Mesalazine

Pharmacologic Category

5-Aminosalicylic Acid Derivative

Dosing: Adult

Note: Asacol HD formulated with DBP has been discontinued in the US for more than 1 year.

Crohn disease management after surgical resection (off-label use): Oral: 1.5 g twice daily (McLeod 1995) or 2.4 to 4 g/day in 3 divided doses (Ardizzone 2004; Caprilli 2003)

Crohn disease, mild to moderate (treatment): Oral: Pentasa (Canadian labeling; not in US labeling): Initial: 1 g 4 times daily

Crohn disease, mild to moderate (maintenance of remission): Oral: Pentasa (Canadian labeling; not in US labeling): 1 g 3 times daily

Distal ulcerative colitis or proctosigmoiditis (treatment):

Mild to moderately active: Retention enema (suspension): Rectal: 4 g at bedtime, retained overnight, ~8 hours. Note: Duration of rectal therapy is 3 to 6 weeks; some patients may require rectal and oral therapy concurrently.

Mildly active: Foam (Mezera [Canadian product]): Rectal: 2 g (2 actuations) once daily at bedtime. If patient unable to retain 2 g dose, may administer as 1 g (1 actuation) in 2 divided doses, 1 dose at bedtime and other dose during the night (after evacuation of first dose) or in early morning. Continue for at least 6 weeks until endoscopic and/or histological remission.

Distal ulcerative colitis (maintenance of remission): Rectal: Retention enema: Salofalk [Canadian product]: 2 g at bedtime daily or 4 g at bedtime every 2 to 3 days

Ulcerative colitis (treatment): Oral: Note: Mesalamine may be dosed once daily instead of multiple times daily in patients with mild to moderate ulcerative colitis; there is no significant difference in efficacy and safety. Dosing schedule should be based on patient preference in order to maximize adherence (ACG [Rubin 2019]; AGA [Ko 2018]). Usual course of therapy is 6 to 8 weeks:

US labeling:

Asacol HD: 1.6 g 3 times daily for 6 weeks

Delzicol: 800 mg 3 times daily for 6 weeks

Lialda: 2.4 or 4.8 g once daily

Pentasa: 1 g 4 times daily

Canadian labeling:

Asacol: 800 mg to 3.2 g in divided doses daily; for severe active disease may increase to 4.8 g daily

Asacol 800: 1.6 g 3 times daily for 6 weeks

Mesasal: 1.5 to 3 g daily in 3 divided doses

Mezavant: 2.4 to 4.8 g once daily

Pentasa: 500 mg 4 times daily; may increase to 1 g 4 times daily if needed

Ulcerative colitis (maintenance of remission): Oral: Note: Mesalamine may be dosed once daily instead of multiple times daily in patients with mild to moderate ulcerative colitis; there is no significant difference in efficacy and safety. Dosing schedule should be based on patient preference in order to maximize adherence (ACG [Rubin 2019]; AGA [Ko 2018]).

US labeling:

Apriso: 1.5 g once daily in the morning

Delzicol: 1.6 g in 2 to 4 divided doses

Lialda: 2.4 g once daily

Pentasa: 1 g 4 times daily

Canadian labeling:

Asacol: 1.6 g daily in divided doses

Mesasal: 1.5 g daily in 3 divided doses

Mezavant: 2.4 g once daily

Pentasa: 500 mg 4 times daily; may increase to 1 g 4 times daily if needed

Ulcerative proctitis, active:

Retention enema (suspension): 4 g at bedtime, retained overnight, approximately 8 hours

Rectal suppository: 1,000 mg (1 suppository) rectally (retain for at least 1 to 3 hours) at bedtime for 3 to 6 weeks.

Salofalk [Canadian product]: One 500 mg suppository in rectum 2 to 3 times daily or one 1,000 mg suppository in rectum once daily at bedtime; retained for at least 1 to 3 hours to achieve maximum benefit. Usual dose: 1 to 1.5 g daily until significant clinical response or remission. Taper off gradually; avoid abrupt discontinuation.

* See Dosage and Administration in AHFS Essentials for additional information.

Dosing: Geriatric

Refer to adult dosing. Use with caution.

Dosing: Renal Impairment: Adult

There are no specific dosage adjustments provided in the manufacturer's labeling; however, dosage adjustment may be necessary since mesalamine is renally eliminated. Use with caution.

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling; use with caution.

Dosing: Pediatric

Note: Some oral products are not bioequivalent and should not be interchanged (ie, two Delzicol 400 mg capsules are not interchangeable or substitutable with one mesalamine 800 mg delayed release tablet).

