NDC 60687-408 Mesalamine

Mesalamine

NDC Product Code 60687-408

NDC Code: 60687-408

Proprietary Name: Mesalamine Additional informationCallout TooltipWhat is the Proprietary Name?
The proprietary name also known as the trade name is the name of the product chosen by the medication labeler for marketing purposes.

Non-Proprietary Name: Mesalamine Additional informationCallout TooltipWhat is the Non-Proprietary Name?
The non-proprietary name is sometimes called the generic name. The generic name usually includes the active ingredient(s) of the product.


Product Characteristics
Color(s):
RED (C48326 - REDDISH-BROWN)
Shape: CAPSULE (C48336)
Size(s):
19 MM
Imprint(s):
435
Score: 1

Code Structure
  • 60687 - American Health Packaging
    • 60687-408 - Mesalamine

NDC 60687-408-25

Package Description: 30 BLISTER PACK in 1 BOX, UNIT-DOSE > 1 TABLET, DELAYED RELEASE in 1 BLISTER PACK (60687-408-95)

NDC Product Information

Mesalamine with NDC 60687-408 is a a human prescription drug product labeled by American Health Packaging. The generic name of Mesalamine is mesalamine. The product's dosage form is tablet, delayed release and is administered via oral form.

Labeler Name: American Health Packaging

Dosage Form: Tablet, Delayed Release - A solid dosage form which releases a drug (or drugs) at a time other than promptly after administration. Enteric-coated articles are delayed release dosage forms.

Product Type: Human Prescription Drug Additional informationCallout TooltipWhat kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.


Mesalamine Active Ingredient(s)

Additional informationCallout TooltipWhat is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.

  • MESALAMINE 800 mg/1

Inactive Ingredient(s)

Additional informationCallout TooltipAbout the Inactive Ingredient(s)
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • ACETYLTRIBUTYL CITRATE (UNII: 0ZBX0N59RZ)
  • SILICON DIOXIDE (UNII: ETJ7Z6XBU4)
  • FERRIC OXIDE RED (UNII: 1K09F3G675)
  • MAGNESIUM STEARATE (UNII: 70097M6I30)
  • METHACRYLIC ACID (UNII: 1CS02G8656)
  • MICROCRYSTALLINE CELLULOSE (UNII: OP1R32D61U)
  • POVIDONE, UNSPECIFIED (UNII: FZ989GH94E)
  • SODIUM STARCH GLYCOLATE TYPE A POTATO (UNII: 5856J3G2A2)
  • TALC (UNII: 7SEV7J4R1U)
  • TITANIUM DIOXIDE (UNII: 15FIX9V2JP)
  • AMMONIA (UNII: 5138Q19F1X)
  • BUTYL ALCOHOL (UNII: 8PJ61P6TS3)
  • FERROSOFERRIC OXIDE (UNII: XM0M87F357)
  • ISOPROPYL ALCOHOL (UNII: ND2M416302)
  • PROPYLENE GLYCOL (UNII: 6DC9Q167V3)
  • SHELLAC (UNII: 46N107B71O)

Administration Route(s)

Additional informationCallout TooltipWhat are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Oral - Administration to or by way of the mouth.

Pharmacological Class(es)

Additional informationCallout TooltipWhat is a Pharmacological Class?
These are the reported pharmacological class categories corresponding to the SubstanceNames listed above.

  • Aminosalicylate - [EPC] (Established Pharmacologic Class)
  • Aminosalicylic Acids - [CS]

Product Labeler Information

Additional informationCallout TooltipWhat is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: American Health Packaging
Labeler Code: 60687
FDA Application Number: ANDA203286 Additional informationCallout TooltipWhat is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: ANDA - A product marketed under an approved Abbreviated New Drug Application. Additional informationCallout TooltipWhat is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 01-10-2019 Additional informationCallout TooltipWhat is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2020 Additional informationCallout TooltipWhat is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N Additional informationCallout TooltipWhat is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA’s requests for correction to deficient or non-compliant submissions. Values = ‘Y’ or ‘N’.

* Please review the disclaimer below.

Information for Patients

Mesalamine

Mesalamine is pronounced as (me sal' a meen)

Why is mesalamine medication prescribed?
Mesalamine is used to treat ulcerative colitis (a condition which causes swelling and sores in the lining of the colon [large intestine] and rectum) and also to maintain ...
[Read More]

* Please review the disclaimer below.

