Clinical and pharmacological group: & nbsp

Antineoplastic antibiotics

Included in the formulation
  • Vero-Mitomycin
    lyophilizate for injections 
    VEROPHARM SA     Russia
  • Mitomycin-C Kiova
    powder for injections 
       
  • Included in the list (Order of the Government of the Russian Federation No. 2782-r of 30.12.2014):

    VED

    АТХ:

    L.01.D.C.03   Mitomycin

    L.01.D.C   Other antineoplastic antibiotics

    Pharmacodynamics:

    Antibacterial agent with antitumor activity, isolated from the culture of the fungus Streptomyces caespitosus. The action is phase-specific, but cells that are in the G and S phases of the cell cycle are most sensitive. After enzymatic activation, a bi- and trifunctional alkylating agent functions in the tissues, causing a disruption in the structure of DNA, inhibiting its synthesis and, to a lesser extent, suppressing the synthesis of RNA and protein.

    Pharmacokinetics:

    From the gastrointestinal tract and after intravesical injection is practically not absorbed. Undergoes biotransformation in the liver (predominantly) and other tissues (including the kidneys). Does not penetrate the blood-brain barrier. The half-life (the initial phase) after the bolus injection at a dose of 30 mg is 5-15 minutes, the half-life (the final phase) is 50 minutes. It is excreted by the kidneys (10% in the form of unchanged substance) and in small amounts with feces. The proportion of the drug excreted in the urine increases with increasing dose due to saturation of metabolic pathways at relatively low doses.

    Indications:

    Stomach cancer.

    Pancreas cancer.

    Esophageal carcinoma.

    Liver cancer.

    Cancer of the bile ducts.

    Cancer of the colon and rectum.

    Mammary cancer.

    Cervical cancer.

    Cancer of the vulva.

    Endometrial cancer.

    Non-small cell lung cancer.

    Mesothelioma.

    Cancer of the renal pelvis and ureter.

    Cancer of the bladder.

    Prostate cancer.

    Malignant tumors of the head and neck.

    Chronic myelocytic leukemia.

    II.C15-C26.C15   Malignant neoplasm of esophagus

    II.C15-C26.C16   Malignant neoplasm of stomach

    II.C15-C26.C18   Malignant neoplasm of colon

    II.C15-C26.C19   Malignant neoplasm of rectosigmoidal joint

    II.C15-C26.C20   Malignant neoplasm of rectum

    II.C15-C26.C22   Malignant neoplasm of the liver and intrahepatic bile ducts

    II.C15-C26.C24.9   Malignant neoplasm of biliary tract, unspecified

    II.C15-C26.C25   Malignant neoplasm of pancreas

    II.C30-C39.C34   Malignant neoplasm of bronchi and lungs

    II.C45-C49.C45   Mesothelioma

    II.C50.C50   Malignant neoplasm of breast

    II.C51-C58.C51   Malignant neoplasm of vulva

    II.C51-C58.C53   Malignant neoplasm of cervix

    II.C51-C58.C54.1   Malignant neoplasm of endometrium

    II.C60-C63.C61   Malignant neoplasm of prostate

    II.C64-C68.C65   Malignant neoplasm of renal pelvis

    II.C64-C68.C66   Malignant neoplasm of ureter

    II.C64-C68.C67   Malignant neoplasm of bladder

    II.C76-C80.C76.0   Malignant neoplasm of head, face, neck

    II.C81-C96.C92.1   Chronic myeloid leukemia

    Contraindications:

    Individual intolerance.

    Chronic renal failure (concentration of creatinine in the blood plasma is more than 150 μmol / l).

    Pregnancy and breastfeeding.

    Childhood.

    Carefully:

    Acute infectious diseases of fungal, bacterial or viral etiology.

    Pronounced oppression of bone marrow function (including in the treatment of cytostatics, with radiation therapy).

    Coagulopathy.

    Pregnancy and lactation:

    The category of FDA recommendations is not defined. Controlled studies in humans are not conducted. The drug is contraindicated in pregnancy during breastfeeding.

    Dosing and Administration:

    The drug is administered intravenously, intravesical (with tumors of the bladder), if necessary - intraarterially, intrapleural or intraperitoneally. Dosage and duration of the course of treatment is selected individually in each case, depending on the diagnosis and severity of the disease, condition and age of the patient. Intravenously drip: with monotherapy - in a single dose of 20 mg / m2 with an interval of 4-6 weekspruce or 2 mg / m2 1 time per day 5 days a week for 2 weeks (from the 1st to the 5th and from the 8th to the 12th days of the course), or 8-10 mg / m2 in the 1st and 8th days every 4-5 weeks. The first (20 mg / m2) is administered completely with a number of leukocytes of at least 3×109/ l, 50% of the dose - at a level below 2×109/ l; repeated administration is possible if the number of leukocytes is at least 4×109/ l and platelets not less than 100×109/ l.

    In case of bladder cancer, the drug is administered intravesically, 20-60 mg once a week for 6-8 weeks.

    The solution is prepared immediately before use.

    Side effects:

    Blood: anemia, leukopenia, thrombocytopenia, cumulative myelosuppression (with repeated administration).

