MITOMYCIN Powder for solution for injection or infusion Ref.[8897] Active ingredients: Mitomycin

Posology

Mitomycin should only be used by doctors experienced in this therapy if there is a strict indication and with continual monitoring of the haematological parameters. It is essential that the injection is administered intravenous. If the medicinal product is injected perivasally, extensive necrosis occurs in the area concerned.

Unless otherwise prescribed, mitomycin is dosed as follows:

Intravenous administration

In cytostatic monochemotherapy mitomycin is usually administered intravenously as a bolus injection. The recommended dosage is 10-20 mg/m² of body surface every 6-8 weeks, 8-12 mg/m² of body surface every 3-4 weeks or 5-10 mg/m² of body surface every 1-6 weeks, depending on the therapeutic scheme used.

A dose greater than 20 mg/m² gives more toxic manifestations without therapeutic benefits. The maximum cumulative dose of mitomycin is 60 mg/m².

In combination therapy the dosage is considerably lower. Because of the risk of additive myelotoxicity, proven treatment protocols may not be deviated from without a specific reason.

Intravesical administration

In intravesical therapy, 20-40 mg of mitomycin in 20-40 ml of phosphate buffer pH 7.4 or sodium chloride (0.9%) solution, is instilled weekly into the bladder. The treatment period is 8 to 12 weeks. In the case of intravesical administration the urine pH should be higher than pH 6.

Alternative dose recommendation in the prevention of recurrent superficial bladder tumours is 4-10 mg (0.06-0.15 mg/kg of body weight) instilled into the bladder though a urethral catheter 1 or 3 times per week. The solution should be retained in the bladder for 1-2 hours.

Special population

The dose must be reduced in patients who have undergone extensive previous cytostatic therapy, in case of myelosuppression or in elderly patients.

Older patients

Insufficient data from clinical studies are available concerning the use of mitomycin in patients ≥65 years of age.

The product should not be used in patients with renal impairment (see section 4.3).

The product is not recommended in patients with hepatic impairment due to lack efficacy and safety data in this group of patients.

Paediatric population

The safety and efficacy of mitomycin in children aged from 0 to 17 years have not been established.

Method of administration

Mitomycin is intended for intravenous injection or infusion or for intravesical instillation after being dissolved. Partial use is applicable.

For preparation of reconstituted solution, see section 6.6.

Mitomycin 2 mg, powder for solution for injection/infusion or intravesical use may not be reconstituted in water, regardless the method of administration (i.e. intravenous or intravesical).

Notes:

• Mitomycin must not be used in mixed injections.
• Other injection solutions or infusion solutions must be administered separately.
• It is essential that the injection is administered intravenous.

In case of overdose severe myelotoxicity or even myelophthisis must be expected, with the full-blown clinical effect only appearing after approximately 2 weeks.

The period until which the number of leucocytes falls to the lowest value may be 4 weeks. Prolonged close haematological monitoring therefore also has to be carried out if an overdose is suspected.

As there are no effective antidotes available, the greatest level of caution is required during each application.

Unopened vial: 2 years

The reconstituted product should be used immediately.

The contents of the vials are intended for single use only. Unused solutions must be discarded.

For storage conditions after reconstitution of the medicinal product, see section 6.3.

Mitomycin is contained within a amber colored, type I glass vial with a bromo butyl rubber stopper and an aluminium seal.

The 2 mg vials are packaged into cartons containing 1, 5 or 10 vials.

Not all pack sizes may be marketed.

Intravenous use

Mitomycin 2 mg, powder for solution for injection/infusion or intravesical use may not be reconstituted in water.

The contents of the vial should be reconstituted with saline or 20% glucose solution in a ration of:

2 ml for the 2 mg of mitomycin.

Intravesical use

Mitomycin 2 mg, powder for solution for injection/infusion or intravesical use may not be reconstituted in water.

The contents of the vial should be reconstituted with saline or phosphate buffer 7.4 in a ration of:

2 ml for the 2 mg of mitomycin.

Pregnant healthcare personnel should not handle and/or administer drug product. Mitomycin should not be allowed to come into contact with the skin. If it does, it should be washed several times with 8.4% sodium bicarbonate solution, followed by soap and water. Hand creams and emollients should not be used as they may assist the penetration of the drug into the epidermal tissue.

In the event of contact with the eye, it should be rinsed several times with saline solution. It should then be observed for several days for evidence of corneal damage. If necessary, appropriate treatment should be instituted.

The reconstituted solution is clear blue-violet colour free from visible particulate matter.

Any unused product or waste material should be disposed of in accordance with local requirements.

Waste material should be destroyed according to hospital standard procedures applicable to cytotoxic agents with due regard to current laws related to the disposal of hazardous waste.