NDC 69918-560 Mesalamine Rectal

Mesalamine

NDC Product Code 69918-560

NDC CODE: 69918-560

Proprietary Name: Mesalamine Rectal What 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 What 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.

Drug Use Information

Drug Use Information
The drug use information is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate. This information is not individual medical advice and does not substitute for the advice of a health care professional. Always ask a health care professional for complete information about this product and your specific health needs.

  • This medication is used to treat a certain bowel disease (ulcerative colitis). It helps to reduce symptoms of ulcerative colitis such as diarrhea, rectal bleeding, and stomach pain. Mesalamine belongs to a class of drugs known as aminosalicylates. It works by decreasing swelling in the colon.

Product Characteristics

Color(s):
WHITE (C48325 - WHITE TO BEIGE)
Shape: BULLET (C48335)

NDC Code Structure

  • 69918 - Amring Pharmaceuticals Inc.

NDC 69918-560-30

Package Description: 30 SUPPOSITORY in 1 BOX

Price per Unit: $3.77833 per EA

NDC Product Information

Mesalamine Rectal with NDC 69918-560 is a a human prescription drug product labeled by Amring Pharmaceuticals Inc.. The generic name of Mesalamine Rectal is mesalamine. The product's dosage form is suppository and is administered via rectal form. The RxNorm Crosswalk for this NDC code indicates a single RxCUI concept is associated to this product: 248420.

Dosage Form: Suppository - A solid body of various weights and shapes, adapted for introduction into the rectal orifice of the human body; they usually melt, soften, or dissolve at body temperature.

Product Type: Human Prescription Drug What 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 Rectal Active Ingredient(s)

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


Inactive Ingredient(s)

About 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.

  • FAT, HARD (UNII: 8334LX7S21)

Administration Route(s)

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

  • Rectal - Administration to the rectum.

Pharmacological Class(es)

What 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

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Amring Pharmaceuticals Inc.
Labeler Code: 69918
FDA Application Number: ANDA208362 What 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. What 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: 06-24-2019 What 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: 12-31-2021 What 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 - NO What 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 ("Y"), or because the listing certification is expired ("E"), or because the listing data was inactivated by FDA ("I"). Values = "Y", "N", "E", or "I".

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Mesalamine Rectal 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 Rectal Suppositories are indicated in adults for the treatment of mildly to moderately active ulcerative proctitis.

2. Dosage And Administration

  • DosageThe recommended dosage of Mesalamine Rectal Suppositories in adults is 1000 mg administered rectally once daily at bedtime for 3 to 6 weeks depending on symptoms and sigmoidoscopic findings. Safety and effectiveness of Mesalamine Rectal Suppositories beyond 6 weeks have not been established.Administration Instructions:Evaluate renal function prior to initiation of Mesalamine Rectal Suppository therapy [see Warnings and Precautions (5.1)].Do not cut or break the suppository.Retain the suppository for one to three hours or longer, if possible.Drink an adequate amount of fluids [see Warnings and Precautions (5.6)]If a dose of Mesalamine Rectal Suppositories is missed, administer as soon as possible, unless it is almost time for next dose. Do not use two Mesalamine Rectal Suppositories at the same time to make up for a missed dose.Mesalamine Rectal Suppositories will cause staining of direct contact surfaces, including but not limited to fabrics, flooring, painted surfaces, marble, granite, vinyl, and enamel. Keep Mesalamine Rectal Suppositories away from these surfaces to prevent staining.

3. Dosage Forms And Strengths

Mesalamine Rectal Suppository: 1000 mg mesalamine in a torpedo shaped, white to beige suppository.

4. Contraindications

Mesalamine Rectal Suppositories are contraindicated in patients with known or suspected hypersensitivity to salicylates or aminosalicylates or to any ingredients in the suppository vehicle [see Warnings and Precautions (5.3), Adverse Reactions (6.2), and Description (11)].

