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). Asacol HD formulated with dibutyl phthalate (DBP) has been discontinued in the United States for >1 year.
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 (Ref); maximum dose: 1,000 mg/dose
Ulcerative colitis; treatment (mild to moderate disease): Note: Oral aminosalicylate (5-ASA) therapy including mesalamine is recommended as first-line induction and maintenance therapy for mild to moderate ulcerative colitis; for induction, if no response after 2 to 3 weeks of oral therapy, treatment modification should be considered. Combination therapy of oral and rectal 5-ASA therapy is more effective than oral monotherapy and may be necessary in some patients (Ref).
Oral:
Fixed dosing:
Delayed-release capsule (twice-daily dosing):
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.
Delayed-release tablet (once-daily dosing):
Lialda: Children and Adolescents weighing ≥24 kg:
24 to 35 kg: Oral: 2,400 mg once daily for the first 8 weeks of therapy, then decrease dose to 1,200 mg once daily.
>35 to 50 kg: Oral: 3,600 mg once daily for the first 8 weeks of therapy, then decrease to 2,400 mg once daily.
>50 kg: Oral: 4,800 mg once daily for the first 8 weeks of therapy, then decrease to 2,400 mg once daily.
Weight-directed dosing: Limited data available: Children and Adolescents: Oral: 60 to 80 mg/kg/day in 2 divided doses or once daily; dosing interval dependent on dosage form; maximum daily dose: 4,800 mg/day (Ref); in patients with milder ulcerative colitis, doses as low as 30 mg/kg/day may be effective (Ref).
Rectal: Limited data available: Children and Adolescents: Rectal enema, foam: 25 mg/kg/dose once daily; maximum dose: 1,000 mg/dose. Note: Although higher doses of up to 4,000 mg have been used, they have not been shown to be more effective. The utility of mesalamine suppository is limited to proctitis (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
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.
There are no dosage adjustments provided in the manufacturer's labeling; evaluate risk versus benefit in patients with preexisting impairment.
(For additional information see "Mesalamine (mesalazine): Drug information")
Note: Product selection: Choose the formulation that delivers mesalamine to the anatomic location of disease (Ref). Oral tablets and capsules generally deliver mesalamine near the terminal ileum of the small intestine and throughout the large intestine, except Pentasa, which delivers therapeutic quantities throughout both the small and large intestines. Rectal suppositories deliver mesalamine to the rectum, rectal foams [Canadian product] reach the sigmoid colon, and rectal suspensions reach the splenic flexure. Dosage forms: Generic products may be available. Asacol HD formulated with dibutyl phthalate (DBP) has been discontinued in the United States for >1 year.
Crohn disease, mild to moderate (alternative agent) (Canadian labeled use; US off-label use):
Note: The Canadian Association of Gastroenterology recommends against routine use of mesalamine for Crohn disease (Ref). In patients with limited ileocolonic involvement who prefer to avoid glucocorticoids, some experts may use an oral mesalamine formulation that delivers mesalamine throughout the small and large intestine (eg, Pentasa) (Ref).
Pentasa: Oral: 1 g 3 to 4 times daily.
Ulcerative colitis, mild to moderate:
Note: Generic products may be available.
Induction of remission:
Note: Choice of specific treatment is dependent on distribution of disease. Ulcerative proctitis: Treatment generally involves suppositories alone; however, in patients who prefer to avoid topical therapy or do not achieve response with topical therapy, consider oral mesalamine (Ref). Ulcerative proctosigmoiditis: Treatment generally involves rectal foam or suspension alone; however, in patients who prefer to avoid topical therapy or do not achieve response with topical therapy, consider oral mesalamine (Ref). Left-sided or extensive colitis: Treatment generally involves both oral and topical mesalamine (Ref).
Initial dosing regimens include:
Topical treatments:
Suppositories: Note: Instruct patient to retain for 1 to 3 hours or longer if possible.
Canasa suppository: Rectal: 1 g once daily at bedtime.
Mezera suppository [Canadian product]: Rectal: 1 g once daily at bedtime.
Pentasa suppository (Canadian labeling; not in US labeling): Rectal: 1 g once daily at bedtime.
Salofalk suppository [Canadian product]: Rectal: 500 mg 2 or 3 times daily or 1 g once daily at bedtime.
