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Mesalamine( 5-aminosalicylic acid , 5-ASA )
Class: GI agent
- Capsules, extended-release 0.375 g
- Tablets, delayed-release 400 mg
- Suppositories 1,000 mg
- Tablets, delayed-release 1.2 g
- Capsules, controlled-release 250 mg
- Capsules, controlled-release 500 mg
- Enema 4 g per 60 mL
Novo-5 ASA (Canada)
Reduces inflammation of colon topically by preventing production of substances involved in inflammatory process, such as arachidonic acid.
Approximately 28% is absorbed; T max is 4 to 12 h ( Asacol ). Approximately 21% to 22% is absorbed; C max is 857 to 2,154 ng/mL; AUC 0-∞ is 9,578 to 44,775 ng•h/mL; T max is 9 to 12 h ( Lialda ). Approximately 20% to 30% is absorbed; C max is 1.8 mcg/mL for N-acetylmesalamine metabolite; T max is approximately 3 h for N-acetylmesalamine ( Pentasa ). C max at steady state is 361 ng/mL; absorption is variable ( Canasa ). C max after 10 to 12 h is 2 mcg/mL, two-thirds of which is the N-acetylmesalamine metabolite ( Rowasa ). Approximately 32% is absorbed; C max is about 2 h; T max is about 4 h ( Apriso ).
Approximately 43% bound to plasma proteins ( Apriso , Lialda ).
Orally administered mesalamine products are rapidly acetylated in the gut mucosal wall and liver. Rectal doseforms are also acetylated, but the site of metabolism is unknown. The major metabolite is N-acetylmesalamine.
Unabsorbed mesalamine is excreted in feces; absorbed amount is excreted mainly in the kidney as N-acetyl-5-aminosalicylic acid. Mean half-life is 2 to 15 h ( Asacol ). Excretion of absorbed dose was 8% as unchanged drug and more than 113% as N-acetyl-5-aminosalicylic acid; the half-life for mesalamine and N-acetyl-5-aminosalicylic acid was 7 to 9 h and 8 to 12 h, respectively ( Lialda ). Mean half-life is 42 min (IV mesalamine) and 19% to 30% of N-acetyl-5-aminosalicylic acid was excreted in urine ( Pentasa ). At steady state, less than 11% of the dose was eliminated in urine as unchanged drug and 3% to 35% was N-acetyl-5-aminosalicylic acid; mean half-life at steady state was 7 h ( Canasa ). The half-life of mesalamine is 0.5 to 1.5 h; the half-life of N-acetyl-5-aminosalicylic acid is 5 to 10 h (mesalamine enema). Half-life is about 9 h; approximately 2% of the administered dose is excreted unchanged in the urine ( Apriso ).
Special PopulationsRenal Function Impairment
No pharmacokinetic information is available.Hepatic Function Impairment
No pharmacokinetic information is available.
Indications and Usage
Treatment of mildly to moderately active ulcerative colitis ( Asacol , Pentasa ); induction of remission in patients with active, mild to moderate ulcerative colitis ( Lialda , Pentasa ); maintenance of remission of ulcerative colitis ( Apriso , Asacol ); treatment of active ulcerative proctitis ( Canasa ); treatment of active mild to moderate distal ulcerative colitis, proctosigmoiditis, or proctitis ( Rowasa ).
Hypersensitivity to salicylates, aminosalicylates, or any component of the product.
Dosage and AdministrationInduction of Remission of Ulcerative Colitis
PO Lialda 2.4 to 4.8 g tablets once daily with a meal for up to 8 wk. PO Pentasa 1 g controlled-release capsules 4 times daily for up to 8 wk.Maintenance of Remission of Ulcerative Colitis
PO Asacol 1.6 g delayed-release tablets daily, in divided doses. PO Apriso 1.5 g once daily in the morning.Treatment of Active, Mild to Moderate Distal Ulcerative Colitis, Proctosigmoiditis, or Proctitis
PR Rowasa 4 g in 60 mL rectal suspension enema as rectal instillation once a day for up to 6 wk, preferably at bedtime, retained for 8 h.Treatment of Active, Mild to Moderate Ulcerative Colitis
PO Asacol 800 mg delayed-release tablets 3 times daily (2.4 g/day) for 6 wk. PO Pentasa 1 g controlled-release capsules 4 times daily for up to 8 wk.Treatment of Active Ulcerative Proctitis
PR Canasa 1,000 mg rectal suppository once daily at bedtime. Retain suppository in rectum for at least 1 to 3 h for max benefit for up to 6 wk. PR Rowasa 4 g in 60 mL rectal suspension enema as rectal instillation every day for up to 6 wk, preferably at bedtime, retained for 8 h.
- Shake Rowasa enema well to make sure suspension is homogeneous.
- Rowasa enema can cause staining of direct contact surfaces, including fabrics, floor covering, painted surfaces, marble, granite, vinyl, and enamel.
- Rowasa enema may darken with time. Slight darkening does not affect potency; however, discard enemas with dark brown contents.
- Apriso may be taken without regards to meals.
- Apriso should not be taken with antacids.
Store at 68° to 77°F ( Asacol , Rowasa ).
Store below 77°F. Keep away from direct heat, light, or humidity; do not freeze ( Canasa ).
Store at 59° to 86°F ( Aprio , Lialda , Pentasa ).
Because the dissolution of the coating of Apriso granules depends on pH, do not administer with antacids.Nephrotoxic agents (including NSAIDs)
Increased risk of renal adverse reactions.Thiopurines (eg, azathioprine, mercaptopurine)
Risk of leukopenia may be increased.Warfarin
Decreased anticoagulant effect of warfarin has been reported in 1 patient.
Laboratory Test Interactions
None well documented.
