Medication

INDICATIONS AND USAGE To reduce the development of drug-resistant bacteria and maintain the effectiveness of sulfamethoxazole and trimethoprim tablets, USP and other antibacterial drugs, sulfamethoxazole and trimethoprim tablets, USP should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy. Urinary Tract Infections: For the treatment of urinary tract infections due to susceptible strains of the following organisms: Escherichia coli , Klebsiella species, Enterobacter species, Morganella morganii , Proteus mirabilis and Proteus vulgaris . It is recommended that initial episodes of uncomplicated urinary tract infections be treated with a single effective antibacterial agent rather than the combination. Acute Otitis Media: For the treatment of acute otitis media in pediatric patients due to susceptible strains of Streptococcus pneumoniae or Haemophilus influenzae when in the judgment of the physician sulfamethoxazole and trimethoprim offers some advantage over the use of other antimicrobial agents. To date, there are limited data on the safety of repeated use of sulfamethoxazole and trimethoprim in pediatric patients under two years of age. Sulfamethoxazole and trimethoprim is not indicated for prophylactic or prolonged administration in otitis media at any age. Acute Exacerbations of Chronic Bronchitis in Adults: For the treatment of acute exacerbations of chronic bronchitis due to susceptible strains of Streptococcus pneumoniae or Haemophilus influenzae when a physician deems that sulfamethoxazole and trimethoprim could offer some advantage over the use of a single antimicrobial agent. Shigellosis: For the treatment of enteritis caused by susceptible strains of Shigella flexneri and Shigella sonnei when antibacterial therapy is indicated. Pneumocystis jiroveci Pneumonia: For the treatment of documented Pneumocystis jiroveci pneumonia and for prophylaxis against P. jiroveci pneumonia in individuals who are immunosuppressed and considered to be at an increased risk of developing P. jiroveci pneumonia. Traveler’s Diarrhea in Adults: For the treatment of traveler’s diarrhea due to susceptible strains of enterotoxigenic E. coli .

DOSAGE AND ADMINISTRATION Sulfamethoxazole and trimethoprim tablets, USP are contraindicated in pediatric patients less than 2 months of age. Urinary Tract Infections and Shigellosis in Adults and Pediatric Patients, and Acute Otitis Media in Children: Adults: The usual adult dosage in the treatment of urinary tract infections is 1 sulfamethoxazole and trimethoprim DS (double strength) tablet, USP or 2 sulfamethoxazole and trimethoprim tablets, USP every 12 hours for 10 to 14 days. An identical daily dosage is used for 5 days in the treatment of shigellosis. Children: The recommended dose for children with urinary tract infections or acute otitis media is 40 mg/kg sulfamethoxazole, USP and 8 mg/kg trimethoprim, USP per 24 hours, given in two divided doses every 12 hours for 10 days. An identical daily dosage is used for 5 days in the treatment of shigellosis. The following table is a guideline for the attainment of this dosage: Children 2 months of age or older: Weight Dose – every 12 hours lb kg Tablets 22 10 - 44 20 1 66 30 1 ½ 88 40 2 or 1 DS tablet For Patients with Impaired Renal Function: When renal function is impaired, a reduced dosage should be employed using the following table: Creatinine Clearance (mL/min) Recommended Dosage Regimen Above 30 Usual standard regimen 15 to 30 1/2 the usual regimen Below 15 Use not recommended Acute Exacerbations of Chronic Bronchitis in Adults: The usual adult dosage in the treatment of acute exacerbations of chronic bronchitis is 1 sulfamethoxazole and trimethoprim double strength tablet, USP, or 2 sulfamethoxazole and trimethoprim single strength tablets, USP, every 12 hours for 14 days. Pneumocystis Jiroveci Pneumonia Treatment: Adults and Children: The recommended dosage for treatment of patients with documented Pneumocystis jiroveci pneumonia is 75 to 100 mg/kg sulfamethoxazole, USP and 15 to 20 mg/kg trimethoprim, USP per 24 hours given in equally divided doses every 6 hours for 14 to 21 days. 11 The following table is a guideline for the upper limit of this dosage: Weight Dose – every 6 hours lb kg Tablets 18 8 - 35 16 1 53 24 1 ½ 70 32 2 or 1 DS tablet 88 40 2 ½ 106 48 3 or 1 ½ DS tablets 141 64 4 or 2 DS tablets 176 80 5 or 2 ½ DS tablets For the lower limit dose (75 mg/kg sulfamethoxazole, USP and 15 mg/kg trimethoprim, USP per 24 hours) administer 75% of the dose in the above table. Prophylaxis Adults: The recommended dosage for prophylaxis in adults is 1 sulfamethoxazole and trimethoprim DS (double strength) tablet, USP daily. 12 Children: For children, the recommended dose is 750 mg/m 2 /day sulfamethoxazole, USP with 150 mg/m 2 /day trimethoprim, USP given orally in equally divided doses twice a day, on 3 consecutive days per week. The total daily dose should not exceed 1600 mg sulfamethoxazole, USP and 320 mg trimethoprim, USP. 13 The following table is a guideline for the attainment of this dosage in children: Body Surface Area Dose – every 12 hours (m 2 ) Tablets 0.26 - 0.53 ½ 1.06 1 Traveler’s Diarrhea in Adults: For the treatment of traveler’s diarrhea, the usual adult dosage is 1 sulfamethoxazole and trimethoprim DS (double strength) tablet, USP or 2 sulfamethoxazole and trimethoprim single strength tablets, USP every 12 hours for 5 days.

