Warnings for Mesnex
Included as part of the PRECAUTIONS section.
Precautions for Mesnex
Hypersensitivity Reactions
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.
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. 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
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. MESNEX injection contains 10.4 mg/mL of the preservative benzyl alcohol. Avoid use of MESNEX injection in premature neonates and low-birth weight infants. MESNEX tablets do not contain benzyl alcohol [see Use In Specific Populations].
Laboratory Test Interferences
False-Positive Urine Tests For Ketone Bodies
A 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 Activity
MESNEX 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 Acid
MESNEX may cause false-positive reactions in Tillman’s reagent-based urine screening tests for ascorbic acid.
Use In Patients With A History Of Adverse Reactions To Thiol Compounds
MESNEX is a thiol compound, i.e., a sulfhydryl (SH) group-containing organic compound. Hypersensitivity reactions to mesna and to amifostine, another thiol compound, have been reported. It is not clear whether patients who experienced an adverse reaction to a thiol compound are at increased risk for a hypersensitivity reaction to MESNEX.
Patient Counseling Information
See FDA-approved patient labeling (PATIENT INFORMATION).
Hypersensitivity
- Advise the patient to discontinue MESNEX and seek immediate medical attention if any signs or symptoms of a hypersensitivity reaction, including systemic anaphylactic reactions occur [see WARNINGS AND PRECAUTIONS].
Dosing Instructions
- Advise the patient to take MESNEX at the exact time and in the exact amount as prescribed. Advise the patient to contact their healthcare provider if they vomit within 2 hours of taking oral MESNEX, or if they miss a dose of oral MESNEX [see DOSAGE AND ADMINISTRATION].
Hemorrhagic Cystitis
- MESNEX does not prevent hemorrhagic cystitis in all patients nor does it prevent or alleviate any of the other adverse reactions or toxicities associated with ifosfamide. Advise the patient to report to their healthcare provider if his/her urine has turned a pink or red color [see DOSAGE AND ADMINISTRATION].
- Advise the patient to drink 1 to 2 liters of fluid each day during MESNEX therapy [see DOSAGE AND ADMINISTRATION].
Dermatologic Toxicity
- Advise the patient that Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug rash with eosinophilia and systemic symptoms and bullous and ulcerative skin and mucosal reactions have occurred with MESNEX. Advise the patient to report to their healthcare provider if signs and symptoms of these syndromes occur [see WARNINGS AND PRECAUTIONS].
Benzyl Alcohol Toxicity
- Advise patients that serious adverse reactions are associated with the benzyl alcohol found in MESNEX and other medications in premature neonates and low-birth weight infants [see WARNINGS AND PRECAUTIONS and Use In Specific Populations].
Embryo-Fetal Toxicity
- MESNEX is used in combination with ifosfamide. Ifosfamide or other cytotoxic agents can cause fetal harm when administered to a pregnant woman. Inform female patients of the risk to a fetus and potential loss of the pregnancy. Advise females to inform their healthcare provider if they are pregnant or become pregnant [see Use In Specific Populations].
Contraception
- Advise females of reproductive potential to use effective contraception during treatment with MESNEX in combination with ifosamide and for 6 months after the last dose [see Use In Specific Populations].
- Advise male patients with female partners of reproductive potential to use effective contraception during treatment with MESNEX in combination with ifosamide and for 3 months after the last dose [see Use In Specific Populations].
Lactation
- Advise lactating women not to breastfeed during treatment with MESNEX or ifosfamide and for 1 week after the last dose [see Use In Specific Populations].
Nonclinical Toxicology
Carcinogenesis, Mutagenesis, Impairment Of Fertility
No long-term studies in animals have been performed to evaluate the carcinogenic potential of mesna.
Mesna was not genotoxic in the in vitro Ames bacterial mutagenicity assay, the in vitro mammalian lymphocyte chromosomal aberration assay or the in vivo mouse micronucleus assay.
No studies on male or female fertility were conducted. No signs of male or female reproductive organ toxicity were seen in 6-month oral rat studies (≤ 2000 mg/kg/day) or 29-week oral dog studies (520 mg/kg/day) at doses approximately 10-fold higher than the maximum recommended human dose on a body surface area basis.
Use In Specific Populations
Pregnancy
Risk Summary
MESNEX 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.
MESNEX 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 2-4% and 15-20%, respectively.
Data
Animal Data
MESNEX 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.
Lactation
Risk Summary
MESNEX 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.
MESNEX 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 MESNEX or ifosfamide.
Females And Males Of Reproductive Potential
MESNEX 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 MESNEX in combination with ifosfamide.
Contraception
Females
Advise females of reproductive potential to use effective contraception during treatment with MESNEX 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 MESNEX in combination with ifosfamide and for 3 months after the last dose.
Pediatric Use
MESNEX 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 MESNEX injection in premature neonates and low-birth weight infants [see WARNINGS AND PRECAUTIONS].
Geriatric Use
Clinical 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.
Use In Patients With Renal Impairment
No clinical studies were conducted to evaluate the effect of renal impairment on the pharmacokinetics of MESNEX.
Use In Patients With Hepatic Impairment
No clinical studies were conducted to evaluate the effect of hepatic impairment on the pharmacokinetics of MESNEX.