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MESNA

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Mesna is a sulfhydryl compound with mucolytic and urothelial protective activity.

Specific Substances

    1) Mesnum
    2) Mistabron(R)
    3) Mistabronco(R)
    4) Mucofluid(R)
    5) Sodium 2-mercaptoethanesulphonate
    6) UCB 3983
    7) Urometixan(R)
    8) Uromitexan(R)
    9) CAS 19767-45-4
    1.2.1) MOLECULAR FORMULA
    1) C2H5NaO3S2

Available Forms Sources

    A) FORMS
    1) Mesna is available as 400 mg oral tablets and 100 mg/mL (1 g) intravenous solution (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    2) Mesna products may contain benzyl alcohol as an antimicrobial preservative. Benzyl alcohol has been associated with serious adverse effects and death (including gasping syndrome) (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    a) Refer to "BENZYL ALCOHOL" management for further information.
    B) USES
    1) Mesna is indicated in adults as prophylaxis to reduce the incidence of hemorrhagic cystitis due to ifosfamide (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: Mesna is indicated in adults as prophylaxis to reduce the incidence of hemorrhagic cystitis due to ifosfamide.
    B) PHARMACOLOGY: Mesna reduces ifosfamide-induced hemorrhagic cystitis by binding to 4-hydroxy-ifosfamide forming a non-urotoxic 4-sulfoethylthioifosfamide. and by binding to the double bonds of acrolein and other urotoxic ifosfamide metabolites thereby inhibiting their toxic effects on the bladder.
    C) EPIDEMIOLOGY: Overdose is rare.
    D) WITH THERAPEUTIC USE
    1) MESNA ALONE: MOST COMMON: Headache, injection site reactions, flushing, dizziness, nausea, vomiting, somnolence, diarrhea, anorexia, fever, pharyngitis, hyperesthesia, influenza-life symptoms, and cough. OTHER EFFECTS: Abdominal pain/colic, epigastric pain/burning, lightheadedness, back pain, arthralgia, conjunctivitis, nasal congestion, paresthesia, photophobia, fatigue, lymphadenopathy, extremity pain, malaise, chest pain, dysuria, dry mouth, dyspnea, and hyperhidrosis. MESNA WITH IFOSFAMIDE: Nausea, vomiting, constipation, leukopenia, fatigue, fever, anorexia, thrombocytopenia, anemia, granulocytopenia, asthenia, abdominal pain, alopecia, dyspnea, chest pain, hypokalemia, diarrhea, dizziness, headache, pain, increased sweating, back pain, hematuria, injection site reaction, edema, peripheral edema, somnolence, anxiety, confusion, facial edema, insomnia, cough, dyspepsia, hypotension, pneumonia, tachycardia, and flushing.
    2) Mesna products may contain benzyl alcohol as an antimicrobial preservative. Benzyl alcohol has been associated with serious adverse effects and death (including gasping syndrome).
    a) Refer to "BENZYL ALCOHOL" management for further information.
    E) WITH POISONING/EXPOSURE
    1) Overdose data are limited. Overdose effects are expected to be an extension of adverse effects reported with therapeutic use. Hypersensitivity reactions, including mild hypotension, shortness of breath, asthma exacerbation, rash, and flushing have been reported in patients who received 4.5 to 6.9 g of mesna. Nausea, vomiting, diarrhea, and fever have been reported in patients receiving mesna in combination with ifosfamide or cyclophosphamide.
    0.2.20) REPRODUCTIVE
    A) Mesna is classified as FDA pregnancy category B. At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy in humans. No teratogenicity was found in animal studies of mesna.
    0.2.21) CARCINOGENICITY
    A) At the time of this review, no data were available to assess the carcinogenic or mutagenic potential of this agent.

Laboratory Monitoring

    A) Plasma concentrations are not readily available or clinically useful in the management of overdose.
    B) Monitor vital signs and mental status.
    C) Monitor CBC with differential and platelet count, renal function, and liver enzymes in symptomatic patients.
    D) Monitor serum electrolytes in patients with significant vomiting and/or diarrhea. Since a few patients experienced hypokalemia, potassium levels should be monitored.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Treatment is symptomatic and supportive. Manage mild hypotension with IV fluids. Correct any significant fluid and/or electrolyte abnormalities in patients with severe diarrhea and/or vomiting. Treat nausea and vomiting with antiemetics.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) Treatment is symptomatic and supportive. Treat severe hypotension with IV 0.9% NaCl at 10 to 20 mL/kg. Add dopamine or norepinephrine, if unresponsive to fluids. Leukopenia, granulocytopenia, thrombocytopenia, and anemia have been reported in patients receiving ifosfamide with mesna. Monitor serial CBC with differential. For severe neutropenia, administer colony stimulating factor (eg; filgrastim, sargramostim). Transfusion of platelets and/or packed red cells may be needed in patients with severe thrombocytopenia, anemia or hemorrhage.
    C) DECONTAMINATION
    1) PREHOSPITAL: Consider activated charcoal if the overdose is recent, the patient is not vomiting, and is able to maintain their airway.
    2) HOSPITAL: Consider activated charcoal if the overdose is recent, the patient is not vomiting, and is able to maintain their airway.
    D) AIRWAY MANAGEMENT
    1) Ensure adequate ventilation and perform endotracheal intubation early in patients with severe allergic reactions.
    E) ANTIDOTE
    1) None.
    F) HYPERSENSITIVITY REACTIONS
    1) MILD/MODERATE: Antihistamines with or without inhaled beta agonists, corticosteroids or epinephrine. SEVERE: Administer oxygen, aggressive airway management, antihistamines, epinephrine, corticosteroids, ECG monitoring, and IV fluids.
    G) MYELOSUPPRESSION
    1) Leukopenia, granulocytopenia, thrombocytopenia, and anemia have been reported in patients receiving ifosfamide with mesna. Administer colony stimulating factors in patients who develop severe neutropenia or neutropenic sepsis. Filgrastim: 5 mcg/kg/day IV or subQ. Sargramostim: 250 mcg/m(2)/day IV over 4 hours. Monitor CBC with differential and platelet count daily for evidence of bone marrow suppression until recovery has occurred. Transfusion of platelets and/or packed red cells may be needed in patients with severe thrombocytopenia, anemia or hemorrhage. Patients with severe neutropenia should be in protective isolation. Transfer to a bone marrow transplant center should be considered.
    H) ENHANCED ELIMINATION
    1) It is unknown if hemodialysis, hemoperfusion and plasmapheresis are likely to be useful following an oral exposure.
    I) PATIENT DISPOSITION
    1) HOME CRITERIA: A patient with an inadvertent exposure, that remains asymptomatic can be managed at home.
    2) OBSERVATION CRITERIA: Patients with a deliberate overdose, and those who are symptomatic, need to be monitored until they are clearly improving and clinically stable.
    3) ADMISSION CRITERIA: Patients with severe symptoms despite treatment should be admitted.
    4) CONSULT CRITERIA: Consult a regional poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear.
    J) PITFALLS
    1) Symptoms in patients may be delayed (particularly myelosuppression) so reliable follow-up is imperative. Patients taking these medications may have severe co-morbidities and access to other drugs with significant toxicity; consider coingestants.
    K) PHARMACOKINETICS
    1) Tmax: oral: 1.5 to 4 hours (free mesna); 3 to 7 hours (total mesna). Bioavailability: oral: average 58% (range, 45% to 71%; free mesna); average 89% (range, 74% to 104%; total mesna). Vd: Mean apparent Vd was 0.652 +/- 0.242 L/kg following IV administration. Metabolism: Rapidly oxidized to its major metabolite, mesna disulfide (dimesna). Plasma concentrations of mesna are greater than dimesna following either oral or IV administration. Excretion: renal: Approximately 32% of a single 800-mg IV mesna dose was eliminated in urine in 24 hours and 33% excreted as the dimesna metabolite. Elimination half-life: 0.36 hours.
    L) DIFFERENTIAL DIAGNOSIS
    1) Includes other agents that may cause myelosuppression, hypersensitivity reactions, hypokalemia, or hypotension.
    0.4.3) INHALATION EXPOSURE
    A) INHALATION: Move patient to fresh air. Monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with an inhaled beta2-adrenergic agonist. Consider systemic corticosteroids in patients with significant bronchospasm.
    0.4.4) EYE EXPOSURE
    A) DECONTAMINATION: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, the patient should be seen in a healthcare facility.
    0.4.5) DERMAL EXPOSURE
    A) OVERVIEW
    1) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Range Of Toxicity