Crohn disease; treatment (mild to moderate disease); maintenance of remission: Limited data available: Children and Adolescents: Oral: 50 to 100 mg/kg/day divided every 6 to 12 hours (Fish 2004); maximum dose: 1,000 mg/dose

Ulcerative colitis; treatment (mild to moderate disease):

Oral:

Manufacturer's labeling: Delayed release capsule: Delzicol: Children ≥5 years and Adolescents:

17 to <33 kg: Oral: 800 mg in the morning and 400 mg in the evening for 6 weeks; maximum daily dose: 1,200 mg/day

33 to <54 kg: Oral: 1,200 mg in the morning and 800 mg in the evening for 6 weeks; maximum daily dose: 2,000 mg/day

54 to 90 kg: Oral: 1,200 mg in the morning and 1,200 mg in the evening for 6 weeks; maximum daily dose: 2,400 mg/day

Alternate dosing (including proctitis): Limited data available: Usual course of therapy is 3 to 8 weeks dependent on type of treatment: Children and Adolescents: Oral: 30 to 60 mg/kg/day divided every 6 to 12 hours; doses as high as 100 mg/kg/day have been used; maximum daily dose: 4,000 mg/day (Baldassano 1999; Fish 2004; Leichtner 1995; Tomomasa 2004)

Rectal: Limited data available: Older Children and Adolescents:

Enema: 4,000 mg once daily at bedtime (Baldassano 1999)

Suppository: 500 mg once daily at bedtime; some have used twice daily (Baldassano 1999; Heyman 2010)

Dosing: Renal Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer’s labeling; however, dosage adjustments may be necessary since mesalamine is renally eliminated; use with caution.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer’s labeling; use with caution.

Use: Labeled Indications

US labeling:

Oral:

Apriso: Maintenance of remission of ulcerative colitis in patients ≥18 years

Asacol HD: Treatment of moderately active ulcerative colitis in adults

Delzicol: Treatment of mildly to moderately active ulcerative colitis in patients ≥5 years; maintenance of remission of ulcerative colitis in adults

Lialda, Pentasa: Treatment and maintenance of remission of mildly to moderately active ulcerative colitis

Rectal: Treatment of active mild to moderate distal ulcerative colitis (suspension only), proctosigmoiditis (suspension only), or proctitis (suspension and suppository)

Canadian labeling:

Oral:

Asacol, Mezavant: Treatment and maintenance of remission of mildly- to moderately-active ulcerative colitis

Asacol 800: Treatment of moderately active ulcerative colitis

Mesasal: Treatment and maintenance of remission of ulcerative colitis

Pentasa: Treatment and maintenance of remission of mildly to moderately active ulcerative colitis; treatment and maintenance of remission of mild to moderate Crohn disease

Rectal foam: Mezera: Treatment of mildly active ulcerative colitis of the sigmoid colon and rectum

Rectal suppository and suspension: Treatment and maintenance of remission of distal ulcerative colitis (extending to splenic flexure) and as adjunctive therapy in more extensive disease (suspension only); treatment and maintenance of ulcerative proctitis (suppository only)

* See Uses in AHFS Essentials for additional information.

Use: Off-Label: Adult

Crohn disease (management after surgical resection)Level of Evidence [C, G]

Data from randomized, double-blinded, placebo controlled and prospective controlled trials support the use of mesalamine to prevent recurrence of Crohn disease after surgically induced remission and has demonstrated a modest benefit to decrease risk of postoperative endoscopic and clinical recurrence rates ^Ref. It may be appropriate to reserve mesalamine for patients unwilling to consider agents with more side effects or for those patients who have a lower risk of clinical recurrence ^Ref.

Based on the American Gastroenterological Association Institute Guidelines for the Management of Crohn's Disease after Surgical Resection, mesalamine is not recommended to prevent postoperative clinical recurrence. However, the National Institute for Health and Care Excellence (NICE) guidelines do recommend to consider mesalamine to maintain remission after surgery. Controversy around the effectiveness of mesalamine in place of other therapies needs to be investigated; although, it remains a safe and well-tolerated alternative ^Ref.

Level of Evidence Definitions

Level of Evidence Scale

Comparative Efficacy

• MESALAMINE

Clinical Practice Guidelines

Crohn Disease:

American College of Gastroenterology, “Management of Crohn's Disease in Adults,” March 2018

American College of Gastroenterology, “Management of Crohn’s Disease after Surgical Resection,” January 2017

Ulcerative Colitis:

American College of Gastroenterology, "Ulcerative Colitis in Adults," March 2019

American Gastroenterological Association, “Guideline on the Management of Mild-to-Moderate Ulcerative Colitis,” December 2018

Administration: Oral

Capsules: Administer with or without food

Apriso: Do not administer with antacids. 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.

