Canasa

Aminosalicyclic Acid and Related Intestinal Antiinflammatory Agents

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 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]

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

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

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

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

Rx

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)

800 mg PO 3 times daily for 6 weeks, then 800 mg PO twice daily or 400 mg PO 4 times daily.

1,200 mg PO twice daily (Dose range: 27 to 44 mg/kg/day) for 6 weeks. Safety and effectiveness beyond 6 weeks have not been established.

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. Safety and effectiveness beyond 6 weeks have not been established.

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. Safety and effectiveness beyond 6 weeks have not been established.

1.6 g PO 3 times daily for 6 weeks. Safety and effectiveness beyond 6 weeks have not been established.

2.4 to 4.8 g PO once daily, initially, then 2.4 g PO once daily.

4.8 g PO once daily for 8 weeks, then 2.4 g PO once daily.

3.6 g PO once daily for 8 weeks, then 2.4 g PO once daily.

2.4 g PO once daily for 8 weeks, then 1.2 g PO once daily.

Note: Mesalamine extended-release capsules are indicated for the maintenance of remission of ulcerative colitis.

1.5 g PO once daily in the morning.

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

NOTE: Mesalamine enema is indicated for mildly to moderately active distal ulcerative colitis.

1 to 4 g rectally once daily at bedtime for 3 to 6 weeks. Safety and effectiveness beyond 6 weeks have not been established.

1 to 4 g rectally once daily at bedtime for 3 to 6 weeks. Safety and effectiveness beyond 6 weeks have not been established.[56613] Guidelines suggest enemas rather than oral mesalamine in persons with left-sided mild to moderate ulcerative proctosigmoiditis or proctitis.[64377]

1 g rectally once daily at bedtime for 3 to 6 weeks. Safety and effectiveness beyond 6 weeks have not been established.[56597] Guidelines suggest suppositories rather than oral mesalamine in persons with left-sided mild to moderate ulcerative proctosigmoiditis or proctitis.[64377]

800 to 3,000 mg/day PO as a single dose or in divided doses.

†Indicates off-label use

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

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.

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.
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.
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.
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.

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

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).

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).

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

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.

Safety and efficacy have not been established.

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.

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.

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]

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]

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.