(MES na)
Prevention of ifosfamide-induced hemorrhagic cystitis: Preventive agent to reduce the incidence of ifosfamide-induced hemorrhagic cystitis
Limitations of use: Mesna is not indicted to reduce the risk of hematuria due to other conditions such as thrombocytopenia
Hypersensitivity to mesna or any component of the formulation
Note: Mesna dosing schedule should be repeated each day ifosfamide is received. If ifosfamide dose is adjusted (decreased or increased), the mesna dose should also be modified to maintain the mesna-to-ifosfamide ratio.
Prevention of ifosfamide-induced hemorrhagic cystitis:
Standard-dose ifosfamide (manufacturer 's labeling): IV: Mesna dose is equal to 20% of the ifosfamide dose given for 3 doses: With the ifosfamide dose, hour 4, and at hour 8 after the ifosfamide dose (total daily mesna dose is 60% of the ifosfamide dose)
Oral mesna (following IV mesna; for ifosfamide doses ≤2 g/m2/day): Mesna dose (IV) is equal to 20% of the ifosfamide dose at hour 0, followed by mesna dose (orally) equal to 40% of the ifosfamide dose given 2 and 6 hours after the ifosfamide dose (total daily mesna dose is 100% of the ifosfamide dose). Note: If the oral mesna dose is vomited within 2 hours of administration, repeat the dose or administer IV mesna.
Short infusion standard-dose ifosfamide (<2.5 g/m2/day): ASCO guidelines: IV: Total mesna dose is equal to 60% of the ifosfamide dose, in 3 divided doses (each mesna dose as 20% of ifosfamide dose), given 15 minutes before the ifosfamide dose, and 4 and 8 hours after each dose of ifosfamide (Hensley, 2009)
Continuous infusion standard-dose ifosfamide (<2.5 g/m2/day): ASCO guidelines: IV: Mesna dose (as a bolus) is equal to 20% of the ifosfamide dose, followed by a continuous infusion of mesna at 40% of the ifosfamide dose; continue mesna infusion for 12-24 hours after completion of ifosfamide infusion (Hensley, 2009)
High-dose ifosfamide (>2.5 g/m2/day): ASCO guidelines: Evidence for use is inadequate; more frequent and prolonged mesna administration regimens may be required (Hensley, 2009)
Other dosing strategies used in combination with ifosfamide (off-label dosing):
Mesna continuous infusion: IV: 1.8 g/m2/day to 5 g/m2/day as a continuous infusion (100% of the ifosfamide dose), repeated each day ifosfamide is received; see protocols for specific details (Bacci, 2003; Kolb, 2003; Moskowitz, 2011)
Mesna bolus followed by continuous infusion: IV: 1000 mg/m2 1 hour prior to ifosfamide on day 1, followed by 3000 mg/m2/day continuous infusion (continuous infusion is 100% of the ifosfamide dose) on days 1, 2, and 3 (with sufficient hydration) every 3 weeks for 6 courses (Juergens, 2006)
Prevention of cyclophosphamide-induced hemorrhagic cystitis (off-label use):
HDCAV/IE regimen for Ewing sarcoma: Children ≥4 years and Adults <40 years: IV: 2100 mg/m2/day continuous infusion (mesna dose is equivalent to the cyclophosphamide dose) for 2 days with cyclophosphamide infusion during cycles 1, 2, 3, and 6 (Kolb, 2003)
Hyper-CVAD regimen for ALL: Adults: IV: 600 mg/m2/day continuous infusion (mesna continuous infusion is same total dose as cyclophosphamide) on days 1, 2, and 3, beginning with cyclophosphamide and ending 6 hours after the last cyclophosphamide dose during odd-numbered cycles (cycles 1, 3, 5, 7) of an 8-cycle phase (Kantarjian, 2000)
Refer to adult dosing.
Prevention of ifosfamide-induced hemorrhagic cystitis (off-label use):
Short infusion standard-dose ifosfamide (<2.5 g/m2/day): ASCO guidelines: Refer to adult dosing.
Continuous infusion standard-dose ifosfamide (<2.5 g/m2/day): ASCO guidelines: Refer to adult dosing.
