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A - Drug Name

mesna

SYNONYM(S):   Sodium 2-mercaptoethane sulfonate

COMMON TRADE NAME(S):   Uromitexan® (multiple brands available)

 
B - Mechanism of Action and Pharmacokinetics

Mesna reacts with acrolein and other urotoxic metabolites of oxazaphosphorines (cyclophosphamide or ifosfamide) in the urine to form stable, non-urotoxic compounds.  Mesna does not have any antitumour activity, nor does it appear to interfere with the antitumour activity of antineoplastic drugs



Absorption
Bioavailability oral: 50% (i.e., oral dose usually 2 x IV dose); provides lower but more prolonged urinary levels and higher systemic exposure, with total urinary recovery comparable to IV.  Urinary bioavailability not affected by food.

Distribution

Hydrophilic, does not enter most cells (i.e., remains in intravascular space).

Cross blood brain barrier? no
PPB 69-75 %
Metabolism

Rapidly oxidized in plasma to dimesna (mesna disulfide).  No hepatic metabolism.

Active metabolites no
Inactive metabolites

Dimesna (only metabolite)

Elimination

Rapidly cleared from plasma, filtered by glomerulus and partially (33%) reduced by the glutathione system back to mesna in renal tubules, then secreted into urine as a free thiol.

Urine IV: 32% mesna and 33% dimesna within 24 hours
Half-life

 ± 1 hr (up to 8 hours with PO)

 
C - Indications and Status
Health Canada Approvals:

  • Prevention and reduction of hemorrhagic cystitis secondary to cyclophosphamide or ifosfamide (oxazaphosphorines)


 
D - Adverse Effects

Emetogenic Potential:  

Not applicable

Extravasation Potential:   Irritant (undiluted)

The following adverse effects were observed in healthy patients who received IV/PO mesna without concurrent chemotherapy.

ORGAN SITE SIDE EFFECT* (%) ONSET**
Cardiovascular Flushing (11%) I
Hypotension (rare, may be fluid refractory) I
Palpitations (1%) I
Dermatological Rash (may be severe) I  E
Gastrointestinal Abdominal pain (22%) (more frequent with oral use) I  E
Anorexia (8%) I
Constipation (2%) E
Diarrhea (12%) (more frequent with oral use) I  E
Dry mouth (2%) I  E
Flatulence (9%) E
Nausea, vomiting (12%) (mild, more frequent with oral use) I
Other (4%) (GI pain - epigastric) I
General Fatigue (4%) E
Flu-like symptoms (11%) I
Hematological Lymphopenia (may be severe, generally reversible) I
Hepatobiliary ↑ LFTs (1%) E
Hypersensitivity Hypersensitivity (rare) I
Injection site Injection site reaction (25%) (venous irritation- rare, when undiluted) I
Metabolic / Endocrine Other (↑ PO4; moderate, transient) E
Musculoskeletal Musculoskeletal pain (8%) E
Nervous System Cognitive disturbance (1%) E
Dizziness (16%) I
Dysgeusia (100%) (unpleasant taste) I
Headache (36%) I
Paresthesia (5%) E
Ophthalmic Blurred vision (1%) I  E
Conjunctivitis (6%) I
Photophobia (4%) I  E
Respiratory Cough, dyspnea (4%) I


* "Incidence" may refer to an absolute value or the higher value from a reported range.
"Rare" may refer to events with < 1% incidence, reported in post-marketing, phase 1 studies,
isolated data or anecdotal reports.
Dose-limiting side effects are underlined.

** I = immediate (onset in hours to days)     E = early (days to weeks)
D = delayed (weeks to months)      L = late (months to years)

No venous irritation was observed when mesna was diluted with water 1:3. 

Hypersensitivity reactions, from mild allergic reactions to anaphylactic reactions, have occurred in patients receiving mesna. The incidence of hypersensitivity reactions appeared to be higher in patients with autoimmune disorders who were treated with cyclophosphamide; most of these patients received oral mesna. Reactions may occur during or after a first treatment or may be delayed until after several weeks or months of mesna exposure. Recurrence of reactions, in some cases with increased severity, has been reported with re-exposure.  Skin reactions include local or generalized rashes, and may be severe in some cases (e.g. Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms (DRESS) syndrome).   Some skin reactions were accompanied by flu-like or systemic symptoms (e.g. cardiovascular, pulmonary symptoms, prolonged prothrombin time, hematological changes, ↑LFTs or conjunctivitis, etc).  Photodistribution of a rash has also been reported.

 
E - Dosing

Refer to protocol by which patient is being treated. Numerous dosing schedules exist and depend on disease, response and concomitant therapy. Various mesna dosages have been used; optimum dosages and methods of administration have been established. Total daily IV dosage of mesna generally is equivalent to 60-160% of the total daily dosage of the oxazaphosphorine derivative (e.g. cyclophosphamide or ifosfamide); however, doses greater than 120% of oxazaphosphorine dose may be associated with increased gastrointestinal toxicity.

Adults:

Dosage expressed as percentage of oxazaphosphorine dose given. Note: 0 hr indicates start of the infusionThe mesna dosing schedule should be repeated on each day that the oxazaphosphorine is administered.  If the oxazaphosphorine dose is adjusted, the mesna dose should also be modified to maintain the mesna-to-oxazaphosphorine drug ratio.
IV Bolus:        20% of the oxazaphosphorine dose at 0 hr, 4 hrs and 8 hrs


Oral:              20% IV at 0 hr, 40% p.o at 4 hrs and 8 hrs OR 40% p.o and 0, 4 and 8 hrs.
Vomiting within 2 hours of oral mesna should be reported to the physician so that IV mesna can be given.



