Professional Information
Balsalazide (Systemic)
VA CLASSIFICATION
Primary: GA400
Commonly used brand name(s): Colozal.
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).
†Not commercially available in Canada.
Category:
Bowel disease (inflammatory) suppressant —
Indications
Accepted
Ulcerative colitis (treatment)—Balsalazide is indicated for the treatment of mildly to moderately active ulcerative colitis.{01}
Pharmacology/Pharmacokinetics
Physicochemical characteristics:
Molecular weight—
437.32{01}
Mechanism of action/Effect:
Mesalamine (5–aminosalicylic acid), a therapeutically active byproduct cleaved from balsalazide by bacterial azoreduction, is created in the colon and acts to diminish colon inflammation by inhibiting the production of arachidonic acid metabolites.{01}
Absorption:
Low variable; intact balsalazide is poorly absorbed systemically{01}
Protein binding:
Very high (³ 99%) {01}
Biotransformation:
Cleaved in the colon via bacterial azoreduction to 5–aminosalicylic acid (5–ASA) and 4–aminobenzoyl-beta-alanine, the inactive carrier moiety.{01}
Half-life:
Could not be determined because of the great variability in the balsalazide plasma concentration versus time profiles of the healthy subjects studies.{01}
Time to peak concentration:
Approximately 1 to 2 hours after single oral doses of 1.5 grams or 2.25 grams.{01}
Elimination:
Renal— Less than 1% of dose recovered as parent compound, 25% of dose recovered as N-acetylated metabolites.{01}
Feces— Less than 1% of dose recovered as parent compound, 65% of dose recovered as N-acetylated metabolites, 5–ASA and carrier moiety.{01}
Precautions to Consider
Cross-sensitivity and/or related problems
Patients allergic to salicylates may also be allergic to balsalazide.{01}
Carcinogenicity/Tumorigenicity
Rats given balsalazide disodium orally at doses up to 2 grams per kg of body weight per day (2.4 times the recommended human dose on a body surface area basis for a 50-kg person of average height) for 24 months did not exhibit any tumorigenic effects.{01}
Mutagenicity
Long–term studies evaluating the mutagenic potential of balsalazide disodium in humans have not been done{01}. Genotoxicity was detected in the in vitro Chinese hamster lung cell (CH V79/HGPRT) forward mutation test .{01}However, the genotoxic potential of balsalazide disodium was not demonstrated in the following tests: the Ames test, the human lymphocyte chromosomal aberration test, the mouse lymphoma cell (L5178Y/TK+/-) forward mutation test, or the mouse micronucleus test {01}. Four–aminobenzoyl–β–alanine, a metabolite of balsalazide was shown to be genotoxic in the human lymphocyte chromosomal aberration test and non–genotoxic in the Ames test and the mouse lymphoma cell (L5178Y/TK+/-) forward mutation test{01}. N–acetyl–4–aminobenzoyl–β–alanine, another metabolite of balsalazide, was not shown to be genotoxic in any of the three previously mentioned tests done on 4–aminobenzoyl–β–alanine{01}.
Pregnancy/Reproduction
Fertility—
Adequate and well-controlled studies in humans have not been done{01}. Fertility was not affected when rats and rabbits were administered balsalazide disodium at oral doses up to 2 grams per kg of body weight per day (2.4 and 4.7 times the recommended human dose based on body surface area, respectively) {01}.
Pregnancy—
Adequate and well controlled studies have not been done in humans{01}. .
No evidence of teratogenicity was found when rats and rabbits were administered up to 2 grams per kg of body weight per day (2.4 and 4.7 times the recommended human dose based on body surface area, respectively) of balsalazide disodium.{01}
FDA Pregnancy Category B.{01}
Breast-feeding
It is not known whether balsalazide is distributed into breast milk{01}.
Pediatrics
No information is available on the relationship of age to the effects of balsalazide in the pediatric population. Safety and efficacy have not been established.{01}.
