Mesnex

Generic Name: Mesna
Class: Protective Agents
VA Class: AD900
CAS Number: 19767-45-4

Introduction

Uroprotective agent; a synthetic sulfhydryl (thiol) compound.1 3 4 5

Uses for Mesnex

Prophylaxis of Ifosfamide-induced Hemorrhagic Cystitis

Reduction in the incidence of ifosfamide-induced hemorrhagic cystitis;1 2 3 4 5 6 8 9 37 38 39 40 43 44 47 60 use recommended by ASCO.60 61 Designated an orphan drug by FDA for this use.27

Slideshow: View Frightful (But Dead Serious) Drug Side Effects

Prophylaxis of Cyclophosphamide-induced Hemorrhagic Cystitis

Reduction in the incidence of hemorrhagic cystitis associated with high-dose cyclophosphamide in bone marrow transplantation (BMT) patients;7 9 10 11 12 13 14 26 28 45 46 60 ASCO currently recommends using either mesna plus saline diuresis or forced saline diuresis for this purpose.60 61

Designated an orphan drug by FDA for inhibition of urotoxic effects of oxazaphosphorine compounds (e.g., cyclophosphamide).27

Mesnex Dosage and Administration

General

  • To maintain adequate urinary protection, administer mesna regimen with each dose of ifosfamide1 2 3 or cyclophosphamide.7 11 12 45 46

  • Employ adequate oral and/or IV hydration.1 3 4 To prevent ifosfamide-induced hemorrhagic cystitis, hydrate with at least 1 L of oral or IV fluid daily before and during ifosfamide therapy.1 3 4 8 10 12 15 35 38 39 41 44 52 53

Administration

Administer orally1 or IV.1 2 3 7 8 10 15 34 38 41 43 44

Oral Administration

Administer orally.1

Prior to availability of oral dosage form, extemporaneous oral solutions3 4 5 6 8 16 26 29 were prepared by diluting the appropriate dose of mesna injection in syrup, carbonated beverages, or fruit (i.e., apple, orange) juice.3 5 6 26 (See Extemporaneous Oral Solutions under Stability.)

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer diluted (20 mg/mL) solution by IV injection.1 2 3 7 8 10 15 34 38 41 43 44

Has been administered as a 20-mg/mL solution by IV infusion over 15–30 minutes.18 32

Also has been administered by continuous IV infusion.3 4 5 10 17 34 37 38 39 40 41 42 60 For continuous IV infusion, may admix with ifosfamide and administer both drugs simultaneously.3 4 5 17 18 39 40

Dilution

Withdraw appropriate dose from vial containing 100 mg/mL and dilute with an appropriate volume of a compatible IV solution (see Solution Compatibility under Stability) to obtain a final solution containing 20 mg/mL.1 2 4 18

Dosage

Adults

Prophylaxis of Ifosfamide-induced Hemorrhagic Cystitis

If ifosfamide dosage is increased or decreased, maintain constant mesna-to-ifosfamide ratio.1

IV

IV injection: For daily ifosfamide dosages <2.5 g/m2,60 administer a mesna dosage equivalent to 20% weight/weight (w/w) of the daily ifosfamide dosage 15 minutes before60 or at the time of ifosfamide administration and then at 4 and 8 hours after the ifosfamide dose;1 2 3 60 61 total daily mesna dosage is equivalent to 60% w/w of the daily ifosfamide dosage.1 In patients receiving ifosfamide 1.2 g/m2, administer mesna 240 mg/m2 15 minutes60 before or at the time of ifosfamide administration, followed by 240 mg/m2 at 4 and 8 hours after the ifosfamide dose.1 2

Continuous IV infusion: For daily ifosfamide dosages <2.5 g/m2,60 ASCO recommends administering a mesna loading dose equivalent to 20% w/w of the daily ifosfamide dosage by IV injection, followed by 40% w/w of the daily ifosfamide dosage by continuous IV infusion, continued for 12–24 hours after completion of the ifosfamide infusion.60

For daily ifosfamide dosages >2.5 g/m2, there are insufficient data to recommend a mesna dosage; however, ASCO recommends more frequent and prolonged administration of mesna for maximum protection against urotoxicity.60 61 (See Prescribing Limits.)

IV, then Oral

For daily ifosfamide dosages <2 g/m2, administer a mesna dosage equivalent to 20% w/w of the daily ifosfamide dosage by IV injection at the time of ifosfamide administration, followed by 40% w/w of the daily ifosfamide dosage orally at 2 and 6 hours after the ifosfamide dose;1 60 total daily mesna dosage is equivalent to 100% w/w of the daily ifosfamide dosage.1

In patients receiving 1.2 g/m2 of ifosfamide, administer mesna 240 mg/m2 by IV injection at the time of ifosfamide administration, followed by 480 mg/m2 orally at 2 and 6 hours after the ifosfamide dose.1

If patient vomits oral dose within 2 hours of administration, repeat dose or consider IV administration.1 60

