MITOMYCIN

What it is

Mitomycin is an injection available in single use vials containing either 2 mg, 10 mg or 20 mg of mitomycin C. Mitomycin is an antibiotic isolated from the broth of Streptomyces caespitosus which has anti-tumour activity and inhibits the synthesis of deoxyribonucleic acid (DNA).

Approved indications

Mitomycin is indicated in the palliative treatment of carcinoma of the stomach, pancreas, colon, lung (non-small cell), breast, cervix, head and neck, liver and bladder. — Palliative treatment of gastric carcinoma — Palliative treatment of pancreatic carcinoma — Palliative treatment of colorectal carcinoma — Palliative treatment of non-small cell lung carcinoma — Palliative treatment of breast carcinoma — Palliative treatment of cervical carcinoma — Palliative treatment of head and neck carcinoma — Palliative treatment of hepatic carcinoma — Palliative treatment of bladder carcinoma

Dosing overview

Mitomycin is administered by slow intravenous infusion. After full haematological recovery from any previous chemotherapy, either of the following dosage schedules may be used at 6-to-8-week intervals. One schedule uses 20 mg/m² intravenously as a single dose via a functioning intravenous catheter. Alternatively, 2 mg/m²/day intravenously for 5 days may be given, and after a drug-free interval of 2 days, 2 mg/m²/day for 5 days, making the total initial dose 20 mg/m² given over 10 days. For the treatment of bladder tumours, the reconstituted 20 mg dose is further diluted to 50 mL with sterile Water for Injection and immediately instilled directly into the bladder via a catheter. Dosage adjustment is guided by leukocyte and platelet nadir counts, with no repeat dosage given until leukocyte count has returned to 3000 and platelet count to 75,000.

Key safety warnings

Mitomycin results in a high incidence of bone marrow suppression, particularly thrombocytopenia and leukopenia, which may contribute to haemorrhage and overwhelming infections. Platelet count, white blood cell count, differential and haemoglobin should be obtained repeatedly during therapy and for at least 7 weeks following therapy, and a platelet count below 100,000 or WBC below 4,000 is an indication for interruption of therapy. Deaths have been reported due to septicaemia as a result of leukopenia due to the drug. Haemolytic Uremic Syndrome (HUS), a serious complication consisting primarily of microangiopathic haemolytic anaemia, thrombocytopenia, and irreversible renal failure, has been reported in patients receiving systemic mitomycin, with most cases occurring at doses greater than 60 mg of mitomycin. A high mortality rate of 52% has been associated with this syndrome. Acute shortness of breath and severe bronchospasm have been reported following the administration of vinca alkaloids in patients who had previously or simultaneously received mitomycin, with onset occurring within minutes to hours after the vinca alkaloid injection. Caution should be exercised, and only enough oxygen to provide adequate arterial saturation should be used since oxygen itself can be toxic to the lungs. Mitomycin should be administered using care to avoid extravasation of the compound, as cellulitis, ulceration and slough may result. Reports of bladder fibrosis and contraction following intravesical administration, which in rare cases have required cystectomy, and of bladder necrosis and penile necrosis have been received.

Contraindications

Mitomycin is contraindicated in patients who have demonstrated a hypersensitive or idiosyncratic reaction to it or to any of the excipients. Mitomycin is contraindicated in patients with pancytopenia or isolated leukopenia/thrombocytopenia, haemorrhagic diathesis, acute infections, or an increase in bleeding tendency due to other causes. Mitomycin is contraindicated in breastfeeding. Mitomycin is contraindicated in patients with coagulation disorder. Perforation of the bladder wall is an absolute contraindication for intravesical therapy.

Regulatory history

Mitomycin OMEGAPHARM was first listed on the Australian Register of Therapeutic Goods on 8 March 2016, with registrations for 2 mg, 10 mg and 20 mg vials.