NDC 54868-6137 Balsalazide Disodium

NDC Product Code 54868-6137

NDC CODE: 54868-6137

Proprietary Name: Balsalazide Disodium 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.

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.

  • Balsalazide 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. Balsalazide belongs to a class of drugs known as aminosalicylates. It works by decreasing swelling in the colon.

Product Characteristics

Color(s):
ORANGE (C48331)
Shape: CAPSULE (C48336)
Size(s):
1 MM
Imprint(s):
54;795
Score: 1

NDC Code Structure

  • 54868 - Physicians Total Care, Inc.

NDC 54868-6137-0

Package Description: 280 CAPSULE in 1 BOTTLE

This product is EXCLUDED from the official NDC directory because the listing data was inactivated by the FDA.

NDC Product Information

Balsalazide Disodium with NDC 54868-6137 is a product labeled by Physicians Total Care, Inc.. The product's dosage form is and is administered via form. The RxNorm Crosswalk for this NDC code indicates a single RxCUI concept is associated to this product: 885857.

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.

  • AMMONIA (UNII: 5138Q19F1X)
  • SILICON DIOXIDE (UNII: ETJ7Z6XBU4)
  • FD&C BLUE NO. 1 (UNII: H3R47K3TBD)
  • FD&C RED NO. 40 (UNII: WZB9127XOA)
  • FD&C YELLOW NO. 6 (UNII: H77VEI93A8)
  • GELATIN (UNII: 2G86QN327L)
  • FERROSOFERRIC OXIDE (UNII: XM0M87F357)
  • ISOPROPYL ALCOHOL (UNII: ND2M416302)
  • MAGNESIUM STEARATE (UNII: 70097M6I30)
  • BUTYL ALCOHOL (UNII: 8PJ61P6TS3)
  • PROPYLENE GLYCOL (UNII: 6DC9Q167V3)
  • SHELLAC (UNII: 46N107B71O)
  • TITANIUM DIOXIDE (UNII: 15FIX9V2JP)

Product Labeler Information

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

Labeler Name: Physicians Total Care, Inc.
Labeler Code: 54868
Start Marketing Date: 08-18-2010 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: 12-31-2017 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: I - INACTIVATED, the listing data was inactivated by the FDA. 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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Information for Patients

Balsalazide

Balsalazide is pronounced as (bal sal' a zide)

Why is balsalazide medication prescribed?
Balsalazide is used to treat ulcerative colitis (a condition which causes swelling and sores in the lining of the colon [large intestine] and rectum). Balsalazide is an a...
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Balsalazide Disodium 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

Balsalazide Disodium Capsules are indicated for the treatment of mildly to moderately active ulcerative colitis in adults. Safety and effectiveness of Balsalazide Disodium Capsules beyond 12 weeks in adults have not been established.

2.1 Adult Dose

For treatment of active ulcerative colitis in adult patients, the usual dose is three 750 mg balsalazide capsules to be taken 3 times a day (6.75 g per day) for up to 8 weeks. Some patients in the adult clinical trials required treatment for up to 12 weeks.

2.2 Administration Alternatives

Balsalazide capsules may also be administered by carefully opening the capsule and sprinkling the capsule contents on applesauce. The entire drug/applesauce mixture should be swallowed immediately; the contents may be chewed, if necessary, since contents of balsalazide are NOT coated beads/granules. Patients should be instructed not to store any drug/applesauce mixture for future use.If the capsules are opened for sprinkling, color variation of the powder inside the capsules ranges from orange to yellow and is expected due to color variation of the active pharmaceutical ingredient.Teeth and/or tongue staining may occur in some patients who use balsalazide in sprinkle form with food.

3 Dosage Forms And Strengths

Balsalazide Disodium Capsules are available as light orange opaque capsules containing 750 mg balsalazide disodium and "54 795" imprinted in black ink on the cap and body, containing a yellow-orange powder.

4 Contraindications

Patients with hypersensitivity to salicylates or to any of the components of Balsalazide Disodium Capsules or balsalazide metabolites. Hypersensitivity reactions may include, but are not limited to the following: anaphylaxis, bronchospasm, and skin reaction.