Geriatrics
No information is available on the relationship of age to the effects of balsalazide in geriatric patients. However, elderly patients are more likely to have age-related renal function impairment, which may require caution in elderly patients receiving balsalazide.{01}
Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):
With physiology/laboratory test values
Alanine aminotransferase (ALT [SGPT]){01} and
Alkaline phosphatase{01} and
Aspartate aminotransferase (AST [SGOT]){01} and
Bilirubin{01} and
Gamma-glutamyl transferase (GGT){01} and
Lactate dehydrogenase (LDH){01} (enzyme elevations were reported in post marketing clinical studies{01})
Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).
Risk-benefit should be considered when the following medical problems exist
Hypersensitivity to salicylates, mesalamine, or any other components of balsalazide disodium.{01}
Pyloric stenosis{01}. (prolonged gastric retention of balsalazide capsules may occur{01})
Renal function impairment, or history of{01} (Although there have been no reports of renal toxicity in patients who have taken balsalazide or nephrotoxic effects in rats and dogs given the equivalent of 21 times the recommended human dose, other mesalamine products have been shown to cause renal toxicity in animals and patients; therefore, caution is warranted {01})
Side/Adverse Effects
Note: In clinical trials, 3 cases of exacerbation of the symptoms of colitis, possibly related to balsalazide treatment, have been reported in 259 patients receiving balsalazide at a dose of 6.75 grams per day.{01}
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
Abdominal pain {01}
diarrhea{01}
Incidence less frequent or rare
anorexia {01}(loss of appetite)
Arthralgia {01}(joint pain)
constipation {01}
coughing {01}
cramps {01}
dry mouth {01}
dyspepsia {01}(heart burn or upset stomach)
fatigue {01}
fever {01}
flatulence {01}
flu-like disorder {01}
insomnia {01}(trouble sleeping or getting to sleep)
jaundice{01} (yellowish skin)
myalgia {01}(muscle pain)
pharyngitis {01}(flu–like symptoms )
rhinitis {01}( stuffy nose)
urinary tract infection {01}(blood in urine; lower back pain; pain or burning while urinating)
Note: In post marketing studies, hepatotoxicity, including jaundice, elevated liver function tests, and hepatocellular damage, have been reported. Although some of these cases were fatal, no fatalities were found in these events.{01}
Overdose
For more information on the management of overdose or unintentional ingestion, contact a poison control center (see Poison Control Center Listing).
Treatment of overdose
There are no reported cases of an overdose with balsalazide disodium. However, a 3-year-old boy who ingested 2 grams of another mesalamine product was treated with ipecac and activated charcoal with no adverse reactions.{01} If an overdose does occur, treatment should be primarily symptomatic and supportive with special attention paid to the correction of electrolyte levels.{01}
Supportive care—Patients in whom overdose is confirmed or suspected should be referred for psychiatric consultation.
Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Balsalazide (Systemic).
In providing consultation, consider emphasizing the following selected information (» = major clinical significance):
Before using this medication
» Conditions affecting use, especially:
Sensitivity to balsalazide, balsalazide metabolites, or salicylates
Proper use of this medication
» Proper dosing
Taking as soon as possible; not taking if almost time for next scheduled dose; not doubling doses
Proper storage
Precautions while using this medication
» Regular visits to physician to check progress
» Contacting physician if condition gets worse
For oral dosing forms:
The recommended dose, frequency, and length of treatment should not be exceeded. {01}.
Oral Dosage Forms
BALSALAZIDE DISODIUM CAPSULES
Usual Adult Dose
Ulcerative colitis , active (treatment)
Oral, three 750-mg balsalazide capsules three times a day for a total daily dose of 6.75 grams for a duration of eight weeks. Treatment may last up to twelve weeks in some patients.{01}
Usual adult prescribing limits
The safety and effectiveness of balsalazide disodium treatments over a period of time greater than 12 weeks has not been established.{01}
Usual Pediatric Dose
Safety and efficacy have not been established.{01}
Usual Geriatric Dose
See Usual adult dose.
Strength(s) usually available
U.S.—
750 milligram (Rx) [Colozal ( colloidal silicon dioxide) (magnesium stearate)]
Packaging and storage:
Store at 25 °C (77 °F), excursions permitted to 15°C–30°C (59°F–86°F){01}
Developed: 11/10/2000
References
- Product Information: Colazal™, balsalazide disodium. Salix Pharmaceuticals, Palo Alto, CA, (PI revised 7/2000) reviewed 10/2000.
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