    A) TOXICITY: The maximum tolerated human exposure has not been established. Hypersensitivity reactions, including mild hypotension, shortness of breath, asthma exacerbation, rash, and flushing have been reported in patients after receiving 4.5 to 6.9 g of mesna. Nausea, vomiting, diarrhea, and fever developed in 11 patients after receiving mesna 10 mg/kg to 66 mg/kg IV daily for 3 to 5 days in combination with ifosfamide or cyclophosphamide. These adverse effects also occurred in patients treated with oxazaphosphorine in combination with higher doses of mesna (80 mg/kg).
    B) THERAPEUTIC DOSE: ADULT: The recommended IV dose is 20% of the ifosfamide dosage weight by weight administered at the same time as ifosfamide as a single IV bolus and at 4 and 8 hours after each ifosfamide dose. The recommended dosing schedule is as follows: 0 hour: ifosfamide 1.2 g/m(2) and mesna 240 mg/m(2); 4 hours: mesna 240 mg/m(2); 8 hours: mesna 240 mg/m(2) and MAX dose: 60% of ifosfamide dose. The recommended oral dose is 40% of the ifosfamide dose at 2 and 6 hours following the ifosfamide dose. The recommended IV and oral dosing schedule is as follows: 0 hour: ifosfamide 1.2 g/m(2) and IV mesna 240 mg/m(2); 2 hours: oral mesna 480 mg/m(2); 6 hours: oral mesna 480 mg/m(2) and MAX dose: 100% of ifosfamide dose. PEDIATRIC: Safety and effectiveness have not been established in pediatric patients. A dosage of 25% of the daily ifosfamide dose given at 15 minutes, 4 hours, and 6 hours daily for 5 days was used in a study of 18 children and adolescents.

Clinical Effects

Summary Of Exposure

    A) USES: Mesna is indicated in adults as prophylaxis to reduce the incidence of hemorrhagic cystitis due to ifosfamide.
    B) PHARMACOLOGY: Mesna reduces ifosfamide-induced hemorrhagic cystitis by binding to 4-hydroxy-ifosfamide forming a non-urotoxic 4-sulfoethylthioifosfamide. and by binding to the double bonds of acrolein and other urotoxic ifosfamide metabolites thereby inhibiting their toxic effects on the bladder.
    C) EPIDEMIOLOGY: Overdose is rare.
    D) WITH THERAPEUTIC USE
    1) MESNA ALONE: MOST COMMON: Headache, injection site reactions, flushing, dizziness, nausea, vomiting, somnolence, diarrhea, anorexia, fever, pharyngitis, hyperesthesia, influenza-life symptoms, and cough. OTHER EFFECTS: Abdominal pain/colic, epigastric pain/burning, lightheadedness, back pain, arthralgia, conjunctivitis, nasal congestion, paresthesia, photophobia, fatigue, lymphadenopathy, extremity pain, malaise, chest pain, dysuria, dry mouth, dyspnea, and hyperhidrosis. MESNA WITH IFOSFAMIDE: Nausea, vomiting, constipation, leukopenia, fatigue, fever, anorexia, thrombocytopenia, anemia, granulocytopenia, asthenia, abdominal pain, alopecia, dyspnea, chest pain, hypokalemia, diarrhea, dizziness, headache, pain, increased sweating, back pain, hematuria, injection site reaction, edema, peripheral edema, somnolence, anxiety, confusion, facial edema, insomnia, cough, dyspepsia, hypotension, pneumonia, tachycardia, and flushing.
    2) Mesna products may contain benzyl alcohol as an antimicrobial preservative. Benzyl alcohol has been associated with serious adverse effects and death (including gasping syndrome).
    a) Refer to "BENZYL ALCOHOL" management for further information.
    E) WITH POISONING/EXPOSURE
    1) Overdose data are limited. Overdose effects are expected to be an extension of adverse effects reported with therapeutic use. Hypersensitivity reactions, including mild hypotension, shortness of breath, asthma exacerbation, rash, and flushing have been reported in patients who received 4.5 to 6.9 g of mesna. Nausea, vomiting, diarrhea, and fever have been reported in patients receiving mesna in combination with ifosfamide or cyclophosphamide.

Vital Signs

    3.3.3) TEMPERATURE
    A) WITH THERAPEUTIC USE
    1) FEVER: In 4 phase 1 studies, fever was frequently (in 2 or more healthy volunteers) reported in healthy volunteers receiving either single IV doses of mesna 600 to 1200 mg injection (n=53) or single oral doses of mesna 600 to 2400 mg tablets (n=82) (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    2) FEVER: In 4 controlled trials, fever developed in 20.2% of 119 patients who received IV doses of ifosfamide with mesna followed by IV doses of mesna and 15.1% of 119 patients who received IV doses of ifosfamide with mesna followed by oral doses of mesna (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    B) WITH POISONING/EXPOSURE
    1) Nausea, vomiting, diarrhea, and fever developed in 11 patients who received mesna 10 mg/kg to 66 mg/kg IV daily for 3 to 5 days in combination with ifosfamide or cyclophosphamide. These adverse effects also occurred in patients treated with oxazaphosphorine in combination with higher doses of mesna (80 mg/kg) (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).

Heent

    3.4.3) EYES
    A) WITH THERAPEUTIC USE
    1) CONJUNCTIVITIS: In 4 phase 1 studies, conjunctivitis was reported in healthy volunteers receiving mesna alone (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    3.4.5) NOSE
    A) WITH THERAPEUTIC USE
    1) UNPLEASANT ODOR: An unpleasant odor is the most commonly reported adverse effect of inhalational mesna therapy (Noviant & Gajour, 1972).

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) TACHYCARDIA
    1) WITH THERAPEUTIC USE
    a) In 4 controlled trials, tachycardia developed in 0.8% of 119 patients who received IV doses of ifosfamide with mesna followed by IV doses of mesna and 5.9% of 119 patients who received IV doses of ifosfamide with mesna followed by oral doses of mesna (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    B) EDEMA
    1) WITH THERAPEUTIC USE
    a) In 4 controlled trials, edema developed in 6.7% of 119 patients who received IV doses of ifosfamide with mesna followed by IV doses of mesna and 7.6% of 119 patients who received IV doses of ifosfamide with mesna followed by oral doses of mesna (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    C) PERIPHERAL EDEMA
    1) WITH THERAPEUTIC USE
    a) In 4 controlled trials, peripheral edema developed in 6.7% of 119 patients who received IV doses of ifosfamide with mesna followed by IV doses of mesna and 6.7% of 119 patients who received IV doses of ifosfamide with mesna followed by oral doses of mesna (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    D) EDEMA OF FACE
    1) WITH THERAPEUTIC USE
    a) In 4 controlled trials, face edema developed in 5% of 119 patients who received IV doses of ifosfamide with mesna followed by IV doses of mesna and 4.2% of 119 patients who received IV doses of ifosfamide with mesna followed by oral doses of mesna (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    E) CHEST PAIN
    1) WITH THERAPEUTIC USE
    a) In 4 phase 1 studies, chest pain was reported in healthy volunteers receiving mesna alone (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    b) In 4 controlled trials, chest pain developed in 8.4% of 119 patients who received IV doses of ifosfamide with mesna followed by IV doses of mesna and 9.2% of 119 patients who received IV doses of ifosfamide with mesna followed by oral doses of mesna (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    F) HYPOTENSIVE EPISODE
    1) WITH THERAPEUTIC USE
    a) In 4 controlled trials, hypotensive developed in 3.4% of 119 patients who received IV doses of ifosfamide with mesna followed by IV doses of mesna and 5% of 119 patients who received IV doses of ifosfamide with mesna followed by oral doses of mesna (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).

