Mesna

Oral
Prophylaxis against urothelial toxicity
Adult: Calculate dosage equivalent to 40% w/w of the IV bolus dose of oxazaphosphorine (ifosfamide or cyclophosphamide), given 2 hours before, then 2 and 6 hours after antineoplastic admin (total 3 doses).
Child: Shortened interval between doses and/or increased individual doses may be required.

Intravenous
Prophylaxis against urothelial toxicity
Adult: Calculate dosage equivalent to 20% w/w of the IV bolus dose of oxazaphosphorine (ifosfamide or cyclophosphamide), given simultaneously over 15-30 minutes. Repeat dose at 4 and 8 hours after the first dose. Dose may increase to 40% of the antineoplastic dose, given for 4 doses at 3 hourly intervals (0,3,6,9 hours), if necessary.
Child: Shortened interval between doses and/or increased individual doses may be required.
Incompatibility: IV: Incompatible with platinum derivatives (e.g. carboplatin, cisplatin, nitrogen mustard) and epirubicin.

May be taken with or without food.

Hypersensitivity.

Patient with autoimmune disorders, urothelium damage associated with oxazaphosphorines or pelvic irradiation, conditions associated with inadequate response at standard doses (e.g. history of urinary tract disease), history of hypersensitivity to thiol compounds. Children. Pregnancy and lactation. Patient Counselling This drug may cause drowsiness and dizziness, if affected, do not drive or operate machinery. Monitoring Parameters Monitor urine for haematuria and proteinuria.

Significant: Dermatological toxicities [e.g. rash with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome, toxic epidermal necrolysis]; haematuria. Blood and lymphatic system disorders: Lymphadenopathy. Cardiac disorders: Palpitations, chest pain, dyspnoea. Eye disorders: Conjunctivitis, photophobia, blurred vision. Gastrointestinal disorders: Abdominal pain or colic, diarrhoea, nausea, vomiting, dry mouth, mucosal irritation, constipation, flatulence, gingival bleeding, epigastric pain or burning. General disorders and administration site conditions: Fatigue, malaise, pyrexia, infusion site reactions (IV), influenza-like illness. Hepatobiliary disorders: Increased transaminase levels. Immune system disorders: Bronchospasm. Metabolism and nutrition disorders: Decreased appetite. Musculoskeletal and connective tissue disorders: Arthralgia, myalgia, back pain, pain in extremity, pain in jaw, rigors. Nervous system disorders: Headache, light headedness, lethargy or drowsiness, dizziness, paraesthesia, hyperesthesia, hypoesthesia, syncope. Psychiatric disorders: Disturbance in attention. Renal and urinary disorders: Dysuria. Respiratory, thoracic and mediastinal disorders: Epistaxis, nasal congestion, cough, laryngeal discomfort, pleuritic pain, hypoxia, respiratory distress. Skin and subcutaneous tissue disorders: Rash, pruritus, hyperhidrosis. Vascular disorders: Flushing.
Potentially Fatal: Hypersensitivity (e.g. anaphylaxis, severe bullous and ulcerative skin).

Symptoms: Nausea, vomiting, abdominal pain or colic, diarrhoea, headache, fatigue, limb and joint pains, rash, flushing, hypotension, bradycardia, tachycardia, paraesthesia, fever, bronchospasm.

May cause false positive reactions in nitroprusside sodium-based urine tests (e.g. dipstick tests) for ketone bodies. May cause false positive reactions in Tillman's reagent-based urine screening tests for ascorbic acid. May interfere with enzymatic creatine phosphokinase (CPK) activity tests that use a thiol compound for CPK reactivation thus, may result in a falsely low CPK level.

Mesna is first oxidized into mesna-disulphide or dimesna which is then reduced back into mesna in the renal tubuli epithelium. In the urine, mesna supplies free thiol group that reacts chemically with urotoxic oxazaphosphorine metabolites (e.g. acrolein) of ifosfamide and cyclophosphamide thereby reducing incidence of toxicities (e.g. haemorrhagic cystitits and haematuria) and enhancing excretion of cysteine which may increase uroprotective effect.
Absorption: Bioavailability: 58% (range: 45-71%) as free mesna. Time to peak plasma concentration: 1.5-4 hours (free mesna).
Distribution: Volume of distribution: 0.65 ± 0.24 L/kg. Plasma protein binding: 60-75%.
Metabolism: Rapidly metabolised via oxidation into mesna-disulphide or dimesna in the intravascular compartment.
Excretion: Via urine (32% as mesna, 33% as dimesna). Elimination half-life: Approx 22 minutes (mesna), approx 70 minutes (dimesna).

Intravenous: Store between 20-25°C. Oral: Store between 20-25°C.

Antidotes, Detoxifying Agents & Drugs Used in Substance Dependence

R05CB05 - mesna ; Belongs to the class of mucolytics. Used in the treatment of wet cough.
V03AF01 - mesna ; Belongs to the class of detoxifying agents used in antineoplastic treatment.