Delzicol: Swallow capsule whole with water; do not break, chew, crush, or cut. If a patient is unable to swallow the capsule, may open capsule and swallow capsule contents whole (do not cut, chew, break, or crush the contents).

Pentasa: Swallow capsule whole; do not crush or chew; if a patient is unable to swallow the capsule, may open capsule and sprinkle the entire contents (controlled-release beads) onto yogurt or applesauce.

Tablets: Swallow whole; do not break, chew, cut, or crush.

Asacol [Canadian product]: Administer with or without food.

Asacol HD (product formulated without dibutyl phthalate [DBP]): Administer on an empty stomach (at least 1 hour before or 2 hours after a meal).

Asacol HD (product formulated with DBP); Asacol 800 [Canadian product]: Administer with or without food.

Lialda: Administer with a meal.

Mesasal [Canadian product]: Administer before meals.

Mezavant [Canadian product]: Administer with a meal.

Pentasa [Canadian product]: Administer with meals.

Administration: Rectal

Rectal enema: Shake bottle well. Instruct patient to lie on left side with left leg extended and right leg flexed forward for balance, or in “knee-chest” position. Insert lubricated applicator tip into the rectum and point slightly toward the navel. Grasp bottle firmly and tilt so nozzle is aimed toward the back; squeeze slowly to instill medication. After administration, withdraw and discard bottle. Retain enemas for 8 hours or as long as practical.

Rectal foam (Mezera [Canadian product]): Warm canister to room temperature (15°C to 30°C [59°F to 86°F]). Attach applicator to canister; shake for ~20 seconds. Insert applicator as far into the rectum as comfortable for patient. Press pump dome once and slowly release it to administer dose; hold applicator in rectum for 10 to 15 seconds after dose administered. For the second spray, press dome again and release slowly; wait a further 10 to 15 seconds, then remove the applicator and dispose.

Suppository: Remove foil wrapper; avoid excessive handling. Insert into rectum. Retain suppository for 1 to 3 hours or longer. Do not cut or break suppository.

Administration: Pediatric

Oral:

Capsule: Administer with or without food.

Apriso: 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.

Delzicol: Swallow capsule whole with water; do not break, chew, crush, or cut. If a patient is unable to swallow the capsule, may open capsule and swallow capsule contents whole (do not cut, chew, break, or crush, or cut the contents). Ensure that all contents are swallowed and no contents are retained in the mouth.

Pentasa: 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.

Tablet:

Asacol HD: Take on an empty stomach, at least 1 hour before and 2 hours after a meal. Swallow tablets whole; do not break, chew, or crush; do not break outer coating.

Lialda: Take with a meal. Swallow tablets whole; do not break outer coating.

Rectal:

Enema: Rowasa: Shake well before use. Instruct patient to lie on left side with left leg extended and right leg flexed forward for balance, or in “knee-chest” position. Insert lubricated applicator tip into the rectum and point slightly toward the navel. Grasp bottle firmly and tilt so nozzle is aimed toward the back; squeeze slowly to instill medication. After administration, withdraw and discard bottle. Retain enema for 8 hours or as long as practical

Suppository: Canasa: Remove foil wrapper; avoid excessive handling. Insert into rectum. Retain suppository for at least 1 to 3 hours for maximum benefit

Dietary Considerations

Some products may contain phenylalanine.

Storage/Stability

Capsule, tablet: Store between 15°C and 30°C (59°F and 86°F). Protect from moisture.

Asacol HD: May dispense tablets without desiccant for up to 6 weeks.

Delzicol: Store with desiccant pouch inside bottle with the capsules.

Enema: Store at 20°C to 25°C (68°F to 77°F). Use Rowasa promptly once foil wrap is removed; once the foil wrap is removed from a unit of seven Rowasa bottles, discard any bottles remaining after 14 days. Contents may darken with time (do not use if dark brown).

Foam (Mezera [Canadian product]): Store at 15°C and 30°C (59°F and 86°F). Protect from heat, light, and humidity.

Suppository: Store below 25°C (below 77°F). May store under refrigeration. Protect from direct heat, light, and humidity.

Medication Patient Education with HCAHPS Considerations

What is this drug used for?

• It is used to treat ulcerative colitis.

• It is used to help keep ulcerative colitis flares from coming back.

• It is used to treat mild to moderate disease at the far end of the colon.

• It may be given to you for other reasons. Talk with the doctor.

