INFORMATION FOR PATIENTS SECTION.

17 PATIENT COUNSELING INFORMATION. See FDA-approved patient labeling (Patient Information). Hypersensitivity Advise the patient to discontinue mesna and seek immediate medical attention if any signs or symptoms of hypersensitivity reaction, including systemic anaphylactic reactions occur [see Warnings and Precautions 5.1 )]. Dosing InstructionsAdvise the patient to take mesna at the exact time and in the exact amount as prescribed. Advise the patient to contact their healthcare provider if they vomit within hours of taking oral mesna, or if they miss dose of oral mesna [see Dosage and Administration 2.2 )]. Hemorrhagic CystitisMesna does not prevent hemorrhagic cystitis in all patients nor does it prevent or alleviate any of the other adverse reactions or toxicities associated with ifosfamide. Advise the patient to report to their healthcare provider if his/her urine has turned pink or red color [see Dosage and Administration 2.3 )]. Advise the patient to drink to liters of fluid each day during mesna therapy [see Dosage and Administration 2.3 )]. Dermatologic ToxicityAdvise the patient that Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug rash with eosinophilia and systemic symptoms and bullous and ulcerative skin and mucosal reactions have occurred with mesna. Advise the patient to report to their healthcare provider if signs and symptoms of these syndromes occur [see Warnings and Precautions (5.2)]. Benzyl Alcohol ToxicityAdvise patients that serious adverse reactions are associated with the benzyl alcohol found in Mesna Injection and other medications in premature neonates and low-birth weight infants [see Warnings and Precautions 5.3 and Use in Specific Populations 8.4 )]. Embryo-Fetal ToxicityMesna is used in combination with ifosfamide. Ifosfamide or other cytotoxic agents can cause fetal harm when administered to pregnant woman. Inform female patients of the risk to fetus and potential loss of the pregnancy. Advise females to inform their healthcare provider if they are pregnant or become pregnant [see Use in Specific Populations (8.1)].ContraceptionAdvise females of reproductive potential to use effective contraception during treatment with mesna in combination with ifosfamide and for months after the last dose [see Use in Specific Populations (8.3)].Advise male patients with female partners of reproductive potential to use effective contraception during treatment with mesna in combination with ifosfamide and for months after the last dose [see Use in Specific Populations (8.3)].Lactation Advise lactating women not to breastfeed during treatment with mesna or ifosfamide and for week after the last dose [see Use in Specific Populations (8.2)].. Advise the patient to discontinue mesna and seek immediate medical attention if any signs or symptoms of hypersensitivity reaction, including systemic anaphylactic reactions occur [see Warnings and Precautions 5.1 )]. Advise the patient to take mesna at the exact time and in the exact amount as prescribed. Advise the patient to contact their healthcare provider if they vomit within hours of taking oral mesna, or if they miss dose of oral mesna [see Dosage and Administration 2.2 )]. Mesna does not prevent hemorrhagic cystitis in all patients nor does it prevent or alleviate any of the other adverse reactions or toxicities associated with ifosfamide. Advise the patient to report to their healthcare provider if his/her urine has turned pink or red color [see Dosage and Administration 2.3 )]. Advise the patient to drink to liters of fluid each day during mesna therapy [see Dosage and Administration 2.3 )]. Advise the patient that Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug rash with eosinophilia and systemic symptoms and bullous and ulcerative skin and mucosal reactions have occurred with mesna. Advise the patient to report to their healthcare provider if signs and symptoms of these syndromes occur [see Warnings and Precautions (5.2)]. Advise patients that serious adverse reactions are associated with the benzyl alcohol found in Mesna Injection and other medications in premature neonates and low-birth weight infants [see Warnings and Precautions 5.3 and Use in Specific Populations 8.4 )]. Mesna is used in combination with ifosfamide. Ifosfamide or other cytotoxic agents can cause fetal harm when administered to pregnant woman. Inform female patients of the risk to fetus and potential loss of the pregnancy. Advise females to inform their healthcare provider if they are pregnant or become pregnant [see Use in Specific Populations (8.1)].. Advise females of reproductive potential to use effective contraception during treatment with mesna in combination with ifosfamide and for months after the last dose [see Use in Specific Populations (8.3)].. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with mesna in combination with ifosfamide and for months after the last dose [see Use in Specific Populations (8.3)].

