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Mesna


Mesna

Article Author:
Vamsi Reddy
Article Editor:
Nicole Winston
Updated:
11/17/2020 9:51:35 AM
For CME on this topic:
Mesna CME
PubMed Link:
Mesna

Indications

Mesna is an FDA-approved drug used as a prophylactic medication in reducing the incidence of ifosfamide and cyclophosphamide-induced hemorrhagic cystitis. Other non-FDA approved indications include:

  • Treatment of chemically-assisted dissection of recurrent and residual cholesteatoma[1]
  • Reduction of the incidence of BK viruria following post-transplantation cyclophosphamide[2]
  • Inhibition of propylene glycol induced cholesteatoma formation[3]
  • Treatment of pain following failed back surgery syndrome via epidural injection[4]
  • Treatment of chronic cholesteatomatous otitis media in children[5]

Mechanism of Action

Mesna (sodium 2-mercaptoethane sulfonate) is a detoxifying agent used to prevent hemorrhagic cystitis in patients receiving chemotherapy with either high-dose cyclophosphamide or ifosfamide. Mesna initially becomes inactivated to dimesna (mensa disulfide) in the bloodstream; however, once it is filtered through the kidneys and excreted into the bladder, it is reactivated. As reactivated mesna concentrates in the bladder, mesna detoxifies acrolein, a urotoxic breakdown product of ifosfamide and cyclophosphamide that accumulates in the bladder. Mesna acts as a sulfhydryl donor that forms a conjugate bond with acrolein and inactivates it, preventing hemorrhagic cystitis or bleeding due to irritation of the bladder.[6]

There is some evidence to suggest that this might also occur through the inhibition of lactoperoxidase (LPO). Lactoperoxidase utilizes hydrogen peroxide (HO) and thiocyanate (SCN) to produce hypothiocyanous acid (HOSCN). Mesna's sulfhydryl group binds stably to LPO within the SCN binding site and thus inhibits function resulting in reduction and regulation of local inflammatory effects.[7]

Administration

Mesna administration can be as an injection, IV infusion, or as an oral tablet. Mesna is usually first administered as an injection concurrently with cyclophosphamide or ifosfamide chemotherapy. If the physician deems that it is still necessary after the initial dosage, an oral form (400 mg tablet) is usually administered 2 to 6 hours following subsequent therapy. Due to the strong adverse taste of oral mesna tablets, the administration of the tablet with juice or food is usually the recommendation due to the sulfur odor/taste. Patients are advised to drink at least 4 cups of liquid daily while taking mesna.[8]

Studies have also shown mesna administration as a topical agent for chemically assisted dissection of recurrent and residual cholesteatoma, most commonly in the pediatric population.[9] Another study showed that epidural injection of mesna reduced pain following failed back surgery syndrome (FBSS).[4]

Adverse Effects

Mesna in both oral and IV administrations is commonly associated with gastrointestinal side effects, including nausea, vomiting, constipation, abdominal pain, and bad taste.[10] By far, the most common side effect of mesna administration is due to adverse taste while taking the oral tablet. The patient can often vomit due to unpalatable taste, and it is a strong recommendation to take mesna along with a strong-tasting liquid. Another documented adverse effect of mesna is hypersensitivity reactions, including rash and leukopenia. These have ranged from mild dermatologic reactions to systemic anaphylactic reactions, so it requires close monitoring.[11]

Contraindications

Mesna prophylaxis is contraindicated in patients who have hypersensitivity to thiol compounds as well as patients who have previously had adverse reactions associated with a prior mesna administration.[12]

Monitoring

Along with mesna administration, providers must monitor urine for signs of hematuria as well as monitor urine output and hydration status. Few patients often have break-through hematuria even on mesna prophylaxis. If the physician deems mesna administration to be subtherapeutic as hemorrhagic cystitis is still present, an additional IV bolus or oral tablet may be administered.

