Mesna
Mesna Prescribing Information
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. (
2 DOSAGE AND ADMINISTRATIONMesna 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:
| 0 Hours | 4 Hours | 8 Hours | |
| Ifosfamide | 1.2 g/m2 | - | - |
| Mesna 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 | - | - |
| Mesna injection | 240 mg/m2 | - | - |
| Mesna tablets | - | 480 mg/m2 | 480 mg/m2 |
Maintain sufficient urinary output, as required for ifosfamide treatment, and monitor urine for the presence of hematuria.
2.1 Intravenous DosingMesna injection 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 injection is 60% of the ifosfamide dose. The recommended dosing schedule is outlined below in
1The 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. | |||
0 Hours | 4 Hours | 8 Hours | |
Ifosfamide | 1.2 g/m2 | - | - |
Mesna injection 1 | 240 mg/m2 | 240 mg/m2 | 240 mg/m2 |
2.2 Intravenous and Oral DosingMesna injection may be given on a fractionated dosing schedule of a single bolus injection followed by two oral administrations of mesna tablets as outlined below.
Mesna 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. Mesna 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 mesna is 100% of the ifosfamide dose. The recommended dosing schedule is outlined in
1The 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. | |||
0 Hours | 2 Hours | 6 Hours | |
Ifosfamide | 1.2 g/m2 | - | - |
Mesna injection 1 | 240 mg/m2 | - | - |
Mesna tablets | - | 480 mg/m2 | 480 mg/m2 |
The efficacy and safety of this ratio of intravenous and oral mesna 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 mesna should repeat the dose or receive intravenous mesna injection.
2.3 Monitoring for HematuriaMaintain 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 injection is given according to the recommended dosage schedule, dosage reductions or discontinuation of ifosfamide therapy may be required.
2.4 Preparation for Intravenous Administration and StabilityDetermine 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 per 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 mesna 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 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 injection may be mixed in the same bag provided the final concentration of ifosfamide does not exceed 50 mg per mL. Higher concentrations of ifosfamide may not be compatible with mesna injection 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 | - | - |
| Mesna 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 | - | - |
| Mesna injection | 240 mg/m2 | - | - |
| Mesna 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 Monitoring for HematuriaMaintain 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 injection is given according to the recommended dosage schedule, dosage reductions or discontinuation of ifosfamide therapy may be required.
- 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 PregnancyRisk SummaryMesna 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.
DataAnimal DataMesna 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 LactationRisk SummaryMesna 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.
- 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 PotentialMesna 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 TestingVerify the pregnancy status of females of reproductive potential prior to initiation of mesna in combination with ifosfamide.
ContraceptionFemalesAdvise females of reproductive potential to use effective contraception during treatment with mesna in combination with ifosfamide and for 6 months after the last dose.
MalesAdvise 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 UseMesna 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 ]. - Geriatric use: Dose selection should be cautious. ()
8.5 Geriatric UseClinical 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.
Mesna is contraindicated in patients known to be hypersensitive to mesna or to any of the excipients
5.1 Hypersensitivity ReactionsMesna 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.
- 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 ReactionsMesna 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 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. 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 ToxicitySerious 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 ]. - 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 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 ActivityMesna 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 AcidMesna may cause false-positive reactions in Tillman's reagent-based urine screening tests for ascorbic acid.