mesna (Rx)

>10%

Nausea

Vomiting

Anorexia

Asthenia

Fatigue

Fever

Abdominal pain

Constipation

Anemia

Granulocytopenia

Leukopenia

Thrombocytopenia

Alopecia

1-10%

Anxiety

Confusion

Dizziness

Headache

Insomnia

Pain

Somnolence

Chest pain

Edema

Flushing

Tachycardia

Cough

Dyspnea

Pneumonia

Diarrhea

Hematuria

Hypokalemia

Back pain

Dehydration

Injection site reaction

Pallor

Contraindications

Hypersensitivity to mesna or other thiol compounds

Cautions

Does NOT prevent nephrotoxicity, myelosuppression, or neurotoxicity

Contains benzyl alcohol as preservative ( associated w/ potentially fatal "Gasping Syndrome" in preemies)

Will not prevent hemorrhagic cystitis in all patients; examine morning urine specimen for hematuria prior to ifosfamide or cyclophosphamide treatment

Does not prevent or improve other toxicities associated with ifosfamide or cyclophosphamide

If patient vomits within 2 hr after PO dose, repeat dose or give IV

Mesna does not prevent thrombocytopenia-related hematuria

Injection contains preservative benzyl alcohol which has been associated with serious adverse reactions and death when administered intravenously to premature neonates and low birth weight infants; avoid use

Pregnancy

Drug is used in combination with ifosfamide or other cytotoxic agents; ifosfamide can cause fetal harm when administered to a pregnant woman; refer to the ifosfamide prescribing information for more information on use during pregnancy

Mesna injection contains the preservative benzyl alcohol; because benzyl alcohol is rapidly metabolized by a pregnant woman, benzyl alcohol exposure in the fetus is unlikely

Animal data

• In embryo-fetal development studies, oral administration of mesna to pregnant rats (500, 1000, 1500, and 2000 mg/kg) and rabbits (500 and 1000 mg/kg) during period of organogenesis revealed no adverse developmental outcomes at doses approximately 10 times maximum recommended total daily human equivalent dose based on body surface area

Pregnancy testing

• Verify pregnancy status of females of reproductive potential prior to initiation of drug in combination with ifosfamide

Contraception

• Females: Advise females of reproductive potential to use effective contraception during treatment in combination with ifosfamide and for 6 months after last dose
• Males: Advise males with female partners of reproductive potential to use effective contraception during treatment in combination with ifosfamide and for 3 months after last dose

Lactation

Used in combination with ifosfamide or other cytotoxic agents; ifosfamide is excreted in breast milk; refer to the ifosfamide prescribing information for more information on use during lactation; there are no data on presence of mesna in human or animal milk, effect on breastfed child, or on milk production

Formulation contains preservative benzyl alcohol; because benzyl alcohol is rapidly metabolized by a lactating woman, benzyl alcohol exposure in breastfed infant is unlikely; because of potential for serious adverse reactions in breastfed child, advise lactating women not to breastfeed during treatment and for 1 week after last dose

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Oxidized to dimesna in the blood, and is in turn reduced back to mesna in the kidney; synthetic sulfhydryl (thiol) compound binds & detoxifies ifosfamide metabolite acrolein in bladder/kidney

Mesna disulfide (dimesna): Inert metabolite

Pharmacokinetics

Bioavailability: 45-79 %

Protein Bound: 69-75% (mesna plus dimesna)

Metabolism: Kidney

Metabolites: Mesna disulfide

Excretion: Urine (18-32% as mesna; 33% as dimesna)

Distribution: Does not penetrate tissue

Half-life: 0.36 hr (Mesna); 1.17 hr (dimesna)

Peak plasma time: 4 hr (mesna); 3 hr (dimesna)

Peak plasma concentration: 3.3 mcg/mL (PO; mesna); 7.3 mcg/mL (PO; dimesna)

IV Incompatibilities

Additive: carboplatin, cisplatin, ifosfamide/epirubicin

Syringe: ifosfamide/epirubicin

Y-site: amphotericin B cholesteryl sulfate

IV Compatibilities

Solution: D5W, NS, LR, D5/½NS

Additive: ifosfamide, hydroxyzine

Syringe: ifosfamide

Y-site (partial list): allopurinol, docetaxel, gemcitabine, doxorubicin liposomal, linezolid, granisetron, ondansetron, vinorelbine

IV Preparation

Reconstitute w/ D5W, NS, dextrose/saline or LR to a final concentration of 20 mg/mL

IV Administration

IVP: bolus 15 min before ifosfamide

Intermittent infusion over 15-30 min

Continuous Infusion: may be added to ifosfamide/cyclophosphamide in infusion bag

• Additive compatibility w/ cyclophosphamide shown only in D5W & LR

Multiple protocols exist; check institutional guidelines

Storage

Store unopened vials at 20-25°C (68-77°F)

Opened ampoules will oxidize to dimesna upon exposure to air