|
This information has been developed and provided by an independent third-party source. Merck & Co., Inc. does not endorse and is not responsible for the accuracy of the content, or for practices or
standards of non-Merck sources.
Pronunciation
(me SAL a meen)
Generic Available (U.S.)
Yes: Rectal suspension
Index Terms
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Oral:
Asacol®, Lialda®, Pentasa®: Treatment and maintenance of remission of mildly- to moderately-active ulcerative colitis
Apriso™: Maintenance of remission of ulcerative colitis
Asacol® HD: Treatment of moderately-active ulcerative colitis
Rectal: Treatment of active mild-to-moderate distal ulcerative colitis, proctosigmoiditis, or proctitis
Pregnancy Risk Factor
B/C (product specific)
Pregnancy Considerations
Animal reproduction studies with mesalamine have not demonstrated teratogenicity or fertility impairment. Dibutyl phthalate (DBP) is an inactive ingredient in the enteric coating of Asacol® and Asacol® HD; adverse effects in male rats were noted at doses greater than the recommended human dose. Mesalamine is known to cross the placenta. An increased rate of congenital malformations has not been observed in human studies. Preterm birth, still birth and decreased birth weight have been observed; however, these events may also be due to maternal disease.
Lactation
Enters breast milk/use caution
Breast-Feeding Considerations
Adverse effects (diarrhea) in a nursing infant have been reported while the mother received rectal administration of mesalamine within 12 hours after the first dose. Low concentrations of the parent drug and higher concentrations of the N-acetyl metabolite of the parent drug have been detected in human breast milk.
Contraindications
Hypersensitivity to mesalamine, aminosalicylates, salicylates, or any component of the formulation
Warnings/Precautions
Concerns related to adverse effects:
• Abdominal discomfort: Pancreatitis should be considered in patients with new abdominal discomfort.
• Cardiac effects: Pericarditis or myocarditis have been reported with use and should be considered in patients with chest pain. Use with caution in patients predisposed to these conditions.
• Colitis: Symptomatic worsening of colitis/IBD may occur following initiation of therapy.
• Intolerance syndrome: May cause an acute intolerance syndrome (cramping, acute abdominal pain, bloody diarrhea; sometimes fever, headache, rash); discontinue if this occurs.
• Oligospermia: In males, oligospermia (rare, reversible) has been reported.
• Sulfasalazine hypersensitivity: Patients with hypersensitivity to sulfasalazine may react to mesalamine; although usually well-tolerated in this population, use with caution.
Disease-related concerns:
• Hepatic impairment: Use caution in patients with hepatic dysfunction; hepatic failure has been reported.
• Peptic ulcer: Use with caution in patients with active peptic ulcers.
• Pyloric stenosis: Patients with pyloric stenosis may have prolonged gastric retention of tablets, delaying the release of mesalamine in the colon.
• Renal impairment: Use with caution in patients with renal impairment or a history of renal disease. Renal disease (including minimal change nephropathy, acute/chronic interstitial nephritis, nephrotic syndrome, and rarely renal failure) has been reported; use caution with other medications converted to mesalamine. An evaluation of renal function is recommended prior to initiation of mesalamine products and periodically during treatment.
Special populations:
• Elderly: Use with caution in the elderly; postmarketing reports suggest an increased incidence of blood dyscrasias in patients >65 years of age. In addition, elderly may have difficulty administering and retaining rectal suppositories or may have decreased renal function.
Dosage form specific issues:
• Apriso™: Contains phenylalanine.
• Asacol®: The Asacol® HD 800 mg tablet has not been shown to be bioequivalent to 2 Asacol® 400 mg tablets.
• Canasa® suppositories: Contain saturated vegetable fatty acid esters (contraindicated in patients with allergy to these components).
• Rowasa® enema: Contains potassium metabisulfite; may cause severe hypersensitivity reactions (ie, anaphylaxis) in patients with sulfite allergies.
Adverse Reactions
Adverse effects vary depending upon dosage form. Incidence usually on lower end with enema and suppository dosage forms.