5.1 Exacerbations Of Ulcerative Colitis

In the adult clinical trials, 3 out of 259 patients reported exacerbation of the symptoms of ulcerative colitis. Observe patients closely for worsening of these symptoms while on treatment.

5.2 Pyloric Stenosis

Patients with pyloric stenosis may have prolonged gastric retention of balsalazide capsules.

5.3 Renal

Renal toxicity has been observed in animals and patients given other mesalamine products. Therefore, caution should be exercised when administering balsalazide to patients with known renal dysfunction or a history of renal disease. [See 13 NONCLINICAL TOXICOLOGY (13.2)]

6.1 Clinical Studies Experience

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.

Adult Ulcerative Colitis

During clinical development, 259 adult patients with active ulcerative colitis were exposed to 6.75 g/day balsalazide in 4 controlled trials. In the 4 controlled clinical trials patients receiving a balsalazide dose of 6.75 g/day most frequently reported the following adverse reactions: headache (8%), abdominal pain (6%), diarrhea (5%), nausea (5%), vomiting (4%), respiratory infection (4%), and arthralgia (4%). Withdrawal from therapy due to adverse reactions was comparable among patients on balsalazide and placebo. Adverse reactions reported by 1% or more of patients who participated in the 4 well-controlled, Phase 3 trials are presented by treatment group (Table 1).The number of placebo patients (35), however, is too small for valid comparisons. Some adverse reactions, such as abdominal pain, fatigue, and nausea were reported more frequently in women than in men. Abdominal pain, rectal bleeding, and anemia can be part of the clinical presentation of ulcerative colitis.Table 1: Adverse Reactions Occurring In ≥ 1% of Adult Balsalazide Patients In Controlled Trials
Adverse ReactionBalsalazide 6.75 g/day (N=259)Placebo (N=35)Abdominal Pain16 (6%)1 (3%)Diarrhea14 (5%)1 (3%)Arthralgia9 (4%)0%Rhinitis6 (2%)0%Insomnia6 (2%)0%Fatigue6 (2%)0%Flatulence5 (2%)0%Fever5 (2%)0%Dyspepsia5 (2%)0%Pharyngitis4 (2%)0%Coughing4 (2%)0%Anorexia4 (2%)0%Urinary Tract Infection3 (1%)0%Myalgia3 (1%)0%Flu-Like Disorder3 (1%)0%Dry Mouth3 (1%)0%Cramps3 (1%)0%Constipation3 (1%)0%

6.2 Postmarketing Experience

The following adverse reactions have been identified during post-approval use of balsalazide in clinical practice: myocarditis, pericarditis, vasculitis, pruritus, pleural effusion, pneumonia (with and without eosinophilia), alveolitis, renal failure,interstitial nephritis, pancreatitis, and alopecia.Because these reactions are reported voluntarily from a population of unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These adverse reactions have been chosen for inclusion due to a combination of seriousness, frequency of reporting, or potential causal connection to balsalazide.

Hepatic

Postmarketing adverse reactions of hepatotoxicity have been reported for products which contain (or are metabolized to) mesalamine, including elevated liver function tests (SGOT/AST, SGPT/ALT, GGT, LDH, alkaline phosphatase, bilirubin), jaundice, cholestatic jaundice, cirrhosis, hepatocellular damage including liver necrosis and liver failure. Some of these cases were fatal; however, no fatalities associated with these adverse reactions were reported in balsalazide clinical trials. One case of Kawasaki-like syndrome which included hepatic function changes was also reported, however, this adverse reaction was not reported in balsalazide clinical trials.

7 Drug Interactions

In an in vitro study using human liver microsomes, balsalazide and its metabolites [5-aminosalicylic acid (5-ASA), N-acetyl-5-aminosalicylic acid (N-Ac-5-ASA), 4-aminobenzoyl-ß-alanine (4-ABA) and N-acetyl-4-aminobenzoyl-ß–alanine (N-Ac-4-ABA)] were not shown to inhibit the major CYP enzymes evaluated (CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4/5). Therefore, balsalazide and its metabolites are not expected to inhibit the metabolism of other drugs which are substrates of CYP1A2, CYP2C9, CYP2C19, CYP2D6, or CYP3A4/5.

