Merkaptopurin
When ATH:
L01BB02
Characteristic.
Antimetaʙolit, It refers to the group of purine analogues. By building close to adenine (6-aminopurin), gipoksantinu (6-oksipurin), guaninu (2-amino-6-oksipurin), It is thiol derivative. Yellow crystalline powder. Practically insoluble in water and alcohol, soluble in hot water, in alkaline solutions. Molecular weight 170,19.
Pharmacological action.
Antitumor, immunosuppressive.
Application.
Acute leukemia lymfoblastnыy, acute myeloid leukemia (incl. Acute leukemia myelotsytarnыy), exacerbation of chronic myeloid leukemia, horionepitelioma uterus, retikulez, hranulotsytarnыy chronic leukemia.
Contraindications.
Hypersensitivity, resistant tumors, suppression of bone marrow function (лейкопения с числом лейкоцитов меньше 3·109/l, тромбоцитопения с числом тромбоцитов меньше 100·109/l), enable vetryanaya, shingles and other infections, the liver and kidneys, gout or nephrolithiasis history.
Pregnancy and breast-feeding.
Contraindicated in pregnancy. Use of mercaptopurine in pregnancy was accompanied by an increased risk of miscarriage or premature birth.
Category actions result in FDA - D. (There is evidence of the risk of adverse effects of drugs on the human fetus, obtained in research or practice, However, the potential benefits, associated with drugs in pregnant, may justify its use, in spite of the possible risk, if the drug is needed in life-threatening situations or severe disease, when safer agents should not be used or are ineffective.)
At the time of treatment should stop breastfeeding.
Side effects.
From the nervous system and sensory organs: headache, weakness.
Cardio-vascular system and blood: the most often-anemia, leukopenia, thrombocytopenia (during active treatment for acute myelogenous leukemia patients often marked a period of relative bone marrow aplasia, it is important to carry out the corresponding maintenance treatment).
From the digestive tract: nausea, vomiting, diarrhea, loss of appetite, hepatotoxic effects (has toxic-allergic origin and often occurs when excess doses 2,5 mg / kg / day) or cholestasis (yellow skin or sclera); rarely is the disease (usually at high doses), ulceration in the gastrointestinal tract, hepatic encephalopathy.
With the genitourinary system: less often is hyperuricemia, or nephropathy.
For the skin: dermatomelasma, skin rash, itch.
Other: lowered immunity and susceptibility to infections.
Cooperation.
Allopurinol, probenecid, sulfinpirazon, colchicine increase (mutually) Activity and Toxicity. Allopurinol increases the toxic effect due to slow metabolism. Against the background of urikozuricheskih protivopodagricakih funds increases the risk of nephropathy. In a joint application with indirect anticoagulants mercaptopurine may increase the anticoagulant activity and / or the risk of bleeding due to a decrease in the hepatic synthesis of coagulation factors and platelet disorders, or reduce the anticoagulant activity by increasing the synthesis or activation of prothrombin. Myelotoxicity drugs or radiotherapy additive depress bone marrow function. Other immunosuppressants (glucocorticoids, azathioprine, khlorambutsil, kortykotropyn, cyclophosphamide, cyclosporine) increase the risk of infections and secondary malignancies (strengthening the immunosuppressive action). Simultaneous treatment with doxorubicin significantly increases the risk of hepatotoxicity. There is complete cross-resistance between mercaptopurine and thioguanine. In combination with live viral vaccines may cause intensification of the process of replication of vaccine virus, increased side effects of vaccines and reducing the production of antibodies in response to both live, and inactivated vaccines.
Overdose.
Symptoms: immediate-anorexia, nausea, vomiting, diarrhea; deferred — mielosuprescia, liver dysfunction, gastroenteritis.
Treatment: symptomatic (No effective antagonist, hemodialysis practically effective).
Dosing and Administration.
Inside. Adults and children initial dose of inside- 2,5 mg/kg/day or 80-100 mg/m2 (average, 100-200 mg-adults, 50 mg — children 5 years of age). Possibly increasing doses up to 5 mg / kg / day (no more) during 4 Sun. Maintenance dose: 1,5-2.5 mg/kg or 50-100 mg/m2 per day. Patients with hepatic and / or renal failure dose reduced. When assigning simultaneously with allopurinol (300-600 mg/day) use only 1 / 3-1 / 4 the normal dose mercaptopurine (decrease in metabolic rate due to the blockade of xanthine oxidase).
The daily dose is usually applied once.
Also used in combination chemotherapy.
Precautions.
Be wary appoint elderly (more likely to age renal dysfunction) and children (It requires a reduction in dosage), patients, which were previously radiation or chemotherapy, patients with tumors of the kidney, in renal and liver failure.
Patients should be warned about the toxicity of the drug and its application inadmissible without consulting your doctor. It may increase the risk of secondary cancer and renal disease (due to increased production of uric acid). To avoid the risk of kidney disease should not be used concurrently with mercaptopurine urikozuricheskih funds. With careful use of anti-tumor or after radiotherapy.
Caution is advised when handling the tablets (dividing them in half) to avoid contamination of hands or inhalation of the drug.
Dental procedures should be completed before the start of therapy or deferred until the normalization of the blood picture (may increase the risk of microbial infection, slowing the healing process, krovotochivosty right). During treatment caution when using toothbrushes, threads or toothpicks.
Exercise caution in combination therapy; each product must be taken in due time.
During treatment, it is important enough fluid intake and urine output for subsequent amplification providing uricosuric.
During the period of treatment is not recommended vaccination virus vaccines, Avoid contact with people, received the vaccine against polio, patients with bacterial infections. Use live virus vaccine in patients with leukemia in remission should not be at least 3 months after the last cycle of chemotherapy. Immunization of oral polio vaccine people, It is in close contact with the patient, especially family members, should be postponed.
The appearance of signs of depression of bone marrow function, unusual bleeding or hemorrhage, black tarry stools, blood in the urine or feces or point of red spots on the skin require immediate doctor's advice.
Use caution to avoid accidental cuts with sharp objects (safety razor, scissors), Avoid contact sports or other situations, which are likely to hemorrhage or trauma.
In patients who develop as a result of mercaptopurine thrombocytopenia recommended special precautions (limit frequency venipuncture, the rejection of the / m injection, a urine test, feces and secret occult blood; prevent constipation, refusal of the use of acetylsalicylic acid, etc.)
Cautions.
Treatment should be under close clinical and haematological control. During and after treatment (during 2 Sun) at least 2 Once a week monitoring of peripheral blood and bone marrow hematopoiesis. Necessary to monitor the functions of the liver and kidneys, levels of uric acid in the blood.
To prevent hyperuricaemia recommend drinking plenty of fluids, If necessary, allopurinol and alkalinization of urine. By reducing the number of leukocytes and platelets below an acceptable level, tendency to bleeding or jaundice mercaptopurine should be abolished. It is necessary to carefully monitor the blood picture and, if necessary, supportive therapy and blood transfusion. Patients who develop leukopenia should be carefully monitored for signs of infection, if necessary, prescribe antibiotics. Neutropenic patients with an increase in body temperature of broad-spectrum antibiotics prescribed empirically until the results of bacteriological examinations and related diagnostic tests.
During treatment of any sexual partners is recommended to use contraception.