>10%:
Central nervous system: Headache (2% to 35%), pain (≤14%)
Gastrointestinal: Abdominal pain (1% to 18%), eructation (16%), nausea (3% to 13%)
Respiratory: Pharyngitis (11%)
1% to 10%:
Cardiovascular: Chest pain (3%), peripheral edema (3%), vasodilation (≥2%)
Central nervous system: Dizziness (2% to 8%), fever (1% to 6%), chills (3%), malaise (2% to 3%), fatigue (<3%), vertigo (<3%), anxiety (≥2%), migraine (≥2%), nervousness (≥2%), insomnia (2%),
Dermatologic: Rash (1% to 6%), pruritus (1% to 3%), alopecia (<3%), acne (1% to 2%)
Endocrine & metabolic: Triglyceride increased (<3%)
Gastrointestinal: Diarrhea (2% to 8%), dyspepsia (1% to 6%), flatulence (1% to 6%), constipation (5%), vomiting (1% to 5%), colitis exacerbation (1% to 3%), rectal bleeding (<3%), abdominal distention (≥2%), gastroenteritis (≥2%), gastrointestinal bleeding (≥2%), stool abnormalities (≥2%), tenesmus (≥2%), rectal pain (1% to 2%), hemorrhoids (1%)
Genitourinary: Polyuria (≥2%)
Hematologic: Hematocrit/hemoglobin decreased (<3%)
Hepatic: Cholestatic hepatitis (<3%), transaminases increased (<3%), ALT increased (1%)
Local: Pain on insertion of enema tip (1%)
Neuromuscular & skeletal: Back pain (1% to 7%), arthralgia (≤5%), hypertonia (5%), myalgia (3%), paresthesia (≥2%), weakness (≥2%), arthritis (2%), leg/joint pain (2%)
Ocular: Vision abnormalities (≥2%), conjunctivitis (2%)
Otic: Tinnitus (<3%), ear pain (≥2%)
Renal: Creatinine clearance decreased (<3%), hematuria (<3%)
Respiratory: Nasopharyngitis (1% to 4%), dyspnea (<3%), bronchitis (≥2%), sinusitis (≥2%), cough (≤2%)
Miscellaneous: Flu-like syndrome (1% to 5%), infection (≥2%), diaphoresis (3%), intolerance syndrome (3%)
Postmarketing and/or case reports: Agranulocytosis, albuminuria, alkaline phosphatase increased, amenorrhea, anemia, angioedema, anorexia, aplastic anemia, asthma exacerbation, bilirubin increased, bloody diarrhea, blurred vision, BUN increased, cholestatic jaundice, cholecystitis, confusion, cramping, depression, disorientation, drug fever, dry skin, dysphagia, dysmenorrhea, dysuria, ear congestion, edema, emotional lability, eosinophilia, eosinophilic pneumonia, epididymitis, erythema nodosum, eye pain, facial edema, fecal incontinence, fibrosing alveolitis, gastritis, GGT increased, gout, granulocytopenia, Guillain-Barré syndrome, hepatic failure, hepatic necrosis, hepatitis, hepatocellular damage, hepatotoxicity, hyperesthesia, hypersensitivity pneumonitis, hyper-/hypotension, indigestion, infertility, interstitial nephritis, interstitial pneumonia, jaundice, Kawasaki-like syndrome, LDH increased, leukopenia, libido decreased, lichen planus, lupus-like syndrome, lymphadenopathy, menorrhagia, metrorrhagia, minimal change nephrotic syndrome, myocarditis, neck pain, nephropathy, nephrotoxicity, neutropenia, oligospermia, oral moniliasis, oral ulcers, palpitation, pancreatitis, pancytopenia, perforated peptic ulcer, pericardial effusion, pericarditis, peripheral neuropathy, pharyngolaryngeal pain, photosensitivity, pleuritis, pneumonitis, prurigo, psoriasis, pyoderma gangrenosum, rectal polyp, renal failure, rheumatoid arthritis, rhinitis, serum creatinine increased, somnolence, stomatitis, systemic lupus erythematosus, tachycardia, taste perversion, thrombocythemia, thrombocytopenia, transverse myelitis, tremor, T-wave abnormalities, urinary urgency, urticaria, xerostomia
Metabolism/Transport Effects
None known.
