Allopurinol

BRAND NAMES:

Zyloprim: It contains allopurinol as a main ingredient. The zyloprim oral tablets have strengths of 100 mg and 300 mg.

Lopurin: It contains allopurinol as a main ingredient. The Lopurin oral tablets have strengths of 100 mg and 300 mg.

MECHANISM OF ACTION:

Allopurinol is metabolized in the liver into its pharmacologically active metabolite, oxypurinol. The half-life of allopurinol is 1 to 2 hours, while that of oxypurinol is around 15 hours. Both allopurinol and oxypurinol are eliminated by the kidney. Both allopurinol and oxypurinol block xanthine oxidase, a purine catabolism enzyme that transforms hypoxanthine to xanthine and thereafter to uric acid. Allopurinol promotes gout tophi dissolution by reducing uric acid levels in the plasma below their solubility limits. Although hypoxanthine and xanthine levels are reported to rise following allopurinol administration, the danger of deposition in renal tissues is lower than that of uric acid because they become more soluble and are quickly eliminated by the kidney. 

PHARMACOKINETICS:

Absorption: A 300 mg oral dose of allopurinol produced maximum plasma levels of approximately 3 mcg/ml allopurinol and 6.5 mcg/ml oxypurinol. This drug is roughly 90% absorbed by the gastrointestinal system. Peak plasma levels of allopurinol and oxypurinol usually peak 1.5 and 4.5 hours after dosage. 

Distribution: The apparent mean volume of distribution of allopurinol is 1.6-2.4 L/kg.

Metabolism: Allopurinol is a structural homolog of hypoxanthine, a naturally occurring purine base. Following consumption, allopurinol is converted in the liver to its active metabolite, oxypurinol, which inhibits the enzyme xanthine oxidase. The purine salvage process also converts allopurinol and oxypurinol into their corresponding ribonucleotides. At present, the effect of these ribonucleotides on allopurinol's hypouric activity in humans has not been well understood. These metabolites may function to prevent de novo purine production by inhibiting the enzyme amidophosphoribosyltransferase. Ribonucleotides were not discovered to be integrated into DNA. 

Excretion: The 20% of ingested allopurinol is excreted in the feces. 80% of orally ingested allopurinol is found excreted in the urine as various metabolites.

PHARMACODYNAMICS:

Allopurinol decreases plasma uric acid levels while increasing plasma levels of hypoxanthin and xanthine. Allopurinol also reduces the amount of uric acid excreted in urine while increasing the amount of hypoxanthin and xanthine excreted in urine.

ADMINISTRATION:

Allopurinol comes in tablet form for oral consumption. It is often taken once or twice a day, preferably after a meal. It can be given orally or intravenously. While oral administration is the usual technique for treating gout, uric acid, and calcium oxalate nephrolithiasis, IV allopurinol is used to prevent tumor lysis syndrome and manage cancer therapy-induced hyperuricemia in patients who are unable to take oral medications.

DOSAGE AND STRENGTHS:

Allopurinol is available as Lopurin, Zyloprim, and generic allopurinol in the following dosage forms that are taken orally.

These doses are available in the strengths of 100 mg, 200 mg, and 300 mg of tablets.

Powder for injection: 500 mg/vial

CONTRAINDICATIONS:

Patients with impaired renal function who use thiazides and allopurinol simultaneously are more likely to develop a hypersensitivity reaction to allopurinol.

DRUG INTERACTIONS:

The drug interaction of allopurinol includes:

• Thiazide diuretics- hydrochlorothiazides and chlorthalidone, which are commonly used to reduce fluid buildup or lower blood pressure.
• Antibiotics- ampicillin and amoxicillin
• Cyclosporine-medicine to suppress your immune system
• Mercaptopurine or azathioprine – used to suppress your immune system in treating certain diseases.
• Theophylline-used to treat certain breathing conditions
• Probenecid- used to treat gout
• Warfarin-used to treat blood thinner

SIDE EFFECTS:

Allopurinol may cause serious side effects. 

• Skin rash
• Painful urination

Inflammation of your blood vessels

• numbness
• Skin rash
• Fever
• Headache
• Body aches
• Weight loss

Signs of infections

• fever
• Chills
• Sore throat 
• Body aches
• Unusual tiredness
• Loss of appetite

Liver problems

• loss of appetite
• Weight loss
• Stomach pain
• Itiching
• Dark urine

Common allopurinol side effects may include:

• Rash 
• Drowsiness
• Abnormal liver function tests
• Nausea
• Vomiting
• Diarrhea

Kidney problems- swelling, urinating less, feeling tired or short of breath

OVERDOSE:

If you take too much of allopurinol it leads to over dose. Symptoms can includes

• Skin rash
• Diarrhea
• Nausea
• Changes in liver function
• Gout flare up

TOXICITY:

Because it is uncertain how allopurinol may affect a nursing infant, it is best to proceed with caution when a nursing mother takes allopurinol. Allopurinol has not been shown to be mutagenic and has no harmful effects on DNA at any stage of the cell cycle. Allopurinol-treated mice did not show any signs of carcinogenicity during a two-year period.

STORAGE:

Maintain allopurinol between 68 and 77 °F (20 and 25 degrees Celsius) at room temperature. When shipped, for example, it can tolerate temperatures from 59 and 86 °F (15 and 30° Celsius) over short periods of time.