Frequently reported side effects of this drug

• Abdominal pain

• Heartburn

• Sore throat

• Constipation

• Diarrhea

• Passing gas

• Burping

• Stuffy nose

• Dizziness

• Headache

• Back pain

• Cough

• Nausea

• Vomiting

• Rectal irritation

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Kidney problems like unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain

• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin

• Chest pain

• Fast heartbeat

• Abnormal heartbeat

• Chills

• Sore throat

• Heart problems like cough or shortness of breath that is new or worse, swelling of the ankles or legs, abnormal heartbeat, weight gain of more than five pounds in 24 hours, dizziness, or passing out

• Bruising

• Bleeding

• Severe loss of strength and energy

• Ulcerative colitis like severe abdominal pain or cramps; bloody stools; fever; headache; or rash

• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Medication Safety Issues

Sound-alike/look-alike issues:

Contraindications

Hypersensitivity to mesalamine, aminosalicylates, salicylates, or any component of the formulation.

Canadian labeling: Additional contraindications (not in the US labeling): Severe renal impairment (GFR <30 mL/minute/1.73 m²); severe hepatic impairment

Additional contraindications per specific Canadian product labeling: Existing gastric or duodenal ulcer, urinary tract obstruction, use in children <2 years of age (Asacol, Asacol 800, Mesasal, Mezera, Pentasa, Salofalk); hemorrhagic diathesis (Mesasal); patients unable to swallow intact tablet (Asacol, Asacol 800); renal parenchymal disease (Pentasa)

Warnings/Precautions

Concerns related to adverse effects:

• Cardiac hypersensitivity effects: Pericarditis and myocarditis (mesalamine-induced cardiac hypersensitivity reactions) have been reported. Use with caution in patients predisposed to these conditions.

• Hypersensitivity reactions: Mesalamine-induced hypersensitivity reactions have been reported and may include internal organ involvement, such as hepatitis, myocarditis, pericarditis, nephritis, hematologic abnormalities, and/or pneumonitis. Discontinue treatment for mesalamine-induced hypersensitivity reactions.

• Intolerance syndrome: May cause an acute intolerance syndrome (cramping, abdominal pain, bloody diarrhea; sometimes fever, headache, malaise, pruritus, rash, conjunctivitis); may be hard to discern from an exacerbation; discontinue immediately if syndrome occurs or is suspected. Symptoms usually abate if drug is discontinued. If rechallenge is performed to validate the hypersensitivity, use a reduced dose and only if clearly needed.

• Photosensitivity: Use with caution in patients with pre-existing skin conditions (including atopic dermatitis and atopic eczema); severe photosensitivity reactions have been reported.

• Renal effects: Renal impairment (including minimal change nephropathy, acute and chronic interstitial nephritis, nephrotic syndrome, and rarely renal failure) has been reported. A renal function evaluation is recommended prior to initiation of therapy and periodically during treatment. Mesalamine-induced nephrotoxicity should be suspected in patients developing renal impairment during treatment.

• Sulfasalazine hypersensitivity: Patients with hypersensitivity to sulfasalazine may react to mesalamine.

Disease-related concerns:

• Hepatic impairment: Use caution in patients with hepatic impairment; hepatic failure has been reported.

• Renal impairment: Use with caution in patients with renal impairment, a history of renal disease, or those on nephrotoxic medications.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Elderly: Use with caution in the elderly; uncontrolled studies and postmarketing reports suggest an increased incidence of blood dyscrasias (ie, agranulocytosis, neutropenia, pancytopenia) in patients >65 years of age.

Dosage form specific issues:

• Apriso: Contains phenylalanine which can be harmful to patients with phenylketonuria (PKU). Before prescribing, consider the combined daily amount of phenylalanine from all sources.

• Asacol HD (formulated without dibutyl phthalate [DBP]), Delzicol: Intact, partially intact, and/or tablet shells have been reported in the stool.

• Canasa suppositories: Contain saturated vegetable fatty acid esters (contraindicated in patients with allergy to these components). May stain surfaces including clothing, other fabrics, flooring, painted surfaces, enamel, granite, marble and vinyl. Avoid contact with these surfaces.

• Mezera foam [Canadian product]: Contains metabisulfite salts, which may cause severe hypersensitivity reactions (ie, anaphylaxis) in patients with sulfite allergies. Also contains propylene glycol, which may cause lactic acidosis, hyperosmolality, hemolysis, and CNS depression; slight to mild skin irritation due to propylene glycol may occur. Additionally, contains cetostearyl alcohol, which may cause local skin reactions (eg, contact dermatitis).

• Rowasa enema: Contain metabisulfite salts that may cause severe hypersensitivity reactions (ie, anaphylaxis) in patients with sulfite allergies.

