SYNONYM(S): 1-4

sodium 2-mercaptoethanesulfonate

COMMON TRADE NAME(S):

UROMITEXAN(r), MESNEX(r) (USA)

CLASSIFICATION:

cytoprotective agent, non-cytotoxic

Special pediatric considerations are noted when applicable, otherwise adult provisions apply.

MECHANISM OF ACTION:

Mesna is a synthetic compound that protects the bladder from the urotoxic metabolites of oxazaphosphorine derivatives (e.g., ifosfamide, cyclophosphamide) by chemically interacting with them and their metabolites as a sulfhydryl donor in urine.

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PHARMACOKINETICS:

Adapted from standard reference1 unless specified otherwise.

SPECIAL PRECAUTIONS:

Contraindicated in patients with a history of hypersensitivity reaction to mesna2,3 or other sulfhydryl (thiol) compounds1,4

Autoimmune disorders 1,4

(e.g., rheumatoid arthritis, systemic lupus erythematosus, nephritis) may put patients at increased risk of developing hypersensitivity reactions to mesna.

Limited place in therapy: Mesna does not prevent nephrotoxicity or non-urologic toxicities associated with oxazaphosphorine derivatives.1 Mesna does not prevent hematuria associated with other conditions such as thrombocytopenia.1 Mesna is not a replacement for adequate hydration (i.e., at least 1 L of oral or IV fluid daily, prior to and during ifosfamide therapy).1 Special populations: Safety and efficacy of mesna in children have not been established; however, mesna has been used for prophylaxis of ifosfamide-induced hemorrhagic cystitis in infants and children 4 months to 16 years of age and for prophylaxis of cyclophosphamide-induced hemorrhagic cystitis in children >=5 months without unusual adverse effects.1 Neonates may potentially be at risk from benzyl alcohol preservative; toxicity has been associated with large amounts (i.e., 100-400 mg/kg daily). Avoid use in neonates if possible, although the American Academy of Pediatrics states that the presence of small amounts of the preservative in a commercially available injection should not preclude its use when indicated. Each mL of mesna in multidose vials contains 10.4 mg of benzyl alcohol as a preservative.1

Carcinogenicity: 2,3

not carcinogenic in rats.

Mutagenicity: not mutagenic in Ames test.1-3 Non-clastogenic in mammalian in vitro and in vivo chromosome tests.1

Fertility:

no information found.

Pregnancy: 1-4

FDA Pregnancy Category B. Animal-reproduction studies have not shown a fetal risk but there are no controlled studies in pregnant women.

Breastfeeding: 1,4

Not recommended due to the potential secretion into breast milk.

INTERACTIONS:

SUPPLY AND STORAGE:

Tablets:

not available in Canada

Injection

: Baxter supplies mesna for injection as a 100 mg/mL solution, in 4 mL and 10 mL ampoules.

Pharmaceutical Partners of Canada supplies mesna for injection as a 100 mg/mL solution, in 10 mL multidose vials. Each mL of mesna in multidose vials contains 10.4 mg of benzyl alcohol as a preservative. See Caution section.

For basic information on the current brand used at the BC Cancer Agency, see Chemotherapy Preparation and Stability Chart in Appendix.

SOLUTION PREPARATION AND COMPATIBILITY:

For basic information on the current brand used at the BC Cancer Agency, see Chemotherapy Preparation and Stability Chart in Appendix.

Compatibility of selected drugs9:

The following are compatible via Y-site injection: allopurinol sodium, amifostine, aztreonam, cefepime HCl, cladribine, cyclophosphamide, docetaxel, doxorubicin HCl liposome, filgrastim, fludarabine phosphate, gatifloxacin, gemcitabine HCl, granisetron, ifosfamide, linezolid, melphalan HCl, methotrexate sodium, ondansetron HCl, paclitaxel, piperacillin sodium-tazobactam sodium, sargramostim, sodium bicarbonate, teniposide, thiotepa, vinorelbine tartrate.

The following are compatible in the same infusion solution: hydroxyzine, ifosfamide.

Incompatibility of selected drugs9:

The following are incompatible via Y-site injection: amphotericin B cholesteryl sulfate complex.

The following are incompatible in the same infusion solution: carboplatin, cisplatin.

PARENTERAL ADMINISTRATION:

DOSAGE GUIDELINES:

Refer to protocol by which patient is being treated. Various mesna dosages have been used, and optimum dosages and methods of administration have not been established.1 Mesna dosing is based on the dosage of the oxazaphosphorine derivative (e.g., ifosfamide or cyclophosphamide).

Dosage is expressed as a percentage of oxazaphosphorine dose given

. Hour 0 is the time of the start of the oxazaphosphorine infusion.

Adults: BCCA usual dose noted in bold, italics

Mesna dose is a percentage of the oxazaphosphorine (e.g., ifosfamide or cyclophosphamide) dose given. Hour 0 is the time of the start of the oxazaphosphorine infusion.

*Oral:

Cycle Length: N/A2,3 40% of the oxazaphosphorine dose at hour 0, 4, and 8 *Extemporaneous oral solutions may be prepared using the parenteral dosage form. Because the injection solution has a disagreeable taste, doses are usually prepared by dilution with syrup, milk, juice, or carbonated beverages.

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Intravenous and Oral Combination:

Intravenous:

If an oral dose is vomited within two hours, the dose should be repeated or IV mesna given.

