Mercaptopurinum

General characteristics. Structure:

Active ingredient: 50 mg of Mercaptopurinum.

Excipients: sucrose, potato starch, calcium stearate.

Drug which has an antineoplastic and immunodepressive effect.

Pharmacological properties:

Pharmacodynamics. Is a competitive antagonist of purine bases. Competes with hypoxanthine and guanine for гипоксантин-гуанинфосфорибозилтрансферазу. It is transformed to mercaptopurinephosphoribosyl which under the influence of thiopurinemethyltransferase turns into Mercaptopurinum. Both of them oppress глутамин-5-фосфорибозилпирофосфатамидотрансферазу — the first enzyme in synthesis of purine ribonucleotides. The mitotic cycle (S-phase), especially in quickly proliferating cells of marrow and tumors is as a result broken, growth of malignant new growths is slowed down and the cytotoxic effect is shown.

Pharmacokinetics. Absorption in digestive tract incomplete (to 50%). Linkng with proteins of plasma — about 20%. Badly passes through a blood-brain barrier and it is found in liquor in insignificant quantities. It is metabolized in a liver. It is removed by kidneys in not changed look and in the form of metabolites. After intake of 46% of the accepted dose it is excreted in the first 24 hours with urine.

Indications to use:

Acute lymphoid leukosis, acute myeloleukemia, chronic miyeloblastny, lymphoblastoid and miyelomnoblastny leukosis (induction of remission and maintenance therapy), Osler's disease, disease Krone.

Route of administration and doses:

Mercaptopurinum is applied inside in the form of tablets. Within the first 3 — 4 weeks of treatment the dose at the rate of 2 — 2,5 mg is daily appointed to 1 kg of body weight of the patient.

The daily dose can be entered at once or into 2 — 3 receptions. If in 4 weeks after an initiation of treatment of clinical improvement does not come and there are no symptoms of intoxication, it is possible to raise the specified dose carefully to 5 mg on 1 kg of body weight, but no more.

Treatment by Mercaptopurinum should be carried out at careful clinical and hematologic control. At the first signs of the expressed decrease in total number of leukocytes in peripheral blood in comparison with initial level, treatment is recommended to be interrupted for 2 — 3 days. If during this term there is no further decrease in maintenance of leukocytes, purpose of drug needs to be resumed.

Features of use:

For prevention of a hyperuricemia plentiful drink, if necessary — Allopyrinolum and alkalifying of urine is recommended.

At reduction of quantity of thrombocytes is lower than tolerance level, tendency to bleedings or emergence of jaundice Mercaptopurinum should be cancelled.

During treatment of any of sexual partners it is recommended to use contraception.

Side effects:

In the recommended doses drug usually is transferred by patients well. But in view of the fact that Mercaptopurinum patients react to treatment individually, development of by-effects is not excluded at some of them.

Possible complications at the same time are the leukopenia, thrombocytopenia and a tendency to hemorrhages. At development of a leukopenia having rummaged in treatment is obligatory, and it can be renewed only at increase of number of leukocytes, however at the accruing hemorrhages Mercaptopurinum should be applied with care (reduction of a dosage, breaks in treatment).

Interaction with other medicines:

At combined use with the medicines blocking canalicular secretion (especially with uricosuric antigouty drugs - пробенецид, Sulfinpyrazonum, colchicine) the risk of development of a nephropathy increases. Vincristinum and a methotrexate increase (mutually) activity and toxicity.

Allopyrinolum and Azathioprinum reduce intensity of metabolism of Mercaptopurinum due to blockade of a xanthineoxidase.

Strengthens effect of indirect anticoagulants, increasing thereby risk of development of bleedings.

The drugs suppressing a marrowy hemopoiesis (including to-trimoksozol), cytostatics, and also radiation therapy increase expressiveness of a leukopenia and thrombocytopenia.

At simultaneous use with glucocorticosteroids, Azathioprinum, hlorambutsily, corticotropin, cyclophosphamide and cyclosporine the risk of development of an infection and secondary tumors (strengthening of an immunodepressive effect) increases.

The concomitant use with doxorubicine considerably increases risk of development of a hepatotoxic.

Cross resistance of cells to Mercaptopurinum and to derivatives of thioguanine is noted.

In combination with live virus vaccines can cause an intensification of process of replication of a vaccinal virus. Strengthening of side effect of a vaccine and decrease in development of antibodies in response to introduction, both the live, and inactivated vaccines is possible.

Contraindications:

Hypersensitivity, resistance of a tumor, oppression of function of marrow, chicken pox, the surrounding herpes and other infections, abnormal liver function and kidneys, gout or a nephrolithiasis in the anamnesis. Pregnancy, a lactation (it is necessary to exclude breastfeeding).

Overdose:

Symptoms: at overdose of drug in addition to a leukopenia, thrombocytopenia and a tendency to hemorrhages the dispepsichesky phenomena (nausea, vomiting, anorexia, diarrhea) can take place; the delayed symptoms: miyelosupressiya, hepatic dysfunction, gastroenteritis.

Treatment: at emergence of the specified complications administration of drug it is necessary to stop and appoint necessary at the same time medical actions immediately. Symptomatic therapy is carried out (there is no effective antagonist, the hemodialysis is almost inefficient).

Storage conditions:

List A. At a temperature not above 25 °C in the place, dry and unavailable to children. Period of validity of 5 years. Not to use after the expiry date specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets of 50 mg in bottles No. 50.