Mesna-LANS® (Solution) Instructions for Use
ATC Code
V03AF01 (Mesna)
Active Substance
Mesna (Rec.INN registered by WHO)
Pharmacotherapeutic Group
Other therapeutic agents; agents for reducing the toxicity of anticancer therapy
Pharmacological Action
Mesna is an antidote to acrolein, a metabolite of antineoplastic agents from the oxazaphosphorine group (ifosfamide, cyclophosphamide), which has an irritating effect on the bladder mucosa.
The protective properties of mesna are due to its interaction with the double bond of the acrolein molecule, leading to the formation of a stable non-toxic thioether. By reducing the urotoxic effects of oxazaphosphorines, Mesna does not weaken their antineoplastic action.
Detailed and extensive pharmacological and toxicological studies have demonstrated that Mesna has no specific pharmacodynamic properties and has low toxicity.
The pharmacological and toxicological inertness of mesna administered systemically and its detoxifying effect in the efferent urinary tract and bladder are due to the pharmacokinetic properties of the agent.
Pharmacokinetics
Mesna, being a free thiol, is easily and rapidly converted by self-oxidation into mesna disulfide (dimesna), which is the only metabolite.
Dimesna remains in the intravascular space and is rapidly transported to the kidneys.
In the epithelium of the renal tubules, dimesna is again reduced to a free thiol compound, which can enter into a chemical reaction with toxic metabolites of oxazaphosphorines in the urine.
Protein binding is 69-75%.
The T1/2 of mesna and dimesna after IV administration of a single dose of 800 mg is 0.36 h and 1.17 h, respectively.
Elimination (almost entirely carried out by the kidneys) begins immediately after administration of the agent.
Excretion in the form of a free thiol (mesna) occurs within the first 4 hours after a single administration, and then predominantly in the form of a disulfide (dimesna).
Most of it is excreted by the kidneys after approximately 8 hours.
After administration of a single dose of 800 mg over 24 hours, approximately 32% of the administered dose is excreted by the kidneys as mesna, and 33% of the administered dose is excreted as dimesna.
The plasma clearance of mesna is 1.23 L/h/kg.
Approximately 30% of the intravenously administered dose is found in the urine as a free thiol (mesna).
Indications
Local detoxification of the urotoxic effects of cytostatics – derivatives of oxazaphosphorines, including during ifosfamide administration; during administration of oxazaphosphorines in high doses (more than 10 mg/kg); in at-risk patients – previous radiation therapy to the pelvic area, development of cystitis during previous therapy with oxazaphosphorines, history of urinary system diseases.
ICD codes
| ICD-10 code | Indication |
| T45.1 | Poisoning by antineoplastic and immunosuppressive drugs |
| Y43.3 | Other antineoplastic drugs |
| Y84.2 | Radiological procedure and radiotherapy |
| ICD-11 code | Indication |
| NE60 | Poisoning by drugs, medicaments or biological substances, not elsewhere classified |
| PK81.C | Radiotherapy causing injury or harm in the course of therapeutic use |
| PL00 | Drugs, medicaments or biological substances causing injury or harm in therapeutic use |
Dosage Regimen
| The method of application and dosage regimen for a specific drug depend on its form of release and other factors. The optimal dosage regimen is determined by the doctor. It is necessary to strictly adhere to the compliance of the dosage form of a specific drug with the indications for use and dosage regimen. |
Administer intravenously only. Determine the total daily dose as a percentage of the oxazaphosphorine (e.g., ifosfamide) dose, typically 60% in divided administrations.
Divide the total daily mesna dose into three or four equal portions. Administer the first portion as a slow intravenous bolus immediately before the oxazaphosphorine infusion. Give subsequent portions at 4 and 8 hours after the start of the cytostatic infusion.
For prolonged or high-dose ifosfamide regimens, administer a fourth dose. Adjust the dosing interval and total number of doses based on the duration of cytostatic excretion.
Ensure adequate hydration and maintain a high urine output (>100 mL/m²/hour) throughout therapy to facilitate detoxification.
In pediatric patients, use the same weight-based or body surface area-based calculation as for adults. Adhere strictly to the divided-dose schedule.
For patients experiencing nocturnal dosing challenges, consider a continuous intravenous infusion. Calculate the total daily dose and administer it evenly over 12 to 24 hours, commencing with the cytostatic therapy.
Monitor urine for hematuria regularly. Increase the mesna dose frequency or total dose if hemorrhagic cystitis occurs, in conjunction with vigorous hydration.
Do not mix Mesna with platinum derivatives (e.g., cisplatin) or epirubicin in the same infusion solution.
Adverse Reactions
From the hematopoietic system frequent – lymphadenopathy; frequency unknown – pancytopenia, leukopenia, lymphopenia, thrombocytopenia, eosinophilia.
From the immune system frequency unknown – hypersensitivity reactions, anaphylaxis.
From metabolism frequent – decreased appetite, dehydration.
