Vero-Mitomycin - instructions for use, doses, side effects, contraindications

Active substanceMitomycinMitomycin

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Vero-Mitomycin

lyophilizate for injections

VEROPHARM SA Russia

Mitomycin-C Kiova

powder for injections

Dosage form: & nbsplIofilizate for solution for injection

Composition:

Active substance: mitomycin - 0.01 g, 0.02 g and 0.002 g.

Excipients: mannitol, glucose.

Description:Porous mass of gray or gray with a violet hue of color.

Pharmacotherapeutic group:Antitumor agent - antibiotic

ATX: & nbsp

L.01.D.C.03 Mitomycin

L.01.D.C Other antineoplastic antibiotics

Pharmacodynamics:

Mitomycin is an antibiotic with antitumor activity, isolated from a fungus culture Streptomyces caespitosus. Interrupts the synthesis of DNA, at high concentrations inhibits the synthesis of protein and RNA. Most active in phases G and S mitosis. After enzymatic activation in tissues, it acts as a bi-trifunctional alkylating agent. Possesses relatively weak immunosuppressive activity. Like other cytotoxic drugs, it has a myelosuppressive effect.

Pharmacokinetics:

With an intravenous route of administration mitomycin is quickly excreted from the blood plasma. With a bolus injection of 30 mg, the concentration of the drug in the plasma is reduced by 50% in 17 minutes. After the administration of 30, 20 or 10 mg of the drug intravenously, the maximum drug concentrations in the serum are 2.4 μg / ml, 1.7 μg / ml and 0.52 μg / ml, respectively.

The clearance of the drug is determined primarily by the degree of its metabolism in the liver, but the drug is metabolized by other tissues. The clearance rate is inversely proportional to the maximum concentration of the drug in the serum. The half-life period is two-phase (5-15 minutes of the initial phase and about 50 minutes - the final phase). Displayed mitomycin mainly by the kidneys (about 10% unchanged). Since the metabolic pathways are saturated at sufficiently low doses of the drug, the percentage of urinary excreted matter rises as the dose increases.

The drug does not penetrate the blood-brain barrier.

In children, the excretion of the intravenously administered drug occurs according to the same laws.

When injected into the bladder is almost not absorbed.

Indications:

Stomach cancer, pancreatic cancer, esophageal cancer, liver cancer, bile duct cancer, colon and rectal cancer, breast cancer, cervical cancer, vulval cancer, non-small cell lung cancer, mesothelioma, bladder cancer, prostate cancer, head tumors and neck.

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

Contraindications:

Hypersensitivity to mitomycin.

Pronounced bone marrow hypoplasia.

Severe form of chronic renal failure (CRF) (at a creatinine concentration in the plasma above 1.7 mg / 100 ml).

Childhood.

Thrombocytopenia, impaired blood clotting, increased bleeding.

Pregnancy and lactation.

Acute infectious diseases of viral, fungal or bacterial nature (including chicken pox, shingles).

Carefully:

Varicella (currently or in history), herpes zoster, infectious diseases, chronic renal failure, marked inhibition of bone marrow function (including in the treatment of cytostatics, radiation therapy).

Dosing and Administration:

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 struino or intravesical (with tumors of the bladder). If necessary, the drug can be administered intraarterially, intrapleural or intraperitoneally.

With monotherapy the following I / O drip schemes are usually used:

- 2 mg / m 2 (increasing the dose does not lead to an increase in the effect) with an interval of 4-6 weeks; or 2 mg / m 2 body surface, 5 days a week for 2 weeks (from 1 to 5 and from 8 to 12 days of the course) every 4 to 6 weeks; or 4-6 mg 1-2 times a week;

- if necessary high-dose therapy - 10-30 mg 1-3 (or more) times a week.

As part of complex therapy: in / in the drip of 10 mg / m 2 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.

AT/a, intrapleural or intraperitoneal injection of 2-10 mg daily.

In the bladder, 30-40 mg (up to 60 mg) dissolved in 0.95 sodium chloride solution to a concentration of not more than 1 mg / ml, once a week, for 6-8 weeks and further every month for 6 months, or 4-10 mg daily or every 2 days.

Considering the possibility of cumulative myelosuppression caused by mitomycin, with subsequent injections of the drug, the dose is adjusted depending on the severity of bone marrow depression, the following scheme is proposed:

Minimum blood values after the administered dose		The subsequent dose of the drug as a percentage of the previous dose
Leukocytes in 1 mm³blood	Platelets in 1 mm³blood
more than 4000	more than 100,000	100
3999-3000	99999-75000	100
2999-2000	74999-25000	70
less than 2000	less than 25000	50

Repeatedly, the drug should be administered only when the number of leukocytes is restored to 4000 / mm³ and platelets to 100,000 / mm³ 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 vial 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.

