Mercaptopurine (Mercaptopurin)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceMercaptopurineMercaptopurine
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    • Dosage form: & nbsppills
    Composition:

    For one tablet:

    active substance: mercaptopurine monohydrate - 50 mg;

    Excipients: lactose monohydrate 17 mg, sodium starch glycolag type A 5 mg, calcium stearate 0.8 mg, potato starch sufficient to produce a tablet weighing 100 mg.

    Description:Tablets of light yellow color, flat-cylindrical, with a facet.
    Pharmacotherapeutic group:Antitumor agent - antimetabolite
    ATX: & nbsp

    L.01.B.B.02   Mercaptopurine

    L.01.B.B   Purine analogues

    Pharmacodynamics:Has antitumor and immunosuppressive effect. It is a competitive antagonist of purine bases. Competing with hypoxanthine and guanine for hypoxanthine guanine phosphoribosyltransferase. It is transformed into mercaptopurine phosphoribosyl, which under the influence of thiopurine methyltransferase is converted to methylmercaptopurine. Both of them inhibit glutamine-5-phosphoribosyl pyrophosphatamidopreferase - the first enzyme in the synthesis of purine ribonucleotides; as a result, the mitotic cycle (S-phase) is violated,especially in rapidly proliferating cells of the bone marrow and tumors, the growth of malignant neoplasms is inhibited and the cytotoxic effect is manifested.
    Pharmacokinetics:

    Absorption after oral administration is variable, an average of about 50%. The connection with plasma proteins is about 20%. It weakly penetrates the blood-brain barrier and is found in spinal fluid in small amounts.

    The half-life period is three-phase: I phase - 47 minutes in adults and 21 minutes in children, II and III phases - 2.5 and 10 hours, quite rapid destruction is associated with its inclusion in the pathway of metabolism inherent in all purines. The pharmacological effect is largely due to metabolites, the excretion of which occurs through the kidneys through tubular secretion and glomerular filtration. In the urine, metabolites are detected only 2 hours after admission, 46% of the drug is excreted within the first 24 hours. Metabolites continue to be detected in the urine for several weeks after discontinuation of treatment; metabolites are pharmacologically active and have a longer half-life than themselves mercaptopurine.

    In the urine after oral intake are determined: unchanged drug,thiourea (formed as a result of direct oxidation involving xanthine oxidase) and several methylated thiopurins.

    The increase in toxicity when co-administered with allopurinol is associated with the blockade of the last xanthine oxidase and, accordingly, the accumulation of pharmacologically active substances.

    Indications:Acute lymphoblastic leukemia, acute myelogenous leukemia, chronic myeloblastic and myelomonoblastic leukemia (remission induction and maintenance therapy).
    Contraindications:Hypersensitivity. Pregnancy and lactation.
    Carefully:Inhibition of bone marrow hematopoiesis, acute viral (in the city chicken pox, shingles) fungal and bacterial diseases, renal and / or liver failure, hyperuricemia, gout or urate nephrourolythiosis, age up to 2 years.
    Dosing and Administration:

    Inside. For adults and children, the initial dose is 2-2.5 mg / kg or 80-100 mg / m2 per day for 4 weeks; further adjusted depending on the effect and state of bone marrow hematopoiesis, the nature and dose of other cytostatics prescribed in combination with mercaptopurine.With good tolerability for 4 weeks and inadequate effect, the dose can be increased to 5 mg / kg per day, but no more. The maintenance dose: 1.5-2.5 mg / kg or 75 mg /m2 per day. Children: 2.5 mg / kg or 75 mg /m2 per day.

    The daily dose is given once or in several doses.

    At the first signs of severe leukopenia, it is recommended to stop taking for 2-3 days. If during this time the leukopenia is not aggravated, the treatment is resumed.

    Patients with hepatic and / or renal insufficiency should be reduced.

    When combined with allopurinol, the dose of mercaptopurine is reduced by 25-35%.

