Mesna Injection | Mesna

05:55 EDT 27th August 2014 | BioPortfolio

Note: While we endeavour to keep our records up-to-date one should not rely on these details being accurate without first consulting a professional. Click here to read our full medical disclaimer.

Mesna Injection is a detoxifying agent to inhibit the hemorrhagic cystitis induced by ifosfamide. The active ingredient mesna is a synthetic sulfhydryl compound designated as sodium-2-mercaptoethane sulfonate with a molecular formula of CHNaOS and a molecular weight of 164.18. Its structural formula is as follows:


Mesna Injection is a sterile, nonpyrogenic, aqueous solution of clear and colorless to light pink appearance in clear glass multidose vials for intravenous administration. Mesna Injection contains 100 mg/mL mesna, 0.25 mg/mL edetate disodium and sodium hydroxide and/or hydrochloric acid for pH adjustment. Mesna Injection multidose vials also contain 10.4 mg of benzyl alcohol as a preservative. The solution has a pH range of 6.5 to 7.3.

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 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 courses) failed to demonstrate interference with antitumor efficacy.

At doses of 2 to 4 g/m, the terminal elimination half-life of ifosfamide is about 4 to 8 hours. As a result, in order to maintain adequate levels of mesna in the urinary bladder during the course of elimination of the urotoxic ifosfamide metabolites, repeated doses of mesna are required.

After intravenous administration of an 800 mg dose, the half-lives of mesna and dimesna in the blood are 0.36 hours and 1.17 hours, respectively. Approximately 32% and 33% of the administered dose was eliminated in the urine in 24 hours as mesna and dimesna, respectively. The majority of the dose recovered was eliminated within 4 hours. Mesna has a plasma clearance of 1.23 L/h/kg.

An analysis was conducted in four males and four female volunteers; no differences in plasma pharmacokinetics were detected.

Pharmacokinetic data of mesna in pediatric and geriatric patients are not available.

No clinical studies were conducted to evaluate the effect of hepatic impairment or renal impairment on the pharmacokinetics of mesna.

No clinical drug interaction studies have been conducted with mesna.

Hemorrhagic cystitis produced by ifosfamide is dose dependent (Table 1). At a dose of 1.2 g/m, 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/hpf or macrohematuria) (Morgan, Einhorn, Costanzi). In contrast, none of the patients who received mesna injection together with this dose of ifosfamide developed hematuria (Einhorn,). In two randomized studies, (Fukuoka, Scheef), higher doses of ifosfamide, from 2 to 4 g/m administered for 3 to 5 days, produced hematuria in 31 to 100% of the patients. When mesna was administered together with these doses of ifosfamide, the incidence of hematuria was less than 7%.

*Ifosfamide dose 1.2 g/m d x 5

**Ifosfamide dose 2 to 4 g/m   d x 3 to 5

Table 1 Percent of Mesna Injection Patients Developing Hematuria (≥RBC/hpf or macrohematuria)
Conventional  Standard Mesna Injection  
Uroprophylaxis IV Regimen
Study (number of patients) (number of patients)
Uncontrolled Studies
MORGAN*    16% (7/44)
COSTANZI*  26% (11/43)
EINHORNa  18% (7/38) 0% (0/21)
EINHORNb 0% (0/32)
Controlled Studies
FUKUOKA**  31%(14/46) 6% (3/46)
SCHEEF**  100% (7/7) 0% (0/8)

Mesna is indicated as a prophylactic agent in reducing the incidence of ifosfamide-induced hemorrhagic cystitis.

Mesna is contraindicated in patients known to be hypersensitive to mesna or other thiol compounds.

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 (>50 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.

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.

No clinical drug studies have been conducted.

No long-term animal studies have been performed to evaluate the carcinogenic potential of mesna.

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.

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).

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.

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.

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.

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.

Mesna adverse reaction data are available from four phase I studies in which single IV bolus doses of 600 to 1200 mg mesna injection without concurrent chemotherapy were administered to a total of 53 subjects.

The most frequently reported side effects (observed in two or more patients) for patients receiving single doses of mesna injection were headache, injection site reactions, flushing, dizziness, nausea, vomiting, somnolence, diarrhea, anorexia, fever, pharyngitis, hyperaesthesia, influenza-like symptoms, and coughing. In addition, constipation was reported by patients who had received repeated doses of mesna injection.

