Sulfasalazine 500 MG Oral Tablet

Generic Name: SULFASALAZINE
Brand Name: Sulfasalazine
  • Substance Name(s):
  • SULFASALAZINE

WARNINGS

Only after critical appraisal should 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 sulfasalazine (see PRECAUTIONS, Laboratory Tests ).

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.

Serious infections, including fatal sepsis and pneumonia, have been reported.

Some infections were associated with agranulocytosis, neutropenia, or myelosuppression.

Discontinue sulfasalazine if a patient develops a serious infection.

Closely monitor patients for the development of signs and symptoms of infection during and after treatment with sulfasalazine.

For a patient who develops a new infection during treatment with sulfasalazine, perform a prompt and complete diagnostic workup for infection and myelosuppression.

Caution should be exercised when considering the use of sulfasalazine in patients with a history of recurring or chronic infections or with underlying conditions or concomitant drugs which may predispose patients to infections.

Severe hypersensitivity reactions may include internal organ involvement, such as hepatitis, nephritis, myocarditis, mononucleosis-like syndrome (i.e., pseudomononucleosis), hematological abnormalities (including hematophagic histiocytosis), and/or pneumonitis including eosinophilic infiltration.

Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported in association with the use of sulfasalazine.

Patients are at highest risk for these events early in therapy, with most events occurring within the first month of treatment.

Sulfasalazine should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.

Severe, life-threatening, systemic hypersensitivity reactions such as drug rash with eosinophilia and systemic symptoms have been reported in patients taking sulfasalazine.

Early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident.

If such signs or symptoms are present, the patient should be evaluated immediately.

Sulfasalazine should be discontinued if an alternative etiology for the signs or symptoms cannot be established.

DRUG INTERACTIONS

Drug Interactions: Reduced absorption of folic acid and digoxin have been reported when those agents were administered concomitantly with 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 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.

Instructions for Overdosage: Gastric lavage or emesis plus catharsis as indicated.

Alkalinize urine.

If kidney function is normal, force fluids.

If anuria is present, restrict fluids and salt, and treat appropriately.

Catheterization of the ureters may be indicated for complete renal blockage by crystals.

The low molecular weight of sulfasalazine and its metabolites may facilitate their removal by dialysis.

DESCRIPTION

Sulfasalazine Tablets USP, 500 mg for oral administration.

Therapeutic Classification: Anti-inflammatory agent.

Chemical Designation: 5-([ p-(2-Pyridylsulfamoyl)phenyl]azo) salicylic acid.

Structural Formula: This is an image of the structural formula for sulfasalazine.

Inactive Ingredients: corn starch, croscarmellose sodium, magnesium stearate, microcrystalline cellulose, povidone, pregelatinized starch, and talc.

HOW SUPPLIED

Sulfasalazine Tablets USP, 500 mg are round, gold-colored, scored tablets, debossed “5904” and “V” on one side and plain on the reverse side.

They are available in the following package sizes: Bottles of 100: 0603-5801-21 Bottles of 180: 0603-5801-04 Bottles of 500: 0603-5801-28 Bottles of 1000: 0603-5801-32 Storage: Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].

GERIATRIC USE

Elderly: Elderly patients with rheumatoid arthritis showed a prolonged plasma half-life for SSZ, SP, and their metabolites.

The clinical impact of this is unknown.

INDICATIONS AND USAGE

Sulfasalazine tablets, USP are indicated: in the treatment of mild to moderate ulcerative colitis, and as adjunctive therapy in severe ulcerative colitis; and for the prolongation of the remission period between acute attacks of ulcerative colitis.

PEDIATRIC USE

Pediatric: Small studies have been reported in the literature in children down to the age of 4 years with ulcerative colitis and inflammatory bowel disease.

In these populations, relative to adults, the pharmacokinetics of SSZ and SP correlated poorly with either age or dose.

PREGNANCY

Pregnancy: Teratogenic Effects: Pregnancy Category B: There are no adequate and well-controlled studies of sulfasalazine in pregnant women.

