Mercaptopurine
Mercaptopurine: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Use in childhood
- 11. In case of impaired renal function
- 12. For violations of liver function
- 13. Use in the elderly
- 14. Drug interactions
- 15. Analogs
- 16. Terms and conditions of storage
- 17. Terms of dispensing from pharmacies
- 18. Reviews
- 19. Price in pharmacies
Latin name: Mercaptopurin
ATX code: L01BB02
Active ingredient: mercaptopurine (mercaptopurine)
Manufacturer: RUE "Belmedpreparaty" (Republic of Belarus), Cadila Healthcare Limited (India), SC Balkan Pharmaceuticals SRL (Republic of Moldova)
Description and photo update: 2018-21-11
Prices in pharmacies: from 830 rubles.
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Mercaptopurine is an antineoplastic, immunosuppressive drug.
Release form and composition
Dosage form of Mercaptopurine - tablets: depending on the manufacturer - flat, square, with rounded edges, a dividing line and overprinting "BP" on one side or flat-cylindrical, with a chamfer; from white to yellowish-white [10 pcs in a blister contour packing, 1, 5 or 10 packs in a cardboard box; in a blister 20 pcs., in a cardboard box 1, 2 or 3 blisters; in a vial 25 or 50 pcs., in a cardboard box 1 or 40 (for hospitals) vials].
Composition of one tablet:
- active substance: mercaptopurine monohydrate - 50 mg;
- auxiliary components: lactose monohydrate, sodium starch glycolate (type A), calcium stearate, potato starch.
Pharmacological properties
Pharmacodynamics
Mercaptopurine monohydrate is an antineoplastic agent from the group of antimetabolites. The substance belongs to analogs of purine bases, such as adenine, guanine, hypoxanthine, which are part of nucleic acids. Taking part in the processes of transformation of purines, mercaptopurine inhibits the synthesis of deoxyribonucleic acid (DNA) with a less intense effect on ribonucleic acid (RNA), as a result of which the S-phase (mitotic cell cycle) is disrupted, mainly in rapidly multiplying tumor and bone marrow cells … This causes the cytotoxic effect of the substance and inhibition of the growth of malignant neoplasms.
Experimental studies have shown that it is possible to recover mercaptopurine from DNA in the form of deoxythioguanosine. A certain amount of the substance is transformed into nucleotide derivatives of 6-thioguanine by sequential actions of xantilate aminase and inosinate dehydrogenase, converting thioinosinic acid to thioguanilic acid. In animals, resistance to malignant tumors is often associated with a decrease in the ability of cells to form thioinosinic acid. But resistance to mercaptopurine, especially in humans, can develop for other reasons.
As established in experimental experiments, mercaptopurine has a carcinogenic effect. The substance also has a mutagenic effect, causing chromosomal aberrations in human and animal cells, and dominantly lethal mutations in male mice. Mercaptopurine monohydrate is embryotoxic and leads to pathological changes in rat embryos.
Pharmacokinetics
Absorption of mercaptopurine in the gastrointestinal tract is incomplete - up to 50%.
About 19% of the substance binds to plasma proteins. In cerebrospinal fluid, it is found in insignificant quantities; it penetrates poorly through the blood-brain barrier.
Metabolism by activation and catabolism occurs in the liver; the enzyme xanthine oxidase is mainly involved in the decomposition.
Mercaptopurine monohydrate is excreted by the kidneys unchanged (from 7 to 39%) and in the form of metabolites (formed by direct oxidation by xanthine oxidase, thiouric acid, methylated thiopurines). The pharmacological effect is mainly due to metabolites. After taking the drug inside, 46% of the dose is excreted by the kidneys on the first day. In the urine, metabolites are detected already 2 hours after administration and are determined there within several weeks after the termination of the use of mercaptopurine. Metabolites have a longer half-life (T 1/2) than mercaptopurine itself. T 1/2 consists of three phases with a duration of 0.75, respectively; 2.5 and 10 hours.
Since mercaptopurine is rapidly metabolized into active intracellular derivatives, hemodialysis is ineffective in reducing the toxicity of the drug.
