Mesna

(BAN, USAN, rINN)
Mesna Chemical formula
Synonyms: D-7093; Mesnum; NSC-113891; UCB-3983. Sodium 2-mercaptoethanesulphonate.
Cyrillic synonym: Месна.

💊 Chemical information

Chemical formula: C2H5NaO3S2 = 164.2.
CAS — 19767-45-4.
ATC — R05CB05; V03AF01.
ATC Vet — QR05CB05; QV03AF01.

Pharmacopoeias.

In Eur..

Ph. Eur. 6.2

(Mesna). A white or slightly yellow, hygroscopic, crystalline powder. Freely soluble in water; slightly soluble in alcohol; practically insoluble in cyclohexane. A 10% solution in water has a pH of 4.5 to 6.0. Store in airtight containers.

Incompatibility and stability.

There was no evidence of degradation of mesna when stored in solution with ifosfamide in polyethylene infusion bags at room temperature for 7 hours 1 or in polypropylene syringes at room temperature or at 4° for 4 weeks. 2 However, in the latter study ifosfamide concentrations fell by about 3% after 7 days and 12% after 4 weeks at both temperatures. Another study 3 found that mixtures of mesna with cyclophosphamide in polyethylene infusion bags were stable for 48 hours at 4° and for 6 hours at room temperature. Mesna has been reported to be incompatible with platinum compounds such as carboplatin and cisplatin. 1. Shaw IC, Rose JWP. Infusion of ifosphamide plus mesna. Lancet 1984; i: 1353–4. 2. Rowland CG, et al. Infusion of ifosfamide plus mesna. Lancet 1984; ii: 468. 3. Menard C, et al. Stability of cyclophosphamide and mesna admixtures in polyethylene infusion bags. Ann Pharmacother 2003; 37: 1789–92.

💊 Adverse Effects and Precautions

Adverse effects that may occur after use of mesna include gastrointestinal effects, headache, fatigue, limb pains, depression, irritability, hypotension (but see below), tachycardia, and skin rash. Bronchospasm has been reported after nebulisation. Mesna may produce a false positive result in diagnostic tests for urinary ketones and may produce a false positive or false negative result in diagnostic tests for urinary erythrocytes.

Effects on blood pressure.

Hypotension may occur with mesna; however, severe hypertension has also been reported1 after use of mesna, either alone or with ifosfamide.
1. Gilleece MH, Davies JM. Mesna therapy and hypertension. DICP Ann Pharmacother 1991; 25: 867.

Effects on the nervous system.

For reports of severe encephalopathy in patients receiving mesna and ifosfamide.

Hypersensitivity.

Hypersensitivity reactions including rash, fever, nausea, facial and periorbital oedema, ulceration of mucous membranes, and tachycardia have been attributed to mesna.1-4 Reactions may be more common in patients with autoimmune disorders; drug eruptions developed in 7 of 16 patients receiving mesna and cyclophosphamide for auto-immune disorders.5 Five of these patients had a rash, with angioedema in 2 cases, and a pseudo-hypersensitivity reaction was diagnosed.
1. Lang E, Goos M. Hypersensitivity to mesna. Lancet 1985; ii: 329
2. Seidel A, et al. Allergic reactions to mesna. Lancet 1991; 338: 381
3. Gross WL, et al. Allergic reactions to mesna. Lancet 1991; 338: 381–2
4. D’Cruz D, et al. Allergic reactions to mesna. Lancet 1991; 338: 705–6
5. Zonzits E, et al. Drug eruptions from mesna: after cyclophosphamide treatment of patients with systemic lupus erythematosus and dermatomyositis. Arch Dermatol 1992; 128: 80–2.

💊 Pharmacokinetics

Mesna is absorbed from the gastrointestinal tract. It is rapidly metabolised after oral or intravenous dosage to mesna disulfide (dimesna) and is excreted in the urine as both metabolite and unchanged drug; dimesna is reduced back to mesna, which is the active form, in the kidney. The half-lives of mesna and dimesna are reported to be about 20 minutes and 70 minutes respectively. After intravenous use, most of the dose is excreted in the urine within 4 hours. Mesna is about 70% bound to plasma proteins.
1. Burkert H, et al. Bioavailability of orally administered mesna. Arzneimittelforschung 1984; 34: 1597–1600
2. James CA, et al. Pharmacokinetics of intravenous and oral sodium 2-mercaptoethane sulphonate (mesna) in normal subjects. Br J Clin Pharmacol 1987; 23: 561–8
3. El-Yazigi A, et al. Pharmacokinetics of mesna and dimesna after simultaneous intravenous bolus and infusion administration in patients undergoing bone marrow transplantation. J Clin Pharmacol 1997; 37: 618–24.