Rectal foam: Note: Instruct patient to retain for up to 8 hours if possible.
Mezera rectal foam [Canadian product]: Rectal: 2 g (2 actuations) once daily at bedtime.
Rectal suspension: Note: Instruct patient to retain for up to 8 hours if possible.
Pentasa rectal suspension (Canadian labeling; not in US labeling): Rectal: 1 g or 4 g enema once daily at bedtime; choose dose based on disease severity.
Rowasa rectal suspension: Rectal: 4 g enema once daily at bedtime.
Salofalk rectal suspension [Canadian product]: Rectal: 4 g enema once daily at bedtime.
Oral treatments: Note: Oral tablets and capsules may be dosed once daily instead of multiple times daily; there is no significant difference in efficacy and safety (Ref). For induction of remission, doses ≥2 g/day are more effective than lower doses and are generally recommended (Ref).
Apriso (off-label use): Oral: 1.5 to 4.5 g once each morning (Ref).
Asacol HD: Oral: 1.6 g 3 times daily.
Delzicol: Oral: 800 mg 3 times daily.
Lialda: Oral: 2.4 to 4.8 g once daily.
Mesalamine 400 mg tablet [Canadian product]: Oral: 2.4 to 4.8 g/day in 3 divided doses (Ref).
Mezavant [Canadian product]: Oral: 2.4 to 4.8 g once daily.
Pentasa: Oral: 1 g 4 times daily.
Salofalk tablet [Canadian product]: Oral: 1 g 3 or 4 times daily.
Duration of induction therapy: Usual course is 4 to 8 weeks before transitioning to maintenance treatment (Ref).
Maintenance of remission: Note: In most cases, it is appropriate to continue the medication(s) used for induction of remission. For ulcerative proctitis, maintenance therapy is generally only indicated for patients with >1 flare per year (Ref).
Topical treatments:
Suppositories: Note: Instruct patient to retain for 1 to 3 hours or longer if possible.
Canasa suppository (off-label use): Rectal: 1 g once daily at bedtime (Ref).
Mezera suppository [Canadian product] (off-label use): Rectal: 1 g once daily at bedtime (Ref).
Pentasa suppository (Canadian labeling; not in US labeling): Rectal: 1 g once daily at bedtime.
Salofalk suppository [Canadian product] (off-label use): Rectal: 500 mg 2 times daily or 1 g once daily at bedtime (Ref).
Rectal suspension: Note: Instruct patient to retain for up to 8 hours if possible.
Pentasa rectal suspension (Canadian labeling; not in US labeling): Rectal: 1 g or 4 g enema once daily at bedtime; choose dose based on disease severity.
Rowasa rectal suspension (off-label use): Rectal: 4 g enema once daily at bedtime (Ref).
Salofalk rectal suspension [Canadian product]: Rectal: 2 g enema once daily at bedtime every day or 4 g enema once daily at bedtime every second or third day.
Oral treatments: Note: Oral maintenance doses may be lower than those used for induction of remission; however, some patients require maintenance doses >3 g/day (Ref). Oral tablets and capsules may be dosed once daily instead of multiple times daily; there is no significant difference in efficacy and safety (Ref).
Apriso: Oral: 1.5 to 3 g once daily (Ref).
Delzicol: Oral: 1.6 to 2.4 g/day in 1 to 4 divided doses (Ref).
Lialda: Oral: 2.4 to 3.6 g once daily (Ref).
Mesalamine 400 mg tablet [Canadian product]: Oral: 1.6 to 2.4 g/day in 1 to 3 divided doses (Ref).
Mezavant [Canadian product]: Oral: 2.4 to 3.6 g once daily (Ref).
Pentasa (Canadian labeling; not in US labeling): Oral: 1.5 to 4 g/day in 3 to 4 divided doses (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Kidney impairment prior to treatment initiation: 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 and evaluate risk versus benefit in patients with preexisting impairment, history of kidney disease, or taking concomitant nephrotoxic medications.
Kidney impairment during treatment: Discontinue use if kidney function deteriorates during treatment.