ADVERSE REACTIONS SECTION.

6 ADVERSE REACTIONS. The following are discussed in more detail in other sections of the labeling.. Hypersensitivity Reactions [see Warnings and Precautions (5.1)] Dermatological Toxicity [see Warnings and Precautions (5.2)] Benzyl Alcohol Toxicity [see Warnings and Precautions (5.3)] Laboratory Test Interferences [see Warnings and Precautions (5.4)] Use in Patients with History of Adverse Reactions to Thiol Compounds [see Warnings and Precautions (5.5)] The most common adverse reactions (> 10%) when mesna is given with ifosfamide are nausea, vomiting, constipation, leukopenia, fatigue, fever, anorexia, thrombocytopenia, anemia, granulocytopenia, diarrhea, asthenia, abdominal pain, headache, alopecia, and somnolence. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Kabi USA, LLC at 1-800-551-7176 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Mesna adverse reaction data are available from four Phase studies in which single intravenous doses of 600 to 1,200 mg mesna injection without concurrent chemotherapy were administered to total of 53 healthy volunteers and single oral doses of 600 to 2,400 mg of mesna tablets were administered to total of 82 healthy volunteers. The most frequently reported side effects (observed in two or more healthy volunteers) for healthy volunteers receiving single doses of mesna injection alone were headache, injection site reactions, flushing, dizziness, nausea, vomiting, somnolence, diarrhea, anorexia, fever, pharyngitis, hyperesthesia, influenza-like symptoms, and coughing. In two Phase multiple-dose studies where healthy volunteers received mesna tablets alone or intravenous mesna injection followed by repeated doses of mesna tablets, flatulence and rhinitis were reported. In addition, constipation was reported by healthy volunteers who had received repeated doses of intravenous mesna injection. Additional adverse reactions in healthy volunteers receiving mesna alone included injection site reactions, abdominal pain/colic, epigastric pain/burning, mucosal irritation, lightheadedness, back pain, arthralgia, myalgia, conjunctivitis, nasal congestion, rigors, paresthesia, photophobia, fatigue, lymphadenopathy, extremity pain, malaise, chest pain, dysuria, pleuritic pain, dry mouth, dyspnea, and hyperhidrosis. In healthy volunteers, mesna was commonly associated with rapid (within 24 hours) decrease in lymphocyte count, which was generally reversible within one week of administration. 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 intravenously and orally in four controlled studies in which patients received ifosfamide or ifosfamide-containing regimens are presented in Table 3. Table 3. Adverse Reactions in >=5% of Patients Receiving Mesna in combination with Ifosfamide-containing Regimens Mesna RegimenIntravenous-Intravenous-Intravenous1 Intravenous-Oral-Oral1 exposed 119 (100%) 119 (100%) Incidence of AEs 101 (84.9%) 106 (89.1%) Nausea 65 (54.6) 64 (53.8) Vomiting 35 (29.4) 45 (37.8) Constipation 28 (23.5) 21 (17.6) Leukopenia 25 (21.0) 21 (17.6) Fatigue 24 (20.2) 24 (20.2) Fever 24 (20.2) 18 (15.1) Anorexia 21 (17.6) 19 (16.0) Thrombocytopenia 21 (17.6) 16 (13.4) Anemia 20 (16.8) 21 (17.6) Granulocytopenia 16 (13.4) 15 (12.6) Asthenia 15 (12.6) 21 (17.6) Abdominal Pain 14 (11.8) 18 (15.1) Alopecia 12 (10.1) 13 (10.9) Dyspnea 11 (9.2) 11 (9.2) Chest Pain 10 (8.4) 11 (9.2) Hypokalemia 10 (8.4) 11 (9.2) Diarrhea (7.6) 17 (14.3) Dizziness (7.6) (4.2) Headache (7.6) 13 (10.9) Pain (7.6) 10 (8.4) Sweating Increased (7.6) (1.7) Back Pain (6.7) (5.0) Hematuria (6.7) (5.9) Injection Site Reaction (6.7) 10 (8.4) Edema (6.7) (7.6) Edema Peripheral (6.7) (6.7) Somnolence (6.7) 12 (10.1) Anxiety (5.9) (3.4) Confusion (5.9) (5.0) Face Edema (5.0) (4.2) Insomnia (5.0) 11 (9.2) Coughing (4.2) 10 (8.4) Dyspepsia (3.4) (5.0) Hypotension (3.4) (5.0) Pallor (3.4) (5.0) Dehydration (2.5) (5.9) Pneumonia (1.7) (6.7) Tachycardia (0.8) (5.9) Flushing (0.8) (5.0) 1Intravenous dosing of ifosfamide and mesna injection followed by either intravenous or oral doses of mesna according to the applicable dosage schedule [see Dosage and Administration (2)].. 6.2 Postmarketing Experience. The following adverse reactions have been reported in the postmarketing experience of patients receiving mesna in combination with ifosfamide or similar drugs, making it difficult to distinguish the adverse reactions which may be due to mesna from those caused by the concomitantly administered cytotoxic agents. Because these reactions are reported from population of unknown size, precise estimates of frequency cannot be made. Cardiovascular: Hypertension Gastrointestinal: Dysgeusia Hepatobiliary: Hepatitis Nervous System: Convulsion Respiratory: Hemoptysis.

