Allopac

Allopac

allopurinol

Manufacturer:

Pacific Pharma

Distributor:

AA Medical
Full Prescribing Info
Contents
Allopurinol.
Indications/Uses
Management of patients with signs and symptoms of primary or secondary gout (acute attacks, tophi, joint destruction, uric acid lithiasis and/or nephropathy).
Management of patients with leukemia, lymphoma and malignancies who are receiving cancer therapy which causes elevations of serum and urinary uric acid levels.
Treatment with allopurinol should be discontinued when the potential overproduction of uric acid is no longer present.
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.
Dosage/Direction for Use
Adults: The dosage of allopurinol to accomplish full control of gout and to lower serum uric acid to normal or near-normal levels varies with the severity of the disease.
The average dose is for patients with mild gout, 200-300 mg/day and for those with moderately severe tophaceous gout, 400-600 mg/day. The appropriate dosage may be administered in divided doses or as a single equivalent dose with the 300 mg tablet. Dosage requirement in excess of 300 mg should be administered in divided doses.
The minimal effective dose is 100-200 mg/day and the maximal recommended dose is 800 mg/day. To reduce the possibility of flare-up of acute gouty attacks, it is recommended that the patient start with a low-dose of allopurinol (100 mg daily) and increase at weekly intervals by 100 mg until a serum uric acid level of ≤6 mg/dL is attained but without exceeding the maximal recommended dose. Normal serum urate levels are usually achieved in 1-3 weeks. The upper limit of normal (ULN) is about 7 mg/dL for men and postmenopausal women and 6 mg/dL for premenopausal women. Too much reliance should not be placed on a single serum uric acid determination since, for technical reasons, estimation of uric acid may be difficult. By selecting the appropriate dosage and, in certain patients, using uricosuric agents concurrently, it is possible to reduce serum uric acid to normal or, if desired, to as low as 2-3 mg/dL and keep it there indefinitely.
Since allopurinol and its metabolites are primarily eliminated only by the kidney, accumulation of the drug can occur in renal failure, and the dose of allopurinol should consequently be reduced. With a creatinine clearance (CrCl) of 10-20 mL/min, a daily dose of 100-200 mg of allopurinol is suitable. When the CrCl is <10 mL/min, the daily dose should not exceed 100 mg. With extreme renal impairment, (CrCl <3 mL/min) the interval between doses may also need to be lengthened. If facilities are available to monitor plasma oxipurinol concentrations, the dose should be adjusted to maintain plasma oxipurinol levels <100 mcmol/mL (15.2 mg/mL).
Contraindications
Known hypersensitivity to allopurinol or to any of the ingredients of Allopac.
Patients who have developed a severe reaction to Allopac should not be restarted on the drug.
Patients with mild uratemia without symptom (uric acid <90 mg/L).
Use in lactation: There are reports which indicates that allopurinol and oxipurinol are excreted in human breastmilk. Therefore, Allopac should not be used during lactation.
Use in children: Allopac is contraindicated in children (except in malignant conditions especially leukemia and certain enzyme disorders eg, Lesch-Nyhan syndrome).
Warnings
Allopurinol should be discontinued at the first appearance of skin rash or other signs which may indicate an allergic reaction.
Special Precautions
Careful administration should be implemented in patients with hepatic impairment and/or renal failure; patients who are taking mercaptopurine and azathioprine; patients under treatment for hypertension or cardiac insufficiency eg, with diuretics or ACE inhibitors, may have some concomitant impairment of renal function and allopurinol should be used with care in this group; patients with disorder of hematopoiesis.
Do not take Allopac other than the stated indications in order to avoid misuse and preserve drug quality.
General Precautions: Allopurinol should be withdrawn immediately when a skin rash or other evidence of sensitivity occurs.
Allopac treatment should not be started until an acute attack of gout has completely subsided, as further attacks may be precipitated.
In the early stages of treatment with Allopac, as with uricosuric agents, an acute attack of gouty arthritis may be precipitated. Therefore, it is advisable to give prophylaxis with a suitable anti-inflammatory agent or colchicine for at least 1 month. The literature should be consulted for details of appropriate dosage, precautions and warnings. It is recommended that the patient start with a low dose of Allopac (100 mg daily) and increase at weekly intervals by 100 mg until a serum uric acid level of ≤6 mg/dL is attained but without exceeding the maximum recommended dose (800 mg/day). If acute attacks develop in patients receiving Allopac, treatment should continue at the same dosage while the acute attack is treated with a suitable anti-inflammatory agent.
A fluid intake sufficient to yield a daily urinary output of at least 2 L and the maintenance of a neutral, or preferably, slightly alkaline urine are desirable to avoid the theoretical possibility of formation of xanthine calculi under the influence of therapy with allopurinol, and help prevent renal precipitation of urates in patients receiving concomitant uricosuric agents.
Periodic liver function tests are recommended during the early stages of therapy.
The dose should be adjusted by monitoring serum urate concentrations and urinary urate/uric acid levels at appropriate levels.