5.1 Renal Impairment

Renal impairment, including minimal change disease, acute and chronic interstitial nephritis, and renal failure, has been reported in patients given products such as Mesalamine Rectal Suppositories that contain mesalamine or are converted to mesalamine. In animal studies, the kidney was the principal organ of mesalamine toxicity [see Adverse Reactions (6.2), Nonclinical Toxicology (13.2)].Evaluate renal function prior to initiation of Mesalamine Rectal Suppositories and periodically while on therapy.Evaluate the risks and benefits of using Mesalamine Rectal Suppositories in patients with known renal impairment or a history of renal disease or taking concomitant nephrotoxic drugs [see Drug Interactions (7.1), Use in Specific Populations (8.6)].

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. Although the exact frequency of occurrence has not been determined, it has occurred in 3% of patients in controlled clinical trials of mesalamine or sulfasalazine. Symptoms include cramping, acute abdominal pain and bloody diarrhea, and sometimes fever, headache, malaise, pruritis, conjunctivitis, and rash. Monitor patients for worsening of these symptoms while on treatment. If acute intolerance syndrome is suspected, promptly discontinue treatment with Mesalamine Rectal Suppositories.

5.3 Hypersensitivity Reactions

Hypersensitivity reactions have been reported in patients taking sulfasalazine. Some patients may have a similar reaction to Mesalamine Rectal Suppositories 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 Rectal Suppositories if an alternative etiology for the signs and 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 other products containing mesalamine. Evaluate the risks and benefits of using Mesalamine Rectal Suppositories in patients with known liver impairment.

5.5 Photosensitivity

In patients treated with mesalamine or sulfasalazine who have pre-existing skin conditions such as atopic dermatitis and atopic eczema have reported more severe photosensitivity reactions. Advise patients to avoid sun exposure, wear protective clothing, and use a broad-spectrum sunscreen when outdoors.

5.6 Nephrolithiasis

Cases of nephrolithiasis have been reported with the use of mesalamine, including stones of 100% mesalamine content. Mesalamine-containing stones are radiotransparent and undetectable by standard radiography or computed tomography (CT). Ensure adequate hydration during treatment with Mesalamine Rectal Suppositories.

5.7 Interaction With Laboratory Test For Urinary Normetanephrine

Use of mesalamine may lead to spuriously elevated test results when measuring urinary normetanephrine by liquid chromatography with electrochemical detection, because of the similarity in the chromatograms of normetanephrine and mesalamine's main metabolite, N-acetylaminosalicylic acid. Consider an alternative, selective assay for normetanephrine.

6. Adverse Reactions

  • The following serious or clinically significant adverse reactions are described elsewhere in labeling: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)]Photosensitivity [see Warnings and Precautions (5.5)]Nephrolithiasis [see Warnings and Precautions (5.6)]

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.The most common adverse reactions in adult patients with mildly to moderately active ulcerative proctitis in double-blind, placebo-controlled trials are summarized in the Table 1 below.Table 1: Adverse Reactions Occurring in More Than 1% of Mesalamine Suppository Treated Patients (Comparison to Placebo)     SymptomMesalamine(n = 177)Placebo(n = 84)N%N%     Dizziness5322.4     Rectal Pain31.800     Fever21.200     Rash21.200     Acne21.200     Colitis21.200In a multicenter, open-label, randomized, parallel group study in 99 patients comparing the Mesalamine Rectal Suppository 1000 mg suppository administered nightly to that of the mesalamine 500 mg suppository twice daily. The most common adverse reactions in both groups were headache (14%), flatulence (5%), abdominal pain (5%), diarrhea (3%), and nausea (3%). Three (3) patients discontinued medication because of an adverse reaction; one of these adverse reactions (headache) was deemed possibly related to study medication. The recommended dosage of Mesalamine Rectal Suppositories is 1000 mg administered rectally once daily at bedtime [see Dosage and Administration (2)].