Mesalamine Product Label Images

Mesalamine Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

1 Indications And Usage

Mesalamine delayed-release tablets are indicated for the treatment of moderately active ulcerative colitis in adults.Limitations of Use:
Safety and effectiveness of mesalamine delayed-release tablets beyond 6 weeks have not been established.

2.1 Important Administration Instructions

  • Do not substitute one mesalamine delayed-release tablet 800 mg for two mesalamine delayed-release 400 mg oral products
  • [see Clinical Pharmacology (
  • 12.3)].
  • Evaluate renal function prior to initiation of mesalamine delayed-release tablets.Take mesalamine delayed-release tablets on an empty stomach, at least 1 hour before and 2 hours after a meal
  • [see Clinical Pharmacology (
  • 12.3)]
  • .
  • Swallow mesalamine delayed-release tablets whole. Do not cut, break or chew the tablets.Intact, partially intact, and/or tablet shells have been reported in the stool; Instruct patients to contact their physician if this occurs repeatedly.Protect mesalamine delayed-release tablets from moisture.

2.2 Dosage Information

For the treatment of moderately active ulcerative colitis, the recommended dosage of mesalamine delayed-release tablets in adults is 1600 mg (two 800 mg tablets) three times daily (total daily dosage of 4.8 grams) for a duration of 6 weeks.

3 Dosage Forms And Strengths

Mesalamine delayed-release tablets are available as reddish-brown colored, capsule-shaped, biconvex, enteric coated tablets, imprinted with "435" on one side and plain on other side.

4 Contraindications

Mesalamine delayed-release tablets are contraindicated in patients with known or suspected hypersensitivity to salicylates or aminosalicylates or to any of the ingredients of mesalamine delayed-release tablets
[see Warnings and Precautions (
5.3), Adverse Reactions (
6.2), and Description (
11)]
.

5.1 Renal Impairment

Renal impairment, including minimal change nephropathy, acute and chronic interstitial nephritis, and, rarely, renal failure, has been reported in patients taking products such as mesalamine delayed-release tablets that contain or are converted to mesalamine
[see Adverse Reactions (
6.2)]
.
Evaluate renal function prior to initiation of mesalamine delayed-release tablets and periodically while on therapy. Evaluate the risks and benefits of using mesalamine delayed-release tablets in patients with known renal impairment or history of renal disease or taking concomitant nephrotoxic drugs
[see Drug Interactions (
7.1), Use in Specific Populations (
8.6) and Nonclinical Toxicology (
13.2)]
.

5.2 Mesalamine-Induced Acute Intolerance Syndrome

Mesalamine has been associated with an acute intolerance syndrome that may be difficult to distinguish from an exacerbation of ulcerative colitis. Exacerbation of the symptoms of colitis has been reported in 2.3% of mesalamine-treated patients in controlled clinical trials. This acute reaction, characterized by cramping, abdominal pain, bloody diarrhea, and occasionally by fever, headache, malaise, pruritus, rash, and conjunctivitis, has been reported after the initiation of mesalamine delayed-release tablets as well as other mesalamine products. Symptoms usually abate when mesalamine delayed-release tablets are discontinued.

5.3 Hypersensitivity Reactions

Hypersensitivity reactions have been reported in patients taking sulfasalazine. Some patients may have a similar reaction to mesalamine delayed-release tablets or to other compounds that contain or are converted to mesalamine.As with sulfasalazine, mesalamine-induced hypersensitivity reactions may present as internal organ involvement, including myocarditis, pericarditis, nephritis, hepatitis, pneumonitis, and hematologic abnormalities. Evaluate patients immediately if signs or symptoms of a hypersensitivity reaction are present. Discontinue mesalamine delayed-release tablets if an alternative etiology for the signs or symptoms cannot be established.

5.4 Hepatic Failure

There have been reports of hepatic failure in patients with pre-existing liver disease who have been administered mesalamine. Caution should be exercised when administering mesalamine delayed-release tablets to patients with liver impairment.