Prophylaxis of Cyclophosphamide-induced Hemorrhagic Cystitis
IV

Mesna dosage equivalent to 60–160% w/w of the daily cyclophosphamide dosage, given by IV injection (in 3–5 divided doses daily) or by continuous IV infusion4 10 11 14 45 46 (continued for ≥24 hours after cyclophosphamide is discontinued).7 11 45 52

Prescribing Limits

Adults

Prophylaxis of Ifosfamide-induced Hemorrhagic Cystitis
IV

Maximum mesna dosage equivalent to 60% w/w of the daily ifosfamide dosage.61

Safety and efficacy of the recommended mesna-to-ifosfamide ratio (see Dosage) not established for ifosfamide dosages >2.5 g/m2 daily.1

IV, then Oral

Safety and efficacy of the recommended mesna-to-ifosfamide ratio (see Dosage) not established for ifosfamide dosages >2 g/m2 daily.1

Special Populations

Geriatric Patients

Cautious dosing recommended; always maintain constant mesna-to-ifosfamide ratio.1 (See Geriatric Use under Cautions.)

Cautions for Mesnex

Contraindications

  • Known hypersensitivity to mesna or other sulfhydryl (thiol) compounds.1 2

Warnings/Precautions

Warnings

Therapy Limitations

Does not prevent ifosfamide- or cyclophosphamide-induced hemorrhagic cystitis in all patients.1 2 36 40 Prior to each scheduled ifosfamide dose, examine morning urine specimen for presence of erythrocytes.1 2 52 If hematuria (>50 erythrocytes/HPF or WHO ≥grade 2) occurs despite mesna prophylaxis, reduce ifosfamide or cyclophosphamide dosage or discontinue these antineoplastic agents.1 2

Does not prevent ifosfamide-induced nephrotoxicity3 4 30 34 or other nonurologic toxicities (e.g., myelosuppression, neurotoxicity, alopecia).1 2 3 8 Does not reduce risk of hematuria associated with other conditions such as thrombocytopenia.1 2 14

Sensitivity Reactions

Hypersensitivity and Anaphylactic Reactions

Hypersensitivity reactions (e.g., pruritus,3 4 19 rash,20 21 23 generalized urticaria,3 19 20 decreased platelet counts,1 facial edema4 19 ) and anaphylaxis reported.1 2 Increased incidence of hypersensitivity reactions in patients with autoimmune disorders receiving cyclophosphamide and mesna; most patients received mesna orally.1

Hypersensitivity reactions may respond to antihistamines and corticosteroids.3 4 19

General Precautions

Lactose Intolerance

Each 400-mg Mesnex tablet contains 59.3 mg lactose;53 patients with a history of lactose intolerance may be sensitive to this formulation of the drug.a

Specific Populations

Pregnancy

Category B.1

Lactation

Not known whether mesna or dimesna is distributed into human milk.1 2 Discontinue nursing or the drug.1 2

Pediatric Use

Safety and efficacy not established;1 53 however, has been used in infants as young as 4 months of age without unusual adverse effects.4 32 33 34

Large amounts of benzyl alcohol (i.e., 100–400 mg/kg daily) have been associated with toxicity in neonates;54 55 56 57 58 59 each mL of mesna in multidose vials contains 1.04 mg of benzyl alcohol.1 2 Do not use multidose vials in neonates and infants (see Preparations for information regarding preservative-free preparation); use multidose vials with caution in children and adolescents.1 2

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.1 3 4 53 Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and potential for concomitant disease and drug therapy.1 (See Geriatric Patients under Dosage and Administration.)

Common Adverse Effects

Mesna monotherapy: Headache, injection site reactions, flushing, dizziness, nausea, vomiting, somnolence, diarrhea, anorexia, fever, pharyngitis, hyperesthesia, influenza-like symptoms, coughing, constipation, flatulence, rhinitis, rigors, back pain, rash, conjunctivitis, arthralgia.1

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, coughing, dyspepsia, hypotension, pallor, dehydration, pneumonia, tachycardia, flushing.1

Interactions for Mesnex

No formal drug interaction studies to date.1

Specific Drugs, Therapies, and Laboratory Tests

Drug, Therapy, or Test

Interaction

Comments

Antineoplastic agents (cyclophosphamide, doxorubicin, ifosfamide, methotrexate, vincristine)

Pharmacologic interaction (loss of antineoplastic effects) unlikely1 2 8 9

Irradiation, total body

Pharmacologic interaction (loss of antineoplastic effects) unlikely7 9 10 11 12 46

May safely use with regimens that include total body irradiation7 9 10 11 12 46

Sodium nitroprusside tests for urinary ketones

Possible false-positive results1 2 3 48 due to interaction between sulfonate group in mesna and sodium nitroprusside reagent4 48

Mesnex Pharmacokinetics

Absorption

Bioavailability

In systemic circulation, mesna is rapidly and almost completely oxidized to dimesna.1 2 3 4 5 29 Following oral administration, peak plasma concentrations of mesna and dimesna are achieved within 4 and 3 hours, respectively.29 Higher systemic exposure with oral (consisting of IV and oral doses) than with IV regimen.1

Peak urine concentrations of mesna and dimesna are achieved within 4 hours after IV administration or 8 hours after oral administration.29

