Mesacol400 mg

Ulcerative Colitis - Induction of Remission

Mesacol 400 mg is an established, FDA-approved treatment for the induction of remission in patients with active mild-to-moderate ulcerative colitis.

Ulcerative Colitis - Maintenance of Remission

Mesacol 400 mg is an established, FDA-approved treatment for the maintenance of remission of ulcerative colitis.

Crohn's Disease (Colonic Involvement)

Mesacol 400 mg has a guideline-supported, though less robust, role in the treatment of mild-to-moderate active Crohn's disease involving the colon. Evidence of benefit is weaker than for ulcerative colitis, and some formulations are not specifically labeled for this use; treatment decisions should be individualized by a physician.

Proctitis and Proctosigmoiditis

Rectal formulations (suppository, enema) of Mesacol 400 mg are established for distal disease limited to the rectum or rectosigmoid colon, and may be used alone or combined with oral formulations for more extensive disease.

Each formulation contains Mesacol 400 mg as the active ingredient. Mesacol 400 mg is available in Bangladesh and internationally as oral tablets and capsules (including delayed-release and extended-release/controlled-release forms designed to deliver drug to specific parts of the colon), oral granules/sachets, and rectal preparations (suppositories and enemas). Strength and release mechanism vary by brand and formulation; the specific product and strength should be selected and confirmed by the prescribing physician or pharmacist.

Mesacol 400 mg (also known as mesalamine) is an aminosalicylate anti-inflammatory agent used primarily in the management of inflammatory bowel disease (IBD). It is chemically related to sulfasalazine, from which the active moiety is derived, but is administered directly, avoiding the sulfapyridine component responsible for many of sulfasalazine's side effects.

Mesacol 400 mg acts topically on the lining of the colon and rectum to reduce inflammation. Various oral formulations use pH-dependent coatings, time-dependent (controlled) release, or multi-matrix delivery systems to release the drug in the ileum and colon, while rectal formulations act locally on the distal bowel.

Mesacol 400 mg belongs to the aminosalicylate (5-ASA) class of anti-inflammatory agents, used in the treatment of inflammatory bowel disease.

Mechanism of Action

The precise mechanism of action of Mesacol 400 mg is not completely established. It is believed to act topically on the colonic mucosa rather than systemically, reducing inflammation through several proposed pathways, including inhibition of cyclooxygenase (COX) and lipoxygenase pathways of arachidonic acid metabolism (reducing prostaglandin and leukotriene production), scavenging of reactive oxygen species, and inhibition of pro-inflammatory cytokine production and nuclear factor-kappa B (NF-kB) activation in the intestinal mucosa.

Pharmacokinetics

Absorption varies by formulation and site of release; a variable fraction is absorbed systemically, with the remainder acting locally and being eliminated in the stool. Absorbed drug is largely acetylated (mainly in the intestinal mucosa and liver) to the less active N-acetyl-5-aminosalicylic acid metabolite. Elimination occurs mainly via the kidneys (as the acetylated metabolite) and in the feces.

Mesacol 400 mg tablets/capsules should generally be taken with food or as directed, and swallowed whole without crushing or chewing (for delayed/extended-release forms). Rectal suppositories and enemas should be administered as directed, preferably at bedtime, and retained for as long as possible to maximize local effect. Consistency in the brand/formulation used is important, as different products release the drug differently along the gastrointestinal tract.

Nephrotoxic Agents

Concurrent use of Mesacol 400 mg with other nephrotoxic drugs, such as NSAIDs (including ibuprofen) and aminoglycoside antibiotics, may increase the risk of additive nephrotoxicity. Renal function should be monitored more closely if such combinations are necessary.

Azathioprine and Mercaptopurine

Concomitant use of Mesacol 400 mg with azathioprine or mercaptopurine may increase the risk of blood disorders (myelosuppression) due to possible interference with the metabolism of these agents. Complete blood counts should be monitored more closely if these drugs are used together.

Lactulose and Other pH-Altering Agents

Lactulose and other agents that lower colonic pH may impair the release of pH-dependent (enteric-coated) formulations of Mesacol 400 mg, potentially reducing efficacy. This is a formulation-specific consideration; consult a physician or pharmacist about specific product compatibility.

Common Side Effects

• Headache
• Nausea
• Abdominal pain or cramping
• Diarrhea (can sometimes be difficult to distinguish from symptoms of the underlying disease)
• Flatulence
• Fatigue

Rare but Serious Side Effects

• Nephrotoxicity: rare cases of interstitial nephritis and other kidney injury have been reported; requires periodic renal function monitoring (see Precautions and Warnings).
• Mesalazine-induced acute intolerance syndrome: a rare reaction presenting as worsening abdominal pain, cramping, bloody diarrhea, and sometimes fever or rash, which can be difficult to distinguish from a flare of the underlying disease (see Precautions and Warnings).
• Rare cases of pancreatitis.
• Rare blood disorders (e.g., leukopenia, thrombocytopenia).
• Rare hepatic effects (e.g., elevated liver enzymes, hepatitis).
• Rare pericarditis and myocarditis.

Mesacol 400 mg is generally regarded, among treatments for inflammatory bowel disease, as one of the better-studied options that is often continued during pregnancy when needed, since uncontrolled disease activity itself carries risks to mother and fetus. However, Mesacol 400 mg should be used during pregnancy only if clearly needed and if the potential benefit justifies the potential risk to the fetus; use should be guided and monitored by a physician rather than self-directed.

Mesacol 400 mg and its metabolites pass into breast milk in small amounts. Diarrhea in the breastfed infant has been reported rarely. Mesacol 400 mg should be used during breastfeeding only under medical supervision, with the infant monitored for any gastrointestinal symptoms; consult a physician before use.

Renal Function Monitoring

Renal impairment, including interstitial nephritis, has been associated with Mesacol 400 mg use. Baseline renal function should be assessed before starting treatment, and periodic monitoring (e.g., serum creatinine) is recommended during therapy, particularly in patients with pre-existing renal disease or those taking other nephrotoxic drugs.

Mesalazine-Induced Acute Intolerance Syndrome

A rare acute intolerance reaction to Mesacol 400 mg can present with worsening abdominal cramping, bloody diarrhea, and sometimes fever, headache, or rash. This can closely mimic a flare of the underlying ulcerative colitis or Crohn's disease. If symptoms worsen after starting or during treatment, a physician should consider this reaction as a possible cause in addition to disease flare, since continuing the drug in this setting could worsen symptoms.

Hepatic Impairment

Caution is advised in patients with pre-existing liver disease; liver function should be monitored if used in this setting.

Cardiac Hypersensitivity

Rare cases of myocarditis and pericarditis have been reported; patients with a history of these conditions should use Mesacol 400 mg with caution and be monitored for symptoms such as chest pain or shortness of breath.

Sulfasalazine Hypersensitivity

Patients with a known hypersensitivity reaction to sulfasalazine may be at increased risk of a similar reaction to Mesacol 400 mg; such patients should be monitored closely if treatment is used.

Limited data are available on overdose with Mesacol 400 mg; based on its salicylate-related structure, overdose could theoretically produce features of salicylate toxicity (such as tinnitus, nausea, vomiting, hyperventilation, or metabolic disturbance) at very high doses. In case of a suspected overdose, seek immediate medical attention or contact emergency services/a poison control center. Treatment is supportive and should be managed by medical professionals; specific home treatment is not recommended.

Store at room temperature (below 30°C), away from light and moisture. Keep out of reach of children. Do not use rectal preparations if the packaging is damaged.

Renal Impairment

Mesacol 400 mg is contraindicated in severe renal impairment and should be used with caution and close renal monitoring in mild-to-moderate renal impairment.

Hepatic Impairment

Mesacol 400 mg is contraindicated in severe hepatic impairment and should be used with caution in mild-to-moderate hepatic impairment, with monitoring of liver function.

Elderly Patients

Elderly patients may have age-related decline in renal function and should be monitored closely for renal adverse effects during treatment with Mesacol 400 mg.

Pediatric Patients

See Pediatric Uses.

Duration of treatment with Mesacol 400 mg depends on the indication: induction regimens for active ulcerative colitis are typically continued for around 6-8 weeks or until remission is achieved, as guided by clinical and, where relevant, endoscopic response, while maintenance therapy is generally continued long-term to sustain remission, per the treating physician's advice. Treatment should not be stopped or altered without consulting a physician.

Aminosalicylate (5-aminosalicylic acid / 5-ASA derivative); gastrointestinal anti-inflammatory agent.

Mesacol 400 mg acts topically on the colonic and rectal mucosa to reduce inflammation, likely through inhibition of cyclooxygenase and lipoxygenase pathways of arachidonic acid metabolism, scavenging of free radicals, and inhibition of pro-inflammatory cytokines and NF-kB activation, thereby reducing the mucosal inflammatory response characteristic of inflammatory bowel disease.

The safety and efficacy of Mesacol 400 mg in pediatric patients have been established for certain oral formulations in children above specific ages (varying by product, generally children and adolescents from around 5-6 years of age and older for some formulations, based on product-specific studies), for the treatment of ulcerative colitis, with weight-based or age-based dosing per the specific product labeling. For other formulations or younger children, safety and efficacy have not been established, and use should only be under specialist (pediatric gastroenterology) supervision.