Mesalamine is a 5-aminosalicylate (5-ASA). Mesalamine is used, either orally or rectally, as an anti-inflammatory agent in treating ulcerative colitis (UC). The clinical response to mesalamine is believed to be due to a local effect. Oral mesalamine is considered first-line therapy for induction and maintenance of remission in both adult and pediatric patients with mild to moderately active ulcerative colitis; there is no evidence to support use of one formulation of oral mesalamine over another. Rectal mesalamine is recommended in combination with oral therapy for induction treatment; the use of rectal mesalamine alone is only recommended in patients with mildly active ulcerative proctitis or distal colitis. In patients with mildly active ulcerative proctitis, rectal mesalamine should be used to maintain remission rather than oral mesalamine. Oral mesalamine has not consistently been demonstrated to be effective compared with placebo for induction of remission and achieving mucosal healing in patients with active Crohn's disease (CD) and should not be used to treat patients with active CD. Mesalamine is ineffective for fistulizing CD. The drug is a safe but minimally effective medication to prevent postoperative CD recurrence; mesalamine is of limited benefit in preventing postoperative CD but is an option (vs. no treatment) for patients with an isolated ileal resection and no risk factors for CD recurrence, or if immunosuppressive therapy (e.g., thiopurine treatment) is not warranted or is contraindicated.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
-Patients should drink an adequate amount of fluids each day during treatment.
Route-Specific Administration
Oral Administration
-Mesalamine delayed-release capsules and delayed-release tablets are not bioequivalent; do not use interchangeably. Do not substitute 1 mesalamine 800 mg delayed-release tablet for 2 mesalamine 400 mg delayed-release oral products.
Oral Solid Formulations
Delayed-release capsules (Delzicol and generic equivalents)
-Administer with or without food.
-Swallow whole; do not cut, break, or chew.
-For patients who are unable to swallow the capsules whole, the capsule may be opened and contents administered:-Carefully open the capsule(s) required to make up a complete dose.
-There are 4 tablets per capsule. Ensure all tablets per capsule are swallowed, and no tablets are retained in the mouth.
-Swallow the tablets whole; do not cut, break, crush or chew the tablets.
-Intact, partially intact, and tablet shells have been reported in the stool. Instruct patients to contact their health care provider if this occurs repeatedly.
Delayed-release tablets (Lialda and generic equivalents)
-Administer with food.
-Swallow whole; do not split or crush.
Delayed-release tablets (Asacol HD and generic equivalents)
-Take on an empty stomach, at least 1 hour before and 2 hours after a meal.
-Swallow whole; do not cut, break, or chew.
-Intact, partially intact, and tablet shells have been reported in the stool. Instruct patients to contact their health care provider if this occurs repeatedly.
Extended-release capsules (Pentasa and generic equivalents)
-Swallow whole; do not cut, break, or chew.
-Alternatively, the capsule may be opened, and the contents may be sprinkled onto applesauce or yogurt. Consume contents immediately. Do not crush or chew capsule contents.
Extended-release capsules (Apriso and generic equivalents)
-Administer in the morning with or without food.
-Swallow whole; do not cut, break, crush, or chew the capsules.
Rectal Administration
-Administer at bedtime.
Rectal suspension
-Shake well prior to administering.
-Instruct patient on proper administration of rectal suspension.
-Encourage patient to retain suspension for at least 8 hours.
Rectal suppository
-Instruct patient on proper use of suppository and to avoid excessive handling of the suppository.
-Do not cut or break the suppository.
-Moisten the suppository with water prior to insertion. If suppository is too soft because of storage in a warm place, chill in the refrigerator for 30 minutes or run cold water over it before removing the wrapper.
-Instruct patient to retain suppository in rectum for at least 1 to 3 hours to ensure maximum benefit.
-Mesalamine suppositories will cause staining of direct contact surfaces, including but not limited to fabrics, flooring, painted surfaces, marble, granite, vinyl, and enamel. Wash hands after use.
-Missed dose: If a dose is missed, administer suppository as soon as possible, unless it is almost time for the next dose. Do not use two suppositories at the same time to make up for a missed dose.
Rectal irritation, including burning, pain, and soreness, and hemorrhoids were reported in approximately 1% to 2% of adult patients receiving rectal formulations of mesalamine in clinical trials. Rectal hemorrhage (less than 3%), hemorrhoids (2% or more), and tenesmus (2% or more) have been reported in adult patients receiving oral mesalamine in clinical trials. Fecal incontinence, rectal bleeding, rectal urgency, rectal polyp, stool discoloration, and stool abnormalities (texture change) have been reported infrequently with oral mesalamine in adult clinical trials. Burning/heat sensation at insertion site was reported in 18% of pediatric patients (n = 49, age 5 to 17 years) receiving mesalamine suppositories for the treatment of ulcerative proctitis. Anal pruritus, frequent bowel movements, mucus stools, proctalgia, painful defecation, and rectal discharge have been reported with mesalamine products during postmarketing surveillance.
Headache (2% to 11%), fatigue (3% or less), dizziness (9% or less), vertigo (3% or less), nervousness (2% or more), and paresthesias (2% or more) were reported in adult patients receiving mesalamine in clinical trials. Drowsiness, insomnia, and tremor were infrequently reported (less than 1%). Dizziness (2% to 7%), headache (5% to 10%), fatigue (2% to 10%), and syncope have been reported in pediatric patients receiving mesalamine in clinical trials. Anxiety, confusion, depression, emotional lability, Guillain-Barre syndrome, hyperesthesia, increased intracranial pressure (intracranial hypertension), migraine, peripheral neuropathy, and transverse myelitis have been reported with mesalamine in postmarketing surveillance.
Abdominal pain (1% to 21%), abdominal distension or enlargement (2% or more), eructation (26% or less), nausea (6% or less), vomiting (2% or less), dyspepsia (1% to 4%), gastroenteritis (2% or more), GI bleeding (2% or more), diarrhea (8% or less), constipation (11% or less), and flatulence (4% to 6%) have been reported in adult patients receiving oral and rectal mesalamine. Other gastrointestinal (GI) adverse reactions occurring in 1% or less of patients include anorexia, colitis or worsening of colitis, duodenal ulcer, esophageal ulceration, dysphagia, oral ulceration, oral moniliasis, thirst, pancreatitis, and melena. Laboratory abnormalities, including increased amylase (hyperamylasemia; less than 1%), increased lipase (less than 1%), and increased triglycerides (i.e., hypertriglyceridemia; less than 3%), were also reported. Abdominal pain (2% to 10%), diarrhea (5%), and vomiting (5% or more) have been reported in pediatric patients receiving mesalamine in clinical trials. Increased lipase occurred in 5% of pediatric patients who received high-dose mesalamine (2 to 4.8 g/day) in clinical trials; none of the patients in the low dose group (1.2 to 2.4 g/day) experienced this increase. Serious GI adverse reactions reported in pediatric patients included abdominal pain and decreased body mass index (n = 1), pancreatitis (n = 1), and bloody diarrhea and sclerosing cholangitis (n = 1). Mesalamine is also associated with an acute intolerance syndrome in approximately 3% of patients which may be difficult to distinguish from an ulcerative colitis exacerbation. Symptoms include abdominal pain or stomach cramps, melena, bloody diarrhea, pyrexia, severe headache, malaise, or skin eruptions. Observe patients closely for worsening of these symptoms while on treatment. Discontinue mesalamine promptly if acute intolerance syndrome is suspected. Dry mouth (xerostomia), increased appetite (appetite stimulation), perforated peptic ulcer, cholecystitis, stomatitis, and gastritis have been reported with postmarketing use of mesalamine.