• Rowasa, sfRowasa: May stain direct contact surfaces including clothing, other fabrics, flooring, painted surfaces, enamel, granite, marble and vinyl. Choose a suitable location for product administration.

• Tablets: Patients with pyloric stenosis or other organic or functional upper gastrointestinal obstructive disorders may have prolonged gastric retention of tablets, delaying the release of mesalamine in the colon.

Other warnings/precautions:

• Appropriate use: Asacol HD: Safety and effectiveness beyond 6 weeks have not been determined.

• Bioequivalence: The Asacol HD 800 mg tablet has not been shown to be bioequivalent to two Delzicol 400 mg capsules. Two Delzicol 400 mg capsules have not been shown to be interchangeable or substitutable with one mesalamine 800 mg delayed-release tablet.

* See Cautions in AHFS Essentials for additional information.

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.

Pregnancy Considerations

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.

Dibutyl phthalate (DBP) may be an inactive ingredient in the enteric coating of some products (eg, Asacol, Asacol HD); adverse effects in male rats were noted at doses greater than the recommended human dose. Refer to product labeling for current formulation.

When treatment for inflammatory bowel disease is needed during pregnancy, mesalamine may be used, although products with DBP should be avoided (Habal 2012; Mottet 2009; van der Woude 2015).

Reversible oligospermia has been reported in males.

Breast-Feeding Considerations

Mesalamine (5-ASA) and the metabolite N-acetyl-5-aminosalicylic acid (Ac-5-ASA) are present in breast milk.

Following oral and rectal doses ranging from 500 mg to 4.8 g/day, lower concentrations of mesalamine (undetectable to 0.5 mg/L) and higher concentrations of the metabolite (0.2 to 9.3 mg/L) have been detected in human breast milk. Based on these concentrations, the estimated exposure to the breastfeeding infant would be 0 to 0.075 mg/kg/day of mesalamine and 0.03 to 1.4 mg/kg/day of Ac-5-ASA.

Adverse effects (diarrhea) in a breastfeeding infant have been reported while the mother received rectal administration of mesalamine within 12 hours after the first dose (Nelis 1989). Treatment with mesalamine is considered to be acceptable while breastfeeding (Habal 2012; Mottet 2009; van der Woude 2015).

Briggs' Drugs in Pregnancy & Lactation

• Mesalamine

Adverse Reactions

Adverse effects vary depending upon dosage form; frequency similar in adult and pediatric patients unless otherwise noted. Incidence usually on lower end with enema and suppository dosage forms.

>10%:

Central nervous system: Headache (3% to 14%)

Gastrointestinal: Eructation (≤26%), abdominal pain (oral: 2% to 21%, children & adolescents: 10%; rectal: 5%), constipation (≤11%)

Respiratory: Nasopharyngitis (children and adolescents: 15%; adults: 1% to 4%)

1% to 10%:

Cardiovascular: Hypertension (≤1%)

Central nervous system: Dizziness (≤9%), fatigue (<3%), pain (<3%), vertigo (<3%), nervousness (≥2%), paresthesia (≥2%)

Dermatologic: Skin rash (≤6%), alopecia (<3%), acne vulgaris (≤1%)

Endocrine & metabolic: Increased serum triglycerides (<3%), weight loss (children and adolescents: 2%)

Gastrointestinal: Diarrhea (≤8%), exacerbation of ulcerative colitis (≤6%), flatulence (≤6%), upper abdominal pain (1% to 5%), dyspepsia (≤4%), nausea (≤4%), lower abdominal pain (<3%), gastroenteritis (≥2%), hemorrhoids (≥2%), tenesmus (≥2%), gastrointestinal hemorrhage (<1% to ≥2%), bloody diarrhea (children and adolescents: 2%), pancreatitis (children and adolescents: 2%), sclerosing cholangitis (children and adolescents: 2%), vomiting (≤2%), rectal pain (rectal: 1% to 2%), abdominal distention (≥1%), anorectal pain (rectal: 1%; includes pain on insertion of enema tip), nausea and vomiting (1%), colitis (≤1%)

Genitourinary: Hematuria (<3%), urinary frequency (<1% to ≥2%)

Hematologic & oncologic: Decreased hematocrit (<3%), decreased hemoglobin (<3%), rectal hemorrhage (<3%)

Hepatic: Cholestatic hepatitis (<3%), increased serum transaminases (<3%), hepatic insufficiency (2%)

Infection: Influenza (1% to 5%), infection (≥2%), viral infection (children and adolescents: 2%; adenovirus)

Neuromuscular & skeletal: Back pain (≤6%), arthralgia (<3%), arthropathy (≥2%), leg pain (rectal: ≤2%)

