Mesna (Ifomes, Mesnex) is available as an oral and intravenous formulation. It is a chemo-protectant and is used to prevent ifosfamide or cyclophosphamide-induced hemorrhagic cystitis.

Mesna (Ifomes, Mesnex) Uses:

• Prevention of ifosfamide-induced hemorrhagic cystitis:

  • Used in the Preventive agent to reduce the incidence of ifosfamide-induced hemorrhagic cystitis.
  • Limitations of use: Mesna is not indicated to reduce the hazard of hematuria due to other conditions such as thrombocytopenia

• Off label Use of Mensa (Ifomes) in Adults:

  • Used in the prevention of cyclophosphamide-induced hemorrhagic cystitis (with high-dose cyclophosphamide)
  • Used in the prevention of cyclophosphamide-induced hemorrhagic cystitis in patients with rheumatic or autoimmune disorders

Mesna (Ifomes, Mesnex) Dose in Adults:

Note:

• Mesna dosing schedule should be repeated each day ifosfamide is considered.
• If the ifosfamide dose is adjusted (decreased or increased), the mesna dose should also be modified to maintain the mesna-to-ifosfamide ratio.

Mesna (Ifomes) Dose in the Prevention of ifosfamide-induced hemorrhagic cystitis:

• Standard-dose ifosfamide (manufacturer’s labeling):

  • IV: Each mesna dose is equal to 20% of the daily ifosfamide dose given for 3 doses:
    • With the ifosfamide dose (hour 0), hour 4, and at hour 8 after the ifosfamide dose (total daily mesna dose is 60% of the daily ifosfamide dose).

  • Oral mesna (following IV mesna; for ifosfamide doses ≤2 g/m²/day):

    • Mesna dose (IV) is equal to 20% of the daily ifosfamide dose at hour 0, followed by 2 mesna doses (orally), each equal to 40% of the daily ifosfamide dose given 2 and 6 hours after the ifosfamide dose (total daily mesna dose is 100% of the daily ifosfamide dose).
    • Note: If the oral mesna dose is vomited within 2 hours of administration, repeat the oral mesna 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 daily ifosfamide dose), given 15 minutes before the ifosfamide dose, and 4 and 8 hours after each dose of ifosfamide.

• Continuous infusion standard-dose ifosfamide (<2.5 g/m²/day):

  • ASCO guidelines: IV:
    • Mesna dose (as a bolus) is equal to 20% of the daily ifosfamide dose, followed by a continuous infusion of mesna at 40% of the daily ifosfamide dose;
    • continue mesna infusion for 12 to 24 hours after completion of ifosfamide infusion.

• 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.

• 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.
  • Mesna bolus followed by continuous infusion:
    • IV: 1 g/m² 1 hour prior to ifosfamide on day 1, followed by 3 g/m²/day continuous infusion (continuous infusion is 100% of the daily ifosfamide dose) on days 1, 2, and 3 (with sufficient hydration) every 3 weeks for 6 courses.

Mesna Dose in the Prevention of cyclophosphamide-induced hemorrhagic cystitis (in patients with cancer; off-label):

• HDCAV/IE regimen for Ewing sarcoma:

  • Adults <40 years of age: IV:

    • Cycles 1, 2, 3, and 6 (cyclophosphamide-containing regimen):
      • 2.1 g/m²/day continuous infusion (mesna dose is equivalent to the daily cyclophosphamide dose) for 2 days with cyclophosphamide infusion during cycles 1, 2, 3, and 6.
    • Cycles 4, 5, and 7 (ifosfamide-containing regimen):
      • 1.8 g/m²/day continuous infusion (mesna dose is equivalent to the daily ifosfamide dose) for 5 days with ifosfamide infusion during cycles 4, 5, and 7.

  • Hyper-CVAD regimen for acute lymphocytic leukemia:

    • IV: 600 mg/m²/day continuous infusion (mesna continuous infusion is same total daily 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.