Asymptomatic elevated hepatic enzymes (2%), which usually resolve during continued use or with discontinuation of the drug, have been reported in adult patients receiving mesalamine. There have also been rare reports of hepatotoxicity, including hepatitis, hyperbilirubinemia, jaundice, cholestasis with jaundice, cirrhosis, hepatotoxicity, and possible hepatocellular damage including, hepatic necrosis and hepatic failure, with mesalamine therapy. Some of these cases were fatal. One case of Kawasaki-like syndrome, that included changes in liver enzymes, has also been reported.
Thrombocytopenia (less than 1%), thrombocythemia (less than 1%), and decreased hematocrit and hemoglobin (less than 3%) were reported in adult patients receiving mesalamine in clinical trials. Anemia was reported in at least 5% of pediatric patients receiving mesalamine in clinical trials. Aplastic anemia, agranulocytosis (severe neutropenia), eosinophilia, granulocytopenia, neutropenia, leukopenia, pancytopenia, and lymphadenopathy have been reported with mesalamine in postmarketing surveillance.
Hypersensitivity reactions, including anaphylactoid reactions, angioedema, and rash, have been reported with mesalamine. Rash (6% or less), acne vulgaris (1% or less), alopecia (3% or less), and pruritus (1% or less) were reported in adult patients receiving mesalamine in clinical trials. Adverse reactions occurring in 1% or less of patients include diaphoresis, erythema nodosum, nail disorder, urticaria, xerosis, lichen planus, ecchymosis, eczema, photosensitivity, and prurigo. Rash was reported in 5% of pediatric patients receiving mesalamine in clinical trials. Severe cutaneous adverse reactions, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP), have also been reported with the use of mesalamine. Discontinue mesalamine at the first appearance of signs or symptoms of severe cutaneous adverse reactions, or other signs of hypersensitivity and consider further evaluation. Other dermatologic adverse reactions reported in adult patients during postmarketing surveillance include psoriasis, pyoderma gangrenosum, facial edema, and erythema. Patients with pre-existing skin conditions, such as atopic dermatitis and eczema, have reported more severe photosensitivity reactions.
Increased urinary frequency (2% or more), albuminuria or proteinuria (less than 1%), hematuria (less than 3%), nephrotic syndrome (less than 1%) and UTI/urinary burning (less than 1%) have been reported in adult patients receiving mesalamine in clinical trials. Cases of nephrolithiasis have been reported with the use of mesalamine, including stones of 100% mesalamine content. Mesalamine-containing stones are radiotransparent and undetectable by standard radiography or computed tomography (CT). Ensure adequate fluid intake during treatment with mesalamine. Renal and urogenital adverse reactions reported in adult patients receiving mesalamine during postmarketing surveillance include dysuria, renal failure (unspecified), elevated serum creatinine, elevated BUN, minimal change nephropathy, interstitial nephritis, nephrogenic diabetes insipidus, dysmenorrhea, menorrhagia, hypomenorrhea, metrorrhagia, libido decrease, epididymitis, reversible oligospermia, and infertility in men. Evaluate renal function in all patients prior to initiating mesalamine and periodically during treatment. The risk of nephrotoxicity may be greater in patients with pre-existing renal impairment or history of renal disease or those taking nephrotoxic drugs. Discontinue mesalamine if renal function deteriorates while on therapy. Patients should be made aware that urine may become discolored reddish-brown while taking mesalamine when it comes in contact with surfaces or water treated with hypochlorite-containing bleach. If urine discoloration is observed, advise patients to observe their urine flow and report to the healthcare provider only if urine is discolored on leaving the body, before contact with any surface or water (e.g., in the toilet).
Hypertension (1%) was reported in adult patients receiving mesalamine in clinical trials. Other cardiovascular adverse reactions reported in less than 1% of adult patients include peripheral vasodilation, edema, palpitations, hypotension, pericarditis, and sinus tachycardia. Chest pain (unspecified) and T-wave abnormalities and mesalamine-induced cardiac hypersensitivity, including myocarditis, pericarditis, and pericardial effusion, have also been reported during postmarketing surveillance.
Fever (1%), asthenia or weakness (less than 1%), and malaise (less than 1%) have been reported in adult patients receiving mesalamine during clinical trials. Fever (7%) has been reported in pediatric patients receiving mesalamine in clinical trials. Fever may also be part of an acute intolerance syndrome which occurs in approximately 3% of patients receiving mesalamine. Discontinue mesalamine promptly if acute intolerance syndrome is suspected. Chills and cases of lupus-like symptoms have been reported with mesalamine in postmarketing surveillance.
Rhinitis (8%), naso-pharyngitis (1% to 4%), influenza or Influenza syndrome (1% to 5%), cough (1%), cold or sore throat (2%), dyspnea (3% or less), and pharyngolaryngeal pain (less than 1%) were reported in adult patients receiving mesalamine in clinical trials. Naso-pharyngitis (12% to 15%), sinusitis (0% to 7%), cough (0% to 5%), upper respiratory tract infection (5% or more), and viral infection (5% or more) have been reported in pediatric patients receiving mesalamine in clinical trials. Asthma exacerbation, bronchitis, pleurisy/pleuritis, pulmonary infiltrates, interstitial lung disease, infection, and hypersensitivity pneumonitis (including allergic and fibrosing alveolitis (pulmonary fibrosis), eosinophilic pneumonia, and interstitial pneumonitis) have been reported with mesalamine in postmarketing surveillance.
Back pain (6% or less), musculoskeletal pain (less than 3%), arthralgia (less than 3%), and leg or joint pain (2%) were reported in adult patients receiving mesalamine in clinical trials. Other musculoskeletal adverse reactions reported with mesalamine during postmarketing surveillance include arthritis, gout, hypertonia, joint disorder, muscle cramps (leg cramps), myalgia, and neck pain.