From the psyche frequent – insomnia, nightmares.
From the nervous system very frequent – presyncope, lethargy, drowsiness; frequent – dizziness, paresthesia, hyperesthesia, attention impairment; frequency unknown – seizures.
From the organ of vision frequent – conjunctivitis, photophobia, blurred vision; frequency unknown – periorbital edema.
From the cardiovascular system very frequent – flushing; frequent – palpitations; frequency unknown – atypical ECG data, tachycardia, decreased blood pressure, increased blood pressure.
From the respiratory system frequent – nasal congestion, cough, pleuritic pain, dry mouth, bronchospasm, shortness of breath, laryngeal discomfort, epistaxis; frequency unknown – respiratory failure, hypoxia, decreased blood oxygen saturation, tachypnea, hemoptysis.
From the digestive system: very frequent – abdominal pain/abdominal cramping pain, nausea, diarrhea; frequent – flatulence, burning pain (retrosternal/in the epigastric region), constipation, gum bleeding; frequency unknown – stomatitis, taste disorders.
From the liver and biliary tract frequent – increased transaminase activity; frequency unknown – hepatitis, increased GGT and ALP activity.
From the skin and subcutaneous tissues: very frequent – rash (including non-itchy, itchy, erythematous/erythematous, eczematous, papular and/or macular eruptions), frequent – pruritus, hyperhidrosis; frequency unknown – toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema, drug rash (with eosinophilia and systemic symptoms), ulcerations and/or bullous rash/blisters (mucocutaneous, mucosal, oral, vulvovaginal, anorectal), angioedema, persistent drug-induced erythema, photosensitivity rash, urticaria, burning sensation, erythema.
From the musculoskeletal system: frequent – arthralgia, back pain, muscle pain, limb pain, jaw pain.
From the urinary system frequent – urination disorders; frequency unknown – acute renal failure.
From laboratory parameters frequency unknown – increased prothrombin time, increased aPTT.
General reactions very frequent – influenza-like illnesses; frequent – shivering, fatigue, chest pain, malaise; frequency unknown – facial edema, peripheral edema, asthenia.
Local reactions very frequent – injection site pruritus, injection site rash; frequent – injection site pain, injection site erythema, injection site urticaria, injection site swelling.
Contraindications
Hypersensitivity to mesna or other thiol compounds; pregnancy, breastfeeding period.
Use in Pregnancy and Lactation
Contraindicated for use during pregnancy and lactation (breastfeeding). If use during lactation is necessary, the issue of discontinuing breastfeeding should be decided.
Pediatric Use
Can be used in children according to indications in recommended doses and regimens.
Special Precautions
Hypersensitivity reactions have been noted after administration of mesna used as a uroprotectant. Such reactions include various symptoms from the skin and subcutaneous tissue.
In addition, cases of severe bullous and ulcerative skin lesions and reactions from the mucous membrane have been noted. Some reactions were considered similar to Stevens-Johnson syndrome, toxic epidermal necrolysis, or exudative multiforme erythema.
In some cases, skin reactions were accompanied by the following symptoms (one or more): fever, symptoms from the cardiovascular and respiratory systems (decreased or increased blood pressure, tachycardia, signs of perimyocarditis on ECG, hypoxia, bronchospasm, tachypnea, cough, bloody sputum), symptoms similar to acute renal failure, hematological parameter disorders, increased liver enzyme activity, nausea, vomiting, pain in the limbs, joints and muscles, malaise, stomatitis and conjunctivitis.
Some reactions manifested as anaphylaxis.
Mesna is a thiol compound, i.e., an organic compound containing sulfhydryl (SH) groups. Thiol compounds have some similarity regarding the profile of adverse reactions, including the ability to cause severe skin reactions. Medicinal products containing thiol compounds include amifostine, penicillamine and captopril.
It is unknown whether patients who have had adverse reactions to a thiol drug have an increased risk of developing any or similar reactions to another thiol compound. However, when considering the possibility of using another thiol compound in such patients, the likelihood of an increased risk of adverse reactions should be taken into account.
Mesna does not prevent hemorrhagic cystitis in all patients, so patients should be monitored appropriately.
It is necessary to monitor the maintenance of a sufficient amount of urine output, as required by treatment with oxazaphosphorines.
During therapy with mesna, false-positive reactions may occur when determining the presence of ketone bodies in the urine if the test is based on the sodium nitroprusside reaction in an alkaline environment (including test strips).
The addition of glacial acetic acid can be used to distinguish a false-positive result (gradually disappearing cherry-red color) from a true-positive result (intensifying red-violet color).
During therapy with mesna, false-positive reactions may occur during screening tests based on the use of Tillman’s reagent to determine the ascorbic acid content in urine.
Effect on ability to drive vehicles and operate machinery
Patients undergoing treatment with mesna may experience adverse effects (including fainting, presyncope, lethargy/drowsiness, dizziness, blurred vision) that may affect the ability to drive vehicles and operate other machinery. The decision to drive vehicles or use other machinery should be made individually in each specific case.
