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  • CLASSES

    Aminosalicyclic Acid and Related Intestinal Antiinflammatory Agents

    DEA CLASS

    Rx

    DESCRIPTION

    5-aminosalicylate (5-ASA); available in oral and rectal formulations; clinical response is due to local effect
    Used as an anti-inflammatory agent for ulcerative colitis; not considered effective for Crohn's disease
    Also used for ulcerative proctitis (rectal formulations, suppository and enema only)

    COMMON BRAND NAMES

    Apriso, Asacol HD, Canasa, Delzicol, Lialda, Pentasa, Rowasa, sfRowasa

    HOW SUPPLIED

    Apriso/Mesalamine/Pentasa Oral Cap ER: 0.375g, 250mg, 500mg
    Asacol HD/Lialda/Mesalamine Oral Tab DR: 1.2g, 800mg
    Canasa/Mesalamine Rectal Supp: 1000mg
    Delzicol/Mesalamine Oral Cap DR Pellets: 400mg
    Mesalamine/Rowasa/sfRowasa Rectal Enema: 4g, 60mL

    DOSAGE & INDICATIONS

    For the treatment of ulcerative colitis.
    For induction of remission of mild to moderate active ulcerative colitis.
    Rectal dosage (suppositories; e.g., Canasa)
    Adults

    1,000 mg PR once daily at bedtime for 3 to 6 weeks depending on symptoms and sigmoidoscopic findings. Safety and effectiveness beyond 6 weeks have not been established.

    Rectal dosage (enema; e.g., Rowasa sulfite-free and Rowasa)
    Adults

    4 grams PR retained for approximately 8 hours if possible each night. While the effect may be seen within 3 to 21 days, the usual course of therapy would be from 3 to 6 weeks depending on symptoms and sigmoidoscopic findings.

    Oral dosage (delayed-release tablets; Asacol HD and generic equivalents)
    Adults

    1,600 mg PO 3 times daily for 6 weeks; total daily dose is 4.8 grams/day.

    Oral dosage (delayed-release tablets; Lialda and generic equivalents)
    Adults

    2.4 grams PO once daily or 4.8 grams PO once daily with a meal. Treatment duration in controlled trials was up to 8 weeks.

    Children and Adolescents 5 years and older weighing more than 50 kg

    4.8 grams PO once daily for 8 weeks, then 2.4 grams PO once daily. Take with food.

    Children and Adolescents 5 years and older weighing more than 35 kg and up to 50 kg

    3.6 grams PO once daily for 8 weeks, then 2.4 grams PO once daily. Take with food.

    Children and Adolescents 5 years and older weighing 24 to 35 kg

    2.4 grams PO once daily for 8 weeks, then 1.2 grams PO once daily. Take with food.

    Oral dosage (extended-release capsules: Pentasa)
    Adults

    1 gram PO 4 times daily. Treatment duration in controlled trials was up to 8 weeks.

    Oral dosage (delayed-release capsules: Delzicol and generic equivalents)
    Adults

    800 mg PO 3 times daily for 6 weeks; total daily dose is 2.4 grams/day. Delzicol capsules and Asacol HD tablets are not bioequivalent; do not use interchangeably.

    Children and Adolescents 5 years and older weighing 54 to 90 kg

    1,200 mg PO twice daily (i.e., 27 to 44 mg/kg/day PO given in 2 divided doses; Max: 2.4 grams/day). Continue therapy for 6 weeks; duration beyond 6 weeks has not been studied. Higher doses of mesalamine (up to 4.8 g/day PO) were not more effective than lower doses. Delzicol capsules and Asacol HD tablets are not bioequivalent; do not use interchangeably.

    Children and Adolescents 5 years and older weighing 33 to 53 kg

    1,200 mg PO in the morning and 800 mg PO in the afternoon (i.e., 37 to 61 mg/kg/day PO given in 2 divided doses; Max: 2 grams/day). Continue therapy for 6 weeks; duration beyond 6 weeks has not been studied. Higher doses of mesalamine (up to 4.8 grams/day PO) were not more effective than lower doses. Delzicol capsules and Asacol HD tablets are not bioequivalent; do not use interchangeably.

