Mercaptopurine-native (Mercaptopurine-nativ)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceMercaptopurineMercaptopurine
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  • Mercaptopurine
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    BELMEDPREPARATY, RUP     Republic of Belarus
  • Mercaptopurine-native
    pills inwards 
    NATIVA, LLC     Russia
  • Puri-Netol®
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    Aspen Pharma Trading Limited    
    • Dosage form: & nbsppills
    Composition:

    Composition per one tablet:

    Component name

    Amount, mg

    Active substance:


    Mercaptopurine monohydrate

    50,0

    Excipients:


    Lactose Monohydrate

    59,0

    Corn starch

    10,0

    Hypromellose

    4,0

    Magnesium stearate

    1,0

    Stearic acid

    0,2
    Description:Round flat pills of light yellow color with a risk and a facet.
    Pharmacotherapeutic group:Antitumor agent - antimetabolite
    ATX: & nbsp

    L.01.B.B.02   Mercaptopurine

    L.01.B.B   Purine analogues

    Pharmacodynamics:

    Mercaptopurine has antitumor and immunosuppressive effects. 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. Mercaptopurine phosphoribosyl and methylmercaptopurine inhibit glutamine-5-phosphorylbosyl pyrophosphate amidotransferase (the first enzyme in the synthesis of purine ribonucleotides); as a result of the mitotic cycle (S-phase), 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:

    Suction. Absorption after oral administration is variable, an average of about 50%. The maximum concentration of mercaptopurine in the blood plasma is observed on average after 2.2 hours (0.5-4.0 h).

    Distribution. The connection with plasma proteins is about 20%. It weakly penetrates the blood-brain barrier and is found in spinal fluid in small amounts.

    Excretion. The half-life (T1 / 2) is approximately 90 to 130 minutes. T1 / 2 three-phase: I phase - 47 min in adults and 21 min in children, II and III phases - 2.5 and 10 h, rather 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 within 2 hours after administration, 46% of mercaptopurine 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 himself mercaptopurine.

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

    The increase in toxicity with simultaneous use 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 myelogenous leukemia (remission induction and maintenance therapy).

    Contraindications:

    - Hypersensitivity to mercaptopurine or other components that make up the drug.

    - Pregnancy and the period of breastfeeding.

    Carefully:

    - Inhibition of the function of bone marrow hematopoiesis.

    - Acute viral (including chicken pox, shingles) fungal and bacterial diseases.

    - Renal and / or hepatic insufficiency.

    - Hyperuricemia.

    - Gout or urate nephrolithiasis.

    - Hereditary lactose intolerance, insufficiency of lactase or impaired absorption of glucose and galactose (the preparation contains lactose monohydrate).

    - Age to 2 years.

    Pregnancy and lactation:

    Application of the drug Mercaptopurine-native contraindicated during pregnancy and during breastfeeding.

    Dosing and Administration:

    A drug Mercaptopurine-native should be taken orally.

    A drug Mercaptopurine-native can be used both as a monotherapy, and in combination with other cytostatics in different doses depending on the scheme therapy. The dose and duration of treatment are determined depending on which cytotoxic agents are administered and in what doses are administered simultaneously with mercaptopurine. With individual selection of the dose of the drug should be guided by data from specialized literature.

    Usually for adults and children the dose of mercaptopurine is 50 - 75 mg / m2 or 2.5 mg / kg per day; in the future, the daily dose of the drug is adjusted depending on the effectiveness of therapy and the state of bone marrow hematopoiesis.

    At the first signs of severe leukopenia, it is recommended to discontinue mercaptopurine for 2 to 3 days. If during this time the leukopenia is not aggravated, the treatment is resumed. When combined with allopurinol, the dose of mercaptopurine is reduced to 25% of the standard dose,as allopurinol reduces the metabolic rate of mercaptopurine.

    Older and older patients

    Older and older patients are recommended to monitor liver and kidney function. In case of signs of renal or hepatic insufficiency, the dose should be reduced.

    Patients with impaired hepatic and renal function

    Patients with hepatic and / or renal insufficiency should be reduced the dose of the drug.

    Side effects:

    The undesirable reactions presented below are listed in accordance with the damage to organs and organ systems and frequency of occurrence. The incidence of adverse reactions is estimated as follows: the occurrence of "very often" -> 10%; "often" -> 1% and <10%, "infrequently" -> 0.1 % and <1%, "rarely" -> 0.01% and <0.1%, "very rarely" - <0.01%, including individual messages, "frequency unknown."