Respiratory

    3.6.2) CLINICAL EFFECTS
    A) DISORDER OF RESPIRATORY SYSTEM
    1) WITH THERAPEUTIC USE
    a) Nebulization of a 10% mesna solution in 10 postoperatively ventilated patients without preexisting pulmonary disease caused a significant increase in inspiratory resistance. Combining mesna with a bronchodilator (albuterol) seemed to block this effect. Expiratory resistance did not change, suggesting that only the larger airways are involved. Although no patient showed clinical signs of bronchospasm, it is worth considering that nebulization of mesna should be performed in combination with a bronchodilator (Zandstra & Stoutenbeek, 1988).
    B) PNEUMONIA
    1) WITH THERAPEUTIC USE
    a) In 4 controlled trials, pneumonia developed in 1.7% of 119 patients who received IV doses of ifosfamide with mesna followed by IV doses of mesna and 6.7% of 119 patients who received IV doses of ifosfamide with mesna followed by oral doses of mesna (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    C) DYSPNEA
    1) WITH THERAPEUTIC USE
    a) In 4 phase 1 studies, dyspnea was reported in healthy volunteers receiving mesna alone (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    b) In 4 controlled trials, dyspnea developed in 9.2% of 119 patients who received IV doses of ifosfamide with mesna followed by IV doses of mesna and 9.2% of 119 patients who received IV doses of ifosfamide with mesna followed by oral doses of mesna (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    D) COUGH
    1) WITH THERAPEUTIC USE
    a) In 4 phase 1 studies, cough was frequently (in 2 or more healthy volunteers) reported in healthy volunteers receiving either single IV doses of mesna 600 to 1200 mg injection (n=53) or single oral doses of mesna 600 to 2400 mg tablets (n=82) (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    b) In 4 controlled trials, cough developed in 4.2% of 119 patients who received IV doses of ifosfamide with mesna followed by IV doses of mesna and 8.4% of 119 patients who received IV doses of ifosfamide with mesna followed by oral doses of mesna (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    E) PHARYNGITIS
    1) WITH THERAPEUTIC USE
    a) In 4 phase 1 studies, pharyngitis was frequently (in 2 or more healthy volunteers) reported in healthy volunteers receiving either single IV doses of mesna 600 to 1200 mg injection (n=53) or single oral doses of mesna 600 to 2400 mg tablets (n=82) (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    F) INFLUENZA-LIKE SYMPTOMS
    1) WITH THERAPEUTIC USE
    a) In 4 phase 1 studies, influenza-like symptoms were frequently (in 2 or more healthy volunteers) reported in healthy volunteers receiving either single IV doses of mesna 600 to 1200 mg injection (n=53) or single oral doses of mesna 600 to 2400 mg tablets (n=82) (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    G) NASAL CONGESTION
    1) WITH THERAPEUTIC USE
    a) In 4 phase 1 studies, nasal congestion was reported in healthy volunteers receiving mesna alone (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) INSOMNIA
    1) WITH THERAPEUTIC USE
    a) In 4 controlled trials, insomnia developed in 5% of 119 patients who received IV doses of ifosfamide with mesna followed by IV doses of mesna and 9.2% of 119 patients who received IV doses of ifosfamide with mesna followed by oral doses of mesna (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    B) CLOUDED CONSCIOUSNESS
    1) WITH THERAPEUTIC USE
    a) In 4 controlled trials, confusion developed in 5.9% of 119 patients who received IV doses of ifosfamide with mesna followed by IV doses of mesna and 5% of 119 patients who received IV doses of ifosfamide with mesna followed by oral doses of mesna (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    C) ASTHENIA
    1) WITH THERAPEUTIC USE
    a) In 4 controlled trials, asthenia developed in 12.6% of 119 patients who received IV doses of ifosfamide with mesna followed by IV doses of mesna and 17.6% of 119 patients who received IV doses of ifosfamide with mesna followed by oral doses of mesna (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    D) DIZZINESS
    1) WITH THERAPEUTIC USE
    a) In 4 phase 1 studies, dizziness was frequently (in 2 or more healthy volunteers) reported in healthy volunteers receiving either single IV doses of mesna 600 to 1200 mg injection (n=53) or single oral doses of mesna 600 to 2400 mg tablets (n=82) (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    b) In 4 controlled trials, dizziness developed in 7.6% of 119 patients who received IV doses of ifosfamide with mesna followed by IV doses of mesna and 4.2% of 119 patients who received IV doses of ifosfamide with mesna followed by oral doses of mesna (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    E) HEADACHE
    1) WITH THERAPEUTIC USE
    a) In 4 phase 1 studies, headache was frequently (in 2 or more healthy volunteers) reported in healthy volunteers receiving either single IV doses of mesna 600 to 1200 mg injection (n=53) or single oral doses of mesna 600 to 2400 mg tablets (n=82) (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    b) In 4 controlled trials, headache developed in 7.6% of 119 patients who received IV doses of ifosfamide with mesna followed by IV doses of mesna and 10.9% of 119 patients who received IV doses of ifosfamide with mesna followed by oral doses of mesna (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    F) DROWSY
    1) WITH THERAPEUTIC USE
    a) In 4 phase 1 studies, somnolence was frequently (in 2 or more healthy volunteers) reported in healthy volunteers receiving either single IV doses of mesna 600 to 1200 mg injection (n=53) or single oral doses of mesna 600 to 2400 mg tablets (n=82) (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    b) In 4 controlled trials, somnolence developed in 6.7% of 119 patients who received IV doses of ifosfamide with mesna followed by IV doses of mesna and 10.1% of 119 patients who received IV doses of ifosfamide with mesna followed by oral doses of mesna (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    G) ANXIETY
    1) WITH THERAPEUTIC USE
    a) In 4 controlled trials, anxiety developed in 5.9% of 119 patients who received IV doses of ifosfamide with mesna followed by IV doses of mesna and 3.4% of 119 patients who received IV doses of ifosfamide with mesna followed by oral doses of mesna (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    H) FATIGUE
    1) WITH THERAPEUTIC USE
    a) In 4 phase 1 studies, fatigue and malaise were reported in healthy volunteers receiving mesna alone (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    b) In 4 controlled trials, fatigue developed in 20.2% of 119 patients who received IV doses of ifosfamide with mesna followed by IV doses of mesna and 20.2% of 119 patients who received IV doses of ifosfamide with mesna followed by oral doses of mesna (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    I) LIGHTHEADEDNESS
    1) WITH THERAPEUTIC USE
    a) In 4 phase 1 studies, lightheadedness was reported in healthy volunteers receiving mesna alone (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) INDIGESTION
    1) WITH THERAPEUTIC USE
    a) In 4 controlled trials, dyspepsia developed in 3.4% of 119 patients who received IV doses of ifosfamide with mesna followed by IV doses of mesna and 5% of 119 patients who received IV doses of ifosfamide with mesna followed by oral doses of mesna (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    B) ABDOMINAL PAIN
    1) WITH THERAPEUTIC USE
    a) In 4 phase 1 studies, abdominal pain/colic and epigastric pain/burning were reported in healthy volunteers receiving mesna alone (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    b) In 4 controlled trials, abdominal pain developed in 11.8% of 119 patients who received IV doses of ifosfamide with mesna followed by IV doses of mesna and 15.1% of 119 patients who received IV doses of ifosfamide with mesna followed by oral doses of mesna (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    C) VOMITING
    1) WITH THERAPEUTIC USE
    a) In 4 phase 1 studies, vomiting was frequently (in 2 or more healthy volunteers) reported in healthy volunteers receiving either single IV doses of mesna 600 to 1200 mg injection (n=53) or single oral doses of mesna 600 to 2400 mg tablets (n=82) (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    b) In 4 controlled trials, vomiting developed in 29.4% of 119 patients who received IV doses of ifosfamide with mesna followed by IV doses of mesna and 37.8% of 119 patients who received IV doses of ifosfamide with mesna followed by oral doses of mesna (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    c) Nausea, vomiting, and diarrhea are adverse effects which have been reported with intravenous mesna therapy. Effects appear to be dose related and occurred at doses of 80 mg/kg but not at 60 mg/kg or less (Scheef et al, 1979a).
    2) WITH POISONING/EXPOSURE
    a) Nausea, vomiting, diarrhea, and fever developed in 11 patients who received mesna 10 mg/kg to 66 mg/kg IV daily for 3 to 5 days in combination with ifosfamide or cyclophosphamide. These adverse effects also occurred in patients treated with oxazaphosphorine in combination with higher doses of mesna (80 mg/kg) (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    D) NAUSEA
    1) WITH THERAPEUTIC USE
    a) In 4 phase 1 studies, nausea was frequently (in 2 or more healthy volunteers) reported in healthy volunteers receiving either single IV doses of mesna 600 to 1200 mg injection (n=53) or single oral doses of mesna 600 to 2400 mg tablets (n=82) (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    b) In 4 controlled trials, nausea developed in 54.6% of 119 patients who received IV doses of ifosfamide with mesna followed by IV doses of mesna and 53.8% of 119 patients who received IV doses of ifosfamide with mesna followed by oral doses of mesna (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    c) Nausea, vomiting, and diarrhea are adverse effects which have been reported with intravenous mesna therapy. Effects appear to be dose related and occurred at doses of 80 mg/kg but not at 60 mg/kg or less (Scheef et al, 1979a).
    2) WITH POISONING/EXPOSURE
    a) Nausea, vomiting, diarrhea, and fever developed in 11 patients who received mesna 10 mg/kg to 66 mg/kg IV daily for 3 to 5 days in combination with ifosfamide or cyclophosphamide. These adverse effects also occurred in patients treated with oxazaphosphorine in combination with higher doses of mesna (80 mg/kg) (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    E) DIARRHEA
    1) WITH THERAPEUTIC USE
    a) In 4 phase 1 studies, diarrhea was frequently (in 2 or more healthy volunteers) reported in healthy volunteers receiving either single IV doses of mesna 600 to 1200 mg injection (n=53) or single oral doses of mesna 600 to 2400 mg tablets (n=82) (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    b) In 4 controlled trials, diarrhea developed in 7.6% of 119 patients who received IV doses of ifosfamide with mesna followed by IV doses of mesna and 14.3% of 119 patients who received IV doses of ifosfamide with mesna followed by oral doses of mesna (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    c) Nausea, vomiting, and diarrhea are adverse effects which have been reported with intravenous mesna therapy. Effects appear to be dose related and occurred at doses of 80 mg/kg but not at 60 mg/kg or less (Scheef et al, 1979a).
    2) WITH POISONING/EXPOSURE
    a) Nausea, vomiting, diarrhea, and fever developed in 11 patients who received mesna 10 mg/kg to 66 mg/kg IV daily for 3 to 5 days in combination with ifosfamide or cyclophosphamide. These adverse effects also occurred in patients treated with oxazaphosphorine in combination with higher doses of mesna (80 mg/kg) (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    F) LOSS OF APPETITE
    1) WITH THERAPEUTIC USE
    a) In 4 phase 1 studies, anorexia was frequently (in 2 or more healthy volunteers) reported in healthy volunteers receiving either single IV doses of mesna 600 to 1200 mg injection (n=53) or single oral doses of mesna 600 to 2400 mg tablets (n=82) (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    b) In 4 controlled trials, loss of appetite developed in 17.6% of 119 patients who received IV doses of ifosfamide with mesna followed by IV doses of mesna and 16% of 119 patients who received IV doses of ifosfamide with mesna followed by oral doses of mesna (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    G) CONSTIPATION
    1) WITH THERAPEUTIC USE
    a) In 4 controlled trials, constipation developed in 23.5% of 119 patients who received IV doses of ifosfamide with mesna followed by IV doses of mesna and 17.6% of 119 patients who received IV doses of ifosfamide with mesna followed by oral doses of mesna (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    H) APTYALISM
    1) WITH THERAPEUTIC USE
    a) In 4 phase 1 studies, dry mouth was reported in healthy volunteers receiving mesna alone (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).

