Mesna is indicated as a prophylactic agent for the prevention of ifosfamide-induced hemorrhagic cystitis (a condition characterized by bladder irritation and bleeding). It is also used to prevent hemorrhagic cystitis caused by high-dose cyclophosphamide therapy.

Mesna was developed to reduce the risk of hemorrhagic cystitis caused by ifosfamide. Structurally similar to the physiological cysteine–cystine system, Mesna is rapidly oxidized in the bloodstream to its main metabolite, mesna disulfide (diMesna). This metabolite remains within the intravascular compartment and is quickly eliminated through the kidneys. In the kidneys, mesna disulfide is reduced back to its active free thiol form (Mesna), which then chemically binds with urotoxic metabolites of ifosfamide such as acrolein and 4-hydroxy-ifosfamide, leading to their detoxification. The initial detoxification step involves binding of Mesna with 4-hydroxy-ifosfamide to form a non-urotoxic compound, 4-sulfoethylthioifosfamide. Mesna also reacts with the double bonds of acrolein and other toxic metabolites, neutralizing their harmful effects on the urinary bladder. In limited studies using human xenograft and rodent tumor models, Mesna given with ifosfamide (at dose ratios up to 20-fold, via IV or IP routes) did not show any reduction in antitumor efficacy.

For the prophylaxis of ifosfamide induced hemorrhagic cystitis, Mesna may be given on a fractionated dosing schedule of three bolus intravenous injections or a single bolus injection followed by IV administration of mesna as outlined below-

Intravenous schedule: Mesna is given as intravenous bolus injection in a dosage equal to 20% of the ifosfamide dosage (w/w) at the time of ifosfamide administration and 4 and 8 hours after each dose of Ifosfamide. The total daily dose of Mesna is 60% of the ifosfamide dose.

Intravenous Dosing: Mesna Injection is given as intravenous bolus injections in a dosage equal to 20% of the Ifosfamide dosage (w/w) at the time of Ifosfamide administration

Preparation of Intravenous Solutions/Stability: For IV administration the drug can be diluted by adding the Mesna Injection solution to any of the following fluids obtaining final concentrations of 20 mg Mesna/ml: 5% Dextrose Injection, 5% Dextrose and 0.2% Sodium Chloride Injection, 5% Dextrose and 0.33% Sodium Chloride Injection, 5% Dextrose and 0.45% Sodium Chloride Injection, 0.92% Sodium Chloride Injection, Lactated Ringer’s Injection.

No clinical drug interaction studies have been performed with Mesna.

Mesna is contraindicated in patients with known hypersensitivity to Mesna or any of the excipients present in the formulation.

Common adverse effects include abdominal colic, depression, diarrhea, fatigue, headache, hypotension, irritability, joint pain, limb pain, nausea, skin rash, tachycardia, and vomiting.

Pregnancy Category B. Adequate and well-controlled studies in pregnant women are not available. It is not known whether Mesna is excreted in human breast milk. Since many drugs are excreted in breast milk and due to the potential risk of serious adverse effects in nursing infants, a decision should be made whether to discontinue breastfeeding or discontinue the drug, considering the importance of treatment for the mother.

Allergic reactions to Mesna ranging from mild hypersensitivity to severe systemic anaphylaxis have been reported. Patients with autoimmune disorders receiving cyclophosphamide and Mesna appear to have a higher incidence of allergic reactions, especially with oral Mesna. Mesna is intended only to reduce the risk of ifosfamide-induced hemorrhagic cystitis and does not prevent other toxic effects of ifosfamide. It is also not effective in all cases; up to 6% of patients may still develop hematuria. Therefore, urine should be examined daily for microscopic hematuria before ifosfamide therapy. If hematuria occurs during recommended Mesna use, dose adjustment or discontinuation of ifosfamide may be required depending on severity. Mesna must be administered with each dose of ifosfamide as per dosing guidelines to reduce risk. It does not prevent hematuria caused by other conditions such as thrombocytopenia. Due to benzyl alcohol content, multidose vials should not be used in neonates or infants and should be used cautiously in older pediatric patients.

No specific antidote for Mesna overdose is known. In animal studies, oral doses of 6.1 g/kg in mice and 4.3 g/kg in rats were fatal, corresponding to approximately 15 and 22 times the maximum recommended human dose based on body surface area. Toxic effects included diarrhea, tremors, convulsions, shortness of breath, and cyanosis prior to death.

Antidote preparations

Store in the original carton at 20°–25°C. Protect from light. Keep out of reach of children.