Mitomitsin-Promomed (Lyophilisate) Instructions for Use

Marketing Authorization Holder

Promomed Rus LLC (Russia)

Manufactured By

Biokhimik, JSC (Russia)

Or

Hubei Honch Pharmaceutical, Co., Ltd (China)

ATC Code

L01DC03 (Mitomycin)

Active Substance

Mitomycin (Rec.INN WHO registered)

Dosage Forms

	Mitomycin-Promomed	Lyophilisate for preparation of solution for injections and intravesical administration 2 mg: vial 1, 3, or 5 pcs.
		Lyophilisate for preparation of solution for injections and intravesical administration 10 mg: vial 1, 3, or 5 pcs.
		Lyophilisate for preparation of solution for injections and intravesical administration 20 mg: vial 1, 3, or 5 pcs.

Dosage Form, Packaging, and Composition

Lyophilisate for preparation of solution for injections and intravesical administration as a porous mass of gray or gray with a violet tint, or blue-violet color; the reconstituted solution is clear blue-violet.

Excipients: mannitol – 40 mg, glucose – 8 mg.

2 mg – dark glass vial (1) – cardboard packs.
2 mg – dark glass vial (3) – cardboard packs.
2 mg – dark glass vial (5) – cardboard packs.

Lyophilisate for preparation of solution for injections and intravesical administration as a porous mass of gray or gray with a violet tint, or blue-violet color; the reconstituted solution is clear blue-violet.

Excipients: mannitol – 200 mg, glucose – 40 mg.

10 mg – dark glass vial (1) – cardboard packs.
10 mg – dark glass vial (3) – cardboard packs.
10 mg – dark glass vial (5) – cardboard packs.

Lyophilisate for preparation of solution for injections and intravesical administration as a porous mass of gray or gray with a violet tint, or blue-violet color; the reconstituted solution is clear blue-violet.

Excipients: mannitol – 400 mg, glucose – 80 mg.

20 mg – dark glass vial (1) – cardboard packs.
20 mg – dark glass vial (3) – cardboard packs.
20 mg – dark glass vial (5) – cardboard packs.

Clinical-Pharmacological Group

Antineoplastic antibiotic

Pharmacotherapeutic Group

Antineoplastic agent, protein kinase inhibitor

Pharmacological Action

Antineoplastic agent from the group of mitosane antibiotics. Mitomycin is isolated from the culture of the fungus Streptomyces caespitosus. It inhibits DNA synthesis; at high concentrations, it suppresses protein and RNA synthesis. It is most active in the G₁ and S phases of mitosis.

After enzymatic activation in tissues, it acts as a bi- or trifunctional alkylating agent. It has relatively weak immunosuppressive activity. Like other cytostatics, it has a myelosuppressive effect.

Pharmacokinetics

It does not penetrate the blood-brain barrier. It is biotransformed mainly in the liver. T_1/2 is biphasic (5-15 min initial phase and about 50 min – terminal phase). It is excreted mainly by the kidneys (about 10% unchanged).

It does not penetrate the blood-brain barrier. When administered into the urinary bladder, it is practically not absorbed.

Indications

Gastric cancer, pancreatic cancer, liver cancer, bile duct cancer, colon and rectal cancer, esophageal cancer, breast cancer, cervical cancer, endometrial cancer, vulvar cancer, non-small cell lung cancer, mesothelioma, cancer of the renal pelvis and ureters, bladder cancer, prostate cancer, malignant tumors of the head and neck.

ICD codes

Dosage Regimen

Determine the dosage individually based on the specific malignancy, disease stage, hematological status, and the chosen anticancer protocol.

Administer via slow intravenous bolus or intravesically for bladder tumors. For specific indications, utilize intra-arterial, intrapleural, or intraperitoneal routes.

For intravenous administration, reconstitute the lyophilisate with Sterile Water for Injection to achieve a concentration of 0.5 mg/mL. Do not use if precipitate is present.

For intravesical use, instill the solution into the bladder via a urethral catheter and retain for one to two hours. Ensure adequate hydration prior to administration.

Adjust the dose based on hematological parameters. Withhold therapy if leukocyte count falls below 4,000/mm³ or platelet count falls below 100,000/mm³.