8.1 Pregnancy

Pregnancy Category B. Reproduction studies were performed in rats and rabbits at oral doses up to 2 g/kg/day, 2.4 and 4.7 times the recommended human dose based on body surface area for the rat and rabbit, respectively, and revealed no evidence of impaired fertility or harm to the fetus due to balsalazide disodium. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

8.3 Nursing Mothers

It is not known whether balsalazide disodium is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when balsalazide is administered to a nursing woman.

8.4 Pediatric Use

Pediatric use information is protected by marketing exclusivity.

10 Overdosage

No case of overdose has occurred with balsalazide. A 3-year-old boy is reported to have ingested 2 g of another mesalamine product. He was treated with ipecac and activated charcoal with no adverse reactions.If an overdose occurs with balsalazide, treatment should be supportive, with particular attention to correction of electrolyte abnormalities.

11 Description

Each Balsalazide Disodium Capsule contains 750 mg of balsalazide disodium, a prodrug that is enzymatically cleaved in the colon to produce mesalamine (5-aminosalicylic acid or 5-ASA), an anti-inflammatory drug. Each capsule of balsalazide (750 mg) is equivalent to 267 mg of mesalamine. Balsalazide disodium has the chemical name (E)-5-[[-4-[[(2-carboxyethyl) amino]carbonyl] phenyl]azo]-2-hydroxybenzoic acid, disodium salt, dihydrate. Its structural formula is:Molecular Weight: 437.32Molecular Formula: C17H13N3O6Na2•2H2OBalsalazide disodium is a stable, odorless orange to yellow microcrystalline powder. It is freely soluble in water and isotonic saline, sparingly soluble in methanol and ethanol, and practically insoluble in all other organic solvents.Inactive Ingredients: Each hard gelatin capsule contains ammonium hydroxide, colloidal silicon dioxide, FD&C Blue #1, FD&C Red #40, FD&C Yellow #6, gelatin, iron oxide black, isopropyl alcohol, magnesium stearate, n-butyl alcohol, propylene glycol, shellac, and titanium dioxide. The sodium content of each capsule is approximately 79 mg.

12.1 Mechanism Of Action

Balsalazide disodium is delivered intact to the colon where it is cleaved by bacterial azoreduction to release equimolar quantities of mesalamine, which is the therapeutically active portion of the molecule, and the 4-aminobenzoyl-ß-alanine carrier moiety. The carrier moiety released when balsalazide disodium is cleaved is only minimally absorbed and is largely inert.The mechanism of action of 5-ASA is unknown, but appears to be local to the colonic mucosa rather than systemic. 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 chronic inflammatory bowel disease, and it is possible that 5-ASA diminishes inflammation by blocking production of arachidonic acid metabolites in the colon.

12.3 Pharmacokinetics

Balsalazide capsules contain a powder of balsalazide disodium that is insoluble in acid and designed to be delivered to the colon as the intact prodrug. Upon reaching the colon, bacterial azoreductases cleave the compound to release 5-ASA, the therapeutically active portion of the molecule, and 4-aminobenzoyl-ß-alanine. The 5-ASA is further metabolized to yield N-acetyl-5-aminosalicylic acid (N-Ac-5-ASA), a second key metabolite.