CLINICAL PHARMACOLOGY SECTION.

12 CLINICAL PHARMACOLOGY. 12.1 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 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. 12.3 Pharmacokinetics. AbsorptionFollowing oral administration, peak plasma concentrations were reached within 1.5 to hours and to 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 healthy volunteers who received 1,200 mg oral or intravenous doses. Food does not affect the urinary availability of orally administered mesna. Distribution 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). Metabolism 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. Excretion Following intravenous administration of 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 plasma clearance of 1.23 L/h/kg.

CLINICAL STUDIES SECTION.

14 CLINICAL STUDIES. 14.1 Intravenous Mesna Injection. Hemorrhagic cystitis produced by ifosfamide is dose dependent (Table 4). At dose of 1.2 g/m2 ifosfamide administered daily for 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 and 4). In two randomized studies, (Studies and 6), higher doses of ifosfamide, from g/m2 to g/m2 administered for to days, produced hematuria in 31 to 100% of the patients. When mesna injection was administered together with these doses of ifosfamide, the incidence of hematuria was less than 7%.Table 4. Percent of Mesna Injection Patients Developing Hematuria (>=50 RBC/hpf or macrohematuria)StudyConventional Uroprophylaxis (number of patients) Standard Mesna Injection Intravenous Regimen (number of patients) Uncontrolled Studies Study 16% (7/44) Study 26% (11/43) Study 18% (7/38) 0% (0/21) Study - 0% (0/32) Controlled Studies+ Study 31% (14/46) 6% (3/46) Study 100% (7/7) 0% (0/8) Ifosfamide dose 1.2 g/m2 x +Ifosfamide dose g/m2 to g/m2 x to 5. 14.2 Oral Mesna. Clinical studies comparing recommended intravenous and oral mesna dosing regimens demonstrated incidences of grade to hematuria of <5%. Study was an open label, randomized, two-way crossover study comparing three intravenous doses with an initial intravenous dose followed by two oral doses of mesna in patients with cancer treated with ifosfamide at dose of 1.2 g/m2 to 2.0 g/m2 for to days. Study was randomized, multicenter study in cancer patients receiving ifosfamide at 2.0 g/m2 for days. In both studies, development of grade or 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 Mesna Patients Developing Grade or Hematuria Mesna Dosing Regimen Study Standard Intravenous Regimen (number of patients) Intravenous Oral Regimen (number of patients) Study 0% (0/30) 3.6% (1/28) Study 3.7% (1/27) 4.3% (1/23).