Because mesna is used in combination with ifosfamide or ifosfamide-containing chemotherapy regimens, it is difficult to distinguish the adverse reactions which may be due to mesna from those caused by the concomitantly administered cytotoxic agents.

Adverse reactions reasonably associated with mesna administered IV in four controlled studies in which patients received ifosfamide or ifosfamide-containing regimens are presented in Table 2.

Table 2 Incidence of Adverse Events and Incidence of Most Frequently Reported Adverse Events in Controlled Studies
Mesna Regimen IV-IV-IV
N exposed 119 (100.0%)
Incidence of AEs 101 (84.9%)
 Most Frequently Reported Adverse Events (Preferred Terms)  
N (%)
Nausea 65 (54.6)
Vomiting 35 (29.4)
Constipation 28 (23.5)
Leukopenia 25 (21.0)
Fatigue 24 (20.2)
Fever 24 (20.2)
Anorexia 21 (17.6)
Thrombocytopenia 21 (17.6)
Anemia 20 (16.8)
Granulocytopenia 16 (13.4)
Asthenia 15 (12.6)
Abdominal Pain 14 (11.8)
Alopecia 12 (10.1)
Dyspnea 11 (9.2)
Chest Pain 10 (8.4)
Hypokalemia 10 (8.4)
Diarrhea 9 (7.6)
Dizziness 9 (7.6)
Headache 9 (7.6)
Pain 9 (7.6)
Sweating Increased 9 (7.6)
Back Pain 8 (6.7)
Hematuria*    8 (6.7)
Injection Site Reaction 8 (6.7)
Edema 8 (6.7)
Edema Peripheral 8 (6.7)
Somnolence 8 (6.7)
Anxiety 7 (5.9)
Confusion 7 (5.9)
Face Edema 6 (5.0)
Insomnia 6 (5.0)
Coughing 5 (4.2)
Dyspepsia 4 (3.4)
Hypotension 4 (3.4)
Pallor 4 (3.4)
Dehydration 3 (2.5)
Pneumonia 2 (1.7)
Tachycardia 1 (0.8)
Flushing 1 (0.8)

Allergic reactions, decreased platelet counts associated with allergic reactions, hypertension, hypotension, increased heart rate, increased liver enzymes, injection site reactions (including pain and erythema), limb pain, malaise, myalgia, ST-segment elevation, tachycardia, and tachypnea have been reported as part of postmarketing surveillance.

There is no known antidote for mesna.

For the prophylaxis of ifosfamide induced hemorrhagic cystitis, mesna may be given on a fractionated dosing schedule of three bolus intravenous injections as outlined below.

Mesna is given as intravenous bolus injections in a dosage equal to 20% of the ifosfamide dosage (w/w) at the time of ifosfamide administration and 4 and 8 hours after each dose of ifosfamide. The total daily dose of mesna is 60% of the ifosfamide dose. The recommended dosing schedule is outlined below:

0 Hours 4 Hours 8 Hours
Ifosfamide 1.2 g/m2
Mesna 240 mg/m2 240 mg/m2 240 mg/m2

The mesna multidose vials may be stored and used for up to 8 days.

For IV administration the drug can be diluted by adding the Mesna Injection solution to any of the following fluids obtaining final concentrations of 20 mg mesna/mL.

5% Dextrose Injection, USP

5% Dextrose and 0.2% Sodium Chloride Injection, USP

5% Dextrose and 0.33% Sodium Chloride Injection, USP

5% Dextrose and 0.45% Sodium Chloride Injection, USP

0.92% Sodium Chloride Injection, USP

Lactated Ringer's Injection, USP

For example:

One mL of Mesna Injection multidose vial 100 mg/mL may be added to 4 mL of any of the solutions listed above to create a final concentration of 20 mg mesna/mL.

Diluted solutions are chemically and physically stable for 24 hours at 25°C (77°F).

Mesna is not compatible with cisplatin or carboplatin.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Mesna Injection is available as follows:

NDC 55390-045-01 1 gram; 10 mL Multidose Vial, individually boxed.

NDC 55390-045-10 1 gram; 10 mL Multidose Vial, carton of 10.