6.2 Postmarketing Experience

  • The following adverse reactions have been identified during post-approval use of Mesalamine Rectal Suppositories or other mesalamine-containing products. 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: drug fever, fatigue, lupus-like syndrome, medication residueCardiac Disorders: myocarditis, pericarditis, pericardial effusion [see Warnings and Precautions (5.3)]Endocrine: Nephrogenic diabetes insipidusEye disorders: eye swellingGastrointestinal Disorders: abdominal cramps, abdominal distension, anal pruritus, anorectal discomfort, constipation, feces discolored, flatulence, frequent bowel movements, gastrointestinal bleeding, mucus stools, nausea, painful defecation, pancreatitis, proctalgia, rectal discharge, rectal tenesmus, stomach discomfort, vomitingHepatic Disorders: cholestatic jaundice, hepatitis, jaundice, Kawasaki-like syndrome including changes in liver enzymes, liver necrosis, liver failureHematologic Disorders: agranulocytosis, aplastic anemia, thrombocytopeniaNeurological/Psychiatric Disorders: Guillain-Barre syndrome, peripheral neuropathy, transverse myelitis, intracranial hypertensionRenal Disorders: interstitial nephritis, renal failure, minimal change disease, nephrolithiasis [see Warnings and Precautions (5.1, 5.6)]Respiratory, Thoracic and Mediastinal Disorders: hypersensitivity pneumonitis (including allergic alveolitis, eosinophilic pneumonitis, interstitial pneumonitis)Skin and Subcutaneous Tissue Disorder: alopecia, erythema, erythema nodosum, pruritus, psoriasis, pyoderma gangrenosum, urticariaUrogenital: reversible oligospermia

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 and/or other drugs known to cause myelotoxicity may increase the risk for blood disorders, bone marrow failure, and associated complications. If concomitant use of Mesalamine Rectal Suppositories and azathioprine or 6-mercaptopurine cannot be avoided, monitor blood tests, including complete blood cell counts and platelet counts.

7.3 Interference With Urinary Normetanephrine Measurements

Use of mesalamine may lead to spuriously elevated test results when measuring urinary normetanephrine by liquid chromatography with electrochemical detection, because of the similarity in the chromatograms of normetanephrine and mesalamine's main metabolite, N-acetylaminosalicylic acid. Consider an alternative, selective assay for normetanephrine [see Warnings and Precautions (5.7)].

8.1 Pregnancy

Risk SummaryLimited published data on mesalamine use in pregnant women are insufficient to inform a drug-associated risk. No evidence of teratogenicity was observed in rats or rabbits when treated during gestation with orally administered mesalamine at doses greater than the recommended human intra-rectal dose (see Data).The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications. 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.DataAnimal DataReproduction studies have been performed in rats at oral doses up to 320 mg/kg/day (about 1.7 times the recommended human intra-rectal dose of Mesalamine Rectal Suppositories, based on body surface area) and in rabbits at oral doses up to 495 mg/kg/day (about 5.4 times the recommended human intra-rectal dose of Mesalamine Rectal Suppositories, based on body surface area) following administration during the period of organogenesis, and have revealed no evidence of impaired fertility or harm to the fetus due to mesalamine.

8.2 Lactation

Risk SummaryMesalamine 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 lack of clinical data during lactation precludes a clear determination of the risk of Mesalamine Rectal Suppositories to an infant during lactation; therefore, the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Mesalamine Rectal Suppositories and any potential adverse effects on the breastfed child from Mesalamine Rectal Suppositories or from the underlying maternal conditions.Clinical ConsiderationsMonitor breastfed infants for diarrhea.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 N-acetyl-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

The safety and effectiveness of Mesalamine Rectal Suppositories in pediatric patients for the treatment of mildly to moderately active ulcerative proctitis have not been established. Mesalamine Rectal Suppositories were evaluated for the treatment of ulcerative proctitis in a 6-week, open-label, single-arm study in 49 patients 5 to 17 years of age, which only included 14 patients with histologically-confirmed cases of ulcerative proctitis. However, efficacy was not demonstrated. Adverse reactions seen in pediatric patients in this trial (abdominal pain, headache, pyrexia, pharyngolaryngeal pain, diarrhea and vomiting) were similar to those seen in adult patients.