    The cardiovascular system: decreased myocardial contractility, development or aggravation of the course of heart failure (in patients who had previously received doxorubicin), cardiotoxicity.

    Respiratory system: pneumopathy (in the form of acute respiratory distress syndrome). Can develop at low cumulative doses (20 mg / m2), but the average cumulative dose for the development of pneumopathy is 78 mg / m2. Premedication with glucocorticoids can reduce the incidence of pulmonary toxicity.

    Digestive system: stomatitis, vomiting with blood, nausea, vomiting, loss of appetite, diarrhea.

    Urinary system: nephrotoxicity (irritation of the urinary tract, increased urea and creatinine in the blood plasma, asymptomatic ulceration of the bladder at the site of resection with intravesical injection, it must be differentiated with a relapse of cancer), eosinophilic cystitis, severe (often irreversible) contractures of the bladder, the formation of papillate calcifications in place resection and calcification of the bladder.

    Nephrotoxicity is represented by hemolytic-uremic syndrome (microangiopathic hemolytic anemia with a decrease in hematocrit to 25% or less), irreversible renal insufficiency, thrombocytopenia (less than 100 × 109/ l), proteinuria, less often - pulmonary hypertension, pulmonary edema, neurologic disorders and hypertension, fainting. Mortality is more than 50%. Cases of renal failure without hemolysis (can occur both with mono- and with polychemotherapy) are described.Transfusion of blood components in a number of patients can exacerbate the clinical picture. The frequency of occurrence is maximal with a cumulative dose of mitomycin exceeding 60 mg. Usually develops within a few months after administration. It may be useful to use epoetin beta, leading to hematological improvement, lowering the frequency of blood transfusions and slowing the progression of chronic renal failure. Interchangeable plasma transfusion and captopril administration may be effective.

    Nervous system: numbness or tingling of fingers or feet, headache, asthenia (myasthenia), nausea, vomiting, confusion.

    Body of vision: blurred vision, flattening of the anterior chamber, cataract, choroidal effusion, hypotonic maculopathy and suprachoroidal hemorrhage, endophthalmitis (with topical application during surgery for glaucoma), irritation, photophobia (with topical application during or after surgery for pterygium). Delayed effects: delayed wound healing, scleral and corneal vascularization, scleral calcification and ulceration, scleral or corneal perforation, necrotic scleritis, iridocyclitis, cataracts, glaucoma, symphobaron.

    Leather: thrombophlebitis, cellulitis (with extravasation), the formation of violet strips on the nails with repeated injections, dermatitis, alopecia.

    Allergy: skin rashes, rash and itching on the hands and in the genital area, severe eczema of the palms and soles (delayed hypersensitivity reaction of type IV), leukocytoclastic vasculitis (hypersensitivity reaction of type III).

    Reproductive system: studies of the effect of mitomycin on fertility have not been carried out, but gonadal suppression (amenorrhea or azoospermia) is a frequent side effect of antitumor therapy (especially in combination with alkylating agents). Effects depend on the dose and duration of treatment and can be irreversible. Men of reproductive age during treatment with mitomycin and within 3 months after the end of therapy need the use of contraceptives.

    Carcinogenicity (mutagenicity): secondary malignant tumors are a potential delayed side effect of many antitumor drugs. It is unclear whether this is due to their mutagenic or immunosuppressive effect. The effect of the dose and duration of treatment is unknown, but it assumes an increased risk with prolonged use. Mitomycin is carcinogenic to rats and mice.

    Others: unusual weakness or fatigue, sepsis, impaired liver function, hepatic vein occlusion, acrocyanosis, hyperthermia.

    Overdose:

    Not described. The specific antidote is unknown. Treatment is symptomatic: colony-stimulating factors, antibacterial drugs, blood transfusion and platelet transfusions.

    Interaction:

    Vinca alkaloids pink - it is possible to develop acute bronchospasm with simultaneous application in patients who received high total doses of mitomycin. When combining, it is necessary to monitor the tolerability of the last treatment cycle: any changes may be an early sign of pulmonary toxicity.

    Doxorubicin - cardiotoxicity may be increased with simultaneous application; It is not recommended to exceed the total lifetime dose of doxorubicin (450 mg / m2).

    Mitomycin may be incompatible with drugs that have an acidic reaction.

    Oxygenotherapy or inhalation of an oxygen-air mixture with an oxygen content of more than 50% - possible development respiratory distress syndrome (with signs of acute asphyxiation and bronchospasm) with simultaneous application.

    Fluorouracil, tamoxifen - increased risk of hemolytic-uremic syndrome with simultaneous application.

    Special instructions:

    It is necessary to monitor hematocrit or hemoglobin, the number of leukocytes, platelets, the determination of fragmented erythrocytes in peripheral blood; the concentration of creatinine and urea in the blood (prior to treatment and periodically during it, depending on the patient's condition, dose and other combination drugs). Duration of monitoring ≥ 8 weeks after discontinuation of treatment (especially at a dose ≥ 60 mg due to the possibility of delayed occurrence of hemolytic-uremic syndrome and myelosuppression).

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