There are no dosage adjustments provided in the manufacturer's labeling; evaluate risk versus benefit in patients with preexisting impairment.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule Delayed Release, Oral:
Delzicol: 400 mg
Generic: 400 mg
Capsule Extended Release, Oral:
Pentasa: 250 mg [contains fd&c blue #1 (brilliant blue), quinoline yellow (d&c yellow #10)]
Pentasa: 500 mg [contains fd&c blue #1 (brilliant blue)]
Generic: 500 mg
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 (edta) disodium, sodium benzoate]
Generic: 4 g (60 mL)
Kit, Rectal:
Rowasa: 4 g [contains edetate (edta) disodium, potassium metabisulfite, sodium benzoate]
Generic: 4 g
Suppository, Rectal:
Canasa: 1000 mg (30 ea, 42 ea [DSC])
Generic: 1000 mg (1 ea, 6 ea, 30 ea)
Tablet Delayed Release, Oral:
Asacol HD: 800 mg
Lialda: 1.2 g
Generic: 800 mg, 1.2 g
Yes
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 (edta) sodium (tetrasodium), sodium metabisulfite]
Salofalk: 2 g (60 g); 4 g (60 g) [contains edetate (edta) 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 [DSC]
Asacol 800: 800 mg [DSC]
Mezavant: 1.2 g
Mezera: 500 mg
Octasa: 800 mg
Salofalk: 500 mg
Generic: 400 mg
Tablet Extended Release, Oral:
Pentasa: 500 mg, 1000 mg
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.
Note: For all formulations, maintain adequate hydration during therapy to minimize nephrolithiasis risk.
Oral:
Capsule: Administer with or without food.
Apriso: Do not administer with antacids. Swallow capsule whole with water; do not break, chew, crush, or cut.
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: Administer 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: Administer 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.
Note: For all formulations, maintain adequate hydration during therapy (to minimize nephrolithiasis risk).
Oral:
Capsules: Administer with or without food.
Apriso: Swallow capsule whole; do not break, chew, crush, or cut. Do not administer with antacids.
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.
Bariatric surgery: Tablet, delayed and extended release: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. Delayed-release and ER tablets should be swallowed whole. Do not cut, chew, or crush. Delayed-release rectal suppository and enema formulations are available but no IR tablet, capsule, or oral solution formulations are available. If safety and efficacy can be effectively monitored, no change in formulation or administration is required after bariatric surgery; however, close clinical monitoring is advised in the immediate postoperative phase for the theoretical circumstance of reduced absorption after bariatric surgery. Consider use or conversion to delayed-release formulation in high-risk scenarios.
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.
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.
Oral: Treatment and/or maintenance of remission of ulcerative colitis (Delzicol: FDA approved in ages ≥5 years and adults; Lialda: FDA approved in pediatric patients weighing ≥24 kg [active treatment] and adults [treatment and maintenance of remission]; Apriso, Asacol HD, Pentasa: FDA approved in adults); has also been used for Crohn disease.
Rectal:
Suspension enema: Treatment of distal ulcerative colitis, proctosigmoiditis, and proctitis (Rowasa: FDA approved in adults).
Suppository: Treatment of ulcerative proctitis (Canasa: FDA approved in adults).
Mesalamine may be confused with mecamylamine, megestrol, memantine, metaxalone, methenamine
Apriso may be confused with Apri
Asacol may be confused with Ansaid, Os-Cal [DSC]
Lialda may be confused with Aldara
Pentasa may be confused with Pancrease, Pangestyme
Delayed hypersensitivity reactions have been associated with mesalamine including drug fever; involvement of the heart (myocarditis/pericarditis); kidney (interstitial nephritis); liver (ranging from asymptomatic and mild increased serum alanine aminotransferase levels to cholestatic or hepatocellular hepatic injury); pancreas (pancreatitis); blood system (neutropenia, thrombocytopenia, aplastic anemia); lung (interstitial pulmonary disease); and serum sickness-like reaction (Ref). Isolated hypereosinophilia (Ref), as well as peripheral eosinophilia and organ involvement, drug reaction with eosinophilia and systemic symptoms (Ref), and eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) (Ref) have been described. Severe cutaneous adverse reactions (SCARs) have also been reported, including Stevens-Johnson syndrome, toxic epidermal necrolysis (Ref), acute generalized exanthematous pustulosis (Ref), and bullous fixed drug eruption (Ref).
