Mesna

Pronunciation: MESS-nah
Class: Cytoprotective agent

Trade Names

Mesnex
- Tablets 400 mg
- Injection 100 mg/mL

Pharmacology

Mesna is used to reduce the incidence of ifosfamide-induced hemorrhagic cystitis. Mesna disulfide is reduced to the free thiol compound, mesna, which reacts chemically with the urotoxic ifosfamide metabolites, resulting in their detoxification.

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Pharmacokinetics

Absorption

Urinary bioavailability of oral mesna is 45% to 79%.

Distribution

Protein binding is 69% to 75%; Vd is 0.652 L/kg.

Metabolism

The major metabolite is dimesna.

Elimination

Approximately 32% is excreted in urine within 24 h. The t _½ is 1.2 to 8.3 h (after IV plus oral dose); the plasma Cl is 1.23 L/kg/h.

The mesna disulfide is reduced to the free thiol compound that reacts chemically with the urotoxic ifosfamide metabolites, resulting in their detoxification. At doses of 2 to 4 g, the terminal elimination t _½ is approximately 4 to 8 h. It is rapidly eliminated by the kidneys.

Indications and Usage

Prevention of ifosfamide-induced hemorrhagic cystitis.

Unlabeled Uses

Prevention of cyclophosphamide-induced hemorrhagic cystitis.

Contraindications

Standard considerations.

Dosage and Administration

IV Mesna dose is given as bolus injections in a dosage equal to 20% of ifosfamide dose at time of administration, 4 h after, and 8 h after each ifosfamide dose (eg, for ifosfamide 1,200 mg/m ² , give mesna 240 mg/m ² at 0, 4, and 8 h after each ifosfamide dose). The total daily dose of mesna is 60% of the ifosfamide dose. Repeat this dosing schedule on each day that ifosfamide is administered. When the dosage of ifosfamide is adjusted, modify the dose of mesna accordingly.

PO Following the initial IV mesna dose (20% of ifosfamide dose), the oral mesna dose is 40% of ifosfamide dose 2 and 6 h after each ifosfamide dose.

General Advice

• Repeat the oral dose or administer IV bolus dose if patient vomits within 2 h of administration.
• For IV bolus administration only. Not for intradermal, subcutaneous, IM, or intra-arterial administration.
• Dilute IV concentrate to final concentration of 20 mg/mL with a compatible IV fluid following manufacturer's recommendations.
• Do not administer injection if cloudiness or particulate matter is noted.

Storage/Stability

Store tablets at controlled room temperature (68° to 77°F). Store vials at controlled room temperature (68° to 77°F). Multidose vial can be used for up to 8 days following initial opening. Diluted solutions are stable for up to 24 h if stored at temperature less than 77°F. Discard any unused solution after 24 h.

Drug Interactions

None well documented.

Laboratory Test Interactions

A false-positive test for urinary ketones may arise in patients treated with mesna.

Adverse Reactions

Because mesna is used in combination with ifosfamide or ifosfamide-containing regimens, it is difficult to distinguish the adverse reactions that may be caused by mesna from those caused by coadministered cytotoxic agents. The following adverse reactions are reasonably associated with mesna administration in patients also receiving ifosfamide or ifosfamide-containing regimens.

Cardiovascular

Tachycardia (6%); hypotension (5%); ST-segment elevation (postmarketing).

CNS

Fatigue (20%); anorexia (18%); headache (11%); somnolence (10%); insomnia (9%); dizziness (8%); anxiety, confusion (6%).

Dermatologic

Alopecia (11%); flushing (5%); injection site reaction including pain and erythema (postmarketing).

GI

Nausea (54%); vomiting (38%); constipation (24%); diarrhea (14%); dyspepsia (5%).

Genitourinary

Hematuria (7%).

Hepatic

Increased liver enzymes (postmarketing).

Hematologic-Lymphatic

Leukopenia (21%); thrombocytopenia, anemia (18%); granulocytopenia (13%).

Metabolic-Nutritional

Hypokalemia (9%); dehydration (6%).

Musculoskeletal

Myalgia (postmarketing).

Respiratory

Dyspnea (9%); coughing (8%); pneumonia (7%); tachypnea (postmarketing).

Miscellaneous

Fever (20%); asthenia (18%); abdominal pain (15%); chest pain, pain, increased sweating, injection site reaction (8%); back pain (7%); edema (8%); peripheral edema (7%); face edema, pallor (5%); allergic reactions, limb pain, malaise (postmarketing).

Precautions

Pregnancy

Category B .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Hypersensitivity

Allergic reactions were reported ranging from mild hypersensitivity to systemic anaphylactic reactions.

Benzyl alcohol

Benzyl alcohol, contained in this product as a preservative, has been associated with a fatal “gasping syndrome” in premature infants.

Hematuria

Mesna does not prevent hemorrhagic cystitis in all patients. Up to 6% treated have developed hematuria (more than 50 rbc/hpf or WHO grade 2 and above).

Ifosfamide toxicities

Mesna prevents ifosfamide-induced hemorrhagic cystitis. It will not prevent or alleviate other adverse reactions or toxicities associated with ifosfamide therapy.

Patient Information

• Advise patient, family, or caregiver to review the patient information sheet before using the first time and with each course of therapy.
• Advise patient, family, or caregiver that injectable medication will be prepared and administered by a health care provider in a health care setting.
• Review dosing schedule with patient, family, or caregiver.
• Instruct patient to take tablets at the exact times given to them by health care provider.
• Advise patient that if a dose is missed, to take it as soon as remembered and then contact health care provider for further instructions. Caution patient not to double the dose.
• Advise patient taking tablets to contact health care provider immediately if vomiting occurs within 2 h of taking the dose.
• Advise patient to drink at least 4 cups (1 quart) of liquid each day that mesna is being used.
• Advise patient, family, or caregiver to immediately report any of the following to health care provider: red or pink-colored urine; rash; itching; hives.
• Advise patient, family, or caregiver to report any of the following to health care provider: persistent nausea, vomiting, diarrhea, appetite loss.

Copyright © 2009 Wolters Kluwer Health.