Genitourinary

    3.10.2) CLINICAL EFFECTS
    A) TOXIC NEPHROPATHY
    1) WITH THERAPEUTIC USE
    a) CHRONIC THERAPY: A dosage of 25 percent of the daily ifosfamide dose given at 15 minutes, 4 hours, and 6 hours daily for 5 days was used in a study of 18 children and adolescents. This study found that the 15 patients with normal NAG enzymes before treatment had no increase in nephrotoxicity during treatment. The 3 patients with increased NAG enzymes pre-treatment had an increase in enzymuria and proteinuria (Goren et al, 1989).
    B) BLOOD IN URINE
    1) WITH THERAPEUTIC USE
    a) In 4 controlled trials, hematuria developed in 6.7% of 119 patients who received IV doses of ifosfamide with mesna followed by IV doses of mesna and 5.9% of 119 patients who received IV doses of ifosfamide with mesna followed by oral doses of mesna (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    C) DYSURIA
    1) WITH THERAPEUTIC USE
    a) In 4 phase 1 studies, dysuria was reported in healthy volunteers receiving mesna alone (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).

Hematologic

    3.13.2) CLINICAL EFFECTS
    A) LEUKOPENIA
    1) WITH THERAPEUTIC USE
    a) In 4 controlled trials, leukopenia developed in 21% of 119 patients who received IV doses of ifosfamide with mesna followed by IV doses of mesna and 17.6% of 119 patients who received IV doses of ifosfamide with mesna followed by oral doses of mesna (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    B) THROMBOCYTOPENIC DISORDER
    1) WITH THERAPEUTIC USE
    a) In 4 controlled trials, thrombocytopenia developed in 17.6% of 119 patients who received IV doses of ifosfamide with mesna followed by IV doses of mesna and 13.4% of 119 patients who received IV doses of ifosfamide with mesna followed by oral doses of mesna (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    C) ANEMIA
    1) WITH THERAPEUTIC USE
    a) In 4 controlled trials, anemia developed in 16.8% of 119 patients who received IV doses of ifosfamide with mesna followed by IV doses of mesna and 17.6% of 119 patients who received IV doses of ifosfamide with mesna followed by oral doses of mesna (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    D) GRANULOCYTOPENIC DISORDER
    1) WITH THERAPEUTIC USE
    a) In 4 controlled trials, granulocytopenia developed in 13.4% of 119 patients who received IV doses of ifosfamide with mesna followed by IV doses of mesna and 12.6% of 119 patients who received IV doses of ifosfamide with mesna followed by oral doses of mesna (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    E) LYMPHADENOPATHY
    1) WITH THERAPEUTIC USE
    a) In 4 phase 1 studies, lymphadenopathy was reported in healthy volunteers receiving mesna alone (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    b) In 4 phase 1 studies, a reversible rapid (within 24 hours) decreased in lymphocyte count was reported in healthy volunteers receiving mesna alone (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) HYPERSENSITIVITY REACTION
    1) WITH THERAPEUTIC USE
    a) CASE REPORT: A severe hypersensitivity reaction occurred in a 25-year-old woman with Hodgkin's disease following IV administration of mesna (50 mg IV followed by 150 mg IV 4 hours later). The patient developed an extensive maculopapular rash on the face and trunk, conjunctivitis, periorbital swelling, chills, nausea, and pain in the extremities. Recovery occurred 13 hours later. Oral challenge 2 days later with mesna produced no reaction; however, a further 2 grams orally given 4 hours following the first oral dose produced an extensive skin rash (Lang & Goos, 1985).
    b) Seidel et al (1991) reported several cases of allergic, widespread macular pruritic rash after oral or intravenous administration of mesna (Seidel et al, 1991).
    B) ERUPTION DUE TO DRUG
    1) WITH THERAPEUTIC USE
    a) Drug rash with eosinophilia and systemic symptoms, and bullous and ulcerative skin reactions as well as mucosal reactions consistent with Stevens-Johnson syndrome or toxic epidermal necrolysis may occur with first exposure or after several months of therapy. Reactions were characterized by rash, urticaria, pruritus, erythema, burning sensation, flushing, stomatitis, periorbital edema, or angioedema (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    C) EXCESSIVE SWEATING
    1) WITH THERAPEUTIC USE
    a) In 4 phase 1 studies, hyperhidrosis was reported in healthy volunteers receiving mesna alone (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    b) In 4 controlled trials, excessive sweating developed in 7.6% of 119 patients who received IV doses of ifosfamide with mesna followed by IV doses of mesna and 1.7% of 119 patients who received IV doses of ifosfamide with mesna followed by oral doses of mesna (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    D) PARESTHESIA
    1) WITH THERAPEUTIC USE
    a) In 4 phase 1 studies, paresthesia was reported in healthy volunteers receiving mesna alone (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    E) ALOPECIA
    1) WITH THERAPEUTIC USE
    a) In 4 controlled trials, alopecia developed in 10.1% of 119 patients who received IV doses of ifosfamide with mesna followed by IV doses of mesna and 10.9% of 119 patients who received IV doses of ifosfamide with mesna followed by oral doses of mesna (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    F) INJECTION SITE REACTION
    1) WITH THERAPEUTIC USE
    a) In 4 phase 1 studies, injection site reaction was frequently (in 2 or more healthy volunteers) reported in healthy volunteers receiving either single IV doses of mesna 600 to 1200 mg injection (n=53) or single oral doses of mesna 600 to 2400 mg tablets (n=82) (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    b) In 4 controlled trials, injection site reaction developed in 6.7% of 119 patients who received IV doses of ifosfamide with mesna followed by IV doses of mesna and 8.4% of 119 patients who received IV doses of ifosfamide with mesna followed by oral doses of mesna (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    G) FLUSHING
    1) WITH THERAPEUTIC USE
    a) In 4 phase 1 studies, flushing was frequently (in 2 or more healthy volunteers) reported in healthy volunteers receiving either single IV doses of mesna 600 to 1200 mg injection (n=53) or single oral doses of mesna 600 to 2400 mg tablets (n=82) (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    b) In 4 controlled trials, flushing developed in 0.8% of 119 patients who received IV doses of ifosfamide with mesna followed by IV doses of mesna and 5% of 119 patients who received IV doses of ifosfamide with mesna followed by oral doses of mesna (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    H) HYPERESTHESIA
    1) WITH THERAPEUTIC USE
    a) In 4 phase 1 studies, hyperesthesia was frequently (in 2 or more healthy volunteers) reported in healthy volunteers receiving either single IV doses of mesna 600 to 1200 mg injection (n=53) or single oral doses of mesna 600 to 2400 mg tablets (n=82) (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    I) PHOTOPHOBIA
    1) WITH THERAPEUTIC USE
    a) In 4 phase 1 studies, photophobia was reported in healthy volunteers receiving mesna alone (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).

Musculoskeletal

    3.15.2) CLINICAL EFFECTS
    A) BACKACHE
    1) WITH THERAPEUTIC USE
    a) In 4 phase 1 studies, back pain was reported in healthy volunteers receiving mesna alone (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    b) In 4 controlled trials, backache developed in 6.7% of 119 patients who received IV doses of ifosfamide with mesna followed by IV doses of mesna and 5% of 119 patients who received IV doses of ifosfamide with mesna followed by oral doses of mesna (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    B) JOINT PAIN
    1) WITH THERAPEUTIC USE
    a) In 4 phase 1 studies, arthralgia was reported in healthy volunteers receiving mesna alone (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    C) MUSCLE PAIN
    1) WITH THERAPEUTIC USE
    a) In 4 phase 1 studies, myalgia was reported in healthy volunteers receiving mesna alone (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).

Immunologic

    3.19.2) CLINICAL EFFECTS
    A) HYPERSENSITIVITY REACTION
    1) WITH THERAPEUTIC USE
    a) Hypersensitivity reactions, including anaphylaxis, have been reported in patients receiving mesna and occur with first dose or after several months of exposure (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    b) CASE REPORT: A severe hypersensitivity reaction (extensive maculopapular rash on the face and trunk, conjunctivitis, periorbital swelling, chills, nausea, and pain in the extremities) occurred in a 25-year-old woman with Hodgkin's disease following administration of mesna (50 mg IV followed by 150 mg IV 4 hours later). Recovery occurred 13 hours later. Oral challenge 2 days later with mesna produced no reaction; however, a further 2 g oral dose given 4 hours following the first oral dose produced an extensive skin rash (Lang & Goos, 1985a).
    2) WITH POISONING/EXPOSURE
    a) Hypersensitivity reactions, including mild hypotension, shortness of breath, asthma exacerbation, rash, and flushing have been reported in patients who received 4.5 to 6.9 g of mesna (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).

Reproductive

    3.20.1) SUMMARY
    A) Mesna is classified as FDA pregnancy category B. At the time of this review, no data were available to assess the potential effects of exposure to this agent during pregnancy in humans. No teratogenicity was found in animal studies of mesna.
    3.20.3) EFFECTS IN PREGNANCY
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the teratogenic potential of this agent (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    B) PREGNANCY CATEGORY
    1) Mesna is classified as FDA pregnancy category B (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    2) There are no data on the use of mesna in pregnant women. The effects, if any, on the developing fetus are unknown. No teratogenicity was found in animal studies of mesna. Because animal reproductive studies are not always predictive of human response, it is recommended that mesna be prescribed to pregnant women only if clearly necessary (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    C) ANIMAL STUDIES
    1) Animal studies in which doses of 1000 mg/kg were used in rabbits and 2000 mg/kg were used in rats, showed no teratogenicity (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) BREAST MILK
    1) It is not known whether mesna is excreted into human breast milk and the potential for adverse effects in the nursing infant from exposure to the drug are unknown. Benzyl alcohol preservative in mesna is likely excreted in milk, and may be absorbed by a breastfeeding infant, and cause life-threatening adverse reactions, such as gasping syndrome (characterized by CNS depression, metabolic acidosis, gasping respirations) in neonates, and low-birth-weight and premature infants. Because potential harm to a nursing infant exists, either breastfeeding or mesna should be discontinued, considering the need for treatment of the mother (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    3.20.5) FERTILITY
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the potential effects on fertility from exposure to this agent (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    B) ANIMAL STUDIES
    1) RATS: No fertility effects were shown in 6-month oral female and male rat studies who were given mesna in doses up to 2000 mg/kg/day (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    2) DOGS: No fertility effects were shown in 29-week oral dog studies who were given mesna in doses of 520 mg/kg/day (approximately 10 times the maximum recommended daily dose in humans, based on body surface area) (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).

Carcinogenicity

    3.21.2) SUMMARY/HUMAN
    A) At the time of this review, no data were available to assess the carcinogenic or mutagenic potential of this agent.
    3.21.3) HUMAN STUDIES
    A) LACK OF INFORMATION
    1) At the time of this review, no data were available to assess the carcinogenic or mutagenic potential of this agent.

Genotoxicity

    A) At the time of this review, no data were available to assess the mutagenic or genotoxic potential of this agent.

