Mitomycin-S Kiova 10 mg N5 powder for solution 1/5

Contraindications

- severe bone marrow hypoplasia;

- severe form of chronic renal failure (with plasma creatinine concentration >1.7 mg/dl);

- acute infectious diseases of a viral, fungal or bacterial nature (including chicken pox, shingles);

- childhood;

—thrombocytopenia, bleeding disorder, increased bleeding;

- pregnancy;

- period of breastfeeding;

- hypersensitivity to mitomycin.

Carefully _

the drug should be used for chickenpox (currently or in history), Herpes zoster, infectious diseases, chronic renal failure, severe suppression of bone marrow function (including during treatment with cytostatics, radiation therapy).

Drug interactions Mitomycin

With previous or simultaneous administration of mitomycin and rose vinca alkaloids, shortness of breath and severe bronchospasm occur. Respiratory problems may occur minutes to hours after administration of vinca alkaloids. Treatment is symptomatic (bronchodilators, corticosteroids, oxygen therapy). Several cases of the development of acute respiratory failure have been described in patients receiving mitomycin in combination with other chemotherapy drugs before surgery, and in the case of using a respiratory mixture containing more than 50% O2 during surgery. In this regard, oxygen therapy in such patients should be approached with caution, prescribing oxygen in the concentration necessary to ensure sufficient saturation of the arterial blood.

List of pharmacies where you can buy Mitomycin:

• Moscow
• Saint Petersburg

Dosage

The dosage regimen is set individually depending on the indications, the patient’s condition and the antitumor therapy regimen used. The drug is administered intravenously or intravesically (for bladder tumors). If necessary, the drug can be administered intraarterially, intrapleurally or intraperitoneally.

For monotherapy, the following intravenous drip regimens are usually used: 2 mg/m2 (increasing the dose does not lead to an increase in effect) with an interval of 4-6 weeks; 2 mg/m2 5 days a week for 2 weeks (1-5 and 8-12 days of the course) every 4-6 weeks; 4-6 mg 1-2 times a week.

If high-dose therapy is necessary, 10-30 mg should be used 1-3 (or more) times a week.

As part of complex therapy: intravenous drip of 10 mg/m2 of body surface 1 time every 6-8 weeks or 2-4 mg 1-2 times a week.

The maximum dose for intravenous administration is 30 mg/day.

Intraarterially, intrapleurally or intraperitoneally, 2-10 mg is administered daily.

30-40 mg (up to 60 mg), dissolved in 0.95 sodium chloride solution to a concentration of not >1 mg/ml, is injected into the bladder once a week for 6-8 weeks and then monthly for 6 months, or 4-10 mg daily or every 2 days.

Considering the possibility of cumulative myelosuppression caused by mitomycin, with subsequent intravenous administrations of the drug the dose is adjusted depending on the severity of bone marrow suppression.

The drug should be re-administered only when the number of leukocytes is restored to 4000/μl and platelets to 100,000/μl of blood. When using mitomycin in combination with other myelosuppressive drugs, the dose of the drug should be adjusted accordingly.

Preparation of the solution: the contents of the bottle are dissolved immediately before use in water for injection to a concentration of 0.4 mg/ml (2 mg of active substance per 5 ml) and shaken until dissolved.

Pharmacological properties of the drug Mitomycin

Antibiotic produced by Streptomyces caespitosus . It has an antitumor effect associated with selective inhibition of DNA synthesis. The content of guanine and cytosine in DNA correlates with the frequency of formation of interstrand cross bridges under the influence of mitomycin. In high concentrations, it reduces the amount of RNA in the cell and inhibits protein biosynthesis. Mitomycin administered intravenously is rapidly cleared from blood plasma. The half-life after a bolus IV administration of 30 mg mitomycin is 17 minutes. The clearance of mitomycin is determined primarily by the extent of its metabolism in the liver, but it is also metabolized in other tissues.

Drug interactions

With the simultaneous use of mitomycin with drugs that have myelotoxic and nephrotoxic effects, as well as in combination with radiation therapy, increased toxicity is possible.

