Allopurinol

Allopurinol

100mg Tablet

300mg Tablet

DRUG CATEGORY:

Antigout Drug

BRAND NAME:

Zyloprim

PHARMACOLOGY:

Allopurinol is used in gout and hyperuricemia to inhibit the enzyme xanthine oxidase, thus preventing the oxidation of hypoxanthine to xanthine and xanthine to uric acid. The urinary purine load, normally almost entirely uric acid, is thereby divided between hypoxanthine, xanthine, and uric acid, each with its independent solubility. This results in the reduction of urate and uric acid concentrations in plasma and urine, ideally to such an extent that deposits of monosodium urate monohydrate or uric acid are dissolved or prevented from forming. At low concentrations Allopurinol acts as a competitive inhibitor of xanthine oxidase and at higher concentrations as a non-competitive inhibitor. However, most of its activity is due to the metabolite oxipurinol which is a non-competitive inhibitor of xanthine oxidase.

Allopurinol is used in patients with chronic gout to correct hyperuricemia thereby reducing the likelihood of acute attacks and preventing the sequel of chronic gout.

In the initial stages of Allopurinol therapy the release of urate and uric acid from deposits may increase concentrations of these compounds circulating in plasma. This may trigger or exacerbate acute attacks, hence Allopurinol should not be started until an acute attack has completely subsided. In addition, it is recommended that treatment should be started with a low dose increased gradually and that an NSAID or Colchicine should also be given during the first few months.

PHARMACOKINETICS:

Up to 90% of a dose of allopurinol is absorbed from the gastrointestinal tract after oral administration; its plasma half-life is about 1 to 2 hours. Allopurinol's major metabolite is oxipurinol (alloxanthine) which is also an inhibitor of xanthine oxidase with a plasma half-life of about 15 or more hours in patients with normal renal function, although this greatly prolonged by renal impairment. Both Allopurinol and oxipurinol are conjugated to form their respective ribonucleosides. Allopurinol and oxipurinol are not bound to plasma proteins.

INDICATION:

For the treatment of hyperuricemia associated with chronic gout, acute uric acid nephropathy, recurrent uric acid stone formation, enzyme disorders, and cancer chemotherapy. It is also used in the management of renal calculi caused by the deposition of calcium oxalate.

DOSAGE AND ADMINISTRATION:

A suggested starting dose of Allopurinol is 100mg daily by mouth, gradually increased by 100mg for example at weekly intervals until the concentration of urate in plasma is reduced to 0.36 mmol per liter (6mg per 100ml) or less. A daily dose range of 100 to 300 mg may be adequate for those with mild to moderate gout and up to 600mg for those with moderately severe tophaceous gout. The maximum recommended daily dose is 800mg in the USA and 900mg in the UK. Up to 300mg may be taken as single daily dose; larger amounts should be taken in divided doses to reduce the risk of gastric irritation. Taking Allopurinol after food will also minimize gastric irritation. Patients should maintain an adequate fluid intake to prevent renal xanthine deposition. Or as prescribed by a physician.

If you forget to take your regular dose of Allopurinol, take the missed dose as soon as possible. If it is time for your next regular dose, double this dose. For example, if your regular dose is 300 mg and you miss a dose, take 600mg at the next usual dose time.

CONTRAINDICATION:

Allopurinol is contraindicated to patients with hypersensitivity reactions. If Allopurinol has taken and developed a rash or any other adverse effects, stop taking the medication immediately and contact your doctor.

Liver toxicity have been associated with Allopurinol; they improved when the drug was stopped. Periodic liver and kidney test should be performed while taking this medicine. People with severely compromising kidney function should take a reduced dose of this medicines.

ADVERSE DRUG REACTIONS:

The most common adverse drug reaction of Allopurinol is skin rash. Rashes are generally maculopapular or pruritic, but more serious hypersensitivity reactions may occur and include exfoliative rashes, the Stevens-Johnson Syndrome, and toxic epidermal necrolysis. It is therefore recommeded that Allopurinol be withdrawn immediately if a rash occurs.

Less common: Nausea, vomiting diarrhea, intermittent stomach pains, effects on blood components, and drowsiness or lack of ability to concentrate.

Rare: Effects on the eyes, loss of hair, fever, chills, difficulty breathing or asthma-like symptoms, arthritis-like symptoms, itching, loosening of the fingernails, pain in the lower back, unexplained nosebleeds, cataracts, conjunctivitis and other eye conditions, numbness, tingling or pain in the hands or feet, confusion, dizziness, fainting, depression, memory loss, ringing or buzzing in the ears, weakness, sleeplessness, and feelings of ill health.

DRUG INTERACTIONS:

1. Drugs that can increase uric acid concentrations may decrease the efficacy of Allopurinol. Aspirin and the salicylates possess this activity and should generally be avoided in hyperuricemia and gout.
2. Large doses of drugs that make your urine more acid, like megadoses of vitamin C, may increase the possibility of kidney stone formation.
3. An increase in hypersensitivity reactions, and possibly also other adverse effects, has been reported to patients with Allopurinol with ACE inhibitors or thiazide diuretics, particularly to patients with impaired renal function.
4. Alcohol, Diazoxide, Mecamylamine, or Pyrazinamide can increase the amount of uric acid in your blood, requiring a possible increase in your Allopurinol dose.
5. Large doses of Allopurinol (more than 600mg per day) may increase the effects of and chances for toxic reactions to Theophylline by interfering with its clearance from the body.
6. The metabolism of Azathioprine, Mercaptopurine, or Cyclophosphamide and other anticancer medicines is inhibited by Allopurinol and their doses should be reduced to one-quarter to one-third of the usual dose when either of them is given with Allopurinol to avoid serious bleeding, or infection, and potentially life-threatening toxicity.
7. Dacarbazine, Probenecid, or Sulfinpyrazone may cause additive reductions in uric acid when taken with Allopurinol.
8. Allopurinol may interact with anticoagulant (blood-thinning) medications, reducing the rater at which the anticoagulant is broken down in the body. Dosage reduction is necessary.
9. Using Vidarabine and Allopurinol together can increase the risk of neurotoxic effects and anemia, nausea, pain and itching.
10. Allopurinol can reduce the breakdown of Chlorpropamide (for diabetes), causing an increase in antidiabetic effect. Dosage adjustment may be necessary.
11. People who are susceptible to Ampicillin, Amoxicillin, Bacampicillin, or Hetacillin rash are more likely to have that problem while also taking Allopurinol.

SPECIAL PRECAUTIONS:

Liver and Kidneys Impairment:

Dosage should be reduced in renal impairment and in hepatic impairment; extra monitoring may be necessary. Care is advised in patients being treated for hypertension or cardiac insufficiency, who may have concomitant renal impairment.

Pregnancy and Lactation:

This drug may cause birth defects or interfere with your baby's development. Check with your doctor before taking it if you are, or might be, pregnant. A nursing mother should not take this medication, since it will pass through the mother's milk to the child.

Elderly:

No special precautions are required. Be sure to follow your doctor's directions and report any side effects at once.

Effects on ability to drive and use machines:

Allopurinol can make you drowsy or make it difficult for you to concentrate. Take care while driving a car or operating hazardous equipment.

STORAGE:

Store at temperatures not exceeding 30^oC