Crystasol

Company name: Memphis Co. for Pharm. & Chem. Ind.

Trade name: Crystasol tablets

Generic name: Allopurinol

Composition:
Each tablet contains:
Allopurinol                         300 mg
Lactose monohydrate       200 mg
Croscarmellose sodium      25 mg
Polyvinyl pyrrolidone K30   20 mg
Magnesium stearate          5 mg

Pharmaceutical form: Tablets

Pharmacological actions:
Allopurinol reduces uric acid concentrations in both serum and urine.
Along with its active metabolite, oxypurinol, allopurinol inhibits xanthine oxidase, the enzyme responsible for the conversion of hypoxanthine to xanthine and of xanthine to uric acid.

Pharmacokinetics:
Absorption of allopurinol in gastro-intestinal tract is rapid but incomplete.
Most of allopurinol is metabolized to oxupurinol.
Elimination is essentially through the kidneys.

Indications:
Crystasol is indicated in:
- Treatment of gout, either primary, or secondary to hyperuricemia which occurs in polycythemia vera, myeloid metaplasia or other blood dyscrasias.

- Treatment of primary or secondary uric acid nephropathy, with or without accompanying symptoms of gout.

- Preventing tissue urate deposition or renal calculi as well as acute urate nephropathy and resultant renal failure in patients with leukemias, lymphomas or other malignancies who are receiving radiation or antineoplastic drugs that will result in elevated uric acid concentrations.

- Preventing occurrence and recurrence of uric acid stones and renal calcium lithiasis in patients with hyperuricemia and/or hyperuricosuria.

Dosage and administration:
- Crystasol is better taken with meals.

- In patients receiving Crystasol, high fluid intake and maintenance of neutral or slightly alkaline urine are recommended to avoid formation of xanthine calculi and prevent renal precipitation of urates.

- Dosage of Crystasol varies with the severity of the disease and should be adjusted according to the response and tolerance of the patient.

Adults:
Dosage range of 100–800 mg daily divided into 1 to 3 doses.
Single dose should not exceed 300 mg.

Gout:
- Crystasol should be initiated at a dose of 100 to 200 mg daily and increased by 100 mg at weekly intervals, until a serum uric acid concenteration of about 360 µmol/L (6 mg/dl) or less is attained or until the maximum recommended dosage of 800 mg/day (in patients with normal renal function) is reached.

- Concurrent administration of colchicines (0.6 mg twice daily) or an NSAID is recommended as prophylaxis during the first 3 to 6 months of Crystasol therapy.

- The average maintenance dose is:
200 to 300 mg/day for patients with mild gout.
400 to 600 mg/day for patients with moderately severe tophaceous gout.
700 to 800 mg/day in severe conditions.

Dosage in renal impairment:
Since allopurinol and its metabolites are excreted by the kidney, drug accumulation can occur if renal function is impaired; the initial dose of Crystasol should consequently be reduced.

Maintenance dose:

Creatinine clearance
 
Dose
 ml/ s  Ml/ min
<0.17
0.17
0.33
0.67
1.00
1.33
1.67
2.00
2.33
<10
10
20
40
60
80
100
120
140
100 mg every 3 days
100 mg every 2 days
100 mg daily
150 mg daily
200 mg daily
250 mg daily
300 mg daily
350 mg daily
400 mg daily

Prevention of uric acid nephropathy during treatment of neoplastic disease:
600 to 800 mg daily for 2 or 3 days starting 1 or 2 days prior to chemotherapy or radiation therapy.

Prophylaxis of hyperuricemia secondary to cancer or chemotherapy:
300 to 400 mg daily.

Prophylaxis of renal calcium lithiasis:
200 to 300 mg daily.

Children:
Children ? 10 years of age: 10 mg/kg/day in two to three divided doses. Maximum 800 mg/24 hours.

Children < 6 years of age: 150 mg/day in three divided doses.

Children 6 to 10 years of age: 300 mg/day in two to three divided doses.

For gout in children > 10 years of age & adults: 200 to 600 mg/day.
Response should be evaluated after approximately 48 hours by monitoring serum uric acid and/or urinary uric acid concentrations and adjusting the dose if necessary.

Contraindications:
Crystasol is contraindicated in patients with hypersensitivity to allopurinol or any of the components of the product.

Side effects:

Dermatologic: Skin rash, usually maculopopular, is the most commonly reported side effects.
Incidence of skin rash may be increased in the presence of renal disorders.
In some instances, rashes may be followed by severe hypersensitivity reactions. Crystasol should be discontinued immediately if such reactions occur.
Exfoliative, urticarial or purpuric lesions, Stevens-Johnson syndrome (erythema multiforme), bulbae and toxic epidermal necrolysis are also reported.
A few cases of alopecia with or without accompanying dermatitis are reported.

Gastrointestinal: Diarrhea, intermittent abdominal pain, nausea, vomiting.

Generalized hypersensitivity: Skin reactions associated with exfoliation, fever, chills, nausea and vomiting, lymphadenopathy, arthralgia and/or eosinophilia.
When generalized hypersensitivity reactions occur, renal and/or hepatic dysfunction are usually present.