Indications for use
- acute lymphocytic leukemia;
- acute myeloid leukemia;
- chronic lymphoblastic, myeloblastic and myelomnoblastic leukemia - for the induction of remission and maintenance therapy;
- primary polycythemia;
- granulomatous enteritis.
Contraindications
Absolute:
- tumor resistance;
- pregnancy, lactation period;
- increased individual sensitivity to mercaptopurine or excipients of the drug.
Relative (the use of Mercaptopurine requires caution):
- diseases accompanied by suppression of bone marrow function;
- impaired renal and / or liver function;
- acute viral (including chickenpox, herpes zoster), bacterial and fungal infections;
- hyperuricemia;
- gout or kidney stones (including a history);
- the period after antitumor, radiation or chemotherapy;
- age up to 2 years.
Instructions for the use of Mercaptopurine: method and dosage
Mercaptopurine tablets are taken orally.
It is recommended for the first 3-4 weeks of therapy to take a daily dose of 2-2.5 mg per 1 kg of patient weight. The daily dose is taken once or in 2-3 doses. If, after 4 weeks from the start of treatment, the clinical effect is not observed and there are no signs of intoxication, you can carefully increase the dose, but not more than up to 5 mg per 1 kg of body weight.
During therapy with Mercaptopurine, careful clinical and hematological control must be carried out. If the first signs of a pronounced decrease in the total number of leukocytes in the peripheral blood appear in relation to the initial indicator, it is recommended to suspend treatment for 2-3 days. Taking the drug can be resumed when, during the indicated break, an even greater decrease in the level of leukocytes does not occur.
Side effects
- on the part of the cardiovascular system and blood: thrombocytopenia, leukopenia, anemia, agranulocytosis, pancytopenia (in acute myelogenous leukemia, during active therapy, there is often a period of relative bone marrow aplasia, which requires appropriate supportive treatment);
- from the nervous system: weakness, headache;
- from the organs of the gastrointestinal tract: nausea, vomiting, loss of appetite, diarrhea, hepatotoxic effect (toxicity to the liver is of toxic-allergic origin and occurs, as a rule, when the dose is exceeded 2.5 mg / kg per day) or cholestasis (yellowness skin or sclera), ulceration of the oral mucosa; rarely - diarrhea, pancreatitis, ulceration of the intestinal mucosa, hepatonecrosis;
- from the genitourinary system: nephropathy, hyperuricemia;
- allergic reactions: itching, rash, drug fever;
- others: increased skin pigmentation, a decrease in the body's immune response and a predisposition to infectious diseases.
Overdose
In case of an overdose of Mercaptopurine, in addition to thrombocytopenia, leukopenia and a tendency to hemorrhages, immediate dyspeptic symptoms may occur: nausea, vomiting, diarrhea, anorexia. Possible delayed symptoms: liver dysfunction, myelosuppression, gastroenteritis.
In the event of the development of these complications, it is necessary to immediately stop taking the pills and take the required therapeutic measures: in the first 60 minutes after the overdose, you can induce vomiting, rinse the stomach and take activated charcoal; further symptomatic treatment is prescribed. There is no effective antagonist of mercaptopurine. The hemodialysis procedure is ineffective.
When used together with allopurinol, the risk of overdose increases.
special instructions
Mercaptopurine therapy should be carried out only under the supervision of a specialist with experience in the use of cytostatics. The patient should be warned about the toxicity of the drug and the inadmissibility of its use without medical advice.
It is necessary to carefully monitor the detailed general blood count and liver tests (at the beginning of treatment - every week, during maintenance therapy - every month), as well as the level of uric acid in the blood serum.
During treatment with Mercaptopurine, a sufficient amount of fluid is recommended to ensure the excretion of uric acid and prevent hyperuricemia. Allopurinol and urine alkalinization are prescribed if necessary.
In case of signs of bone marrow suppression, black tarry stools, unusual bleeding, blood in the urine / stool, or pinpoint red spots on the skin, consult a doctor immediately.