Ophthalmic: Visual disturbance (≥2%)

Otic: Tinnitus (<3%)

Renal: Decreased creatinine clearance (<3%)

Respiratory: Rhinitis (8%), sinusitis (children and adolescents: 7%; adults: <1%), cough (children & adolescents: 5%; adults: <1%), dyspnea (<3%)

Miscellaneous: Intolerance syndrome (3%), fever (≤3%)

<1%, postmarketing, and/or case reports: Abdominal cramps (rectal), abnormal stools, abnormal T waves on ECG, acute renal failure, agranulocytosis, albuminuria, amenorrhea, anaphylaxis, anemia, angioedema, anorectal pain (rectal; discomfort), anorexia, anxiety, aplastic anemia, arthritis, blurred vision, bronchitis, chest pain, chills, cholecystitis, cholestatic jaundice, chronic renal failure, confusion, conjunctivitis, decreased libido, depression, diaphoresis, DRESS syndrome, drowsiness, drug fever, duodenal ulcer, dysgeusia, dysmenorrhea, dysphagia, dysuria, ear disease, ecchymoses, eczema, edema, emotional lability, eosinophilia, eosinophilic pneumonitis, epididymitis, erythema, erythema nodosum, esophageal ulcer, Eustachian tube congestion, exacerbation of asthma, eye pain, facial edema, fecal discoloration (rectal), fecal incontinence, frequent bowel movements (rectal), gastritis, gout, granulocytopenia, Guillain-Barré syndrome, hepatic cirrhosis, hepatic failure, hepatic injury, hepatic necrosis, hepatitis, hepatotoxicity, hyperesthesia, hypermenorrhea, hypersensitivity pneumonitis, hypersensitivity reaction, hypertonia, hypomenorrhea, hypotension, idiopathic nephrotic syndrome, increased amylase, increased appetite, increased blood urea nitrogen, increased gamma-glutamyl transferase, increased lactate dehydrogenase, increased serum alkaline phosphatase, increased serum ALT, increased serum AST, increased serum bilirubin, increased serum creatinine, increased serum lipase, increased thirst, insomnia, interstitial nephritis, interstitial pneumonitis, interstitial pulmonary disease, intracranial hypertension, jaundice, Kawasaki-like syndrome, leg cramps, leukopenia, lichen planus, lupus-like syndrome, lymphadenopathy, malaise, male infertility (rectal), mastalgia, migraine, mucus stools (rectal), myalgia, myocarditis, nail disease, neck pain, nephrogenic diabetes insipidus, nephrotoxicity (rectal), neutropenia (rectal), oligospermia, oral candidiasis, oral mucosa ulcer, otalgia, painful defecation (rectal), palpitations, pancytopenia, perforated peptic ulcer, pericardial effusion, pericarditis, peripheral edema, peripheral neuropathy, pharyngitis, pharyngolaryngeal pain, pleurisy, pneumonitis, prurigo, pruritus, pruritus ani (rectal), psoriasis, pulmonary infiltrates, pulmonary fibrosis, pyoderma gangrenosum, rectal discharge (rectal), rectal polyp, renal disease (including minimal change nephropathy), renal insufficiency, renal failure, rheumatoid arthritis, skin photosensitivity, Stevens-Johnson syndrome, stomach discomfort (rectal), stomatitis, swelling of eye, systemic lupus erythematosus, tachycardia, thrombocythemia, thrombocytopenia, transverse myelitis, tremor, ulcerative colitis (rectal; pancolitis), urinary urgency, urticaria, uterine hemorrhage, vasodilation, weakness, xeroderma, xerostomia

* See Cautions in AHFS Essentials for additional information.

Allergy and Idiosyncratic Reactions

• 5-Aminosalicylic Acid Derivative Allergy

Metabolism/Transport Effects

None known.

Drug Interactions Open 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-Aminosalicylic Acid Derivatives may decrease the serum concentration of Cardiac Glycosides. Risk C: Monitor therapy

Heparin: 5-Aminosalicylic Acid Derivatives may enhance the adverse/toxic effect of Heparin. Specifically, the risk for bleeding/bruising may be increased. Risk C: Monitor therapy

Heparins (Low Molecular Weight): 5-Aminosalicylic Acid Derivatives may enhance the adverse/toxic effect of Heparins (Low Molecular Weight). Specifically, the risk for bleeding/bruising may be increased. Risk C: Monitor therapy

Histamine H2 Receptor 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

Myelosuppressive Agents: Mesalamine may enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: May enhance the nephrotoxic effect of 5-Aminosalicylic Acid Derivatives. 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-Aminosalicylic Acid Derivatives may decrease the metabolism of Thiopurine Analogs. Risk C: Monitor therapy

Varicella Virus-Containing Vaccines: 5-Aminosalicylic Acid 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

Test Interactions

May cause falsely-elevated urinary normetanephrine levels when measured by liquid chromatography with electrochemical detection (due to similarity in the chromatograms of normetanephrine and mesalamine’s main metabolite, N-acetylaminosalicylic acid).