    Children 5 years and older weighing 17 to 32 kg

    800 mg PO in the morning and 400 mg PO in the afternoon (i.e., 36 to 71 mg/kg/day PO given in 2 divided doses; Max: 1.2 grams/day). Continue therapy for 6 weeks; duration beyond 6 weeks has not been studied. Higher doses of mesalamine were not more effective than lower doses. Delzicol capsules and Asacol HD tablets are not bioequivalent; do not use interchangeably.

    For maintenance of remission of ulcerative colitis.
    Oral dosage (extended-release capsules; i.e., Apriso)
    Adults

    1,500 mg PO once daily in the morning with or without meals. The duration of therapy has been as long as 24 months during clinical studies.

    Oral dosage (delayed-release tablets; i.e., Lialda)
    Adults

    2.4 grams PO once daily with a meal.

    Oral dosage (delayed-release capsules; i.e., Delzicol)
    Adults

    1,600 mg per day administered PO in 2 to 4 divided doses. Delzicol capsules and Asacol HD tablets are not bioequivalent; do not use interchangeably.

    For the treatment of active ulcerative proctitis.
    Rectal dosage (suppositories)
    Adults

    1,000 mg PR once daily at bedtime for 3 to 6 weeks depending on symptoms and sigmoidoscopic findings. Safety and effectiveness beyond 6 weeks have not been established.[56597] The American Gastroenterological Association suggests using enemas or suppositories rather than oral mesalamine in patients with mild to moderate ulcerate proctosigmoiditis or proctitis; suppositories have better retention than enemas.[64377]

    Rectal dosage (enema)
    Adults

    4 grams PR each night, retained for approximately 8 hours if possible. While the effect may be seen within 3 to 21 days, the usual course of therapy would be from 3 to 6 weeks depending on symptoms and sigmoidoscopic findings.[56613] The American Gastroenterological Association suggests using enemas or suppositories rather than oral mesalamine in patients with mild to moderate ulcerate proctosigmoiditis or proctitis.[64377]

    MAXIMUM DOSAGE

    Adults

    4 grams/day PR for rectal enema; 1 gram/day PR for rectal suppositories. For oral products: 1.5 grams/day PO for extended-release capsules (i.e., Apriso); 2.4 grams/day PO for delayed-release tablets or capsules (i.e, Delzicol); 4 grams/day PO for controlled-release capsules (i.e., Pentasa); 4.8 grams/day PO for delayed-release tablets (i.e., Asacol HD, Lialda).

    Geriatric

    4 grams/day PR for rectal enema; 1 gram/day PR for rectal suppositories. For oral products: 1.5 grams/day PO for extended-release capsules (i.e., Apriso); 2.4 grams/day PO for delayed-release tablets or capsules (i.e, Delzicol); 4 grams/day PO for controlled-release capsules (i.e., Pentasa); 4.8 grams/day PO for delayed-release tablets (i.e., Asacol HD, Lialda).

    Adolescents

    Delzicol - Maximum dosage determined by weight:
    54 to 90 kg: 44 mg/kg/day PO (Max: 2.4 grams/day)
    33 to 53 kg: 61 mg/kg/day PO (Max: 2 grams/day)
    17 to 32 kg: 71 mg/kg/day PO (Max: 1.2 grams/day)
     
    Lialda - Maximum dosage determined by weight:
    More than 50 kg: 4.8 grams/day PO
    More than 35 kg to 50 kg: 3.6 grams/day PO
    24 kg to 35 kg: 2.4 grams/day PO

    Children

    5 to 12 years: Maximum dosage determined by weight and product chosen:
    Delzicol
    54 to 90 kg: 44 mg/kg/day PO (Max: 2.4 grams/day)
    33 to 53 kg: 61 mg/kg/day PO (Max: 2 grams/day)
    17 to 32 kg: 71 mg/kg/day PO (Max: 1.2 grams/day)
     
    Lialda
    More than 50 kg: 4.8 grams/day PO
    More than 35 kg to 50 kg: 3.6 grams/day PO
    24 kg to 35 kg: 2.4 grams/day PO
     
     
    1 to 4 years: Safety and efficacy have not been established; off-label use reported for some formulations in children as young as 4 years of age.

    Infants

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available.

    Renal Impairment

    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.

    ADMINISTRATION

    Oral Administration
    Oral Solid Formulations

    Delayed-release tablets (Lialda):
    Recommended to be administered with food.[34564]
    Have the patient swallow the tablet whole; do not cut, break, or chew.[53771]
    Patients should drink an adequate amount of fluids each day during treatment.
     
