Uromitexan

mesna

Mesnex, Uromitexan (CA) (UK)

Pharmacologic class: Detoxifying agent

Therapeutic class: Hemorrhagic cystitis inhibitor

Pregnancy risk category B

Action

Reacts in kidney with urotoxic ifosfamide metabolites (acrolein and 4-hydroxy-ifosfamide), resulting in their detoxification. Also binds to double bonds of acrolein and to other urotoxic metabolites.

Availability

Injection: 100 mg/ml in 10-ml vials

Tablets (coated): 400 mg

Indications and dosages

➣ To prevent hemorrhagic cystitis in patients receiving ifosfamide

Adults: Combination I.V. and P.O. regimen-Single I.V. bolus dose of mesna at 20% of ifosfamide dosage, given at same time as ifosfamide, followed by two doses of mesna tablets P.O. at 40% of ifosfamide dosage given 2 and 6 hours after ifosfamide dose. I.V. regimen-I.V. bolus of mesna at 20% of ifosfamide dosage given at same time as ifosfamide, repeated 4 and 8 hours after each ifosfamide dose.

Dosage adjustment

• Children

Contraindications

• Hypersensitivity to drug or other thiol compounds

Precautions

Use cautiously in:

• autoimmune disorders

• pregnant or breastfeeding patients.

Administration

• Dilute with dextrose 5% in water, dextrose 5% in normal saline solution, dextrose 5% in 0.2% sodium chloride solution, dextrose 5% in 0.33% sodium chloride solution, dextrose 5% in 0.45% sodium chloride solution, normal saline solution, or lactated Ringer's solution for injection.

• Give I.V. bolus over at least 1 minute with ifosfamide dose and at prescribed intervals after ifosfamide doses.

See Don't use multidose vial (contains benzyl alcohol) in neonates or infants. In older children, use with caution.

• If patient vomits within 2 hours of oral mesna dose, repeat oral dose or switch to I.V. route.

Adverse reactions

CNS: fatigue, malaise, irritability, headache, dizziness, drowsiness, hyperesthesia, rigors

CV: hypertension, hypotension, ST-segment elevation, tachycardia

EENT: conjunctivitis, pharyngitis, rhinitis

GI: nausea, vomiting, diarrhea, constipation, anorexia, flatulence

Hematologic: hematuria

Musculoskeletal: back pain, joint pain, myalgia

Respiratory: coughing, tachypnea, bronchospasm

Skin: flushing, rash

Other: arm or leg pain, injection site reactions, fever, flulike symptoms, allergic reactions

Interactions

Drug-diagnostic tests. Hepatic enzymes: increased levels

Urinary erythrocytes: false-positive or false-negative results

Urine tests using Ames Multistix: false-positive for ketonuria

Patient monitoring

• Monitor nutritional and hydration status.

• Monitor vital signs and ECG. Watch closely for blood pressure changes and tachycardia.

• Assess body temperature. Stay alert for fever, flulike symptoms, and EENT infections.

• Monitor respiratory status carefully. Watch closely for cough, bronchospasm, and tachypnea.

Patient teaching

• Inform patient that drug may cause significant adverse effects. Reassure him that he will be monitored closely.

• Encourage patient to request analgesics or other pain-relief measures for headache, back or joint pain, hyperesthesia, or muscle ache.

See Advise patient to immediately report breathing difficulties and allergic symptoms.

• Inform patient about drug's adverse CNS effects. Explain safety measures used to prevent injury.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the tests mentioned above.

mesna

(mes-na) mesna,

Mesnex

(trade name),

Uromitexan

(trade name)

Classification

Therapeutic: antidotes
Pharmacologic: ifosfamide detoxifying agents
Pregnancy Category: B

Indications

Prevention of ifosfamide-induced hemorrhagic cystitis (see Ifosfamide monograph).May also prevent hemorrhagic cystitis from cyclophosphamide.

Action

Binds to the toxic metabolites of ifosfamide in the kidneys.