Drug Interactions
Antacids: May diminish the therapeutic effect of Mesalamine. Antacid-mediated increases in gastrointestinal pH may cause the premature release of mesalamine from specific sustained-release mesalamine products. Management: Avoid concurrent administration of antacids with sustained-release mesalamine products. Separating antacid and mesalamine administration, and/or using lower antacid doses may be adequate means of avoiding this interaction. Risk D: Consider therapy modification
Cardiac Glycosides: 5-ASA Derivatives may decrease the serum concentration of Cardiac Glycosides. Risk C: Monitor therapy
H2-Antagonists: May diminish the therapeutic effect of Mesalamine. Histamine H2-Antagonist-mediated increases in gastrointestinal pH may cause the premature release of mesalamine from specific sustained-release mesalamine products. Management: Consider avoiding concurrent administration of high-dose histamine H2-receptor antagonists with sustained-release mesalamine products. Risk D: Consider therapy modification
Heparin: 5-ASA Derivatives may enhance the adverse/toxic effect of Heparin. Specifically, the risk for bleeding/bruising may be increased. Risk C: Monitor therapy
Heparin (Low Molecular Weight): 5-ASA Derivatives may enhance the adverse/toxic effect of Heparin (Low Molecular Weight). Specifically, the risk for bleeding/bruising may be increased. Risk C: Monitor therapy
Proton Pump Inhibitors: May diminish the therapeutic effect of Mesalamine. Proton pump inhibitor-mediated increases in gastrointestinal pH may cause the premature release of mesalamine from specific sustained-release mesalamine products. Management: Consider avoiding concurrent administration of high-dose proton pump inhibitors (PPIs) with sustained-release mesalamine products. Risk D: Consider therapy modification
Thiopurine Analogs: 5-ASA Derivatives may decrease the metabolism of Thiopurine Analogs. Risk C: Monitor therapy
Varicella Virus-Containing Vaccines: 5-ASA Derivatives may enhance the adverse/toxic effect of Varicella Virus-Containing Vaccines. The primary concern is the potential development of Reye's Syndrome, a condition that has been associated with the use of salicylates in children with varicella infections. Risk D: Consider therapy modification
Storage
Capsule:
Apriso™: Store at controlled room temperature of 20°C to 25°C (68°F to 77°F)
Pentasa®: Store at controlled room temperature of 15°C to 30°C (59°F to 86°F). Protect from light.
Enema: Store at controlled room temperature. Use promptly once foil wrap is removed. Contents may darken with time (do not use if dark brown).
Suppository: Store below 25°C (below 77°F). May store under refrigeration; do not freeze. Protect from direct heat, light, and humidity.
Tablet: Store at controlled room temperature:
Asacol®, Asacol® HD: 20°C to 25°C (68°F to 77°F)
Lialda®: 15°C to 30°C (59°F to 86°F)
Mezavant®: 15°C to 25°C (59°F to 77°F)
Mechanism of Action
Mesalamine (5-aminosalicylic acid) is the active component of sulfasalazine; the specific mechanism of action of mesalamine is unknown; however, it is thought that it modulates local chemical mediators of the inflammatory response, especially leukotrienes, and is also postulated to be a free radical scavenger or an inhibitor of tumor necrosis factor (TNF); action appears topical rather than systemic
Pharmacodynamics/Kinetics
Absorption: Rectal: Variable and dependent upon retention time, underlying GI disease, and colonic pH; Oral: Tablet: ~20% to 28%, Capsule: ~20% to 40%
Distribution: ~18 L
Protein binding: Mesalamine (5-ASA): ~43%; N-acetyl-5-ASA: ~78%
Metabolism: Hepatic and via GI tract to N-acetyl-5-aminosalicylic acid
Half-life elimination: 5-ASA: 0.5-10 hours; N-acetyl-5-ASA: 2-15 hours
Time to peak, serum:
Capsule: Apriso™: ~4 hours; Pentasa®: 3 hours
Rectal: 4-7 hours
Tablet: Asacol®: 4-12 hours; Asacol® HD: 10-16 hours; Lialda®: 9-12 hours; Mezavant®: 8 hours
Excretion: Urine (primarily as metabolites, <8% as unchanged drug); feces (<2%)
Dosage
Adults:
Oral:
Treatment of ulcerative colitis (usual course of therapy is 3-8 weeks):
Capsule (Pentasa®): 1 g 4 times/day; Note: Apriso™ capsules are approved for maintenance of remission only.