DOSAGE & ADMINISTRATION SECTION.

2 DOSAGE AND ADMINISTRATION. Mesna Injection may be given on fractionated dosing schedule of three bolus intravenous injections or single bolus injection followed by two oral administrations of mesna 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 mesna to ifosfamide should be maintained. (2) Intravenous Dosing Schedule: Hours4 Hours8 HoursIfosfamide1.2 g/m2 -- -- Mesna injection240 mg/m2 240 mg/m2 240 mg/m2 Intravenous and Oral Dosing Schedule: Hours2 Hours6 HoursIfosfamide1.2 g/m2 -- -- Mesna injection240 mg/m2 -- -- Mesna tablets-- 480 mg/m2 480 mg/m2 Maintain sufficient urinary output, as required for ifosfamide treatment, and monitor urine for the presence of hematuria. (2.3). 2.1 Intravenous Dosing. Mesna Injection may be given on fractionated dosing schedule of three bolus intravenous injections as outlined below.Mesna Injection is given as intravenous bolus injections in dosage equal to 20% of the ifosfamide dosage weight by weight (w/w) at the time of ifosfamide administration and and hours after each dose of ifosfamide. The total daily dose of Mesna Injection is 60% of the ifosfamide dose. The recommended dosing schedule is outlined below in Table 1. Table 1. Recommended Intravenous Dosing Schedule Hours4 Hours8 HoursIfosfamide1.2 g/m2 - Mesna injection1 240 mg/m2 240 mg/m2 240 mg/m2 1The dosing schedule should be repeated on each day that ifosfamide is administered. When the dosage of ifosfamide is increased or decreased, the ratio of Mesna Injection to ifosfamide should be maintained.. 2.2 Intravenous and Oral Dosing. Mesna Injection may be given on fractionated dosing schedule of single bolus injection followed by two oral administrations of mesna tablets as outlined below. Mesna Injection is given as intravenous bolus injections in dosage equal to 20% of the ifosfamide dosage (w/w) at the time of ifosfamide administration. Mesna tablets are given orally in dosage equal to 40% of the ifosfamide dose and hours after each dose of ifosfamide. The total daily dose of mesna is 100% of the ifosfamide dose. The recommended dosing schedule is outlined in Table 2.Table 2. Recommended Intravenous and Oral Dosing Schedule Hours2 Hours6 HoursIfosfamide1.2 g/m2 - Mesna injection1 240 mg/m2 - Mesna tablets- 480 mg/m2 480 mg/m2 1The dosing schedule should be repeated on each day that ifosfamide is administered. When the dosage of ifosfamide is increased or decreased, the ratio of mesna to ifosfamide should be maintained. The efficacy and safety of this ratio of intravenous and oral mesna has not been established as being effective for daily doses of ifosfamide higher than g/m2. Patients who vomit within two hours of taking oral mesna should repeat the dose or receive intravenous Mesna Injection.. 2.3 Monitoring for Hematuria. Maintain adequate hydration and sufficient urinary output, as required for ifosfamide treatment, and monitor urine for the presence of hematuria. If severe hematuria develops when Mesna Injection is given according to the recommended dosage schedule, dosage reductions or discontinuation of ifosfamide therapy may be required.. 2.4 Preparation for Intravenous Administration and Stability. PreparationDetermine the volume of Mesna Injection for the intended dose. Dilute the volume of Mesna Injection for the dose in any of the following fluids to obtain final concentration of 20 mg/mL: 5% Dextrose Injection, USP 5% Dextrose and 0.2% Sodium Chloride Injection, USP 5% Dextrose and 0.33% Sodium Chloride Injection, USP5% Dextrose and 0.45% Sodium Chloride Injection, USP 0.9% Sodium Chloride Injection, USP Lactated Ringers Injection, USP StabilityThe Mesna Injection multiple dose vials may be stored and used for up to days after initial puncture. Store diluted solutions at 25C (77F). Use diluted solutions within 24 hours. Do not mix Mesna Injection with epirubicin, cyclophosphamide, cisplatin, carboplatin, and nitrogen mustard. The benzyl alcohol contained in Mesna Injection vials can reduce the stability of ifosfamide. Ifosfamide and Mesna Injection may be mixed in the same bag provided the final concentration of ifosfamide does not exceed 50 mg/mL. Higher concentrations of ifosfamide may not be compatible with Mesna Injection and may reduce the stability of ifosfamide. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Any solutions which are discolored, hazy, or contain visible particulate matter should not be used.. 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 0.9% Sodium Chloride Injection, USP Lactated Ringers Injection, USP.

