Allopurinol

Allopurinol is a drug that inhibits the formation of uric acid. It is an anti-gout medication that inhibits the binding of uric acid and its salts within the body.

The drug is able to slow down the activity of the enzyme xanthine oxidase, which is involved in the transformation processes hypoxanthine/xanthine and xanthine/uric acid. As a result of such interactions, the serum urate level decreases, which prevents their deposition in the kidneys and tissues. [ 1 ]

Indications Allopurinol

In adults, the medication is used for the following disorders:

• hyperuricemia (with serum uric acid 500+ μmol/L) that cannot be controlled by diet;
• pathologies associated with increased blood uric acid levels (especially urate nephropathy, gout and urate urolithiasis);
• secondary hyperuricemia of various origins (also psoriasis);
• associated with various hemoblastoses (lymphosarcoma, active form of leukemia and chronic myeloleukemia) hyperuricemia of primary or secondary type;
• Cytotoxic treatment for myeloproliferative and neoplastic diseases.

It is prescribed to children for the following diseases:

• urate form of nephropathy that developed during treatment of leukemia;
• secondary hyperuricemia of various origins;
• congenital enzyme deficiency (including complete or partial deficiency of GGPRT; Lesch-Nyen syndrome) and congenital deficiency of APFT.

Release form

The medicinal substance is released in the form of tablets - 10 pieces inside a cellular package. Inside the box - 5 such packages.

Pharmacodynamics

In the body, allopurinol is transformed into oxypurinol, which prevents the formation of uric acid, but its activity is weaker than that of allopurinol.

Pharmacokinetics

After oral administration, the drug is fully and rapidly absorbed. There is almost no absorption inside the stomach, absorption occurs inside the duodenum and in the upper part of the small intestine.

Metabolic processes lead to the formation of the main medicinally active metabolic component of oxypurinol. Cmax values of oxypurinol are noted after 3-4 hours; the rate of formation is associated with the speed and degree of personal presystemic metabolic processes. Oxypurinol with allopurinol almost do not participate in protein synthesis.

The plasma half-life of allopurinol is approximately 40 minutes, and that of oxypurinol is 17-21 hours. 80% of both elements are excreted via the kidneys; 20% is excreted via the intestines. In individuals with renal insufficiency, the half-life of oxypurinol is prolonged.

Dosing and administration

Allopurinol should be taken orally after meals; the tablets are swallowed whole with plain water. The tablets should not be chewed. During therapy, the patient should drink plenty of fluids to maintain stable diuresis. Sometimes, urine alkalinization is performed to improve uric acid excretion.

The dosage and duration of treatment are selected by the attending physician individually, taking into account the severity of the pathology and the clinical situation.

When selecting the daily dosage of the drug, it is necessary to take into account the plasma uric acid level. The patient can take 0.1-0.3 g of the drug per day. The dosage is adjusted once every 1 or 3 weeks. A maximum of 0.8 g of the drug is allowed per day.

• Application for children

It is prohibited to use the medicine in persons under 3 years of age.

Use Allopurinol during pregnancy

There is no information regarding the use of Allopurinol during pregnancy. Since the active element of the drug affects the metabolic processes of purine, and there is no information regarding potential risks to humans, it is prohibited to prescribe the drug to pregnant women.

The drug is excreted in breast milk, which is why it is not used during breastfeeding. Breastfeeding should be discontinued during therapy.

Contraindications

Main contraindications:

• severe intolerance to allopurinol or other components of the medication;
• severe liver/renal dysfunction (creatinine clearance below 2 ml per minute);
• active stage of a gout attack.

Side effects Allopurinol

Side effects include:

• metabolic disorders: at the initial stage of therapy, an active gout attack may develop, which is associated with the mobilization of uric acid in the area of gouty nodules and other depots;
• problems with liver function and gastrointestinal tract: vomiting, treatable increase in blood levels of alkaline phosphatase and transaminases, stomatitis, nausea, hepatitis, diarrhea and active cholangitis;
• disorders of hematopoiesis: leukocytosis, leukopenia or eosinophilia. Severe bone marrow damage (agranulocytosis, thrombocytopenia and aplastic anemia), especially in people with renal insufficiency;
• symptoms associated with the activity of the cardiovascular system: increased blood pressure and bradycardia;
• CNS lesions: drowsiness, headache, fatigue, dizziness, ataxia, weakness, convulsions and neuropathies, as well as myalgia, depression, paresthesia and paresis, as well as peripheral neuritis;
• manifestations associated with the senses: cataracts, taste or visual disturbances;
• urinary disorders: uremia, tubulointerstitial nephritis accompanied by lymphocyte infiltration, xanthogen stones and hematuria;
• signs of allergy: urticaria, TEN, chills, MEE, itching, erythema, fever and arthralgia;
• Others: impotence, diabetes, baldness and gynecomastia.

In patients with renal insufficiency, vasculitis with epidermal changes may occur when using standard dosage; later, this process may spread to the liver and kidneys. If vasculitis develops, Allopurinol should be discontinued immediately.

Overdose

Sometimes, in individuals who do not have renal dysfunction and take 20 g of the drug per day, vomiting, bowel disorders, nausea and dizziness are observed.

Long-term use of the drug in people with renal dysfunction sometimes causes eosinophilia, hyperthermia, epidermal rash and exacerbation of renal pathologies. There is no antidote for the drug, which is why symptomatic measures must be taken in case of poisoning.

Interactions with other drugs

The effect of the drug is weakened when using drugs with a uricosuric effect (probenecid, sulfinpyrazone and benzbromarone), as well as with high doses of salicylates.

Allopurinol is able to slow down the activity of xanthine oxidase, as well as the metabolic processes of purine derivatives (including mercaptopurine and azathioprine), which is why their standard dose should be reduced by 50-75%.

Large doses of the drug reduce the rate of excretion of probenecid and suppress theophylline metabolism processes.

Combining the drug with chlorpropamide requires a reduction in the dosage of the latter.

The introduction of Allopurinol in combination with coumarin anticoagulants requires a reduction in their dose. In addition, it is necessary to regularly monitor blood coagulation parameters.

The use of the drug together with captopril increases the likelihood of developing epidermal symptoms, especially if the patient has chronic renal failure.

Combination with cytostatics may provoke an increase in the frequency of changes in blood parameters (in comparison with the separate use of these medications), which is why it is recommended to perform blood tests more often than usual.

The combination of the drug with amoxicillin and ampicillin increases the likelihood of developing signs of allergy.

Storage conditions

Allopurinol should be stored in a place inaccessible to children. Temperature values - no more than 25 ° C.

Shelf life

Allopurinol can be used within a 5-year period from the date of manufacture of the medicinal substance.

Analogues

An analogue of the drug is the drug Allohexal.