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Pronunciation
(sul fa DYE a zeen)
Generic Available (U.S.)
Yes
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of urinary tract infections and nocardiosis; adjunctive treatment in toxoplasmosis; uncomplicated attack of malaria
Use: Unlabeled/Investigational
Rheumatic fever prophylaxis
Pregnancy Risk Factor
C
Pregnancy Considerations
Adverse events have been observed in animal reproduction studies; therefore, the manufacturer classifies sulfadiazine as pregnancy category C. Sulfadiazine crosses the placenta. Available studies and case reports have failed to show an increased risk for congenital malformations after use. Sulfadiazine is indicated for use in children <2 months of age for the treatment of congenital toxoplasmosis and may be used in pregnancy for the maternal treatment of Toxoplasmic gondii encephalitis and as an alternative agent for the secondary prevention of rheumatic fever. Because of the theoretical increased risk for hyperbilirubinemia and kernicterus, sulfadiazine is contraindicated by the manufacturer for use near term. Neonatal healthcare providers should be informed if maternal sulfonamide therapy is used near the time of delivery.
Lactation
Enters breast milk/contraindicated
Breast-Feeding Considerations
Sulfadiazine distributes into human milk. Per the manufacturer, sulfadiazine is contraindicated in nursing mothers since sulfonamides cross into the milk and may cause kernicterus in the newborn. Because sulfadiazine has therapeutic indications for infants ≥2 months of age, kernicterus after exposure via breast-feeding would not be expected in healthy infants of this age group; however, sulfonamides should not be used while nursing an infant with G6PD deficiency or hyperbilirubinemia. Nondose-related effects could include modification of bowel flora.
Contraindications
Hypersensitivity to any sulfa drug or any component of the formulation; porphyria; children <2 months of age unless indicated for the treatment of congenital toxoplasmosis; sunscreens containing PABA; pregnancy (at term)
Warnings/Precautions
Concerns related to adverse effects:
• Blood dyscrasias: Fatalities associated with severe reactions including agranulocytosis, aplastic anemia and other blood dyscrasias have occurred; discontinue use at first sign of rash.
• Dermatologic reactions: Fatalities associated with severe reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis have occurred; discontinue use at first sign of rash.
• Hepatic necrosis: Fatalities associated with hepatic necrosis have occurred; discontinue use at first sign of rash.
• Sulfonamide allergy: Chemical similarities are present among sulfonamides, sulfonylureas, carbonic anhydrase inhibitors, thiazides, and loop diuretics (except ethacrynic acid). Use in patients with sulfonamide allergy is specifically contraindicated in product labeling, however, a risk of cross-reaction exists in patients with allergy to any of these compounds; avoid use when previous reaction has been severe.
• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns:
• G6PD deficiency: Use with caution in patients with G6PD deficiency; hemolysis may occur.
• Hepatic impairment: Use with caution in patients with hepatic impairment.
• Renal impairment: Use with caution in patients with renal impairment; dosage modification required.
Other warnings/precautions:
• Appropriate use: Fluid intake should be maintained ≥1500 mL/day or administer sodium bicarbonate to keep urine alkaline; more likely to cause crystalluria because it is less soluble than other sulfonamides.
Adverse Reactions
Frequency not defined.
