ORUCOTE

Indications

• Recurrent superficial bladder tumors
• Cytotoxic responsive malignancies

Dosage

Children: Refer to BNF for Children for dosing information in paediatric populations.

Adults: Mitomycin is typically administered at 6-weekly intervals to manage delayed bone-marrow toxicity. Specific dosing will depend on the indication and patient condition; refer to BNF for detailed dosing guidelines.

Mechanism of action

Mitomycin is activated in vivo to a bifunctional and trifunctional alkylating agent, which binds to DNA leading to cross-linking and inhibition of DNA synthesis and function. It acts most prominently during the late G1 and early S phases of the cell cycle. Mitomycin selectively inhibits DNA synthesis and can also inhibit RNA and protein synthesis at high concentrations.

Pharmacodynamics

Mitomycin has been used for decades as a chemotherapy drug with demonstrated antitumor activity. It selectively inhibits DNA synthesis, especially in tissues with high guanine and cytosine content, correlating with the degree of cross-linking induced. It has shown in vitro effects on immune cells, including inhibition of B cell, T cell, and macrophage proliferation, and also impairs antigen presentation and cytokine secretion.

Pharmacokinetics

Mitomycin is administered via intravesical instillation or intravenously, with delayed bone-marrow toxicity being a notable concern. It is recommended to reduce the dose if serum creatinine exceeds certain thresholds, indicating renal impairment. Mitomycin's effects may be cumulative with prolonged use, necessitating careful monitoring of renal function and blood parameters.

Contra-indications

• Acute pulmonary infection

Adverse effects

• Bone marrow disorders
• Cough
• Leucopenia
• Malaise
• Nausea
• Respiratory disorders
• Skin reactions
• Thrombocytopenia
• Diarrhoea
• Dizziness
• Hepatocellular injury
• Decreased oliguria
• Shock
• Urinary disorders
• Venous stenosis
• Pulmonary toxicity
• Mucositis
• Chest X-ray changes indicating potential pulmonary fibrosis
• Acute kidney injury
• Urinary tract discomfort

Interactions

• Live vaccines may increase the risk of generalised infection, possibly life-threatening
• Bleomycin may increase the risk of pulmonary toxicity
• Caution advised with other cytotoxic agents due to potential additive effects

Precautions

• Caution in handling due to tissue irritant properties
• Monitor for pulmonary toxicity, especially in patients with previous bleomycin exposure
• Risk of extravasation necrosis with intravenous use
• Caution in renal impairment; dose adjustments may be necessary

Pregnancy

Avoid use during pregnancy as it has teratogenic effects in animal studies.

Breast-feeding

Discontinue breastfeeding during treatment.

Storage

Store in a cool, dry place away from light. Follow specific storage instructions as per manufacturer.

Formulations

• Mitomycin 5 mg powder for solution for injection (hospital use only)

Mechanism of action

Mitomycin is activated in vivo to a bifunctional and trifunctional alkylating agent. Binding to DNA leads to cross-linking and inhibition of DNA synthesis and function. Mitomycin is cell cycle phase-nonspecific. ... REACTS WITH BACTERIAL DNA BUT NOT WITH ISOLATED DNA, UNLESS ... REDUCING SYSTEM IS ADDED. CROSS LINKING EFFICIENCY ... INCR IN ISOLATED BACTERIAL DNA CONTAINING INCR AMT OF CYTOSINE & GUANOSINE. ITS REDUCED FORM CONTAINS INDOLE GROUP EMBODYING ALLYLIC CARBAMATE RESIDUE. ANTIBIOTIC IS CYTOTOXIC & CARCINOGENIC BUT IS INACTIVE AS CYTOTOXIC AGENT UNLESS REDUCED ... IT ACTS AS DIFUNCTIONAL AGENT IN CROSS LINKING DNA. The drug inhibits DNA synthesis and cross-links DNA at the N6 position of adenine and at the O6 and N2 positions of guanine. In addition, single-strand breakage of DNA is caused by reduced mitomycin; this can be prevented by free radical scavengers. Its action is most prominent during the late G1 and early S phases of the cell cycle. In high concentrations ... /mitomycin/ may ... inhibit RNA and protein synthesis. For more Mechanism of Action (Complete) data for MITOMYCIN C (11 total), please visit the HSDB record page.

Pharmacodynamics

Mitomycin is one of the older chemotherapy drugs, which has been around and in use for decades. It is an antibiotic which has been shown to have antitumor activity. Mitomycin selectively inhibits the synthesis of deoxyribonucleic acid (DNA). The guanine and cytosine content correlates with the degree of mitomycin-induced cross-linking. At high concentrations of the drug, cellular RNA and protein synthesis are also suppressed. Mitomycin has been shown <i>in vitro</i> to inhibit B cell, T cell, and macrophage proliferation and impair antigen presentation, as well as the secretion of interferon gamma, TNFa, and IL-2.