Mesna (Ifomes) Dose in the Prevention of cyclophosphamide-induced hemorrhagic cystitis in patients with rheumatic or autoimmune disorders (off-label; based on limited data):

• IV: Each mesna dose is equal to 20% of the daily cyclophosphamide dose given for 3 doses, 15 to 30 minutes prior to cyclophosphamide (hour 0), and 4 and 8 hours after cyclophosphamide (if administering mesna orally, each oral mesna dose is equal to 40% of the daily cyclophosphamide dose, with the first dose administered 2 hours prior to cyclophosphamide, and 4 and 8 hours after cyclophosphamide) OR
• each mesna dose is equal to 20% of the daily cyclophosphamide dose given for 3 doses at 3, 6, and 8 hours following cyclophosphamide each day for 4 days.

Mesna (Ifomes, Mesnex) Dose in Children:

Note: Dose, frequency, number of doses, and start date may vary by protocol and treatment phase. Refer to individual protocols.

Mesna (Ifomes) Dose in the Prevention of ifosfamide-induced hemorrhagic cystitis:

Mesna dosing schedule should be repeated each day ifosfamide is received according to protocol. If ifosfamide dose is adjusted (decreased or increased), the mesna dose should also be modified to maintain the mesna-to-ifosfamide ratio;

• Children, and Adolescents:

  • Standard-dose ifosfamide:

    • Note: ASCO defines standard-dose ifosfamide IV as <2500 mg/m²/day; other pediatric oncology experts suggest ≤2000 mg/m²/day in protocols.
    • ASCO defines standard-dose ifosfamide oral as ≤2000 mg/m²/day.

    • Manufacturer's labeling:

      • IV: Mesna dose is equal to 20% of the ifosfamide dose given for 3 doses:
        • With the ifosfamide dose (hour 0), at hour 4, and at hour 8 after the ifosfamide dose (total daily mesna dose is 60% of the ifosfamide dose).
        • Note: Safety and efficacy not established for ifosfamide doses >2000 mg/m²/day.

    • Alternate dosing: Limited data available:

    • IV:

      • Short IV infusion (intermittent):

        • ASCO guidelines:
          • Mesna dose equal to 60% of the ifosfamide dose given in 3 divided doses (20% each) 15 minutes before the ifosfamide dose and at 4 and 8 hours after the start of ifosfamide.

      • Continuous IV infusion:

        • Dosing regimens variable: ASCO guidelines:
          • Mesna dose (as an IV bolus) equal to 20% of the ifosfamide dose, followed by a continuous IV infusion of mesna at 40% of the ifosfamide dose;
          • continue mesna infusion for 12 to 24 hours after completion of ifosfamide infusion.
          • Some centers have used a mesna dose equal to 60% to 100% of the ifosfamide dose as a continuous IV infusion beginning 15 to 30 minutes before the first ifosfamide dose and completed at least 8 hours after the end of the ifosfamide infusion.

    • Oral:

      • ASCO guidelines:

        • Total mesna dose equal to 100 percent of the ifosfamide dose, begin with IV dose equal to 20 percent for initial dose followed by oral dose at 40 percent of the ifosfamide dose at 2 and 6 hours after the start of ifosfamide;
        • Note: Typically, oral doses of mesna are twice the IV dose.

      • High-dose ifosfamide:

      • Note: ASCO defines high dose as ifosfamide dosage 2500  or more than 2500 mg per m² per day;
      • other pediatric oncology experts suggest 2000 or more than 2000 mg per m² per day in protocols:
        • Limited data available; dosing regimens variable:
        • IV: ASCO considers the evidence for use inadequate and dosing recommendations are not established;
        • more frequent and prolonged mesna administration regimens may be required.
        • Some centers have used a mesna dose equal to 100 percent of the ifosfamide dose as a short IV infusion 5 divided doses (0, 3, 6, 9, and 12) hours after the start of ifosfamide) OR as a continuous IV infusion beginning 15 to 30 minutes before the first ifosfamide dose and completed at least 12 hours after the end of the ifosfamide infusion.
      • Other dosing strategies have been used in combination with ifosfamide for specific regimens/protocols: Limited data available:

      • Mesna continuous IV infusion:

        • Children and Adolescents:
        • IV: 1800 mg per m² per day to 5000 mg per m² per day as a continuous infusion (100 percent of the ifosfamide dose), repeated each day ifosfamide is received; see protocols for specific details.