Therapeutic effects

Prevents hemorrhagic cystitis from ifosfamide.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability; 45–79% absorbed after oral administration. Following IV with PO dosing ↑ systemic exposure.Distribution: Unknown.Metabolism and Excretion: Rapidly converted to mesna disulfide, then back to mesna in the kidneys, where it binds to toxic metabolites of ifosfamide (18–26% excreted as free mesna in urine after IV and PO dosing).Half-life: Mesna—0.36 hr (IV); 1.2—8.3 hr (IV followed by PO); mesna disulfide—1.17 hr.

Time/action profile (detoxifying action)

ROUTEONSETPEAKDURATION
PO, IVrapidunknown4 hr

Contraindications/Precautions

Contraindicated in: Hypersensitivity to mesna or other thiol (rubber) compounds.Use Cautiously in: Obstetric / Lactation: Safety not established.

Adverse Reactions/Side Effects

Central nervous system

  • dizziness
  • drowsiness
  • headache

Gastrointestinal

  • anorexia
  • diarrhea
  • nausea
  • unpleasant taste
  • vomiting

Dermatologic

  • flushing

Local

  • injection site reactions

Miscellaneous

  • flu-like symptoms

Interactions

Drug-Drug interaction

None significant.

Route/Dosage

Intravenous (Adults) Give a dose of mesna equal to 20% of the ifosfamide dose at the same time as ifosfamide and 4 and 8 hr after.Oral Intravenous (Adults) Give a dose of IV mesna equal to 20% of the ifosfamide dose at the same time as ifosfamide; then give PO mesna equal to 40% of the ifosfamide dose 2 and 6 hr after ifosfamide (total mesna dose is 100% of ifosfamide dose).

Availability (generic available)

Tablets: 400 mg Injection: 100 mg/mL In combination with: In a kit with ifosfamide.

Nursing implications

Nursing assessment

  • Monitor for development of hemorrhagic cystitis in patients receiving ifosfamide.
  • Lab Test Considerations: Causes a false-positive result when testing urinary ketones.

Potential Nursing Diagnoses

Deficient knowledge, related to medication regimen (Patient/Family Teaching)

Implementation

  • Initial IV bolus is to be given at time of ifosfamide administration.
  • Oral: If second and third doses are given orally, administer 2 and 6 hr after IV dose.
    • If PO mesna is vomited within 2 hr of administration, repeat dose or use IV mesna.
  • Intravenous Administration
  • pH: 7.5–8.5.
  • Intermittent Infusion: 2nd IV dose is given 4 hr later, 3rd dose is given 8 hr after initial dose. This schedule must be repeated with each subsequent dose of ifosfamide. Diluent: Dilute 2-, 4-, and 10-mL ampules, containing a concentration of 100 mg/mL in 8 mL, 16 mL, or 50 mL, respectively, of D5W, 0.9% NaCl, D5/0.9% NaCl, D5/0.2% NaCl, D5/0.33% NaCl, or LR.Concentration: 20 mg/mL. Refrigerate to store. Use within 6 hr. Discard unused solution.
  • Rate: Administer over 15–30 min or as a continuous infusion.
  • Syringe Compatibility: ifosfamide
  • Y-Site Compatibility: allopurinol, amifostine, aztreonam, cefepime, docetaxel, doxorubicin liposome, etoposide phosphate, filgrastim, fludarabine, gemcitabine, granisetron, linezolid, melphalan, methotrexate, ondansetron, oxaliplatin, paclitaxel, pemetrexed, piperacillin/tazobactam, sargramostim, sodium bicarbonate, teniposide, thiotepa, vinorelbine
  • Y-Site Incompatibility: amphotericin B cholesteryl complex, lansoprazole
  • Additive Compatibility: ifosfamide
  • Additive Incompatibility: carboplatin, cisplatin

Patient/Family Teaching

  • Inform patient that unpleasant taste may occur during administration.
  • Advise patient to notify health care professional if nausea, vomiting, or diarrhea persists or is severe.

Evaluation/Desired Outcomes

  • Prevention of hemorrhagic cystitis associated with ifosfamide therapy.

mesna

An agent that may act as an antioxidant, protecting the urogenital tract from toxic effects of ifosfamide and cyclophosphamide by binding them with its sulfhydryl-moieties, thereby reducing the incidence of haemorrhagic cystitis and haematuria. 
Adverse effects
Rash, itching, diarrheoa, nausea, vomiting.

Uromitexan

A brand name for MESNA.