    Disorders from the blood and lymphatic system: very often - leukopenia, thrombocytopenia, anemia.

    Immune system disorders: hypersensitivity reactions: rarely - arthralgia, skin rash, drug fever; rarely - swelling of the face.

    Disorders from the gastrointestinal tract: often - nausea, vomiting, anorexia, intrahepatic cholestasis, hepatotoxicity (liver toxicity is toxic and allergic genesis and occurs more frequently in excess of the recommended dose of 2.5 mg / kg / day or 75 mg / m2/day); rarely - ulceration of the mucous membrane of the cavity mouth, diarrhea, pancreatitis, hepatonecrosis; rarely - ulceration of the intestinal mucosa.

    Disturbance of the skin and subcutaneous tissues: rarely - alopecia.

    Violations of the genitals and the breast: very rare - transient oligospermia.

    Other: reduction of immunity, attachment of secondary infections, hyperpigmentation of the skin; Hyperuricemia and nephropathy due to tumor lysis; rarely development of secondary leukemia, myelodysplasia gepatolienalny and T-cell lymphoma with the combination with the antagonists of the tumor necrosis factor (anti-TNF therapy).

    Overdose:

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

    Risk of overdose increases with simultaneous reception of allopurinol.

    Treatment: symptomatic (there is no effective antagonist, hemodialysis is practically ineffective). In the first 60 minutes after an overdose can be used inside Activated carbon. Treatment should be based on a clinical picture.

    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 azathioprine reduce the intensity of metabolism of mercaptopurine due to inhibition of xanthine oxidase.

    Mercaptopurine enhances the action of indirect anticoagulants, thereby increasing the risk of bleeding.

    Drugs that suppress bone marrow hemopoiesis (including co-trimoxazole), cytostatics, as well as radiotherapy 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.

    With the simultaneous administration of drugs that inhibit thiopurin methyltransferase (for example, olsalazine, mesalazine, sulfasalazine) - more rapid development of myelosuppression. 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:

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

    The treatment should be carried out under the careful control of a developed general blood test (daily monitoring is recommended during the induction of remission), as well as "liver" tests (every week at the beginning of therapy, every month during maintenance) and uric acid in the blood plasma.

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

    With a decrease in the number of white blood cells and platelets below the acceptable level, the tendency to bleeding, the appearance of jaundice or other signs of hepatotoxicity mercaptopurine should be canceled.With the timely withdrawal of the drug, myelosuppression and hepatotoxicity are reversible.

    During the induction of remission of acute myeloblastic leukemia, patients often experience a period of relative bone marrow aplasia, which requires appropriate maintenance therapy.

    To prevent hyperuricemia, an abundant drink is recommended, if necessary allopurinol and alkalinization of urine.

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

    In rare cases, some people have congenital deficiency of thiopurin methyltransferase (TPMT) enzyme. Patients with a shortage of TSMT can be in more susceptible to the rapid development of myelosuppression after the appointment of mercaptopurine.

    There was also reported a possible association between the decreased activity of TSMT and secondary leukemia and myelodysplasia in persons receiving mercaptopurine in combination with other cytostatic drugs.

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

    During treatment, and at least 3 months after it is completed, vaccination with live vaccines should be discarded and avoid contact with people immunized with live vaccines and given an oral polio vaccine.

    Care must be taken when handling the drug tablets Mercaptopurine-native to avoid contamination of hands or inhalation of the preparation.

    Effect on the ability to drive transp. cf. and fur:

    Since the use of the drug Mercaptopurine-native possibly the occurrence of side effects such as nausea, vomiting, diarrhea, arthralgia, etc., care must be taken when driving vehicles and working with mechanisms, as well as when engaging in other potentially hazardous activities requiring increased concentration of attention and speed of psychomotor reactions.

    Form release / dosage:

    Tablets of 50 mg.

    Packaging:

    On 25 or 50 tablets in bottles made of polyethylene terephthalate, sealed with lids made of polyethylene with a control ring of the first opening or without it. The labels are glued on the vials.

    On 1 bottle together with the instruction on application place in a pack a cardboard.

    Storage conditions:

    In the dark place at a temperature of no higher than 25 ° C. Keep out of the reach of children.

    Shelf life:

    2 years.

    Do not use after the expiration date printed on the package.

    Terms of leave from pharmacies:On prescription
    Registration number:LP-004446
    Date of registration:01.09.2017
    Expiration Date:01.09.2022
    The owner of the registration certificate:NATIVA, LLC NATIVA, LLC Russia
    Manufacturer: & nbsp
    Information update date: & nbsp28.09.2017
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