Mercaptopurine tablets 50mg, No. 25

Acute lymphoblastic leukemia, acute myeloid leukemia, chronic myeloblastic and myelomonoblastic leukemia (induction of remission and supportive therapy).

Inside. For adults and children, the initial dose is 2-2.5 mg / kg or 80-100 mg / m? per day for 4 weeks; in the future it is 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 tolerance for 4 weeks and insufficient severity of the effect, the dose can be increased to 5 mg / kg per day, but no more. 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 prescribed once or in several doses.
At the first signs of severe leukopenia, it is recommended to interrupt the intake for 2-3 days. If during this time the leukopenia does not worsen, the treatment is resumed.
For patients with hepatic and / or renal insufficiency, the dose should be reduced.
When used together with allopurinol, the dose of mercaptopurine is reduced by 25-35%.

1 tablet contains:
active substance: mercaptopurine 50 mg
excipients: sucrose, potato starch, calcium stearate.

Hypersensitivity. Pregnancy and lactation.

With caution - suppression of bone marrow hematopoiesis, acute viral (including chickenpox, shingles) fungal and bacterial diseases, renal and / or hepatic failure, hyperuricemia, gout or urate nephrourolithiasis, age up to 2 years.

Trade name of the drug : Mercaptopurine

International non-proprietary name : mercaptopurine

Dosage form : tablets

Composition
1 tablet contains:
active substance: mercaptopurine 50 mg
excipients: sucrose, potato starch, calcium stearate.

Description
Tablets are light yellow, flat-cylindrical, with a bevel.

Pharmacological properties
Pharmacotherapeutic group : antineoplastic agent - antimetabolite.
ATC code - L01BB02
Pharmacodynamics
It has antitumor and immunosuppressive effects. It is a competitive antagonist of purine bases. It competes with hypoxanthine and guanine for hypoxanthine-guanine-phosphoribosyltransferase. It is transformed into mercaptopurine phosphoribosyl, which, under the influence of thiopurine methyltransferase, is converted into methyl mercaptopurine. Both of them inhibit glutamine-5-phosphoribosylpyrophosphate amidotransferase - the first enzyme in the synthesis of purine ribonucleotides; As a result, the mitotic cycle (S-phase) is disrupted, especially in rapidly proliferating bone marrow cells and tumors, the growth of malignant neoplasms is inhibited and a cytotoxic effect is manifested.
Pharmacokinetics
Absorption after oral administration is variable, averaging about 50%. The connection with plasma proteins is about 20%. Weakly penetrates the blood-brain barrier and is found in cerebrospinal fluid in small quantities.
The half-life is three-phase: phase I - 47 minutes in adults and 21 minutes in children, phase II and III - 2.5 and 10 hours, rather rapid destruction is associated with its inclusion in the metabolic pathways characteristic of all purines. The pharmacological effect is largely due to metabolites, which are excreted through the kidneys by tubular secretion and glomerular filtration. In the urine, metabolites are found already 2 hours after administration, 46% of the drug is excreted in the first day. Metabolites continue to be detected in the urine for several weeks after stopping treatment; metabolites are pharmacologically active and have a longer half-life than mercaptopurine itself.
In urine after oral administration, the following are determined: unchanged drug, thiouric acid (formed as a result of direct oxidation with the participation of xanthine oxidase) and several methylated thiopurines.
An increase in toxicity when administered together with allopurinol is associated with the blockade of xanthine oxidase by the latter and, accordingly, with the accumulation of pharmacologically active substances.

Indications for use
Acute lymphoblastic leukemia, acute myeloid leukemia, chronic myeloblastic and myelomonoblastic leukemia (induction of remission and maintenance therapy).

Contraindications
Hypersensitivity. Pregnancy and lactation.

With caution - suppression of bone marrow hematopoiesis, acute viral (including chickenpox, shingles) fungal and bacterial diseases, renal and / or hepatic failure, hyperuricemia, gout or urate nephrourolithiasis, 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 / m? per day for 4 weeks; in the future it is 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 tolerance for 4 weeks and insufficient severity of the effect, the dose can be increased to 5 mg / kg per day, but no more. 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 prescribed once or in several doses.
At the first signs of severe leukopenia, it is recommended to interrupt the intake for 2-3 days. If during this time the leukopenia does not worsen, the treatment is resumed.
For patients with hepatic and / or renal insufficiency, the dose should be reduced.
When used together with allopurinol, the dose of mercaptopurine is reduced by 25-35%.

Side effect
On the part of hematopoietic organs: 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 genesis and more often than the recommended dose 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.
Others: decreased immunity, accession of secondary infections, skin pigmentation, alopecia, hyperuricemia, nephropathy, transient oligospermia.
Potentially possible - mutagenicity, carcinogenicity.

Overdose
Symptoms : immediate - nausea, vomiting, anorexia, diarrhea; delayed - myelosuppression, liver dysfunction, 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 gastric lavage.

Interaction with other drugs and other forms of interaction
When combined with drugs that block tubular secretion (especially with uricosuric anti-gout drugs - probenecid, sulfinpyrazone, colchicine), the risk of developing nephropathy increases. Vincristine and methotrexate increase (mutually) activity and toxicity.
Allopurinol and azathiaprine reduce the metabolic rate of mercaptopurine by blocking xanthine oxidase.
Enhances the effect of indirect anticoagulants, thereby increasing the risk of bleeding.
Drugs that suppress bone marrow hematopoiesis (including co-trimoxozol), cytostatics, and radiation therapy increase the severity of leukopenia and thrombocytopenia.
With simultaneous use with glucocorticosteroids, azathioprine, chlorambucil, corticotropin, cyclophosphamide and cyclosporine, the risk of infection and secondary tumors increases (increased immunosuppressive action).
Concomitant use with doxorubicin significantly increases the risk of developing hepatotoxicity.
Cross-resistance of cells to mercaptopurine and thioguanine derivatives is noted.
In combination with live viral vaccines, it can intensify the replication of the vaccine virus. It is possible to increase the side effects of the vaccine and reduce the production of antibodies in response to the introduction of both live and inactivated vaccines.

Special instructions
Mercaptopurine should be used only under the supervision of doctors with experience in the use of cytostatics.
Treatment should be carried out under the close supervision of a complete complete blood count, as well as 'liver' tests (every week - at the beginning of therapy, every month - during the period of maintenance therapy) and the content of uric acid in the blood serum.
With the use of mercaptopurine, a delayed myelotoxic effect may be observed.
To prevent hyperuricemia, it is recommended to drink plenty of fluids, if necessary - allopurinol and alkalinization of urine.
With a decrease in the number of leukocytes and platelets below the permissible level, a tendency to bleeding or the appearance of jaundice, mercaptopurine should be canceled.
During the treatment period of any of the sexual partners, it is recommended to use reliable methods of contraception.
The drug may increase the risk of secondary malignant neoplasm and nephropathy (due to increased production of uric acid). Care is advised when handling the tablets (for example, dividing them in half) to avoid contamination of the hands or inhalation of the drug.
During treatment, and for at least 3 months after, immunization should be abandoned and contact with people who have received oral polio vaccine should be avoided.

Release form
50 tablets in vials. 1 bottle in a cardboard box, with the attached instructions for use.

Storage conditions
List A. At a temperature not exceeding 25 ? C in a dry place out of the reach of children.

Shelf life:

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

Terms of dispensing from pharmacies
Prescription.