mesalamine (5-aminosalicylic acid)
Asacol, Canasa, Pentasa, Rowasa

Available forms
Available by prescription only
Capsules (controlled-release): 250 mg
Rectal suspension: 4 g/60 ml, in units of 7 disposable bottles
Suppositories: 500 mg
Tablets (delayed-release): 400 mg

Indications and dosages
 Active mild to moderate distal ulcerative colitis, proctosigmoiditis, proctitis. Adults: 800 mg (delayed-release tablets) P.O. t.i.d. for 6 weeks or 1 g (controlled-release capsules) q.i.d. for up to 8 weeks.
 Or, use 1 rectal suppository b.i.d. for 3 to 6 weeks. May increase to 1 rectal suppository t.i.d. after 2 weeks. For maximum benefit, the suppository should be retained for 1 to 3 hours or longer. Usual dosage of mesalamine suspension enema in 60-ml units is one rectal instillation (4 g) once daily, preferably h.s., retained for about 8 hours.
 Lower doses of suspension enemas of 4 g q 2 to 3 nights or 1 g daily have been effective ◇.
 Maintenance of remission of ulcerative colitis ◇. Adults: 1.6 g P.O. daily in divided doses for 6 months. Or, 60 ml (4 g) rectal suspension q 2 to 3 nights or 1 to 3 g rectal suspension daily.

Pharmacodynamics
Anti-inflammatory action: Unknown, but action appears to be topical rather than systemic. Mucosal production of arachidonic acid metabolites, both through cyclooxygenase pathways (such as prostaglandins) and lipoxygenase pathways (such as leukotrienes and hydroxyeicosatetraenoic acids) is increased in patients with chronic inflammatory bowel disease; possibly, mesalamine may diminish inflammation by blocking cyclooxygenase and inhibiting prostaglandin production in the colon.

Pharmacokinetics
Absorption: Drug given by rectal suppository or suspension enema is poorly absorbed from the colon. Extent of absorption depends on retention time, with considerable individual variation. Oral tablets are coated with an acrylic resin that delays the release of drug until tablet is beyond the terminal ileum. About 72% of a dose reaches the colon; 28% of a dose is absorbed. Absorption isn’t affected by food. Capsules are formulated to release therapeutic levels throughout the GI tract. About 20% to 30% is absorbed.
Distribution: Maximum plasma levels of oral mesalamine and N-acetyl 5-aminosalicylic acid are about twice as high as those seen with sulfasalazine therapy. At steady state, about 10% to 30% of daily 4-g rectal dose can be recovered in cumulative 24-hour urine collections.
Metabolism: Undergoes acetylation, but site is unknown. Most absorbed drug is excreted in urine as the N-acetyl-5-aminosalicylic acid metabolite. Elimination half-life of drug is 1/2 to 1 1/2 hours; half-life of acetylated metabolite is 5 to 10 hours. Steady state plasma levels show no accumulation of either free or metabolized drug during repeated daily administrations.
Excretion: After rectal administration, drug is mostly excreted in feces as parent drug and metabolite. After oral administration, drug is mostly excreted in urine as metabolite.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug, its components (sulfite in rectal preparation), or salicylates. Canasa is contraindicated in children.
  Use cautiously in patients with impaired renal function.

Interactions
None reported.

Adverse reactions
CNS: headache, dizziness, fatigue, malaise, asthenia, chills, anxiety, depression, hyperesthesia, paresthesia, tremor, fever.
CV: chest pain.
GI: abdominal pain, cramps, discomfort, flatulence, diarrhea, rectal pain, bloating, nausea, pancolitis, pancreatitis, vomiting, constipation, eructation.
GU: dysuria, hematuria, urinary urgency.
Musculoskeletal: arthralgia, myalgia, back pain.
Respiratory: wheezing.
Skin: itching, rash, urticaria, hair loss, acne.
Other: hypertonia.

Effects on lab test results
• May increase BUN, creatinine, AST, ALT, alkaline phosphatase, LDH, amylase, and lipase levels.

Overdose and treatment
No information available.

Special considerations
• Drug has been used to treat Crohn’s disease.
• Rectal suspension contains potassium meta-bisulfite, which may produce an allergic reaction in susceptible people.
• Although effects of drug may be evident in 3 to 21 days, usual course of therapy is 3 to 6 weeks depending on symptoms and sigmoidoscopic findings. Clinical studies haven’t determined whether suspension enema will modify relapse rates after the 6-week, short-term treatment.
• Monitor renal function studies during therapy.
Breast-feeding patients
• It isn’t known if drug or its metabolites appear in breast milk. Women should avoid breast-feeding during therapy.
Pediatric patients
• Safety and efficacy for use in children haven’t been established.

Patient education
• Tell patient to swallow tablets whole and not to crush or chew them.
• Tell patient to retain suppository as long as possible (at least 1 to 3 hours) for maximum effectiveness.
• Instruct patient in correct use of rectal suspension. - Shake bottle well to make sure the suspension is homogeneous.
- Remove the protective sheath from the applicator tip. Holding the bottle at the neck won’t cause medication to be discharged.
- Lie on the left side (to facilitate migration into the sigmoid colon) with the lower leg extended and the upper right leg flexed forward for balance; or use the knee-chest position.
- Gently insert the applicator tip in the rectum, pointing toward the umbilicus.
- Steadily squeeze the bottle to discharge the preparation into the colon.
• Patient instructions are included with every 7 units.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use