6 Adverse Reactions

  • The most serious adverse reactions seen in mesalamine delayed-release tablets clinical trials or with other products that contain mesalamine or are metabolized to mesalamine were:Renal Impairment
  • [see Warnings and Precautions (
  • 5.1)]
  • Mesalamine-Induced Acute Intolerance Syndrome
  • [see Warnings and Precautions (
  • 5.2)]
  • Hypersensitivity Reactions
  • [see Warnings and Precautions (
  • 5.3)]
  • Hepatic Failure
  • [see Warnings and Precautions (
  • 5.4)]

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.Mesalamine has been evaluated in 896 patients with ulcerative colitis in controlled studies. Three six-week, active-controlled studies were conducted comparing mesalamine 4.8 grams per day with mesalamine-delayed release tablets 2.4 grams per day in patients with mildly to moderately active ulcerative colitis. In these studies, 727 patients were dosed with the mesalamine delayed-release tablet, 800 mg and 732 patients were dosed with mesalamine delayed-release tablets, 400 mg.The most common reactions reported in the mesalamine group were headache (4.7%), nausea (2.8%), nasopharyngitis (2.5%), abdominal pain (2.3%), diarrhea (1.7%), and dyspepsia (1.7%); Table 1 enumerates adverse reactions that occurred in the three studies. The most common reactions in patients with moderately active ulcerative colitis (602 patients dosed with mesalamine delayed-release tablet, 800 mg and 618 patients dosed with the mesalamine delayed-release tablet, 400 mg) were the same as all treated patients.Discontinuations due to adverse reactions occurred in 3.9% of patients in the mesalamine delayed-release tablet, 800 mg group and in 4.2% of patients in the mesalamine delayed-release tablet, 400 mg comparator group. The most common cause for discontinuation was gastrointestinal symptoms associated with ulcerative colitis.Serious adverse reactions occurred in 0.8% of patients in the mesalamine delayed-release tablet, 800 mg group and in 1.8% of patients in the mesalamine delayed-release tablet, 400 mg comparator group. The majority involved the gastrointestinal system.Table 1 Adverse Reactions Occurring in ≥1% of All Treated Patients (Three studies combined)N = number of patients within specified treatment groupPercent = percentage of patients in category and treatment groupAdverse ReactionMesalamine delayed-release2.4 grams per day(400 mg Tablet)(N = 732)Mesalamine delayed-release4.8 grams per day(800 mg Tablet)(N = 727)Headache4.9 %4.7 %Nausea2.9 %2.8 %Nasopharyngitis1.4 %2.5 %Abdominal pain2.3 %2.3 %Diarrhea1.9 %1.7 %Dyspepsia0.8 %1.7 %Vomiting1.6 %1.4 %Flatulence0.7 %1.2 %Influenza1.2 %1.0 %Pyrexia1.2 %0.7 %Cough1.4 %0.3 %

6.2 Postmarketing Experience

In addition to the adverse reactions reported above in clinical trials involving the mesalamine delayed-release tablet 800 mg, the adverse events listed below have been reported in postmarketing experience with other mesalamine-containing products or products that are metabolized to mesalamine. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.Body as a Whole
Facial edema, edema, peripheral edema, asthenia, chills, infection, malaise, pain, neck pain, chest pain, back pain, abdominal enlargement, lupus-like syndrome, drug fever (rare).
Cardiovascular
Pericarditis (rare) and myocarditis (rare) [
see Warnings and Precautions (
5.3)
], pericardial effusion, vasodilation, migraine.
Endocrine: Nephrogenic diabetes insipidus.
Gastrointestinal
Dry mouth, stomatitis, oral ulcers, anorexia, increased appetite, eructation, pancreatitis, cholecystitis, gastritis, gastroenteritis, gastrointestinal bleeding, perforated peptic ulcer (rare), constipation, hemorrhoids, rectal hemorrhage, bloody diarrhea, tenesmus, stool abnormality.
Hepatic
There have been rare reports of hepatotoxicity, including jaundice, cholestatic jaundice, hepatitis, and possible hepatocellular damage including liver necrosis and liver failure. Some of these cases were fatal. Asymptomatic elevations of liver enzymes which usually resolve during continued use or with discontinuation of the drug have also been reported. One case of Kawasaki-like syndrome, that included changes in liver enzymes, was also reported
[see Warnings and Precautions (
5.4)].
Hematologic
Agranulocytosis (rare), aplastic anemia (rare), anemia, thrombocytopenia, leukopenia, eosinophilia, lymphadenopathy.
Musculoskeletal
Gout, rheumatoid arthritis, arthritis, arthralgia, joint disorder, myalgia, hypertonia.
Neurological/Psychiatric
Anxiety, depression, somnolence, insomnia, nervousness, confusion, emotional lability, dizziness, vertigo, tremor, paresthesia, hyperesthesia, peripheral neuropathy (rare), Guillain-Barre syndrome (rare), and transverse myelitis (rare), intracranial hypertension.
Respiratory/Pulmonary
Sinusitis, rhinitis, pharyngitis, asthma exacerbation, pleuritis, bronchitis, eosinophilic pneumonia, interstitial pneumonitis.
Skin
Alopecia, psoriasis (rare), pyoderma gangrenosum (rare), erythema nodosum, acne, dry skin, sweating, pruritus, urticaria, rash.
Special Senses
Ear pain, tinnitus, ear congestion, ear disorder, conjunctivitis, eye pain, blurred vision, vision abnormality, taste perversion.
Renal/Urogenital
Renal failure (rare), interstitial nephritis, minimal change nephropathy
[see Warnings and Precautions (
5.1)]
, dysuria, urinary frequency and urgency, hematuria, epididymitis, decreased libido, dysmenorrhea, menorrhagia.
Laboratory Abnormalities
Elevated AST (SGOT) or ALT (SGPT), elevated alkaline phosphatase, elevated GGT, elevated LDH, elevated bilirubin, elevated serum creatinine and BUN.