An important consideration of mesna administration is the breastfeeding status of females who are of reproductive age.[13] It is not well understood if mesna is present in breast milk; however, benzyl alcohol is often a component of mesna intravenous formulations. The manufacturer indicated that exposure to the breastfeeding infant is unlikely in part due to maternal metabolism. Nonetheless, benzyl alcohol has been linked to adverse events in infants, and therefore breastfeeding is not recommended for at least one week after the last mesna injection.

Finally, it is important to monitor patients for signs/symptoms of hypersensitivity or dermatologic toxicity. Reactions associated with mesna are rare; however, mesna has the potential to lead to severe hypersensitivity reactions, including anaphylactic shock.[14]

Toxicity

There is no indicated antidote to mesna overdose. Mesna administration is usually via IV bolus or oral tablet, and therefore, unlike a drip, it cannot be immediately stopped with the appearance of adverse effects. If a hypersensitivity reaction is present after administration, supportive care with fluid administration is the recommended course.

Enhancing Healthcare Team Outcomes

Managing adverse reactions associated with any drug administration requires an interprofessional team of healthcare professionals that includes a nurse, laboratory technologists, pharmacists, and a number of physicians involved in the care of a patient. Studies have shown that interprofessional communication in the healthcare environment has a significant improvement in patient outcomes as well as cost-burden of healthcare in regards to repeat-imaging, labs, and advanced testing.[15][16][17] [Level 2, Level 3]

The most common adverse effect associated with mesna administration, particularly in the oral form, is bad taste. Unfortunately, this can affect patient compliance with medication. If patients do not adhere to the regimen, it may lead to urinary tract irritation and hemorrhagic cystitis associated with ifosfamide and cyclophosphamide. To avoid this, healthcare providers at every level must effectively communicate the importance of taking this drug and discuss strategies to help make it more palatable. Examples of such measures include administering the drug with a strong-tasting liquid such as grape juice or crushing up the oral drug and mixing it into more palatable foods such as apple sauce. 

However, beyond the taste of mesna, there are additional adverse effects that one cannot afford to miss. Without proper management and monitoring, these can potentially lead to more dire consequences, such as hypersensitivity reactions. As mesna is not a drug that is commonly associated with these serious adverse effects, healthcare providers are prone to take these reactions for granted or not consider mesna as the culprit. As soon as the patient presents with any adverse reaction to the nursing staff, they must promptly notify a physician. Once notified, it is also imperative that physicians speak with the inter-professional team and involve pharmacists to identify and target the cause of such a reaction. There have been numerous case series associated with the adverse effects of mesna usage.[18][11][19] [Level 5]