Mechanism: Non–dose-related; immunologic or idiosyncratic. Delayed hypersensitivity reactions: Non–dose-related, immunologic. SCARs are T-cell mediated (Ref). Myocarditis/pericarditis: May be caused by direct toxic effect on the myocardium or pericardium, cell-mediated hypersensitivity reaction, or humoral antibody response (Ref).
Onset: Delayed hypersensitivity reactions: Varied. SCARs usually occur 1 to 8 weeks after initiation (Ref), although onset has been described within 3 days after mesalamine administration (Ref). Myocarditis/pericarditis: Usually within 28 days of mesalamine initiation (Ref). Acute interstitial nephritis: Within 6 months of mesalamine initiation (Ref).
Risk factors:
• History of hypersensitivity to aspirin, although there is shared structural similarity, unlikely to lead to cross-reactions with mesalamine (Ref) and several reports document tolerance of mesalamine in the setting of aspirin hypersensitivity (Ref)
• Cross-reactivity was postulated in patients with history of sulfasalazine hypersensitivity (Ref)
Exacerbation of diarrhea, fever, and abdominal pain (intolerance syndrome) has been noted in 7% to 14% of patients with ulcerative colitis in the literature (Ref). These symptoms are often misdiagnosed as exacerbation of ulcerative colitis, resulting in unnecessary treatment, including increased risk of colectomy (Ref) and increased risk of hospitalization (Ref). Symptoms resolve upon drug discontinuation (Ref).
Mechanism: Unknown. Dysbiosis may contribute to the development of intolerance (Ref). Alternatively, diarrhea may result due to inhibition of ileal and colonic Na+/K+ ATPase or alteration of arachidonic acid metabolism (Ref).
Onset: Delayed; symptoms usually develop within 7 to 17 days after initiation of mesalamine (Ref).
Risk factors:
• Age <60 years (Ref)
• Females (Ref)
• Ulcerative colitis, in particular pancolitis (Ref)
Kidney impairment, including minimal change disease, acute and chronic interstitial nephritis, and renal failure syndrome has been associated with mesalamine (Ref). Nephrolithiasis has also been reported (Ref). Nephrotoxicity has been estimated at one in 4,000 patients/year (Ref). In patients with chronic renal damage, discontinuation of mesalamine results in resolution in approximately one-third of cases (Ref). Baseline kidney function and periodic monitoring is recommended (Ref)).
Mechanism: Unknown, likely idiosyncratic (Ref). Salicylates, including mesalamine, inhibit synthesis of intra-renal prostaglandins, which may lead to nephrotoxicity (Ref).
Onset: Delayed; chronic interstitial nephritis occurs within 1 year after initiation of mesalamine, although may be delayed up to 5 years (Ref).
Risk factors:
• Higher doses (>3 g/day) of mesalamine (reported in association with tubular proteinuria) (Ref)
• Males (Ref)
• Possible association with HLA-DRB1*03:01 (3-fold increased risk of nephrotoxicity after 5-aminosalicylate [5-ASA] administration) (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. 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%:
Gastrointestinal: Abdominal pain (1% to 21%) (table 1), constipation (≤11%), eructation (≤26%)
|
Drug (Mesalamine) |
Placebo |
Population |
Dose |
Dosage Form |
Indication |
Number of Patients (Mesalamine) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|---|---|---|---|
|
10% |
N/A |
Children and adolescents |
1.2 to 2.4 g/day |
Delayed-release capsules |
Ulcerative colitis |
41 |
N/A |
N/A |
|
21% |
12% |
Adults |
2.4 g/day |
Delayed-release capsules |
Ulcerative colitis |
53 |
52 |
N/A |
|
2% |
N/A |
Adults |
4.8 g/day |
Delayed-release tablets |
Ulcerative colitis |
727 |
N/A |
N/A |
|
2% |
N/A |
Adults |
2.4 g/day |
Delayed-release capsules |