Urinary bioavailability following oral administration is approximately 45–79% of that following IV administration.1

Food

Food does not appear to affect urinary bioavailability of orally administered mesna.1

Distribution

Extent

Hydrophilic; does not enter most cells, including tumor cells.3 4 5 7 8 9

Not known whether mesna or dimesna is distributed into human milk.1 2

Does not cross the blood-brain barrier.6

Plasma Protein Binding

Approximately 69–75%.1

Elimination

Metabolism

In systemic circulation, mesna is rapidly and almost completely oxidized to dimesna, a chemically stable, pharmacologically inert metabolite.1 2 3 4 5 29

Mesna and dimesna do not undergo hepatic metabolism.1 2 4

Elimination Route

Dimesna is rapidly filtered and eliminated by the kidneys; in the kidneys, dimesna is partially reduced to the active drug, mesna.1 2 3 4 5 29 62

Excreted principally in urine as mesna (18–32%) or dimesna (33%);1 29 majority of IV dose excreted within 4 hours.1 2

More sustained urinary excretion over 24-hour period with IV and oral regimen than with IV regimen.1

Half-life

IV regimen: 0.36 hours (for mesna) or 1.17 hours (for dimesna).1 2 4 29

IV and oral regimen: 1.2–8.3 hours (for mesna).1

Stability

Storage

Oral

Tablets

20–25°C.1

Parenteral

Injection

15–30°C.1 2 For multidose vials, may store and use for up to 8 days after initial entry.1 For preservative-free ampuls, discard unused portion.4 18

When diluted as directed (see Dilution under Dosage and Administration and also Solution Compatibility under Stability), stable at 25°C for up to 24 hours.1 2

Do not store in glass or plastic syringes with Luer-Lok fittings for >12 hours because particulates may form.4 18 53

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Oral

Extemporaneous Oral Solutions

Mesna 20 or 50 mg/mL in flavored syrup is stable at 24°C for up to 7 days;26 mesna 1, 10, or 50 mg/mL in carbonated beverages or apple or orange juice is stable at 5°C for at least 24 hours.26

Parenteral

Solution CompatibilityHID

Compatible

Dextrose 5% in sodium chloride 0.2 or 0.45%1

Dextrose 5% in water

Ringer’s injection, lactated

Sodium chloride 0.9%

Drug Compatibility
Admixture CompatibilityHID

Compatible

Hydroxyzine HCl

Ifosfamide

Incompatible

Carboplatin

Cisplatin

Variable

Cyclophosphamide

Y-Site CompatibilityHID

Compatible

Allopurinol sodium

Amifostine

Aztreonam

Cladribine

Docetaxel

Doxorubicin HCl liposome injection

Etoposide phosphate

Filgrastim

Fludarabine phosphate

Gallium nitrate

Gemcitabine HCl

Granisetron HCl

Linezolid

Melphalan HCl

Methotrexate sodium

Micafungin sodium

Ondansetron HCl

Paclitaxel

Pemetrexed disodium

Piperacillin sodium–tazobactam sodium

Sargramostim

Sodium bicarbonate

Teniposide

Thiotepa

Vinorelbine tartrate

Incompatible

Amphotericin B cholesteryl sulfate complex

Actions

  • Exhibits detoxification activity in urinary tract only; does not appear to alter systemic activity or nonurologic toxicity of oxazaphosphorine derivatives (e.g., ifosfamide, cyclophosphamide).62

  • Sulfydryl donor; contains free sulfhydryl groups that interact chemically (in urine) with urotoxic metabolites of ifosfamide or cyclophosphamide and their precursors, resulting in detoxification of these metabolites.1 2 3 4 5

  • Enhances urinary excretion of cysteine, which can react chemically with acrolein, thus further contributing to uroprotective activity.5 6

  • Reduces the viscosity of pulmonary secretions.5 8

Advice to Patients

  • Importance of drinking at least 1 quart (4 cups) of liquid a day.1 Importance of notifying clinician if discoloration of urine (e.g., pink, red) occurs.1

  • Importance of notifying clinician if vomiting occurs within 2 hours of administering tablets or if a dose is missed.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses (e.g., autoimmune disorders).1

  • Importance of women informing their clinician if they are or plan to become pregnant or to breast-feed.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Although not commercially available, a preservative-free formulation (containing 200 mg of mesna in single-use ampuls) is available through a compassionate use program for selected patients.53 For more information, contact the manufacturer at 800-437-0994.53

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Mesna

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

400 mg

Mesnex

Bristol-Myers Squibb

Parenteral

Injection

100 mg/mL*

Mesna Injection

Mesnex

Bristol-Myers Squibb

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions July 13, 2013. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

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2. American Pharmaceutical Partners, Inc. Mesna injection prescribing information. Los Angeles, CA; 2001 Jun.

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HID. Trissel LA. Handbook on injectable drugs. 17th ed. Bethesda, MD: American Society of Health-System Pharmacists; 2013:749-52.

a. AHFS drug information 2003. McEvoy GK, ed. Mesna. Bethesda, MD: American Society of Health-System Pharmacists; 2004:3693-7.

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