MITOMYCIN-C 2 mg POWDER FOR INJECTION; MITOMYCIN-C 10 mg POWDER FOR INJECTION

INDICATIONS CONTRA-INDICATIONS DOSAGE SIDE-EFFECTS PREGNANCY OVERDOSE IDENTIFICATION PATIENT INFORMATION

MITOMYCIN-C 2 mg POWDER FOR INJECTION
MITOMYCIN-C 10 mg POWDER FOR INJECTION

SCHEDULING STATUS:
S4

PROPRIETARY NAME
(and dosage form):

MITOMYCIN-C 2 mg POWDER FOR INJECTION
MITOMYCIN-C 10 mg POWDER FOR INJECTION

COMPOSITION:
Each vial of Mitomycin-C 2 mg contains 2 mg of crystalline Mitomycin-C and 48 mg of sodium chloride.
Each vial of Mitomycin-C 10 mg contains 10 mg of crystalline Mitomycin-C and 240 mg of sodium chloride.

PHARMACOLOGICAL CLASSIFICATION:
A 26 –Cytostatic Agents

PHARMACOLOGICAL ACTION:
Mitomycin-C acts as a bifunctional or trifunctional alkylating agent. It inhibits DNA synthesis and cross-links DNA to an extent proportional to its content of guanine and cytosine. Its action is most prominent during the late G1 and early S phases of the cell cycle.

INDICATIONS:
Mitomycin-C is a broad spectrum cytostatic. Used on its own Mitomycin-C may be effective in the treatment of a wide variety of malignant tumours such as breast cancer and gastro-intestinal cancer. It is, however, very often used in combination with other cytostatics particularly in the treatment of gastric and pancreatic cancers. Mitomycin-C has also been reported to have an effect in the treatment of bladder cancer, non-small cell lung cancer, head and neck squamous cell cancer, and colorectal cancer.

CONTRA-INDICATIONS:
Mitomycin-C should not be used in patients suffering from an active infection.
Mitomycin-C is contra-indicated in pregnancy. Safety during lactation has not been established. Patients with a history of hypersensitivity to Mitomycin-C. Use with caution in patients with hepatic disorder, renal disorder, bone marrow suppression or in patients with varicella (fatal systemic disorders may occur). Administration to children and reproducible patients should be carried out considering its potential effects to the gonads.

DOSAGE AND DIRECTIONS FOR USE:

There is limited but increasing evidence and concern that personnel involved in preparation and administration of parenteral antineoplastics may be at some risk because of the potential mutagenicity, teratogenicity, and/or carcinogenicity of these agents although the actual risk is unknown. Cautious handling both in the preparation and disposal of antineoplastic agents is recommended. Precautions include:
*	use of a biological containment cabinet during reconstitution and dilution of parenteral medications and wearing of disposable surgical gloves and masks
*	use of proper technique to prevent contamination of the medication, word area, and operator during transfer between containers (including proper training of personnel in this technique)
*	cautious and proper disposal of needles, syringes, vials, ampoules, and unused medication

As a single cytostatic:
12 - 14 mg/m² once a month or every 35 days by intravenous infusion.
The crystals are dissolved in 200 mL of a 5% glucose solution which is then administered over a period of 30 minutes, preferably with Vitamin B Compound.

In combination therapy:
Mitomycin-C is usually administered along with other agents (e.g. FOAM –5 FU plus oncovin plus adriamycin plus mitomycin; SMF –streptozotocin plus mitomycin plus 5 FU; AM – adriamycin plus mitomycin; FAM –5 FU plus adriamycin plus mitomycin) in a dosage of 10 mg/m² every 6 - 9 weeks. Higher doses have also been given.

Although Mitomycin-C is primarily administered intravenously other methods of administration have been used.
Intra-arterial injection:
Intra-arterial injection is used only when high concentrations of Mitomycin-C are required to attack the tumour. Water, saline or 5% dextrose/water may be used. The vehicle of choice is saline.
Intravesical infusion:
After catheterization with a Nelaton's catheter, 10 to 40 mg, dissolved in 20 - 40 mL of sterile distilled water, is injected for the treatment of bladder tumours.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Haematologic
Prolonged depression of the hemogram may occur. Leukocytopaenia, thrombocytopenia, haemorrhage, anaemia and microangiopathic haemolytic anaemia may occur. Regular full blood counts should be taken, paying special attention to the count of leucocytes and platelets. Treatment should not be repeated until these counts (leucocytes and platelets) return to normal.
Hepatic
Hepatic disorders may occur.
Renal
Since haemolytic uraemic syndrome and proteinuria, haematuria, oedema, and hypertension may occur, monitor the patients carefully by periodical examinations. If any abnormal findings are observed, discontinue administration, or adequate measures should be taken.
Gastrointestinal
Anorexia, nausea and vomiting, and stomatitis may occur.
Hypersensitivity
Hypersensitivity reactions such as rash may occur.
Urinary
Cystitis, haematuria, or atrophy of the bladder caused by bladder instillation therapy may occur.
Respiratory
Interstitial pneumonia and pulmonary fibrosis may occur.
Others
Fever, malaise and alopecia may occur.
Special precautions
To avoid necrosis, phlebitis and thrombosis, intravenous administration should be carried out as slowly as possible, paying careful attention to the injection site and method, lest extravasation occur.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
See side-effects. Treatment is symptomatic.

IDENTIFICATION:
Bluish-purple crystals.

PRESENTATION:
Individual vials each containing 2 mg or 10 mg.

STORAGE INSTRUCTIONS:
Store below 25°C. Protect from light. The product reconstituted with water, saline or 5% glucose solution is stable at room temperature for 6 hours.
KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBER:

Mitomycin-C 2 mg:	H.2764 (Act 101/1965)
Mitomycin-C 10 mg:	R/26/48

NAME AND BUSINESS ADDRESS OF THE APPLICANT:
Intramed (Pty) Ltd
6 Gibaud Road
Port Elizabeth
6001

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
8 October 1985

	12-227/1-95
	Tradepak PE