Uromesan

Mesna.

Each mL contains: Mesna 100 mg.
Excipients/Inactive Ingredients: Edetate Disodium, Sodium Hydroxide, Water for Injection.

Pharmacology: Mesna is sulfhydryl containing compound which is excreted in the urine. Co-administration with Oxazaphosphorine alkylating agents such as Ifosfamide and Cyclophosphamide significantly reduces their urotoxic effects by reacting with the causal metabolites, including acrolein, in the urinary system. No reduction in the anti-tumour activity of these Oxazaphosphorine compounds has been detected.

Prevention of urothelial toxicity due to Oxazaphosphorines.
UROMESAN should always be given in tumour therapy with Ifosfamide. Where Cyclophosphamide is being used for tumour therapy, UROMESAN should always be given with bolus doses (over 10 mg/kg) of the cytotoxic agent and in all patients at special risk.
The principle risk factors are: Previous pelvic radiotherapy, cystitis with previous Ifosfamide, Cyclophosphamide therapy or a history of disorders of the urinary tract.

Unless otherwise prescribed, UROMESAN is normally administered intravenously to adults at a dose of 20% of the Oxazaphosphorine dose at time zero (the time of administration of the Oxazaphosphorine), and then at 4 and 8 hours.
Example of UROMESAN administration with Oxazaphosphorine Injection: See Table 1.


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Clinical experience with children has shown that it is beneficial in individual cases to give UROMESAN at shorter intervals (e.g. every three hours, total UROMESAN dose = 60 % of Oxazaphosphorine dose). With very high-dose Oxazaphosphorine cytostatic therapy (e.g. before bone marrow transplantation), the total UROMESAN dose can be increased to between 120 and 160% of the Oxazaphosphorine dose. It is recommended that after administration of 20%, UROMESAN (related to the total dose of Oxazaphosphorine) at time zero the remaining calculated dose should be given continuously i.v. over a period of 24 hours with a perfusor. Alternatively an intermittent bolus injection is possible.
For adults 3 x 40% (at times 0, 4, 8 hours) or 4 x 40% (at times 0, 3, 6, 9 hours) respectively. For children due to more frequent micturition, the bolus injections should always be given in 3-hour intervals (e.g. 20% at time 0, 1, 3, 6, 9. 12 hours). Instead of a bolus injection, short infusions of 15 minutes duration are possible.
With continuous infusions of Ifosfamide, it has been shown to be of benefit to give UROMESAN at time zero following the initial 20% bolus injection (start of infusion, time 0), followed by infusion to up to 100% of the Ifosfamide dose, and to continue uroprotection for a further 6 to 12 hours after termination of the Ifosfamide infusion.
Example of UROMESAN administration with a 24-hours Ifosfamide infusion: See Table 2.


Click on icon to see table/diagram/image

Known hypersensitivity to Mesna or other thiol containing compounds.

The occurrence of hypersensitivity reactions (hyperergic reactions) following Mesna therapy has been reported more frequently in patients with autoimmune disorders than in tumour patients. Skin and mucosal reactions have been observed (rash, urticaria, exanthema, enanthema), a rise in liver transaminases and non-specific common symptoms like fever, exhaustion, nausea and vomiting. Isolated circulatory reactions with hypotension and tachycardia have been observed as well. Protection of the urinary tract with Mesna should therefore only be undertaken in patients following careful risk-benefit analysis and under medical supervision.
As Mesna is used as a uroprotector in the context of cytostatic treatment with Oxazaphosphorines, its use during pregnancy and lactation is governed by the criteria for this type of cytostatic therapy. Animal studies have shown no evidence of embryotoxic or teratogenic effects of Mesna.
The protective action of Mesna applies only to the urinary tract. All other recommended precautions are unaffected by its use and recommendations relating to them remain in force.

Isolated cases of partially organ-related hypersensitivity reactions (hyperergic reactions), e.g. skin and mucosal reactions of varying extent and severity (itching, redness, vesiculation), local tissue swelling (urticarial oedema), rare cases of drop in blood pressure and increased pulse rate above 100/min (tachycardia) due to severe acute hypersensitivity reactions (anaphylactoid reactions), and also a transient rise in certain liver function tests (transaminases) have been reported. There have been rare cases of venous irritation at the injection site.
In a tolerability study using high intravenous and oral doses of Mesna, single doses of 60 mg/kg body weight and above were associated with nausea-vomiting, diarrhoea, headache, joint pain, drop in blood pressure, tachycardia, skin reactions, exhaustion and weakness.
During treatment, the previously mentioned side-effects can not always be clearly differentiated from those caused by Oxazaphosphorines (Ifosfamide, Cyclophosphamide), or other concomitant medication.

Mesna is incompatible in vitro with Cisplatin, Carboplatin and nitrogen mustard.

Store below 30°C.
Attention: The protective effect of Mesna is restricted to the urinary passages. All other prophylactic measures recommended for Oxazaphosphorine treatment are not affected and should continue to be used. Treatment with UROMESAN can give rise to a false-positive test for ketone bodies.

Antidotes & Detoxifying Agents / Supportive Care Therapy

V03AF01 - mesna ; Belongs to the class of detoxifying agents used in antineoplastic treatment.

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