7.1 Nephrotoxic Agents, Including Non-Steroidal Anti-Inflammatory Drugs

The concurrent use of mesalamine with known nephrotoxic agents, including nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of nephrotoxicity. Monitor patients taking nephrotoxic drugs for changes in renal function and mesalamine-related adverse reactions
[see Warnings and Precautions (
5.1)].

7.2 Azathioprine Or 6-Mercaptopurine

The concurrent use of mesalamine with azathioprine or 6-mercaptopurine may increase the risk for blood disorders. If concomitant use of mesalamine delayed-release tablet 800 mg and azathioprine or 6- mercaptopurine cannot be avoided, monitor blood tests, including complete blood cell counts and platelet counts.

8.1 Pregnancy:

Risk Summary
Limited published data on mesalamine use in pregnant women are insufficient to inform a drug-associated risk. No fetal harm was observed in animal reproduction studies of mesalamine in rats and rabbits at oral doses approximately 0.97 times (rat) and 1.95 times (rabbit) the recommended human dose [see
Data].
The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.Data
Animal Data

Reproduction studies with mesalamine were performed during organogenesis in rats and rabbits at oral doses up to 480 mg/kg/day. There was no evidence of harm to the fetus. These mesalamine doses were about 0.97 times (rat) and 1.95 times (rabbit) the recommended human dose of 4.8 grams per day, based on body surface area.

8.2 Lactation

Risk Summary
Mesalamine and its N-acetyl metabolite are present in human milk in undetectable to small amounts [
see Data]. There are limited reports of diarrhea in breastfed infants. There is no information on the effects of the drug on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for mesalamine and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition.
Clinical Considerations
Monitor breastfed infants for diarrhea.
Data
Human Data

In published lactation studies, maternal mesalamine doses from various oral and rectal formulations and products ranged from 500 mg to 3 g daily. The concentration of mesalamine in milk ranged from non-detectable to 0.11 mg/L. The concentration of the Nacetyl-5-aminosalicylic acid metabolite ranged from 5 to 18.1 mg/L. Based on these concentrations, estimated infant daily dosages 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.

8.4 Pediatric Use

Safety and effectiveness of mesalamine in pediatric patients have not been established. See the prescribing information for other approved mesalamine products for the safety and effectiveness of these products in pediatric patients.

8.5 Geriatric Use

Clinical studies of mesalamine delayed-release tablets did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently than younger patients. Reports from uncontrolled clinical studies and postmarketing experience for another oral formulation of mesalamine suggest a higher incidence of blood dyscrasias (agranulocytosis, neutropenia, pancytopenia) in patients who were 65 years or older compared to younger patients. Monitor complete blood cell counts and platelet counts in elderly patients during therapy with mesalamine delayed-release tablets.In general, the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy in elderly patients should be considered when prescribing mesalamine delayed-release tablets
[see Use in Specific Populations (
8.6)]
.

