

The FDA lists this product in 4 strengths and forms.

Indications

THIS IS NOT AN INNOCUOUS DRUG. IT IS NOT RECOMMENDED FOR THE TREATMENT OF ASYMPTOMATIC HYPERURICEMIA. Allopurinol reduces serum and urinary uric acid concentrations. Its use should be individualized for each patient and requires an understanding of its mode of action and pharmacokinetics (see CLINICAL PHARMACOLOGY , CONTRAINDICATIONS , WARNINGS and PRECAUTIONS ). Allopurinol is indicated in: the management of patients with signs and symptoms of primary or secondary gout (acute attacks, tophi, joint destruction, uric acid lithiasis and/or nephropathy). the management of patients with leukemia, lymphoma and malignancies who are receiving cancer therapy which causes elevations of serum and urinary uric acid levels.

Allopurinol treatment should be discontinued when the potential for overproduction of uric acid is no longer present. the management of patients with recurrent calcium oxalate calculi whose daily uric acid excretion exceeds 800 mg/day in male patients and 750 mg/day in female patients. Therapy in such patients should be carefully assessed initially and reassessed periodically to determine in each case that treatment is beneficial and that the benefits outweigh the risks.

Contraindications

Patients who have developed a severe reaction to allopurinol should not be restarted on the drug.

Warnings and precautions

ALLOPURINOL SHOULD BE DISCONTINUED AT THE FIRST APPEARANCE OF SKIN RASH OR OTHER SIGNS WHICH MAY INDICATE AN ALLERGIC REACTION. In some instances a skin rash may be followed by more severe hypersensitivity reactions such as exfoliative, urticarial and purpuric lesions as well as Stevens-Johnson syndrome (erythema multiforme exudativum), and/or generalized vasculitis, irre- versible hepatotoxicity and on rare occasions death.

In patients receiving Purinethol® (mercaptopurine) or Imuran® (azathioprine), 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 (see CLINICAL PHARMACOLOGY ).

Indications

Warnings and precautions

Interactions

Drug Interactions In patients receiving Purinethol® (mercaptopurine) or Imuran® (azathioprine), 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 (see CLINICAL PHARMACOLOGY ).

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. 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.

The reports that 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 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.

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. 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. 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.

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.

Adverse reactions

Data upon which the following estimates of incidence of adverse reactions are made are derived from experiences reported in the literature, unpublished clinical trials and voluntary reports since marketing of allopurinol began. Past experience suggested that the most frequent event following the initiation of allopurinol treatment was an increase in acute attacks of gout (average 6% in early studies). An analysis of current usage suggests that the incidence of acute gouty attacks has diminished to less than 1%.

The explanation for this decrease has not been determined but may be due in part to initiating therapy more gradually (see PRECAUTIONS and DOSAGE AND ADMINISTRATION ). The most frequent adverse reaction to allopurinol is skin rash. Skin reactions can be severe and sometimes fatal. Therefore, treatment with allopurinol should be discontinued immediately if a rash develops (see WARNINGS ). Some patients with the most severe reaction also had fever, chills, arthralgias, cholestatic jaundice, eosinophilia and mild leukocytosis or leukopenia.

Among 55 patients with gout treated with allopurinol for 3 to 34 months (average greater than 1 year) and followed prospectively, Rundles observed that 3% of patients developed a type of drug reaction which was predominantly a pruritic maculopapular skin eruption, sometimes scaly or exfoliative. However, with current usage, skin reactions have been observed less frequently than 1%. The explanation for this decrease is not obvious.

The incidence of skin rash may be increased in the presence of renal insufficiency. The frequency of skin rash among patients receiving ampicillin or amoxicillin concurrently with allopurinol has been reported to be increased (see PRECAUTIONS ). Most Common Reactions* Probably Causally Related Gastrointestinal : diarrhea, nausea, alkaline phosphatase increase, SGOT/SGPT increase. Metabolic and Nutritional : acute attacks of gout.

Skin and Appendages : rash, maculopapular rash. *Early clinical studies and incidence rates from early clinical experience with allopurinol suggested that these adverse reactions were found to occur at a rate of greater than 1%. The most frequent event observed was acute attacks of gout following the initiation of therapy. Analyses of current usage suggest that the incidence of these adverse reactions is now less than 1%.

The explanation for this decrease has not been determined, but it may be due to following recommended usage (see ADVERSE REACTIONS introduction, INDICATIONS , PRECAUTIONS and DOSAGE AND ADMINISTRATION ). Incidence Less Than 1% Probably Causally Related Body as a whole : ecchymosis, fever, headache. Cardiovascular : necrotizing angiitis, vasculitis. Gastrointestinal : hepatic necrosis, granulomatous hepatitis, hepatomegaly, hyperbilirubinemia, cholestatic jaundice, vomiting, intermittent abdominal pain, gastritis, dyspepsia.

Hemic and Lymphatic : thrombocytopenia, eosinophilia, leukocytosis, leukopenia. Musculoskeletal : myopathy, arthralgias. Nervous : peripheral neuropathy, neuritis, paresthesia, somnolence. Respiratory : epistaxis. Skin and Appendages : erythema multiforme exudativum (Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell’s syndrome), hypersensitivity vasculitis, purpura, vesicular bullous dermatitis, exfoliative dermatitis, eczematoid dermatitis, pruritus, urticaria, alopecia, onycholysis, lichen planus.

Special Senses : taste loss/perversion. Urogenital : renal failure, uremia (see PRECAUTIONS ). Incidence Less Than 1% Causal Relationship Unknown Body as a whole : malaise. Cardiovascular : pericarditis, peripheral vascular disease, thrombophlebitis, bradycardia, vasodilation. Endocrine : infertility (male), hypercalcemia, gynecomastia (male). Gastrointestinal : hemorrhagic pancreatitis, gastrointestinal bleeding, stomatitis, salivary gland swelling, hyperlipidemia, tongue edema, anorexia.

Hemic and Lymphatic : aplastic anemia, agranulocytosis, eosinophilic fibrohistiocytic lesion of bone marrow, pancytopenia, prothrombin decrease, anemia, hemolytic anemia, reticulocytosis, lymphadenopathy, lymphocytosis. Musculoskeletal : myalgia. Nervous : optic neuritis, confusion, dizziness, vertigo, foot drop, decrease in libido, depression, amnesia, tinnitis, asthenia, insomnia. Respiratory : bronchospasm, asthma, pharyngitis, rhinitis.

Skin and Appendages : furunculosis, facial edema, sweating, skin edema. Special Senses : cataracts, macular retinitis, iritis, conjunctivitis, amblyopia. Urogenital : nephritis, impotence, primary hematuria, albuminuria.

Lopurin

Indications

Contraindications

Warnings and precautions

Two medicines in one question?

Lopurin

Indications

Contraindications

Warnings and precautions

Two medicines in one question?

Interactions

Pregnancy and breastfeeding

Adverse reactions

Composition

Strengths and forms

Official product information

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