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Mesalamine (USAN)


Mesalamine (USAN)

Article Author:
Justyn Nakashima
Article Editor:
Charles Preuss
Updated:
9/28/2020 10:36:35 AM
For CME on this topic:
Mesalamine (USAN) CME
PubMed Link:
Mesalamine (USAN)

Indications

Mesalamine is useful in the induction or maintenance of remission in ulcerative colitis. It is usually used in mildly to moderately active ulcerative colitis.[1] For off-label use, clinicians may use mesalamine in Crohn disease after surgical resection of the affected bowel.[2][3][4]

First-line treatment for mild to moderate ulcerative colitis is topical mesalamine.[5] For disease localized to the rectum, a suppository formulation is an option, but for disease that extends into the sigmoid colon, mesalamine enemas are preferable. Overall, topical mesalamine formulations are preferred over oral forms and topical glucocorticoids unless the patient is unable to tolerate or is unwilling to use topical mesalamine.[6]

If the patient does not feel any relief after four weeks of therapy, mesalamine can be supplemented with other drug options such as an addition of topical or oral glucocorticoid, oral 5-ASA, budesonide multi-matrix, or a TNFα inhibitor depending on the severity of the disease.[7][5]

Mesalamine is also used in maintenance therapy for those who had more than one episode or flare-up per year, patients with ulcerative proctosigmoiditis, or ulcerative colitis that extends into the sigmoid colon. The use of topical mesalamine significantly decreases the risk of relapse.[6][7][8][4]

Mechanism of Action

The exact mechanism of mesalamine is unknown. However, the hypothesis is that it modulates the inflammatory response derived from the cyclooxygenase and lipooxygenase pathways, thus decreasing the synthesis of prostaglandins and leukotrienes. Other potential mechanisms include interference with the production of inflammatory cytokines via decreasing the activity nuclear factor­ κB (NF-κB), and inhibition of tumor necrosis factor, cellular functions of mucosal lymphocytes, macrophages, and natural killer cells. Mesalamine has also been postulated to be a free radical scavenger and an antioxidant.[3][9]

Depending on the formulation of the drug, mesalamine can get released at different sites along the GI tract. For example, the 5-ASA delayed-release capsules can be released anywhere from the jejunum to the rectum, the 5-ASA pH-dependent release can be released anywhere from the ileum to the rectum, Sulfasalazine (prodrug) can be released anywhere from the proximal colon to the rectum, 5-ASA enemas get released in the distal colon and rectum, and 5-ASA suppositories are released only in the rectum.[6][10]

Administration

Mesalamine can be taken orally as a capsule or a tablet with or without food. Some formulations are delayed-release or pH-dependent to target specific inflamed sites along the GI tract. The effectiveness of mesalamine depends on the concentration at the site of active disease and is thought to work topically.[4]

Mesalamine can also be administered rectally as an enema, foam, or a suppository. Topical formulations such as the suppository and the enema are preferable for the treatment of ulcerative colitis.[3]

Adverse Effects

Patients tolerate most mesalamine (5-ASA) formulations well. However, adverse effects may include nausea, GI upset, abdominal pain, headaches, nasopharyngitis, rash, arthralgias, agranulocytosis, aplastic anemia, myalgias, bone marrow suppression, oligospermia, hematuria, and cholestatic hepatitis. Renal impairment, including interstitial nephritis, nephrotic syndrome, and renal failure, can be seen and must be carefully monitored before initiating treatment and during treatment for these reasons.[4]

Hypersensitivity reactions are also common and have been reports on pericarditis, myocarditis, hepatitis, nephritis, pneumonitis, and hematology associated reactions. Patients may also be intolerant to mesalamine and cause symptoms such as cramping, headache, fever, malaise, pruritis, rash, and abdominal pain. Treatment must discontinue if such issues occur.

Drug interactions:

  • Antacids: May disrupt the pH-dependent formulations of mesalamine. This condition can result in the premature release and a decrease in the therapeutic effect of mesalamine.
  • Heparin: 5-ASA can enhance the toxic effects of heparin and can subsequently increase the risk of bleeding or bruising.
  • Cardiac glycosides: 5-ASA may decrease the concentration of cardiac glycosides in the blood.
  • Myelosuppressive agents (e.g., mercaptopurine): Increase bone marrow suppression risk.
  • H2 receptor blocker: May increase gastrointestinal pH and cause premature release of mesalamine and decrease its therapeutic effect.
  • NSAIDs: Increases the risk of nephrotoxicity.
  • Thiopurine analogs (e.g., mercaptopurine): Interaction with 5-ASA may decrease the metabolism of thiopurine analogs.
  • Proton pump inhibitors: May increase gastrointestinal pH and cause premature release of mesalamine and decrease the therapeutic effect.
  • Varicella vaccine: Increases risk of Reye syndrome and may enhance the toxic effects of these vaccines.[4]