PHARMACOKINETICS SECTION.

12.3 Pharmacokinetics. AbsorptionFollowing oral administration, peak plasma concentrations were reached within 1.5 to hours and to 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 healthy volunteers who received 1,200 mg oral or intravenous doses. Food does not affect the urinary availability of orally administered mesna. Distribution 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). Metabolism 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. Excretion Following intravenous administration of 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 plasma clearance of 1.23 L/h/kg.

PREGNANCY SECTION.

8.1 Pregnancy. Risk Summary Mesna Injection is used in combination with ifosfamide or other cytotoxic agents. Ifosfamide can cause fetal harm when administered to pregnant woman. Refer to the ifosfamide prescribing information for more information on use during pregnancy.Mesna Injection contains the preservative benzyl alcohol. Because benzyl alcohol is rapidly metabolized by pregnant woman, benzyl alcohol exposure in the fetus is unlikely [see Warnings and Precautions (5.3) and Use in Specific Populations (8.4)]. The estimated background risk of major birth defects and miscarriage for the indicated populations are unknown. All pregnancies have background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is to 4% and 15 to 20%, respectively. Data Animal Data Mesna Injection is used in combination with ifosfamide or other cytotoxic agents. Ifosfamide can cause fetal harm including embryo-fetal lethality. Refer to the ifosfamide prescribing information for more information on use during pregnancy. In embryo-fetal development studies, oral administration of mesna to pregnant rats (500, 1,000, 1,500, and 2,000 mg/kg) and rabbits (500 and 1,000 mg/kg) during the period of organogenesis revealed no adverse developmental outcomes at doses approximately 10 times the maximum recommended total daily human equivalent dose based on body surface area.

SPL PATIENT PACKAGE INSERT SECTION.