8.5 Geriatric Use

Clinical trials of Mesalamine Rectal Suppositories did not include sufficient numbers of patients aged 65 years and over to determine whether they respond differently from younger patients. Reports from uncontrolled clinical studies and postmarketing reporting systems suggested a higher incidence of blood dyscrasias (i.e., agranulocytosis, neutropenia and pancytopenia) in patients receiving mesalamine-containing products such as Mesalamine Rectal Suppositories who were 65 years or older compared to younger patients. Monitor complete blood cell counts and platelet counts in elderly patients during treatment with Mesalamine Rectal Suppositories. In general, consider the greater frequency of decreased hepatic, renal, or cardiac function, and of concurrent disease or other drug therapy in elderly patients when prescribing Mesalamine Rectal Suppositories [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 Rectal Suppository 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

Mesalamine absorption from the colon is limited; however, Mesalamine Rectal Suppositories are an aminosalicylate, and symptoms of salicylate toxicity include nausea, vomiting and abdominal pain, tachypnea, hyperpnea, tinnitus, and neurologic symptoms (headache, dizziness, confusion, seizures). Severe salicylate intoxication may lead to electrolyte and blood pH imbalance and potentially to other organ (e.g., renal and liver) involvement. There is no specific antidote for mesalamine overdose. Correct fluid and electrolyte imbalance by the administration of appropriate intravenous therapy and maintain adequate renal function.

11. Description

The active ingredient in Mesalamine Rectal Suppository 1000 mg suppositories for rectal use is mesalamine, also known as mesalazine or 5- aminosalicylic acid (5-ASA). Chemically, mesalamine is 5-amino-2-hydroxybenzoic acid, and is classified as an aminosalicylate. Each Mesalamine Rectal Suppository contains 1000 mg of mesalamine (USP) in a base of Hard Fat, NF. The empirical formula is C7H7NO3, representing a molecular weight of 153.14. The structural formula is:

12.1 Mechanism Of Action

The mechanism of action of mesalamine is not fully understood, but appears to be a topical anti-inflammatory effect on colonic epithelial cells. Mucosal production of arachidonic acid metabolites, both through the cyclooxygenase pathways, i.e., prostanoids, and through the lipoxygenase pathways, i.e., leukotrienes and hydroxyeicosatetraenoic acids, is increased in patients with ulcerative colitis, and it is possible that mesalamine diminishes inflammation by blocking cyclooxygenase and inhibiting prostaglandin production in the colon.

12.3 Pharmacokinetics

AbsorptionMesalamine (5-ASA) administered as a rectal suppository is variably absorbed. In patients with ulcerative colitis treated with mesalamine 500 mg rectal suppositories, administered once every eight hours for six 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%). Absorbed mesalamine does not accumulate in the plasma.DistributionMesalamine administered as a rectal suppository distributes in rectal tissue to some extent.EliminationIn patients with ulcerative proctitis treated with mesalamine 500 mg as a rectal suppository every 8 hours for 6 days, the mean elimination half-life was 5 hours (CV=73%) for 5-ASA and 5 hours (CV=63%) for N-acetyl-5-ASA, the active metabolite, following the initial dose. At steady state, the mean elimination half-life was 7 hours for both 5-ASA and N-acetyl-5-ASA (CV=102% for 5-ASA and 82% for N-acetyl-5-ASA).MetabolismThe absorbed mesalamine is extensively metabolized, mainly to N-acetyl-5-ASA in the liver and in the gut mucosal wall. In patients with ulcerative colitis treated with one mesalamine 500 mg rectal suppository every eight hours for six days, the peak concentration (Cmax) of N-acetyl-5-ASA ranged from 467 ng/mL to 1399 ng/mL following the initial dose and from 193 ng/mL to 1304 ng/mL at steady state.ExcretionMesalamine is eliminated from plasma mainly by urinary excretion, predominantly as N-acetyl-5-ASA. In patients with ulcerative proctitis treated with mesalamine 500 mg as a rectal suppository every 8 hours for 6 days, 12% or less of the dose was eliminated in urine as unchanged 5-ASA and 8% to 77% was eliminated as N-acetyl-5-ASA following the initial dose. At steady state, 11% or less of the dose was eliminated in the urine as unchanged 5-ASA and 3% to 35% was eliminated as N-acetyl-5-ASA.