Note: Higher doses and more frequent administration are required when used for myeloablation. May be given as a continuous infusion when used with continuous infusion ifosfamide (load-20%, then 40% as a continuous infusion continuing for 8-24 hrs after completion of ifosfamide)
Dosage with Toxicity:

Dosage in myelosuppression:    No adjustment required.


Dosage with Hepatic Impairment:

No adjustment required.

Dosage with Renal Impairment:

No adjustment required.

Dosage in the elderly:

No dose adjustment required. Maintain ratio between ifosfamide and mesna doses.

Children:

Consult protocol being used. Generally use higher doses or more frequent administration.

 
F - Administration Guidelines

  • May be diluted in 50-100mL of diluent (D5W, NS) up to final concentration of 1 mg/mL to 20 mg/mL and given IV over 15-30 minutes.
  • May be diluted in larger volumes (1 mg/mL to 20 mg/mL) for continuous infusion over 3-24 hours.
  • May be infused concurrently with ifosfamide.  Note:  Benzyl alcohol in multi-dose vials can reduce the stability of ifosfamide and cyclophosphamide.
  • Incompatible in solution with cisplatin or carboplatin, nitrogen mustard.  Admixtures with epirubicin lead to inactivation of epirubicin.
  • In addition to mesna use, sufficient hydration and urine output should still be maintained.
  • IV solution may be given PO; may be mixed with juice, cola or milk to mask unpleasant taste. The manufacturer (for Uromitexan®) reccomends that multi-dose vials should not be used for PO doses.
  • Store ampoules and multi-dose vials at 15-25°C.


 
G - Special Precautions
Other:

Mesna is contraindicated in patients with known hypersensitivity to the drug. Use with caution in patients with hypersensitivity to other thiols. Formulations containing benzyl alcohol should not be used in pediatric patients who are 12 years old and younger.

Mesna does not prevent ifosfamide-induced nephrotoxicity nor prevent / decrease the incidence of non-urologic toxicities (i.e. myelosuppression, neurotoxicity) associated with oxazaphosphorines.  Mesna does not replace hydration and other prophylactic or supportive measures used in oxazaphosphorines treatment.   The half-life of mesna is shorter than the half-life of ifosfamide or cyclophosphamide, therefore multiple doses or continuous infusion of mesna, for 8-24 hours beyond the end of the oxazaphosphorine infusion is required to prevent urotoxicity.

Although mesna has not been shown to be fetotoxic, carcinogenic, or mutagenic in animal or in vitro studies, it is able to cross the placenta.  However, its safety in pregnancy and effect on fertility have not been established.  Breast feeding is not recommended due to the potential secretion into breast milk.

 
H - Interactions

AGENT EFFECT MECHANISM MANAGEMENT
Test for ketones in urine False positive, colour is reddish purple rather than purple Sulfonate group in mesna presumed to interact with the sodium nitroprusside reagent Caution
Serum CPK testing Lower values were observed in samples taken 24 h after mesna than pre-mesna samples Possibly due to significant interference with thiol dependent enzymatic CPK tests Caution
Urine screening tests for ascorbic acid False positive reactions in Tillman’s reagent-based tests Unknown Caution
 
I - Recommended Clinical Monitoring

Recommended Clinical Monitoring

Monitor Type Monitor Frequency
Clinical assessment of rash, GI symptoms, infusion site reactions and hypersensitivity
Also refer to monitoring parameters for other drugs used in the regimen

Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version

 
K - References

McEvoy GK, editor. AHFS Drug Information 2013. Bethesda, Maryland: American Society of Health-System Pharmacists, p. 3772-6.

Medeffect Health Professional Information: Mesna (Uromitexan®), multi-dose vials - association with fatal gasping syndrome in neonates and infants. Health Canada, September 6, 2011

Product Monograph:  Mesna.  Pharmaceutical Partners of Canada, January 15, 2008.

Product Monograph: Uromitexan® (mesna): Baxter Corp., August 6, 2013.


November 2017 republished to enable search by "cancer type" filter

 
L - Disclaimer

Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.

The information set out in the drug monographs, regimen monographs, appendices and symptom management information (for health professionals) contained in the Drug Formulary (the "Formulary") is intended for healthcare providers and is to be used for informational purposes only. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects of a particular drug, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for a given condition. The information in the Formulary is not intended to constitute or be a substitute for medical advice and should not be relied upon in any such regard. All uses of the Formulary are subject to clinical judgment and actual prescribing patterns may not follow the information provided in the Formulary.

The format and content of the drug monographs, regimen monographs, appendices and symptom management information contained in the Formulary will change as they are reviewed and revised on a periodic basis. The date of last revision will be visible on each page of the monograph and regimen. Since standards of usage are constantly evolving, it is advised that the Formulary not be used as the sole source of information. It is strongly recommended that original references or product monograph be consulted prior to using a chemotherapy regimen for the first time.

Some Formulary documents, such as the medication information sheets, regimen information sheets and symptom management information (for patients), are intended for patients. Patients should always consult with their healthcare provider if they have questions regarding any information set out in the Formulary documents.

While care has been taken in the preparation of the information contained in the Formulary, such information is provided on an “as-is” basis, without any representation, warranty, or condition, whether express, or implied, statutory or otherwise, as to the information’s quality, accuracy, currency, completeness, or reliability.

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