PATIENT INFORMATION Mesna (MEZ nah) injection What is the most important information should know about Mesna Injection Mesna Injection can cause serious allergic reactions and skin reactions. These serious reactions can happen the first time you are treated with Mesna Injection or after several months of treatment with Mesna Injection. Stop treatment with Mesna Injection and go to the nearest hospital emergency room right away if you develop any of the symptoms listed below: fever swelling of your face, lips, mouth, or tongue trouble breathing or wheezing itching burning skin rash or hives skin redness or swelling skin blisters or peeling feel lightheaded or faint feel like your heart is racing nausea vomiting joint or muscle aches mouth sores See What are the possible side effects of Mesna Injection for more information about side effects. What is Mesna Injection Mesna Injection is prescription medicine used to reduce the risk of inflammation and bleeding of the bladder (hemorrhagic cystitis) in people who receive ifosfamide (a medicine used to treat cancer). Mesna Injection is not for use to reduce the risk of blood in the urine (hematuria) due to other medical conditions. Do not receive Mesna Injection if you are allergic to mesna or any of the ingredients in mesna injection. See the end of this leaflet for complete list of ingredients in Mesna Injection.Before you receive Mesna Injection, tell your healthcare provider about all of your medical conditions, including if you: are allergic to any medicines are pregnant or plan to become pregnant. Females who are able to become pregnant: Your healthcare provider will verify if you are pregnant or not before you start treatment with mesna and ifosfamide. You should use effective birth control (contraception) during treatment with mesna and ifosfamide and for months after the last dose. Tell your healthcare provider if you become pregnant during treatment with mesna and ifosfamide. Males with female partners who are able to become pregnant should use effective birth control during treatment with mesna and ifosfamide and for months after the last dose. You should also read the ifosfamide Prescribing Information for important pregnancy, contraception, and infertility information. are breastfeeding or plan to breastfeed. It is not known if mesna passes into your breast milk. Do not breastfeed during treatment and for week after the last dose of mesna or ifosfamide. Tell your healthcare provider about all the medicines you take, including prescription and over-the- counter medicines, vitamins, and herbal supplements. How will receive Mesna Injection Mesna is given on the same day that you receive ifosfamide. Mesna can be given by an intravenous (IV) infusion into vein or tablets taken by mouth. You will receive mesna in one of two ways: Mesna intravenous (IV) infusion into vein at the time you receive ifosfamide and and hours after you receive ifosfamide, OR Mesna intravenous (IV) infusion into vein at the time you receive ifosfamide and Mesna tablets taken by mouth and hours after you receive ifosfamide. Take mesna tablets at the exact times and the exact dose your healthcare provider tells you to take it. During treatment with mesna by intravenous (IV) infusion or mesna tablets, you should drink to cups of liquid (1 to liters) each day. Tell your healthcare provider if you: vomit within hours of taking mesna tablets by mouth miss dose of mesna tablets have pink or red colored urine What are the possible side effects of Mesna Injection Mesna Injection may cause serious side effects, including: See What is the most important information should know about Mesna Injection Mesna Injection that is given by intravenous (IV) infusion contains the preservative benzyl alcohol. Benzyl alcohol has been shown to cause serious side effects and death in premature newborns and low-birth weight babies. Avoid use of Mesna Injection in premature newborns and low birth weight infants. Mesna tablets do not contain benzyl alcohol. The most common side effects of Mesna Injection when given with ifosfamide include: nausea vomiting constipation decreased white blood cell count tiredness fever decreased appetite decreased platelet count decreased red blood cell count diarrhea weakness stomach (abdomen) pain headache hair loss sleepinessThese are not all the possible side effects of Mesna Injection. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. General information about the safe and effective use of Mesna Injection. Medicines are sometimes prescribed for purposes other than those listed in Patient Information leaflet. Do not use Mesna Injection for condition for which it was not prescribed. Do not give mesna injection to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about Mesna Injection that is written for health professionals.What are the ingredients in Mesna InjectionActive ingredient: mesna Inactive ingredients: edetate disodium, sodium hydroxide, and benzyl alcohol as preservative. For more information, go to www.fresenius-kabi.com/us or call 1-800-551-7176. This Patient Information has been approved by the U.S. Food and Drug Administration. Revised: 4/2019.

USE IN SPECIFIC POPULATIONS SECTION.

