Usage
Mesna is a cytoprotective agent primarily used to prevent ifosfamide-induced hemorrhagic cystitis (bleeding from the bladder). It can also be used off-label to reduce the risk of hemorrhagic cystitis caused by cyclophosphamide. Its pharmacological classification is a uroprotector. Mesna acts by binding to and detoxifying acrolein, a toxic metabolite of ifosfamide and cyclophosphamide that is responsible for bladder damage.
Alternate Names
The drug is also commonly known by its international nonproprietary name (INN) mesna. A popular brand name under which it’s marketed is Mesnex.
How It Works
Pharmacodynamics: Mesna itself has no antitumor activity. Its protective effect is confined to the urinary tract where it neutralizes the urotoxic metabolites of ifosfamide and cyclophosphamide.
Pharmacokinetics:
- Absorption: Mesna is rapidly absorbed after oral administration.
- Metabolism: Mesna is metabolized in the liver to dimesna, an inactive disulfide form, which is then reduced back to mesna in the kidneys.
- Elimination: Mesna and dimesna are primarily excreted in the urine. Elimination is mainly renal.
Mode of action: Mesna, specifically its reduced sulfhydryl form, reacts with acrolein in the urine to form a non-toxic thioether conjugate. This prevents acrolein from damaging the bladder lining. There is no receptor binding, enzyme inhibition, or neurotransmitter modulation involved.
Dosage
Standard Dosage
Adults:
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IV: 20% of the ifosfamide dose (w/w) administered intravenously 15 minutes before ifosfamide, followed by 20% of the ifosfamide dose 4 and 8 hours after ifosfamide administration. The total daily dose of mesna should be equal to at least 60% of the ifosfamide dose. The dosage can also be 40% (w/w) of the ifosfamide dose at 0, 3, 6, and 9 hours if needed, bringing the total daily dose up to 160%.
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Oral: 20% of the ifosfamide dose IV at the time of ifosfamide administration followed by 40% of the ifosfamide dose orally at 2 and 6 hours after each dose of ifosfamide. The total daily dose of mesna will be 100% of the ifosfamide dose. Oral mesna is not recommended as the initial dose.
Children:
Dosing regimens for children are similar to those for adults, but higher doses or more frequent administration may be necessary. For children, the dosing schedule is the same as for adults with a possible increase in frequency or dose.
Special Cases:
- Elderly Patients: No specific dose adjustment is required for elderly patients, but caution should be exercised due to the potential for age-related decline in renal function. The ratio of ifosfamide to mesna should be maintained.
- Patients with Renal Impairment: No dose adjustment is usually necessary.
- Patients with Hepatic Dysfunction: No dose adjustment is usually necessary.
- Patients with Comorbid Conditions: Consider comorbidities when determining the appropriate dose, especially for conditions that might increase the risk of adverse effects.
Clinical Use Cases Mesna is given in conjunction with ifosfamide or cyclophosphamide therapy. Its usage is specifically linked to the administration of these chemotherapeutic agents, rather than specific clinical settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.
Dosage Adjustments
Dosage adjustments are not typically required for renal or hepatic dysfunction. However, consider individual patient factors like history of urinary tract disease and adjust the ifosfamide dose as needed.
Side Effects
Common Side Effects
Nausea, vomiting, diarrhea, constipation, fatigue, headache, fever, flu-like symptoms.
Rare but Serious Side Effects
Allergic reactions (including anaphylaxis), low blood cell counts, bleeding, unusual bruising, chest pain, and severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis).
Long-Term Effects
No specific long-term side effects are uniquely associated with mesna, but monitor patients receiving ifosfamide or cyclophosphamide for potential long-term complications of those medications.
Adverse Drug Reactions (ADR)
Hypersensitivity reactions (anaphylaxis, hypotension, rash, dyspnea), hepatic dysfunction.
Contraindications
Hypersensitivity to mesna or other thiol compounds.
Drug Interactions
Limited clinically significant drug interactions have been reported. However, caution should be exercised with concomitant use of warfarin. Mesna can interfere with urine ketone tests giving a false-positive result.
Pregnancy and Breastfeeding
Mesna itself has not shown harm to the fetus in animal studies, however, it is used with ifosfamide, which can cause fetal harm. Breastfeeding is not recommended during treatment and for one week after the last dose due to the potential for serious adverse reactions in the breastfed infant.
Drug Profile Summary
- Mechanism of Action: Detoxifies urotoxic metabolites of ifosfamide and cyclophosphamide in the urine.
- Side Effects: Nausea, vomiting, diarrhea, constipation, fatigue, headache, fever, allergic reactions.
- Contraindications: Hypersensitivity to mesna or other thiol compounds.
- Drug Interactions: Warfarin; interference with urine ketone tests.
- Pregnancy & Breastfeeding: Not recommended during pregnancy or breastfeeding if administered with ifosfamide.
- Dosage: 20-40% of the ifosfamide dose given IV or orally at various time points related to ifosfamide administration.
- Monitoring Parameters: Monitor urine for hematuria, proteinuria, and adequate output; complete blood counts.
Popular Combinations
Mesna is most commonly used in combination with ifosfamide or cyclophosphamide.
Precautions
- General Precautions: Monitor urine output, hematuria, and proteinuria. Monitor for allergic reactions.
- Specific Populations: Use with caution in pregnant women and avoid during breastfeeding. No specific precautions for children or elderly other than dose adjustments based on individual requirements.
- Lifestyle Considerations: No specific lifestyle considerations uniquely associated with mesna.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Mesna?
A: The dosage of mesna depends on the dosage of ifosfamide or cyclophosphamide. The total daily mesna dose generally ranges from 60% to 160% of the total daily oxazaphosphorine dose, given in divided doses intravenously or orally.
Q2: How does Mesna work to prevent hemorrhagic cystitis?
A: Mesna binds to and inactivates acrolein, a toxic metabolite of ifosfamide and cyclophosphamide, in the urine. This prevents acrolein from damaging the bladder lining.
Q3: What are the most common side effects of Mesna?
A: Nausea, vomiting, diarrhea, constipation, fatigue, headache, and fever.
Q4: Are there any contraindications to using Mesna?
A: Yes, hypersensitivity to mesna or other thiol compounds is a contraindication.
Q5: Can Mesna be used during pregnancy or breastfeeding?
A: It’s generally not recommended due to the potential risks to the fetus or infant, particularly when given with ifosfamide.
Q6: How should Mesna be administered?
A: Mesna can be administered intravenously or orally, with dosing tied to the administration of ifosfamide or cyclophosphamide.
Q7: Does Mesna interact with other medications?
A: Limited clinically significant drug interactions have been reported. Caution is advised with concomitant use of warfarin.
Q8: Are there any special considerations for elderly patients?
A: While no specific dose adjustment is required, use with caution in elderly patients due to potential age-related decline in renal function. Maintain the ifosfamide to mesna ratio.
Q9: What should I monitor in patients receiving Mesna?
A: Monitor for hematuria, proteinuria, and adequate urine output. Monitor complete blood counts to detect any myelosuppression caused by ifosfamide or cyclophosphamide. Observe for any signs of allergic reactions.