    Delayed-release tablets (Asacol HD):
    Take on an empty stomach, at least 1 hour before and 2 hours after a meal.
    Have the patient swallow the tablet whole; do not cut, break, or chew.
    Intact, partially intact, and tablet shells have been reported in the stool. Instruct patients to contact their physician if this occurs repeatedly.
    Patients should drink an adequate amount of fluids each day during treatment.[41195]
     
    Extended-release capsules (Apriso):
    Administer in the morning with or without food.[34565]
    Have the patient swallow the capsule whole; do not chew or crush the capsule or its contents.
    Patients should drink an adequate amount of fluids each day during treatment.[53771]
     
    Delayed-release capsules (Delzicol):
    May be administered without regard to food.
    Have the patient swallow the capsule whole; do not open, cut, break, or chew.
    For patients who are unable to swallow the capsules whole, carefully open the capsule (s) and swallow the contents (four 100 mg tablets). Open the number of capsules 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.
    Intact, partially intact, and tablet shells have been reported in the stool. Instruct patients to contact their physician if this occurs repeatedly.
    Patients should drink an adequate amount of fluids each day during treatment.[53141]
     
    Controlled-release capsules (Pentasa):
    Have the patient swallow the capsule whole; do not cut, break, or chew.[53771]
    Alternatively, the capsule may be opened, and the contents may be sprinkled onto applesauce or yogurt. Consume contents immediately. The capsule contents should not be crushed or chewed.
    Patients should drink an adequate amount of fluids each day during treatment.[33460]

    Rectal Administration

    Rectal products are for rectal use only.
     
    Rectal suspension
    Administer at bedtime. Shake well before administering.
    Instruct patient on proper administration of rectal suspension.
    Encourage patient to retain suspension for at least 8 hours.[56613]
     
    Rectal suppository
    Instruct patient on the proper use of suppository and to avoid excessive handling of the suppository.
    Do not cut or break the suppository.
    Moisten the suppository with water before insertion. If the 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.
    The suppository should be retained in the rectum for at least 1 to 3 hour 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.[56597]

    STORAGE

    Apriso:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Asacol:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Asacol HD:
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Canasa:
    - Avoid excessive humidity
    - May be refrigerated
    - Protect from extreme heat
    - Protect from light
    - Store below 77 degrees F
    Delzicol:
    - Excursions permitted to 59 to 86 degrees F
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Lialda:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Pentasa:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Rowasa:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    sfRowasa:
    - After opening the foil pouch, product should be used within 2 weeks
    - Store at controlled room temperature (between 68 and 77 degrees F)
    - Store in a cool, well ventilated, dry place

    CONTRAINDICATIONS / PRECAUTIONS

    5-aminosalicylates hypersensitivity, colitis, salicylate hypersensitivity, serious rash

    Mesalamine, 5-ASA 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. As with sulfasalazine, mesalamine-induced hypersensitivity reactions may present as internal organ involvement, including myocarditis, pericarditis, nephritis, hepatitis, pneumonitis, and hematologic abnormalities. Serious rash including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported. Evaluate patients immediately if signs or symptoms of a hypersensitivity reaction are present. Discontinue mesalamine if an alternative etiology for the signs or symptoms cannot be established. Mesalamine suppositories are contraindicated in patients who have demonstrated hypersensitivity to the suppository vehicle (saturated vegetable fatty acid esters; Hard Fat, NF). 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 (melena and hematochezia), fever, headache, malaise, pruritus, rash (unspecified), and conjunctivitis. In rare cases, pancolitis has occurred. In cases of acute exacerbation of disease, prompt withdrawal of mesalamine therapy is required; symptoms typically resolve after discontinuation. The patient's history of sulfasalazine intolerance, if any, should be re-evaluated.

    Hepatic disease

    Hepatic failure has been reported in patients with pre-existing hepatic disease who received mesalamine. Caution is advised if mesalamine is administered to a patient with hepatic disease; consider the risks and benefits of mesalamine treatment.

    Renal disease, renal failure, renal impairment

    Evaluate renal function prior to prescribing mesalamine, 5-ASA, and periodically during treatment. 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. Monitor patients with a known history of renal disease or taking nephrotoxic drugs for decreased renal function and mesalamine-related adverse reactions. Mesalamine-induced nephrotoxicity, including nephropathy and interstitial nephritis, can occur.