Contraindications

Contraindications for mesalamine include hypersensitivity to mesalamine, salicylates, or aminosalicylates. Contraindications also include patients with severe renal or hepatic impairment due to the toxic nature of mesalamine in the kidneys and the liver. Other contraindications for the use of mesalamine are urinary tract obstruction, use in infants, and patients with existing gastric or duodenal ulcers.[4]

Monitoring

Due to mesalamine's toxic nature to the kidneys, the healthcare team should monitor the patient's renal function before and during the use of this drug. CBC should also be checked to look out for bone marrow suppression, especially in elderly patients. The hepatic function requires monitoring due to the possible risk of hepatic failure, cholestatic hepatitis, hepatic insufficiency, and other signs and symptoms of hepatotoxicity.[3][8]

Mesalamine is metabolized in the liver and by the GI tract to N-acetyl-5-aminosalicylic acid via N-acetylation (NAT). The half-life elimination of mesalamine is about 25 hours on average. Excretion of mesalamine is by urine and by feces depending on the formulation of the drug.[11][10]

Enhancing Healthcare Team Outcomes

The goal for patients with ulcerative colitis is to improve mucosal healing and achieve remission. Symptoms may start to improve within a week, but remission may take four to six weeks or even longer. Proper understanding of mesalamine and the use of adjuvant therapy is important for people contributing to the management of this disease. After achieving remission, healthcare professionals need to monitor the patient with the use of blood work and colonoscopies. Colonoscopy should be done six to twelve months following remission. Laboratory monitoring of inflammatory markers such as CRP, liver function, renal function, anemia, and stool marker (calprotectin) will be helpful in the health maintenance of ulcerative colitis.[9] Routine health maintenance, including nutrition or dietary therapy managed by dieticians, screening, and prevention of other diseases such as colon cancer, need to be appropriately addressed by health care professionals.[12] Primary care physicians need to make sure patients with inflammatory bowel disease (IBD) receive required and recommended vaccinations as well. Due to the use of immunosuppressive therapy in patients with IBD, patients need to be informed about the risk of infection, osteoporosis, and certain cancers, including colon, cervical, and skin cancer. As a result of the complexity of this disease, shared decision making, interprofessional communication, and collaboration between members of the healthcare team is critical, and doing so will provide the best possible outcome for the patient.[6][7][8][4] [Level I]

When using mesalamine, an interprofessional team approach is the most beneficial methodology. When the clinician prescribes the drug, a pharmacist should check for any drug interactions, verify dosing, and counsel the patient on potential adverse events. Nursing should also counsel the patient, perform monitoring and followup on subsequent visits, and also counsel the patient, reporting any issues to the prescriber. This interprofessional activity will improve outcomes with mesalamine. [Level 5]


References

[1] Conrad K,Roggenbuck D,Laass MW, Diagnosis and classification of ulcerative colitis. Autoimmunity reviews. 2014 Apr-May;     [PubMed PMID: 24424198]
[2] Mesalamine 2006;     [PubMed PMID: 30000377]
[3] Garud S,Peppercorn MA, Ulcerative colitis: current treatment strategies and future prospects. Therapeutic advances in gastroenterology. 2009 Mar;     [PubMed PMID: 21180538]
[4] Ham M,Moss AC, Mesalamine in the treatment and maintenance of remission of ulcerative colitis. Expert review of clinical pharmacology. 2012 Mar;     [PubMed PMID: 22390554]
[5] Adams SM,Bornemann PH, Ulcerative colitis. American family physician. 2013 May 15;     [PubMed PMID: 23939448]
[6] Collins P,Rhodes J, Ulcerative colitis: diagnosis and management. BMJ (Clinical research ed.). 2006 Aug 12;     [PubMed PMID: 16902215]
[7] Gajendran M,Loganathan P,Jimenez G,Catinella AP,Ng N,Umapathy C,Ziade N,Hashash JG, A comprehensive review and update on ulcerative colitis{sup/}. Disease-a-month : DM. 2019 Mar 2;     [PubMed PMID: 30837080]
[8] Tripathi K,Feuerstein JD, New developments in ulcerative colitis: latest evidence on management, treatment, and maintenance. Drugs in context. 2019;     [PubMed PMID: 31065290]
[9] Meier J,Sturm A, Current treatment of ulcerative colitis. World journal of gastroenterology. 2011 Jul 21;     [PubMed PMID: 21912469]
[10] Small RE,Schraa CC, Chemistry, pharmacology, pharmacokinetics, and clinical applications of mesalamine for the treatment of inflammatory bowel disease. Pharmacotherapy. 1994 Jul-Aug;     [PubMed PMID: 7937276]
[11] Karagozian R,Burakoff R, The role of mesalamine in the treatment of ulcerative colitis. Therapeutics and clinical risk management. 2007 Oct;     [PubMed PMID: 18473013]
[12] Fell JM,Muhammed R,Spray C,Crook K,Russell RK, Management of ulcerative colitis. Archives of disease in childhood. 2016 May;     [PubMed PMID: 26553909]