MESNA Film-coated tablets Ref.[9333] Active ingredients: Mesna

Sufficient Mesna must be given to adequately protect the patient from the urotoxic effects of the oxazaphosphorine.

The duration of Mesna treatment should equal that of the oxazaphosphorine treatment plus the time taken for the urinary concentration of oxazaphosphorine metabolites to fall to non-toxic levels. This usually occurs within 8-12 hours after the end of oxazaphosphorine treatment but may vary depending on the scheduling of oxazaphosphorine. When calculating the dose of Mesna the quantity should be rounded down to the nearest whole tablet. Urinary output should be maintained at 100 ml/hr (as required for oxazaphosphorine treatment) and the urine monitored for haematuria and proteinuria throughout the treatment period.

Compared with intravenous administration, overall availability of Mesna in urine after oral administration is approximately 50%; and the onset of urinary excretion is delayed by up to 2 hours and is more prolonged than following intravenous dosing.

For intermittent oxazaphosphorine therapy

Oral administration of 40% of the dosage of the oxazaphosphorine on a weight for weight basis rounded down to the nearest whole tablet. The oral dose of Mesna should be taken 2 hours before and at 2 hours and 6 hours after oxazaphosphorine dosing.

If the Mesna is to be administered intravenously in the first instance, the oral administration at -2 hours should be replaced by the i.v. at 0 hours.

Example dosage schedule:

Where ifosfamide is used as a 24 hour infusion

Oral Mesna should be taken as the combined infusion of ifosfamide and Mesna finishes. Then at 2 hours and 6 hours after the time at the finish of the infusion. All doses are 40% (w/w) of the ifosfamide dose rounded down to the nearest whole tablet.

Example dosage schedule:

Where ifosfamide is used as a long-term continuous infusion

Oral Mesna should be taken as the combined infusion of ifosfamide and Mesna finishes, then at 2 hours and 6 hours after the time at the finish of the infusion. All oral Mesna doses should be 40% (w/w) of the final 24 hour ifosfamide dose rounded down to the nearest whole tablet.

Example dosage schedule:

Children

In children it may be necessary to shorten the interval between doses and/or to increase the number of individual doses. This regime protects children who generally have increased micturition.

Elderly

No specific information is available. Clinical trials have included patients over 65 and no adverse reactions specific to this age group have been reported.

High risk patients

Patients who have damaged urothelium from previous treatment with oxazaphosphorines or pelvic irradiation, or who are not adequately protected by Mesna at the standard dose, e.g. patients with case history of urinary tract disease: the dose of 40% of oxazaphosphorine dose should be given at intervals shorter than 4 hours and/or the number of doses increased.

Reports of inadvertent overdose and observations from a high-dose tolerability study in healthy volunteers showed that, in adults, single doses in the range of approximately 4g to 7g of mesna can cause symptoms such as nausea, vomiting, abdominal pain/colic, diarrhoea, headache, fatigue, limb and joint pains, rash, flushing, hypotension, bradycardia, tachycardia, paresthesia, fever, and bronchospasm.

A markedly increased rate of nausea, vomiting and diarrhoea has also been found in oxazaphosphorine-treated patients receiving ≥80 mg mesna per kg per day intravenously compared with patients receiving lower doses or hydration treatment only.

A specific antidote to Mesna is not known.

Shelf life: 5 years.

No specific storage conditions necessary.

Folding box containing blister packs consisting of: aluminium 20 µm (top layer),polyamide 25 µm, aluminium 45 µm, PVC 60 µm (bottom layer).

One blister strip contains 10 tablets. Pack sizes: 10 tablets, 20 tablets, 50 tablets.

No special instructions necessary.