    GI obstruction, pyloric stenosis

    Patients with pyloric stenosis or any other functional or organic upper GI obstruction can have prolonged gastric retention of mesalamine, 5-ASA delayed-release tablets or capsules, which could delay release in the colon. Avoid in patients at risk of upper GI tract obstruction.

    Geriatric

    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. Caution should be taken to 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.

    Pregnancy

    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.

    Breast-feeding

    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.

    Eczema, skin photosensitivity disorder, sunlight (UV) exposure

    Photosensitivity has been reported in patients receiving systemic dosage forms of mesalamine. Patients should be advised to limit sunlight (UV) exposure. Patients with pre-existing skin conditions such as atopic dermatitis and atopic eczema have reported more severe photosensitivity reactions. Use with caution in patients with a previous history of a skin photosensitivity disorder. Instruct patients to avoid sunlight (UV) exposure and tanning booths, and to wear sunscreen (and if possible protective clothing) on exposed skin.

    Children, infants, neonates

    Mesalamine has been used in children 4 years and older with inflammatory bowel disease (ulcerative colitis); selection of a dosage form that is age-appropriate is required for treatment. Mesalamine delayed-release capsule (Delzicol) and mesalamine delayed-release tablet (Lialda) use in pediatric patients is supported by well-controlled trials in patients aged 5 to 17 years of age. Other mesalamine oral and rectal dosage forms have not been formally approved for use in pediatric patients, infants, or neonates. As with adults, there is little evidence of efficacy for the use of mesalamine in inducing or maintaining remission in pediatric patients with Crohn's disease.

    Laboratory test interference

    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, Nacetylaminosalicylic acid (N-Ac-5-ASA). Consider an alternative, selective assay for normetanephrine.

    Phenylketonuria

    The Apriso brand of mesalamine extended-release capsules and some of the 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.

    Hemochromatosis

    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.

    Sulfite hypersensitivity

    Some mesalamine, 5-ASA rectal suspensions may cause an allergic-type reaction in patients with sulfite hypersensitivity. Some of the rectal suspensions contain potassium metabisulfite. Sensitivity to such sulfites appears to be increased in asthmatic compared with non-asthmatic patients. Exposure to sulfites has caused anaphylaxis including life-threatening or less severe asthmatic episodes. Sulfite-free formulas are also available for product selection.

    Nephrolithiasis

    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.     

    ADVERSE REACTIONS

    Severe

    esophageal ulceration / Delayed / 0-1.0
    pancreatitis / Delayed / 0-1.0
    GI bleeding / Delayed / 2.0
    cholecystitis / Delayed / Incidence not known
    hepatic necrosis / Delayed / Incidence not known
    hepatic failure / Delayed / Incidence not known
    hepatotoxicity / Delayed / Incidence not known
    aplastic anemia / Delayed / Incidence not known
    agranulocytosis / Delayed / Incidence not known
    pancytopenia / Delayed / Incidence not known
    erythema nodosum / Delayed / Incidence not known
    nephrotic syndrome / Delayed / Incidence not known
    interstitial nephritis / Delayed / Incidence not known
    renal failure (unspecified) / Delayed / Incidence not known
    diabetes insipidus / Delayed / Incidence not known
    nephrotoxicity / Delayed / Incidence not known
    acute generalized exanthematous pustulosis (AGEP) / Delayed / Incidence not known
    Stevens-Johnson syndrome / Delayed / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / Delayed / Incidence not known
    angioedema / Rapid / Incidence not known
    toxic epidermal necrolysis / Delayed / Incidence not known
    pericardial effusion / Delayed / Incidence not known
    pericarditis / Delayed / Incidence not known
    myocarditis / Delayed / Incidence not known
    increased intracranial pressure / Early / Incidence not known
    Guillain-Barre syndrome / Delayed / Incidence not known
    lupus-like symptoms / Delayed / Incidence not known
    pulmonary fibrosis / Delayed / Incidence not known
    myelitis / Delayed / Incidence not known

