sulfadiazine

Available forms
Available by prescription only
Tablets: 500 mg

Indications and dosages
 Urinary tract infection. Adults: Initially, 2 to 4 g P.O.; then 2 to 4 g daily in three to six divided doses.
Children age 2 months and older: Initially, 75 mg/kg or 2 g/m² P.O.; then 150 mg/kg daily P.O. in four to six divided doses. Maximum daily dose, 6 g.
 Rheumatic fever prophylaxis, as an alternative to penicillin. Children who weigh more than 30 kg (66 lb): 1 g P.O. daily.
Children who weigh less than 30 kg: 500 mg P.O. daily.
 Adjunctive treatment in toxoplasmosis. Adults: 1 to 1.5 g P.O. q.i.d. for 3 to 4 weeks; given with pyrimethamine.
Children: 100 to 200 mg/kg P.O. daily in divided doses q 6 hours for 3 to 4 weeks; given with pyrimethamine.
 Prevention of toxoplasmosis relapse in patients with HIV infection. Adults and adolescents: 0.5 to 1 g P.O. q 6 hours with pyrimethamine and leucovorin.
Infants and children: 85 to 120 mg/kg P.O. in two to four divided doses with pyrimethamine and leucovorin.
 Nocardiasis. Adults: 4 to 8 g P.O. daily in divided doses q 6 hours for 6 weeks.
 Asymptomatic meningococcal carrier. Adults: 1 g P.O. b.i.d. for 2 days.
Children ages 1 to 12: 500 mg P.O. b.i.d. for 2 days.
Children ages 2 months to 12 months: 500 mg P.O. daily for 2 days.

Pharmacodynamics
Antibacterial action: Sulfadiazine is bacteriostatic. It inhibits formation of tetrahydrofolic acid from para-aminobenzoic acid (PABA), preventing bacterial cell synthesis of folic acid. Drug is active against many gram-positive bacteria, Chlamydia trachomatis, many Enterobacteriaceae, and some strains of Toxoplasma gondii and Plasmodium falciparum.

Pharmacokinetics
Absorption: Absorbed from the GI tract after oral administration.
Distribution: Distributed widely into most body tissues and fluids, including synovial, pleural, amniotic, prostatic, peritoneal, and seminal fluids; CSF penetration, however, is poor. Drug crosses the placental barrier, and is 32% to 56% protein-bound.
Metabolism: Metabolized partially in the liver.
Excretion: Both unchanged drug and metabolites are excreted primarily in urine by glomerular filtration and, to a lesser extent, renal tubular secretion; some drug appears in breast milk. Urine solubility of unchanged drug increases as urine pH increases.

Contraindications and precautions
Contraindicated in patients hypersensitive to sulfonamides, in those with porphyria, in infants younger than age 2 months (except in congenital toxoplasmosis), in pregnant women at term, and during breast-feeding.
  Use cautiously in patients with impaired renal or hepatic function, bronchial asthma, multiple allergies, G6PD deficiency, or blood dyscrasia.

Interactions
Drug-drug. Oral anticoagulants: Inhibits hepatic metabolism of these drugs and enhances anticoagulant effects. Monitor PT, INR, blood levels, and patient for bleeding.
Oral antidiabetics, including sulfonylureas: Enhances hypoglycemic effects. Monitor blood glucose levels.
PABA: Antagonizes sulfonamide effects. Don’t use together.
Pyrimethamine and trimethoprim (folic acid antagonists with different mechanisms of action): Causes synergistic antibacterial effects and delays or prevents bacterial resistance. Don’t use together.
Drug-lifestyle. Sun exposure: May cause photosensitivity reactions. Advise patient to take precautions.

Adverse reactions
CNS: headache, depression, seizures, hallucinations.
GI: nausea, vomiting, diarrhea, abdominal pain, anorexia, stomatitis.
GU: toxic nephrosis with oliguria and anuria, crystalluria, hematuria.
Hematologic: agranulocytosis, aplastic anemia, hemolytic anemia, thrombocytopenia, megaloblastic anemia, leukopenia.
Hepatic: jaundice.
Skin: erythema multiforme (Stevens-Johnson syndrome), generalized skin eruption, epidermal necrolysis, exfoliative dermatitis, photosensitivity, urticaria, pruritus.
Other: hypersensitivity reactions (serum sickness, drug fever, anaphylaxis), local irritation, extravasation.

Effects on lab test results
• May increase BUN, creatinine, transaminase, and bilirubin levels.
• May increase eosinophil count. May decrease hemoglobin, PT, and fibrinogen, granulocyte, platelet, and WBC counts.

Overdose and treatment
Signs and symptoms of overdose include dizziness, drowsiness, headache, unconsciousness, anorexia, abdominal pain, nausea, and vomiting. More severe complications, including hemolytic anemia, agranulocytosis, dermatitis, acidosis, sensitivity reactions, and jaundice, may be fatal.
 Treatment includes gastric lavage if ingestion has occurred within the preceding 4 hours followed by correction of acidosis, forced fluids, and urinary alkalinization to enhance solubility and excretion. Treatment of renal failure as well as transfusion of appropriate blood products (in severe hematologic toxicity) may be required.

Special considerations
 ALERT Don’t confuse sulfadiazine and sulfasalazine.
• Sulfadiazine is a less soluble sulfonamide; therefore, it’s more likely to cause crystalluria. Avoid using drug with urine acidifiers and ensure adequate fluid intake. If adequate fluid intake can’t be ensured, recommend sodium bicarbonate to reduce risk of crystalluria.
• Don’t use sulfadiazine for Group A beta-hemolytic streptococcal infections.
• Sulfadiazine alters urine glucose tests using cupric sulfate (Benedict’s reagent or Clinitest).
• Monitor renal and liver function test results.
• Monitor patient for signs of blood dyscrasia.
• Monitor urine cultures and CBCs, and conduct urinalyses before and during therapy.
Breast-feeding patients
• Drug appears in breast milk. Don’t use in breast-feeding women.
Pediatric patients
• Contraindicated in children younger than age 2 months.

Patient education
• Instruct patient to report adverse reactions promptly.
• Patient should drink 8 ounces of water with each dose and extra water daily as tolerated to prevent crystalluria.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use