Mesna (Page 4 of 4)

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

No long-term studies in animals 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 (≤ 2,000 mg/kg/day) or 29-week oral dog studies (520 mg/kg/day) at doses approximately 10-fold higher than the maximum recommended human dose on a body surface area basis.

14 CLINICAL STUDIES

14.1 Intravenous Mesna Injection

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 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)

Study Conventional Uroprophylaxis (number of patients) Standard Mesna Injection 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

14.2 Oral Mesna

Clinical studies comparing recommended intravenous and oral mesna 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 mesna 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 Mesna Patients Developing Grade 3 or 4 Hematuria

Mesna Dosing Regimen
Study 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)

16 HOW SUPPLIED/STORAGE AND HANDLING

Mesna Injection, is available as:

Product Code Unit of Sale Strength Each
730310 NDC 63323-733-10 Unit of 10 1 gram per 10 mL(100 mg per mL) NDC 63323-733-01 10 mL Multiple Dose Vial
730311 NDC 63323-733-11 Individually packaged. 1 gram per 10 mL(100 mg per mL) 10 mL Multiple Dose Vial

The container closure is not made with natural rubber latex.
Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. If Mesna is co-administered with ifosfamide, refer to the ifosfamide prescribing information for safe handling instructions.

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 a hypersensitivity reaction, including systemic anaphylactic reactions occur [see Warnings and Precautions ( 5.1)].

Dosing Instructions

  • 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 2 hours of taking oral mesna, or if they miss a dose of oral mesna [see Dosage and Administration ( 2.2)].

Hemorrhagic Cystitis

  • 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 a pink or red color [see Dosage and Administration ( 2.3)].
  • Advise the patient to drink 1 to 2 liters of fluid each day during mesna therapy [see Dosage and Administration ( 2.3)].

Dermatologic Toxicity

  • 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)].

Benzyl Alcohol Toxicity

  • 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)].

Embryo-Fetal Toxicity

  • Mesna is used in combination with ifosfamide. Ifosfamide or other cytotoxic agents can cause fetal harm when administered to a pregnant woman. Inform female patients of the risk to a 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)].

Contraception

  • Advise females of reproductive potential to use effective contraception during treatment with mesna in combination with ifosfamide and for 6 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 3 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 1 week after the last dose [see Use in Specific Populations (8.2)].

PATIENT INFORMATION Mesna (MEZ nah) injection
What is the most important information I 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 a 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 a 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: o Your healthcare provider will verify if you are pregnant or not before you start treatment with mesna and ifosfamide. o You should use effective birth control (contraception) during treatment with mesna and ifosfamide and for 6 months after the last dose. o 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 3 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 1 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 I receive Mesna Injection? • Mesna is given on the same day that you receive ifosfamide. • Mesna can be given by an intravenous (IV) infusion into a vein or tablets taken by mouth. • You will receive mesna in one of two ways: o Mesna intravenous (IV) infusion into a vein at the time you receive ifosfamide and 4 and 8 hours after you receive ifosfamide, OR o Mesna intravenous (IV) infusion into a vein at the time you receive ifosfamide and Mesna tablets taken by mouth 2 and 6 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 4 to 8 cups of liquid (1 to 2 liters) each day. • Tell your healthcare provider if you: o vomit within 2 hours of taking mesna tablets by mouth o miss a dose of mesna tablets o 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 I 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 a Patient Information leaflet. Do not use Mesna Injection for a 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 Injection? Active ingredient: mesna Inactive ingredients: edetate disodium, sodium hydroxide, and benzyl alcohol as a 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


address

www.fresenius-kabi.com/us
45888G
Revised: April 2019

PACKAGE LABEL — PRINCIPAL DISPLAY — Mesna 10 mL Multiple Dose Vial Label

NDC 63323-733-01 730310
Mesna
Injection

1 gram per 10 mL
(100 mg per mL)

FOR INTRAVENOUS USE
10 mL
Multiple Dose Vial

Rx only

vial label
PACKAGE LABEL — PRINCIPAL DISPLAY — Mesna 10 mL Multiple Dose Vial Tray Label

NDC 63323-733-10 730310
Mesna
Injection

1 gram per 10 mL
(100 mg per mL)

FOR INTRAVENOUS USE
10 x 10 mL
Multiple Dose Vials

Rx only tray label

MESNA mesna injection, solution
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:63323-733
Route of Administration INTRAVENOUS DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
MESNA (2-MERCAPTOETHANESULFONIC ACID) MESNA 100 mg in 1 mL
Inactive Ingredients
Ingredient Name Strength
EDETATE DISODIUM 0.25 mg in 1 mL
BENZYL ALCOHOL 10.4 mg in 1 mL
SODIUM HYDROXIDE
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:63323-733-10 10 VIAL, MULTI-DOSE in 1 TRAY contains a VIAL, MULTI-DOSE (63323-733-01)
1 NDC:63323-733-01 10 mL in 1 VIAL, MULTI-DOSE This package is contained within the TRAY (63323-733-10)
2 NDC:63323-733-11 1 VIAL, MULTI-DOSE in 1 BOX contains a VIAL, MULTI-DOSE
2 10 mL in 1 VIAL, MULTI-DOSE This package is contained within the BOX (63323-733-11)
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA075811 09/05/2001
Labeler — Fresenius Kabi USA, LLC (608775388)
Establishment
Name Address ID/FEI Operations
Fresenius Kabi USA, LLC 023648251 MANUFACTURE (63323-733)

Revised: 04/2019 Fresenius Kabi USA, LLC

Page 4 of 4 1 2 3 4

All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.

This site is provided for educational and informational purposes only, in accordance with our Terms of Use, and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.

Privacy Policy | Copyright © 2022. All Rights Reserved.