Canasa - Drug Monograph

Introduction

Canasa (mesalamine) is an aminosalicylate anti-inflammatory medication used primarily for the treatment of ulcerative colitis. It is formulated as a rectal suppository designed to deliver the active drug directly to the site of inflammation in the distal colon and rectum, providing localized therapy with minimal systemic absorption.

Mechanism of Action

Mesalamine, the active component of Canasa, exerts its therapeutic effect through local anti-inflammatory action in the colon. While the exact mechanism is not fully understood, it appears to work through multiple pathways:

• Inhibition of cyclooxygenase and lipoxygenase pathways, reducing prostaglandin and leukotriene production
• Scavenging of reactive oxygen species that contribute to mucosal damage
• Inhibition of neutrophil chemotaxis and mast cell degranulation
• Interference with cytokine production (particularly IL-1 and TNF-α)

These actions collectively reduce inflammation in the colonic mucosa without the systemic effects of corticosteroids.

Indications

Canasa is FDA-approved for:

• Treatment of active mild to moderate distal ulcerative colitis, proctosigmoiditis, or proctitis
• Maintenance of remission in ulcerative proctitis

Dosage and Administration

• Duration: 3-6 weeks for symptomatic treatment

• Remove foil wrapper and moisten suppository with water
• Insert suppository completely into rectum with pointed end first
• Remain recumbent for 15-30 minutes after insertion to retain suppository
• Use at bedtime to maximize contact time with colonic mucosa

• Renal impairment: Use with caution in patients with renal dysfunction
• Hepatic impairment: No specific dosage adjustment recommended
• Elderly: No specific dosage adjustment required
• Pediatrics: Safety and effectiveness not established

Pharmacokinetics

• Primary action is local to the colorectal mucosa
• Plasma concentrations are low and variable

• Low protein binding (approximately 43%)

• Metabolized to N-acetyl-5-aminosalicylic acid (acetylation phenotype dependent)

• Renal excretion of absorbed drug: half-life approximately 7-9 hours
• Total body clearance: Approximately 10 L/hour

Contraindications

• Hypersensitivity to mesalamine, salicylates, or any component of the formulation
• History of hypersensitivity reactions to sulfasalazine

Warnings and Precautions

• Mesalamine has been associated with renal toxicity (interstitial nephritis)
• Evaluate renal function at baseline and periodically during treatment

• Discontinue therapy if this syndrome occurs

• Monitor liver enzymes in patients with pre-existing liver disease

• Limited human data; animal studies show no evidence of harm

Drug Interactions

• Monitor INR closely when initiating or discontinuing Canasa

• Monitor complete blood count regularly

• Use with caution and monitor renal function

Adverse Effects

• Gastrointestinal: Abdominal pain/cramps (5%), flatulence (4%), diarrhea (3%), nausea (2%)
• Neurological: Headache (4%), dizziness (2%)
• Dermatological: Rash (2%), pruritus (1%)
• Other: Fever (2%), flu-like syndrome (1%)

• Renal impairment/interstitial nephritis
• Acute mesalamine intolerance syndrome
• Hepatic impairment/hepatitis
• Pulmonary fibrosis
• Blood dyscrasias (pancytopenia, agranulocytosis)
• Pericarditis
• Pancreatitis

Monitoring Parameters

• Efficacy: Symptom improvement, endoscopic evaluation when indicated
• Renal function: Serum creatinine, BUN at baseline and every 3-6 months
• Liver function: Liver enzymes at baseline and periodically
• Hematologic: Complete blood count at baseline and periodically
• Adverse effects: Monitor for signs of intolerance syndrome, pulmonary symptoms

Patient Education

• Use exactly as prescribed, typically once daily at bedtime
• Proper administration technique is crucial for effectiveness
• Remain lying down for 15-30 minutes after insertion
• Store suppositories in refrigerator (2-8°C/36-46°F)
• Report any of the following immediately:

- Worsening abdominal pain or bloody diarrhea - Fever, rash, or difficulty breathing - Decreased urine output or unusual fatigue - Yellowing of skin or eyes

• Inform all healthcare providers about Canasa use, especially before surgery
• Do not stop medication without consulting healthcare provider, even if feeling better
• Suppository may cause staining of clothing and bedding

References

1. FDA Prescribing Information: Canasa (mesalamine) rectal suppository 2. Sandborn WJ. Mesalamine in the treatment of ulcerative colitis. Gastroenterol Hepatol. 2011;7(1):3-8 3. Kornbluth A, Sachar DB. Ulcerative colitis practice guidelines in adults: American College of Gastroenterology, Practice Parameters Committee. Am J Gastroenterol. 2010;105(3):501-523 4. Hanauer SB. Medical therapy for ulcerative colitis. Gastroenterol Clin North Am. 2004;33(2):147-166 5. Loftus EV Jr. Clinical epidemiology of inflammatory bowel disease: incidence, prevalence, and environmental influences. Gastroenterology. 2004;126(6):1504-1517 6. Kamm MA, Sandborn WJ, Gassull M, et al. Once-daily, high-concentration MMX mesalamine in active ulcerative colitis. Gastroenterology. 2007;132(1):66-75 7. Tremaine WJ. Refractory IBD: medical management. N Engl J Med. 2003;349(4):307-309