Store at 20° to 25°C (68° to 77°F). See USP for controlled room temperature.

Manufactured by: Manufactured for:
Ben Venue Laboratories, Inc. Bedford Laboratories™
Bedford, OH 44146 Bedford, OH 44146
January 2004 MSN-P00
IMAGE 03a21767-f467-4e23-8c9f-ee5373c21c24-01.jpgIMAGE 03a21767-f467-4e23-8c9f-ee5373c21c24-02.jpg


Bedford Laboratories

Active Ingredients


Drugs and Medications [10 Associated Drugs and Medications listed on BioPortfolio]

Mesna [Bedford Laboratories]

Mesna Injection

Mesna [Sagent Pharmaceuticals]

Mesna Injection 100 mg per mL(For IV Use)

Mesna injection [Amerinet Choice]


Mesnex [Baxter Healthcare Corporation]

MESNEX (mesna) InjectionMESNEX (mesna) TabletsRx only

Mesnex [Baxter Healthcare Corporation]

MESNEX (mesna) InjectionMESNEX (mesna) TabletsRx only

Clinical Trials [83 Associated Clinical Trials listed on BioPortfolio]

Chemically Assisted Capsulectomy-A New Clinical Approach

The purpose of this study is to make available an agent,Mesna, which can assist the surgeon during the procedure of capsulectomy.

MESNA for Prevention of Acute Deterioration of Renal Function Following Contrast Agent Application

The purpose of this study is to determine wether Mesna could prevent contrast-induced nephropathy

A Randomized Study of the Effect of Adjuvant Chemotherapy With Doxorubicin and Ifosfamide With Mesna in the Treatment of High-Grade Adult Extremity Soft Tissue Sarcoma

Randomized study. All patients must be randomized to treatment on Arms I and II within 3 months of definitive surgery on Regimen A. Regimen A: Surgery followed, as indicated, by Radioth...

Combination Chemotherapy in Treating Patients With Metastatic Breast Cancer

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. Drugs such a...

HLA-Mismatched Unrelated Donor Bone Marrow Transplantation With Post-Transplantation Cyclophosphamide

This is a multi-center, single arm Phase II study of hematopoietic cell transplantation (HCT) using human leukocyte antigen (HLA)-mismatched unrelated bone marrow transplantation donors an...

PubMed Articles [4 Associated PubMed Articles listed on BioPortfolio]

Neoadjuvant Interdigitated Chemoradiotherapy Using Mesna, Doxorubicin, and Ifosfamide for Large, High-grade, Soft Tissue Sarcomas of the Extremity: Improved Efficacy and Reduced Toxicity.

Patients with large, high-grade extremity soft tissue sarcoma (STS) are at high risk for both local and distant recurrence. RTOG 95-14, using a regimen of neoadjuvant interdigitated chemoradiotherapy ...

Site-specific Protein Labeling with NHS-Esters and the Analysis of Ubiquitin Ligase Mechanisms.

N-hydroxysuccinimide (NHS)-esters are widely used to label proteins non-selectively on free amino groups. Such broad labeling can be disadvantageous because it can interfere with protein structure or ...

A unique manifestation of Langerhans cell histiocytosis: Diagnostic and therapeutic considerations of atypical cases.

Langerhans cell histiocytosis (LCH) is regarded as a clonal disease, usually carrying the activating BRAF mutation V600E. Although LCH theoretically may affect all types of human tissue and typically ...

Neutrophils contribute to the pathogenesis of hemorrhagic cystitis induced by ifosfamide.

Ifosfamide (IFO) is an antineoplastic drug that is commonly used to treat gynecological and breast cancers. Hemorrhagic cystitis (HC) is a common side effect associated with IFO injection, which cours...

Quick Search


Relevant Topics

Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...

Nephrology - kidney function
Nephrology is a specialty of medicine and pediatrics that concerns itself with the study of normal kidney function, kidney problems, the treatment of kidney problems and renal replacement therapy (dialysis and kidney transplantation). Systemic conditions...

Benign Prostatic Hyperplasia (BPH) Erectile Dysfunction Urology Urology is the branch of medicine concerned with the urinary tract and diseases that affect it. Examples include urethritis, urethrostenosis and incontinence. Urology is a su...

Drugs and Medication Quicklinks

Searches Linking to this Drug Record