Tablet: Initial:
Asacol®: 800 mg 3 times/day for 6 weeks
Asacol® HD: 1.6 g 3 times/day for 6 weeks
Lialda®, Mezavant®: 2.4-4.8 g once daily for up to 8 weeks
Maintenance of remission of ulcerative colitis:
Capsule:
Apriso™: 1.5 g once daily in the morning
Pentasa®: 1 g 4 times/day
Tablet:
Asacol®): 1.6 g/day in divided doses
Lialda®: 2.4 g once daily
Note: Asacol® HD and Mezavant® tablets are approved for treatment only.
Rectal:
Active mild-to-moderate distal ulcerative colitis, proctosigmoiditis, or proctitis: Retention enema: 60 mL (4 g) at bedtime, retained overnight, approximately 8 hours
Active ulcerative proctitis: Rectal suppository (Canasa®): Insert one 1000 mg suppository in rectum daily at bedtime; retained for at least 1-3 hours to achieve maximum benefit
Note: Duration of rectal therapy is 3-6 weeks; some patients may require rectal and oral therapy concurrently.
Elderly: See adult dosing; use with caution
Administration: Oral
Oral: Swallow capsules or tablets whole, do not break, chew, or crush.
Capsules:
Apriso™: Administer with or without food; do not administer with antacids. The capsule should be swallowed whole per the manufacturer's labeling; however, opening the capsule and placing the contents (delayed release granules) on food with a pH <6 is not expected to affect the release of mesalamine once ingested (data on file, Salix Pharmaceuticals Medical Information). There is no safety/efficacy information regarding this practice. The contents of the capsules should not be chewed or crushed.
Pentasa®: Administer with or without food. Although the manufacturer recommends swallowing the capsule whole, if a patient is unable to swallow the capsule, some clinicians support opening the capsules and placing the contents (controlled-release beads) on yogurt or peanut butter (Crohn's & Colitis Foundation of America). There are currently no published data evaluating the safety/efficacy of this practice. The contents of the capsules should not be chewed or crushed.
Tablets:
Asacol®: Do not break outer coating.
Asacol® HD: Do not break outer coating; administer with or without food.
Lialda®: Do not break outer coating; should be administered once daily with a meal
Mezavant®: Do not break outer coating; should be administered once daily with a meal
Administration: Other
Rectal enema: Shake bottle well. Retain enemas for 8 hours or as long as practical.
Suppository: Remove foil wrapper; avoid excessive handling. Should be retained for at least 1-3 hours to achieve maximum benefit.
Monitoring Parameters
Renal function (prior to and periodically during therapy); CBC (particularly in elderly patients)
Dietary Considerations
Some products may contain phenylalanine.
Apriso™: Take with or without food; do not administer with antacids.
Asacol® HD: Take with or without food.
Canasa® rectal suppository contains saturated vegetable fatty acid esters.
Patient Education
Do not take any new prescriptions, OTC medications, or herbal products during therapy unless approved by prescriber. Take exactly as directed. Symptomatic exacerbation of colitis/IBD may occur when beginning treatment; this should resolve in a short time. May cause fatigue, dizziness, or insomnia (avoid driving or engaging in tasks requiring alertness until response to drug is known); mild gastrointestinal disturbance (eg, gas, constipation, nausea); back, joint, or muscle pain; or flu-like syndrome or cough (consult prescriber if persistent). Report immediately severe new abdominal pain or diarrhea; chest pain or rapid heartbeat; unusual pain (back, joint, muscle, or chest) or swelling of extremities; rash; ringing in ears or change in hearing; or other persistent adverse effects or lack of improvement.