When vinca alkaloids are administered to patients prior or simultaneously with mitomycin, acute respiratory distress syndrome may develop. Also, the development of this syndrome was noted in patients treated with mitomycin and breathing a mixture containing >50% oxygen before surgery.

In patients previously treated with doxorubicin, congestive heart failure may develop during treatment with mitomycin. When mitomycin is used simultaneously with doxorubicin, the cardiotoxic effect may be enhanced (the total dose of doxorubicin should not exceed 450 mg/m2).

Use of the drug Mitomycin

Administered only intravenously. Only with complete restoration of hematological parameters after previous chemotherapy, one of the mitomycin administration regimens given below is used with an interval between courses of 6–8 weeks. Because cumulative myelosuppressive effects are possible, the dose of mitomycin should be adjusted based on the patient's condition after each course of treatment. When mitomycin is used at a dose above 20 mg/m2, the effectiveness of treatment does not increase, but toxicity increases. 1. A dose of 20 mg/m2 is administered intravenously once through a catheter. 2. A dose of 2 mg/m2 per day is administered intravenously for 5 days, then after a 2-day break in treatment, mitomycin is administered at a dose of 2 mg/m2 per day for 5 days. Thus, the total dose administered over 10 days is 20 mg/m2. Dosage adjustment of mitomycin should be carried out according to the following scheme: mitomycin should not be re-administered when the number of leukocytes is less than 4000 per 1 mm3, and platelets less than 100,000 per 1 mm3. If mitomycin is prescribed concomitantly with other drugs that have a myelosuppressive effect, appropriate dose adjustment is necessary. If the disease progresses further after two courses of mitomycin therapy, treatment should be discontinued.

Side effects

From the respiratory system:

acute suffocation, bronchospasm, shortness of breath, dry cough, infiltrates in the lungs.

From the hematopoietic system:

leukopenia, thrombocytopenia, anemia.

From the urinary system:

increased concentration of creatinine in the blood serum, impaired renal function (proteinuria, hematuria), edema, hypercreatinemia, syncope, hemolytic uremic syndrome (thrombocytopenia, microangiopathic hemolytic anemia with fragmentation of erythrocytes and anuric form of acute renal failure; less often - pulmonary edema, neuropathy). The development of hemolytic uremic syndrome was observed in patients receiving intravenous mitomycin as monotherapy or in combination with other cytostatics in doses exceeding 60 mg.

From the cardiovascular system:

arterial hypertension, decreased myocardial contractility, development or worsening of heart failure in patients previously treated with doxorubicin.

From the digestive system:

diarrhea, liver dysfunction, stomatitis, esophagitis, nausea, vomiting, anorexia.

Dermatological reactions:

skin ulcerations, reversible alopecia; sometimes - skin rash.

Local reactions:

thrombophlebitis, cellulite, if the drug gets under the skin - redness, pain.

Other:

acrocyanosis, headache, fever, numbness or tingling sensation in the fingers and toes, purple streaks on the nails, unusual tiredness, weakness.

For intravesical use:

bladder atrophy, urinary tract irritation, dysuria, cystitis, nocturnal enuresis, increased frequency of urination, hematuria and other symptoms of local irritation. Rash and itching on the hands and genital area.

Side effects of the drug Mitomycin

thrombocytopenia, leukopenia, skin rash, stomatitis, alopecia, infiltration at the injection site, tissue necrosis in case of solution extravasation, nephrotoxic effect, pulmonary toxicity (shortness of breath, nonproductive cough, radiological signs of pulmonary infiltrates), hemolytic uremic syndrome (hemolytic anemia, microangiopathy , thrombocytopenia, irreversible renal failure), fever, anorexia, nausea, vomiting, headache, impaired visual acuity, confusion, drowsiness, fainting, fatigue, edema, thrombophlebitis, diarrhea.

special instructions

Mitomycin should be used under the supervision of a physician experienced in working with anticancer drugs.

Mitomycin should be administered slowly and strictly intravenously, avoiding extravasation.

If pulmonary toxicity occurs, use of mitomycin should be discontinued and treatment with corticosteroids should be initiated.

During the course of treatment and for 8 weeks after its completion, monitoring of peripheral blood parameters (number of leukocytes, neutrophils, platelets, hemoglobin) and the concentration of creatinine and urea in the blood serum is necessary. If serum creatinine concentrations increase >150 µmol/L or disease progression occurs, mitomycin therapy should be discontinued.