Blurred vision, conjunctivitis, ocular pain, visual impairment, eye swelling, ear congestion/disorder/pain (otalgia), tinnitus, and taste perversion (dysgeusia) have been reported with mesalamine in postmarketing surveillance.
Mesalamine is contraindicated in patients with salicylate hypersensitivity. Patients sensitive to sulfasalazine, balsalazide, or olsalazine also may demonstrate cross-sensitivity; therefore, do not use in patients with a history of 5-aminosalicylates hypersensitivity. Mesalamine suppositories are contraindicated in patients who have demonstrated hypersensitivity to the suppository vehicle (saturated vegetable fatty acid esters; Hard Fat, NF). As with sulfasalazine, mesalamine-induced hypersensitivity reactions may present as internal organ involvement, including myocarditis, pericarditis, nephritis, hepatitis, pneumonitis, and hematologic abnormalities. Serious rash and cutaneous reactions, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS), have also been reported with mesalamine therapy. Evaluate patients immediately if signs or symptoms of a hypersensitivity or severe cutaneous reaction are present. Discontinue mesalamine if an alternative etiology for the signs or symptoms cannot be established. Mesalamine has been implicated in the production of an acute intolerance syndrome characterized by worsening colitis and symptoms such as abdominal cramping, acute abdominal pain, bloody diarrhea, fever, headache, malaise, pruritus, rash, and conjunctivitis. Symptoms usually resolve when mesalamine is discontinued. Monitor patients for worsening of these symptoms while on treatment. If acute intolerance syndrome is suspected, promptly discontinue treatment with mesalamine.
Some mesalamine rectal suspensions contain potassium metabisulfite and are contraindicated in patients with a sulfite hypersensitivity. Exposure to sulfites may cause allergic-type reactions, including anaphylaxis and life-threatening or less severe asthmatic episodes. Sensitivity to such sulfites appears to be increased in asthmatic or in atopic nonasthmatic patients. Sulfite-free formulas are also available for product selection.
Use mesalamine with caution in patients with hepatic impairment. Hepatic failure has been reported in patients with pre-existing hepatic disease who received mesalamine.
Mesalamine is known to be substantially excreted by the kidney, and the risk of adverse reactions may be greater in patients with renal impairment or renal failure. Renal impairment, including minimal change disease, acute and chronic interstitial nephritis, and renal failure, has been reported in patients receiving mesalamine. Evaluate renal function in all patients prior to initiating mesalamine and periodically during treatment. Monitor patients with known renal impairment or history of renal disease or taking nephrotoxic drugs for decreased renal function and mesalamine-related adverse reactions. Discontinue mesalamine if renal function deteriorates while on therapy.
Avoid use of mesalamine tablets or capsules in patients with pyloric stenosis or any other functional or organic upper GI obstruction. Patients with these conditions can have prolonged gastric retention of the tablets or capsules, which could delay release in the colon.
Cases of nephrolithiasis have been reported with the use of mesalamine, including kidney stones of 100% mesalamine content. Mesalamine-containing stones are radiotransparent and undetectable by standard radiography or computed tomography (CT). Ensure adequate fluid intake during treatment with mesalamine.
Use mesalamine with caution in patients with a previous history of a skin photosensitivity disorder. Photosensitivity has been reported in patients receiving systemic dosage forms of mesalamine. Patients with pre-existing skin conditions, such as atopic dermatitis and atopic eczema, have reported more severe photosensitivity reactions. Advise patients to avoid sunlight (UV) exposure and tanning booths, and to wear sunscreen (and if possible protective clothing) on exposed skin during mesalamine treatment.
The use of mesalamine may lead to laboratory test interference. Spuriously elevated test results may occur when measuring urinary normetanephrine by liquid chromatography with electrochemical detection because of the similarity in the chromatograms of normetanephrine and mesalamine's main metabolite, N-acetyl-5-aminosalicylic acid (N-Ac-5-ASA). Consider an alternative, selective assay for normetanephrine.
The Apriso brand of mesalamine extended-release capsules and some equivalent generics to this product contain aspartame, which is a source of phenylalanine. These specific products should be used with caution in patients with phenylketonuria.
Reported clinical experience has not identified differences in efficacy responses between older and younger adults receiving mesalamine. Reports from uncontrolled clinical studies and postmarketing reporting systems suggest a higher incidence of blood dyscrasias (i.e., agranulocytosis, neutropenia, pancytopenia) in geriatric subjects (65 years and older) receiving mesalamine vs. younger adult patients, which may also be associated with ulcerative colitis, use of interacting drugs, or reduced renal function. Use caution and closely monitor complete blood cell (CBC) and platelet counts during drug therapy, especially if the patient is also taking anticoagulants. Because older adult patients are more likely to have decreased renal function, care should be taken when prescribing mesalamine.
There is no evidence that mesalamine is associated with poor pregnancy outcomes; experts recommend that patients maintained on mesalamine pre-pregnancy continue their treatment regimens. The use of mesalamine during pregnancy appears to pose no significant harm to the developing fetus, and the maternal benefits of therapy may outweigh any potential for risk to the fetus. Mesalamine is known to cross the placental barrier. However, only small amounts of mesalamine are systemically circulating in the body, and most of any systemically available drug is rapidly excreted in the urine. Published human data (including case series, prospective controlled studies, and population-based cohorts) suggest no increase risk of congenital malformations with mesalamine use. Data from some studies have shown an increased rate of preterm birth, stillbirth, and low birth weight; however, it is not certain whether these adverse outcomes are attributable to mesalamine therapy, underlying inflammatory bowel disease (IBD), or both. Animal studies have revealed no evidence of harm to the fetus from mesalamine. Dibutyl phthalate (DBP), which was an ingredient in some products historically, has been associated with external and skeletal malformations as well as other adverse effects on the male reproductive system in animal studies; the reproductive anomalies were consistent with a disruption of androgenic-dependent development by the phthalates; female offspring were not affected. All mesalamine preparations are now phthalate-free. Guidelines state that medical therapy for IBD, including mesalamine, does not decrease fertility.
Some mesalamine oral products contain iron oxide (ferric oxide) as a colorant. Before prescribing these mesalamine delayed-release dosage forms to patients receiving iron supplementation or those at risk of developing iron overload (e.g., hemochromatosis, chronic transfusional iron overload), consider the combined daily amount of iron from all sources, including the mesalamine product.
