Balsalazide Disodium (Page 3 of 3)

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 NONCLINICAL TOXICOLOGY

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.

13.2 Animal Toxicology and/or Pharmacology

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 CLINICAL STUDIES

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 Weeks

figure 1
(click image for full-size original)

A 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 280
NDC 54868-6137-0

Storage

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.]

Roxane Laboratories, Inc.

Relabeling of “Additional” barcode label by:
Physicians Total Care, Inc.
Tulsa, OK 74146

17 PATIENT COUNSELING INFORMATION

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

PRINCIPAL DISPLAY PANEL

Balsalazide Disodium Capsules, 750 mg

NDC 54868-6137-0

image of package label
(click image for full-size original)
BALSALAZIDE DISODIUM
balsalazide disodium capsule
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:54868-6137(NDC:0054-0079)
Route of Administration ORAL DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
BALSALAZIDE DISODIUM (BALSALAZIDE) BALSALAZIDE DISODIUM 750 mg
Inactive Ingredients
Ingredient Name Strength
AMMONIA
SILICON DIOXIDE
FD&C BLUE NO. 1
FD&C RED NO. 40
FD&C YELLOW NO. 6
GELATIN
FERROSOFERRIC OXIDE
ISOPROPYL ALCOHOL
MAGNESIUM STEARATE
BUTYL ALCOHOL
PROPYLENE GLYCOL
SHELLAC
TITANIUM DIOXIDE
Product Characteristics
Color orange Score no score
Shape CAPSULE Size 1mm
Flavor Imprint Code 54;795
Contains
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:54868-6137-0 280 CAPSULE (CAPSULE) in 1 BOTTLE None
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA077806 08/18/2010
Labeler — Physicians Total Care, Inc. (194123980)
Establishment
Name Address ID/FEI Operations
Physicians Total Care, Inc. 194123980 relabel

Revised: 05/2010 Physicians Total Care, Inc.

Page 3 of 3 1 2 3

All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.

This site is provided for educational and informational purposes only, in accordance with our Terms of Use, and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.

Privacy Policy | Copyright © 2024. All Rights Reserved.