Women and men should use reliable methods of contraception during treatment and for 3 months after the end of mitomycin therapy.

Use as a substitute for surgery and radiation treatment is not recommended; monotherapy or first-line chemotherapy is carried out in case of special need.

The drug should be used with caution in cases of dysfunction of the bone marrow, liver, kidneys, or infections.

Bone marrow suppression may occur at any time within 8 weeks. The greatest decrease in the number of leukocytes and platelets is observed after 4 weeks; restoration of blood counts is observed 10 weeks after administration of the drug.

Patients should be informed about the cumulative myelosuppression caused by mitomycin.

Mitomycin, being an immunosuppressant, may reduce the response to vaccination if it is administered simultaneously with mitoxantrone therapy. The interval between stopping the use of immunosuppressants and regaining the ability to respond to a vaccine (inactivated or live) depends on the dose, underlying disease and other factors and varies from 3 to 12 months. It is recommended not to immunize unless approved by a physician. Household members of the patient should also avoid immunization with oral polio vaccine, avoid contact with people who have received polio vaccine, or wear a face mask over the nose and mouth.

Avoid contact with patients susceptible to bacterial infections.

When using different solvents, the stability of the solution changes: 5% dextrose solution - stability 3 hours, 0.9% sodium chloride solution - 12 hours, sodium lactate for injection - 24 hours.

Particularly careful monitoring is required during long-term treatment (monitor for side effects).

During the treatment period and for 7-8 weeks after its completion, regular monitoring of the cellular composition of peripheral blood, functional indicators of the liver and kidneys is necessary.

If you experience unusual bleeding or hemorrhaging, black tarry stools, blood in your urine or stool, or pinpoint red spots on your skin, consult your doctor immediately.

It is important to drink enough fluids and then increase diuresis to ensure the elimination of uric acid.
In case of impaired renal function
The drug should be used with caution in chronic renal failure. The use of the drug is contraindicated in severe chronic renal failure (with plasma creatinine concentration >1.7 mg/100 ml).

Vero-Mitomycin (Vero-Mitomycin) Mitomycin (Mitomycin) [1aR-(1a alpha,8beta,8a alpha,8b alpha)]-6-Amino-8-[[(aminocarbonyl)oxy]methyl]-1,1a,2 ,8,8a,8b-hexahydro-8a-methoxy-5-methylazirino[2′,3′:3,4]pyrrolo[1,2-a]indole-4,7-dione

Types of tumors » Medicines in this group »

Pharmacotherapeutic group: Antitumor agent, antibiotic. ATX code: [L01DC03]. Dosage form: Lyophilisate for the preparation of solution for injection.

Composition: Active substance:

mitomycin - 0.01 g, 0.02 g and 0.002 g.
Excipients:
mannitol, glucose.

Description: A porous mass of gray or gray with a violet tint.

Pharmacological action: Mitomycin is an antibiotic with antitumor activity, isolated from a culture of the fungus Streptomyces ceaspitosus

. Interrupts DNA synthesis; at high concentrations, suppresses protein and RNA synthesis. It is most active in phases C and 5 of mitosis. After enzymatic activation in tissues, it acts as a bi- and trifunctional alkylating agent. Has relatively weak immunosuppressive activity. Like other cytostatics, it has a myelosuppressive effect.

Pharmacokinetics: When administered intravenously, mitomycin is rapidly cleared from blood plasma. With a bolus administration of 30 mg, the plasma concentration of the drug decreases by 50% in 17 minutes. After administration of 30, 20 or 10 mg of the drug intravenously, the maximum concentrations of the drug in serum are 2.4 mcg/ml, 1/7 mcg/ml and 0/52 mcg/ml, respectively. The clearance of the drug is determined primarily by the degree of its metabolism in the liver, but the drug is also metabolized by other tissues. The rate of clearance is inversely proportional to the maximum serum concentration of the drug. The half-life is biphasic (5-15 minutes initial phase and about 50 minutes final phase). Mitomycin is excreted mainly by the kidneys (about 10% unchanged). Since metabolic pathways are saturated at fairly low doses of the drug, the percentage of the substance excreted in the urine increases with increasing dose.

