Mesna Drug Information

Mesna Injection is indicated as a prophylactic agent in reducing the incidence of ifosfamide-induced hemorrhagic cystitis. Mesna Injection is a cytoprotective agent indicated as a prophylactic agent in reducing the incidence of ifosfamide-induced hemorrhagic cystitis. Limitation of Use: Mesna Injection is not indicated to reduce the risk of hematuria due to other pathological conditions such as thrombocytopenia.

Limitation of Use: Mesna Injection is not indicated to reduce the risk of hematuria due to other pathological conditions such as thrombocytopenia.

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 to 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 two Phase 1 multiple-dose studies where healthy volunteers received mesna tablets alone or intravenous mesna 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. 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 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 1 Intravenous dosing of ifosfamide and mesna followed by either intravenous or oral doses of mesna according to the applicable dosage schedule.

Mesna Regimen Intravenous-Intravenous-Intravenous 1 Intravenous-Oral-Oral 1 N exposed 119 (100.0%) 119 (100%) Incidence of AEs 101 (84.9%) 106 (89.1%) Nausea 65 64 Vomiting 35 45 Constipation 28 21 Leukopenia 25 21 Fatigue 24 24 Fever 24 18 Anorexia 21 19 Thrombocytopenia 21 16 Anemia 20 21 Granulocytopenia 16 15 Asthenia 15 21 Abdominal Pain 14 18 Alopecia 12 13 Dyspnea 11 11 Chest Pain 10 11 Hypokalemia 10 11 Diarrhea 9 17 Dizziness 9 5 Headache 9 13 Pain 9 10 Sweating Increased 9 2 Back Pain 8 6 Hematuria 8 7 Injection Site Reaction 8 10 Edema 8 9 Edema Peripheral 8 8 Somnolence 8 12 Anxiety 7 4 Confusion 7 6 Face Edema 6 5 Insomnia 6 11 Coughing 5 10 Dyspepsia 4 6 Hypotension 4 6 Pallor 4 6 Dehydration 3 7 Pneumonia 2 8 Tachycardia 1 7 Flushing 1 6

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 a population of unknown size, precise estimates of frequency cannot be made. Cardiovascular : Hypertension Gastrointestinal : Dysgeusia Hepatobiliary : Hepatitis Nervous System : Convulsion Respiratory : Hemoptysis

No clinical drug interaction studies have been conducted with mesna.

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. 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, 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.

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 .

Mesna is contraindicated in patients known to be hypersensitive to mesna or to any of the excipients. Known hypersensitivity to mesna or to any of the excipients in mesna, including benzyl alcohol.

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 grams to 6.9 grams of mesna resulted in hypersensitivity reactions including mild hypotension, shortness of breath, asthma exacerbation, rash, and flushing.