Mesnex

Approved Indications:

• Prevention of Hemorrhagic Cystitis:
• Indicated for prophylaxis against ifosfamide- or cyclophosphamide-induced hemorrhagic cystitis, especially in high-dose regimens.

Clinically Accepted Off-label Uses:

• Detoxification of urinary tract toxins produced by oxazaphosphorine chemotherapy agents.
• Supportive agent in high-dose chemotherapy protocols, especially when urotoxic metabolites are anticipated.

Route of Administration: Intravenous (IV), Oral

Adults:

• IV Mesna with Ifosfamide:
• 20% of the ifosfamide dose (by weight) at time 0 (start of chemo), followed by 20% at 4 and 8 hours post-chemo.
• Alternatively, 60% as a continuous IV infusion over 24 hours starting at the time of ifosfamide administration.
• Oral Mesna:
• 40% of the ifosfamide dose orally at 2 hours and 6 hours after an initial 20% IV dose.

Pediatrics:

• Dosing mirrors adult protocols, adjusted by body surface area or weight.

Renal Impairment:

• Dose adjustment may be necessary. Maintain adequate hydration. Monitor urinary output and renal function.

Hepatic Impairment:

• No specific dose adjustment is generally required.

Elderly:

• Use adult dosage. Monitor renal function and hydration status closely.

Mesna (2-mercaptoethane sulfonate sodium) is a synthetic thiol compound that protects the urinary tract by detoxifying acrolein, a toxic metabolite of oxazaphosphorine chemotherapy drugs like ifosfamide and cyclophosphamide. In the renal tubules and bladder, Mesna’s sulfhydryl group reacts with acrolein to form non-toxic, water-soluble complexes, which are then excreted in urine. This prevents damage to the bladder epithelium and reduces the risk of hemorrhagic cystitis.

• Absorption (oral): Rapid; bioavailability ~50%
• Onset of Action: Within 15–30 minutes (IV)
• Distribution: Mainly extracellular fluid; does not cross the blood-brain barrier
• Metabolism: Undergoes reversible oxidation to inactive disulfide (dimesna); reactivated in renal tubules
• Half-life: 0.4 to 1.2 hours
• Excretion: Primarily renal (unchanged and metabolites)

• Pregnancy:
• FDA Category B: Animal studies do not indicate fetal harm, but human studies are insufficient. Use only when clearly needed.
• Lactation:
• Unknown whether Mesna is excreted in human breast milk. Caution is advised during breastfeeding. Monitor infant for adverse effects if used.

• Primary Class: Cytoprotective Agent
• Subclass: Uroprotective Thiol Compound

• Known hypersensitivity to Mesna or any of its excipients
• Not effective for treatment of established hemorrhagic cystitis
• Use with caution in patients with autoimmune diseases due to rare hypersensitivity

• Hypersensitivity reactions: Rash, flushing, anaphylaxis, and hypotension have been reported.
• Dermatological reactions: Rare severe skin reactions including Stevens-Johnson syndrome.
• Hydration status: Ensure adequate hydration to support renal excretion and urinary protection.
• Monitoring: Urinary output, renal function, and presence of hematuria should be regularly assessed.
• Laboratory interference: May cause false-positive results for urinary ketones.

Common:

• Nausea, vomiting
• Diarrhea, abdominal cramps
• Flushing, fatigue
• Headache, fever
• Rash or urticaria

Serious/Rare:

• Anaphylaxis
• Severe allergic skin reactions (e.g., SJS/TEN)
• Hypotension
• Elevated liver enzymes
• Hematologic effects (rare)

Timing: Most adverse effects occur shortly after administration and are dose-related.

• Cyclophosphamide/Ifosfamide: Required combination; no reduction in antineoplastic efficacy.
• Live vaccines: Avoid due to immunosuppressive nature of chemotherapy protocols.
• Urine dipstick interference: May lead to false-positive tests for urinary ketones, bilirubin, or protein.

CYP Involvement:
Mesna is not significantly metabolized via CYP450 enzymes; thus, it has minimal CYP-related interactions.

• NCCN & ASCO: Continued recommendation of Mesna for high-dose ifosfamide regimens.
• EMA Safety Review: No significant safety changes; reaffirmed current dosing guidelines.
• Pediatric Oncology Protocols: Confirmed suitability and effectiveness of IV/oral sequential administration schedules.

• IV Formulation:
• Store at 2°C to 8°C (refrigerated).
• Protect from light.
• Do not freeze.
• Use within 24 hours of dilution.
• Oral Tablets/Solution:
• Store at 20°C to 25°C (68°F to 77°F).
• Keep container tightly closed.
• Protect from moisture.
• General Handling:
• Do not use discolored or particulate-containing solutions.
• Maintain aseptic technique during preparation.