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.
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.
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.
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.
Mitomycin (Mitomycinum)
Blood:
anemia, leukopenia, thrombocytopenia, cumulative myelosuppression (with repeated administrations).
The cardiovascular system:
decreased myocardial contractility, development or worsening of heart failure (in patients previously treated with 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 may reduce the incidence of pulmonary toxicity.
Digestive system:
stomatitis, vomiting blood, nausea, vomiting, loss of appetite, diarrhea.
Urinary system:
nephrotoxicity (irritation of the urinary tract, increased concentrations of urea and creatinine in the blood plasma, asymptomatic ulcerations of the bladder at the site of resection with intravesical administration; must be differentiated from relapse of cancer), eosinophilic cystitis, severe (often irreversible) contractures of the bladder, formation of papillary calcifications at the site resection and calcification of the bladder.
Nephrotoxicity
presented by hemolytic-uremic syndrome (microangiopathic hemolytic anemia with a decrease in hematocrit to 25% or less), irreversible renal failure, thrombocytopenia (less than 100 × 109 / l), proteinuria, less often - pulmonary hypertension, pulmonary edema, neurological disorders and hypertension, fainting. Mortality is more than 50%. Cases of renal failure without hemolysis have been described (can occur with both mono- and polychemotherapy). Transfusion of blood components may worsen the clinical picture in some patients. The incidence is greatest when the cumulative dose of mitomycin exceeds 60 mg. Usually develops within several months after administration. The use of epoetin beta may be beneficial, leading to hematological improvement, a decrease in the frequency of blood transfusions and a slowdown in the progression of chronic renal failure. Plasma exchange transfusion and captopril may be effective.
Nervous system:
numbness or tingling of the fingers or toes, headache, asthenia (myasthenia gravis), nausea, vomiting, confusion.
Organ of vision:
blurred vision, flattening of the anterior chamber, cataract, choroidal effusion, hypotonic maculopathy and suprachoroidal hemorrhage, endophthalmitis (when applied topically during surgery for glaucoma), irritation, photophobia (when applied topically during or after surgery for pterygium). Delayed effects: delayed wound healing, vascularization of the sclera and cornea, calcification and ulceration of the sclera, perforation of the sclera or cornea, necrotizing scleritis, iridocyclitis, cataracts, glaucoma, symblepharon.
Leather:
thrombophlebitis, cellulitis (with extravasation), the formation of purple stripes on the nails with repeated injections, dermatitis, alopecia.
Allergy:
skin rashes, rashes and itching on the hands and genital area, severe eczema of the palms and soles (delayed type IV hypersensitivity reaction), leukocytoclastic vasculitis (type III hypersensitivity reaction).
Reproductive system:
Studies of the effect of mitomycin on fertility have not been conducted, but gonadal suppression (amenorrhea or azoospermia) is a common side effect of anticancer therapy (especially in combination with alkylating agents). The effects depend on the dose and duration of treatment and may be irreversible. Men of reproductive age must use contraceptives during treatment with mitomycin and for 3 months after the end of therapy.
Carcinogenicity (mutagenicity):
Secondary malignancies are a potential delayed side effect of many anticancer drugs. It is unclear whether this is due to their mutagenic or immunosuppressive effects. The effect of dose and duration of treatment is unknown, but an increased risk is suspected with long-term use. Mitomycin is carcinogenic to rats and mice.
Other:
unusual weakness or fatigue, sepsis, impaired liver function, hepatic vein occlusion, acrocyanosis, hyperthermia.
Special instructions for the use of Mitomycin
Mitomycin is not used for primary chemotherapy; its use is not an alternative to surgical treatment and/or radiation therapy. Due to the myelosuppressive effect of mitomycin, once a week during treatment and at least 8 weeks after its completion, it is necessary to conduct a study of the composition of peripheral blood with mandatory counting of the number of platelets, leukocytes and determination of hemoglobin level. If the platelet count is less than 100,000 per 1 mm3 or leukocyte count less than 4000 per 1 mm3, as well as with a continuing decrease in any of these indicators, mitomycin should be discontinued until these parameters normalize. Due to possible nephrotoxic effects, mitomycin should not be administered to patients whose serum creatinine levels exceed 1.7 mg/L.
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
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).
