Mesalamine

Pronunciation
( 5-aminosalicylic acid , 5-ASA )

Pronunciation: me-SAL-a-meen
Class: GI agent

Trade Names

Apriso
- Capsules, extended-release 0.375 g

Asacol
- Tablets, delayed-release 400 mg

Canasa
- Suppositories 1,000 mg

Lialda
- Tablets, delayed-release 1.2 g

Pentasa
- Capsules, controlled-release 250 mg
- Capsules, controlled-release 500 mg

Rowasa
- Enema 4 g per 60 mL

Asacol 800 (Canada)
Mesasal (Canada)
Mezavant (Canada)
Novo-5 ASA (Canada)
Salofalk (Canada)

Pharmacology

Reduces inflammation of colon topically by preventing production of substances involved in inflammatory process, such as arachidonic acid.

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Pharmacokinetics

Absorption

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 ).

Distribution

Approximately 43% bound to plasma proteins ( Apriso , Lialda ).

Metabolism

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.

Elimination

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 Populations

Renal 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 ).

Contraindications

Hypersensitivity to salicylates, aminosalicylates, or any component of the product.

Dosage and Administration

Induction of Remission of Ulcerative Colitis
Adults

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
Adults

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
Adults

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
Adults

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
Adults

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.

General Advice

  • 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.

Storage/Stability

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 ).

Drug Interactions

Antacids

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.

Adverse Reactions

Cardiovascular

Vasodilation (at least 2%); myocarditis, pericardial effusion, pericarditis (postmarketing).

CNS

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).

Dermatologic

Rash (6%); pruritus, sweating (3%); alopecia (less than 3%); acne (2%); dry skin, erythema nodosum, psoriasis, pyoderma gangrenosum, urticaria (postmarketing).

EENT

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).

GI

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).

Genitourinary

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).

Hematologic-Lymphatic

Agranulocytosis, anemia, aplastic anemia, eosinophilia, granulocytopenia, leukopenia, lymphadenopathy, thrombocytopenia (postmarketing).

Hepatic

Cholestatic hepatitis, increased transaminases (at least 3%); cirrhosis, hepatocellular damage (including liver necrosis and liver failure), hepatotoxicity (including cholestatic jaundice, hepatitis, and jaundice) (postmarketing).

Lab Tests

Decreased hematocrit and hemoglobin, increased triglycerides (less than 3%); elevated alkaline phosphatase, ALT, AST, bilirubin, BUN, gamma-glutamyltransferase, LDH, and serum creatinine (postmarketing).

Local

Pain on insertion of enema tip, rectal pain with suppositories (1%).

Metabolic-Nutritional

Peripheral edema (9%); edema, facial edema (postmarketing).

Musculoskeletal

Back pain (7%); arthralgia (5%); myalgia (3%); joint disorder (at least 2%); arthritis, joint pain, leg pain (2%); gout, neck pain (postmarketing).

Respiratory

Dyspnea (less than 3%); bronchitis (at least 2%); cold, increased cough, sore throat (2%); eosinophilic pneumonia, exacerbated asthma, interstitial pneumonitis, pleuritis (postmarketing).

Miscellaneous

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).

Precautions

Monitor

Evaluate renal function prior to starting therapy. Monitor renal function in patients with preexisting renal disease.


Pregnancy

Category B .

Lactation

Excreted in breast milk ( Apriso , Asacol , Lialda , Pentasa ). Undermined ( Canasa , Rowasa ).

Children

Safety and efficacy not established.

Elderly

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.

Hypersensitivity

Some patients who have experienced a hypersensitivity reaction to sulfasalazine may have a similar reaction to mesalamine.

Renal Function

Patients with history of renal function impairment or disease may have worsening of renal function.

Hepatic Function

Use with caution. There have been reports of hepatic failure in patients with preexisting liver disease.

Sulfite Sensitivity

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.

Pericarditis

Rarely, pericarditis has been reported. Observe for chest pain or dyspnea.

Pyloric stenosis

Gastric retention of oral mesalamine may occur in patients with pyloric stenosis.

Worsening symptoms

Worsening of colitis or symptoms of inflammatory bowel disease, including melena and hematochezia, may occur after starting mesalamine.

Overdosage

Symptoms

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.

Patient Information

  • 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.

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