References

[1] de la Torre C,Villamor P, Chemically Assisted Dissection With Sodium 2-Mercaptoethanesulfonate (MESNA) in the Surgical Management of Pediatric Cholesteatoma. Otology     [PubMed PMID: 31083092]
[2] Jaiswal SR,Singhal P,Thatai A,Bhagwati G,Aiyer HM,Chakrabarti A,Chakrabarti S, Impact of extended infusional mesna prophylaxis on the incidence of BK viruria and hemorrhagic cystitis following post-transplantation cyclophosphamide and CTLA4Ig-based haploidentical transplantation. Annals of hematology. 2020 Feb 5;     [PubMed PMID: 32025839]
[3] Ismi O,Karabulut YY,Bal KK,Vayisoglu Y,Unal M, Single dose intratympanic mesna application inhibits propylene glycol induced cholesteatoma formation. The Journal of laryngology and otology. 2017 Mar;     [PubMed PMID: 27995828]
[4] Carassiti M,Di Martino A,Centonze A,Quattrocchi CC,Caldaria A,Agrò F,Denaro V, Failed back surgery syndrome: a new strategy by the epidural injection of MESNA. Musculoskeletal surgery. 2018 Aug;     [PubMed PMID: 29098646]
[5] de la Torre González C,Huante-Guido M,Velázquez Guadarrama N,Preciado D,Patiño López G, Changes in biofilm in chronic cholesteatomatous otitis media in children following the application of sodium 2-mercaptoethanesulfonate (MESNA). International journal of pediatric otorhinolaryngology. 2018 Jul;     [PubMed PMID: 29859586]
[6] Shaw IC,Graham MI, Mesna--a short review. Cancer treatment reviews. 1987 Jun;     [PubMed PMID: 3119211]
[7] Jahanbakhsh S,Dekhne MS,Kohan-Ghadr HR,Bai D,Awonuga A,Morris RT,Yang Z,Abu-Soud HM, The inhibition of lactoperoxidase catalytic activity through mesna (2-mercaptoethane sodium sulfonate). Journal of inorganic biochemistry. 2020 Feb;     [PubMed PMID: 31734539]
[8] Sannu A,Radha R,Mathews A,Padmakumari Mony R,Prahladan A,James FV, Ifosfamide-Induced Malignancy of Ureter and Bladder. Cureus. 2017 Aug 22;     [PubMed PMID: 29062626]
[9] Eğilmez OK,Kökten N,Baran M,Kalcıoğlu MT,Doğan Ekici I,Tekin M, Electrophysiological and Histopathological Evaluation of Effects of Sodium-2 Mercaptoethanesulfonate Used for Middle Ear Surgery on Facial Nerve Functions. The journal of international advanced otology. 2018 Aug;     [PubMed PMID: 29283098]
[10] Matz EL,Hsieh MH, Review of Advances in Uroprotective Agents for Cyclophosphamide- and Ifosfamide-induced Hemorrhagic Cystitis. Urology. 2017 Feb;     [PubMed PMID: 27566144]
[11] Robertson LM,Clark A, Looking beyond the angiotensin receptor blocker: A case of anaphylaxis to mesna. Annals of allergy, asthma     [PubMed PMID: 27424127]
[12] Shimogori K,Araki M,Shibazaki S,Tuda K,Miura K, Nonimmediate allergic reactions induced by Mesna. Journal of general and family medicine. 2017 Oct;     [PubMed PMID: 29264044]
[13] Ninane J,Baurain R,de Kraker J,Ferster A,Trouet A,Cornu G, Alkylating activity in serum, urine, and CSF following high-dose ifosfamide in children. Cancer chemotherapy and pharmacology. 1989;     [PubMed PMID: 2503256]
[14] Lin CY,Keefe M, Mesna-induced photodistributed dermatosis. Clinical and experimental dermatology. 2012 Jun;     [PubMed PMID: 22103595]
[15] O'Leary KJ,Johnson JK,Manojlovich M,Goldstein JD,Lee J,Williams MV, Redesigning systems to improve teamwork and quality for hospitalized patients (RESET): study protocol evaluating the effect of mentored implementation to redesign clinical microsystems. BMC health services research. 2019 May 8;     [PubMed PMID: 31068161]
[16] Golom FD,Schreck JS, The Journey to Interprofessional Collaborative Practice: Are We There Yet? Pediatric clinics of North America. 2018 Feb;     [PubMed PMID: 29173710]
[17] Bentley M,Freeman T,Baum F,Javanparast S, Interprofessional teamwork in comprehensive primary healthcare services: Findings from a mixed methods study. Journal of interprofessional care. 2018 May;     [PubMed PMID: 29182411]
[18] Khaw SL,Downie PA,Waters KD,Ashley DM,Heath JA, Adverse hypersensitivity reactions to mesna as adjunctive therapy for cyclophosphamide. Pediatric blood     [PubMed PMID: 16333822]
[19] Ercan N,Aysegul E,Burcak B,Ilknur B, Sepsis like acute hypersensitivity syndrome related to mesna. Journal of the European Academy of Dermatology and Venereology : JEADV. 2017 Sep;     [PubMed PMID: 28271573]