mesna

Action and Spectrum

Actions and Spectrum: 

The precise mechanism of action of mesna is not fully understood, but it is believed to involve the following processes: 

• Detoxification: mesna undergoes a chemical reaction with the urotoxic metabolites of cyclophosphamide and ifosfamide, known as acrolein and 4-hydroxycyclophosphamide, respectively. These metabolites are responsible for the urinary tract toxicity associated with these chemotherapy drugs. mesna binds to acrolein and 4-hydroxycyclophosphamide, forming stable, nontoxic compounds excreted in the urine. 
• Free Radical Scavenging: mesna possesses antioxidant properties and acts as a scavenger of free radicals generated during the metabolism of cyclophosphamide and ifosfamide. By neutralizing free radicals, mesna helps prevent oxidative damage to the urinary tract cells. 
• Preservation of Thiol Groups: mesna can protect the sulfhydryl (thiol) groups in the bladder lining, which is vulnerable to acrolein and other toxic metabolite damage. By preserving these thiol groups, mesna helps maintain the integrity of the bladder epithelium. 
• The spectrum of activity of mesna is limited to its protective effects on the urinary system during high-dose chemotherapy with cyclophosphamide and ifosfamide. It does not possess any direct antineoplastic (anti-cancer) activity. mesna is specifically used to prevent hemorrhagic cystitis, a condition characterized by bleeding and inflammation of the bladder, which can occur as a side effect of cyclophosphamide and ifosfamide. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Vomiting 

Asthenia 

Fever 

Constipation 

Granulocytopenia 

Thrombocytopenia 

Nausea 

Anorexia 

Fatigue 

Abdominal pain 

Anemia 

Leukopenia 

Alopecia 

1-10% 

Confusion 

Headache 

Pain 

Chest pain 

Flushing 

Cough 

Pneumonia 

Anxiety 

Dizziness 

Insomnia 

Somnolence 

Edema 

Tachycardia 

Dyspnea 

Hypokalemia 

Dehydration 

Pallor 

Hematuria 

Back pain 

Injection site reaction 

Black Box Warning

Black box warning: 

None 

Contraindication / Caution

Contraindications/caution: 

Contraindications: 

• Hypersensitivity: mesna is contraindicated in individuals with known hypersensitivity or allergy to mesna or its components. Hypersensitivity reactions can range from mild skin reactions to severe allergic reactions, including anaphylaxis. 
• Hematuria: mesna is contraindicated in patients with severe hematuria (blood in the urine) at the start of chemotherapy. mesna may not be effective in preventing further hemorrhagic cystitis in these cases. 
• Bladder Rupture: mesna should not be used in patients with known bladder rupture or perforation, as it may interfere with properly managing these conditions. 
• Children Under 2 Years of Age: The safety and efficacy of mesna have not been established in children under 2, so its use in this population is generally avoided. 
• Breastfeeding: It is not well-established whether mesna is excreted in breast milk. Therefore, caution should be exercised when considering the use of mesna in breastfeeding women, and the potential benefits and risks should be carefully evaluated. 

Caution: 

• Renal impairment: mesna is primarily excreted by the kidneys, so caution should be exercised when administering mesna to individuals with impaired renal function. Dosage adjustments may be necessary in such cases to prevent drug accumulation. 
• Electrolyte Imbalance: mesna contains sodium as a component, so caution should be exercised in patients on a sodium-restricted diet or with conditions requiring sodium intake monitoring, such as congestive heart failure or high blood pressure. 
• Fluid Overload: mesna administration may involve the use of intravenous fluids. Excessive fluid administration may lead to fluid overload in patients with impaired cardiac or renal function. Close monitoring of fluid balance is essential in such cases. 
• Concurrent Medications: mesna can interact with certain medications. For example, ifosfamide is a chemotherapeutic agent commonly used in conjunction with mesna, and the dosing schedule of mesna must be carefully coordinated with ifosfamide administration. Other medications that may interact with mesna should be evaluated for potential drug-drug interactions. 
• Monitoring: Regular monitoring of renal function, complete blood counts, and urine output may be necessary during mesna therapy to ensure safety and early detection of any potential adverse effects. 
• Pregnancy: The safety of mesna use during pregnancy has not been well-established. It should be used cautiously in pregnant women, and the potential risks and benefits should be carefully assessed. 
• Hepatic impairment: mesna is primarily metabolized in the liver. Although hepatic impairment does not significantly affect its elimination, caution should still be exercised in patients with severe liver dysfunction. 