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Plasma concentrations are not readily available or clinically useful in the management of overdose.
    B) Monitor vital signs and mental status.
    C) Monitor CBC with differential and platelet count, renal function, and liver enzymes in symptomatic patients.
    D) Monitor serum electrolytes in patients with significant vomiting and/or diarrhea. Since a few patients experienced hypokalemia, potassium levels should be monitored.
    4.1.2) SERUM/BLOOD
    A) OTHER
    1) FALSE POSITIVE RESULTS
    a) Mesna may produce a false positive result in diagnostic tests for urinary ketones and either a false positive or negative result in diagnostic tests for urinary erythrocytes (JEF Reynolds , 2000).
    1) KETONES, URINE: Urine testing using AMES Multistix(R) during ifosfamide and mesna usually revealed false-positive ketonuria in moderate to large amounts.
    2) A more detailed examination of this phenomenon was made in 43 patients, 39 with small cell lung cancer and 4 with pleural mesotheliomas. Nine patients received other cytotoxic drugs with ifosfamide and mesna and 34 patients did not.
    a) Each patient had a minimum of two urine tests for ketones during therapy. A total of 354 urine tests were made during 87 ifosfamide and mesna courses, all tests revealed false-positive ketonuria.
    3) False-positive ketonuria is common if not invariable during IV mesna therapy and could cause confusion in diabetic patients. Its presence is a useful check that patients received mesna.
    4) It is believed that sulfide components of mesna react with sodium nitroprusside of the test reagent to yield these false positive results (Cantwell et al, 1986).

Methods

    A) CHROMATOGRAPHY
    1) Determined in plasma by HPLC (James & Rogers, 1986).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) Patients with severe symptoms despite treatment should be admitted.
    6.3.1.2) HOME CRITERIA/ORAL
    A) A patient with an inadvertent exposure, that remains asymptomatic can be managed at home.
    6.3.1.3) CONSULT CRITERIA/ORAL
    A) Consult a regional poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Patients with a deliberate overdose, and those who are symptomatic, need to be monitored until they are clearly improving and clinically stable.

