Mesna

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

Mesna injection may be given on a fractionated dosing schedule of three bolus intravenous injections or a 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. (

Intravenous Dosing Schedule:

Intravenous and Oral Dosing Schedule:

Maintain sufficient urinary output, as required for ifosfamide treatment, and monitor urine for the presence of hematuria. (

• Mesna Injection: 1 gram Multi-Dose Vial, 100 mg per mL

• Pregnancy: Mesna in combination with ifosfamide can cause fetal harm. Advise patients of potential risk to a fetus. (
  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 and Use in Specific Populations ].

  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.
  )
• Lactation: Do not breastfeed. (
  8.2 Lactation

  Risk Summary

  Mesna 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 a 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 and Use in Specific Populations ]

  .

  Because of the potential for serious adverse reactions in a breastfed child, advise lactating women not to breastfeed during treatment and for 1 week after the last dose of mesna or ifosfamide.
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• Females and Males of Reproductive Potential: Advise patients to use effective contraception. Verify pregnancy status prior to initiation of mesna in combination with ifosfamide. (
  8.3 Females and Males of Reproductive Potential

  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 contraception and effects on fertility.

  Pregnancy Testing

  Verify the pregnancy status of females of reproductive potential prior to initiation of mesna in combination with ifosfamide.

  Contraception

  Females

  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.

  Males

  Advise males 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.
  )
• Pediatric use: In premature neonates and low-birth weight infants, avoid use of benzyl alcohol–containing solutions. (
  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 ]

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• Geriatric use: Dose selection should be cautious. (
  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.
  )

• Hypersensitivity reactions: Anaphylactic reactions have been reported. Less severe hypersensitivity reactions may also occur. Monitor patients. If a reaction occurs, discontinue mesna and provide supportive care. (
  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.
  )
• 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 a reaction occurs, 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.
  )
• 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 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. Mesna tablets do not contain benzyl alcohol

  [see Use in Specific Populations ]

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• Laboratory test alterations: False positive tests for urinary ketones and interference with enzymatic CPK activity tests have been seen. (
  5.4 Laboratory Test Interferences

  False-Positive Urine Tests for Ketone Bodies

  A 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 a false positive result (cherry-red color that fades) and a 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 a thiol compound (e.g., N-acetylcysteine) for CPK reactivation. This may result in a falsely low CPK level.

  False-Positive Tests for Ascorbic Acid

  Mesna may cause false-positive reactions in Tillman's reagent-based urine screening tests for ascorbic acid.
  )