8 USE IN SPECIFIC POPULATIONS. Pregnancy: Mesna Injection in combination with ifosfamide can cause fetal harm. Advise patients of potential risk to fetus. (8.1)Lactation: Do not breastfeed. (8.2) Females and Males of Reproductive Potential: Advise patients to use effective contraception. Verify pregnancy status prior to initiation of Mesna Injection in combination with ifosfamide. (8.3)Pediatric use: In premature neonates and low-birth weight infants, avoid use of benzyl alcohol-containing solutions. (8.4)Geriatric use: Dose selection should be cautious. (8.5) Pregnancy: Mesna Injection in combination with ifosfamide can cause fetal harm. Advise patients of potential risk to fetus. (8.1). Lactation: Do not breastfeed. (8.2) Females and Males of Reproductive Potential: Advise patients to use effective contraception. Verify pregnancy status prior to initiation of Mesna Injection in combination with ifosfamide. (8.3). Pediatric use: In premature neonates and low-birth weight infants, avoid use of benzyl alcohol-containing solutions. (8.4). Geriatric use: Dose selection should be cautious. (8.5) 8.1 Pregnancy. Risk Summary Mesna Injection is used in combination with ifosfamide or other cytotoxic agents. Ifosfamide can cause fetal harm when administered to pregnant woman. Refer to the ifosfamide prescribing information for more information on use during pregnancy.Mesna Injection contains the preservative benzyl alcohol. Because benzyl alcohol is rapidly metabolized by pregnant woman, benzyl alcohol exposure in the fetus is unlikely [see Warnings and Precautions (5.3) and Use in Specific Populations (8.4)]. The estimated background risk of major birth defects and miscarriage for the indicated populations are unknown. All pregnancies have background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is to 4% and 15 to 20%, respectively. Data Animal Data Mesna Injection is used in combination with ifosfamide or other cytotoxic agents. Ifosfamide can cause fetal harm including embryo-fetal lethality. Refer to the ifosfamide prescribing information for more information on use during pregnancy. In embryo-fetal development studies, oral administration of mesna to pregnant rats (500, 1,000, 1,500, and 2,000 mg/kg) and rabbits (500 and 1,000 mg/kg) during the period of organogenesis revealed no adverse developmental outcomes at doses approximately 10 times the maximum recommended total daily human equivalent dose based on body surface area.. 8.2 Lactation. Risk Summary Mesna Injection is used in combination with ifosfamide or other cytotoxic agents. Ifosfamide is excreted in breast milk. Refer to the ifosfamide prescribing information for more information on use during lactation. There are no data on the presence of mesna in human or animal milk, the effect on the breastfed child, or the effect on milk production. Mesna Injection contains the preservative benzyl alcohol. Because benzyl alcohol is rapidly metabolized by lactating woman, benzyl alcohol exposure in the breastfed infant is unlikely. However, adverse reactions have occurred in premature neonates and low birth weight infants who received intravenously administered benzyl alcohol-containing drugs [see Warnings and Precautions (5.3) and Use in Specific Populations (8.4)]. Because of the potential for serious adverse reactions in breastfed child, advise lactating women not to breastfeed during treatment and for week after the last dose of mesna or ifosfamide.. 8.3 Females and Males of Reproductive Potential. Mesna Injection is used in combination with ifosfamide or other cytotoxic agents. Ifosfamide can cause fetal harm when administered to pregnant woman. Refer to the ifosfamide prescribing information for more information on contraception and effects on fertility. Pregnancy Testing Verify the pregnancy status of females of reproductive potential prior to initiation of Mesna Injection in combination with ifosfamide. Contraception Females Advise females of reproductive potential to use effective contraception during treatment with Mesna Injection in combination with ifosfamide and for months after the last dose. Males Advise males with female partners of reproductive potential to use effective contraception during treatment with Mesna Injection in combination with ifosfamide and for months after the last dose.. 8.4 Pediatric Use. Mesna Injection contains the preservative benzyl alcohol which has been associated with serious adverse reactions and death when administered intravenously to premature neonates and low birth weight infants. Avoid use of Mesna Injection in premature neonates and low-birth weight infants [see Warnings and Precautions (5.3)].. 8.5 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. The ratio of ifosfamide to mesna should remain unchanged. 8.6 Use in Patients with Renal Impairment. No clinical studies were conducted to evaluate the effect of renal impairment on the pharmacokinetics of mesna.. 8.7 Use in Patients with Hepatic Impairment. No clinical studies were conducted to evaluate the effect of hepatic impairment on the pharmacokinetics of mesna.

WARNINGS AND PRECAUTIONS SECTION.

