Mesnex
(Mesna)Mesnex Prescribing Information
MESNEX is indicated as a prophylactic agent in reducing the incidence of ifosfamide-induced hemorrhagic cystitis.
MESNEX is not indicated to reduce the risk of hematuria due to other pathological conditions such as thrombocytopenia.
MESNEX may be given on a fractionated dosing schedule of three bolus intravenous injections or a single bolus injection followed by two oral administrations of MESNEX 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 MESNEX to ifosfamide should be maintained.
MESNEX may be given on a fractionated dosing schedule of three bolus intravenous injections or a single bolus injection followed by two oral administrations of MESNEX 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 MESNEX to ifosfamide should be maintained. (2)
Intravenous Dosing Schedule:
0 Hours | 4 Hours | 8 Hours | |
Ifosfamide | 1.2 g/m2 | -- | -- |
MESNEX Injection | 240 mg/m2 | 240 mg/m2 | 240 mg/m2 |
Intravenous and Oral Dosing Schedule:
0 Hours | 2 Hours | 6 Hours | |
Ifosfamide | 1.2 g/m2 | -- | -- |
MESNEX Injection | 240 mg/m2 | -- | -- |
MESNEX 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)
MESNEX may be given on a fractionated dosing schedule of three bolus intravenous injections as outlined below.
MESNEX 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 MESNEX is 60% of the ifosfamide dose. The recommended dosing schedule is outlined below in .
Table 1. Recommended Intravenous Dosing Schedule | |||
0 Hours | 4 Hours | 8 Hours | |
Ifosfamide | 1.2 g/m2 | - | - |
MESNEX Injection 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 MESNEX to ifosfamide should be maintained. | 240 mg/m2 | 240 mg/m2 | 240 mg/m2 |
MESNEX may be given on a fractionated dosing schedule of a single bolus injection followed by two oral administrations of MESNEX tablets as outlined below.
MESNEX injection is given as intravenous bolus injections in a dosage equal to 20% of the ifosfamide dosage (w/w) at the time of ifosfamide administration. MESNEX tablets are given orally in a dosage equal to 40% of the ifosfamide dose 2 and 6 hours after each dose of ifosfamide. The total daily dose of MESNEX is 100% of the ifosfamide dose. The recommended dosing schedule is outlined in .
Table 2. Recommended Intravenous and Oral Dosing Schedule | |||
0 Hours | 2 Hours | 6 Hours | |
Ifosfamide | 1.2 g/m2 | - | - |
MESNEX injection 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 MESNEX to ifosfamide should be maintained. | 240 mg/m2 | - | - |
MESNEX tablets | - | 480 mg/m2 | 480 mg/m2 |
The efficacy and safety of this ratio of intravenous and oral MESNEX has not been established as being effective for daily doses of ifosfamide higher than 2 g/m2.
Patients who vomit within two hours of taking oral MESNEX should repeat the dose or receive intravenous MESNEX.
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 MESNEX is given according to the recommended dosage schedule, dosage reductions or discontinuation of ifosfamide therapy may be required.
Determine the volume of MESNEX injection for the intended dose.
Dilute the volume of MESNEX 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
The MESNEX injection multidose 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 MESNEX injection with epirubicin, cyclophosphamide, cisplatin, carboplatin, and nitrogen mustard.
The benzyl alcohol contained in MESNEX injection vials can reduce the stability of ifosfamide. Ifosfamide and MESNEX 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 MESNEX 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.
Intravenous Dosing Schedule:
0 Hours | 4 Hours | 8 Hours | |
Ifosfamide | 1.2 g/m2 | -- | -- |
MESNEX Injection | 240 mg/m2 | 240 mg/m2 | 240 mg/m2 |
Intravenous and Oral Dosing Schedule:
0 Hours | 2 Hours | 6 Hours | |
Ifosfamide | 1.2 g/m2 | -- | -- |
MESNEX Injection | 240 mg/m2 | -- | -- |
MESNEX Tablets | -- | 480 mg/m2 | 480 mg/m2 |
Maintain sufficient urinary output, as required for ifosfamide treatment, and monitor urine for the presence of 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 MESNEX is given according to the recommended dosage schedule, dosage reductions or discontinuation of ifosfamide therapy may be required.
• MESNEX injection: 1 g Multidose Vial, 100 mg/mL• MESNEX tablets: 400 mg film-coated tablets with functional score
• Pregnancy: Use only if clearly needed.8.1 PregnancyPregnancy Category BRisk SummaryThere are no studies of MESNEX in pregnant women. Reproduction studies performed in rats and rabbits at oral doses approximately 10 times the maximum recommended total daily intravenous-oral-oral human dose on a body surface area basis (1000 mg/kg in rabbits and 2000 mg/kg in rats) revealed no evidence of harm to the fetus due to mesna. The incidence of malformations in human pregnancies has not been established for MESNEX. All pregnancies, regardless of drug exposure, have a background rate of 2 to 4% for major malformations and 15 to 20% for pregnancy loss. Because animal reproductive studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
• Nursing mothers: Women should not breastfeed during therapy.8.3 Nursing MothersIt is not known whether mesna or dimesna is excreted in human milk. Benzyl alcohol present in maternal serum is likely to cross into human milk and may be orally absorbed by a nursing infant. Because many drugs are excreted in human milk and because of the potential for adverse reactions in nursing infants from MESNEX, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
• Geriatric use: Dose selection should be cautious.8.5 Geriatric UseClinical studies of MESNEX 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 MESNEX should remain unchanged.
MESNEX is contraindicated in patients known to be hypersensitive to MESNEX or to any of the excipients
MESNEX 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 MESNEX and provide supportive care.
• Hypersensitivity reactions: Anaphylactic reactions have been reported. Less severe hypersensitivity reactions may also occur. Monitor patients. If a reaction occurs, discontinue MESNEX and provide supportive care.5.1 Hypersensitivity ReactionsMESNEX 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 MESNEX 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 MESNEX and provide supportive care.5.2 Dermatologic ToxicityDrug 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. MESNEX 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 MESNEX and provide supportive care.
• Benzyl alcohol toxicity: The preservative benzyl alcohol has been associated with serious adverse reactions and death in neonates and premature infants. Avoid use in neonates, premature, and low-birth weight infants.5.3 Benzyl Alcohol ToxicityBenzyl alcohol, a preservative in MESNEX, has been associated with serious adverse reactions and death (including gasping syndrome) in neonates, premature, and low-birth weight infants. The minimum amount of benzyl alcohol at which toxicity may occur is not known. Consider the combined daily metabolic load of benzyl alcohol from all sources when prescribing MESNEX (10.4 mg benzyl alcohol per mL). Neonates, premature, and low-birth weight infants, as well as patients receiving high dosages, may be more likely to develop toxicity. Monitor patients for signs or symptoms of toxicity. Avoid use in neonates, premature, and low-birth weight infants
[See Use in Specific Populations (8.4)].• Laboratory test alterations: False positive tests for urinary ketones and interference with enzymatic CPK activity tests have been seen.5.4 Laboratory Test InterferencesFalse-Positive Urine Tests for Ketone BodiesA false positive test for urinary ketones may arise in patients treated with MESNEX 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 ActivityMESNEX may interfere with enzymatic creatinine phosphokinase (CPK) activity tests that use a thiol compound (e.g., N-acetylcysteine) for CPK reactiviation. This may result in a falsely low CPK level.
False-Positive Tests for Ascorbic AcidMESNEX may cause false-positive reactions in Tillman’s reagent-based urine screening tests for ascorbic acid.