Pregnancy / Lactation

Pregnancy consideration: Insufficient data available 

Lactation: Excretion of the drug in human breast milk is unknown 

Pregnancy category: 

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology: 

mesna (sodium 2-mercaptoethanesulfonate) is a chemoprotective agent primarily used to prevent the urotoxic side effects of certain chemotherapy drugs, particularly cyclophosphamide, and ifosfamide. 

Pharmacodynamics: 

The pharmacodynamics of mesna mainly revolve around its protective actions against urotoxicity caused by specific chemotherapy drugs. By detoxifying urotoxic metabolites, scavenging free radicals, and preserving thiol groups, mesna helps prevent bladder damage and other urinary system complications associated with cyclophosphamide and ifosfamide therapy. 

Pharmacokinetics: 

Absorption 

mesna is available in both oral and intravenous formulations. When administered orally, mesna is rapidly and well absorbed from the gastrointestinal tract, with peak plasma concentrations reached within 0.5 to 2 hours after ingestion. Intravenous administration results in immediate and complete bioavailability. 

Distribution 

mesna has a relatively large volume of distribution, indicating that it distributes extensively throughout the body. It readily crosses the placenta and is detected in fetal circulation. The binding of mesna to plasma proteins is low (approximately 10%). 

Metabolism 

mesna undergoes minimal metabolism in the liver. It is primarily excreted unchanged in the urine. Only a tiny portion of mesna undergoes oxidation to form mesna disulfide (dimesna), which is pharmacologically inactive. The conversion of mesna-to-mesna disulfide is reversible, and the disulfide is reduced back to mesna in the presence of thiols. 

Elimination and Excretion 

mesna is primarily eliminated by renal excretion. Following intravenous administration, the half-life of mesna is approximately 1.2 hours. Renal impairment can significantly affect the elimination of mesna, and dosage adjustments may be necessary for patients with impaired renal function. 

Adminstartion

Administration: 

mesna (sodium 2-mercaptoethanesulfonate) can be administered orally or intravenously, depending on the specific treatment regimen and formulation available. The administration of mesna is typically tailored to the chemotherapy drugs being used and the associated risk of urotoxicity. Here are the standard methods of mesna administration: 

• Oral administration: mesna is available in tablet or capsule form. The recommended dosage and frequency of oral mesna may vary depending on the chemotherapy regimen. It is usually taken at specific intervals before and after administering cyclophosphamide or ifosfamide. The tablets or capsules should be swallowed whole with water and may be taken with or without food, as directed by the healthcare professional. 
• Intravenous (IV) Administration: mesna is available as an intravenous solution for administration directly into a vein. IV mesna is often used when high-dose chemotherapy, such as high-dose ifosfamide, is administered. It is typically given as a slow intravenous infusion over a specified period. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: mesna 

Why do we use mesna? 

mesna (sodium 2-mercaptoethanesulfonate) is primarily used as a chemoprotective agent to prevent urotoxicity associated with certain chemotherapy drugs, particularly cyclophosphamide, and ifosfamide. The main uses of mesna are as follows: 

• Prevention of Hemorrhagic Cystitis: Hemorrhagic cystitis is a condition characterized by bleeding and inflammation of the bladder. It is a known side effect of high-dose chemotherapy drugs like cyclophosphamide and ifosfamide. mesna is used as a prophylactic measure to prevent or reduce the incidence and severity of hemorrhagic cystitis in patients receiving these chemotherapy agents. 
• Uroprotection during High-Dose Chemotherapy: mesna is commonly used with high-dose chemotherapy regimens involving cyclophosphamide or ifosfamide. These drugs are associated with the potential for urotoxicity, including bladder and urinary tract damage. mesna helps protect the urinary system by detoxifying urotoxic metabolites, scavenging free radicals, and preserving the integrity of bladder tissues.