Experts and guidelines consider mesalamine compatible and safe for use during breast-feeding. In published lactation studies, maternal mesalamine doses from various oral and rectal formulations and products ranged from 500 mg to 3 grams daily. The concentration of mesalamine in milk ranged from non-detectable to 0.11 mg/L. The concentration of the N-acetyl-5-aminosalicylic acid metabolite ranged from 5 to 18.1 mg/L. Based on these concentrations, estimated infant daily doses for an exclusively breastfed infant are 0 to 0.017 mg/kg/day of mesalamine and 0.75 to 2.72 mg/kg/day of N-acetyl-5-aminosalicylic acid. Carefully monitor the nursing infant for alterations in bowel function, such as persistent changes in stool frequency. Infant diarrhea has been infrequently reported with maternal use of mesalamine during breast-feeding. Among the 5-ASA agents, the drugs mesalamine, balsalazide, and olsalazine are preferred to sulfasalazine due to the unknown side effects of sulfasalzine's sulfapyridine metabolite, which is excreted into milk at higher concentrations than the parent drug and has hemolytic and antimicrobial properties.
General Dosing Information
-Mesalamine delayed-release capsules and delayed-release tablets are not bioequivalent; do not use interchangeably. Do not substitute 1 mesalamine delayed-release tablet 800 mg for two mesalamine delayed-release 400 mg oral products.
-Oral mesalamine is considered first-line therapy for induction and maintenance of remission in both adult and pediatric patients with mild to moderately active ulcerative colitis; there is no evidence to support use of one formulation of oral mesalamine over another.
-Combination therapy with oral and rectal mesalamine is more effective than oral monotherapy and is recommended for induction therapy when tolerated; if oral mesalamine alone is initiated and no response is seen within 2 weeks, consider the addition of rectal mesalamine.
-Maintenance therapy with mesalamine is recommended to be continued indefinitely due to its high degree of effectiveness and favorable safety profile.
Adults
-Standard-dose mesalamine (i.e., 2 to 3 g/day) is recommended over high-dose mesalamine (4.8 g/day) for induction and maintenance of remission as there is no difference in the remission rate. Standard-dose mesalamine is superior to low-dose mesalamine for maintenance of remission (RR, 0.63; 95% CI: 0.55 to 0.78).
-In patients with suboptimal response to standard-dose therapy, escalation to high-dose oral mesalamine (i.e., more than 3 g/day) in combination with rectal mesalamine is recommended.
-Once-daily dosing of oral mesalamine is recommended over more frequent dosing regimens as once daily dosing has been demonstrated to be as effective as multiple daily dosing and may facilitate compliance.
-In patients with mildly active ulcerative proctitis or distal colitis, rectal mesalamine is recommended over oral mesalamine for induction and maintenance. Mesalamine suppositories are recommended over enemas when rectal therapy is chosen.
-Rectal mesalamine is superior to rectal corticosteroids for induction of remission. Those patients with suboptimal response or intolerance to rectal mesalamine may opt to use rectal corticosteroid enemas or foams.
Pediatrics
-Treatment with rectal mesalamine alone is only recommended in pediatric patients with mild to moderate proctitis, an uncommon pediatric phenotype.
For the treatment of mildly to moderately active ulcerative colitis, including ulcerative proctitis:
Oral dosage (delayed-release capsules; Delzicol and generic equivalents):
Adults: 800 mg PO 3 times daily for 6 weeks, then 800 mg PO twice daily or 400 mg PO 4 times daily is the FDA-approved dosage. However, guidelines recommend standard-dose mesalamine (2 to 3 g/day) for maintenance of remission.
Children and Adolescents 5 to 17 years weighing 54 to 90 kg: 1,200 mg PO twice daily (dose range: 27 to 44 mg/kg/day) for 6 weeks. Although the FDA-approved labeling recommends 6 weeks of treatment, guidelines recommend the effective induction dose also be continued as the maintenance dose. Once sustained remission is achieved, doses may be decreased to the lower end of the dosing range and maintenance therapy continued. Once daily dosing may also be considered for induction and maintenance and has been shown to be as effective as twice daily dosing for inducing remission.
Children and Adolescents 5 to 17 years weighing 33 to 53 kg: 1,200 mg PO once daily in the morning and 800 mg PO once daily in the afternoon (dose range: 37 to 61 mg/kg/day) for 6 weeks. Although the FDA-approved labeling recommends 6 weeks of treatment, guidelines recommend the effective induction dose also be continued as the maintenance dose. Once sustained remission is achieved, doses may be decreased to the lower end of the dosing range and maintenance therapy continued. Once daily dosing may also be considered for induction and maintenance and has been shown to be as effective as twice daily dosing for inducing remission.
Children and Adolescents 5 to 17 years weighing 17 to 32 kg: 800 mg PO once daily in the morning and 400 mg PO once daily in the afternoon (dose range: 36 to 71 mg/kg/day) for 6 weeks. Although the FDA-approved labeling recommends 6 weeks of treatment, guidelines recommend the effective induction dose also be continued as the maintenance dose. Once sustained remission is achieved, doses may be decreased to the lower end of the dosing range and maintenance therapy continued. Once daily dosing may also be considered for induction and maintenance and has been shown to be as effective as twice daily dosing for inducing remission.
Children younger than 5 years or weighing less than 17 kg*: 60 to 80 mg/kg/day PO given in 2 divided doses, rounded to the nearest capsule size. Guidelines recommend the effective induction dose also be continued as the maintenance dose. Once sustained remission is achieved, doses may be decreased to the lower end of the dosing range and maintenance therapy continued. Once daily dosing may also be considered for induction and maintenance and has been shown to be as effective as twice daily dosing for inducing remission.
Oral dosage (delayed-release tablets; Lialda and generic equivalents):
Adults: 2.4 to 4.8 g PO once daily, initially, then 2.4 g PO once daily.
Children and Adolescents weighing more than 50 kg: 4.8 g PO once daily for 8 weeks, then 2.4 g PO once daily.
Children and Adolescents weighing 36 to 50 kg: 3.6 g PO once daily for 8 weeks, then 2.4 g PO once daily.
Children and Adolescents weighing 24 to 35 kg: 2.4 g PO once daily for 8 weeks, then 1.2 g PO once daily.
Children weighing less than 24 kg*: 60 to 80 mg/kg/dose PO once daily, rounded to the nearest tablet size. Guidelines recommend the effective induction dose also be continued as the maintenance dose. Once sustained remission is achieved, doses may be decreased to the lower end of the dosing range and maintenance therapy continued.
Oral dosage (delayed-release tablets; Asacol HD and generic equivalents):
Adults: 1.6 g PO 3 times daily for 6 weeks. Although the FDA-approved labeling recommends 6 weeks of treatment, guidelines recommend standard-dose mesalamine (2 to 3 g/day) be continued for maintenance of remission.
Children* and Adolescents*: 60 to 80 mg/kg/day (Max: 4.8 g/day) PO given in 2 divided doses, rounded to the nearest tablet size. Guidelines recommend the effective induction dose also be continued as the maintenance dose. Once sustained remission is achieved, doses may be decreased to the lower end of the dosing range and maintenance therapy continued. Once daily dosing may also be considered for induction and maintenance and has been shown to be as effective as twice daily dosing for inducing remission.