Monitoring Parameters

Renal function (prior to and periodically during therapy); CBC (particularly in elderly patients); hepatic function; signs/symptoms of worsening acute intolerance syndrome

Advanced Practitioners 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.

Nursing Physical Assessment/Monitoring

Patient allergy history to salicylates should be assessed prior to beginning therapy. Monitor laboratory tests, therapeutic effectiveness, and adverse reactions (chest pain, CNS effects, gastrointestinal upset, exacerbation of colitis) on a regular basis throughout therapy. Teach patient proper use (according to formulation), possible side effects/appropriate interventions (eg, importance of adequate hydration), and adverse symptoms to report.

Product Availability

Asacol HD formulated without dibutyl phthalate (DBP) (NDC: 0023-5901-18) is available in the US as of May 2017.

Asacol HD formulated with DBP (NDC: 00430-0783-27) may still be available in the marketplace and on pharmacy shelves.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule Delayed Release, Oral:

Delzicol: 400 mg

Generic: 400 mg

Capsule Extended Release, Oral:

Pentasa: 250 mg [contains brilliant blue fcf (fd&c blue #1), fd&c yellow #10 (quinoline yellow)]

Pentasa: 500 mg [contains brilliant blue fcf (fd&c blue #1)]

Capsule Extended Release 24 Hour, Oral:

Apriso: 0.375 g [contains aspartame]

Generic: 0.375 g

Enema, Rectal:

SfRowasa: 4 g/60 mL (60 mL) [sulfite free; contains edetate disodium, sodium benzoate]

Generic: 4 g (60 mL)

Kit, Rectal:

Rowasa: 4 g [contains edetate disodium, potassium metabisulfite, sodium benzoate]

Generic: 4 g

Suppository, Rectal:

Canasa: 1000 mg (30 ea, 42 ea)

Generic: 1000 mg (30 ea)

Tablet Delayed Release, Oral:

Asacol HD: 800 mg

Lialda: 1.2 g

Generic: 800 mg, 1.2 g

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Enema, Rectal:

Pentasa: 1 g (100 mL); 4 g (100 mL) [contains edetate sodium (tetrasodium), sodium metabisulfite]

Salofalk: 2 g (60 g); 4 g (60 g) [contains edetate disodium, potassium metabisulfite, sodium benzoate]

Foam, Rectal:

Mezera: 1 g/actuation (80 g) [contains cetostearyl alcohol, disodium edta, propylene glycol, sodium metabisulfite]

Suppository, Rectal:

Mezera: 1000 mg (30 ea)

Pentasa: 1000 mg (10 ea, 30 ea)

Salofalk: 500 mg (30 ea); 1000 mg (30 ea)

Tablet Delayed Release, Oral:

Asacol: 400 mg

Asacol 800: 800 mg

Mesasal: 500 mg [DSC]

Mezavant: 1.2 g

Salofalk: 500 mg [contains polysorbate 80]

Generic: 400 mg

Tablet Extended Release, Oral:

Pentasa: 500 mg, 1000 mg

Anatomic Therapeutic Chemical (ATC) Classification

• A07EC02

Generic Available (US)

May be product dependent

Pricing: US

Capsule ER 24 Hour Therapy Pack (Apriso Oral)

0.375 g (per each): $5.10

Capsule ER 24 Hour Therapy Pack (Mesalamine ER Oral)

0.375 g (per each): $4.59

Capsule, controlled release (Pentasa Oral)

250 mg (per each): $3.64

500 mg (per each): $7.29

Capsule, delayed release (Delzicol Oral)

400 mg (per each): $4.66

Capsule, delayed release (Mesalamine Oral)

400 mg (per each): $4.19 - $4.42

Enema (Mesalamine Rectal)

4 g (per mL): $0.38 - $0.41

Enema (SfRowasa Rectal)

4 g/60 mL (per mL): $1.07

Kit (Mesalamine-Cleanser Rectal)

4 g (per each): $167.35 - $171.05

Kit (Rowasa Rectal)

4 g (per each): $476.41

Suppository (Canasa Rectal)

1000 mg (per each): $46.47

Suppository (Mesalamine Rectal)