Central nervous system: Dizziness, fever, headache
Dermatologic: Lyell's syndrome, Stevens-Johnson syndrome, itching, rash, photosensitivity
Endocrine & metabolic: Thyroid function disturbance
Gastrointestinal: Anorexia, diarrhea, nausea, vomiting
Genitourinary: Crystalluria
Hematologic: Aplastic anemia, granulocytopenia, hemolytic anemia, leukopenia, thrombocytopenia
Hepatic: Hepatitis, jaundice
Renal: Hematuria, acute nephropathy, interstitial nephritis
Miscellaneous: Serum sickness-like reactions
Metabolism/Transport Effects
Substrate of CYP2C9 (major), 2E1 (minor), 3A4 (minor); Inhibits CYP2C9 (strong)
Drug Interactions
BCG: Antibiotics may diminish the therapeutic effect of BCG. Risk X: Avoid combination
Carvedilol: CYP2C9 Inhibitors (Strong) may increase the serum concentration of Carvedilol. Specifically, concentrations of the S-carvedilol enantiomer may be increased. Risk C: Monitor therapy
Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Management: Upon completion/discontinuation of conivaptan, allow at least 7 days before initiating therapy with drugs that are CYP3A4 substrates. Risk D: Consider therapy modification
CycloSPORINE: Sulfonamide Derivatives may enhance the nephrotoxic effect of CycloSPORINE. Sulfonamide Derivatives may decrease the serum concentration of CycloSPORINE. Risk C: Monitor therapy
CycloSPORINE (Systemic): Sulfonamide Derivatives may enhance the nephrotoxic effect of CycloSPORINE (Systemic). Sulfonamide Derivatives may decrease the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy
CYP2C9 Inducers (Highly Effective): May increase the metabolism of CYP2C9 Substrates (High risk). Risk C: Monitor therapy
CYP2C9 Inhibitors (Moderate): May decrease the metabolism of CYP2C9 Substrates (High risk). Risk C: Monitor therapy
CYP2C9 Inhibitors (Strong): May decrease the metabolism of CYP2C9 Substrates (High risk). Risk D: Consider therapy modification
CYP2C9 Substrates (High risk): CYP2C9 Inhibitors (Strong) may decrease the metabolism of CYP2C9 Substrates (High risk). Risk D: Consider therapy modification
Fosphenytoin: Sulfonamide Derivatives may increase the serum concentration of Fosphenytoin. Risk C: Monitor therapy
Methenamine: May enhance the adverse/toxic effect of Sulfonamide Derivatives. Specifically, the combination may result in the formation of an insoluble precipitate in the urine. Risk X: Avoid combination
Methotrexate: Sulfonamide Derivatives may enhance the adverse/toxic effect of Methotrexate. Management: Consider avoiding concomitant use of methotrexate and either sulfamethoxazole or trimethoprim. If used concomitantly, monitor for the development of signs and symptoms of methotrexate toxicity (eg, bone marrow suppression). Risk D: Consider therapy modification
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2C9 Substrates (High risk). Risk C: Monitor therapy
Phenytoin: Sulfonamide Derivatives may increase the serum concentration of Phenytoin. Risk C: Monitor therapy
Potassium P-Aminobenzoate: May diminish the therapeutic effect of Sulfonamide Derivatives. Risk X: Avoid combination
Procaine: May diminish the therapeutic effect of Sulfonamide Derivatives. Risk X: Avoid combination
Sulfonylureas: Sulfonamide Derivatives may enhance the hypoglycemic effect of Sulfonylureas. Risk C: Monitor therapy
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 24 hours after cessation of antibacterial agents. Risk D: Consider therapy modification
Vitamin K Antagonists (eg, warfarin): Sulfonamide Derivatives may enhance the anticoagulant effect of Vitamin K Antagonists. Risk D: Consider therapy modification
Ethanol/Nutrition/Herb Interactions
Food: Avoid large quantities of vitamin C or acidifying agents (cranberry juice) to prevent crystalluria.
Herb/Nutraceutical: Avoid dong quai, St John's wort (may also cause photosensitization).
Storage
Tablets may be crushed to prepare oral suspension of the drug in water or with a sucrose-containing solution. Aqueous suspension with concentrations of 100 mg/mL should be stored in the refrigerator and used within 7 days.