Other dosing strategies used in combination with ifosfamide (off-label dosing):
Mesna continuous infusion: IV: 1.8 g/m2/day to 5 g/m2/day as a continuous infusion (100% of the ifosfamide dose), repeated each day ifosfamide is received; see protocols for specific details (Bacci, 2003; Kolb, 2003; Moskowitz, 2011)
Mesna bolus followed by continuous infusion: IV: 1000 mg/m2 1 hour prior to ifosfamide on day 1, followed by 3000 mg/m2/day continuous infusion (continuous infusion is 100% of the ifosfamide dose) on days 1, 2, and 3 (with sufficient hydration) every 3 weeks for 6 courses (Juergens, 2006)
Mesna (20% higher than ifosfamide) continuous infusion: IV: 3600 mg/m2/day continuous infusion for 4 days (mesna dose is 20% higher than ifosfamide), with hydration, during weeks 4 and 9 (3 additional postop courses were administered in good responders) (Le Deley, 2007)
Prevention of cyclophosphamide-induced hemorrhagic cystitis (off-label use): HDCAV/IE regimen for Ewing sarcoma: Children ≥4 years and Adults <40 years: IV: 2100 mg/m2/day continuous infusion (mesna dose is equivalent to the cyclophosphamide dose) for 2 days with cyclophosphamide infusion during cycles 1, 2, 3, and 6 (Kolb, 2003)
There are no dosage adjustments provided in the manufacturer 's labeling (has not been studied)
There are no dosage adjustments provided in the manufacturer 's labeling (has not been studied)
IV: Dilute in D5W, NS, D51/4NS, D51/3NS, D51/2NS, or lactated Ringers to a final concentration of 20 mg/mL.
Maintain adequate hydration and urinary output during ifosfamide treatment
IV: Administer as an IV bolus (per manufacturer); may also be administered by short infusion or continuous infusion (maintain continuous infusion for 12-24 hours after completion of ifosfamide infusion) (Hensley, 2009); refer to specific protocol for administration rate/details
Oral: Administer orally in tablet formulation; patients who vomit within 2 hours after taking oral mesna should repeat the dose or receive IV mesna. A solution may be prepared from solution for injection by dilution in syrup, juice, carbonate beverages, or milk (Goren, 1991); see Extemporaneously Prepared section.
Store intact vials and tablets at room temperature of 20 � �C to 25 � �C (68 � �F to 77 � �F); excursions are permitted between 15 � �C and 30 � �C (59 � �F and 86 � �F). Opened multidose vials may be stored and used for use up to 8 days after initial puncture. Solutions diluted for infusion in D5W, NS, D51/4NS, D51/3NS, D51/2NS, or lactated Ringers and stored at room temperature should be used within 24 hours. According to the manufacturer, mesna and ifosfamide may be mixed in the same bag if the final ifosfamide concentration is ≤50 mg/mL. Solutions of mesna and ifosfamide (1:1) in NS at a concentration of up to 20 mg/mL are stable for 14 days in PVC bags (Zhang, 2014). Solutions of mesna (0.5 to 3.2 mg/mL) and cyclophosphamide (1.8 to 10.8 mg/mL) in D5W are stable for 48 hours refrigerated or 6 hours at room temperature (Menard, 2003). Mesna injection prepared for oral administration is stable for at least 9 days undiluted in polypropylene syringes and stored at 5 � �C, 24 � �C, 35 � �C; for 7 days when diluted 1:2 or 1:5 with syrups and stored at 24 � �C in capped tubes; or for 24 hours at 5 � �C when diluted to 1:2, 1:10, and 1:100 in orange or apple juice, milk, or carbonated beverages (Goren, 1991).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Mesnex: 100 mg/mL (10 mL) [contains benzyl alcohol, edetate disodium]
Generic: 100 mg/mL (10 mL)
Tablet, Oral:
Mesnex: 400 mg [scored]
An oral solution may be prepared from mesna solution for injection. Dilute solution for injection to 20 mg/mL or 50 mg/mL with orange or grape syrup. Prior to administration, syrup-diluted solutions may be diluted to a final concentration of 1, 10, or 50 mg/mL with any of the following: carbonated beverages, apple juice, orange juice, or milk. Mesna injection prepared for oral administration is stable for at least 9 days undiluted in polypropylene syringes and stored at 5 � �C, 24 � �C, 35 � �C; for 7 days when diluted 1:2 or 1:5 with syrups and stored at 24 � �C in capped tubes; or for 24 hours at 5 � �C when diluted to 1:2, 1:10, and 1:100 in orange or apple juice, milk, or carbonated beverages. Dilution of mesna with diet or sugar-free preparations has not been evaluated.
Goren MP, Lyman BA, Li JT. The stability of mesna in beverages and syrup for oral administration. Cancer Chemother Pharmacol. 1991;28(4):298-301.[PMID: 1908750]Stable in D51/4NS, D51/3NS, D51/2NS, D5W, LR, NS.
Y-site administration: Incompatible with amphotericin B cholesteryl sulfate complex.
There are no known significant interactions.
Monitor urine for hematuria; urine output and hydration status; monitor for signs/symptoms of hypersensitivity or dermatologic toxicity
Urinary ketones: False-positive tests for urinary ketones may occur in patients receiving mesna with the use of nitroprusside-based urine tests, including dipstick tests.