Drug Interactions
Mesna does not affect the systemic effects of oxazaphosphorines. It has been shown that the use of mesna in increased doses does not reduce the acute and subacute toxicity, pathological effect on leukocytes and immunosuppressive efficacy of oxazaphosphorines.
Animal studies with ifosfamide and cyclophosphamide for various tumors have also revealed that Mesna does not affect the antineoplastic activity of these drugs.
Mesna also does not affect the antineoplastic efficacy of other cytostatics (for example, adriamycin, bischloroethylnitrosourea (carmustine), methotrexate, vincristine), and does not affect the therapeutic effects of other drugs, such as cardiac glycosides.
Food intake does not affect the absorption and renal excretion of mesna.
The agent is not compatible with platinum derivatives (for example, cisplatin, carboplatin, chloromethane), therefore mesna should not be mixed in the same solution with platinum derivatives.
Mixing mesna with epirubicin leads to inactivation of epirubicin, which should be avoided.
Storage Conditions
Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.
Dispensing Status
Rx Only
Important Safety Information
This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.
Medical DisclaimerBrand (or Active Substance), Marketing Authorisation Holder, Dosage Form
Solution for intravenous administration 100 mg/ml
Marketing Authorization Holder
Atoll LLC (Russia)
Manufactured By
Ozon, LLC (Russia)
Dosage Form
 |
Mesna | Solution for intravenous administration 100 mg/ml |
Dosage Form, Packaging, and Composition
Solution for intravenous administration
| 1 ml | |
| Mesna | 100 mg |
2 ml – ampoules (10 pcs.) – cardboard packs (10 pcs.) – Prescription only
2 ml – ampoules (5 pcs.) – cardboard packs (5 pcs.) – Prescription only
4 ml – ampoules (10 pcs.) – cardboard packs (10 pcs.) – Prescription only
4 ml – ampoules (5 pcs.) – cardboard packs (5 pcs.) – Prescription only
Solution for intravenous administration 100 mg/ml
Marketing Authorization Holder
Moscow Endocrine Plant FSUE (Russia)
Dosage Form
|
Mesna | Solution for intravenous administration 100 mg/ml |
Dosage Form, Packaging, and Composition
Solution for intravenous administration
| 1 ml | |
| Mesna | 100 mg |
4 ml – ampoules (10 pcs.) – cardboard packs – Prescription only
Solution for intravenous administration 100 mg/1 ml: fl. 2 ml or 4 ml 1, 3, 5 or 10 pcs.
Marketing Authorization Holder
Veropharm, LLC (Russia)
Dosage Form
|
Mesna-LANS® | Solution for intravenous administration 100 mg/1 ml: fl. 2 ml or 4 ml 1, 3, 5 or 10 pcs. |
Dosage Form, Packaging, and Composition
Solution for intravenous administration in the form of a transparent liquid with slight opalescence, colorless or slightly colored.
| 1 ml | |
| Mesna | 100 mg |
Excipients : sodium benzoate – 3 mg, disodium edetate (Trilon B) – 0.25 mg, sodium hydroxide – to pH 7.0, water for injections – up to 1 ml.
2 ml – glass vials (1) – cardboard packs.
2 ml – glass vials (3) – cardboard packs with partitions.
2 ml – glass vials (5) – cardboard packs with partitions.
2 ml – glass vials (10) – cardboard packs with partitions.
4 ml – glass vials (1) – cardboard packs.
4 ml – glass vials (3) – cardboard packs with partitions.
4 ml – glass vials (5) – cardboard packs with partitions.
4 ml – glass vials (10) – cardboard packs with partitions.
Solution for intravenous administration 100 mg/1 ml: fl. 2 ml or 4 ml 1, 3, 5 or 10 pcs.
Marketing Authorization Holder
Lens-Pharm, LLC (Russia)
Dosage Form
|
Mesna-LANS® | Solution for intravenous administration 100 mg/1 ml: fl. 2 ml or 4 ml 1, 3, 5 or 10 pcs. |
Dosage Form, Packaging, and Composition
Solution for intravenous administration in the form of a transparent liquid with slight opalescence, colorless or slightly colored.
| 1 ml | |
| Mesna | 100 mg |
Excipients : sodium benzoate, disodium edetate (Trilon B), sodium hydroxide (caustic soda), water for injections.
2 ml – vials (1) – cardboard packs.
2 ml – vials (3) – cardboard packs.
2 ml – vials (5) – cardboard packs.
2 ml – vials (10) – cardboard packs.
4 ml – vials (1) – cardboard packs.
4 ml – vials (3) – cardboard packs.
4 ml – vials (5) – cardboard packs.
4 ml – vials (10) – cardboard packs.
![Mesna-LANS® [Solution] 1](https://www.medixlife.com/wp-content/uploads/Medixlife_favi_512.png "Mesna-LANS® [Solution] 2")