Oral dosage (extended-release capsules; Pentasa and generic equivalents):
Adults: 1 g PO 4 times daily. Treatment duration in controlled trials was up to 8 weeks. Although the FDA-approved labeling recommends 8 weeks of treatment, guidelines recommend standard-dose mesalamine (2 to 3 g/day) be continued for maintenance of remission.
Children* and Adolescents*: 60 to 80 mg/kg/day (Max: 4 g/day) PO given in 2 divided doses, rounded to the nearest capsule size. Guidelines recommend the effective induction dose also be continued as the maintenance dose. Once sustained remission is achieved, doses may be decreased to the lower end of the dosing range and maintenance therapy continued. Once daily dosing may also be considered for induction and maintenance and has been shown to be as effective as twice daily dosing for inducing remission.
Oral dosage (extended-release capsules; Apriso and generic equivalents):
NOTE: Mesalamine extended-release capsules are indicated only for the maintenance of remission of ulcerative colitis.
Adults: 1.5 g PO once daily in the morning is the FDA-approved dosage. However, guidelines recommend standard-dose mesalamine (2 to 3 g/day) for maintenance of remission.
Rectal dosage (enema):
Adults: 1 to 4 g rectally once daily at bedtime for 3 to 6 weeks. Studies have shown no significant differences in efficacy for rectal doses of 1 g/day vs. 4 g/day for inducing remission. Although the FDA-approved labeling recommends 3 to 6 weeks of treatment, guidelines recommend rectal mesalamine at a dose of 1 g/day be continued for maintenance of remission.
Children* and Adolescents*: 25 mg/kg/dose (Max: 1 g/dose) rectally at bedtime. Although higher doses (up to 4 g rectally) have been used in adults, evidence has not shown these doses to be more effective.
Rectal dosage (suppositories):
NOTE: Mesalamine suppositories are indicated for mildly to moderately active ulcerative proctitis; however, they are used off-label for all types of ulcerative colitis.
Adults: 1 g rectally once daily at bedtime for 3 to 6 weeks. Although the FDA-approved labeling recommends 3 to 6 weeks of treatment, guidelines recommend rectal mesalamine at a dose of 1 g/day be continued for maintenance of remission.
Children* and Adolescents*: 1 g rectally once daily at bedtime.
For the reduction of symptoms after acute diverticulitis*:
Oral dosage:
Adults: 800 to 3,000 mg/day PO as a single dose or in divided doses.
Maximum Dosage Limits:
-Adults
1.5 g/day PO for biphasic-release capsules (i.e., Apriso); 2.4 g/day PO for delayed-release capsules (i.e, Delzicol); 4 g/day PO for extended-release capsules (i.e., Pentasa); 4.8 g/day PO for delayed-release tablets (i.e., Asacol HD, Lialda); 4 g/day rectally for enema; 1 g/day rectally for suppositories.
-Geriatric
1.5 g/day PO for biphasic-release capsules (i.e., Apriso); 2.4 g/day PO for delayed-release capsules (i.e, Delzicol); 4 g/day PO for extended-release capsules (i.e., Pentasa); 4.8 g/day PO for delayed-release tablets (i.e., Asacol HD, Lialda); 4 g/day rectally for enema; 1 g/day rectally for suppositories.
-Adolescents
weighing more than 53 kg: 2.4 g/day PO for delayed-release capsules (i.e, Delzicol); 4.8 g/day PO for delayed-release tablets (i.e., Lialda); safety and efficacy of other formulations have not been established; however, doses up to 80 mg/kg/day (Max: 4.8 g/day) PO and 1 g/day rectally are recommended off-label.
weighing 51 to 53 kg: 2 g/day PO for delayed-release capsules (i.e, Delzicol); 4.8 g/day PO for delayed-release tablets (i.e., Lialda); safety and efficacy of other formulations have not been established; however, doses up to 80 mg/kg/day PO and 1 g/day rectally are recommended off-label.
weighing 36 to 50 kg: 2 g/day PO for delayed-release capsules (i.e, Delzicol); 3.6 g/day PO for delayed-release tablets (i.e., Lialda); safety and efficacy of other formulations have not been established; however, doses up to 80 mg/kg/day PO and 1 g/day rectally are recommended off-label.
weighing 33 to 35 kg: 2 g/day PO for delayed-release capsules (i.e, Delzicol); 2.4 g/day PO for delayed-release tablets (i.e., Lialda); safety and efficacy of other formulations have not been established; however, doses up to 80 mg/kg/day PO and 1 g/day rectally are recommended off-label.
weighing 24 to 32 kg: 1.2 g/day PO for delayed-release capsules (i.e, Delzicol); 2.4 g/day PO for delayed-release tablets (i.e., Lialda); safety and efficacy of other formulations have not been established; however, doses up to 80 mg/kg/day PO and 1 g/day rectally are recommended off-label.
-Children
5 to 12 years weighing more than 53 kg: 2.4 g/day PO for delayed-release capsules (i.e, Delzicol); 4.8 g/day PO for delayed-release tablets (i.e., Lialda); safety and efficacy of other formulations have not been established; however, doses up to 80 mg/kg/day (Max: 4.8 g/day) PO and 1 g/day rectally are recommended off-label.
5 to 12 years weighing 51 to 53 kg: 2 g/day PO for delayed-release capsules (i.e, Delzicol); 4.8 g/day PO for delayed-release tablets (i.e., Lialda); safety and efficacy of other formulations have not been established; however, doses up to 80 mg/kg/day PO and 1 g/day rectally are recommended off-label.
5 to 12 years weighing 36 to 50 kg: 2 g/day PO for delayed-release capsules (i.e, Delzicol); 3.6 g/day PO for delayed-release tablets (i.e., Lialda); safety and efficacy of other formulations have not been established; however, doses up to 80 mg/kg/day PO and 1 g/day rectally are recommended off-label.
5 to 12 years weighing 33 to 35 kg: 2 g/day PO for delayed-release capsules (i.e, Delzicol); 2.4 g/day PO for delayed-release tablets (i.e., Lialda); safety and efficacy of other formulations have not been established; however, doses up to 80 mg/kg/day PO and 1 g/day rectally are recommended off-label.
5 to 12 years weighing 24 to 32 kg: 1.2 g/day PO for delayed-release capsules (i.e, Delzicol); 2.4 g/day PO for delayed-release tablets (i.e., Lialda); safety and efficacy of other formulations have not been established; however, doses up to 80 mg/kg/day PO and 1 g/day rectally are recommended off-label.
5 to 12 years weighing 17 to 23 kg: 1.2 g/day PO for delayed-release capsules (i.e, Delzicol); safety and efficacy of other formulations have not been established; however, doses up to 80 mg/kg/day PO and 1 g/day rectally are recommended off-label.
