WARNINGS
Allergic reactions to mesna ranging from mild hypersensitivity to systemic anaphylactic reactions have been reported. Patients with autoimmune disorders who were treated with cyclophosphamide and mesna appeared to have a higher incidence of allergic reactions. The majority of these patients received mesna orally.
Mesna has been developed as an agent to reduce the risk of ifosfamide-induced hemorrhagic cystitis. It will not prevent or alleviate any of the other adverse reactions or toxicities associated with ifosfamide therapy.
Mesna does not prevent hemorrhagic cystitis in all patients. Up to 6% of patients treated with mesna have developed hematuria (³50 RBC/hpf or WHO grade 2 and above). As a result, a morning specimen of urine should be examined for the presence of hematuria (microscopic evidence of red blood cells) each day prior to ifosfamide therapy. If hematuria develops when Mesna is given with ifosfamide according to the recommended dosage schedule, depending on the severity of the hematuria, dosage reductions or discontinuation of ifosfamide therapy may be initiated.
In order to reduce the risk of hematuria, Mesna must be administered with each dose of ifosfamide as outlined in the DOSAGE AND ADMINISTRATION section. Mesna is not effective in reducing the risk of hematuria due to other pathological conditions such as thrombocytopenia.
Because of the benzyl alcohol content, the multidose vial should not be used in neonates or infants and should be used with caution in older pediatric patients.
PRECAUTIONS
Information for Patients
Healthcare providers should advise patients taking Mesna to drink at least a quart of liquid a day. Patients should be informed to report if their urine has turned a pink or red color, if they vomit within 2 hours of taking oral Mesna, or if they miss a dose of oral Mesna. See Patient Information Leaflet for Mesnex Tablets.
Laboratory Tests
A false positive test for urinary ketones may arise in patients treated with Mesna. In this test, a red-violet color develops which, with the addition of glacial acetic acid, will return to violet.
Drug Interactions
No clinical drug studies have been conducted.
Carcinogenesis, Mutagenesis, and Impairment of Fertility
Carcinogenesis
No long-term studies in animals have been performed to evaluate the carcinogenic potential of Mesna.
Mutagenesis
Mesna was not genotoxic in the in vitro Ames bacterial mutagenicity assay, the in vitro mammalian lymphocyte chromosomal aberration assay or the in vivo mouse micronucleus assay.
Impairment of Fertility
No studies on male or female fertility were conducted. No signs of male or female reproductive organ toxicity were seen in 6-month oral rat studies (at doses up to 2000 mg/kg/day) or 29-week oral dog studies (520 mg/kg/day; both studies approximately 10-fold higher than the maximum recommended human dose on a body surface area basis).
Pregnancy
Pregnancy Category B
Reproduction studies have been performed in rats and rabbits at oral doses of 1000 mg/kg in rabbits and 2000 mg/kg in rats (approximately 10 times the maximum recommended total daily IV-oral-oral human dose on a body surface area basis) and have revealed no evidence of harm to the fetus due to mesna. There are however, no adequate and well-controlled studies in pregnant women. Because animal reproductive studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Nursing Mothers
It is not known whether mesna or dimesna is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for adverse reactions in nursing infants from mesna, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
Pediatric Use
Safety and effectiveness of Mesnex Tablets in pediatric patients have not been established.
Because of the benzyl alcohol content in Mesna Injection, the multidose vial should not be used in neonates or infants and should be used with caution in older pediatric patients.
Geriatric Use
Clinical studies of mesna did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. However, the ratio of ifosfamide to mesna should remain unchanged.
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