Allohexal

Allohexal is a drug that inhibits the production of uric acid.

The substance allopurinol is a structural analogue of the component hypoxanthine. It prevents the binding of uric acid and has urostatic activity, which acts mainly due to the fact that allopurinol is able to suppress the enzyme xanthine oxidase. As a result, the oxidation of hypoxanthine is catalyzed with the formation of xanthine, from which uric acid is formed. This allows for a decrease in uric acid levels and helps dissolve urates. [ 1 ]

Indications Allohexal

In pediatrics it is used for the following disorders:

• urate nephropathy developed during treatment of leukemia;
• secondary hyperuricemia, which has a different nature;
• congenital enzyme deficiency - for example, Lesch-Nyhan syndrome or congenital deficiency of the APRT component.

In adults it is used in the following cases:

• hyperuricemia (serum uric acid levels of 500+ μmol) that cannot be controlled by diet;
• psoriasis;
• diseases associated with increased blood levels of uric acid (especially in the case of nephropathy or urate urolithiasis, as well as gout);
• secondary hyperuricemia of various origins;
• hyperuricemia of secondary or primary type, arising against the background of various hemoblastoses (chronic myeloleukemia, leukemia in the active phase and lymphosarcoma);
• radiation or cytostatic procedures for the treatment of neoplasms;
• use of GCS in large volumes.

Release form

The medicinal substance is released in the form of tablets - 10 pieces in a cell pack; in a box - 5 such packs.

Pharmacokinetics

When administered orally, allopurinol is completely and rapidly absorbed into the blood. Gastric absorption is almost not observed. Suitable conditions for absorption are observed in the upper part of the small intestine and the duodenum. After taking a standard therapeutic dose of 0.3 g, the plasma Cmax of allopurinol is recorded approximately after 1 hour and is 1-2.6 mcg/ml (average value - 1.8 mcg/ml).

Metabolic transformations allow obtaining the metabolic element oxypurinol, which has a therapeutic effect. It reaches its Cmax values after 3-4 hours (they are 5-11 mcg/ml (the average value is 8.4 mcg/ml)). The rate of formation is determined by the speed and intensity of pre-systemic metabolic processes in humans.

Allopurinol and oxypurinol are almost not involved in the synthesis of blood protein.

The plasma half-life of allopurinol is approximately 40 minutes, and that of oxypurinol is within 17-21 hours. In almost a third of patients, the expected half-life of oxypurinol is 9-16 hours.

80% of the above components are excreted through the kidneys, and another 20% through the intestines. In individuals with renal insufficiency, the half-life of oxypurinol increases.

Dosing and administration

For children aged 3-6 years, the medicine is used in a dose of 5 mg/kg. For people aged 6-10 years - 10 mg/kg. The medicine should be taken 3 times a day.

For an adult, the daily dosage is selected individually, taking into account serum uric acid levels; it is often 0.1-0.3 g of the drug per day. If necessary, the dose can be gradually increased by 0.1 g at 1-3-week intervals until the maximum result is achieved.

The maintenance dose is 0.2-0.6 g per day; sometimes it can be increased to 0.6-0.8 g. If the daily dose is higher than 0.3 g, it is necessary to divide it into 2-4 equal portions for consumption. In case of increasing the dose, it is necessary to monitor the serum oxypurinol levels (they should not be higher than 15 mcg/ml).

Persons with renal insufficiency.

Therapy should be started with a daily dosage of 0.1 g; it can be increased only in cases where the effect obtained from the medication is too weak. Dosage selection schemes:

• the level of CC is higher than 20 ml per minute – 0.1-0.3 g of LS per day;
• indicator within 10-20 ml per minute – 0.1-0.2 g of allopurinol per day;
• values below 10 ml per minute – 0.1 g of the substance or higher doses, but taken at longer intervals (for example, 1-2+ days – taking into account the patient’s condition and kidney function).

For people undergoing hemodialysis, 0.3 g of Allohexal is administered during each session (2-3 times per week).

To prevent the development of hyperuricemia during chemo- and radiation therapy of neoplasms, an average of 0.4 g per day is used. It is necessary to start taking it 2-3 days before or simultaneously with antineoplastic treatment; the use of the drug should be continued for several days after the completion of specific therapy.

The tablets should be taken without chewing, with plenty of liquid, after meals.

The duration of the treatment cycle is determined by the course of the underlying pathology.

• Application for children

The medication is not used in children under 3 years of age.

Use Allohexal during pregnancy

It is prohibited to prescribe Allohexal during pregnancy or breastfeeding.

Contraindications

Main contraindications:

• severe hypersensitivity to allopurinol or other components of the drug;
• severe liver/renal dysfunction.

Side effects Allohexal

At the initial stage of therapy, a reactive gout attack may develop.

Sometimes problems with the gastrointestinal tract (vomiting, diarrhea and nausea) or epidermal disorders (urticaria, erythema or itching) are noted.

Fatigue, paresis, visual disturbances, weakness, depression and neuropathy occur occasionally. In addition, ataxia, cataracts, convulsions, dizziness, paresthesia, headaches, taste disturbances and drowsiness are observed.

In people with renal insufficiency (when the drug dosage is not reduced), vasculitis with epidermal changes and involvement of the liver and kidneys may occur. If the patient has vasculitis, therapy should be discontinued immediately.

Other side effects include:

• symptoms of intolerance - epidermal manifestations, fever, arthralgia and chills;
• changes in blood counts (leukocytosis or leukopenia, as well as eosinophilia) and severe bone marrow damage (agranulocytosis, thrombocytopenia or aplastic anemia), especially in people with renal insufficiency;
• epidermal lesions - TEN or MEE;
• liver dysfunctions (curable increase in transaminase and alkaline phosphatase levels in the blood), stomatitis and hepatitis;
• alopecia;
• peripheral neuritis or myalgia;
• drug-allergy-associated tubulointerstitial nephritis with lymphocytic infiltration;
• hematuria or uremia;
• cholangitis in the active phase;
• xanthogenic stones;
• gynecomastia or erectile dysfunction;
• increased blood pressure, diabetes mellitus or bradycardia.

Overdose

Signs of poisoning: vomiting, dizziness, diarrhea, oliguria and nausea.

Peritoneal and hemodialysis procedures, as well as forced diuresis, are performed.

Interactions with other drugs

The therapeutic effect of allopurinol is weakened when used with substances that have a uricosuric effect (probenecid, sulfinpyrazone and benzbromarone), as well as with large doses of salicylates.

Allopurinol can potentiate the effect of many medications. For example, because allopurinol can slow down the action of xanthine oxidase, the metabolic processes of purine derivatives (mercaptopurine with azathioprine) slow down. Because of this, their standard dose should be reduced by 50-75%. At the same time, large doses of Allohexal inhibit the excretion of probenecid and theophylline metabolism processes.

The use of drugs together with coumarin anticoagulants requires a reduction in the dose of the latter; it is also necessary to regularly monitor blood coagulation values.

The dosage of the hypoglycemic agent chlorpropamide also needs to be reduced.

The drug may increase the intensity of negative effects of certain drugs.

Combination with captopril increases the likelihood of developing epidermal symptoms, especially in chronic renal failure.

Administration in combination with cytostatics increases the frequency of changes in blood counts, which is why it is necessary to frequently take blood tests.

Taking it with amoxicillin or ampicillin increases the likelihood of developing allergy symptoms.

Storage conditions

Allohexal should be stored in a place closed to small children. Temperature values - no more than 25°C.

Shelf life

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

Analogues

Analogues of the drug are Febux and Allopurinol.