Active substanceMercaptopurineMercaptopurine Similar drugsTo uncover Mercaptopurine pills inwards BELMEDPREPARATY, RUP Republic of Belarus Mercaptopurine-native pills inwards NATIVA, LLC Russia Puri-Netol® pills inwards Aspen Pharma Trading Limited Dosage form: & nbspPills. Composition:One tablet contains:Active substance: mercaptopurine 50.0 mg. Excipients: lactose monohydrate 59.0 mg, corn starch 10.3 mg, oxidized starch 4.0 mg, magnesium stearate 0.75 mg, stearic acid 0.15 mg. Description:Round biconvex tablets, pale yellow, with a fracture line on one side of the tablet. Above the fault line, the inscription "GX" is pushed out, under the fault line the inscription "ЕХ2" Pharmacotherapeutic group:Antitumor agent - antimetabolite. ATX: & nbspL.01.B.B.02 MercaptopurineL.01.B.B Purine analogues Pharmacodynamics:Puri-Netol 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. Both of them inhibit glutamine-5-phosphoribosyl pyrophosphate amidotransferase - 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%, which is associated with the metabolism of the first passage through the liver of a significant part of the mercaptopurine that has been administered. The maximum concentration of mercaptopurine in plasma is observed on average after 2.2 hours (0.5-4.0 h). It weakly penetrates the blood-brain barrier and is found in spinal fluid in small amounts. The connection with plasma proteins is about 20%.The half-life of mercaptopurine is approximately 90 to 130 minutes. 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 urine, after oral administration, the unchanged drug, 6-thiourea acid (formed as a result of direct oxidation involving xanthine oxidase) and several methylated thiopurins are determined.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, and chronic myelogenous leukemia (remission induction and maintenance therapy). Contraindications:Hypersensitivity to mercaptopurine or other components that make up the drug.Pregnancy and lactation. Carefully:Oppression of the function of bone marrow hematopoiesis, acute viral (including chicken pox, shingles), fungal and bacterial diseases, renal and / or liver failure, hyperuricemia, gout or urate nephrolithiasis, age up to 2 years. Dosing and Administration:Inside.Puri-Netol can be used both as a monotherapy and in combination with other cytostatics in different doses depending on the therapy scheme.For individual dose selection, reference should be made to the literature.Usually for adults and children the dose is 50 - 75 mg /m2 or 2.5 mg / kg per day; In the future, the daily dose of Puri-Netol is adjusted depending on the effect and state of bone marrow hematopoiesis.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.In elderly patients, it is recommended to monitor the function of the liver and kidneys. In case of signs of renal or hepatic insufficiency, the dose should be reduced.Patients with hepatic and / or renal insufficiency should be reduced.When combined with allopurinol, the dose of mercaptopurine is reduced to 25% of the standard dose, since allopurinol reduces the metabolic rate of mercaptopurine. Side effects:By frequency, the side effects were divided into the following categories: very frequent ≥ 1/10; frequent ≥ 1/100 and <1/10; infrequent ≥ 1/1000 and <1/100; rare ≥ 1/10 000 and <1/1000; very rare <1/10 000.From the hematopoiesis: very often - leukopenia, thrombocytopenia, anemia.From the immune system: hypersensitivity reactions: rarely - arthralgia, skin rash, drug fever; very rarely - swelling of the face. On the part of the digestive system: often - nausea, vomiting, anorexia, intrahepatic cholestasis, hepatotoxicity (hepatotoxicity has a toxic-allergic origin and often occurs when exceeding the recommended dose of 2.5 mg / kg / day or 75 mg / m2 / day); rarely - ulceration of the oral mucosa, diarrhea, pancreatitis, hepatonecrosis; very rarely ulceration of the intestinal mucosaFrom the skin and skin appendages: rarely - alopecia.On the part of the reproductive system: very rarely - transient oligospermia Other: decreased immunity, secondary infections, hyperpigmentation of the skin; Hyperuricemia and nephropathy due to tumor lysis; very rarely the development of secondary leukemias, myelodysplasia and genotolyenate T-cell lymphoma when combined with tumor necrosis factor antagonists (anti-TNF therapy). Overdose:Symptoms: immediate - nausea, vomiting, anorexia, diarrhea; delayed-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 or according to the recommendations of the National Toxicology Center. 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 blockade of xanthine oxidase.Strengthens 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 increases the risk of infection and secondary tumors (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:Puri-Netol 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 (daily monitoring is recommended during remission induction), 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.When using the drug, delayed myelotoxic effect can be observed.With a decrease in the number of white blood cells and platelets below the tolerable level, the tendency to bleeding, the appearance of jaundice or other signs of hepatotoxicity Puri-Netol should be discarded. With the timely cancellation of Puri-Netol, myelosuppression and hepatotoxicity are reversible.During the induction of remission of acute myelogenous 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, as well as nephropathy due to increased formation of uric acid.In rare cases, some people have congenital deficiency of thiopurin methyltransferase (TPMT) enzyme. Patients with TMP deficiency may be more susceptible to the rapid development of myelosuppression after Puri-Netol administration.Also, a possible association was reported between the decreased activity of thiopurin methyltransferase and secondary leukemia and myelodysplasia in persons receiving Puri-Netol in combination with other cytotoxic drugs.It is recommended to use reliable methods of contraception during the treatment of any of the sexual partners.Care must be taken when handling the Puri-Netol tablets to avoid contamination of hands or inhalation of the drug.During treatment and at least 3 months after, vaccination with live vaccines should be avoided and avoid contact with people immunized with live vaccines. Form release / dosage:Tablets of 50 mg. Packaging:For 25 tablets in dark glass bottles sealed with a snap-in lid of low-density polyethylene with a first-opening control or a high-density polyethylene / polypropylene lid with an anti-tampering device. 1 bottle with instructions for use in a cardboard pack. Storage conditions:At a temperature of no higher than 25 ° C, in a dry, dark place.Keep out of the reach of children. Shelf life:5 years.Do not use after the expiry date printed on the package. Terms of leave from pharmacies:On prescription Registration number:П N011416 / 01 Date of registration:05.05.2010 / 03.06.2015 Expiration Date:Unlimited The owner of the registration certificate:Aspen Pharma Trading LimitedAspen Pharma Trading Limited Manufacturer: & nbspEXCELLA, GmbH Germany Representation: & nbspAspen Hells Ltd.Aspen Hells Ltd. Information update date: & nbsp2016-08-24 Illustrated instructions × Illustrated instructions Instructions