5 to 12 years weighing less than 17 kg: Safety and efficacy have not been established; however, doses up to 80 mg/kg/day PO and 1 g/day rectally are recommended off-label.
1 to 4 years: Safety and efficacy have not been established; however, doses up to 80 mg/kg/day PO and 1 g/day rectally are recommended off-label.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Mesalamine is known to be substantially excreted by the kidney, and the risk of toxic reactions may be greater in patients with impaired renal function. Dosage adjustments may be needed; however, specific guidelines for dosage adjustments in renal impairment are not available. Discontinue mesalamine if renal function deteriorates while on therapy.
*non-FDA-approved indication
Acetaminophen; Ibuprofen: (Minor) The concurrent use of mesalamine with known nephrotoxic agents such as nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of nephrotoxicity.
Aldesleukin, IL-2: (Major) Avoid concomitant use of mesalamine and aldesleukin; coadministration may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Aluminum Hydroxide: (Moderate) Do not coadminister mesalamine extended-release capsules (Apriso) with antacids. Apriso is a pH-dependent, delayed-release capsule product with an enteric coating that dissolves at a pH of at least 6. Other mesalamine products do not have an interaction with antacids.
Aluminum Hydroxide; Magnesium Carbonate: (Moderate) Do not coadminister mesalamine extended-release capsules (Apriso) with antacids. Apriso is a pH-dependent, delayed-release capsule product with an enteric coating that dissolves at a pH of at least 6. Other mesalamine products do not have an interaction with antacids.
Aluminum Hydroxide; Magnesium Hydroxide: (Moderate) Do not coadminister mesalamine extended-release capsules (Apriso) with antacids. Apriso is a pH-dependent, delayed-release capsule product with an enteric coating that dissolves at a pH of at least 6. Other mesalamine products do not have an interaction with antacids.
Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Moderate) Do not coadminister mesalamine extended-release capsules (Apriso) with antacids. Apriso is a pH-dependent, delayed-release capsule product with an enteric coating that dissolves at a pH of at least 6. Other mesalamine products do not have an interaction with antacids.
Aluminum Hydroxide; Magnesium Trisilicate: (Moderate) Do not coadminister mesalamine extended-release capsules (Apriso) with antacids. Apriso is a pH-dependent, delayed-release capsule product with an enteric coating that dissolves at a pH of at least 6. Other mesalamine products do not have an interaction with antacids.
Amlodipine; Celecoxib: (Minor) The concurrent use of mesalamine with known nephrotoxic agents such as nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of nephrotoxicity.
Antacids: (Moderate) Do not coadminister mesalamine extended-release capsules (Apriso) with antacids. Apriso is a pH-dependent, delayed-release capsule product with an enteric coating that dissolves at a pH of at least 6. Other mesalamine products do not have an interaction with antacids.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) Do not coadminister mesalamine extended-release capsules (Apriso) with antacids. Apriso is a pH-dependent, delayed-release capsule product with an enteric coating that dissolves at a pH of at least 6. Other mesalamine products do not have an interaction with antacids.
Azathioprine: (Moderate) 5-aminosalicylates (e.g., sulfasalazine, mesalamine, olsalazine) may interact with azathioprine and increase the risk of azathioprine-related toxicity. The inhibition of thiopurine methyltransferase activity, one of the enzymes responsible for azathioprine metabolism, by 5-aminosalicylates has been described via in vitro and in vivo study. Theoretically, this interaction could result in a higher risk of bone marrow suppression or other azathioprine dose-related side effects. If concurrent therapy cannot be avoided, closely monitor platelet and complete blood cell counts.
Bupivacaine; Meloxicam: (Minor) The concurrent use of mesalamine with known nephrotoxic agents such as nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of nephrotoxicity.
Calcium Carbonate: (Moderate) Do not coadminister mesalamine extended-release capsules (Apriso) with antacids. Apriso is a pH-dependent, delayed-release capsule product with an enteric coating that dissolves at a pH of at least 6. Other mesalamine products do not have an interaction with antacids.
Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Moderate) Do not coadminister mesalamine extended-release capsules (Apriso) with antacids. Apriso is a pH-dependent, delayed-release capsule product with an enteric coating that dissolves at a pH of at least 6. Other mesalamine products do not have an interaction with antacids.
Calcium Carbonate; Magnesium Hydroxide: (Moderate) Do not coadminister mesalamine extended-release capsules (Apriso) with antacids. Apriso is a pH-dependent, delayed-release capsule product with an enteric coating that dissolves at a pH of at least 6. Other mesalamine products do not have an interaction with antacids.
Calcium Carbonate; Magnesium Hydroxide; Simethicone: (Moderate) Do not coadminister mesalamine extended-release capsules (Apriso) with antacids. Apriso is a pH-dependent, delayed-release capsule product with an enteric coating that dissolves at a pH of at least 6. Other mesalamine products do not have an interaction with antacids.
Calcium Carbonate; Simethicone: (Moderate) Do not coadminister mesalamine extended-release capsules (Apriso) with antacids. Apriso is a pH-dependent, delayed-release capsule product with an enteric coating that dissolves at a pH of at least 6. Other mesalamine products do not have an interaction with antacids.
Calcium; Vitamin D: (Moderate) Do not coadminister mesalamine extended-release capsules (Apriso) with antacids. Apriso is a pH-dependent, delayed-release capsule product with an enteric coating that dissolves at a pH of at least 6. Other mesalamine products do not have an interaction with antacids.
Celecoxib: (Minor) The concurrent use of mesalamine with known nephrotoxic agents such as nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of nephrotoxicity.
Celecoxib; Tramadol: (Minor) The concurrent use of mesalamine with known nephrotoxic agents such as nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of nephrotoxicity.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Minor) The concurrent use of mesalamine with known nephrotoxic agents such as nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of nephrotoxicity.
Clindamycin: (Moderate) Concomitant use of mesalamine and clindamycin may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Dalteparin: (Moderate) Coadministration of 5-aminosalicylates and low molecular weight heparins may result in an increased risk of bleeding (i.e., hematomas) following neuraxial anesthesia. Discontinue 5-aminosalicylates prior to the initiation of a low molecular weight heparins. If this is not possible, it is recommended to monitor patients closely for bleeding.
Diclofenac: (Minor) The concurrent use of mesalamine with known nephrotoxic agents such as nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of nephrotoxicity.
Diclofenac; Misoprostol: (Minor) The concurrent use of mesalamine with known nephrotoxic agents such as nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of nephrotoxicity.
Diflunisal: (Minor) The concurrent use of mesalamine with known nephrotoxic agents such as nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of nephrotoxicity.
