1 vial [ampoule] MESNA Stada 100mg/ml, 4ml solution for injection contains: mesna 400mg (100 mg/ml).
Excipient/Inactive Ingredients: 1ml solution for injection contains 14.3 mg sodium. Sodium edetate (Ph. Eur.), sodium hydroxide, water for injections.
Substance or indication group: Sodium 2-mercaptoethanesulphonate. Antidote to oxazaphosphorines.
Pharmacology: Pharmacodynamics: The mode of action of the uroprotector mesna is based on the stabilisation of the urotoxic hydroxy metabolites of oxazaphosphorines on the one hand and on the other hand on formation of non-toxic compounds with acrolein. A regional detoxification in the kidneys and the lower urinary tract is achieved due to this reaction.
Pharmacokinetics: Following administration, the mesna monomer (free thiol compound) is rapidly metabolised to mesna disulphide (dimesna) in serum, which is again reduced in considerable amounts to the free thiol compound following glomerular filtration.
Mesna is almost exclusively eliminated via the kidneys and hardly via the bile. Following administration, renal elimination begins immediately and is largely completed after 8 hours. Within the first 4 hours after administration, mesna is mainly eliminated as free SH compound and then almost exclusively in form of the disulphide (dimesna).
Bioavailability: With regard to protection of the urinary bladder, the relevant compartment is the urine, where approx. 30% is bioavailable as free SH mesna after intravenous administration.
Toxicology: Preclinical safety data: Mesna is a pharmacologically and physiologically almost inert and non-toxic thiol compound which is excreted rapidly via the kidneys and does not penetrate tissues. In animal experiments, mesna showed no mutagenic, carcinogenic or teratogenic properties.
Acute toxicity: The LD50 in male and female mice as well as in male and female rats is on average 1929 mg/kg i.v.; 1720 mg/kg i.p., 5605 mg/kg p.o.
Chronic toxicity: In preclinical studies in several animal species (rat, rabbit and dog) mesna showed very low chronic toxicity.
Prevention of urinary tract toxicity of oxazaphosphorines (e.g. ifosfamide, cyclophosphamide or trofosfamide).
In the case of a tumour therapy with ifosfamide, MESNA Stada must always be given. In the case of a tumour therapy with cyclophosphamide or trofosfamide, MESNA Stada must always be given when dosages above 10 mg/kg are used and in patients at risk. Risks are in particular: previous radiation therapy in the area of the true pelvis, cystitis following previous therapy with ifosfamide, cyclophosphamide or trofosfamide and a history of uropathy.
Unless otherwise prescribed, MESNA Stada is usually administered in adults intravenously at time 0 (time of oxazaphosphorine administration), after 4 hours and after 8 hours, with each dose being 20% of the oxazaphosphorine dose.
Example of MESNA Stada administration in oxazaphosphorine injection:
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Therapeutic experience in children has shown that a more frequent (e.g. six times) administration at shorter intervals (e.g. 3 hours) is useful (total dose of MESNA Stada 60% of the oxazaphosphorine dose).
The total dose of MESNA Stada may be increased up to 120% of the oxazaphosphorine dose in high dose cytotoxic therapy with oxazaphosphorines (e.g. conditioning prior to bone marrow transplantation).
In the case of continuous infusions of ifosfamide, it has proven effective to administer a mesna bolus injection (20% of the ifosfamide dose) at time 0 (start of infusion) and to add MESNA Stada to the continuous infusion at a dose of up to 100% of the ifosfamide dose. To maintain the uroprotection after the end of the ifosfamide infusion, a mesna dose equivalent to up to 50% of the ifosfamide dose should be given for further 6-12 hours.
Example of MESNA Stada administration with a 24-hour ifosfamide infusion:
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The duration of use of MESNA Stada is defined by the duration of the oxazaphosphorine therapy.
A specific antidote to mesna is not known.
In connection with the anaphylactoid reactions in patients with autoimmune disease described in Contraindications and Adverse Reactions, suitable emergency medicine should be available.
Overdose may lead to the reactions described in Adverse Reactions (single doses exceeding 60 mg/kg BW).
Known hypersensitivity to mesna, other thiol compounds or to any of the excipients.
Notes: In the presence of autoimmune disease, there is an increased risk to develop allergic or anaphylactoid reactions (see also Adverse Reactions). Therefore, protection of the urinary tract with MESNA Stada should only be carried out in these patients after a careful risk-benefit assessment and under medical supervision.
As mesna is only indicated in combination with oxazaphosphorines, the contraindications which apply to cyclophosphamide, ifosfamide and trofosfamide should also be observed.
Please refer to Precautions and Use in Pregnancy & Lactation.
The protective effect of MESNA Stada applies only to the urinary tract. Other precautions and concomitant measures recommended for the use of oxazaphosphorines (ifosfamide, cyclophosphamide, trofosfamide) are not affected and should be continued.
A false-positive detection of urinary ketones may arise during the treatment with MESNA Stada. The colour is red-violet rather than violet, it is less stable and it will fade immediately on the addition of glacial acetic acid.
This medicinal product contains less than 1 mmol sodium (23 mg) per 1ml solution for injection.
Effects on ability to drive and use machines: Administration of MESNA Stada may result in an impairment caused by nausea and vomiting, also due to the concurrent tumour therapy.
As MESNA Stada is only used in combination with oxazaphosphorines (ifosfamide, cyclophosphamide or trofosfamide) for uroprotection in cytostatic therapy, criteria of such cytostatic therapy apply for use in pregnancy and lactation. Animal experiments have shown no evidence of embryotoxic or teratogenic effects of MESNA Stada.
The occurrence of anaphylactoid and other hyperergic reactions have been reported occassionally following the use of mesna. This risk is approx. 3.5 times higher in patients with autoimmune disease than in patients with tumour disease (without autoimmune disease).
Skin and mucous membrane reactions (urticaria, itching, exanthema, enanthema), increase in transaminases and general symptoms such as fever, exhaustion, nausea and vomiting occurred. Circulatory reactions such as fall in blood pressure and tachycardia have been observed rarely. Local oedema occurred in isolated cases; in rare cases venous irritation at the injection site.
In a tolerability study with high oral or intravenous doses of mesna, nausea, vomiting, diarrhoea, headache and limb pain, fall in blood pressure and tachycardia, skin reactions, exhaustion and weakness occurred, when a single dose of 60 mg/kg body weight was administered.
During treatment, the undesirable effects mentioned above cannot always be distinguished from those of the oxazaphosphorines (ifosfamide, cyclophosphamide, trofosfamide) or other concomitant medication.
In vitro, Mesna is incompatible with Carboplatin, Cisplatin and Nitrogen mustard.
Incompatibilities: In vitro, mesna is incompatible with carboplatin, cisplatin and nitrogen mustard.
Single use vial - discard appropriately any contents remaining after first use.
Shelf life: The shelf life of MESNA Stada is 5 years.
Chemical and physical in-use stability after dilution with 5% glucose solution and a solution containing ifosfamide has been demonstrated for 4 days at 2°C to 8°C and after dilution with 0.9% sodium chloride solution and a solution containing ifosfamide for 4 days at 25°C.
From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2°C to 8°C, unless dilution has taken place in controlled and validated aseptic conditions.
V03AF01 - mesna ; Belongs to the class of detoxifying agents used in antineoplastic treatment.
Soln for inj (clear, colourless solution, free from particles) (ampoule) 100 mg/mL x 4 mL x 10's.