8.6 Renal Impairment

Mesalamine is known to be substantially excreted by the kidney, and the risk of adverse reactions may be greater in patients with impaired renal function. Evaluate renal function in all patients prior to initiation and periodically while on mesalamine delayed-release tablets therapy. Monitor patients with known renal impairment or history of renal disease or taking nephrotoxic drugs for decreased renal function and mesalamine-related adverse reactions [
see Warnings and Precautions (
5.1), Drug Interactions (
7.1) and Adverse Reactions (
6.2)
].

10 Overdosage

There is no specific antidote for mesalamine overdose and treatment for suspected acute severe toxicity with mesalamine should be symptomatic and supportive. This may include prevention of further gastrointestinal tract absorption, correction of fluid electrolyte imbalance, and maintenance of adequate renal function. Mesalamine delayed-release tablet is a pH dependent delayed-release product and this factor should be considered when treating a suspected overdose.Single oral doses of 5000 mg/kg mesalamine suspension in mice (approximately 4.2 times the recommended human dose of mesalamine based on body surface area), 4595 mg/kg in rats (approximately 7.8 times the recommended human dose of mesalamine based on body surface area) and 3000 mg/kg in cynomolgus monkeys (approximately 10 times the recommended human dose of mesalamine based on body surface area) were lethal.

11 Description

Each mesalamine delayed-release tablet for oral administration contains 800 mg of mesalamine USP, an aminosalicylate. Mesalamine, USP is light tan to pink colored, needle-shaped crystals. Color may darken on exposure to air. It is odorless or may have a slight characteristic odor, slightly soluble in water; very slightly soluble in methanol, in dehydrated alcohol, and in acetone; practically insoluble in n


-butyl alcohol, in chloroform, in ether, in ethyl acetate, in n-hexane, in methylene chloride, and in n-propyl alcohol and soluble in dilute hydrochloric acid and in dilute alkali hydroxides. Mesalamine delayed-release tablets 800 mg have single layered coating consisting of an acrylic based resin Eudragit S (methacrylic acid copolymer B, NF), which dissolves at pH 7 or greater, releasing mesalamine for topical anti-inflammatory action in the colon. Mesalamine (also referred to as 5-aminosalicylic acid or 5-ASA) has the chemical name 5-amino-2-hydroxybenzoic acid and its structural formula is:


Each mesalamine delayed-release tablet contains 800 mg of mesalamine. In addition, each tablet contains the following inactive ingredients: acetyltributyl citrate, colloidal silicone dioxide, ferric oxide red, magnesium stearate, methacrylic acid copolymer type B, microcrystalline cellulose, povidone, sodium starch glycolate, talc and titanium dioxide. The tablet is printed with opacode black S-1-17823 which contains following ingredients: ammonium hydroxide, butyl alcohol, ferrosoferric oxide, isopropyl alcohol, propylene glycol and shellac.

12.1 Mechanism Of Action

The mechanism of action of mesalamine is unknown, but appears to be topical rather than systemic. Mucosal production of arachidonic acid metabolites, both through the cyclooxygenase pathways, that is, prostanoids, and through the lipoxygenase pathways, that is, leukotrienes and hydroxyeicosatetraenoic acids, is increased in patients with chronic inflammatory bowel disease, and it is possible that mesalamine diminishes inflammation by blocking cyclooxygenase and inhibiting prostaglandin production in the colon.

12.3 Pharmacokinetics

Absorption
Plasma concentrations of mesalamine (5-aminosalicylic acid; 5-ASA) and its metabolite, N-acetyl-5-aminosalicylic acid (N-Ac-5-ASA) are highly variable following administration of mesalamine delayed-release tablets. Following single dose oral administration of mesalamine delayed-release tablet 800 mg in healthy subjects (N = 139) under fasted conditions, the mean C
max, AUC
8-48h and AUC
0-tldc values were 208 ng/mL, 2296 ng.h/mL, and 2533 ng.h/mL, respectively. The median [range] T
max for mesalamine following administration of mesalamine delayed-release tablet 800 mg was approximately 24 hours [4 to 72 hours], reflecting the delayed-release characteristics of the formulation.
Based on cumulative urinary recovery of mesalamine and N-Ac-5-ASA from single dose studies in healthy subjects, approximately 20% of the orally administered mesalamine in mesalamine delayed-release tablets is systemically absorbed.Food Effect: A high calorie (800 to 1000 calories), high fat (approximately 50 % of total caloric content) meal increased mesalamine C
max by 2.4-fold and mesalamine systemic exposure (AUC
8-48 and AUC
0-tldc) by 2.8-fold; the median lag-time increased by 8 hours and median t
max by 6 hours (from 24 to 30 hours)
[see Dosage and Administration (
2.1)]
.
Comparative exposure between one mesalamine delayed-release tablet 800 mg and two mesalamine delayed-release 400 mg oral products is unknown
[see Dosage and Administration (
2.1)].
Elimination
Metabolism
The absorbed mesalamine is acetylated in the gut mucosal wall and by the liver to N-Ac- 5-ASA.
Excretion
Absorbed mesalamine is excreted mainly by the kidneys as N-acetyl-5-aminosalicylic acid. Unabsorbed mesalamine is excreted in feces.