1000 mg (per each): $18.59 - $40.32

Tablet, EC (Asacol HD Oral)

800 mg (per each): $11.28

Tablet, EC (Lialda Oral)

1.2 g (per each): $11.23

Tablet, EC (Mesalamine Oral)

1.2 g (per each): $10.11 - $10.67

800 mg (per each): $7.76 - $9.27

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Mechanism of Action

Mesalamine (5-aminosalicylic acid) is the active component of sulfasalazine; the specific mechanism of action is unknown; however, it is thought that mesalamine 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 43%

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 and N-acetyl-5-ASA: Variable; ~ 25 hours (range: 2 to 296 hours)

Time to peak, serum:

Capsule: Apriso: ~4 hours; Delzicol: ~10 hours; Pentasa: ~3 hours

Foam: Mezera [Canadian product]: ~1 hour

Rectal: Pentasa, Salofalk [Canadian products]: 2 to 6 hours

Tablet: Asacol HD (formulated with dibutyl phthalate [DBP]): 10 to 16 hours; Asacol HD (formulated without DBP): ~24 hours (mean); Lialda: 9 to 12 hours

Canadian products: Asacol: 7 hours; Asacol 800: 10 hours; Mesasal: ~7 hours; Mezavant: 8 hours (range: 4 to 34 hours)

Excretion:

Oral, suppository: Urine (primarily as N-acetyl-5-ASA, ≤12% as unchanged drug); feces (unabsorbed mesalamine)

Enema: Feces (primarily); urine (10% to 30%)

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Pharyngitis.

Effects on Bleeding

No information available to require special precautions

Related Information

• Oral Medications That Should Not Be Crushed or Altered

Index Terms

5-Aminosalicylic Acid; 5-ASA; Asacol; Fisalamine; Mesalazine

FDA Approval Date

December 24, 1987

References

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Asacol HD (mesalamine) delayed-release tablets [prescribing information]. Rockaway, NJ: Warner Chilcott; April 2018.

Asacol HD (mesalamine formulated with DBP) delayed-release tablets [prescribing information]. Rockaway, NJ: Warner Chilcott; October 2013.

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Mezavant (mesalamine) [product monograph]. Toronto, Ontario, Canada: Shire Pharma Canada ULC; June 2019.

Mezera (mesalamine) [product monograph]. Blainville, Quebec, Canada: AVIR Pharma Inc; August 2018.

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Pentasa (mesalamine) extended-release capsules [prescribing information]. Lexington, MA: Shire US Inc; July 2019.

Pentasa (mesalamine) [product monograph]. North York, Ontario, Canada: Ferring Inc; January 2020.

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Brand Names: International

5-ASA 400 (AR, PY); Asacol (AE, BH, CH, CY, DK, ES, FI, GB, GR, HK, HR, IL, IT, JO, JP, KR, KW, LB, LU, LV, MT, MX, NL, NO, NZ, PK, PT, QA, SA, SE, SG, TW); Asacolon (CO, IE); Asalit (BR); Asasol (UA); Canasa (BD, CO); Claversal (AT, BE, DE, ES, IT, LU, PT); Colitofalk (BE, LU); Coloncure (TW); Huma-Col-Asa (HU); Ibsol (LK); Lialda (JP); Lixacol (ES); Mecolzine (CR, DO, GT, HN, NI, PA, SV); Mesacol (BF, BJ, CI, ET, GH, GM, GN, IN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZM, ZW); Mesala (EG); Mesalin (KR); Mesasal (AU, DK, NO, ZA); Meslamin (BD); Mezacol (AE); Mezavant (BE, IE); Mezavant XL (GB, HK, SG); Octasa (GB); Pentasa (AE, AU, BB, BE, BH, CH, CN, CY, DK, EG, ES, FR, GB, HK, HR, HU, IE, IQ, IR, IS, JO, JP, KW, LB, LU, LV, LY, MT, MY, NL, NO, OM, PH, QA, RO, RU, SA, SE, SG, SI, SK, SY, TH, TR, TW, UA, VN, YE); Pentasa Enema (NZ); Pentasa SR (AE, BH, CY, IL, IQ, IR, JO, KR, KW, LY, OM, SA, SY, YE); Pentasa Tab (NZ); Rafassal (IL); Salazine (EG); Salofalk (AT, AU, BG, CH, CL, CN, CO, CZ, DE, EE, ES, GB, HK, HR, HU, ID, IE, KR, LB, LK, LT, LV, MT, MY, NL, PE, PH, PL, RO, SG, SI, SK, TH, TR, UA, UY); Salofalk Foam Enema (AU); Suprimal (EC)

Last Updated 3/6/20