Absorption

The plasma pharmacokinetics of balsalazide and its key metabolites from a crossover study in healthy volunteers are summarized in Table 2. In this study, a single oral dose of balsalazide 2.25 g was administered to healthy volunteers as intact capsules (3 x 750 mg) under fasting conditions, as intact capsules (3 x 750 mg) after a high-fat meal, and unencapuslated (3 x 750 mg) as sprinkles on applesauce.Table 2: Plasma Pharmacokinetics for Balsalazide and Key Metabolites (5-ASA and N-Ac-5-ASA) with Administration of Balsalazide Following a Fast, a High-Fat Meal, and Drug Contents Sprinkled on Applesauce (Mean ± SD)Fasting (N=17)High-Fat Meal (N=17)Sprinkled (N=17)Cmax (mcg/mL) Balsalazide0.51 ± 0.320.45 ± 0.390.21 ± 0.12 5-ASA0.22 ± 0.120.11 ± 0.1360.29 ± 0.17 N-Ac-5-ASA0.88 ± 0.390.64 ± 0.5341.04 ± 0.57AUClast (mcg·hr/mL) Balsalazide1.35 ± 0.731.52 ± 1.010.87 ± 0.48 5-ASA2.59 ± 1.462.1 ± 2.582.99 ± 1.7 N-Ac-5-ASA17.8 ± 8.1417.7 ± 13.720 ± 11.4Tmax (h) Balsalazide0.8 ± 0.851.2 ± 1.111.6 ± 0.44 5-ASA8.2 ± 1.9822 ± 8.238.7 ± 1.99 N-Ac-5-ASA9.9 ± 2.4920.2 ± 8.9410.8 ± 5.39A relatively low systemic exposure was observed under all three administered conditions (fasting, fed with high-fat meal, sprinkled on applesauce), which reflects the variable, but minimal absorption of balsalazide disodium and its metabolites. The data indicate that both Cmax and AUClast were lower, while Tmax was markedly prolonged, under fed (high-fat meal) compared to fasted conditions. Moreover, the data suggest that dosing balsalazide disodium as a sprinkle or as a capsule provides highly variable, but relatively similar mean pharmacokinetic parameter values. No inference can be made as to how the systemic exposure differences of balsalazide and its metabolites in this study might predict the clinical efficacy under different dosing conditions (i.e., fasted, fed with high-fat meal, or sprinkled on applesauce) since clinical efficacy after balsalazide disodium administration is presumed to be primarily due to the local effects of 5-ASA on the colonic mucosa.In a separate study of adult patients with ulcerative colitis, who received balsalazide, 1.5 g twice daily, for over 1 year, systemic drug exposure, based on mean AUC values, was up to 60 times greater (0.008 mcg·hr/mL to 0.48 mcg·hr/mL) when compared to that obtained in healthy subjects who received the same dose.

Distribution

The binding of balsalazide to human plasma proteins was ≥99%.

Metabolism

The products of the azoreduction of this compound, 5-ASA and 4-aminobenzoyl-ß-alanine, and their N-acetylated metabolites have been identified in plasma, urine and feces.

Elimination

Following single-dose administration of 2.25 g balsalazide (three 750 mg capsules) under fasting conditions in healthy subjects, mean urinary recovery of balsalazide, 5-ASA, and N-Ac-5-ASA was 0.2%, 0.22% and 10.2%, respectively.In a multiple-dose study in healthy subjects receiving a balsalazide dose of two 750 mg capsules twice daily (3 g/day) for 10 days, mean urinary recovery of balsalazide, 5-ASA, and N-Ac-5-ASA was 0.1%, 0%, and 11.3%, respectively. During this study, subjects received their morning dose 0.5 hours after being fed a standard meal, and subjects received their evening dose 2 hours after being fed a standard meal.In a study with 10 healthy volunteers, 65% of a single 2.25 g dose of balsalazide was recovered as 5-ASA, 4-aminobenzoyl-ß-alanine, and the N-acetylated metabolites in feces, while <1% of the dose was recovered as parent compound.In a study that examined the disposition of balsalazide in patients who were taking 3 to 6 g of balsalazide daily for more than 1 year and who were in remission from ulcerative colitis, less than 1% of an oral dose was recovered as intact balsalazide in the urine. Less than 4% of the dose was recovered as 5-ASA, while virtually no 4-aminobenzoyl-ß-alanine was detected in urine. The mean urinary recovery of N-Ac-5-ASA and N-acetyl-4-aminobenzoyl-ß-alanine comprised <16% and <12% of the balsalazide dose, respectively. No fecal recovery studies were performed in this population.All pharmacokinetic studies with balsalazide are characterized by large variability in the plasma concentration versus time profiles for balsalazide and its metabolites, thus half-life estimates of these analytes are indeterminate.