13.1 Carcinogenesis, Mutagenesis, Impairment Of Fertility

Dietary mesalamine was not carcinogenic in rats at doses as high as 480 mg/kg/day, or in mice at 2000 mg/kg/day. These doses are approximately 0.97 and 2.0 times the 4.8 grams per day mesalamine delayed-release tablets dose (based on body surface area). Mesalamine was not genotoxic in the Ames test, the Chinese hamster ovary cell chromosomal aberration assay, and the mouse micronucleus test. Mesalamine, at oral doses up to 480 mg/kg/day (about 0.97 times the recommended human treatment dose based on body surface area), was found to have no effect on fertility or reproductive performance of male and female rats.

13.2 Animal Toxicology And/Or Pharmacology

In animal studies (rats, mice, dogs), the kidney was the principal organ for toxicity. (In the following, comparisons of animal dosing to recommended human dosing are based on body surface area and a 4.8 grams per day dose for a 60 kg person).Mesalamine causes renal papillary necrosis in rats at single doses of approximately 750 mg/kg to 1000 mg/kg (1.5 to 2.0 times the recommended human dose). Doses of 170 and 360 mg/kg/day (about 0.3 and 0.73 times the recommended human dose) given to rats for six months produced papillary necrosis, papillary edema, tubular degeneration, tubular mineralization, and urothelial hyperplasia.In mice, oral doses of 4000 mg/kg/day (approximately 4.1 times the recommended human dose) for three months produced tubular nephrosis, multifocal/diffuse tubulo-interstitial inflammation, and multifocal/diffuse papillary necrosis.In dogs, single doses of 6000 mg (approximately 6.25 times the recommended human dose) of delayed-release mesalamine tablets resulted in renal papillary necrosis but were not fatal. Renal changes have occurred in dogs given chronic administration of mesalamine at doses of 80 mg/kg/day (0.5 times the recommended human dose).

14.1 Moderately Active Ulcerative Colitis

The efficacy of mesalamine delayed-release tablets at 4.8 grams per day was studied in a six-week, randomized, double-blind, active-controlled study in 772 patients with moderately active ulcerative colitis (UC). Moderately active UC was defined as a Physician's Global Assessment (PGA) score of 2; the PGA is a four-point scale (0 to 3) that encompasses the clinical assessments of rectal bleeding, stool frequency, and sigmoidoscopy findings.Patients were randomized 1:1 to the mesalamine delayed-release tablets 4.8 grams per day group (two mesalamine delayed-release tablets three times a day) or the mesalamine delayed-release 2.4 grams per day group (two mesalamine delayed-release 400 mg tablets three times a day).Patients characteristically had a history of previous use of oral 5-ASAs (86%), steroids (41%), and rectal therapies (49%), and demonstrated clinical symptoms of three or more stools over normal per day (87%) and obvious blood in the stool most or all of the time (70%). The study population was primarily Caucasian (97%), had a mean age of 43 years (8% aged 65 years or older), and included slightly more males (56%) than females (44%).The primary endpoint was treatment success defined as improvement from baseline to Week 6 based on the PGA. Treatment success rates were similar in the two groups: 70% in the mesalamine group and 66% in the mesalamine delayed-release 400 mg tablets group (difference: 5%; 95% CI: [-1.9%, 11.2%]).A second controlled study supported the efficacy of mesalamine at 4.8 grams per day. Treatment success was 72% in patients with moderately active UC treated with mesalamine.

16 How Supplied/Storage And Handling

Mesalamine Delayed-release Tablets, USP 800 mg are reddish-brown colored, capsule-shaped, biconvex, enteric coated tablets, imprinted with "435" on one side and plain on other side and are supplied as follows:

Unit dose packages of 30 (5 x 6) NDC 60687-408-25
Storage
Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].

