Sulfasalazine 500 mg Tablet, 30-count — NDC 70518-1829-3 (Billing 70518-1829-03)

WARNINGS Hepatic, Renal, and Hematologic Toxicity or Other Conditions 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. Discontinue sulfasalazine tablets if renal function deteriorates while on therapy.

Oligospermia and Infertility Oligospermia and infertility have been observed in men treated with sulfasalazine; however, withdrawal of the drug appears to reverse these effects. Serious Infections 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. Hypersensitivity Reactions 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.

Severe Cutaneous Adverse Reactions Drug Reactions with Eosinophilia and Systemic Symptoms (DRESS) Severe, life-threatening, systemic hypersensitivity reactions such as drug reaction with eosinophilia and systemic symptoms (DRESS) 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, evaluate the patient immediately.

Discontinue sulfasalazine tablets if an alternative etiology for the signs or symptoms cannot be established. Other Severe Cutaneous Adverse Reactions Other severe cutaneous adverse reactions, including exfoliative dermatitis, Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP) have been reported in association with the use of sulfasalazine (see ADVERSE REACTIONS ). Severe cutaneous adverse reactions can be serious and are sometimes fatal.

Patients are at highest risk for these events early in therapy, with most events occurring within the first month of treatment. Discontinue sulfasalazine tablets at the first appearance of signs or symptoms of severe cutaneous adverse reactions or other signs of hypersensitivity and consider further evaluation.

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 sulfasalazine tablets are administered. Less common or rare adverse reactions include: Blood dyscrasias: aplastic anemia, agranulocytosis, leukopenia, megaloblastic (macrocytic) anemia, purpura, thrombocytopenia, hypoprothrombinemia, methemoglobinemia, congenital neutropenia, and myelodysplastic syndrome.

Hypersensitivity reactions: erythema multiforme, epidermal necrolysis (SJS/TEN) with corneal damage, exfoliative dermatitis, DRESS, anaphylaxis, serum sickness syndrome, interstitial lung disease, pneumonitis with or without eosinophilia, vasculitis, fibrosing alveolitis, pleurisy/pleuritis, pericarditis with or without tamponade, allergic myocarditis, polyarteritis nodosa, lupus erythematosus-like syndrome, hepatitis and hepatic necrosis with or without immune complexes, fulminant hepatitis, sometimes leading to liver transplantation, parapsoriasis varioliformis acuta (Mucha-Haberman syndrome), rhabdomyolysis, photosensitization, arthralgia, periorbital edema, conjunctival and scleral injection, and alopecia.

Gastrointestinal reactions: hepatitis, hepatic failure, pancreatitis, bloody diarrhea, impaired folic acid absorption, impaired digoxin absorption, stomatitis, diarrhea, abdominal pains, and neutropenic enterocolitis. Central nervous system reactions: transverse myelitis, convulsions, meningitis, transient lesions of the posterior spinal column, cauda equina syndrome, Guillian-Barre syndrome, peripheral neuropathy, mental depression, vertigo, hearing loss, insomnia, ataxia, hallucinations, tinnitus, and drowsiness. Renal reactions: toxic nephrosis with oliguria and anuria, nephritis, nephrotic syndrome, urinary tract infections, hematuria, crystalluria, proteinuria, and hemolytic-uremic syndrome.

Other reactions: urine discoloration and skin discoloration. 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. Postmarketing Reports The following events have been identified during post-approval use of products which contain (or are metabolized to) mesalamine in clinical practice.

Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events have been chosen for inclusion due to a combination of seriousness, frequency of reporting, or potential causal connection to mesalamine: Blood dyscrasias: pseudomononucleosis Cardiac disorders: myocarditis Hepatobiliary disorders: reports of hepatotoxicity, including elevated liver function tests (SGOT/AST, SGPT/ALT, GGT, LDH, alkaline phosphatase, bilirubin), jaundice, cholestatic jaundice, cirrhosis, hepatitis cholestatic, cholestasis and possible hepatocellular damage including liver necrosis and liver failure.

Some of these cases were fatal. One case of Kawasaki-like syndrome, which included hepatic function… [Excerpted — this section continues on DailyMed.]

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

Drug/Laboratory Test Interactions: Several reports of possible interference with measurements, by liquid chromatography, of urinary normetanephrine causing a false-positive test result have been observed in patients exposed to sulfasalazine or its metabolite, mesalamine/mesalazine. Sulfasalazine or its metabolite, sulfapyridine, may interfere with ultraviolet absorbance, particularly at 340 nm, and may cause interference with some laboratory assays that use nicotinamide adenine dinucleotide [NAD(H)] or nicotinamide adenine dinucleotide phosphate [NADP(H)] to measure ultraviolet absorbance around that wavelength.

Examples of such assays may include alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine kinase-muscle/brain (CK-MB), ammonia, thyroxine or glucose. Erroneous laboratory results may be observed in patients receiving higher than recommended dosages of sulfasalazine.

PRECAUTIONS General: Sulfasalazine tablets should be given with caution to patients with severe allergy or bronchial asthma. Adequate fluid intake must be maintained in order to prevent crystalluria and stone formation. Patients with glucose-6 phosphate dehydrogenase deficiency should be observed closely for signs of hemolytic anemia.

This reaction is frequently dose related. If toxic or hypersensitivity reactions occur, the drug should be discontinued immediately. 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 tablets 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. Repackaged By / Distributed By: RemedyRepack Inc.

625 Kolter Drive, Indiana, PA 15701 (724) 465-8762 Laboratory Tests: Complete blood counts, including differential white cell count, and liver function tests, should be performed before starting 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 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. Drug Interactions: Reduced absorption of folic acid and digoxin have been reported when those agents were administered concomitantly with sulfasalazine. Drug/Laboratory Test Interactions: Several reports of possible interference with measurements, by liquid chromatography, of urinary normetanephrine causing a false-positive test result have been observed in patients exposed to sulfasalazine or its metabolite, mesalamine/mesalazine.

Sulfasalazine or its metabolite, sulfapyridine, may interfere with ultraviolet absorbance, particularly at 340 nm, and may cause interference with some laboratory assays that use nicotinamide adenine dinucleotide [NAD(H)] or nicotinamide adenine dinucleotide phosphate [NADP(H)] to measure ultraviolet absorbance around that wavelength. Examples of such assays may include alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine kinase-muscle/brain (CK-MB), ammonia, thyroxine or glucose. Erroneous laboratory results may be observed in patients receiving higher than recommended dosages of sulfasalazine.

Carcinogenesis, Mutagenesis, Impairment of Fertility: 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 2 ), 168 (991 mg/m 2 ), and 337.5 (1991 mg/m 2 ) 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 2 ), 1350 (4050 mg/m 2 ), and 2700 (8100 mg/m 2 ) 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. Sulfa… [Excerpted — this section continues on DailyMed.]

DRUG ABUSE AND DEPENDENCE None reported.