Vasodilation (at least 2%); myocarditis, pericardial effusion, pericarditis (postmarketing).
Headache (35%); dizziness (8%); asthenia (7%); hypertonia (5%); fatigue, malaise, tiredness, weakness (6%); anxiety, migraine, nervousness, paresthesia (at least 2%); insomnia (2%); confusion, depression, emotional lability, Guillain-Barré syndrome, hyperesthesia, peripheral neuropathy, somnolence, transverse myelitis, tremor (postmarketing).
Rash (6%); pruritus, sweating (3%); alopecia (less than 3%); acne (2%); dry skin, erythema nodosum, psoriasis, pyoderma gangrenosum, urticaria (postmarketing).
Pharyngitis (11%); rhinitis (5%); nasopharyngitis (4%); tinnitus, vertigo (less than 3%); ear disorder, ear pain, sinusitis, visual abnormalities (at least 2%); conjunctivitis, sore throat (2%); blurred vision, eye pain, taste perversion (postmarketing).
Abdominal pain (18%); eructation (16%); nausea (13%); abdominal cramps/discomfort (8%); diarrhea (7%); dyspepsia, flatulence (6%); constipation, vomiting (5%); colitis exacerbation (3%); lower abdominal pain, rectal hemorrhage (less than 3%); abdominal enlargement, gastroenteritis, GI hemorrhage, rectal disorder, stool abnormalities, tenesmus (at least 2%); bloating, rectal pain (2%); anorexia, hemorrhoids, melena (1%); bloody diarrhea, cholecystitis, dry mouth, gastritis, increased appetite, oral ulcers, pancreatitis, perforated peptic ulcer (postmarketing).
Dysmenorrhea, UTI (3%); decreased CrCl, hematuria (less than 3%); urinary frequency (at least 2%); dysuria, epididymitis, interstitial nephritis, menorrhagia, minimal change nephropathy, renal failure, reversible oligospermia, urinary urgency (postmarketing).
Agranulocytosis, anemia, aplastic anemia, eosinophilia, granulocytopenia, leukopenia, lymphadenopathy, thrombocytopenia (postmarketing).
Cholestatic hepatitis, increased transaminases (at least 3%); cirrhosis, hepatocellular damage (including liver necrosis and liver failure), hepatotoxicity (including cholestatic jaundice, hepatitis, and jaundice) (postmarketing).
Decreased hematocrit and hemoglobin, increased triglycerides (less than 3%); elevated alkaline phosphatase, ALT, AST, bilirubin, BUN, gamma-glutamyltransferase, LDH, and serum creatinine (postmarketing).
Pain on insertion of enema tip, rectal pain with suppositories (1%).
Peripheral edema (9%); edema, facial edema (postmarketing).
Back pain (7%); arthralgia (5%); myalgia (3%); joint disorder (at least 2%); arthritis, joint pain, leg pain (2%); gout, neck pain (postmarketing).
Dyspnea (less than 3%); bronchitis (at least 2%); cold, increased cough, sore throat (2%); eosinophilic pneumonia, exacerbated asthma, interstitial pneumonitis, pleuritis (postmarketing).
Pain (14%); fever (6%); flu syndrome (5%); chest pain, chills (3%); infection (at least 2%); itching (1%); angioedema, drug fever, Kawasaki-like syndrome lupus-like syndrome, SLE (postmarketing).
Evaluate renal function prior to starting therapy. Monitor renal function in patients with preexisting renal disease.
Category B .
Excreted in breast milk ( Apriso , Asacol , Lialda , Pentasa ). Undermined ( Canasa , Rowasa ).
Safety and efficacy not established.
Use with caution, usually starting at the low end of the dosage range, because of the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant diseases or other drug therapy.
Some patients who have experienced a hypersensitivity reaction to sulfasalazine may have a similar reaction to mesalamine.
Patients with history of renal function impairment or disease may have worsening of renal function.
Use with caution. There have been reports of hepatic failure in patients with preexisting liver disease.
Some products may contain sulfites, which may cause allergic reactions in susceptible individuals.
Intolerance and colitis exacerbation
Some patients may develop acute intolerance syndrome or exacerbation of colitis characterized by cramping, acute abdominal pain, bloody diarrhea, and, occasionally, fever, headache, malaise, pruritus, conjunctivitis, and rash. Symptoms generally abate when mesalamine is discontinued.
Rarely, pericarditis has been reported. Observe for chest pain or dyspnea.
Gastric retention of oral mesalamine may occur in patients with pyloric stenosis.
Worsening of colitis or symptoms of inflammatory bowel disease, including melena and hematochezia, may occur after starting mesalamine.
Products are salicylates; symptoms of salicylate toxicity may include confusion, deafness, dehydration, diarrhea, drowsiness, dyspnea, electrolyte and blood pH imbalance, headache, hematemesis, hyperpnea, hyperthermia, hyperventilation, lethargy, seizures, sweating, tachypnea, tinnitus, vertigo, vomiting.
- Tell patient to swallow capsules or tablets whole. Explain that outer coating must be intact to pass through stomach and travel to sigmoid colon.
- Tell patient to notify health care provider if any remnant of capsule or tablet is seen in stool.
- Tell patient to retain suppository 1 to 3 h or to retain enema for 8 h.
- Teach patient proper positioning and technique for self-administering enema. Include knee-chest and left side positions to promote medication advancement to sigmoid colon.
- Tell patient to report the following symptoms to health care provider: increase in abdominal pain, diarrhea, or vomiting.
- Instruct patient to notify health care provider of fever, hives, itching, rash, or wheezing.
- Tell patients that Rowasa enema can cause staining of direct contact surfaces, including fabrics, floor covering, painted surfaces, marble, granite, vinyl, and enamel.
Copyright © 2009 Wolters Kluwer Health.