Diphenhydramine; Ibuprofen: (Minor) The concurrent use of mesalamine with known nephrotoxic agents such as nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of nephrotoxicity.
Diphenhydramine; Naproxen: (Minor) The concurrent use of mesalamine with known nephrotoxic agents such as nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of nephrotoxicity.
Enoxaparin: (Moderate) Coadministration of 5-aminosalicylates and low molecular weight heparins may result in an increased risk of bleeding (i.e., hematomas) following neuraxial anesthesia. Discontinue 5-aminosalicylates prior to the initiation of a low molecular weight heparins. If this is not possible, it is recommended to monitor patients closely for bleeding.
Etodolac: (Minor) The concurrent use of mesalamine with known nephrotoxic agents such as nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of nephrotoxicity.
Fenoprofen: (Minor) The concurrent use of mesalamine with known nephrotoxic agents such as nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of nephrotoxicity.
Flurbiprofen: (Minor) The concurrent use of mesalamine with known nephrotoxic agents such as nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of nephrotoxicity.
Heparin: (Moderate) Coadministration of 5-aminosalicylates and heparin may result in an increased risk of bleeding (i.e., hematomas) following neuraxial anesthesia. Discontinue 5-aminosalicylates prior to the initiation of heparin. If this is not possible, it is recommended to monitor patients closely for bleeding.
Hydrocodone; Ibuprofen: (Minor) The concurrent use of mesalamine with known nephrotoxic agents such as nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of nephrotoxicity.
Ibuprofen: (Minor) The concurrent use of mesalamine with known nephrotoxic agents such as nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of nephrotoxicity.
Ibuprofen; Famotidine: (Minor) The concurrent use of mesalamine with known nephrotoxic agents such as nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of nephrotoxicity.
Ibuprofen; Oxycodone: (Minor) The concurrent use of mesalamine with known nephrotoxic agents such as nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of nephrotoxicity.
Ibuprofen; Pseudoephedrine: (Minor) The concurrent use of mesalamine with known nephrotoxic agents such as nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of nephrotoxicity.
Indomethacin: (Minor) The concurrent use of mesalamine with known nephrotoxic agents such as nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of nephrotoxicity.
Ketoprofen: (Minor) The concurrent use of mesalamine with known nephrotoxic agents such as nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of nephrotoxicity.
Ketorolac: (Minor) The concurrent use of mesalamine with known nephrotoxic agents such as nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of nephrotoxicity.
Low Molecular Weight Heparins: (Moderate) Coadministration of 5-aminosalicylates and low molecular weight heparins may result in an increased risk of bleeding (i.e., hematomas) following neuraxial anesthesia. Discontinue 5-aminosalicylates prior to the initiation of a low molecular weight heparins. If this is not possible, it is recommended to monitor patients closely for bleeding.
Magnesium Hydroxide: (Moderate) Do not coadminister mesalamine extended-release capsules (Apriso) with antacids. Apriso is a pH-dependent, delayed-release capsule product with an enteric coating that dissolves at a pH of at least 6. Other mesalamine products do not have an interaction with antacids.
Magnesium Salts: (Moderate) Do not coadminister mesalamine extended-release capsules (Apriso) with antacids. Apriso is a pH-dependent, delayed-release capsule product with an enteric coating that dissolves at a pH of at least 6. Other mesalamine products do not have an interaction with antacids.
Meclofenamate Sodium: (Minor) The concurrent use of mesalamine with known nephrotoxic agents such as nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of nephrotoxicity.
Mefenamic Acid: (Minor) The concurrent use of mesalamine with known nephrotoxic agents such as nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of nephrotoxicity.
Meloxicam: (Minor) The concurrent use of mesalamine with known nephrotoxic agents such as nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of nephrotoxicity.
Mercaptopurine, 6-MP: (Moderate) Increased bone marrow suppression may occur if mercaptopurine is coadministered with mesalamine. If concomitant use is necessary, use the lowest possible doses of each drug and closely monitor the patient for myelosuppression. 5-Aminosalicylates, such as mesalamine, have been shown to inhibit the thiopurine methyltransferase (TPMT) enzyme in vitro. Mercaptopurine is inactivated via the TPMT enzyme.
Nabumetone: (Minor) The concurrent use of mesalamine with known nephrotoxic agents such as nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of nephrotoxicity.
Naproxen: (Minor) The concurrent use of mesalamine with known nephrotoxic agents such as nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of nephrotoxicity.
Naproxen; Esomeprazole: (Minor) The concurrent use of mesalamine with known nephrotoxic agents such as nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of nephrotoxicity.
Naproxen; Pseudoephedrine: (Minor) The concurrent use of mesalamine with known nephrotoxic agents such as nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of nephrotoxicity.
Nonsteroidal antiinflammatory drugs: (Minor) The concurrent use of mesalamine with known nephrotoxic agents such as nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of nephrotoxicity.
Omeprazole; Sodium Bicarbonate: (Moderate) Do not coadminister mesalamine extended-release capsules (Apriso) with antacids. Apriso is a pH-dependent, delayed-release capsule product with an enteric coating that dissolves at a pH of at least 6. Other mesalamine products do not have an interaction with antacids.
Oxaprozin: (Minor) The concurrent use of mesalamine with known nephrotoxic agents such as nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of nephrotoxicity.
Piroxicam: (Minor) The concurrent use of mesalamine with known nephrotoxic agents such as nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of nephrotoxicity.
Porfimer: (Major) Avoid coadministration of porfimer with mesalamine due to the risk of increased photosensitivity. All patients treated with porfimer will be photosensitive. Concomitant use of other photosensitizing agents like mesalamine may increase the risk of a photosensitivity reaction.
Sodium Bicarbonate: (Moderate) Do not coadminister mesalamine extended-release capsules (Apriso) with antacids. Apriso is a pH-dependent, delayed-release capsule product with an enteric coating that dissolves at a pH of at least 6. Other mesalamine products do not have an interaction with antacids.
Sulindac: (Minor) The concurrent use of mesalamine with known nephrotoxic agents such as nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of nephrotoxicity.
Sumatriptan; Naproxen: (Minor) The concurrent use of mesalamine with known nephrotoxic agents such as nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of nephrotoxicity.
Thioguanine, 6-TG: (Moderate) Use these drugs together with caution; concomitant use may result in reduced metabolism of thioguanine via TPMT and an increased risk for thioguanine-induced toxicity. Monitor patients for signs and symptoms of hematologic and hepatic toxicity. There is in vitro evidence that 5-aminosalicylate derivatives inhibit thiopurine methyltransferase (TPMT), the enzyme that metabolizes thioguanine. Increased thioguanine concentrations can lead to an increased risk for severe thioguanine-induced myelosuppression. In cases of bone marrow suppression, a dose reduction of thioguanine may be necessary.
