Azulfidine Information
Azulfidine (Sulfasalazine) Description
Azulfidine (Sulfasalazine) Tablets contain sulfasalazine, 500 mg, for oral administration.
Azulfidine (Sulfasalazine) Indications And Usage
Azulfidine (Sulfasalazine) Tablets are indicated:
Azulfidine (Sulfasalazine) Contraindications
Azulfidine (Sulfasalazine) Tablets are contraindicated in:
Azulfidine (Sulfasalazine) Warnings
Only after critical appraisal should Azulfidine (Sulfasalazine) Tablets be given to patients with hepatic or renal damage or blood dyscrasias. Deaths associated with the administration of sulfasalazine have been reported from hypersensitivity reactions, agranulocytosis, aplastic anemia, other blood dyscrasias, renal and liver damage, irreversible neuromuscular and central nervous system changes, and fibrosing alveolitis. The presence of clinical signs such as sore throat, fever, pallor, purpura, or jaundice may be indications of serious blood disorders or hepatotoxicity. Complete blood counts, as well as urinalysis with careful microscopic examination, should be done frequently in patients receiving Azulfidine (Sulfasalazine) (see ). Discontinue treatment with sulfasalazine while awaiting the results of blood tests. Oligospermia and infertility have been observed in men treated with sulfasalazine; however, withdrawal of the drug appears to reverse these effects.
Azulfidine (Sulfasalazine) Precautions
Complete blood counts, including differential white cell count and liver function tests, should be performed before starting Azulfidine (Sulfasalazine) and every second week during the first three months of therapy. During the second three months, the same tests should be done once monthly and thereafter once every three months, and as clinically indicated. Urinalysis and an assessment of renal function should also be done periodically during treatment with Azulfidine (Sulfasalazine) .
The determination of serum sulfapyridine levels may be useful since concentrations greater than 50 µg/mL appear to be associated with an increased incidence of adverse reactions.
Two-year oral carcinogenicity studies were conducted in male and female F344/N rats and B6C3F1 mice. Sulfasalazine was tested at 84 (496 mg/m), 168 (991 mg/m), and 337.5 (1991 mg/m) mg/kg/day doses in rats. A statistically significant increase in the incidence of urinary bladder transitional cell papillomas was observed in male rats. In female rats, two (4%) of the 337.5 mg/kg rats had transitional cell papilloma of the kidney. The increased incidence of neoplasms in the urinary bladder and kidney of rats was also associated with an increase in the renal calculi formation and hyperplasia of transitional cell epithelium. For the mouse study, sulfasalazine was tested at 675 (2025 mg/m), 1350 (4050 mg/m), and 2700 (8100 mg/m) mg/kg/day. The incidence of hepatocellular adenoma or carcinoma in male and female mice was significantly greater than the control at all doses tested.
Sulfasalazine did not show mutagenicity in the bacterial reverse mutation assay (Ames test) and in L51784 mouse lymphoma cell assay at the HGPRT gene. However, sulfasalazine showed equivocal mutagenic response in the micronucleus assay of mouse and rat bone marrow and mouse peripheral RBC and in the sister chromatid exchange, chromosomal aberration, and micronucleus assays in lymphocytes obtained from humans.
Impairment of male fertility was observed in reproductive studies performed in rats at a dose of 800 mg/kg/day (4800 mg/m). Oligospermia and infertility have been described in men treated with sulfasalazine. Withdrawal of the drug appears to reverse these effects.
Azulfidine (Sulfasalazine) Adverse Reactions
The most common adverse reactions associated with sulfasalazine are anorexia, headache, nausea, vomiting, gastric distress, and apparently reversible oligospermia. These occur in about one-third of the patients. Less frequent adverse reactions are skin rash, pruritus, urticaria, fever, Heinz body anemia, hemolytic anemia, and cyanosis, which may occur at a frequency of one in every thirty patients or less. Experience suggests that with a daily dosage of 4 g or more, or total serum sulfapyridine levels above 50 µg/mL, the incidence of adverse reactions tends to increase.
Although the listing which follows includes a few adverse reactions which have not been reported with this specific drug, the pharmacological similarities among the sulfonamides require that each of these reactions be considered when Azulfidine (Sulfasalazine) Tablets are administered. Less common or rare adverse reactions include:
The sulfonamides bear certain chemical similarities to some goitrogens, diuretics (acetazolamide and the thiazides), and oral hypoglycemic agents. Goiter production, diuresis and hypoglycemia have occurred rarely in patients receiving sulfonamides. Cross-sensitivity may exist with these agents. Rats appear to be especially susceptible to the goitrogenic effects of sulfonamides and long-term administration has produced thyroid malignancies in this species.
