Usage
Mesalamine is prescribed for the treatment of inflammatory bowel diseases (IBD), primarily ulcerative colitis and Crohn’s disease. It belongs to the aminosalicylate classification and works by reducing inflammation in the intestinal lining. Its mechanism of action is primarily topical, exerting its anti-inflammatory effects directly on the affected areas of the gut.
Alternate Names
Mesalamine is also known as mesalazine (international nonproprietary name) or 5-aminosalicylic acid (5-ASA). Brand names for mesalamine include Asacol, Pentasa, Apriso, Lialda, Delzicol, Rowasa, and Canasa.
How It Works
Pharmacodynamics: Mesalamine’s primary action is anti-inflammatory, achieved by inhibiting cyclooxygenase (COX) and lipoxygenase pathways, reducing the production of inflammatory mediators like prostaglandins and leukotrienes. It also scavenges free radicals and may inhibit tumor necrosis factor (TNF-α).
Pharmacokinetics: Mesalamine is available in oral and rectal formulations designed to release the drug throughout the gastrointestinal tract. Oral formulations are designed as delayed-release or extended-release to target specific areas of the intestine. Rectal formulations (suppositories and enemas) are used to treat distal colitis. Absorption varies depending on the formulation and location of release within the GI tract. It is metabolized in the intestinal wall and liver, primarily by N-acetylation to N-acetyl-5-aminosalicylic acid, and excreted in urine and feces. Elimination is primarily renal, with some hepatic excretion.
Dosage
Standard Dosage
Adults:
Oral mesalamine dosage for adults typically ranges from 2.4 g to 4.8 g daily, administered in divided doses. The specific dosage and formulation depend on the location and severity of the inflammation. For maintenance of remission, lower doses may be sufficient.
Children:
Oral mesalamine is generally recommended for children older than 5 years. Dosing is weight-based and should be determined by a physician. The typical dosage range is 27 to 71 mg/kg/day, divided into two doses, not exceeding the maximum daily limit (which varies by weight). Rectal mesalamine can be considered for children over 12 years old, with dosing and administration guided by a physician.
Special Cases:
- Elderly Patients: Dose adjustments are usually not necessary unless there is significant renal or hepatic impairment. Close monitoring for adverse effects is recommended.
- Patients with Renal Impairment: Mesalamine should be used with caution in patients with renal impairment. Dose adjustments may be necessary based on the degree of impairment.
- Patients with Hepatic Dysfunction: Mesalamine should be used with caution in patients with hepatic dysfunction. Dose adjustments may be necessary based on the severity of the impairment.
- Patients with Comorbid Conditions: Dosage adjustments may be needed for patients with certain comorbid conditions, such as heart or lung disease.
Clinical Use Cases
Mesalamine’s clinical use is mainly focused on IBD management. The use cases below relate to maintaining adequate oxygenation and ventilation, scenarios not directly related to Mesalamine’s therapeutic indication:
- Intubation/Surgical Procedures/Mechanical Ventilation/ICU Use/Emergency Situations: Mesalamine does not have a direct role in these scenarios. The management of IBD in patients undergoing these procedures or in critical care settings requires careful consideration of the patient’s IBD status and potential drug interactions.
Dosage Adjustments
Dose adjustments are based on patient-specific factors such as renal or hepatic dysfunction, disease severity, and response to therapy. Therapeutic drug monitoring can be helpful in optimizing the dose.
Side Effects
Common Side Effects:
Headache, nausea, abdominal pain, diarrhea, flatulence, dizziness, rash, flu-like symptoms (runny nose, sneezing, sore throat).
Rare but Serious Side Effects:
Severe allergic reactions, pancreatitis, pericarditis, nephritis, blood disorders (agranulocytosis, pancytopenia), worsening of colitis symptoms.
Long-Term Effects:
Chronic kidney disease (rare), hair loss (rare), decreased male fertility (rare).
Adverse Drug Reactions (ADR):
Hypersensitivity reactions, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug-induced lupus, myocarditis.
Contraindications
Hypersensitivity to mesalamine or salicylates, severe renal or hepatic impairment, pyloric stenosis, active peptic ulcer disease.
Drug Interactions
Azathioprine, 6-mercaptopurine, certain antacids, NSAIDs, warfarin, and other medications metabolized by CYP450 enzymes.
Pregnancy and Breastfeeding
Mesalamine is generally considered safe during pregnancy (Pregnancy Category B or C, depending on the formulation). Small amounts are excreted in breast milk. While generally considered safe, infants should be monitored for diarrhea.
Drug Profile Summary
- Mechanism of Action: Inhibits inflammatory pathways and scavenges free radicals in the intestinal mucosa.
- Side Effects: Headache, nausea, abdominal pain, diarrhea, rash, rare serious reactions like blood disorders or nephritis.
- Contraindications: Hypersensitivity to salicylates, severe renal/hepatic impairment.
- Drug Interactions: Azathioprine, 6-mercaptopurine, NSAIDs, warfarin.
- Pregnancy & Breastfeeding: Generally safe, monitor infants for diarrhea during breastfeeding.
- Dosage: 2.4-4.8 g/day for adults, weight-based for children.
- Monitoring Parameters: Complete blood count, liver function tests, renal function tests (especially in children and patients with renal impairment).
Popular Combinations
Mesalamine is often used in combination with other medications for IBD, such as corticosteroids or immunomodulators, for enhanced efficacy.
Precautions
Monitor renal and hepatic function, particularly in patients with pre-existing impairment. Observe for signs of blood disorders or hypersensitivity reactions. Caution is advised in patients with asthma or pulmonary disease.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Mesalamine?
A: The recommended dosage varies based on the formulation, indication (induction or maintenance of remission), and patient factors (age, weight, renal/hepatic function). Adults typically receive 2.4-4.8 g/day in divided doses. Children’s dosage is weight-based (27-71 mg/kg/day divided twice daily).
Q2: What are the common side effects of Mesalamine?
A: Common side effects include headache, nausea, abdominal pain, diarrhea, flatulence, and flu-like symptoms.
Q3: What are the serious side effects of Mesalamine?
A: Rare but serious side effects include blood disorders (agranulocytosis, pancytopenia), allergic reactions, nephritis, pericarditis, and worsening of colitis.
Q4: Can Mesalamine be used during pregnancy?
A: Mesalamine is generally considered safe during pregnancy but should be used under the guidance of a physician.
Q5: Can Mesalamine be used during breastfeeding?
A: Mesalamine is excreted in breast milk in small amounts and is generally considered compatible with breastfeeding. Monitor the infant for diarrhea.
Q6: How does Mesalamine work?
A: It acts locally in the gut to reduce inflammation by inhibiting COX and lipoxygenase pathways, scavenging free radicals, and potentially inhibiting TNF-α.
Q7: What are the contraindications to Mesalamine?
A: Contraindications include hypersensitivity to mesalamine or salicylates, severe renal or hepatic impairment, and pyloric stenosis.
Q8: What are the drug interactions with Mesalamine?
A: Mesalamine can interact with azathioprine, 6-mercaptopurine, NSAIDs, some antacids, and warfarin.
Q9: What monitoring parameters should be considered for patients on Mesalamine?
A: Monitor complete blood count, liver function tests, and renal function tests, especially in children and patients with pre-existing renal issues.
A: Yes, mesalamine comes in various oral (tablets, capsules, granules) and rectal (suppositories, enemas) formulations. The formulations are designed to release mesalamine in specific parts of the gastrointestinal tract to target the inflammation site effectively. Different brands and formulations have varying release mechanisms (delayed-release, extended-release, pH-dependent release).
