Mesna

FDA Drug Information • Also known as: Mesna, Mesnex

Brand Names
Mesna, Mesnex
Dosage Form
POWDER
Product Type
BULK INGREDIENT

Description

11 DESCRIPTION Mesna 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 C 2 H 5 NaO 3 S 2 and a molecular weight of 164.18. Its structural formula is as follows: HS–CH2–CH2SO3–Na+ Mesna injection is a sterile, nonpyrogenic, aqueous solution of clear and colorless appearance in clear glass Multiple-Dose vials for intravenous administration. Mesna injection contains 100 mg/mL mesna, 0.25 mg/mL edetate disodium and sodium hydroxide for pH adjustment. Mesna Injection Multiple-Dose vials also contain 10.4 mg/mL of benzyl alcohol as a preservative. The solution has a pH range of 6.5 to 7.3.

What Is Mesna Used For?

1 INDICATIONS AND USAGE Mesna Injection is indicated as a prophylactic agent in reducing the incidence of ifosfamide-induced hemorrhagic cystitis L imitation of Use: Mesna Injection is not indicated to reduce the risk of hematuria due to other pathological conditions such as thrombocytopenia. Mesna isa cytoprotective agent indicated asa prophylactic agent in reducing the incidence of ifosfamide-induced hemorrhagic cystitis. ( 1 ) Limitation of Use: Mesna is not indicated to reduce the risk of hematuria due to other pathological conditions such as thrombocytopenia. ( 1 )

Dosage and Administration

2 DOSAGE AND ADMINISTRATION Mesna may be given on a fractionated dosing schedule of three bolus intravenous injections. 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: 0 Hours 4 Hours 8 Hours Ifosfamide 1.2 g/m 2 -‑ -‑ Mesna Injection 240 mg/m 2 240 mg/m 2 240 mg/m 2 Maintain sufficient urinary output, as required for ifosfamide treatment, and monitor urine for the presence of hematuria. ( 2.3 ) 2.1 Intravenous Dosing Mesna may be given on a fractionated dosing schedule of three bolus intravenous injections as outlined below. Mesna injection is given as intravenous bolus injections in a dosage equal to 20% of the ifosfamide dosage weight by weight (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 in Table 1 . T able 1. Recommended Intravenous Dosing Schedule 0 Hours 4 Hours 8 Hours Ifosfamide 1.2 g/m 2 - - Mesna Injection 1 240 mg/m 2 240 mg/m 2 240 mg/m 2 1 The 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. 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 is given according to the recommended dosage schedule, dosage reductions or discontinuation of ifosfamide therapy may be required. 2.4 Preparation for Intravenous Administrationand Stability P re paration Determine 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 a 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, USP
  • 5% Dextrose and 0.45% Sodium Chloride Injection, USP
  • 0.9% Sodium Chloride Injection, USP
  • Lactated Ringer’s Injection, USP S tability The mesna injection multiple-dose vials may be stored and used for up to 8 days after initial puncture. Store diluted solutions at 25°C (77°F). 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 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 and may reduce the stability of ifosfamide. Parenteral drug products should be inspected visually for particulate matter and discoloration...

  • Side Effects (Adverse Reactions)

    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 a 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 Hikma Pharmaceuticals USA Inc. at 1-877-845-0689 or FDA at 1-800-332-1088 or www.fda.gov/medwatch. "1-800-FDA-1088" 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a 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 1 studies in which single intravenous doses of 600-1200 mg mesna Injection without concurrent chemotherapy were administered to a total of 53 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 addition, constipation was reported by healthy volunteers who had received repeated doses of intravenous mesna. 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 a 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 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 Regimen I ntravenous-Intravenous-Intravenous 1 N exposed 119 (100%) Incidence of AEs 101 (84.9%) Nausea 65 (54.6) Vomiting 35 (29.4) Constipation 28 (23.5) Leukopenia 25 (21) 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) Insomnia 6 (5) 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) 1 Intravenous dosing of ifosfamide and mesna followed by intravenous doses of mesna...

  • Drug Interactions

    7 DRUG INTERACTIONS No clinical drug interaction studies have been conducted with mesna.

    Contraindications

    4 CONTRAINDICATIONS Mesna is contraindicated in patients known to be hypersensitive to mesna or to any of the excipients [see Warnings and Precautions (5.1 )].

  • Known hypersensitivity to mesna or to any of the excipients, including benzyl alcohol. ( 4 )

  • Pregnancy and Breastfeeding

    8.1 Pregnancy Risk Summary Mesna is used in combination with ifosfamide or other cytotoxic agents. Ifosfamide can cause fetal harm when administered to a 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 a 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 a 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 2 to 4% and 15 to 20%, respectively. Data Animal Data Mesna 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, 1000, 1500, and 2000 mg/kg) and rabbits (500 and 1000 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.

    Overdosage

    10 OVERDOSAGE There is no known antidote for mesna. In a clinical trial, 11 patients received intravenous mesna 10 mg/kg to 66 mg/kg per day for 3 to 5 days. Patients also received ifosfamide or cyclophosphamide. Adverse reactions included nausea, vomiting, diarrhea and fever. An increased rate of these adverse reactions has also been found in oxazaphosphorine-treated patients receiving ≥80 mg mesna per kg per day intravenously compared with patients receiving lower doses or hydration treatment only. Postmarketing, administration of 4.5 g to 6.9 g of mesna resulted in hypersensitivity reactions including mild hypotension, shortness of breath, asthma exacerbation, rash, and flushing.

    How Supplied

    16 HOW SUPPLIED/STORAGE AND HANDLING Mesna Injection is available as follows: NDC 0143-9260-01 1 gram; 10 mL Multiple-Dose Vial, individually boxed. Store at 20° to 25°C (68° to 77°F) [see USP for Controlled Room Temperature]. If mesna is co-administered with ifosfamide, refer to the ifosfamide prescribing information for safe handling instructions.

    About This Information

    This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

    What are side effects?

    Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

    What are drug interactions?

    Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.