Hematologic:
Reduction in the number of circulating formed elements of the blood including bone marrow suppression, granulocytopenia and thrombocytopenia usually in association with renal and/or hepatic disorders or in whom concomitant drugs have been administered  which have a potential for causing these reactions.

Miscellaneous:
Fever, general malaise, headache, vertigo, somnolence, taste perversion, hepatic necrosis, granulomatous hepatitis, abnormal liver function tests, rise in urea, hyperlipidemia, visual disorder, cataracts, macular changes, neuropathy, impotence, diabetes mellitus, furunculosis, hypertension, hematuria, edema, drowsiness, peripheral neuritis.

Drug interactions:
- Concurrent administration of ACE inhibitors and Crystasol may increase the risk of hypersensitivity reactions (e.g. Stevens-Johnson syndrome), especially in patients with chronic renal failure.

Uricosuric effect of Crystasol may be decreased by alcohol.-
 
Concurrent administration of Aluminium hydroxide-containing antacids with Crystasol may reduce gastrointestinal absorption of Crystasol.
Crystasol should be given at least 3 hours before the antacid.

- Patients on oral anticoagulants and Crystasol develop an enhanced anticoagulant effect.

- Crystasol increases the pharmacologic and toxic effects of Azathioprine, Mercaptopurine and Vidarabine by inhibiting their metabolism.
Concurrent administration of azathioprine or mercaptopurine with Crystasol requires that initial thioprine doses be reduced to 25% or 33% of the recommended initial dose.
Subsequent doses should be adjusted according to clinical response.

- Crystasol can compete with chlorpropamide for renal tubular secretion. When renal function is poor, the recognized risk of chlorpropamide's prolonged hypoglycemic activity may be increased if Crystasol is given concomitantly.

- A few cases of thrombocytopenia have been reported in patients receiving Co-trimoxazole with Crystasol.
 
- Concurrent Cyclophosphamide and Crystasol therapy may increase the incidence of bone marrow depression as compared with Cyclophosphamide alone.

- Thiazides and ethacrynic acid, when given with Crystasol may increase risk of serious Crystasol toxicity particularly in patients with decreased renal function.

Doses exceeding 600 mg/day of Crystasol may decrease theophylline - clearance when both drugs are used for longer than 2 weeks, some patients may require monitoring for signs of possible theophylline toxicity and dosage adjustments during concurrent Crystasol therapy.

- Concomitant administration of a uricosuric agent e.g. Probenecid and Crystasol may alter the disposition of both drugs.
The combination usually results in an additive lowering of the serum uric acid level.

- Crystasol can inhibit the metabolism of an active metabolite of vidarabine and may increase the risk of CNS toxicity.

Pregnancy:
Crystasol is used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Lactation:
Use of Crystasol is contraindicated during lactation.

Precautions & Warnings:
- Crystasol should be discontinued at first appearance of skin rash or any sign of serious adverse reactions.
Skin rash may sometimes be followed by more severe hypersensitivity reactions such as exfoliative, urticarial or purpuric lesions, as well as Stevens-Johnson syndrome and very rarely a generalized vasculitis which may lead to irreversible hepatotoxicity and death.
Hypersensitivity reactions, frequently marked by fever and eosinophilia, usually begin 2 to 4 weeks after start of therapy and appear to be more common in patients with pre-existing renal dysfunction, elevated oxypurinol plasma levels and/or concurrent thiazide therapy.

- Liver enzymes, renal function tests and complete blood counts should be performed before starting therapy with Crystasol then periodically during therapy especially in patients with pre-existing liver disease, impaired renal function or diseases that may affect renal function.

- Crystasol is not effective for treatment of acute gouty attacks, however, it is continued during acute attacks at the same dosage, in patients already established on Crystasol therapy.

- When Crystasol therapy is initiated, acute gouty attacks may be precipitated, and these may continue even after serum uric acid concentrations begin to fall, usually for the first 6–12 months.

- Crystasol should be reserved for use when uricosurics can not be used because of adverse effects, allergy, renal insufficiency or inadequate response.

- Crystasol should not be given to children except those with hyperuricemia secondary to malignancy or with Lesch-Nyhan syndrome, because safety and effectiveness have not been established in other conditions.

- Drowsiness may occur. Patients should be cautioned not to engage in activities where alertness is mandatory until their response to Crystasol is known.

Therapeutic category:
Antihyperuricemic, antigout.

Legal category: POM.


Package:

Box containing 10 tablets.

Storage:

Store in a dry place, at a temperature not exceeding 30°C.

THIS IS A MEDICAMENT
Medicament is a product, which affects your health and its consumption contrary to instructions is dangerous for you. Follow strictly the doctor’s prescription, the method of use and the instructions of the pharmacist who sold the medicament.
- The doctor and the pharmacist are the experts in medicines, their benefits and risks.
- Do not by yourself interrupt the period of treatment prescribed.
- Do not repeat the same prescription without consulting your doctor.
- Keep all medicaments out of reach of children.

Council of Arab Health Ministers, Union of Arab Pharmacists.