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Mechanism Of Action

Mesna 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 non-urotoxic 4-sulfoethylthioifosfamide. Mesna also binds to the double bonds of acrolein and to other urotoxic metabolites and inhibits their effects on the bladder.



Following oral administration, peak plasma concentrations were reached within 1.5 to 4 hours and 3 to 7 hours for free mesna and total mesna (mesna plus dimesna and mixed disulfides), respectively. Oral bioavailability averaged 58% (range 45 to 71%) for free mesna and 89% (range 74 to 104%) for total mesna based on plasma AUC data from 8 healthy volunteers who received 1200 mg oral or intravenous doses.

Food does not affect the urinary availability of orally administered MESNEX.


Mean apparent volume of distribution (Vd) for mesna is 0.652 ± 0.242 L/kg after intravenous administration which suggests distribution to total body water (plasma, extracellular fluid, and intracellular water).


Analogous to the physiological cysteine-cystine system, mesna is rapidly oxidized to its major metabolite, mesna disulfide (dimesna). Plasma concentrations of mesna exceed those of dimesna after oral or intravenous administration.


Following intravenous administration of a single 800 mg dose, approximately 32% and 33% of the administered dose was eliminated in the urine in 24 hours as mesna and dimesna, respectively. Mean plasma elimination half-lives of mesna and dimesna are 0.36 hours and 1.17 hours, respectively. Mesna has a plasma clearance of 1.23 L/h/kg.

Clinical Studies

Intravenous MESNEX

Hemorrhagic cystitis produced by ifosfamide is dose dependent (Table 4). At a dose of 1.2 g/m² ifosfamide administered daily for 5 days, 16 to 26% of the patients who received conventional uroprophylaxis (high fluid intake, alkalinization of the urine, and the administration of diuretics) developed hematuria ( > 50 RBC per hpf or macrohematuria) (Studies 1, 2, and 3). In contrast, none of the patients who received mesna injection together with this dose of ifosfamide developed hematuria (Studies 3 and 4). In two randomized studies, (Studies 5 and 6), higher doses of ifosfamide, from 2 g/m² to 4 g/m² administered for 3 to 5 days, produced hematuria in 31 to 100% of the patients. When MESNEX was administered together with these doses of ifosfamide, the incidence of hematuria was less than 7%.

Table 4: Percent of MESNEX Patients Developing Hematuria ( ≥ 50 RBC/hpf or macrohematuria)

Study Conventional Uroprophylaxis (number of patients) Standard MESNEX Intravenous Regimen (number of patients)
Uncontrolled Studies*
Study 1 16% (7/44) -
Study 2 26% (11/43) -
Study 3 18% (7/38) 0% (0/21)
Study 4 - 0% (0/32)
Controlled Studies†
Study 5 31% (14/46) 6% (3/46)
Study 6 100% (7/7) 0% (0/8)
*Ifosfamide dose 1.2 g/m² d x 5
†Ifosfamide dose 2 g/m² to 4 g/m² d x 3 to 5


Clinical studies comparing recommended intravenous and oral MESNEX dosing regimens demonstrated incidences of grade 3 to 4 hematuria of < 5%. Study 7 was an open label, randomized, two-way crossover study comparing three intravenous doses with an initial intravenous dose followed by two oral doses of MESNEX in patients with cancer treated with ifosfamide at a dose of 1.2 g/m² to 2.0 g/m² for 3 to 5 days. Study 8 was a randomized, multicenter study in cancer patients receiving ifosfamide at 2.0 g/m² for 5 days. In both studies, development of grade 3 or 4 hematuria was the primary efficacy endpoint. The percent of patients developing hematuria in each of these studies is presented in Table 5.

Table 5: Percent of MESNEX Patients Developing Grade 3 or 4 Hematuria

Study MESNEX Dosing Regimen
Standard Intravenous Regimen (number of patients) Intravenous + Oral Regimen (number of patients)
Study 7 0% (0/30) 3.6% (1/28)
Study 8 3.7% (1/27) 4.3% (1/23)

Last reviewed on RxList: 4/1/2014
This monograph has been modified to include the generic and brand name in many instances.


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