The drug may increase the risk of secondary cancer and nephropathy (due to increased production of uric acid).
With a decrease in the level of leukocytes and platelets below the permissible level, the appearance of jaundice, and also with a tendency to bleeding, Mercaptopurine should be canceled. It is important to carefully monitor the blood picture, and, if necessary, provide supportive treatment and blood transfusion. Patients with developed leukopenia need medical supervision to detect signs of infections and timely prescribe antibiotics. When the body temperature rises, such patients are prescribed broad-spectrum antibiotics empirically, until the results of bacteriological analyzes and appropriate diagnostic tests are obtained.
When handling mercaptopurine tablets (dividing them in half), care should be taken to avoid inhalation of the drug and contamination of hands.
Avoid accidental cuts with sharp objects, contact sports, or other situations that could lead to injury or hemorrhage.
Dental manipulations must be completed before starting treatment with the drug or postponed until the general blood count is normalized (due to the increased risk of microbial infections, slowing of healing processes, bleeding of the gums). During the treatment period, care should be taken when using toothbrushes, threads, toothpicks.
In combination therapy, it is important to take each drug at the scheduled time.
It is recommended to use reliable contraception during treatment with Mercaptopurine of one of the sexual partners.
Application during pregnancy and lactation
The drug is contraindicated for use in pregnant women due to teratogenic and embryotoxic properties. Taking mercaptopurine during pregnancy has been associated with an increased risk of miscarriage or premature birth. The drug is classified in category D by the FDA (Food and Drug Administration of the US Department of Health) of possible risks to the fetus.
Breastfeeding should be discontinued during treatment with Mercaptopurine.
Pediatric use
The drug should be prescribed with caution to children, especially under the age of 2 years. As a rule, a dose reduction is required in pediatric and adolescent patients.
With impaired renal function
Renal failure, renal tumors are relative contraindications for the use of Mercaptopurine. Dose adjustment is required depending on the degree of kidney function.
For violations of liver function
Prescribing the drug to patients with impaired liver function requires correction of the dosage regimen.
Use in the elderly
According to the instructions, Mercaptopurine is prescribed with caution to elderly patients due to the more likely age-related impairment of renal function.
Drug interactions
- allopurinol, sulfinpyrazone, probenecid, colchicine: mutual increase in activity and toxicity. Allopurinol increases the toxic effect by slowing down the metabolism;
- anti-gout uricosuric drugs: increased risk of developing nephropathy;
- indirect anticoagulants: an increase in their activity and / or the risk of bleeding due to a decrease in the synthesis of coagulation factors in the liver and suppression of platelet formation, or a decrease in anticoagulant activity by increasing the synthesis or activation of prothrombin;
- myelotoxic drugs or radiation therapy: additive suppression of bone marrow function;
- glucocorticoids, cyclosporine, cyclophosphamide, corticotropin, chlorambucil, azathioprine and other immunosuppressants: increased risk of infections and secondary tumors (due to increased immunosuppressive action);
- doxorubicin: increasing the likelihood of hepatotoxicity;
- thioguanine: complete cross-resistance with mercaptopurine;
- live viral vaccines: possible intensification of the replication process of the vaccine virus, increased side effects of the vaccine and decreased antibody production after administration of both inactivated and live vaccines.
Analogs
Mercaptopurine analogs are: Mercaptopurine-native and Puri-Netol.
Terms and conditions of storage
Store in a dark, dry place at temperatures from 15 to 25 ° C.
Keep out of the reach of children.
Shelf life is 3 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Mercaptopurine
At this time, users did not leave real reviews about Mercaptopurine, by which one could judge the effectiveness and disadvantages of the drug.
Price for Mercaptopurine in pharmacies
The price of Mercaptopurine for a pack of 25 tablets is approximately 880 rubles.
Mercaptopurine: prices in online pharmacies
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Drug name Price Pharmacy |
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Mercaptopurine 50 mg tablets 25 pcs. RUB 830 Buy |
Maria Kulkes Medical journalist About the author
Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