      • Mesna IV bolus followed by continuous IV infusion:

        • Children and Adolescents:
        • 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);
        • administer with subsequent ifosfamide doses.

      • Mesna (20 percent higher than ifosfamide) continuous IV infusion:

        • Children and Adolescents:
        • IV: 3600 mg per m² per day continuous infusion for 4 days (mesna dose is 20 percent higher than ifosfamide), with hydration, administer with subsequent ifosfamide doses.

Mesna (Ifomes) Dose in the Prevention of cyclophosphamide-induced hemorrhagic cystitis:

Note:

• Specific protocols should be consulted for combination regimens with cyclophosphamide.
• Mesna dosing schedule is typically repeated with each day cyclophosphamide is received; mesna dosing should be adjusted if cyclophosphamide dose is adjusted (decreased or increased) to maintain the mesna-to-cyclophosphamide ratio for the protocol;

• Infants, Children, and Adolescents:

  • Standard (low)-dose cyclophosphamide:

  • Note: Some pediatric oncology experts have defined as cyclophosphamide dose <1800 mg/m /day in protocols.
    • IV: Reported regimens variable:
      • Mesna doses equivalent to usually 60% to 100% of the cyclophosphamide daily dose although some protocols have used up to 160%.

  • Short IV infusion (intermittent):

    • Mesna dose equal to 60 percent of the cyclophosphamide dose given in 3 divided doses (0, 4, and 8 hours after the start of cyclophosphamide) has been used by some centers;
    • others have used a mesna dose equal to 100 percent of the cyclophosphamide dose as short IV infusions in 5 divided doses (0, 3, 6, 9, and 12 hours after the start of cyclophosphamide).

  • Continuous IV infusion:

    • Some centers have used a mesna dose equal to 60 percent of the cyclophosphamide dose as a continuous IV infusion beginning 15 to 30 minutes before the first cyclophosphamide dose and completed at least 8 hours after the end of the cyclophosphamide infusion.
    • Oral: Some centers have used a total mesna dose equal to 100 percent of the cyclophosphamide dose, begin with an IV dose equal to 20 percent for the initial dose followed by an oral dose at 40 percent of the cyclophosphamide dose at 2 and 6 hours after the start of cyclophosphamide;
    • Note: Typically, oral doses of mesna are twice the IV dose.

  • High-dose cyclophosphamide:

  • Note: Some pediatric oncology experts have defined cyclophosphamide dose ≥1800 mg/m²/day in protocols:
    • IV: Some centers have used a mesna dose equal to 100% of the cyclophosphamide dose as short IV infusions in 5 divided doses (0, 3, 6, 9, and 12 hours after the start) or as a continuous IV infusion beginning 15 to 30 minutes before the first cyclophosphamide dose.

  • Other dosing strategies have been used in combination with cyclophosphamide for specific regimens/protocols:

    • Limited data available: HDCAV/IE regimen for Ewing sarcoma: Children and Adolescents:
      • 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.

Mesna Pregnancy Category: B

• Reports have indicated that mesna can be used to treat ifosfamide-induced hemorhagic cystitis during pregnancy.
• Mesna injection uses benzyl alcohol to preserve it. Fetuses are unlikely to be exposed due to rapid maternal metabolism.
• Combining Mesna with cytotoxic drugs that can cause harm to fetal health (refer specific monographs) is a good idea.
• Before treatment begins in females with reproductive potential, verify your pregnancy status. 
• Effective contraception should be used by females with reproductive potential during treatment with mesna/ifosfamide and for six months following the last mesna/ifosfamide dosage.
• Effective contraception should be used by males who have female partners with reproductive potential during mesna/ifosfamide treatment as well as for three months following the last mesna/ifosfamide dosage.

Mesna (Ifomes) use during breastfeeding:

• It is unknown if breast milk contains mesna.
• Some formulations contain benzyl alcohol as a component.
• Manufacturer notes that exposure to breastfeeding infants is unlikely because of rapid maternal metabolism.
• However, adverse reactions have been reported in premature neonates and infants born to low birth weights who received benzyl Alcohol IV.
• Therefore, breastfeeding is not recommended for therapy or for at least one week after receiving the last mesna.
• Mesna can be administered with cytotoxic drugs that could cause harm to breastfed infants (refer to the specific monographs).