The drug does not penetrate the blood-brain barrier. In children, excretion of an intravenously administered drug occurs according to the same laws. When introduced into the bladder, it is practically not absorbed.

Indications for use: Stomach cancer, pancreatic cancer, esophageal cancer, liver cancer, bile duct cancer, colon and rectal cancer, breast cancer, cervical cancer, vulvar cancer, non-small cell lung cancer, mesothelioma, bladder cancer, prostate cancer glands, tumors of the head and neck.

The drug is recommended both for monotherapy and in combination with other highly effective chemotherapy drugs, as well as for palliative treatment in the absence of a positive response to treatment with previously used drugs.

Contraindications: Hypersensitivity to mitomycin; severe form of chronic renal failure (CRF) (with plasma creatinine concentration above 1.7 mg/100 ml); pregnancy and lactation; childhood; severe bone marrow hypoplasia.

With caution: Acute infectious diseases of a viral, fungal or bacterial nature (including chicken pox, shingles); chronic renal failure; pronounced inhibition of bone marrow function (including during treatment with cytostatics, radiation therapy); coagulopathy (thrombocytopenia, bleeding disorder, increased bleeding).

Directions for use and doses

The dosage regimen is set individually depending on the indications, the patient’s condition and the antitumor therapy regimen used.

The drug is administered intravenously or intravesically (for bladder tumors). If necessary, the drug can be administered intraarterially, intrapleurally or intraperitoneally.

For monotherapy, the following intravenous drip regimens are usually used:

• 2 mg/sq.m (increasing the dose does not lead to an increase in effect) with an interval of 4-6 weeks;
• 2 mg/sq.m of body surface, 5 days a week for 2 weeks (from 1 to 5 and from 8 to 12 days of the course) every 4-6 weeks;
• 4-6 mg 1-2 times a week;
• if high-dose therapy is necessary, ≈ 10-30 mg 1-3 (or more) times a week;
• as part of complex therapy: intravenous drip of 10 mg/sq.m of body surface 1 time every 6-8 weeks or 2-4 mg 1-2 times a week.

The maximum dose for intravenous administration is 30 mg/day. V/a, intrapleurally or intraperitoneally, 2-10 mg is administered daily. 30-40 mg (up to 60 mg) dissolved in 0.95 sodium chloride solution to a concentration of no more than 1 mg/ml is injected into the bladder, once a week, for 6-8 weeks and then monthly for 6 months, either 4-10 mg daily or every 2 days.

Taking into account the possibility of cumulative myelosuppression caused by Mitomycin, during subsequent intravenous administrations of the drug the dose is adjusted depending on the severity of inhibition of bone marrow function. The following scheme is proposed:

The drug should be re-administered only when the number of leukocytes is restored to 4000/mm3 and platelets to 100,000/mm3 of blood. When using mitomycin in combination with other myelosuppressive drugs, the dose of the drug should be adjusted accordingly.

Preparation of the solution: the contents of the bottle are dissolved immediately before use in water for injection to a concentration of 0.4 mg/ml (2 mg of active substance per 5 ml) and shaken until dissolved.

Side effects

From the respiratory system: acute suffocation, bronchospasm.

From the hematopoietic system: leukopenia, thrombocytopenia, anemia.

From the respiratory system: shortness of breath, dry cough, infiltrates in the lungs.

From the urinary system: impaired renal function (proteinuria, hematuria), edema, hypercreatininemia, hemolyticouremic syndrome (accompanied mainly by thrombocytopenia, microangiopathic hemolytic anemia with fragmentation of erythrocytes and anuric form of acute renal failure). More rare manifestations of the syndrome may be pulmonary edema, neuropathy and increased blood pressure, and fainting. The development of hemolyticouremic syndrome was observed in patients receiving intravenous mitomycin in doses exceeding 60 mg.

From the cardiovascular system: arterial hypertension, decreased myocardial contractility, development or worsening of the severity of heart failure (in patients who previously received doxorubicin).

From the digestive system: diarrhea, liver dysfunction, stomatitis or esophagitis, nausea, vomiting, anorexia.