13.1 Carcinogenesis, Mutagenesis, Impairment Of Fertility

Mesalamine caused no increase in the incidence of neoplastic lesions over controls in a two-year study of Wistar rats fed up to 320 mg/kg/day of mesalamine admixed with diet (about 1.7 times the recommended human intra-rectal dose of Mesalamine Rectal Suppositories, based on body surface area).Mesalamine was not mutagenic in the Ames test, the mouse lymphoma cell (TK+/-) forward mutation test, or the mouse micronucleus test.No effects on fertility or reproductive performance of the male and female rats were observed at oral mesalamine doses up to 320 mg/kg/day (about 1.7 times the recommended human intra-rectal dose of Mesalamine Rectal Suppositories, based on body surface area).

13.2 Animal Toxicology And/Or Pharmacology

Toxicology studies of mesalamine were conducted in rats, mice, rabbits and dogs, and the kidney was the main target organ of toxicity. In rats, adverse renal effects were observed at a single oral dose of 600 mg/kg (about 3.2 times the recommended human intra-rectal dose of Mesalamine Rectal Suppository, based on body surface area) and at intravenous doses of >214 mg/kg (about 1.2 times the recommended human intra-rectal dose of Mesalamine Rectal Suppository, based on body surface area). In a 13-week oral gavage toxicity study in rats, papillary necrosis and/or multifocal tubular injury were observed in males receiving 160 mg/kg (about 0.86 times the recommended human intra-rectal dose of Mesalamine Rectal Suppository, based on body surface area) and in both males and females at 640 mg/kg (about 3.5 times the recommended human intra-rectal dose of Mesalamine Rectal Suppository, based on body surface area). In a combined 52-week toxicity and 127-week carcinogenicity study in rats, degeneration of the kidneys and hyalinization of basement membranes and Bowman’s capsule were observed at oral doses of 100 mg/kg/day (about 0.54 times the recommended human intra-rectal dose of Mesalamine Rectal Suppository, based on body surface area) and above. In a 14-day rectal toxicity study of mesalamine suppositories in rabbits, intra-rectal doses up to 800 mg/kg (about 8.6 times the recommended human intra-rectal dose of Mesalamine Rectal Suppository, based on body surface area) was not associated with any adverse effects. In a six-month oral toxicity study in dogs, doses of 80 mg/kg (about 1.4 times the recommended human intra-rectal dose of Mesalamine Rectal Suppository, based on body surface area) and higher caused renal pathology similar to that described for the rat. In a rectal toxicity study of mesalamine suppositories in dogs, a dose of 166.6 mg/kg (about 3 times the recommended human intra-rectal dose of Mesalamine Rectal Suppository, based on body surface area) produced chronic nephritis and pyelitis. In the 12-month eye toxicity study in dogs, keratoconjunctivitis sicca (KCS) occurred at oral doses of 40 mg/kg (about 0.72 times the recommended human intra-rectal dose of Mesalamine Rectal Suppository, based on body surface area) and above.