    Side effects:

    From the hematopoiesis: anemia, leukopenia, neutropenia, agranulocytosis, thrombocytopenia, pancytopenia

    On the part of the digestive system: loss of appetite, nausea, vomiting, diarrhea, hepatonecrosis, intrahepatic cholestasis (hepatotoxicity has a toxic-allergic origin and often occurs when exceeding the recommended dose of 2.5 mg / kg / day), ulceration of the oral mucosa, less often ulceration of the intestinal mucosa, pancreatitis .

    Allergic reactions: skin rash, itching, rarely - drug fever.

    Other: reduction of immunity, attachment of secondary infections, skin pigmentation, alopecia, hyperuricemia, nephropathy, transient oligospermia.

    Potentially possible - mutagenicity, carcinogenicity.

    Overdose:

    Symptoms: immediate - nausea, vomiting, anorexia, diarrhea; delayed-myelosuppression, a violation of liver function, gastroenteritis.

    Treatment: symptomatic (there is no effective antagonist, hemodialysis is practically ineffective). In the first 60 minutes after an overdose, you can induce vomiting and rinse the stomach.

    Interaction:

    When combined with drugs that block tubular secretion (especially with uricosuric antidotal drugs - probenecid, sulfinpyrazone, colchicine) increases the risk of developing nephropathy. Vincristine and methotrexate increase (mutually) activity and toxicity.

    Allopurinol and azathiaprin reduce the intensity of the metabolism of mercaptopurine due to the blockade of xanthine oxidase.

    Increases the effect of indirect anticoagulants, thereby increasing the risk of bleeding.

    Drugs that suppress bone marrow hematopoiesis (including co-trimoxozole), cytostatics, as well as radiation therapy increase the severity of leukopenia and thrombocytopenia.

    When used simultaneously with glucocorticosteroids, azathioprine, chlorambucil, corticotropin, cyclophosphamide and cyclosporine, the risk of infection and secondary tumors increases (increased immunosuppressive action).

    Simultaneous reception with doxorubicin significantly increases the risk of hepatotoxicity.

    Cross-resistance of cells to mercaptopurine and to thioguanine derivatives is noted.

    In combination with live viral vaccines, it can cause intensification of the replication process of the vaccine virus. It is possible to increase the side effect of the vaccine and reduce the production of antibodies in response to the administration of both live and inactivated vaccines.

    Special instructions:

    Mercaptopurine should be used only under the supervision of physicians with experience in the use of cytostatics.

    Treatment should be carried out under careful control of a developed general blood test, as well as "liver" tests (every week - at the beginning of therapy, every month - in the period of maintenance therapy) and the content of uric acid in the serum.

    With the use of mercaptopurine, a delayed myelotoxic effect can be observed.

    To prevent hyperuricemia, a generous drink is recommended, if necessary - allopurinol and alkalinization of urine.

    With a decrease in the number of white blood cells and platelets below the acceptable level, a tendency to bleeding or the appearance of jaundice mercaptopurine should be canceled.

    It is recommended to use reliable methods of contraception during the treatment of any of the sexual partners.

    The drug may increase the risk of secondary malignant neoplasm and nephropathy (due to increased uric acid formation).

    Care is advised when handling tablets (for example, dividing them in half) to avoid contamination of hands or inhaling the drug.

    During treatment, and at least 3 months after, immunization should be avoided and avoid contact with people who received oral polio vaccine.

    Form release / dosage:Tablets 50 mg.
    Packaging:

    For 25 or 50 tablets in bottles, corked plastic.

    Free space in vials is filled with cotton absorbent medical absorbent cotton.

    Each vial with instructions for use is placed in a pack of cardboard.

    Packing for hospitals: 40 bottles with an equal number of instructions for use are placed in a cardboard box.

    Storage conditions:List A. At a temperature not higher than 25 ° C in a dry and inaccessible place for children.
    Shelf life:Do not use after the expiry date printed on the package.
    Terms of leave from pharmacies:On prescription
    Registration number:П N016224 / 01
    Date of registration:25.02.2010 / 10.06.2015
    Expiration Date:Unlimited
    The owner of the registration certificate:BELMEDPREPARATY, RUP BELMEDPREPARATY, RUP Republic of Belarus
    Manufacturer: & nbsp
    BELMEDPREPARATY, RUP Republic of Belarus
    Information update date: & nbsp01.05.2018
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