Ulcerative colitis |
732 |
N/A |
N/A |
|
1% |
4% |
Adults |
4 g/day |
Extended-release capsules |
Ulcerative colitis |
451 |
173 |
N/A |
|
8% |
8% |
Adults |
N/A |
Rectal suspension enema |
N/A |
815 |
128 |
Defined as "abdominal pain/cramps/discomfort" |
Nervous system: Headache (3% to 14%)
Respiratory: Nasopharyngitis (children and adolescents: 15%; adults: 1% to 4%)
1% to 10%:
Cardiovascular: Hypertension (≤1%)
Dermatologic: Acne vulgaris (≤1%), alopecia (<3%), pruritus (≤1%), skin rash (≤6%)
Endocrine & metabolic: Increased serum triglycerides (<3%), weight loss (children and adolescents: 2%)
Gastrointestinal: Abdominal distention (1%), anorectal pain (rectal: 1%; includes discomfort and pain on insertion of enema tip), bloody diarrhea (children and adolescents: 2%), diarrhea (2% to 8%) (table 2), dyspepsia (≤4%), flatulence (≤6%), gastroenteritis (≥2%), gastrointestinal hemorrhage, hemorrhoids (≥1%), lower abdominal pain (<3%), nausea (≤4%), pancreatitis (≤2%), rectal pain (rectal: 1% to 2%), sclerosing cholangitis (children and adolescents: 2%), tenesmus (≥2%), upper abdominal pain (1% to 5%), vomiting
|
Drug (Mesalamine) |
Placebo |
Population |
Dose |
Dosage Form |
Indication |
Number of Patients (Mesalamine) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|---|
|
8% |
7% |
Adults |
1.5 g/daily |
Extended-release capsules |
Ulcerative colitis |
367 |
185 |
|
4% |
8% |
Adults |
4 g/day |
Extended-release capsules |
Ulcerative colitis |
451 |
173 |
|
2% |
N/A |
Adults |
4.8 g/day |
Delayed-release tablets |
Ulcerative colitis |
727 |
N/A |
|
2% |
N/A |
Adults |
2.4 g/day |
Delayed-release capsules |
Ulcerative colitis |
732 |
N/A |
|
2% |
4% |
Adults |
N/A |
Rectal suspension enema |
N/A |
815 |
128 |
Genitourinary: Hematuria (<3%), urinary frequency
Hematologic & oncologic: Decreased hematocrit (<3%), decreased hemoglobin (<3%), rectal hemorrhage (<3%)
Hepatic: Cholestatic hepatitis (<3%)
Infection: Infection (≥2%), influenza (1% to 5%) viral infection (children and adolescents: ≥2%; including adenovirus)
Nervous system: Dizziness (≤9%), fatigue (<3%), nervousness (≥2%), pain (<3%), paresthesia (≥2%), vertigo (<3%)
Neuromuscular & skeletal: Arthralgia (<3%), arthropathy (≥2%), back pain (≤6%), lower extremity pain (rectal: ≤2%)
Ophthalmic: Visual disturbance (≥2%)
Otic: Tinnitus (<3%)
Renal: Decreased creatinine clearance (<3%)
Respiratory: Cough (children & adolescents: 5%; adults: ≤1%), dyspnea (<3%), flu-like symptoms (4%), rhinitis (8%), sinusitis (children and adolescents: 7%), upper respiratory tract infection (children and adolescents: ≥5%)
Miscellaneous: Fever (≤3%) (table 3), intolerance syndrome (2% to 3%; 7% to 14% in literature) (Mizuno 2020; Shimizu 2017)
|
Drug (Mesalamine) |
Placebo |
Population |
Dose |
Dosage Form |
Indication |
Number of Patients (Mesalamine) |
Number of Patients (Placebo) |
|---|---|---|---|---|---|---|---|
|
0% |
N/A |
Children and adolescents |
1.2 to 2.4 g/day |
Delayed-release capsules |
Ulcerative colitis |
41 |
N/A |
|
1% |
N/A |
Adults |
2.4 g/day |
Delayed-release capsules |
Ulcerative colitis |
732 |
N/A |
|
0.9% |
1% |
Adults |
4 g/day |
Extended-release capsules |
Ulcerative colitis |
451 |
173 |
|
0.7% |
N/A |
Adults |
4.8 g/day |
Delayed-release tablets |
Ulcerative colitis |
727 |
N/A |
|
1% |
0% |
Adults |
N/A |
Rectal suppositories |
Ulcerative proctitis |
177 |
84 |
|
3% |
0% |
Adults |
N/A |
Rectal suspension enema |
N/A |
815 |
128 |
<1%:
Cardiovascular: Edema, facial edema, hypotension, palpitations, pericarditis (Brown 2016), tachycardia, vasodilation
Dermatologic: Diaphoresis, ecchymoses, eczema, erythema nodosum, lichen planus, nail disease, prurigo, skin photosensitivity, urticaria, xeroderma
