It is a cytoprotective agent indicated as a prophylactic agent in reducing the incidence of ifosfamide-induced hemorrhagic cystitis. Limitation of Use: It is not indicated to reduce the risk of hematuria due to other pathological conditions such as thrombocytopenia.
Mesna was developed as a prophylactic agent to reduce the risk of hemorrhagic cystitis induced by ifosfamide. Analogous to the physiological cysteine-cystine system, Mesna is rapidly oxidized to its major metabolite, Mesna disulfide (diMesna). Mesna disulfide remains in the intravascular compartment and is rapidly eliminated by the kidneys. In the kidney, the Mesna disulfide is reduced to the free thiol compound, Mesna, which reacts chemically with the urotoxic ifosfamide metabolites (acrolein and 4-hydroxy-ifosfamide) resulting in their detoxification. The first step in the detoxification process is the binding of Mesna to 4-hydroxy-ifosfamide forming a nonurotoxic 4-sulfoethylthioifosfamide. Mesna also binds to the double bonds of acrolein and to other urotoxic metabolites. In multiple human xenograft or rodent tumor model studies of limited scope, using IV or IP routes of administration, Mesna in combination with ifosfamide (at dose ratios of up to 20-fold as single or multiple course) failed to demonstrate interference with antitumor efficacy.
It may be given on a fractionated dosing schedule of three bolus intravenous injections or a single bolus injection followed by two oral administrations of it Tablets as outlined below. The dosing schedule should be repeated on each day that ifosfamide is administered. When the dosage of ifosfamide is adjusted,the ratio of MESNEX to ifosfamide should be maintained. (2) Intravenous Dosing Schedule: 0 Hours 4 Hours 8 Hours Ifosfamide 1.2 g/m2 -? -? Injection 240 mg/m2 240 mg/m2 240 mg/m2 Intravenous and Oral Dosing Schedule: 0 Hours 2 Hours 6 Hours Ifosfamide 1.2 g/m2 -? -? Injection 240 mg/m2 -? -? Tablets -? 480 mg/m2 480 mg/m2 Maintain sufficient urinary output,as required for ifosfamide treatment,and monitor urine for the presence of hematuria. -
No clinical drug interaction studies have been conducted with Mesna.
Known hypersensitivity to MESNEX or to any of the excipients, including benzyl alcohol. ? Hypersensitivity reactions: Anaphylactic reactions have been reported. Less severe hypersensitivity reactions may also occur. Monitor patients. If a reaction occurs,discontinue MESNEX and provide supportive care. ? Dermatologic toxicity: Skin rash with eosinophilia and systemic symptoms,Stevens-Johnson syndrome,and toxic epidermal necrolysis have occurred. Skin rash,urticaria,and angioedema have also been seen. Monitor patients. If a reaction occurs,discontinue it and provide supportive care. ? Benzyl alcohol toxicity: The preservative benzyl alcohol has been associated with serious adverse reactions and death in neonates and premature infants. Avoid use in neonates,premature,and low-birth weight infants. ? Laboratory test alterations: False positive tests for urinary ketones and interference with enzymatic CPK activity tests have been seen.
nausea,vomiting,constipation,leukopenia,fatigue,fever, anorexia,thrombocytopenia,anemia,granulocytopenia,diarrhea,asthenia, abdominal pain,headache,alopecia,and somnolence.
Pregnancy: Use only if clearly needed. Nursing mothers: Women should not breastfeed during therapy.
There is no known antidote for Mesna. Oral doses of 6.1 and 4.3 g/kg were lethal to mice and rats, respectively. These doses are approximately 15 and 22 times the maximum recommended human dose on a body surface area basis. Death was preceded by diarrhea, tremor, convulsions, dyspnea, and cyanosis.
Store in the original carton at 20°-25°C. Protect from light. Keep out of the reach of children.
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