Uromitexan

Uromitexan

mesna

Manufacturer:

Baxter Oncology

Distributor:

Transmedic
Full Prescribing Info
Contents
Mesna.
Action
Uroprotector.
Pharmacology: Mesna, an SH-group-containing compound, prevents lesions of the urinary bladder mucosa by binding to reactive metabolites of the oxazaphosphorines. It is an inert and nontoxic thiol compound which is eliminated very rapidly via the kidneys and virtually does not pass into the tissues. The detoxifying effect is limited to the kidneys and urinary tract; the systemic side effects and antitumoural efficacy of cytostatic drugs are not affected.
The mechanism of action of the uroprotector Uromitexan is based on the formation of nontoxic addition compounds with acrolein on one hand and on the stabilization of the 4-hydroxy-metabolites of the oxazaphosphorines on the other. These reactions bring about regional detoxification in the kidneys and urinary tract. As it is excreted more quickly than the oxazaphosphorines and their reactive metabolites, mesna injection must be repeated after 4 and 8 hrs.
Pharmacokinetics: Mesna given as a free thiol compound is rapidly transformed in the serum into its metabolite mesna disulfide, which after glomerular filtration is reduced to the free thiol compound again to a considerable extent. Elimination takes place almost entirely via the kidneys. Renal elimination begins immediately after administration and is largely complete after about 8 hrs. During the first 4 hrs, the elimination is mainly as free SH-compound and thereafter almost exclusively as disulfide.
Indications/Uses
Prevention of toxicity on the urinary passages by oxazaphosphorines (cyclophosphamide, ifosfamide). Concomitant administration is advisable always in cases of cytostatic therapy with ifosfamide, as well as massive dose therapy (>10 mg/kg) with cyclophosphamide and in risk patients. Risks include previous irradiation of the small pelvis region, cystitis during previous oxazaphosphorine therapy, patients with a history of urinary tract disorders.
Dosage/Direction for Use
Tablet: Adults: 40% of the dose of oxazaphosphorine (rounded to the nearest whole tablet) to be taken at -2, 2 and 6 hrs after oxazaphosphorine dosing. If Uromitexan is given by IV at 1st instance, the oral dose at -2 hrs should be replaced by IV at 0 hr.
Children: Doses given at greater frequency and at shorter intervals.
IV: Unless prescribed otherwise, Uromitexan is usually given to adults in a dose of 20%, the dose of oxazaphosphorine in each case at the points in time 0 (administration of the oxazaphosphorine), after 4 and 8 hrs. (See Table 1.)

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Clinical experience with children has shown that it is beneficial in individual cases to give Uromitexan at shorter intervals (eg, every 3 hrs, total Uromitexan dose = 60% of oxazaphosphorine dose). With very high-dose oxazaphosphorine cytostatic therapy (eg, before bone marrow transplantation), the total Uromitexan dose can be increased to between 120% and 160% of the oxazaphosphorine dose. It is recommended that after administration of 20% Uromitexan (related to the total dose of oxazaphosphorine) at time 0, the remaining calculated dose should be given continuously IV over a period of 24 hrs with a perfusor. Alternatively, an intermittent bolus injection is possible: For adults 3 x 40% (at times 0, 4, 8 hrs) or 4 x 40% (at times 0, 3, 6, 9 hrs), respectively. For children due to more frequent micturition, the bolus injections should always be given in 3-hr intervals (eg, 20% at times 0, 1, 3, 6, 9, 12 hrs). Instead of a bolus injection, short infusions of 15-min duration are possible.
With a continuous infusion of ifosfamide (Holoxan), it has been found useful, following a bolus injection, to add Uromitexan to the continuous infusion in a dosage of up to 100% of the ifosfamide dose given at the point in time 0* (start of the infusion) simultaneously with the ifosfamide, and to still maintain the uroprotection for a further 6-12 hrs after the end of the ifosfamide administration. (See Table 2.)

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Overdosage
A specific antidote to Uromitexan is not known.
Contraindications
Known hypersensitivity to mesna and other thiol compounds.
Special Precautions
The protective effect of Uromitexan applies only to the urinary tract. Other precautionary and concomitant measures recommended during treatment with oxazaphosphorines are therefore not affected and should still be carried out as usual.
During treatment with Uromitexan there may be false-positive result of tests for ketone bodies in the urine. However, the colour is red-violet rather than violet, it is less stable, and the addition of glacial acetic acid produces immediate decolorization.
Side Effects
Isolated cases of partially organ-related hypersensitivity reactions (hyperergic reactions) eg, 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 >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 IV and oral doses of mesna, single doses of ≥60 mg/kg body weight were associated with nausea, vomiting, diarrhea, headache, joint pain, drop in blood pressure, tachycardia, skin reactions, exhaustion and weakness. During treatment, the previously mentioned side effects cannot always be clearly differentiated from those caused by oxazaphosphorines (Holoxan, Endoxan), or other concomitant medication.
Drug Interactions
Mesna is incompatible in vitro with cisplatin and nitrogen mustard.
ATC Classification
V03AF01 - mesna ; Belongs to the class of detoxifying agents used in antineoplastic treatment.
Presentation/Packing
Tab 400 mg x 10's. Inj (amp) 400 mg x 4 mL x 15's.
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