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N/A2,3 20% of the oxazaphosphorine dose IV at hour 0, followed by 40% of the oxazphosphorine dose PO at hour 4 and 8 N/A1,4,10 20% of the oxazaphosphorine dose IV at hour 0, followed by 40% of the oxazphosphorine dose PO at hour 2 and 6 N/A11 20% of the oxazaphosphorine dose IV at hour 0, followed by 40% of the oxazaphosphorine dose PO at hour 5 and 9 N/A12,13 20% of the oxazaphosphorine dose IV at hour 0, followed by 48% of the oxazaphosphorine dose PO at hour 3 and 7 N/A2,3,10 20% of the oxazaphosphorine dose at hour 0, 4, and 8 N/A2,3 10-12 mg/kg at hour 0, 4, and 8 N/A4 20% of the oxazaphosphorine dose at hour 0, 3, 6, and 9 BCCA usual dose noted in bold, italics

Mesna dose is a percentage of the oxazaphosphorine (e.g., ifosfamide or cyclophosphamide) dose given. Hour 0 is the time of the start of the oxazaphosphorine infusion.

Cycle Length: N/A14 12% of the ifosfamide dose at hour 0, then 50% of the ifosfamide dose admixed with ifosfamide and infused over

24 hours, followed by 25% of the ifosfamide dose over 12 hours

N/A11-13 20% of the oxazaphosphorine dose at hour 0, 5, and 9

Concurrent radiation:

Dosage in myelosuppression:

Dosage in renal failure: Dosage in hepatic failure:

results from in vitro test systems and clinical experience indicate that mesna may safely be used in regimens that include total body irradiation1 modify according to protocol by which patient is being treated; if no guidelines available, refer to Appendix 6 "Dosage Modification for Myelosuppression" no adjustment required1 no adjustment required1

Dosage in dialysis:

no information found

Dosage in elderly:

Although geriatric individuals were included in clinical studies, it has not been determined whether geriatric patients respond differently than younger adults. The ratio of ifosfamide to mesna should remain unchanged.1

Children:

Intravenous:

Cycle Length: N/A2,3 20% of the oxazaphosphorine dose at hour 0, 1, 3, 6, 9, and 12 N/A2,3 30% of the oxazaphosphorine dose at hour 0, 4, and 8

REFERENCES:

1. McEvoy GK, editor. AHFS 2007 Drug Information. Bethesda, Maryland: American Society of Health-System Pharmacists, Inc. p. 3785-8.

2. Pharmaceutical Partners of Canada. MESNA for Injection. Richmond Hill, Ontario; 10 October 2006.

3. Baxter Corporation. UROMITEXAN(r) product monograph. Mississauga, Ontario; 11 October 2006.

4. Rose BD, editor. Mesna. Waltham, Massachusetts: UpToDate 15.2; 2007.

5. National Institute for Occupational Safety and Health (NIOSH). Preventing occupational exposures to antineoplastic and other hazardous drugs in healthcare settings. Cincinnati, Ohio: NIOSH - Publications Dissemination; September 2004. p. 31-40.

6. Meg Knowling, MD. BC Cancer Agency Sarcoma Tumour Group. Personal communication. Vancouver, British Columbia; 22 September 2007.

7. BC Cancer Agency Provincial Systemic Therapy Program. Provincial Systemic Therapy Program Policy III-20: Prevention and management of extravasation of chemotherapy. Vancouver, British Columbia: BC Cancer Agency; 1 September 2006.

8. BC Cancer Agency. (SCNAUSEA) Guidelines for Prevention and Treatment of Chemotherapy-induced Nausea and Vomiting in Adults. Vancouver, British Columbia: BC Cancer Agency; 1 November 2005.

Trissel LA. Handbook on Injectable Drugs. 13 ed. Bethesda, Maryland: American Society of Health-System Pharmacists, Inc.; 2005. p. 979-82.

Schuchter LM, Hensley ML, Meropol NJ, et al. 2002 Update of recommendations for the use of chemotherapy and radiotherapy protectants: clinical practice guidelines of the American Society of Clinical Oncology. J Clin Oncol 2002; 20(12):2895-903.

BC Cancer Agency Sarcoma Tumour Group. (SAIME) BCCA Protocol Summary for Etoposide, Ifosfamide-Mesna for Patients with Newly Diagnosed Ewing's Sarcoma/Peripheral Neuroectodermal Tumour (PNET) or Rhabdomyosarcoma or Advanced Soft Tissue or Bony Sarcomas (This may be alternated with SAVAC or SAVAC+M). Vancouver, British Columbia: BC Cancer Agency; 1 October 2005.

BC Cancer Agency Genitourinary Tumour Group. (GUVIP2) BCCA Protocol Summary for Nonseminoma Consolidation/Salvage Using Etoposide, Cisplatin, Ifosfamide and Mesna. Vancouver, British Columbia: BC Cancer Agency; 1 February 2007.

BC Cancer Agency Genitourinary Tumour Group. (GUVEIP) BCCA Protocol Summary for Consolidation/Salvage Treatment for Germ Cell Cancer Using Vinblastine, Cisplatin, Ifosfamide and Mesna. Vancouver, British Columbia: BC Cancer Agency; 1 February 2007.

BC Cancer Agency Sarcoma Tumour Group. (SAAI) BCCA Protocol Summary for ADRIAMYCIN(r)-Ifosfamide-Mesna For Use In Patients With Advanced Soft Tissue Sarcoma. Vancouver, British Columbia: BC Cancer Agency; 1 August 2003.