Oral: Swallow tablets or capsules whole; do not break, crush, or chew. Notify prescriber if unable to swallow the medication. Notify prescriber if whole or partial tablets are repeatedly found in stool; should be taken with a meal.
Enema: Follow package insert direction for administering enema. Shake well before using; retain for 8 hours or as long as possible. May cause staining of clothing and undergarments. Do not use if solution is dark brown.
Suppository: Do not refrigerate; store at room temperature. After removing foil wrapper, insert high in rectum without excessive handling (warmth will melt suppository). Lubricating gel may be used if needed to assist insertion. Retain suppositories for at least 1-3 hours to achieve maximum benefit. May cause staining of clothing and undergarments.
Geriatric Considerations
Use with caution. Elderly may have difficulty administering and retaining rectal suppositories. Given renal function decline with aging, monitor serum creatinine often during therapy.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Pharyngitis.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
Malaise is common
Mental Health: Effects on Psychiatric Treatment
None reported
Nursing: Physical Assessment/Monitoring
Assess history of hypersensitivity to salicylates prior to beginning treatment. Use caution in presence of impaired hepatic or renal function, predisposition to pericarditis or myocarditis, or active peptic ulcers. Assess potential for interactions or toxicity with other pharmacological agents or herbal products the patient may be taking (eg, other medications converted to mesalamine). Assess results of laboratory tests (CBC and renal function), therapeutic effectiveness, and adverse reactions on a regular basis throughout therapy (acute intolerance syndrome may necessitate discontinuing). Teach patient proper use (according to formulation), possible side effects/appropriate interventions (eg, importance of adequate hydration), and adverse symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, controlled release, oral:
Pentasa®: 250 mg, 500 mg
Capsule, delayed and extended release, oral:
Apriso™: 0.375 g [contains phenylalanine 0.56 mg/capsule]
Suppository, rectal:
Canasa®: 1000 mg (30s, 42s) [contains saturated vegetable fatty esters]
Suspension, rectal: 4 g/60 mL (7s, 28s)
Rowasa®: 4 g/60 mL (7s) [contains potassium metabisulfite, sodium benzoate; packaged with wipes]
Rowasa®: 4 g/60 mL (28s) [contains potassium metabisulfite, sodium benzoate; packaged with wipes]
sfRowasa™: 4 g/60 mL (7s, 28s) [contains sodium benzoate]
Tablet, delayed release, enteric coated, oral:
Asacol®: 400 mg
Asacol® HD: 800 mg
Lialda®: 1.2 g
Pricing: U.S. (www.drugstore.com)
Capsule, 24-hour (Apriso)
0.375 g (120): $298.10
Capsule, controlled release (Pentasa)
250 mg (240): $332.01
500 mg (30): $90.99
Enema (Mesalamine)
4 g (60): $35.99
Suppository (Canasa)
1000 mg (30): $573.68
Tablet, EC (Lialda)
1.2 g (120): $766.97
References
American Academy of Pediatrics Committee on Drugs, "Transfer of Drugs and Other Chemicals Into Human Milk," Pediatrics, 2001, 108(3):776-89.
Crohn's & Colitis Foundation of America (CCFA). Available at http://www.ccfa.org/info/treatment/kidsmeds
Grand RJ, Ramakrishna J, and Calenda KA, “Inflammatory Bowel Disease in the Pediatric Patient,” Gastroenterol Clin North Am, 1995, 24(3):613-32.
Kamm MA, Sandborn WJ, Gassull M, et al, “Once-Daily, High-Concentration MMX Mesalamine in Active Ulcerative Colitis,” Gastroenterology, 2007, 132(1):66-75.
Kornbluth A and Sachar DB, “Ulcerative Colitis Practice Guidelines in Adults: American College of Gastroenterology, Practice Parameters Committee,” Am J Gastroenterol, 2010, 105(3):501-23.
Lichtenstein GR, Hanauer SB, and Sandborn WJ, “Management of Crohn's Disease in Adults,” Am J Gastroenterol, 2009, 104(2):465-83.
International Brand Names
Lexi-Comp.com
Last full review/revision March 2012
|
