Lialda

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Lialda

Classes

Aminosalicyclic Acid and Related Intestinal Antiinflammatory Agents

Administration

Patients should drink an adequate amount of fluids each day during treatment.

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.

Adverse Reactions
Severe

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

Moderate

constipation / Delayed / 0-11.0
hypertriglyceridemia / Delayed / 0-3.0
hematuria / Delayed / 0-3.0
dyspnea / Early / 0-3.0
elevated hepatic enzymes / Delayed / 2.0-2.0
fecal incontinence / Early / 0-1.0
depression / Delayed / 0-1.0
colitis / Delayed / 0-1.0
melena / Delayed / 0-1.0
dysphagia / Delayed / 0-1.0
oral ulceration / Delayed / 0-1.0
hyperamylasemia / Delayed / 0-1.0
thrombocytopenia / Delayed / 0-1.0
proteinuria / Delayed / 0-1.0
hypertension / Early / 1.0-1.0
hypotension / Rapid / 0-1.0
sinus tachycardia / Rapid / 0-1.0
palpitations / Early / 0-1.0
peripheral vasodilation / Rapid / 0-1.0
edema / Delayed / 0-1.0
hemorrhoids / Delayed / 2.0
anemia / Delayed / 5.0
migraine / Early / Incidence not known
confusion / Early / Incidence not known
hyperesthesia / Delayed / Incidence not known
peripheral neuropathy / Delayed / Incidence not known
cholangitis / Delayed / Incidence not known
gastritis / Delayed / Incidence not known
stomatitis / Delayed / Incidence not known
cholestasis / Delayed / Incidence not known
hepatitis / Delayed / Incidence not known
jaundice / Delayed / Incidence not known
hyperbilirubinemia / Delayed / Incidence not known
eosinophilia / Delayed / Incidence not known
neutropenia / Delayed / Incidence not known
leukopenia / Delayed / Incidence not known
lymphadenopathy / Delayed / Incidence not known
psoriasis / Delayed / Incidence not known
dysuria / Early / Incidence not known
infertility / Delayed / Incidence not known
nephrolithiasis / Delayed / Incidence not known
chest pain (unspecified) / Early / Incidence not known
interstitial lung disease / Delayed / Incidence not known
pneumonitis / Delayed / Incidence not known
gout / Delayed / Incidence not known
hypertonia / Delayed / Incidence not known
blurred vision / Early / Incidence not known
conjunctivitis / Delayed / Incidence not known

Mild

eructation / Early / 0-26.0
abdominal pain / Early / 1.0-21.0
pharyngitis / Delayed / 1.0-15.0
headache / Early / 2.0-11.0
fatigue / Early / 0-10.0
dizziness / Early / 0-9.0
diarrhea / Early / 0-8.0
rhinitis / Early / 8.0-8.0
fever / Early / 1.0-7.0
sinusitis / Delayed / 0-7.0
flatulence / Early / 4.0-6.0
nausea / Early / 0-6.0
rash / Early / 0-6.0
back pain / Delayed / 0-6.0
vomiting / Early / 0-5.0
cough / Delayed / 0-5.0
influenza / Delayed / 1.0-5.0
dyspepsia / Early / 1.0-4.0
vertigo / Early / 0-3.0
alopecia / Delayed / 0-3.0
arthralgia / Delayed / 0-3.0
musculoskeletal pain / Early / 0-3.0
stool discoloration / Delayed / 0-1.0
drowsiness / Early / 0-1.0
insomnia / Early / 0-1.0
tremor / Early / 0-1.0
anorexia / Delayed / 0-1.0
acne vulgaris / Delayed / 0-1.0
diaphoresis / Early / 0-1.0
pruritus / Rapid / 0-1.0
urticaria / Rapid / 0-1.0
photosensitivity / Delayed / 0-1.0
xerosis / Delayed / 0-1.0
ecchymosis / Delayed / 0-1.0
weakness / Early / 0-1.0
asthenia / Delayed / 0-1.0
malaise / Early / 0-1.0
tenesmus / Delayed / 2.0
paresthesias / Delayed / 2.0
increased urinary frequency / Early / 2.0
infection / Delayed / 5.0
syncope / Early / Incidence not known
anxiety / Delayed / Incidence not known
emotional lability / Early / Incidence not known
xerostomia / Early / Incidence not known
appetite stimulation / Delayed / Incidence not known
urine discoloration / Early / Incidence not known
dysmenorrhea / Delayed / Incidence not known
libido decrease / Delayed / Incidence not known
menorrhagia / Delayed / Incidence not known
oligospermia / Delayed / Incidence not known
chills / Rapid / Incidence not known
myalgia / Early / Incidence not known
muscle cramps / Delayed / Incidence not known
dysgeusia / Early / Incidence not known
ocular pain / Early / Incidence not known
otalgia / Early / Incidence not known
tinnitus / Delayed / Incidence not known

Common Brand Names

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

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 in treating ulcerative colitis and ulcerative proctitis; not considered effective for Crohn's disease
Oral mesalamine considered first-line therapy for mild to moderately active ulcerative colitis

Dosage And Indications
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.

†Indicates off-label use

Dosing Considerations
Hepatic Impairment

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

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. Discontinue mesalamine if renal function deteriorates while on therapy.

Drug Interactions

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.
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.

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

Maximum Dosage
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.

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. 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]

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.