CPK activity: Mesna may interfere with enzymatic creatine kinase (CPK) activity tests which use a thiol compound (eg, N-acetylcysteine) for CPK reactivation; may result in a falsely low CPK level.
Ascorbic acid: Mesna may result in false-positive reactions in Tillman 's reagent-based urine screening tests for ascorbic acid.
Mesna alone (frequency not defined):
Cardiovascular: Flushing
Central nervous system: Dizziness, drowsiness, headache, hyperesthesia, rigors
Dermatologic: Skin rash
Gastrointestinal: Anorexia, constipation, diarrhea, dysgeusia (with oral administration), flatulence, nausea, unpleasant taste (with oral administration), vomiting
Local: Injection site reaction
Neuromuscular & skeletal: Arthralgia, back pain
Ophthalmic: Conjunctivitis
Respiratory: Cough, flu-like symptoms, pharyngitis, rhinitis
Miscellaneous: Fever
<1% (Limited to important or life-threatening; mesna alone or in combination): Anaphylaxis, erythema at injection site, hypersensitivity reaction, hypertension, hypotension, increased serum transaminases, increased ST segment on ECG, limb pain, malaise, myalgia, pain at injection site, tachycardia, tachypnea, thrombocytopenia
Concerns related to adverse effects:
- Anaphylaxis/hypersensitivity reactions: Hypersensitivity reactions have been reported; symptoms ranged from mild hypersensitivity to systemic anaphylactic reactions and may include fever, hypotension, tachycardia, acute renal impairment, hypoxia, respiratory distress, urticaria, angioedema, signs of disseminated intravascular coagulation, hematologic abnormalities, increased liver enzymes, nausea, vomiting, arthralgia, and myalgia. Reactions may occur with the first exposure, or after several months of treatment. Monitor for signs/symptoms of reactions. May require discontinuation. Patients with autoimmune disorders receiving cyclophosphamide and mesna may be at increased risk. Mesna is a thiol compound; it is unknown if the risk for reaction is increased in patients who have had a reaction to other thiol compounds (eg, amifostine).
- Dermatologic toxicity: Drug rash with eosinophilia and systemic symptoms and bullous/ulcerative skin, and mucosal reactions consistent with Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) have been reported. The skin and mucosal reactions may be characterized by rash, pruritus, urticaria, erythema, burning sensation, angioedema, periorbital edema, flushing, and stomatitis. Reactions may occur with the first exposure, or after several months of treatment. May require discontinuation.
- Hematuria: Monitor urine for hematuria. Severe hematuria despite utilization of mesna may require ifosfamide dose reduction or discontinuation. Examine morning urine specimen for hematuria prior to ifosfamide or cyclophosphamide treatment; if hematuria (>50 RBC/HPF) develops, reduce the ifosfamide/cyclophosphamide dose or discontinue the drug; will not prevent hemorrhagic cystitis in all patients. Mesna will not reduce the risk of hematuria related to thrombocytopenia. Patients should receive adequate hydration during treatment.
- Ifosfamide/cyclophosphamide toxicities: Mesna is intended for the prevention of hemorrhagic cystitis and will not prevent or alleviate other toxicities associated with ifosfamide or cyclophosphamide.
Dosage form specific issues:
- Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol; large amounts of benzyl alcohol ( ≥99 mg/kg/day) have been associated with a potentially fatal toxicity ( "gasping syndrome " �) in neonates; the "gasping syndrome " � consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP [Inactive" 1997]; CDC, 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors, 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer 's labeling.
B
Adverse effects were not observed in animal reproduction studies. Use during pregnancy only if clearly needed.
In blood, mesna is oxidized to dimesna which in turn is reduced in the kidney back to mesna, supplying a free thiol group which binds to and inactivates acrolein, the urotoxic metabolite of ifosfamide and cyclophosphamide
0.65 � � 0.24 L/kg; distributed to total body water
Rapidly oxidized to mesna disulfide (dimesna) in the intravascular compartment. Mesna and dimesna do not undergo hepatic metabolism.
Urine (32% as mesna; 33% as dimesna); majority of IV dose excreted within 4 hours
Plasma: Oral: Free mesna: 1.5 to 4 hours
Mesna: ~22 minutes; Dimesna: ~70 minutes
69% to 75%
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience diarrhea, constipation, fatigue, lack of appetite, hair loss, headache, abdominal pain, or injection site irritation. Have patient report immediately to prescriber signs of infection, burning sensation, urinary retention, change in amount of urine passed, flushing, muscle pain, joint pain, severe nausea, severe vomiting, severe loss of strength and energy, wheezing, angina, shortness of breath, tachycardia, hematuria, bruising, bleeding, severe dizziness, passing out, flu-like syndrome, or signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes) (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.