Endocrine & metabolic: Albuminuria, amenorrhea, heavy menstrual bleeding, increased amylase, increased gamma-glutamyl transferase, increased lactate dehydrogenase, increased thirst, Kawasaki-like syndrome (Waanders 1992)
Gastrointestinal: Abnormal stools, anorexia, duodenal ulcer, dysphagia, esophageal ulcer, fecal incontinence, increased serum lipase, oral candidiasis, oral mucosa ulcer, rectal polyp, rectal tenesmus
Genitourinary: Hypomenorrhea, mastalgia, uterine hemorrhage
Hematologic & oncologic: Thrombocythemia, thrombocytopenia
Hepatic: Increased serum alanine aminotransferase, increased serum alkaline phosphatase, increased serum aspartate aminotransferase
Nervous system: Depression, drowsiness, insomnia, malaise
Neuromuscular & skeletal: Asthenia, lower limb cramp, myalgia, tremor
Ophthalmic: Conjunctivitis
Otic: Otalgia
Respiratory: Pharyngolaryngeal pain, pulmonary infiltrates
Postmarketing:
Cardiovascular: Abnormal T waves on ECG, chest pain, eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) (Sinico 2006), myocarditis (Brown 2016), pericardial effusion, peripheral edema
Dermatologic: Acute generalized exanthematous pustulosis (Rocci 2017), erythema of skin, psoriasis, pyoderma gangrenosum, Stevens-Johnson syndrome (Núñez Ortiz 2018), toxic epidermal necrolysis (Fukunaga 2007)
Endocrine & metabolic: Decreased libido, gout, nephrogenic diabetes insipidus
Gastrointestinal: Abdominal cramps, cholecystitis, dysgeusia, fecal discoloration, frequent bowel movements, gastritis, increased appetite, mucus stools, perforated peptic ulcer, pruritus ani, rectal discharge, stomach discomfort, stomatitis, xerostomia
Genitourinary: Dysmenorrhea, dysuria, epididymitis, male infertility, oligospermia (reversible), urinary urgency
Hematologic & oncologic: Agranulocytosis, aplastic anemia, eosinophilia (Usta 2009), granulocytopenia, leukopenia, lymphadenopathy, neutropenia (Frattini 2013), pancytopenia
Hepatic: Cholestatic jaundice, hepatic cirrhosis, hepatic failure, hepatic injury (cholestatic or hepatocellular) (Sehgal 2018), hepatic necrosis, hepatitis, hepatotoxicity, increased serum bilirubin, jaundice
Hypersensitivity: Anaphylaxis, angioedema, fixed drug eruption (Salman 2018)
Immunologic: Drug reaction with eosinophilia and systemic symptoms (Lim 1994)
Nervous system: Anxiety, chills, confusion, drug fever, emotional lability, Guillain-Barré syndrome, hyperesthesia, hypertonia, intracranial hypertension (Rosa 2003), migraine, painful defecation, peripheral neuropathy, transverse myelitis
Neuromuscular & skeletal: Arthritis, lupus-like syndrome (Kirkpatrick 1999; Pent 1992), neck pain, rheumatoid arthritis, systemic lupus erythematosus (Gunnarsson 1999)
Ophthalmic: Blurred vision, eye pain, swelling of eye
Otic: Ear disease, eustachian tube congestion
Renal: Acute kidney injury (Sehgal 2018), chronic renal failure, idiopathic nephrotic syndrome, increased blood urea nitrogen, increased serum creatinine (Sehgal 2018), interstitial nephritis (Adiga 2020), nephrolithiasis (Simske 2019), nephrotoxicity, renal disease (including minimal change nephropathy), renal failure syndrome (Sehgal 2018), renal insufficiency (Sehgal 2018)
Respiratory: Bronchitis, eosinophilic pneumonitis, exacerbation of asthma, hypersensitivity pneumonitis, interstitial pneumonitis, interstitial pulmonary disease (including allergic alveolitis) (Huang 2018), pharyngitis, pleurisy, pneumonitis, pulmonary fibrosis (alveolitis)
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 (Mesasal, Mezera, Pentasa, Salofalk); use in children <2 years of age (Mesasal, Mezera, Pentasa); hemorrhagic diathesis (Mesasal); patients unable to swallow intact tablet (Asacol, Asacol 800); renal parenchymal disease (Pentasa).
