Allopurinol 300 MG Oral Tablet
Generic Name: ALLOPURINOL
Brand Name: ALLOPURINOL
- Substance Name(s):
- ALLOPURINOL
WARNINGS
ALLOPURINOL TABLETS 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, irreversible hepatotoxicity, and, on rare occasions, death.
In patients receiving mercaptopurine or azathioprine, the concomitant administration of 300 to 600 mg of allopurinol tablets 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).
A few cases of reversible clinical hepatotoxicity have been noted in patients taking allopurinol tablets, and in some patients, asymptomatic rises in serum alkaline phosphatase or serum transaminase have been observed.
If anorexia, weight loss, or pruritus develop in patients on allopurinol tablets, evaluation of liver function should be part of their diagnostic workup.
In patients with pre-existing liver disease, periodic liver function tests are recommended during the early stages of therapy.
Due to the occasional occurrence of drowsiness, patients should be alerted to the need for due precaution when engaging in activities where alertness is mandatory.
The occurrence of hypersensitivity reactions to allopurinol tablets may be increased in patients with decreased renal function receiving thiazides and allopurinol tablets concurrently.
For this reason, in this clinical setting, such combinations should be administered with caution and patients should be observed closely.
OVERDOSAGE
Massive overdosing or acute poisoning by allopurinol tablets has not been reported.
In mice, the 50% lethal dose (LD50) is 160 mg/kg given intraperitoneally (IP) with deaths delayed up to 5 days and 700 mg/kg orally (PO) (approximately 140 times the usual human dose) with deaths delayed up to 3 days.
In rats, the acute LD50 is 750 mg/kg IP and 6000 mg/kg PO (approximately 1200 times the human dose).
In the management of overdosage there is no specific antidote for allopurinol tablets.
There has been no clinical experience in the management of a patient who has taken massive amounts of allopurinol tablets.
Both allopurinol and oxipurinol are dialyzable; however, the usefulness of hemodialysis or peritoneal dialysis in the management of an overdose of allopurinol tablets is unknown.
DESCRIPTION
Allopurinol is known chemically as 1, 5-dihydro-4H-pyrazolo [3, 4-d] pyrimidin-4-one.
It is a xanthine oxidase inhibitor which is administered orally.
Its solubility in water at 37°C is 80.0 mg/dL and is greater in an alkaline solution.
Each scored white to off-white tablet contains 100 mg allopurinol and the inactive ingredients lactose monohydrate, corn starch, sodium starch glycolate, povidone and stearic acid.
Each scored peach tablet contains 300 mg allopurinol and the inactive ingredients lactose monohydrate, corn starch, sodium starch glycolate , FD & C yellow no.
6, povidone and stearic acid.
INDICATIONS AND USAGE
INDICATIONS & USAGE THIS IS NOT AN INNOCUOUS DRUG.
IT IS NOT RECOMMENDED FOR THE TREATMENT OF ASYMPTOMATIC HYPERURICEMIA.
Allopurinol tablets reduce 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 tablets are 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.
Treatment with allopurinol tablets 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.
DOSAGE AND ADMINISTRATION
DOSAGE & ADMINISTRATION The dosage of allopurinol tablets 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 is 200 to 300 mg/day for patients with mild gout and 400 to 600 mg/day for those with moderately severe tophaceous gout.
The appropriate dosage may be administered in divided doses or as a single equivalent dose with the 300 mg tablet.
Dosage requirements in excess of 300 mg should be administered in divided doses.
The minimal effective dosage is 100 to 200 mg daily and the maximal recommended dosage is 800 mg daily.
To reduce the possibility of flare-up of acute gouty attacks, it is recommended that the patient start with a low dose of allopurinol tablets (100 mg daily) and increase at weekly intervals by 100 mg until a serum uric acid level of 6 mg/dL or less is attained but without exceeding the maximal recommended dosage.
Normal serum urate levels are usually achieved in 1 to 3 weeks.
The upper limit of normal 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 to 3 mg/dL and keep it there indefinitely.
While adjusting the dosage of allopurinol tablets in patients who are being treated with colchicine and/or anti-inflammatory agents, it is wise to continue the latter therapy until serum uric acid has been normalized and there has been freedom from acute gouty attacks for several months.
In transferring a patient from a uricosuric agent to allopurinol tablets, the dose of the uricosuric agent should be gradually reduced over a period of several weeks and the dose of allopurinol tablets gradually increased to the required dose needed to maintain a normal serum uric acid level.
It should also be noted that allopurinol tablets are generally better tolerated if taken following meals.
A fluid intake sufficient to yield a daily urinary output of at least 2 liters and the maintenance of a neutral or, preferably, slightly alkaline urine are desirable.
Since allopurinol tablets and its metabolites are primarily eliminated only by the kidney, accumulation of the drug can occur in renal failure, and the dose of allopurinol tablets should consequently be reduced.
With a creatinine clearance of 10 to 20 mL/min, a daily dosage of 200 mg of allopurinol tablets is suitable.
When the creatinine clearance is less than 10 mL/min, the daily dosage should not exceed 100 mg.
With extreme renal impairment (creatinine clearance less than 3 mL/min) the interval between doses may also need to be lengthened.
The correct size and frequency of dosage for maintaining the serum uric acid just within the normal range is best determined by using the serum uric acid level as an index.
For the prevention of uric acid nephropathy during the vigorous therapy of neoplastic disease, treatment with 600 to 800 mg daily for 2 or 3 days is advisable together with a high fluid intake.
Otherwise similar considerations to the above recommendations for treating patients with gout govern the regulation of dosage for maintenance purposes in secondary hyperuricemia.
The dose of allopurinol tablets recommended for management of recurrent calcium oxalate stones in hyperuricosuric patients is 200 to 300 mg/day in divided doses or as the single equivalent.
This dose may be adjusted up or down depending upon the resultant control of the hyperuricosuria based upon subsequent 24 hour urinary urate determinations.
Clinical experience suggests that patients with recurrent calcium oxalate stones may also benefit from dietary changes such as the reduction of animal protein, sodium, refined sugars, oxalate-rich foods, and excessive calcium intake, as well as an increase in oral fluids and dietary fiber.
Children, 6 to 10 years of age, with secondary hyperuricemia associated with malignancies may be given 300 mg allopurinol tablets daily while those under 6 years are generally given 150 mg daily.
The response is evaluated after approximately 48 hours of therapy and a dosage adjustment is made if necessary.