Ifomes Dose in Kidney Disease:

Manufacturer’s labeling doesn't provide any dosage adjustments (has not been studied)

Ifomes Dose in Liver disease:

Manufacturer’s labeling doesn't provided any dosage adjustments (has not been studied)

Side effects of Mesna (Ifomes):

• 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

Contraindications to Mesna (Ifomes):

Hypersensitivity to mesna, or any component of the formula.

Warnings and precautions

• Dermatologic toxicities:

  • Reports of drug rash with eosinophilia, systemic symptoms, bullous/ulcerative and mucosal reactions consistent in Stevens-Johnson syndrome and toxic epidermal necrolysis have been made.
  • Skin and mucosal reactions can include erythema and pruritus, urticaria and burning sensations.
  • You may experience reactions after the first mesna treatment or after several months. Stop mesna treatment immediately if severe dermatologic toxicity is observed.

• Hematuria

  • Observe urine for hematuria. If severe hematuria is not due to mesna use, you may need to reduce or stop taking mesna.
  • Examine urine specimen for hematuria prior to ifosfamide (or cyclophosphamide) treatment; if hematuria (>50 RBC/HPF) develops, reduce the ifosfamide/cyclophosphamide dose or discontinue; mesna may not prevent hemorrhagic cystitis in all patients. Patients must be hydrated during treatment.

• Hypersensitivity

  • Reports of hypersensitivity reactions, including anaphylaxis, have been made.
  • You may also experience symptoms like fever, tachycardia and acute renal impairment, hypotension or urticaria, hypoxia, angioedema, angioedema and hypoxia.
  • You may experience reactions after the first mesna treatment or after prolonged treatment.
  • Pay attention to any signs or symptoms of allergic reactions. Stop mesna immediately and seek supportive care if hypersensitivity develops.
  • Mesna is a compound made of thiols. It is not known if patients who have experienced reactions to other thiol compounds, such as amifostine, are at greater risk.

• Ifosfamide/cyclophosphamide toxicities:

  • Mesna is used to treat hemorhagic cystitis. It will not reduce or eliminate other toxicities that can be caused by cyclophosphamide and ifosfamide.

Monitoring parameters:

• Monitor urine for signs of hematuria;
• monitor urine output and hydration status;
• verify pregnancy status prior to treatment initiation in females of reproductive potential.
• Monitor for signs/symptoms of hypersensitivity or dermatologic toxicity.

How to administer Mesna (Ifomes)?

Maintain adequate hydration and urinary output during ifosfamide (or cyclophosphamide) treatment. IV:

• Administer as an IV bolus (per manufacturer);
• It may also be administered by a short infusion or continuous infusion (maintain continuous infusion for 12 to 24 hours after completion of ifosfamide infusion).

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, carbonated beverages, or milk.

Mechanism of action of Mesna (Ifomes):

• Mesna is oxidized in blood to dimesna.
• This in turn is decreased in the kidney back into mesna.

Protein binding:

• From 69 to 75 percent

Metabolism:

• Rapidly oxidized to mesna diulfide (dimesna), in the intravascular compartment. Mesna and dimesna are not subject to hepatic metabolism.

Bioavailability: Oral:

• Free: 58 percent (range: 45 percent to 71 percent); not affected by food.

Half-life elimination:

• Mesna: ~22 minutes;
• Dimesna: ~70 minutes.

Time to peak, plasma: Oral:

• Free mesna: 1.5 to 4 hours;
• Total mesna: 3 to 7 hours.

Excretion:

• Urine (32 percent as mesna; 33 percent as dimesna).

International Brand Names of Mesna:

• Mesnex
• Uromitexan
• Delinar
• Ifomes
• Mescryo
• Mesnil
• Mesodal
• Mistabron
• Mitexan
• Mucofluid
• Novacarel
• Uromes
• Uromitexan
• Uroprot

Mesna Brand Names in Pakistan: