Evemesa

Approved Indications:

• Ulcerative Colitis (UC):
• Induction of remission in mild-to-moderate UC.
• Maintenance of remission in UC.
• Proctitis and Proctosigmoiditis (distal ulcerative colitis).
• Crohn's Disease (CD):
• Treatment of mild-to-moderate Crohn’s disease (ileal or colonic involvement); less commonly used.
• Postoperative prophylaxis to prevent recurrence in Crohn’s disease (off-label).
• Microscopic colitis (off-label use in some cases).

Route of Administration: Oral, Rectal (suppository or enema)

Oral Formulations:

Adults (Ulcerative Colitis):

• Induction of remission:
  2.4–4.8 g/day in divided doses or once daily, depending on the formulation.
• Maintenance of remission:
  1.2–2.4 g/day, usually given once daily or in two divided doses.

Children (Ulcerative Colitis):

• Induction:
  60–100 mg/kg/day (max 4.8 g/day), in divided doses.
• Maintenance:
  30–50 mg/kg/day (max 2 g/day), in divided doses.

Rectal Formulations:

• Suppository:
  500 mg or 1 g once daily or twice daily.
• Enema:
  1–4 g once daily at bedtime or in divided doses.

Special Populations:

• Renal Impairment:
  Avoid or use with caution; monitor renal function regularly.
• Hepatic Impairment:
  Use with caution; limited data available.
• Elderly:
  Dose adjustment may be required based on renal function.

Mesalazine exerts a local anti-inflammatory effect on the colonic mucosa. It acts primarily by inhibiting cyclooxygenase and lipoxygenase pathways, thereby reducing the production of pro-inflammatory prostaglandins and leukotrienes. It also modulates cytokine production, scavenges reactive oxygen species, and inhibits nuclear factor-kappa B (NF-κB) activation in intestinal epithelial cells. These combined effects reduce inflammation and promote mucosal healing, particularly in ulcerative colitis.

• Absorption: Variable; depends on the formulation. Delayed-release and pH-dependent formulations allow delivery to the colon.
• Distribution: Mainly localized to the gastrointestinal tract; minimal systemic distribution.
• Protein Binding: ~43% (mesalazine), ~80% (N-acetyl-5-ASA)
• Metabolism: Rapidly acetylated in the intestinal wall and liver to inactive metabolite N-acetyl-5-ASA.
• Half-life: 0.5–1.5 hours (mesalazine); 5–10 hours (metabolite).
• Excretion: Primarily renal (as metabolite); small portion fecal.

Pregnancy:

• FDA Category: B
• Safe in pregnancy when clinically indicated. No evidence of fetal harm in humans.

Lactation:

• Excreted in breast milk in small amounts.
• Generally considered safe; monitor infant for diarrhea or bloody stools.

• Primary Class: Anti-inflammatory agent for IBD
• Subclass: Aminosalicylate derivative (5-ASA)

• Known hypersensitivity to mesalazine, salicylates (e.g., aspirin), or any formulation excipients.
• Severe renal impairment (e.g., GFR <30 mL/min).
• Severe hepatic impairment (precaution advised).
• History of mesalazine-induced myocarditis or pericarditis.

• Renal Toxicity:
  Risk of interstitial nephritis; monitor renal function before and during treatment.
• Hepatic Impairment:
  Use with caution; monitor liver function periodically.
• Hematologic Effects:
  Rare cases of blood dyscrasias reported (e.g., agranulocytosis, pancytopenia).
• Hypersensitivity Reactions:
  May cause fever, rash, or lupus-like syndrome.
• Cardiac Effects:
  Rare myocarditis or pericarditis; discontinue if suspected.
• Gastrointestinal:
  Use with caution in patients with pyloric stenosis or active peptic ulcer.

Common:

• Gastrointestinal: Nausea, abdominal pain, diarrhea, flatulence.
• CNS: Headache, dizziness.
• Dermatologic: Rash, pruritus.

Serious/Rare:

• Nephrotoxicity: Interstitial nephritis, renal failure.
• Hypersensitivity: Fever, chest pain, myalgia.
• Hematologic: Leukopenia, thrombocytopenia, aplastic anemia (rare).
• Hepatotoxicity: Elevated liver enzymes, hepatitis.
• Pancreatitis, myocarditis, pericarditis (very rare).

Timing:

• Adverse events may appear within days to weeks after initiation.

• Nephrotoxic Drugs (e.g., NSAIDs, cyclosporine):
  Increased risk of renal impairment.
• Azathioprine, 6-mercaptopurine:
  Increased risk of bone marrow suppression; monitor blood counts.
• Antacids or proton pump inhibitors:
  May affect pH-dependent release formulations.
• Lactulose:
  May delay mesalazine release by altering intestinal pH.

CYP450 Enzymes:
Mesalazine is not significantly involved with CYP450 enzyme metabolism.

• ECCO Guidelines 2023: Recommend mesalazine as first-line therapy for induction and maintenance in mild-to-moderate ulcerative colitis.
• AGA 2023 Clinical Updates: Support once-daily dosing for improved adherence.
• Pediatric IBD Guidelines (NASPGHAN): Mesalazine remains a preferred first-line agent for mild pediatric UC.

• Oral Tablets/Capsules:
  Store at 20°C to 25°C (68°F to 77°F). Protect from moisture and light. Do not crush or chew extended-release forms.
• Suppositories/Enemas:
  Store below 25°C. Do not freeze. Protect from light and keep tightly closed.
• General Handling:
  Use within expiration date. Do not use if tablets are discolored or broken. Avoid excessive heat and humidity.