Bottle by:	Quantity of solvent
2 mg	4 ml
10 mg	20 ml
20 mg	40 ml

Side effects:

From the respiratory system: acute asthma, bronchospasm.

On the part of the hematopoiesis system: leukopenia, thrombocytopenia, anemia.

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

From the urinary system: increased serum creatinine concentration, hemolytic uremic syndrome, accompanied mainly by thrombocytopenia, microangiopathic hemolytic anemia with erythrocyte fragmentation and anuric form of acute renal failure

Impaired renal function (proteinuria, hematuria), edema, hypercritetinemia, syncopal conditions. Other more rare manifestations of the syndrome may be pulmonary edema, neuropathy.

The development of hemolytic uremic syndrome was observed in patients who received mitomycin intravenously in the form of monotherapy or in combination with other cytostatics in doses exceeding 60 mg.

On the part of the CAS: arterial hypertension, decreased myocardial contractility, development or aggravation of the course of heart failure (in patients previously received doxorubicin)

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

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

Local Reactions: thrombophlebitis, cellulite, if the product gets under the skin - redness, pain.

Other: acrocyanosis, headache, fever, a feeling of numbness or tingling in the fingers and toes; purple stripes on the nails, unusual tiredness or weakness.

With intravesical application - atrophy of the bladder, irritation of the urogenital tract, dysuria, cystitis, nocturnal enuresis, increased frequency of urination, hematuria and other symptoms of local irritation.Rash and itching on the arms and in the genital area.

Overdose:

Specific antidote for overdose is not known, should be symptomatic therapy.

Interaction:

With the simultaneous use of mitomycin with drugs that have a myelotoxic and nephrotoxic effect, and in combination with radiation therapy, toxicity can be increased.

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

In patients who had previously received doxorubicin, in the treatment of mitomycin, the development of congestive heart failure is possible. With simultaneous use with doxorubicin, cardiotoxic effect may be increased (the total dose of doxorubicin should not exceed 450 mg / m 2).

Special instructions:

Mitomycin should be used under the supervision of a doctor who has experience with antitumor drugs.

Mitomycin should be administered slowly slowly intravenously, avoiding extravasation.

In case of occurrence of pulmonary toxicity, the use of mitomycin should be discontinued and glucocorticosteroid treatment should be prescribed.

During the course of treatment and within 8 weeks after its completion, control of peripheral blood counts (the number of leukocytes, neutrophils, platelets, hemoglobin) and the concentration of creatinine and urea in the blood serum is necessary.

If the serum creatinine concentration is increased above 150 μmol / l or the disease progresses, mitomycin therapy is discontinued.

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

It is not recommended to use instead of surgical and radiation treatment; monotherapy or chemotherapy of the first line is carried out in case of special need.

With caution appoint if the function of the bone marrow, liver, kidneys, infections.

Be careful when signs of oppression of bone marrow function appear. The inhibition of bone marrow function can occur at any time for 8 weeks. The greatest decrease in the number of leukocytes and platelets is observed on average in 4 weeks,recovery of blood values on average 10 weeks after the administration of the drug. Mitomycin causes cumulative myelosuppression, which patients must be informed of.

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

With the use of various solvents, the stability of the solution varies: 5% dextrose solution - stability 3 hours, 0.9% sodium chloride solution - 12 hours, sodium lactate for - injection - 24 hours.

Avoid contact with sick bacterial infections.

It requires particularly careful monitoring with long-term treatment (observe side effects!).

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

If unusual bleeding or hemorrhage occurs, black tarry stools, blood in the urine or feces, or spot red spots on the skin immediately consult a doctor.

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

Form release / dosage:

Lyophilizate for solution for injection, 0.002 g, 0.01 g and 0.02 g.

Packaging:

1, 3 or 5 bottles in a cardboard box with instructions for use.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

The drug should not be used after the expiry date indicated on the package.

Terms of leave from pharmacies:On prescription

Registration number:P N002367 / 01

Date of registration:09.04.2008 / 04.08.2016

Expiration Date:Unlimited

The owner of the registration certificate:VEROPHARM SA VEROPHARM SA Russia

Manufacturer: & nbsp

VEROPHARM SA Russia

Information update date: & nbsp01.02.2017

Illustrated instructions

Instructions

Vero-Mitomycin (Vero-Mitomycin)