Monitoring

    A) Plasma concentrations are not readily available or clinically useful in the management of overdose.
    B) Monitor vital signs and mental status.
    C) Monitor CBC with differential and platelet count, renal function, and liver enzymes in symptomatic patients.
    D) Monitor serum electrolytes in patients with significant vomiting and/or diarrhea. Since a few patients experienced hypokalemia, potassium levels should be monitored.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) ACTIVATED CHARCOAL
    1) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION
    a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).
    1) In patients who are at risk for the abrupt onset of seizures or mental status depression, activated charcoal should not be administered in the prehospital setting, due to the risk of aspiration in the event of spontaneous emesis.
    2) The addition of flavoring agents (cola drinks, chocolate milk, cherry syrup) to activated charcoal improves the palatability for children and may facilitate successful administration (Guenther Skokan et al, 2001; Dagnone et al, 2002).
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.2) PREVENTION OF ABSORPTION
    A) ACTIVATED CHARCOAL
    1) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.3) TREATMENT
    A) SUPPORT
    1) MANAGEMENT OF MILD TO MODERATE TOXICITY
    a) Treatment is symptomatic and supportive. Manage mild hypotension with IV fluids. Correct any significant fluid and/or electrolyte abnormalities in patients with severe diarrhea and/or vomiting. Treat nausea and vomiting with antiemetics.
    2) MANAGEMENT OF SEVERE TOXICITY
    a) Treatment is symptomatic and supportive. Treat severe hypotension with IV 0.9% NaCl at 10 to 20 mL/kg. Add dopamine or norepinephrine if unresponsive to fluids. Leukopenia, granulocytopenia, thrombocytopenia, and anemia have been reported in patients receiving ifosfamide with mesna. Monitor serial CBC with differential. For severe neutropenia, administer colony stimulating factor (eg; filgrastim, sargramostim). Transfusion of platelets and/or packed red cells may be needed in patients with severe thrombocytopenia, anemia or hemorrhage.
    B) MONITORING OF PATIENT
    1) Plasma concentrations are not readily available or clinically useful in the management of overdose.
    2) Monitor vital signs and mental status.
    3) Monitor CBC with differential and platelet count, renal function, and liver enzymes in symptomatic patients.
    4) Monitor serum electrolytes in patients with significant vomiting and/or diarrhea. Hypokalemia has developed, monitor potassium levels as indicated.
    C) ACUTE ALLERGIC REACTION
    1) SUMMARY
    a) Mild to moderate allergic reactions may be treated with antihistamines with or without inhaled beta adrenergic agonists, corticosteroids or epinephrine. Treatment of severe anaphylaxis also includes oxygen supplementation, aggressive airway management, epinephrine, ECG monitoring, and IV fluids.
    2) BRONCHOSPASM
    a) ALBUTEROL
    1) ADULT: 2.5 to 5 milligrams in 2 to 4.5 milliliters of normal saline delivered per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 2.5 to 10 mg every 1 to 4 hours as needed, or 10 to 15 mg/hr by continuous nebulization as needed (National Heart,Lung,and Blood Institute, 2007). CHILD: 0.15 milligram/kilogram (minimum 2.5 milligrams) per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 0.15 to 0.3 mg/kg (up to 10 mg) every 1 to 4 hours as needed, or 0.5 mg/kg/hr by continuous nebulization (National Heart,Lung,and Blood Institute, 2007).
    3) CORTICOSTEROIDS
    a) Consider systemic corticosteroids in patients with significant bronchospasm.
    b) PREDNISONE: ADULT: 40 to 80 milligrams/day. CHILD: 1 to 2 milligrams/kilogram/day (maximum 60 mg) in 1 to 2 divided doses divided twice daily (National Heart,Lung,and Blood Institute, 2007).
    4) MILD CASES
    a) DIPHENHYDRAMINE
    1) SUMMARY: Oral diphenhydramine, as well as other H1 antihistamines can be used as indicated (Lieberman et al, 2010).
    2) ADULT: 50 milligrams orally, or 10 to 50 mg intravenously at a rate not to exceed 25 mg/min or may be given by deep intramuscular injection. A total of 100 mg may be administered if needed. Maximum daily dosage is 400 mg (Prod Info diphenhydramine HCl intravenous injection solution, intramuscular injection solution, 2013).
    3) CHILD: 5 mg/kg/24 hours or 150 mg/m(2)/24 hours. Divided into 4 doses, administered intravenously at a rate not exceeding 25 mg/min or by deep intramuscular injection. Maximum daily dosage is 300 mg (Prod Info diphenhydramine HCl intravenous injection solution, intramuscular injection solution, 2013).
    5) MODERATE CASES
    a) EPINEPHRINE: INJECTABLE SOLUTION: It should be administered early in patients by IM injection. Using a 1:1000 (1 mg/mL) solution of epinephrine. Initial Dose: 0.01 mg/kg intramuscularly with a maximum dose of 0.5 mg in adults and 0.3 mg in children. The dose may be repeated every 5 to 15 minutes, if no clinical improvement. Most patients respond to 1 or 2 doses (Nowak & Macias, 2014).
    6) SEVERE CASES
    a) EPINEPHRINE
    1) INTRAVENOUS BOLUS: ADULT: 1 mg intravenously as a 1:10,000 (0.1 mg/mL) solution; CHILD: 0.01 mL/kg intravenously to a maximum single dose of 1 mg given as a 1:10,000 (0.1 mg/mL) solution. It can be repeated every 3 to 5 minutes as needed. The dose can also be given by the intraosseous route if IV access cannot be established (Lieberman et al, 2015). ALTERNATIVE ROUTE: ENDOTRACHEAL ADMINISTRATION: If IV/IO access is unavailable. DOSE: ADULT: Administer 2 to 2.5 mg of 1:1000 (1 mg/mL) solution diluted in 5 to 10 mL of sterile water via endotracheal tube. CHILD: DOSE: 0.1 mg/kg to a maximum of 2.5 mg administered as a 1:1000 (1 mg/mL) solution diluted in 5 to 10 mL of sterile water via endotracheal tube (Lieberman et al, 2015).
    2) INTRAVENOUS INFUSION: Intravenous administration may be considered in patients poorly responsive to IM or SubQ epinephrine. An epinephrine infusion may be prepared by adding 1 mg (1 mL of 1:1000 (1 mg/mL) solution) to 250 mL D5W, yielding a concentration of 4 mcg/mL, and infuse this solution IV at a rate of 1 mcg/min to 10 mcg/min (maximum rate). CHILD: A dosage of 0.01 mg/kg (0.1 mL/kg of a 1:10,000 (0.1 mg/mL) solution up to 10 mcg/min (maximum dose 0.3 mg) is recommended for children (Lieberman et al, 2010). Careful titration of a continuous infusion of IV epinephrine, based on the severity of the reaction, along with a crystalloid infusion can be considered in the treatment of anaphylactic shock. It appears to be a reasonable alternative to IV boluses, if the patient is not in cardiac arrest (Vanden Hoek,TL,et al).
    7) AIRWAY MANAGEMENT
    a) OXYGEN: 5 to 10 liters/minute via high flow mask.
    b) INTUBATION: Perform early if any stridor or signs of airway obstruction.
    c) CRICOTHYROTOMY: Use if unable to intubate with complete airway obstruction (Vanden Hoek,TL,et al).
    d) BRONCHODILATORS are recommended for mild to severe bronchospasm.