Protect from moisture.
FOR YOUR PROTECTION: Do not use if blister is torn or broken.

17 Patient Counseling Information

  • Administration
  • [see Dosage and Administration (
  • 2.1)]
  • Inform patients that if they are switching from a previous oral mesalamine therapy to mesalamine delayed-release tablets to discontinue their previous oral mesalamine therapy and follow the dosing instructions for mesalamine delayed-release tablets. One mesalamine delayed-release tablet 800 mg is not substitutable for two mesalamine delayed-release 400 mg oral products.Inform patients to take mesalamine delayed-release tablets on an empty stomach, at least 1 hour before and 2 hours after a meal.Instruct patients to swallow the mesalamine delayed-release tablets whole, taking care not to break, cut, or chew the tablets, because the coating is an important part of the delayed-release formulation.Inform patients that intact, partially intact, and/or tablet shells have been reported in the stool. Instruct patients to contact their physician if this occurs repeatedly.Instruct patients to protect mesalamine delayed-release tablets from moisture.Renal ImpairmentInform patients that mesalamine delayed-release tablets may decrease their renal function, especially if they have known renal impairment or are taking nephrotoxic drugs, and periodic monitoring of renal function will be performed while they are on therapy. Advise patients to complete all blood tests ordered by their physician
  • [see Warnings and Precautions (
  • 5.1)].
  • Mesalamine-Induced Acute Intolerance SyndromeInstruct patients to report to their physician if they experience new or worsening symptoms of cramping, abdominal pain, bloody diarrhea, and sometimes fever, headache, and rash
  • [see Warnings and Precautions (
  • 5.2)].
  • Hypersensitivity ReactionsInform patients of the signs and symptoms of hypersensitivity reactions, and advise them seek immediate medical care should signs and symptoms occur
  • [see Warnings and Precautions (
  • 5.3)].
  • Hepatic FailureInform patients with known liver disease of the signs and symptoms of worsening liver function and advise them to report to their physician if they experience such signs or symptoms
  • [see Warnings and Precautions (
  • 5.4)].
  • Blood DisordersInform elderly patients and those taking azathioprine or 6-mercaptopurine of the risk for blood disorders and the need for periodic monitoring of complete blood cell counts and platelet counts while on therapy. Advise patients to complete all blood tests ordered by their physician
  • [see Drug Interactions (
  • 7.2), Use in Specific Populations (
  • 8.5)].
  • Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Packaging Information

American Health Packaging unit dose blisters (see How Supplied section) contain drug product from Zydus Pharmaceuticals (USA) Inc. as follows:

(800 mg / 30 UD) NDC 60687-408-25 packaged from NDC 68382-435
Distributed by:
American Health Packaging
Columbus, OH 43217
8440825/0918F

Package/Label Display Panel – Carton – 800 Mg

NDC 60687-
408-25
Mesalamine
Delayed-release

Tablets, USP
800 mg30 Tablets (5 x 6) Rx OnlyDo not substitute one Mesalamine

Delayed-release Tablets 800 mg with two

Mesalamine Delayed-release 400 mg oral products
Each Delayed-Release Tablet Contains:
Mesalamine, USP...................................................... 800 mg
Usual Dosage: For the treatment of moderately active

ulcerative colitis,
the recommended dose of mesalamine

delayed-release tablets in adults is two 800 mg tablets to

be taken three times daily with or without food, for a total

daily dose of 4.8 gm, for a duration of 6 weeks.
See package insert for full prescribing information.Swallow Mesalamine Delayed-Release Tablets whole.

Do not cut, break, or chew the tablets.
Store at 20° to 25°C (68° to 77°F); excursions permitted

between 15° to 30°C (59° to 86°F) [see USP Controlled

Room Temperature]. Protect from moisture.
Keep this and all drugs out of reach of children.FOR YOUR PROTECTION: Do not use if blister is torn or

broken.
The drug product contained in this package is from

NDC # 68382-435, Zydus Pharmaceuticals (USA) Inc.
Distributed by:

American Health Packaging

Columbus, Ohio 43217
740825

0440825/0918OS

Package/Label Display Panel – Blister – 800 Mg

Mesalamine

Delayed-release

Tablet, USP
800 mg

* Please review the disclaimer below.

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