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mesna
mesna
SYNONYM(S): Sodium 2-mercaptoethane sulfonate
COMMON TRADE NAME(S): Uromitexan® (multiple brands available)
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
| 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. |
Hydrophilic, does not enter most cells (i.e., remains in intravascular space).
| Cross blood brain barrier? | no |
| PPB | 69-75 % |
Rapidly oxidized in plasma to dimesna (mesna disulfide). No hepatic metabolism.
| Active metabolites | no |
| Inactive metabolites |
Dimesna (only metabolite) |
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) |
- Prevention and reduction of hemorrhagic cystitis secondary to cyclophosphamide or ifosfamide (oxazaphosphorines)
Emetogenic Potential:
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.
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)
- 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.
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.
| 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 |
| 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
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
Refer to the New Drug Funding Program or Ontario Public Drug Programs websites for the most up-to-date public funding information.
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