    e) ALBUTEROL: ADULT: 2.5 to 5 milligrams in 2 to 4.5 milliliters of normal saline delivered per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 2.5 to 10 mg every 1 to 4 hours as needed, or 10 to 15 mg/hr by continuous nebulization as needed (National Heart,Lung,and Blood Institute, 2007).
    f) ALBUTEROL: CHILD: 0.15 milligram/kilogram (minimum 2.5 milligrams) per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 0.15 to 0.3 milligram/kilogram (maximum 10 milligrams) every 1 to 4 hours as needed OR administer 0.5 mg/kg/hr by continuous nebulization (National Heart,Lung,and Blood Institute, 2007).
    8) MONITORING
    a) CARDIAC MONITOR: All complicated cases.
    b) IV ACCESS: Routine in all complicated cases.
    9) HYPOTENSION
    a) If hypotensive give 500 to 2000 milliliters crystalloid initially (20 milliliters/kilogram in children) and titrate to desired effect (stabilization of vital signs, mentation, urine output); adults may require up to 6 to 10 L/24 hours. Central venous or pulmonary artery pressure monitoring is recommended in patients with persistent hypotension.
    1) VASOPRESSORS: Should be used in refractory cases unresponsive to repeated doses of epinephrine and after vigorous intravenous crystalloid rehydration (Lieberman et al, 2010).
    2) DOPAMINE: Initial Dose: 2 to 20 micrograms/kilogram/minute intravenously; titrate to maintain systolic blood pressure greater than 90 mm Hg (Lieberman et al, 2010).
    10) H1 and H2 ANTIHISTAMINES
    a) SUMMARY: Antihistamines are second-line therapy and are used as supportive therapy and should not be used in place of epinephrine (Lieberman et al, 2010).
    1) DIPHENHYDRAMINE: ADULT: 25 to 50 milligrams via a slow intravenous infusion or IM. PEDIATRIC: 1 milligram/kilogram via slow intravenous infusion or IM up to 50 mg in children (Lieberman et al, 2010).
    b) RANITIDINE: ADULT: 1 mg/kg parenterally; CHILD: 12.5 to 50 mg parenterally. If the intravenous route is used, ranitidine should be infused over 10 to 15 minutes or diluted in 5% dextrose to a volume of 20 mL and injected over 5 minutes (Lieberman et al, 2010).
    c) Oral diphenhydramine, as well as other H1 antihistamines, can also be used as indicated (Lieberman et al, 2010).
    11) DYSRHYTHMIAS
    a) Dysrhythmias and cardiac dysfunction may occur primarily or iatrogenically as a result of pharmacologic treatment (epinephrine) (Vanden Hoek,TL,et al). Monitor and correct serum electrolytes, oxygenation and tissue perfusion. Treat with antiarrhythmic agents as indicated.
    12) OTHER THERAPIES
    a) There have been a few reports of patients with anaphylaxis, with or without cardiac arrest, that have responded to vasopressin therapy that did not respond to standard therapy. Although there are no randomized controlled trials, other alternative vasoactive therapies (ie, vasopressin, norepinephrine, methoxamine, and metaraminol) may be considered in patients in cardiac arrest secondary to anaphylaxis that do not respond to epinephrine (Vanden Hoek,TL,et al).
    D) HYPOTENSIVE EPISODE
    1) SUMMARY
    a) Infuse 10 to 20 milliliters/kilogram of isotonic fluid and keep the patient supine. If hypotension persists, administer dopamine or norepinephrine. Consider central venous pressure monitoring to guide further fluid therapy.
    2) DOPAMINE
    a) DOSE: Begin at 5 micrograms per kilogram per minute progressing in 5 micrograms per kilogram per minute increments as needed (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). If hypotension persists, dopamine may need to be discontinued and a more potent vasoconstrictor (eg, norepinephrine) should be considered (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
    b) CAUTION: If ventricular dysrhythmias occur, decrease rate of administration (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). Extravasation may cause local tissue necrosis, administration through a central venous catheter is preferred (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
    3) NOREPINEPHRINE
    a) PREPARATION: 4 milligrams (1 amp) added to 1000 milliliters of diluent provides a concentration of 4 micrograms/milliliter of norepinephrine base. Norepinephrine bitartrate should be mixed in dextrose solutions (dextrose 5% in water, dextrose 5% in saline) since dextrose-containing solutions protect against excessive oxidation and subsequent potency loss. Administration in saline alone is not recommended (Prod Info norepinephrine bitartrate injection, 2005).
    b) DOSE
    1) ADULT: Dose range: 0.1 to 0.5 microgram/kilogram/minute (eg, 70 kg adult 7 to 35 mcg/min); titrate to maintain adequate blood pressure (Peberdy et al, 2010).
    2) CHILD: Dose range: 0.1 to 2 micrograms/kilogram/minute; titrate to maintain adequate blood pressure (Kleinman et al, 2010).
    3) CAUTION: Extravasation may cause local tissue ischemia, administration by central venous catheter is advised (Peberdy et al, 2010).
    E) MYELOSUPPRESSION
    1) Leukopenia, granulocytopenia, thrombocytopenia, and anemia have been reported in patients receiving ifosfamide with mesna (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    2) There is little data on the use of hematopoietic colony stimulating factors to treat neutropenia after drug overdose or idiosyncratic reactions. These agents have been shown to shorten the duration of severe neutropenia in patients receiving cancer chemotherapy (Hartman et al, 1997; Stull et al, 2005). They have also been used to treat agranulocytosis induced by nonchemotherapy drugs (Beauchesne & Shalansky, 1999). They may be considered in patients with severe neutropenia who have or are at significant risk for developing febrile neutropenia.
    a) Filgrastim: The usual starting dose in adults is 5 micrograms/kilogram/day by intravenous infusion or subcutaneous injection (Prod Info NEUPOGEN(R) injection, 2006).
    b) Sargramostim: Usual dose is 250 micrograms/square meter/day infused IV over 4 hours (Prod Info LEUKINE(R) injection, 2006).
    c) Monitor CBC with differential.
    3) Transfusion of platelets and/or packed red cells may be needed in patients with severe thrombocytopenia or hemorrhage.

Inhalation Exposure

    6.7.1) DECONTAMINATION
    A) Move patient from the toxic environment to fresh air. Monitor for respiratory distress. If cough or difficulty in breathing develops, evaluate for hypoxia, respiratory tract irritation, bronchitis, or pneumonitis.
    B) OBSERVATION: Carefully observe patients with inhalation exposure for the development of any systemic signs or symptoms and administer symptomatic treatment as necessary.
    C) INITIAL TREATMENT: Administer 100% humidified supplemental oxygen, perform endotracheal intubation and provide assisted ventilation as required. Administer inhaled beta-2 adrenergic agonists, if bronchospasm develops. Consider systemic corticosteroids in patients with significant bronchospasm (National Heart,Lung,and Blood Institute, 2007). Exposed skin and eyes should be flushed with copious amounts of water.