Reproduction studies have been performed in rats and rabbits at doses up to 6 times the human maintenance dose of 2 g/day based on body surface area and have revealed no evidence of impaired female fertility or harm to the fetus due to sulfasalazine.

Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

There have been case reports of neural tube defects (NTDs) in infants born to mothers who were exposed to sulfasalazine during pregnancy, but the role of sulfasalazine in these defects has not been established.

However, oral sulfasalazine inhibits the absorption and metabolism of folic acid which may interfere with folic acid supplementation (see Drug Interactions) and diminish the effect of periconceptional folic acid supplementation that has been shown to decrease the risk of NTDs.

A national survey evaluated the outcome of pregnancies associated with inflammatory bowel disease (IBD).

In a group of 186 women treated with sulfasalazine alone or sulfasalazine and concomitant steroid therapy, the incidence of fetal morbidity and mortality was comparable to that for 245 untreated IBD pregnancies as well as to pregnancies in the general population.

1 A study of 1,455 pregnancies associated with exposure to sulfonamides indicated that this group of drugs, including sulfasalazine, did not appear to be associated with fetal malformation.

2 A review of the medical literature covering 1,155 pregnancies in women with ulcerative colitis suggested that the outcome was similar to that expected in the general population.

3 No clinical studies have been performed to evaluate the effect of sulfasalazine on the growth development and functional maturation of children whose mothers received the drug during pregnancy.

Clinical Considerations: Sulfasalazine and its metabolite, sulfapyridine, pass through the placenta.

Sulfasalazine and its metabolite are also present in human milk.

In the newborn, sulfonamides compete with bilirubin for binding sites on the plasma proteins and may cause kernicterus.

Although sulfapyridine has been shown to have a poor bilirubin-displacing capacity, monitor the newborn for the potential for kernicterus.

A case of agranulocytosis has been reported in an infant whose mother was taking both sulfasalazine and prednisone throughout pregnancy.

NUSRING MOTHERS

Nursing Mothers: Sulfonamides, including sulfasalazine, are present in human milk (see Pregnancy, Clinical Considerations).

Insignificant amounts of sulfasalazine have been found in milk, whereas levels of the active metabolite sulfapyridine in milk are about 30 to 60 percent of those in the maternal serum.

Caution should be exercised when sulfasalazine is administered to a nursing mother.

There are reports with limited data of bloody stools or diarrhea in human milk fed infants of mothers taking sulfasalazine.

In cases where the outcome was reported, bloody stools or diarrhea resolved in the infant after discontinuation of sulfasalazine in the mother or discontinuation of breastfeeding.

Due to limited data, a causal relationship between sulfasalazine exposure and bloody stools or diarrhea cannot be confirmed or denied.

Monitor human milk fed infants of mothers taking sulfasalazine for signs and symptoms of diarrhea and/or bloody stools.

INFORMATION FOR PATIENTS

Information for Patients: Patients should be informed of the possibility of adverse reactions and of the need for careful medical supervision.

The occurrence of sore throat, fever, pallor, purpura, or jaundice may indicate a serious blood disorder.

Should any of these occur, the patient should seek medical advice.

They should also be made aware that ulcerative colitis rarely remits completely, and that the risk of relapse can be reduced by continued administration of sulfasalazine at a maintenance dosage.

Patients should be instructed to take sulfasalazine in evenly divided doses preferably after meals.

Additionally, patients should be advised that sulfasalazine may produce an orange-yellow discoloration of the urine or skin.

INACTIVE INGREDIENTS

Inactive Ingredients: corn starch, croscarmellose sodium, magnesium stearate, microcrystalline cellulose, povidone, pregelatinized starch, and talc.

DOSAGE AND ADMINISTRATION

The dosage of sulfasalazine tablets should be adjusted to each individual’s response and tolerance.

Initial Therapy: 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.

Maintenance Therapy: 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 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 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 sulfasalazine, they are probably due to increased serum levels of total sulfapyridine and may be alleviated by halving the daily dose of 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, 4 7 of 8 patients, 5 and 19 of 20 patients.

6 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, 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.