13.1 Carcinogenesis, Mutagenesis, Impairment Of Fertility

In a 24-month rat (Sprague Dawley) carcinogenicity study, oral (dietary) balsalazide disodium at doses up to 2 g/kg/day was not tumorigenic. For a 50 kg person of average height this dose represents 2.4 times the recommended human dose on a body surface area basis. Balsalazide disodium was not genotoxic in the following in vitro or in vivo tests: Ames test, human lymphocyte chromosomal aberration test, and mouse lymphoma cell (L5178Y/TK+/-) forward mutation test, or mouse micronucleus test. However, it was genotoxic in the in vitro Chinese hamster lung cell (CH V79/HGPRT) forward mutation test.4-aminobenzoyl-ß-alanine, a metabolite of balsalazide disodium, was not genotoxic in the Ames test and the mouse lymphoma cell (L5178Y/TK+/-) forward mutation test but was positive in the human lymphocyte chromosomal aberration test. N-acetyl-4-aminobenzoyl-ß-alanine, a conjugated metabolite of balsalazide disodium, was not genotoxic in Ames test, the mouse lymphoma cell (L5178Y/TK+/-) forward mutation test, or the human lymphocyte chromosomal aberration test. Balsalazide disodium at oral doses up to 2 g/kg/day, 2.4 times the recommended human dose based on body surface area, was found to have no effect on fertility and reproductive performance in rats.

Renal Toxicity

In animal studies conducted at doses up to 2000 mg/kg (approximately 21 times the recommended 6.75 g/day dose on a mg/kg basis for a 70 kg person), balsalazide demonstrated no nephrotoxic effects in rats or dogs.

Overdosage

A single oral dose of balsalazide disodium at 5 g/kg or 4-aminobenzoyl-ß-alanine, a metabolite of balsalazide disodium, at 1 g/kg was non-lethal in mice and rats. No symptoms of acute toxicity were seen at these doses.

14.1 Adult Studies

Two randomized, double-blind studies were conducted in adults. In the first trial, 103 patients with active mild-to-moderate ulcerative colitis with sigmoidoscopy findings of friable or spontaneously bleeding mucosa were randomized and treated with balsalazide 6.75 g/day or balsalazide 2.25 g/day. The primary efficacy endpoint was reduction of rectal bleeding and improvement of at least one of the other assessed symptoms (stool frequency, patient functional assessment, abdominal pain, sigmoidoscopic grade, and physician’s global assessment [PGA]). Outcome assessment for rectal bleeding at each interim period (week 2, 4, and 8) encompassed a 4-day period (96 hours). Results demonstrated a statistically significant difference between high and low doses of balsalazide (Figure 1). Figure 1: Percentage of Patients Improved at 8 WeeksA second study, conducted in Europe, confirmed findings of symptomatic improvement.

16 How Supplied/Storage And Handling

Balsalazide Disodium Capsules are supplied as light orange opaque capsules containing 750 mg balsalazide disodium and "54 795" printed in black ink on the cap and body, containing a yellow-orange powder.Bottles of 280NDC 54868-6137-0 StorageStore 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.]

Other

Roxane Laboratories, Inc.Relabeling of "Additional" barcode label by:Physicians Total Care, Inc.Tulsa, OK       74146

17.1 Important Precautions Regarding Balsalazide

  • Instruct patients not to take balsalazide if they have a hypersensitivity to salicylates (e.g., aspirin).Patients should be instructed to contact their health care provider under the following circumstances:If they experience a worsening of their ulcerative colitis symptoms.If they are diagnosed with pyloric stenosis, because balsalazide capsules may be slow to pass through their digestive tract.If they are diagnosed with renal dysfunction. Damage to the kidney has been observed in people given medications similar to balsalazide.

17.2 What Patients Should Know About Adverse Reactions

  • In adult clinical trials the most common adverse reactions were headache, abdominal pain, diarrhea, nausea, vomiting, respiratory infection, and arthralgia.Inform patients that this listing of adverse reactions is not complete and not all adverse reactions can be anticipated. If appropriate, a more comprehensive list of adverse reactions can be discussed with patients.

17.3 What Patients Should Know About Taking Balsalazide With Other Medication

  • Based upon limited studies conducted in a test tube, balsalazide is not believed to interfere with other drugs by preventing how the liver functions. However, as the studies were limited in scope, you should always consult your doctor and discuss potential interactions prior to initiating any new drug. 10003708/04 Revised October 2010 ©RLI, 2010

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