Azulfidine (Sulfasalazine) Drug Abuse And Dependence
Azulfidine (Sulfasalazine) Overdosage
There is evidence that the incidence and severity of toxicity following overdosage are directly related to the total serum sulfapyridine concentration. Symptoms of overdosage may include nausea, vomiting, gastric distress, and abdominal pains. In more advanced cases, central nervous system symptoms such as drowsiness, convulsions, etc., may be observed. Serum sulfapyridine concentrations may be used to monitor the progress of recovery from overdosage.
There are no documented reports of deaths due to ingestion of large single doses of sulfasalazine.
Doses of Azulfidine (Sulfasalazine) tablets of 16 g per day have been given to patients without mortality. A single oral dose of 12 g/kg was not lethal to mice.
Azulfidine (Sulfasalazine) Dosage And Administration
The dosage of Azulfidine (Sulfasalazine) Tablets should be adjusted to each individual's response and tolerance.
Adults: 3 to 4 g daily in evenly divided doses with dosage intervals not exceeding eight hours. In some cases, it is advisable to initiate therapy with a smaller dosage, e.g., 1 to 2 g daily, to reduce possible gastrointestinal intolerance. If daily doses exceeding 4 g are required to achieve desired effects, the increased risk of toxicity should be kept in mind.
Children, six years of age and older: 40 to 60 mg/kg body weight in each 24-hour period, divided into 3 to 6 doses.
Adults: 2 g daily.
Children, six years of age and older: 30 mg/kg body weight in each 24-hour period, divided into 4 doses.
The response of acute ulcerative colitis to Azulfidine (Sulfasalazine) Tablets can be evaluated by clinical criteria, including the presence of fever, weight changes, and degree and frequency of diarrhea and bleeding, as well as by sigmoidoscopy and the evaluation of biopsy samples. It is often necessary to continue medication even when clinical symptoms, including diarrhea, have been controlled. When endoscopic examination confirms satisfactory improvement, the dosage of Azulfidine (Sulfasalazine) should be reduced to a maintenance level. If diarrhea recurs, the dosage should be increased to previously effective levels. If symptoms of gastric intolerance (anorexia, nausea, vomiting, etc.) occur after the first few doses of Azulfidine (Sulfasalazine) , they are probably due to increased serum levels of total sulfapyridine and may be alleviated by halving the daily dose of Azulfidine (Sulfasalazine) and subsequently increasing it gradually over several days. If gastric intolerance continues, the drug should be stopped for 5 to 7 days, then reintroduced at a lower daily dose.
Some patients may be sensitive to treatment with sulfasalazine. Various desensitization-like regimens have been reported to be effective in 34 of 53 patients, 7 of 8 patients, and 19 of 20 patients. These regimens suggest starting with a total daily dose of 50 to 250 mg sulfasalazine initially, and doubling it every 4 to 7 days until the desired therapeutic level is achieved. If the symptoms of sensitivity recur, Azulfidine (Sulfasalazine) should be discontinued. Desensitization should not be attempted in patients who have a history of agranulocytosis, or who have experienced an anaphylactoid reaction while previously receiving sulfasalazine.
Azulfidine (Sulfasalazine) How Supplied
Azulfidine (Sulfasalazine) Tablets, 500 mg, are round, gold-colored, scored tablets, monogrammed "101" on one side and "KPh" on the other. They are available in the following package sizes:
Bottles of 100 NDC 0013-0101-01 Bottles of 300 NDC 0013-0101-20 Unit Dose (100) NDC 0013-0101-11
Store at 25° C (77° F); excursions permitted to 15–30° C (59–86° F) [see USP Controlled Room Temperature].
Sulfasalazine is also available as Azulfidine (Sulfasalazine) EN-tabs brand of sulfasalazine delayed release tablets, USP, 500 mg, in the following package sizes:
Bottles of 100 NDC 0013-0102-01 Bottles of 300 NDC 0013-0102-20
Azulfidine (Sulfasalazine)
Azulfidine (Sulfasalazine) Principal Display Panel - Mg Tablet Bottle