Monitor peripheral blood counts, including leukocytes, neutrophils, platelets, and hemoglobin, weekly during therapy and for eight weeks post-treatment.

Assess renal function before initiation and periodically during treatment. Do not administer if serum creatinine exceeds 1.7 mg/dL.

Be aware of cumulative myelosuppression. The nadir in blood counts typically occurs at four weeks, with recovery around ten weeks.

Discontinue treatment immediately if signs of hemolytic-uremic syndrome or pulmonary toxicity develop.

Adverse Reactions

From the hematopoietic system: leukopenia, thrombocytopenia, anemia. Bone marrow function suppression can occur at any time within 8 weeks. The greatest decrease in the number of leukocytes and platelets is observed on average at 4 weeks, with blood count recovery on average 10 weeks after administration. Mitomycin causes cumulative myelosuppression.

From the respiratory system: dyspnea, dry cough, lung infiltrates. In case of pulmonary toxicity, mitomycin use should be discontinued and glucocorticosteroid treatment prescribed.

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. The development of hemolytic-uremic syndrome was observed in patients receiving Mitomycin IV as monotherapy or in combination with other cytostatics in doses exceeding 60 mg.

From the digestive system: stomatitis, esophagitis, nausea, vomiting, anorexia, diarrhea, impaired liver function.

From the skin and subcutaneous tissues: reversible alopecia; sometimes – skin rash, ulcerations.

From the cardiovascular system: decreased myocardial contractility, development or worsening of heart failure (in patients previously treated with doxorubicin).

Local reactions: with IV administration – thrombophlebitis; if the drug gets under the skin – redness, pain, inflammation of the subcutaneous adipose tissue, necrosis.

With intravesical use: irritation of the genitourinary tract, dysuric disorders, nocturnal enuresis, increased frequency of urination, cystitis, hematuria and other symptoms of local irritation, bladder atrophy. Rash and itching on the hands and in the genital area.

Other: increased body temperature, sensation of numbness or tingling in the fingers and toes; purple streaks on the nails, increased fatigue or weakness.

Contraindications

Hypersensitivity to mitomycin; pronounced suppression of bone marrow function; severe renal impairment; blood clotting disorders, increased bleeding; pregnancy, breastfeeding period.

With caution acute infectious diseases of viral, fungal, or bacterial etiology, childhood.

Use in Pregnancy and Lactation

Mitomycin is contraindicated for use during pregnancy. If it is necessary to use during lactation, breastfeeding should be discontinued.

Women of childbearing potential should use reliable methods of contraception throughout the entire period of mitomycin use.

In experimental studies, the teratogenic effect of mitomycin has been established.

Use in Renal Impairment

Contraindicated in severe renal impairment.

Pediatric Use

Should be used with caution in children.

Special Precautions

Mitomycin should be used under the supervision of a physician experienced in the use of antineoplastic drugs.

IV administration should be slow, with great caution (carefully avoiding the solution entering the extravascular space).

Throughout the course of treatment and for 8 weeks after its completion, monitoring of peripheral blood counts (number of leukocytes, neutrophils, platelets, hemoglobin) and serum creatinine and urea concentrations is necessary.

Determination of blood urea nitrogen and creatinine levels should be performed before starting and periodically during therapy. The frequency of monitoring laboratory parameters depends on the patient’s clinical condition, dosage regimen, and the drug therapy regimen used.

Fatal outcomes due to sepsis resulting from leukopenia have been reported. Mitomycin should not be prescribed to patients with a serum creatinine level greater than 1.7 mg/dL.

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

Drug Interactions

With simultaneous use of mitomycin with drugs that have myelotoxic and nephrotoxic effects, as well as in combination with radiation therapy, toxicity may be enhanced.

With prior or simultaneous administration of vinca alkaloids with mitomycin to patients, the development of acute respiratory distress syndrome is possible. The development of this syndrome was also noted in patients receiving treatment with mitomycin and oxygen therapy (inhalation of a mixture containing more than 50% oxygen).

In patients previously treated with doxorubicin, congestive heart failure may develop during treatment with mitomycin.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.