5 WARNINGS AND PRECAUTIONS. Hypersensitivity reactions: Anaphylactic reactions have been reported. Less severe hypersensitivity reactions may also occur. Monitor patients. If reaction occurs, discontinue mesna and provide supportive care. (5.1) 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 reaction occurs, discontinue mesna and provide supportive care. (5.2) Benzyl alcohol toxicity: Serious and fatal adverse reactions can occur in premature neonates and low-birth weight infants treated with benzyl alcohol-preserved drugs, including Mesna Injection. Avoid use in premature neonates and low-birth weight infants. (5.3) Laboratory test alterations: False positive tests for urinary ketones and interference with enzymatic CPK activity tests have been seen. (5.4). Hypersensitivity reactions: Anaphylactic reactions have been reported. Less severe hypersensitivity reactions may also occur. Monitor patients. If reaction occurs, discontinue mesna and provide supportive care. (5.1). 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 reaction occurs, discontinue mesna and provide supportive care. (5.2). Benzyl alcohol toxicity: Serious and fatal adverse reactions can occur in premature neonates and low-birth weight infants treated with benzyl alcohol-preserved drugs, including Mesna Injection. Avoid use in premature neonates and low-birth weight infants. (5.3). Laboratory test alterations: False positive tests for urinary ketones and interference with enzymatic CPK activity tests have been seen. (5.4). 5.1 Hypersensitivity Reactions. Mesna may cause systemic hypersensitivity reactions, including anaphylaxis. These reactions may include fever, cardiovascular symptoms (hypotension, tachycardia), acute renal impairment, hypoxia, respiratory distress, urticaria, angioedema, laboratory signs of disseminated intravascular coagulation, hematological abnormalities, increased liver enzymes, nausea, vomiting, arthralgia, and myalgia. These reactions may occur with the first exposure or after several months of exposure. Monitor for signs or symptoms. Discontinue mesna and provide supportive care.. 5.2 Dermatologic Toxicity. Drug rash with eosinophilia and systemic symptoms and bullous and ulcerative skin and mucosal reactions, consistent with Stevens-Johnson syndrome or toxic epidermal necrolysis have occurred. Mesna may cause skin and mucosal reactions characterized by urticaria, rash, erythema, pruritus, burning sensation, angioedema, periorbital edema, flushing and stomatitis. These reactions may occur with the first exposure or after several months of exposure. Discontinue mesna and provide supportive care.. 5.3 Benzyl Alcohol Toxicity. Serious adverse reactions including fatal reactions and the gasping syndrome occurred in premature neonates and low-birth weight infants who received benzyl alcohol dosages of 99 to 234 mg/kg/day (blood levels of benzyl alcohol were 0.61 to 1.378 mmol/L). Symptoms associated with gasping syndrome and other potential adverse reactions include gradual neurological deterioration, seizures, intracranial hemorrhage, hematological abnormalities, skin breakdown, hepatic and renal failure, hypotension, bradycardia, and cardiovascular collapse. Premature neonates and low-birth weight infants may be more likely to develop these reactions because they may be less able to metabolize benzyl alcohol. The minimum amount of benzyl alcohol at which toxicity may occur is not known. Mesna injection contains 10.4 mg/mL of the preservative benzyl alcohol. Avoid use of Mesna Injection in premature neonates and low-birth weight infants. [see Use in Specific Populations (8.4)] .. 5.4 Laboratory Test Interferences. False-Positive Urine Tests for Ketone Bodies false positive test for urinary ketones may arise in patients treated with mesna when using nitroprusside sodium-based urine tests (including dipstick tests). The addition of glacial acetic acid can be used to differentiate between false positive result (cherry-red color that fades) and true positive result (red-violet color that intensifies). False-Negative Tests for Enzymatic CPK Activity Mesna may interfere with enzymatic creatinine phosphokinase (CPK) activity tests that use thiol compound (e.g., N-acetylcysteine) for CPK reactivation. This may result in falsely low CPK level. False-Positive Tests for Ascorbic Acid Mesna may cause false-positive reactions in Tillmans reagent-based urine screening tests for ascorbic acid.. 5.5 Use in Patients with History of Adverse Reactions to Thiol Compounds. Mesna is thiol compound, i.e., sulfhydryl (SH) group-containing organic compound. Hypersensitivity reactions to mesna and to amifostine, another thiol compound, have been reported. It is not clear whether patients who experienced an adverse reaction to thiol compound are at increased risk for hypersensitivity reaction to Mesna Injection.