    Moderate

    colitis / Delayed / 3.0-12.0
    constipation / Delayed / 1.0-11.0
    chest pain (unspecified) / Early / 0-3.0
    proctitis / Delayed / 0.6-1.8
    fecal incontinence / Early / 0-1.0
    depression / Delayed / 0-1.0
    dysphagia / Delayed / 0-1.0
    oral ulceration / Delayed / 0-1.0
    elevated hepatic enzymes / Delayed / 0-1.0
    hyperamylasemia / Delayed / 0-1.0
    anemia / Delayed / 0-1.0
    conjunctivitis / Delayed / 0-1.0
    proteinuria / Delayed / 0-1.0
    hematuria / Delayed / 0-1.0
    hypertension / Early / 0-1.0
    sinus tachycardia / Rapid / 0-1.0
    palpitations / Early / 0-1.0
    hypotension / Rapid / 0-1.0
    edema / Delayed / 0-1.0
    cholangitis / Delayed / 0-0.1
    hemorrhoids / Delayed / 2.0
    migraine / Early / 2.0
    peripheral vasodilation / Rapid / 2.0
    melena / Delayed / Incidence not known
    gastritis / Delayed / Incidence not known
    jaundice / Delayed / Incidence not known
    cholestasis / Delayed / Incidence not known
    hepatitis / Delayed / Incidence not known
    thrombocytopenia / Delayed / Incidence not known
    neutropenia / Delayed / Incidence not known
    eosinophilia / Delayed / Incidence not known
    lymphadenopathy / Delayed / Incidence not known
    leukopenia / Delayed / Incidence not known
    psoriasis / Delayed / Incidence not known
    dyspnea / Early / Incidence not known
    peripheral neuropathy / Delayed / Incidence not known
    interstitial lung disease / Delayed / Incidence not known
    pneumonitis / Delayed / Incidence not known
    nephrolithiasis / Delayed / Incidence not known

    Mild

    headache / Early / 5.0-53.0
    eructation / Early / 16.0-26.0
    abdominal pain / Early / 2.0-21.0
    dizziness / Early / 2.0-15.0
    pharyngitis / Delayed / 0-15.0
    fatigue / Early / 1.0-10.0
    sinusitis / Delayed / 0-7.0
    flatulence / Early / 4.0-6.1
    nausea / Early / 0-6.0
    rash / Early / 5.0-6.0
    vomiting / Early / 5.0-5.0
    diarrhea / Early / 1.7-5.0
    cough / Delayed / 0-5.0
    dyspepsia / Early / 4.0-4.0
    acne vulgaris / Delayed / 0-3.0
    pruritus / Rapid / 0-3.0
    urticaria / Rapid / 0-3.0
    diaphoresis / Early / 0-3.0
    malaise / Early / 0-3.0
    myalgia / Early / 0-3.0
    stool discoloration / Delayed / 0-1.0
    tremor / Early / 0-1.0
    drowsiness / Early / 0-1.0
    syncope / Early / 0-1.0
    alopecia / Delayed / 0-1.0
    ecchymosis / Delayed / 0-1.0
    increased urinary frequency / Early / 0-1.0
    menorrhagia / Delayed / 0-1.0
    tenesmus / Delayed / 2.0
    paresthesias / Delayed / 2.0
    fever / Early / 5.0
    rhinitis / Early / 5.0
    infection / Delayed / 4.0
    influenza / Delayed / 4.0
    back pain / Delayed / 5.0
    arthralgia / Delayed / 5.0
    insomnia / Early / Incidence not known
    anorexia / Delayed / Incidence not known
    xerosis / Delayed / Incidence not known
    photosensitivity / Delayed / Incidence not known
    weakness / Early / Incidence not known
    oligospermia / Delayed / Incidence not known

    DRUG INTERACTIONS

    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.
    Ardeparin: (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.
    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; Risedronate: (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.
    Famotidine; Ibuprofen: (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; 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.
    Lansoprazole; Naproxen: (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.
    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.
    Rofecoxib: (Minor) The concurrent use of mesalamine with known nephrotoxic agents such as nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of nephrotoxicity.
    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.
    Tinzaparin: (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.
    Tolmetin: (Minor) The concurrent use of mesalamine with known nephrotoxic agents such as nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of nephrotoxicity.
    Valdecoxib: (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.

    PREGNANCY AND LACTATION

    Pregnancy

    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.

    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.

    MECHANISM OF ACTION

    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. Recent 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.

    PHARMACOKINETICS

    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.

    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.[34564] [34565] [41195] [53141] 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.[41195]

    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.[56613]
    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.[56597]