Tolmetin: (Minor) The concurrent use of mesalamine with known nephrotoxic agents such as nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of nephrotoxicity.
Verteporfin: (Moderate) Use caution if coadministration of verteporfin with mesalamine is necessary due to the risk of increased photosensitivity. Verteporfin is a light-activated drug used in photodynamic therapy; all patients treated with verteporfin will be photosensitive. Concomitant use of other photosensitizing agents like mesalamine may increase the risk of a photosensitivity reaction.
Voclosporin: (Moderate) Concomitant use of voclosporin and mesalamine may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
Warfarin: (Moderate) Mesalamine may alter the anticoagulant effects of warfarin. Closely monitor a patient's PT and INR during and following concomitant mesalamine therapy; dosage adjustments of anticoagulants may be necessary. In elderly patients taking mesalamine with anticoagulants, consider regularly monitoring complete blood cell counts and platelet counts, as an increased risk for blood dyscrasia has been reported in geriatric adults. In a published case study, a decreased effect of warfarin was reported when mesalamine was prescribed. Iincreased prothrombin time (PT) in patients taking concomitant warfarin has been reported during mesalamine treatment.
The antiinflammatory actions of mesalamine are believed to be secondary to, at least in part, the inhibition of arachidonic acid in the bowel mucosa by the enzyme cyclooxygenase. Inhibition of cyclooxygenase effectively diminishes the production prostaglandins, thereby reducing colonic inflammation. Production of these arachidonic metabolites appears to be increased in patients with inflammatory bowel disease. Mesalamine also interferes with leukotriene synthesis, possibly by inhibiting the lipoxygenase enzyme. In support of prostaglandins as a mediator for inflammatory bowel disease are reports of disease exacerbation after oral administration of misoprostol. However, specific inhibitors of prostaglandin and leukotriene synthesis, respectively, are less effective than mesalamine and related compounds. Thus, the exact mechanism of action of mesalamine is as yet uncertain.
Inhibition of colonic mucosal sulfidopeptide leukotriene synthesis and chemotactic stimuli for polymorphonuclear leukocytes also may occur. Mesalamine inhibits accumulation of thromboxane A and superoxide formation in the rectal mucosa, which may contribute to its antiinflammatory action. Other possible mechanisms include alterations in colonic fluid balance, immunosuppression, and alteration of the GI bacterial flora. Data also support the mechanism that mesalamine may inhibit the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), a nuclear protein complex that controls transcription of DNA, cytokine and other pro-inflammatory protein production, and cell survival.
Mesalamine (5-ASA) is administered by rectal suspension or suppository, or by oral delayed-release tablets or capsules. The clinical response of 5-ASA is believed to be due to a local effect. Therefore, mesalamine preparations are designed to deliver drug to the large bowel where its therapeutic action is driven by intestinal lumen absorption. Following administration, 5-ASA absorption is variable and highly dependent on disease activity and colonic pH. Altered mucosal uptake of 5-ASA can occur during periods of active disease when local inflammation causes histological changes to the mucosa as well as epithelial damage and increased blood flow. In addition, as luminal pH drops across the gastric mucosa so does 5-ASA absorption. Mesalamine may be distributed to the kidneys, but the overall distribution is uncertain. Mesalamine is acted upon by N-acetyltransferse in the liver and intestinal mucosa to produce N-acetylsalicylic acid (N-acetyl-5-ASA). The activity of N-acetyl-5-ASA, the major metabolite, is unknown. Any systemically absorbed mesalamine is eliminated from plasma mainly by urinary excretion, predominantly as N-acetyl-5-ASA; less than 8% of the absorbed dose is excreted unchanged in the urine. The mean elimination half-life at steady-state for both mesalamine and N-acetyl-5-ASA is 7-12 hours. Absorbed 5-ASA does not accumulate in plasma with repeated daily dosing.
Affected cytochrome P450 isoenzymes and drug transporters: thiopurine methyltransferase (TPMT)
Aminosalicylates, such as mesalamine, have been shown to inhibit the TPMT enzyme in vitro. The inhibition of TPMT activity could result in a higher risk of bone marrow suppression or other dose-related side effects of drugs that are metabolized by this enzyme.
-Route-Specific Pharmacokinetics
Oral Route
Uncoated mesalamine tablets are absorbed extensively in the proximal portion of the GI tract; therefore, delayed-release tablets are used to achieve a local effect in the colon. After oral administration, 20% to 30% of a dose is absorbed, with peak plasma concentrations achieved in 3 to 12 hours. Administering mesalamine delayed-release tablets with a high-fat meal results in delayed absorption and increased systemic exposure. In a single-dose pharmacokinetic study in healthy volunteers, the mean mesalamine Cmax and AUC were 36% and 25% lower, respectively, after administration of 1 Asacol HD 800 mg tablet compared to 2 Asacol 400 mg tablets. Due to the topical mechanism of mesalamine, the clinical effects of this difference in systemic exposure is not known.
Other Route(s)
Rectal Route
-Mesalamine rectal suspension: The extent of absorption is dependent upon the retention time of the drug product, and there is considerable individual variation. At steady-state, approximately 10% to 30% of the daily 4-gram dose can be recovered in cumulative 24-hour urine collections.
-Mesalamine rectal suppository: Mesalamine rectal suppository is variably absorbed. In patients with ulcerative colitis treated with mesalamine 500 mg rectal suppositories given once every 8 hours for 6 days, the mean mesalamine peak plasma concentration (Cmax) was 353 ng/mL (CV=55%) following the initial dose and 361 ng/mL (CV = 67%) at steady state. The mean minimum steady-state plasma concentration (Cmin) was 89 ng/mL (CV = 89%). Any absorbed mesalamine does not accumulate in the plasma.
-Special Populations
Pediatrics
In pediatric patients 5 to 17 years of age diagnosed with ulcerative colitis, systemic exposure of mesalamine, as measured by mean steady-state AUC and Cmax, increased in a dose-proportional manner between 30 and 60 mg/kg/day PO of mesalamine delayed-release tablets and increased in a less than proportional manner between 60 and 100 mg/kg/day doses. Pharmacokinetic parameters had moderate to high inter-subject variability with CV% ranging from 36% to 52% in pediatric patients. The overall systemic exposure of mesalamine following oral administration of 4.8 g once daily for 7 days in a limited number of pediatric patients 5 years to 17 years of age (AUC range of 30,556 to 50,388 ng x hour/mL, n = 3) was a similar range to that was observed in the healthy adults (AUC of 41,434 +/- 26,640 ng x hour/mL, n = 48) after single-dose administration. The mean renal clearance (CLR) of mesalamine in pediatric patients (range approximately 5 to 6.5 L/hour) seems to be similar to that observed with healthy adult subjects after multiple-dose administration.