ADVERSE REACTIONS The most common adverse effects are gastrointestinal disturbances (nausea, vomiting, anorexia) and allergic skin reactions (such as rash and urticaria). FATALITIES ASSOCIATED WITH THE ADMINISTRATION OF SULFONAMIDES, ALTHOUGH RARE, HAVE OCCURRED DUE TO SEVERE REACTIONS, INCLUDING STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS, FULMINANT HEPATIC NECROSIS, AGRANULOCYTOSIS, APLASTIC ANEMIA AND OTHER BLOOD DYSCRASIAS (SEE WARNINGS SECTION). Hematologic : Agranulocytosis, aplastic anemia, thrombocytopenia, leukopenia, neutropenia, hemolytic anemia, megaloblastic anemia, hypoprothrombinemia, methemoglobinemia, eosinophilia. Allergic Reactions : Stevens-Johnson syndrome, toxic epidermal necrolysis, anaphylaxis, allergic myocarditis, erythema multiforme, exfoliative dermatitis, angioedema, drug fever, chills, Henoch-Schoenlein purpura, serum sickness-like syndrome, generalized allergic reactions, generalized skin eruptions, photosensitivity, conjunctival and scleral injection, pruritus, urticaria and rash. In addition, periarteritis nodosa and systemic lupus erythematosus have been reported. Gastrointestinal : Hepatitis (including cholestatic jaundice and hepatic necrosis), elevation of serum transaminase and bilirubin, pseudomembranous enterocolitis, pancreatitis, stomatitis, glossitis, nausea, emesis, abdominal pain, diarrhea, anorexia. Genitourinary : Renal failure, interstitial nephritis, BUN and serum creatinine elevation, toxic nephrosis with oliguria and anuria, crystalluria and nephrotoxicity in association with cyclosporine. Metabolic and Nutritional : Hyperkalemia, hyponatremia (see PRECAUTIONS: Electrolyte Abnormalities ). Neurologic : Aseptic meningitis, convulsions, peripheral neuritis, ataxia, vertigo, tinnitus, headache. Psychiatric : Hallucinations, depression, apathy, nervousness. Endocrine : The sulfonamides bear certain chemical similarities to some goitrogens, diuretics (acetazolamide and the thiazides) and oral hypoglycemic agents. Cross-sensitivity may exist with these agents. Diuresis and hypoglycemia have occurred rarely in patients receiving sulfonamides. Musculoskeletal : Arthralgia and myalgia. Isolated cases of rhabdomyolysis have been reported with sulfamethoxazole and trimethoprim, mainly in AIDS patients. Respiratory : Cough, shortness of breath and pulmonary infiltrates (see WARNINGS ). Miscellaneous : Weakness, fatigue, insomnia. Postmarketing Experience The following adverse reactions have been identified during post-approval use of trimethoprim-sulfamethoxazole. Because these reactions were reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure: Thrombotic thrombocytopenia purpura Idiopathic thrombocytopenic purpura QT prolongation resulting in ventricular tachycardia and torsade de pointes