Mesna

Before and during your treatment with mesna, you may need frequent urine tests.

Follow all directions on your prescription label. Do not use this medicine in larger or smaller amounts or for longer than recommended.

Oral mesna is taken by mouth. Mesna injection is injected into a vein through an IV. Mesna is usually given in a series of 3 injections, or as a single injection followed by 2 oral doses.

A healthcare provider will give you the injection at the same time you receive ifosfamide. Oral mesna is usually taken 2 and 6 hours after you receive ifosfamide. Follow your doctor's dosing instructions carefully.

Call your doctor if you vomit within 2 hours after taking oral mesna. You may need to take another oral dose or receive a mesna injection.

Drink at least 1 quart (32 ounces) of liquid each day while you are using mesna.

Call your doctor if you have red or pink urine. This may be a sign that your mesna dose needs to be changed.

This medication can cause false results with certain urine tests. Tell any doctor who treats you that you are using mesna.

Store mesna tablets at room temperature away from moisture and heat.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Call your doctor for instructions if you miss a dose of mesna.

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Mesna falls into category B:

There are no well-done studies that have been done in humans with Mesna. But in animal studies, pregnant animals were given this medication, and the babies did not show any medical issues related to this medication.

OR

In animal studies, pregnant animals were given Mesna, and some babies had problems. But in human studies, pregnant women were given this medication and their babies did not have any problems related to this medication.

Take mesna exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The Mesna dose your doctor recommends will be based on the following (use any or all that apply):

• the condition being treated
• other medical conditions you have
• other medications you are taking
• how you respond to this medication
• your weight
• your height
• your age
• your gender

Mesna is available in the following doses:

• Ifosfamide-mesna 1 G-1 G Intravenous Kit
• Ifosfamide-mesna 3 G-1 G Intravenous Kit
• Mesna 100 Mg/ml Injectable Solution
• Mesna 400 Mg Oral Tablet
• Mesna Intravenous Kit

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

Storage

Oral

20–25°C.1

Parenteral

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

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

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

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For mesna, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to mesna or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of mesna in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of mesna in the elderly. However, elderly patients are more likely to have age-related kidney problems, which may require caution and an adjustment in the dose for patients receiving mesna.

Pregnancy

Breast Feeding

Studies suggest that this medication may alter milk production or composition. If an alternative to this medication is not prescribed, you should monitor the infant for side effects and adequate milk intake.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking mesna, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using mesna with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Warfarin

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of mesna. Make sure you tell your doctor if you have any other medical problems, especially:

• Allergy to thiol compounds (eg, amifostine), history of—Use with caution. May increase risk of an allergic reaction to occur again.

Pregnancy

Pregnancy Category B.

Risk Summary

There are no studies of Mesna in pregnant women.  Reproduction studies performed in rats and rabbits at oral doses approximately 10 times the maximum recommended total daily intravenous-oral-oral human dose on a body surface area basis (1,000 mg/kg in rabbits and 2,000 mg/kg in rats) revealed no evidence of harm to the fetus due to Mesna.  The incidence of malformations in human pregnancies has not been established for Mesna.  All pregnancies, regardless of drug exposure, have a background rate of 2 to 4% for major malformations and 15 to 20% for pregnancy loss.  Because animal reproductive studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers

It is not known whether Mesna or diMesna is excreted in human milk.  Benzyl alcohol present in maternal serum is likely to cross into human milk and may be orally absorbed by a nursing infant.  Because many drugs are excreted in human milk and because of the potential for adverse reactions in nursing infants from Mesna, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

Safety and effectiveness of Mesna in pediatric patients have not been established.  Mesna injection contains benzyl alcohol (10.4 mg benzyl alcohol per mL) which has been associated with serious adverse reactions and death in pediatric patients.  The “gasping syndrome,” (characterized by central nervous system depression, metabolic acidosis and gasping respirations) has been associated with benzyl alcohol dosages >99 mg/kg/day in neonates, premature, and low-birth weight infants.  Additional symptoms may include gradual neurological deterioration, seizures, intracranial hemorrhage, hematologic abnormalities, skin breakdown, hepatic and renal failure, hypotension, bradycardia, and cardiovascular collapse.  The minimum amount of benzyl alcohol at which toxicity may occur is not known.  Neonates, premature, and low-birth weight infants, as well as patients receiving high dosages, may be more likely to develop toxicity.  Practitioners administering this and other medications containing benzyl alcohol should consider the combined daily metabolic load of benzyl alcohol from all sources [see Warnings and Precautions (5.3)].

Geriatric Use

Clinical studies of Mesna did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.  In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.  The ratio of ifosfamide to Mesna should remain unchanged.

Use in Patients with Renal Impairment

No clinical studies were conducted to evaluate the effect of renal impairment on the pharmacokinetics of Mesna.

Use in Patients with Hepatic Impairment

No clinical studies were conducted to evaluate the effect of hepatic impairment on the pharmacokinetics of Mesna.

There is no known antidote for Mesna.

In a clinical trial, 11 patients received intravenous Mesna injection 10 mg/kg to 66 mg/kg per day for 3 to 5 days.  Patients also received ifosfamide or cyclophosphamide.  Adverse reactions included nausea, vomiting, diarrhea and fever.  An increased rate of these adverse reactions has also been found in oxazaphosphorine-treated patients receiving ≥80 mg Mesna injection per kg per day intravenously compared with patients receiving lower doses or hydration treatment only.

Postmarketing, administration of 4.5 g to 6.9 g of Mesna resulted in hypersensitivity reactions including mild hypotension, shortness of breath, asthma exacerbation, rash, and flushing.

Mesna Injection, is available as:

The container closure is not made with natural rubber latex.

Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].

(MES na)

• Mercaptoethane Sulfonate
• Sodium 2-Mercaptoethane Sulfonate

• Mesnex

Hypersensitivity to mesna or any component of the formulation

Prevention of ifosfamide-induced hemorrhagic cystitis (off-label use):

Short infusion standard-dose ifosfamide (<2.5 g/m2/day): ASCO guidelines: Refer to adult dosing.

Continuous infusion standard-dose ifosfamide (<2.5 g/m2/day): ASCO guidelines: Refer to adult dosing.

Other dosing strategies used in combination with ifosfamide (off-label dosing):

Mesna continuous infusion: IV: 1.8 g/m2/day to 5 g/m2/day as a continuous infusion (100% of the ifosfamide dose), repeated each day ifosfamide is received; see protocols for specific details (Bacci, 2003; Kolb, 2003; Moskowitz, 2011)

Mesna bolus followed by continuous infusion: IV: 1000 mg/m2 1 hour prior to ifosfamide on day 1, followed by 3000 mg/m2/day continuous infusion (continuous infusion is 100% of the ifosfamide dose) on days 1, 2, and 3 (with sufficient hydration) every 3 weeks for 6 courses (Juergens, 2006)

Mesna (20% higher than ifosfamide) continuous infusion: IV: 3600 mg/m2/day continuous infusion for 4 days (mesna dose is 20% higher than ifosfamide), with hydration, during weeks 4 and 9 (3 additional postop courses were administered in good responders) (Le Deley, 2007)

Prevention of cyclophosphamide-induced hemorrhagic cystitis (off-label use): HDCAV/IE regimen for Ewing sarcoma: Children ≥4 years and Adults <40 years: IV: 2100 mg/m2/day continuous infusion (mesna dose is equivalent to the cyclophosphamide dose) for 2 days with cyclophosphamide infusion during cycles 1, 2, 3, and 6 (Kolb, 2003)

There are no known significant interactions.