Eye Exposure

    6.8.1) DECONTAMINATION
    A) EYE IRRIGATION, ROUTINE: Remove contact lenses and irrigate exposed eyes with copious amounts of room temperature 0.9% saline or water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist after 15 minutes of irrigation, an ophthalmologic examination should be performed (Peate, 2007; Naradzay & Barish, 2006).

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) DERMAL DECONTAMINATION
    1) DECONTAMINATION: Remove contaminated clothing and wash exposed area thoroughly with soap and water for 10 to 15 minutes. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Enhanced Elimination

    A) SUMMARY
    1) It is unknown if hemodialysis, hemoperfusion and plasmapheresis are likely to be useful following an oral exposure.

Range Of Toxicity

Summary

    A) TOXICITY: The maximum tolerated human exposure has not been established. Hypersensitivity reactions, including mild hypotension, shortness of breath, asthma exacerbation, rash, and flushing have been reported in patients after receiving 4.5 to 6.9 g of mesna. Nausea, vomiting, diarrhea, and fever developed in 11 patients after receiving mesna 10 mg/kg to 66 mg/kg IV daily for 3 to 5 days in combination with ifosfamide or cyclophosphamide. These adverse effects also occurred in patients treated with oxazaphosphorine in combination with higher doses of mesna (80 mg/kg).
    B) THERAPEUTIC DOSE: ADULT: The recommended IV dose is 20% of the ifosfamide dosage weight by weight administered at the same time as ifosfamide as a single IV bolus and at 4 and 8 hours after each ifosfamide dose. The recommended dosing schedule is as follows: 0 hour: ifosfamide 1.2 g/m(2) and mesna 240 mg/m(2); 4 hours: mesna 240 mg/m(2); 8 hours: mesna 240 mg/m(2) and MAX dose: 60% of ifosfamide dose. The recommended oral dose is 40% of the ifosfamide dose at 2 and 6 hours following the ifosfamide dose. The recommended IV and oral dosing schedule is as follows: 0 hour: ifosfamide 1.2 g/m(2) and IV mesna 240 mg/m(2); 2 hours: oral mesna 480 mg/m(2); 6 hours: oral mesna 480 mg/m(2) and MAX dose: 100% of ifosfamide dose. PEDIATRIC: Safety and effectiveness have not been established in pediatric patients. A dosage of 25% of the daily ifosfamide dose given at 15 minutes, 4 hours, and 6 hours daily for 5 days was used in a study of 18 children and adolescents.

Therapeutic Dose

    7.2.1) ADULT
    A) ROUTE OF ADMINISTRATION
    1) INTRAVENOUS
    a) The recommended dose is 20% of the ifosfamide dosage weight by weight administered at the same time as ifosfamide as a single IV bolus and at 4 and 8 hours after each ifosfamide dose. The recommended IV dosing schedule is as follows (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014):
    1) 0 hour: ifosfamide 1.2 g/m(2) and mesna 240 mg/m(2)
    2) 4 hours: mesna 240 mg/m(2)
    3) 8 hours: mesna 240 mg/m(2)
    4) MAX dose: 60% of ifosfamide dose
    2) INTRAVENOUS AND ORAL
    a) The recommended IV dose is 20% of the ifosfamide dosage weight by weight administered at the same time as ifosfamide. The recommended oral dose is 40% of the ifosfamide dose at 2 and 6 hours following the ifosfamide dose. The recommended IV and oral dosing schedule is as follows (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014):
    1) 0 hour: ifosfamide 1.2 g/m(2) and IV mesna 240 mg/m(2)
    2) 2 hours: oral mesna 480 mg/m(2)
    3) 6 hours: oral mesna 480 mg/m(2)
    4) MAX dose: 100% of ifosfamide dose
    3) IV REGIMEN WITH CONTINUOUS INFUSION IFOSFAMIDE
    a) GUIDELINE DOSE: Mesna as an IV bolus dose equal to 20% of the total ifosfamide dose followed by a continuous infusion of mesna equal to 40% of the ifosfamide dose, continuing for 12 to 24 hours after the completion of the ifosfamide infusion (Hensley et al, 2009).
    b) MAID REGIMEN FOR METASTATIC SOFT TISSUE SARCOMA USED IN CLINICAL TRIAL: Doxorubicin 60 mg/m(2) and dacarbazine 1000 mg/m(2), mixed or administered separately via continuous IV infusion over 4 days, plus ifosfamide 6000 mg/m(2) and mesna 10,000 mg/m(2) mixed or infused separately over 3 days (ifosfamide) and 4 days (mesna). MAID is administered every 21 days if tolerated (Antman et al, 1993).
    c) MAID REGIMEN FOR METASTATIC OR UNRESECTABLE SARCOMA USED IN CLINICAL TRIAL: Doxorubicin 60 mg/m(2) and dacarbazine 900 mg/m(2), mixed and administered through central venous access via continuous IV infusion over 3 days, ifosfamide 7500 mg/m(2) and mesna 10,000 mg/m(2) mixed or infused separately through a peripheral line via a continuous IV infusion over 3 days (ifosfamide) and 4 days (mesna). MAID is administered every 21 days if tolerated (Elias et al, 1989).
    4) INHALATION
    a) In clinical trials, mesna 5% to 20% has been utilized by aerosolization, bronchial installation, or bronchial lavage for its mucolytic properties (Gobert et al, 1972; Corbeel, 1972; Noviant & Gajour, 1972; Hirsch et al, 1970; Clarke et al, 1979; Tekeres et al, 1981).
    7.2.2) PEDIATRIC
    A) ROUTE OF ADMINISTRATION
    1) INTRAVENOUS/ORAL
    a) Safety and effectiveness have not been established in pediatric patients (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    2) PARENTERAL
    a) A dosage of 25% of the daily ifosfamide dose given at 15 minutes, 4 hours, and 6 hours daily for 5 days was used in a study of 18 children and adolescents (Goren et al, 1989).

Maximum Tolerated Exposure

    A) The maximum tolerated human exposure to this agent has not been established.
    B) Hypersensitivity reactions, including mild hypotension, shortness of breath, asthma exacerbation, rash, and flushing have been reported in patients after receiving 4.5 to 6.9 g of mesna (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    C) Nausea, vomiting, diarrhea, and fever developed in 11 patients after receiving mesna 10 mg/kg to 66 mg/kg IV daily for 3 to 5 days in combination with ifosfamide or cyclophosphamide. These adverse effects also occurred in patients treated with oxazaphosphorine in combination with higher doses of mesna (80 mg/kg) (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) LD50- (INTRAPERITONEAL)MOUSE:
    1) 2005 mg/kg ((RTECS, 2000))
    B) LD50- (ORAL)MOUSE:
    1) 6102 mg/kg ((RTECS, 2000))
    C) LD50- (SUBCUTANEOUS)MOUSE:
    1) 1200 mg/kg ((RTECS, 2000))
    D) LD50- (INTRAPERITONEAL)RAT:
    1) 1251 mg/kg ((RTECS, 2000))
    E) LD50- (ORAL)RAT:
    1) 4440 mg/kg ((RTECS, 2000))
    F) LD50- (SUBCUTANEOUS)RAT:
    1) 2313 mg/kg ((RTECS, 2000))

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Mesna reduces ifosfamide-induced hemorrhagic cystitis by binding to 4-hydroxy-ifosfamide forming a non-urotoxic 4-sulfoethylthioifosfamide. and by binding to the double bonds of acrolein and other urotoxic ifosfamide metabolites thereby inhibiting their toxic effects on the bladder (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).
    B) Mesna inactivates acrolein and prevents urothelial toxicity without affecting the cytostatic activity of the other metabolites (Scheef et al, 1979).

Physicochemical

Physical Characteristics

    A) Mesna injection is a clear, colorless, aqueous solution that is nonpyrogenic. Mesna tablets are white (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014).

Ph

    A) 7.5 to 8.5 (solution) (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014)

Molecular Weight

    A) 164.18 (Prod Info MESNEX(TM) oral tablets, intravenous injection, 2014)

References

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