Effects on the Ability to Drive or Operate Machineries: Since adverse reactions eg, somnolence, vertigo and ataxia have been reported in patients receiving Allopac, patients should exercise caution before driving, using machinery or participating in dangerous activities until they are reasonably certain that Allopac does not adversely affect performance.
Use in pregnancy & lactation: Teratogenesis has not been observed in animal tests. Allopac should only be used during pregnancy if the potential benefit justifies the risk to the mother and fetus.
Reports indicate that allopurinol and oxipurinol are excreted in human breast milk. Therefore, Allopac should not be used in nursing mothers.
Use in the elderly: In the absence of specific data, the lowest dosage which produces satisfactory urate reduction should be used.
Use In Pregnancy & Lactation
Teratogenesis has not been observed in animal tests. Allopac should only be used during pregnancy if the potential benefit justifies the risk to the mother and fetus. Reports indicate that allopurinol and oxipurinol are excreted in human breast milk. Therefore, Allopac should not be used in nursing mothers.
Use in lactation: There are reports which indicates that allopurinol and oxipurinol are excreted in human breastmilk. Therefore, Allopac should not be used during lactation.
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 experiences 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 <1%. The explanation for this decrease has not been determined but may be due in part to initiating therapy more gradually.
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. 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 Allopac for 3-34 months (average >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 frequently <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.
Most Common Reactions*: Probably Causally Related: Gastrointestinal: Diarrhea, nausea, increased alkaline phosphatase and SGOT/SGPT.
Metabolic and Nutritional: Acute gout attacks.
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 >1%. The most frequent event observed was acute attacks of gout following the initiation of therapy. Analyses of current usage suggest that incidence of these adverse reactions is now <1%. The explanation for this decrease has not been determined, but it may be due to following recommended usage.
Incidence <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 necrosis (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.
Incidence <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, decreased prothrombin, anemia, hemolytic anemia, reticulocytosis, lymphadenopathy, lymphocytosis.
Musculoskeletal: Myalgia.
Nervous: Optic neuritis, confusion, dizziness, vertigo, foot drop, decrease in libido, depression, amnesia, tinnitus, 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.
Drug Interactions
Azathioprine is metabolized to 6-mercaptopurine which is inactivated by the action of xanthine oxidase. When 6-mercaptopurine or azathioprine is given concurrently with allopurinol, only ¼ of the usual dose of 6-mercaptopurine or azathioprine should be given because inhibition of xanthine oxidase will prolong their activity.
If allopurinol 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. There have been rare reports of increased effect of warfarin and other coumarin anticoagulants when co-administered with allopurinol; therefore, all patients receiving anticoagulants must be carefully monitored.
In animal test, there is a report that hepatic iron uptake may be increased in combination use with iron supplements.
Enhanced bone marrow suppression by cyclophosphamide and other cytotoxic agents has been reported among patients with neoplastic disease (other than leukaemia), in the presence of allopurinol.
Allopurinol may inhibit hepatic oxidation of phenytoin but the clinical significance has not been demonstrated.
Reports suggest that the plasma concentration of ciclosporin may be increased during concomitant treatment with allopurinol. The possibility of enhanced ciclosporin toxicity should be considered if the drugs are co-administered.
Inhibition of the metabolism of theophylline has been reported. The mechanism of interaction may be explained by the xanthine oxidase being involved in the biotransformation of theophylline in man. Theophylline levels should be monitored in patients starting or increasing allopurinol therapy.
Evidence suggests that the plasma half-life of vidarabine is increased in the presence of allopurinol. When the 2 products are used concomitantly, extra vigilance is necessary to recognize enhanced toxic effects.
An increase in 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. However, it is recommended that in patients receiving allopurinol an alternative to ampicillin or amoxicillin is used where available.
Oxipurinol, the major metabolite of allopurinol and itself therapeutically active, is excreted by the kidney in a similar way to urate. Hence, drugs with uricosuric activity eg, probenecid or large doses of salicylate may accelerate the excretion of oxipurinol. This may decrease the therapeutic activity of allopurinol, but the significance needs to be assessed in each case.
Allopurinol may enhance the action of salicylates.
Storage
Store at room temperature in a well-closed container.
MIMS Class
Hyperuricemia & Gout Preparations
ATC Classification
M04AA01 - allopurinol ; Belongs to the class of preparations inhibiting uric acid production. Used in the treatment of gout.
Presentation/Packing
Tab (white, round) 100 mg x 10 x 10's.
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