💊 Uses and Administration

Mesna is used for the prevention of urothelial toxicity in patients being treated with the antineoplastics ifosfamide or cyclophosphamide. In the kidney, dimesna, the inactive metabolite of mesna, is reduced to free mesna. This has thiol groups that react with the metabolites of ifosfamide and cyclophosphamide, including acrolein, which are considered to be responsible for the toxic effects on the bladder. The aim of mesna therapy is to ensure adequate levels of mesna in the urine throughout the period during which these toxic metabolites are present. The duration of mesna treatment should therefore equal that of the antineoplastic treatment plus the time taken for the concentration of antineoplastic metabolites in the urine to fall to non-toxic concentrations. Urinary output should be maintained and the urine monitored for haematuria and proteinuria throughout the treatment period. However, frequent emptying of the bladder should be avoided. Mesna may be given intravenously or orally for the prevention of urothelial toxicity, the dosage and frequency depending on the antineoplastic regimen used. After oral use, availability of mesna in urine is about 50% of that after intravenous use and excretion in urine is delayed up to 2 hours and is more prolonged. The intravenous preparation may be given orally added to a flavoured drink; this mixture may be stored in a sealed container in a refrigerator for up to 24 hours. Alternatively, tablets are available. Intravenous bolus antineoplastic regimens. If ifosfamide or cyclophosphamide is given as an intravenous bolus, the intravenous dose of mesna is 20% of the dose of the antineoplastic on a weight for weight basis given on 3 occasions over 15 to 30 minutes at intervals of 4 hours beginning at the same time as the antineoplastic injection; thus the total dose of mesna is equivalent to 60% of the antineoplastic given. This regimen is repeated each time the antineoplastic is used. Each individual dose of mesna may be increased to 40% of the dose of the antineoplastic and given 4 times at intervals of 3 hours for children and patients at high risk of urotoxicity; in such cases the total dose of mesna is equivalent to 160% of the antineoplastic given. The oral dose of mesna is 40% of the dose of the antineoplastic given on 3 occasions at intervals of 4 hours beginning 2 hours before the antineoplastic injection; thus a total dose of mesna equivalent to 120% of the antineoplastic is given. Alternatively, the initial dose of mesna may be given intravenously (20% of the dose of the antineoplastic), followed by two oral doses (each 40% of the dose of the antineoplastic) given 2 and 6 hours after the intravenous dose. Any of these regimens may be used if cyclophosphamide is given orally. Intravenous infusion antineoplastic regimens. If the antineoplastic is given as an intravenous infusion over 24 hours, an initial intravenous injection of mesna as 20% of the total antineoplastic dose is followed by 100% of the total dose by intravenous infusion concurrently over 24 hours, followed by 60% by intravenous infusion over a further 12 hours (total dose 180% of the antineoplastic). The final 12-hour infusion may be replaced either by 3 intravenous injections each of 20% of the antineoplastic dose at intervals of 4 hours, the first injection being given 4 hours after the infusion has been stopped, or by oral mesna given in 3 doses each of 40% of the antineoplastic dose, the first dose being given when the 24-hour infusion is stopped, and the second and third doses being given 2 and 6 hours later. Mesna is also used as a mucolytic in the management of some respiratory-tract disorders. The usual daily dose is 0.6 to 1.2 g given by a nebuliser; it may also be given by direct endotracheal instillation.
1. Schoenike SE, Dana WJ. Ifosfamide and mesna. Clin Pharm 1990; 9: 179–91
2. Siu LL, Moore MJ. Use of mesna to prevent ifosfamide-induced urotoxicity. Support Care Cancer 1998; 6: 144–54.

💊 Preparations

Proprietary Preparations

Arg.: Delinar; Mesnex†; Mestian; Neper; Uromitexan†; Varimesna; Austral.: Uromitexan; Austria: Mistabron; Uromitexan; Belg.: Mistabron; Uromitexan; Braz.: Mitexan; Canad.: Uromitexan; Chile: Mucofluid; Uromitexan; Uroprot; Cz.: Mistabron; Uromitexan; Denm.: Uromitexan; Fin.: Uromitexan; Fr.: Mucofluid; Uromitexan; Ger.: Mistabronco†; Uromitexan; Gr.: Uromitexan; Hong Kong: Mistabron; Uromitexan; Hung.: Uromitexan; India: Uromitexan; Indon.: Uromitexan; Irl.: Uromitexan; Israel: Mexan; Ital.: Mucofluid†; Mucolene†; Uromitexan; Jpn: Uromitexan; Malaysia: Mistabron†; Uromitexan†; Mex.: Mesnil; Mesodal; Uromes; Uromitexan†; Uroprot; Ziken; Neth.: Mistabron; Uromitexan; Norw.: Uromitexan; NZ: Uromitexan; Philipp.: Mistabron; Uromitexan; Pol.: Anti-Uron; Mistabron; Mucofluid; Uromitexan; Port.: Uromitexan; S.Afr.: Mistabron; Uromitexan; Singapore: Mistabron; Uromitexan; Spain: Mucofluid; Uromitexan; Swed.: Uromitexan; Switz.: Mistabron†; Uromitexan; Thai.: Mistabron†; Uromitexan; Turk.: Uromitexan; UK: Uromitexan†; USA: Mesnex. Multi-ingredient: India: Holoxan Uromitexan; Ifex-M; Ipamide with Mesna.
Published November 22, 2018.