14. Clinical Studies

Two double-blind, placebo-controlled, multicenter trials of mesalamine suppositories were conducted in North America in adult patients with mildly to moderately active ulcerative proctitis. The regimen in Study 1 was a 500 mg mesalamine suppository administered rectally three times daily and in Study 2 was a 500 mg mesalamine suppository administered rectally twice daily. In both trials, patients had an average extent of proctitis (upper disease boundary) of approximately 10 cm and approximately 80% of patients had multiple prior episodes of proctitis. A total of 173 patients were evaluated (Study 1, N=79; Study 2, N=94), of which 89 patients received mesalamine, and 84 patients received placebo. The mean age of patients was 39 years (range 17 to 73 years), 60% were female, and 97% were white.The primary measures of efficacy were clinical disease activity index (DAI) and histologic evaluations in both trials. The DAI is a composite index reflecting rectal bleeding, stool frequency, mucosal appearance at endoscopy, and a physician’s global assessment of disease. Patients were evaluated clinically and sigmoidoscopically after 3 and 6 weeks of treatment.Compared to placebo, mesalamine suppositories were statistically (p<0.01) superior to placebo in both trials with respect to improvement in stool frequency, rectal bleeding, mucosal appearance, disease severity, and overall disease activity after 3 and 6 weeks of treatment. The effectiveness of mesalamine suppositories was statistically significant irrespective of sex, extent of proctitis, duration of current episode, or duration of disease.An additional multicenter, open-label, randomized, parallel group study in 99 patients diagnosed with mildly to moderately ulcerative proctitis compared 1000 mg Mesalamine Rectal Suppositories administered rectally once daily at bedtime (N=35) to 500 mg mesalamine suppository administered rectally twice daily, in the morning and at bedtime (N=46), for 6 weeks.The primary measures of efficacy included the clinical disease activity index (DAI) and histologic evaluations. Patients were evaluated clinically and sigmoidoscopically at 3 and 6 weeks of treatment.The efficacy at 6 weeks was not different between the treatment groups. Both were effective in the treatment of ulcerative proctitis and resulted in a significant decrease at 6 weeks in DAI: in the mesalamine 500 mg twice daily group, the mean DAI value decreased from 6.6 to 1.6, and in the 1000 mg at bedtime group, the mean DAI value decreased from 6.2 to 1.3, which represents a decrease of greater than 75% in both groups. After 6 weeks of treatment, a DAI score of less than 3 was achieved in 78% of patients in the mesalamine 500 mg twice daily group and 86% of patients in the Mesalamine Rectal Suppositories 1000 mg once daily group. The recommended dosage of Mesalamine Rectal Suppository is 1000 mg administered rectally once daily at bedtime [see Dosage and Administration (2)].

16. How Supplied/Storage And Handling

Mesalamine Rectal Suppositories 1000 mg for rectal administration are available as torpedo shaped, white to beige suppositories containing 1000 mg mesalamine supplied in boxes of 30 (NDC 69918-560-30).Store below 25ºC (77ºF), may be refrigerated. Keep away from direct heat, light or humidity.

17. Patient Counseling Information

  • Advise patients to read the FDA-approved patient labeling (Patient Information)Administration [see Dosage and Administration (2)]Advise patients:Do not cut or break the suppository.Retain the suppository for one to three hours or longer, if possible.Drink an adequate amount of fluids.If a dose of Mesalamine Rectal Suppositories is missed, administer as soon as possible, unless it is almost time for next dose. Do not use two Mesalamine Rectal Suppositories at the same time to make up for a missed dose.Mesalamine Rectal Suppositories will cause staining of direct contact surfaces, including but not limited to fabrics, flooring, painted surfaces, marble, granite, vinyl, and enamel. Keep Mesalamine Rectal Suppositories away from these surfaces to prevent staining.Renal ImpairmentInform patients that Mesalamine Rectal Suppositories may decrease their renal function, especially if they have known renal impairment or are taking nephrotoxic drugs, including NSAIDs, and periodic monitoring of renal function will be performed while they are on therapy. Advise patients to complete all blood tests ordered by their healthcare provider [see Warnings and Precautions (5.1), Drug Interactions (7.1)].Mesalamine-Induced Acute Intolerance Syndrome and Other Hypersensitivity ReactionsInform patients of the signs and symptoms of hypersensitivity reactions. Instruct patients to stop taking Mesalamine Rectal Suppositories and report to their healthcare provider if they experience new or worsening symptoms Acute Intolerance Syndrome (cramping, abdominal pain, bloody diarrhea, fever, headache, malaise, conjunctivitis and rash) or other symptoms suggestive of mesalamine-induced hypersensitivity [see Warnings and Precautions (5.2, 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 healthcare provider if they experience such signs or symptoms [see Warnings and Precautions (5.4)].PhotosensitivityAdvise patients with pre-existing skin conditions to avoid sun exposure, wear protective clothing, and use a broad-spectrum sunscreen when outdoors [see Warnings and Precautions (5.5)].NephrolithiasisInstruct patients to drink an adequate amount of fluids during treatment in order to minimize the risk of kidney stone formation and to contact their healthcare provider if they experience signs or symptoms of a kidney stone (e.g., severe side or back pain, blood in the urine) [see Warnings and Precautions (5.6)].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 healthcare provider [see Drug Interactions (7.2), Use in Specific Populations (8.5)].Manufactured for:
  • Amring Pharmaceuticals Inc.
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