From the skin: skin ulcerations, reversible alopecia, sometimes skin rash.

Local reactions: thrombophlebitis, cellulite, if the drug gets under the skin - redness, pain.

Other: acrocyanosis, headache, fever, numbness or tingling sensation in the fingers and toes; purple streaks on the nails, unusual tiredness or weakness.

With intravesical use: bladder atrophy, urinary tract irritation, dysuria, cystitis, nocturnal enuresis, increased frequency of urination, hematuria and other symptoms of local irritation; rash and itching on the hands and genital area.

Overdose: A specific antidote for overdose is unknown; symptomatic therapy should be carried out.

Interaction with other drugs: When mitomycin is used simultaneously with drugs that have myelotoxic and nephrotoxic effects, as well as in combination with radiation therapy, toxicity may increase.

With preliminary or simultaneous administration of vinca alkaloids to patients with the drug mitomycin, acute respiratory distress syndrome may develop. Also, the development of this syndrome was noted in patients treated with mitomycin and breathing a mixture containing more than 50% oxygen before surgery.

In patients who have previously received doxorubicin, congestive heart failure may develop during treatment with mitomycin. When used simultaneously with doxorubicin, the cardiotoxic effect may be enhanced (the total dose of doxorubicin should not exceed 450 mg/m2).

Special instructions: Mitomycin should be used under the supervision of a physician experienced in working with anticancer drugs.

Mitomycin should be administered slowly and strictly intravenously, avoiding extravasation. If pulmonary toxicity occurs, mitomycin should be discontinued and treatment with corticosteroids should be initiated.

During the course of treatment and for 8 weeks after its completion, monitoring of peripheral blood parameters (number of leukocytes, neutrophils, platelets, hemoglobin) and the concentration of creatinine and urea in the blood serum is necessary. If the serum creatinine concentration increases above 150 μmol/L or the disease progresses, mitomycin therapy is discontinued.

Women and men should use reliable methods of contraception during treatment and for 3 months after the end of Mitomycin therapy.

Use as a substitute for surgery and radiation treatment is not recommended; monotherapy or first-line chemotherapy is carried out in case of special need. Prescribe with caution in cases of dysfunction of the bone marrow, liver, kidneys, or infections.

Use caution if signs of bone marrow suppression appear. Bone marrow suppression may occur at any time within 8 weeks. The greatest decrease in the number of leukocytes and platelets is observed on average after 4 weeks, the restoration of blood counts on average 10 weeks after administration of the drug.

Mitomycin causes cumulative myelosuppression, about which patients should be informed.

Mitomycin, being an immunosuppressant, may reduce the response to vaccination if it is administered simultaneously with mitoxantrone therapy. The interval between stopping the use of immunosuppressants and regaining the ability to respond to a vaccine (inactivated or live) depends on the dose, underlying disease and other factors and varies from 3 months. up to 1 year. It is recommended not to immunize unless approved by a physician; other family members of the patient living with him should also refuse immunization with the oral polio vaccine; Avoid contact with people who have received the polio vaccine or wear a protective mask that covers your nose and mouth.

When using different solvents, the stability of the solution changes: 5% dextrose solution - stability 3 hours, 0.9% sodium chloride solution - 12 hours, sodium lactate for injection - 24 hours.

Avoid contact with people with bacterial infections.

Particularly careful monitoring is required during long-term treatment (monitor for side effects!). During the treatment period and for 7-8 weeks after its completion, regular monitoring of the cellular composition of peripheral blood, functional indicators of the liver and kidneys is necessary. If you notice unusual bleeding or bruising, black tarry stools, blood in your urine or stool, or pinpoint red spots on your skin, consult your doctor immediately.

It is important to drink enough fluids and then increase diuresis to ensure the elimination of uric acid.

Release form: Lyophilisate for the preparation of solution for injection. 1, 3 or 5 bottles in a cardboard box with instructions for use.

Storage conditions: List B. In a dry place, protected from light, at a temperature not exceeding 25°C. Keep out of the reach of children.

Shelf life: 2 years. The drug should not be used after the expiration date indicated on the package.

Conditions for dispensing from pharmacies: By prescription.