Concerns related to adverse effects:
• Photosensitivity: Use with caution in patients with pre-existing skin conditions (including atopic dermatitis and atopic eczema); severe photosensitivity reactions have been reported. Use skin protection (protective clothing and broad-spectrum sunscreen) and avoid prolonged exposure to sunlight and ultraviolet light.
Disease-related concerns:
• Hepatic impairment: Evaluate risk versus benefit of therapy 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.
Special populations:
• Older adult: Use with caution in older adults; 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): Intact, partially intact, and/or tablet shells have been reported in the stool. Contains iron (4.9 mg per 800 mg tablet); use caution in patients receiving iron supplementation or at risk of iron overload.
• 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.
• Delzicol: Intact, partially intact, and/or tablet shells have been reported in the stool. Contains iron (2.7 mg/400 mg capsule); use caution in patients receiving iron supplementation or at risk of iron overload.
• 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 GI obstructive disorders may have prolonged gastric retention of tablets, delaying the release of mesalamine in the colon; avoid use in patients at risk of upper GI obstruction.
Other warnings/precautions:
• 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.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program
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 the Apriso brand of mesalamine extended-release capsules. The optimal duration of dose separation is unknown. Other mesalamine products do not contain this interaction warning. Risk D: Consider therapy modification
Cardiac Glycosides: 5-Aminosalicylic Acid Derivatives may decrease the serum concentration of Cardiac Glycosides. Risk C: Monitor therapy
Myelosuppressive Agents: 5-Aminosalicylic Acid Derivatives 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
Thiopurine Analogs: 5-Aminosalicylic Acid Derivatives may enhance the myelosuppressive effect of Thiopurine Analogs. 5-Aminosalicylic Acid Derivatives may increase serum concentrations of the active metabolite(s) of Thiopurine Analogs. Specifically, exposure to the active 6-thioguanine nucleotides (6-TGN) may be increased. 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. Management: Avoid administration of salicylates for at least 6 weeks after adminstration of a varicella virus-containing vaccine. Risk D: Consider therapy modification
Vitamin K Antagonists (eg, warfarin): 5-Aminosalicylic Acid Derivatives may enhance the anticoagulant effect of Vitamin K Antagonists. 5-Aminosalicylic Acid Derivatives may diminish the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Some products may contain phenylalanine.
Oligospermia, which was improved following discontinuation of the drug, has been reported in males taking mesalamine for inflammatory bowel disease (Shin 2014).
Mesalamine does not impair fertility in females with inflammatory bowel disease (Mahadevan 2019).
Mesalamine (5-ASA) and the metabolite N-acetyl-5-aminosalicylic acid (Ac-5-ASA) cross the placenta (Klotz 1993).
An increased rate of congenital malformations has not been observed in human studies.
Inflammatory bowel disease is associated with adverse pregnancy outcomes, including an increased risk of miscarriage, premature delivery, delivery of a low birth weight infant, and poor maternal weight gain. Treatment decreases disease flares, disease activity, and the incidence of adverse pregnancy outcomes. When treatment for inflammatory bowel disease is needed in pregnant patients, mesalamine can be continued without interruption (Mahadevan 2019).
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.
Renal function (prior to and periodically during therapy); CBC; hepatic function; signs/symptoms of worsening acute intolerance syndrome
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
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%)
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): $1.50 - $4.85
Capsule, controlled release (Mesalamine ER Oral)
500 mg (per each): $6.56
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): $499.75
Suppository (Canasa Rectal)
1000 mg (per each): $46.47
Suppository (Mesalamine Rectal)
1000 mg (per each): $19.36 - $44.15
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.