Mechanism of Action
Interferes with bacterial growth by inhibiting bacterial folic acid synthesis through competitive antagonism of PABA
Pharmacodynamics/Kinetics
Absorption: Well absorbed
Distribution: Throughout body tissues and fluids including pleural, peritoneal, synovial, and ocular fluids; throughout total body water; readily diffused into CSF
Protein binding: 38% to 48%
Metabolism: Via N-acetylation
Half-life elimination: 10 hours
Time to peak: Within 3-6 hours
Excretion: Urine (43% to 60% as unchanged drug, 15% to 40% as metabolites)
Dosage
Oral:
Asymptomatic meningococcal carriers: Adults: 1 g twice daily for 2 days
Congenital toxoplasmosis:
Newborns and Children <2 months: 100 mg/kg/day divided every 6 hours in conjunction with pyrimethamine 1 mg/kg/day once daily and supplemental leucovorin calcium 5 mg every 3 days for 6 months
Children >2 months: 25-50 mg/kg/dose 4 times/day
Nocardiosis: 4-8 g/day for a minimum of 6 weeks
Toxoplasmosis:
Children >2 months: Loading dose: 75 mg/kg; maintenance dose: 120-150 mg/kg/day, maximum dose: 6 g/day; divided every 4-6 hours in conjunction with pyrimethamine 2 mg/kg/day divided every 12 hours for 3 days followed by 1 mg/kg/day once daily with supplemental leucovorin calcium
Secondary prophylaxis of toxoplasmosis in HIV-exposed/-positive patients (unlabeled use: CDC, 2009): Infants and Children: 85-120 mg/kg/day divided every 6-12 hours (maximum: 4 g/day) plus pyrimethamine and leucovorin calcium
Adults: 2-6 g/day in divided doses every 6 hours in conjunction with pyrimethamine 50-75 mg/day and with supplemental leucovorin calcium
Prevention of recurrent attacks of rheumatic fever (unlabeled use):
<30 kg: 0.5 g/day
>30 kg: 1 g/day
Administration: Oral
Tablets may be crushed to prepare oral suspension of the drug in water or with a sucrose-containing solution. Aqueous suspension with concentrations of 100 mg/mL should be stored in the refrigerator and used within 7 days. Administer around-the-clock to promote less variation in peak and trough serum levels.
Dietary Considerations
Supplemental leucovorin calcium should be administered to reverse symptoms or prevent problems due to folic acid deficiency.
Patient Education
Inform prescriber of any allergies you have. Take as directed at regular intervals around-the-clock. Take on an empty stomach, 1 hour before or 2 hours after meals with full glass of water. Avoid large quantities of vitamin C. Maintain adequate hydration to prevent kidney damage, unless instructed to restrict fluid intake. May cause dizziness, headache, photosensitivity, nausea, vomiting, or loss of appetite. Report skin rash, persistent nausea, vomiting, diarrhea, opportunistic infection (sore throat, fever, vaginal itching or discharge, unusual bruising or bleeding, fatigue), blood in urine or change in urinary pattern, persistent headache, abdominal pain, or respiratory difficulty.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
Dizziness is common; sulfonamides reported to cause restlessness, irritability, depression, euphoria, disorientation, panic, hallucinations, and delusions
Mental Health: Effects on Psychiatric Treatment
Photosensitivity is common; use caution with concurrent psychotropics; may cause granulocytopenia; caution with clozapine and carbamazepine
Nursing: Physical Assessment/Monitoring
Assess for allergy history prior to starting therapy (sulfonamides). Monitor for rash, photosensitivity, gastrointestinal disturbance (nausea, vomiting, anorexia), anemia, jaundice, and hematuria.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, oral: 500 mg
Pricing: U.S. (www.drugstore.com)
Tablets (SulfADIAZINE)
500 mg (30): $79.99
Extemporaneously Prepared
A 200 mg/mL oral suspension may be made with sulfadiazine powder and sterile water. Place 50 g sulfadiazine powder in a glass mortar. Add small portions of sterile water and mix to a uniform paste; mix while incrementally adding sterile water to almost 250 mL; transfer to a calibrated bottle, rinse mortar with sterile water, and add sufficient quantity of sterile water to make 250 mL. Label "shake well" and "refrigerate". Stable for 3 days refrigerated. Note: Suspension may also be prepared by crushing one-hundred 500 mg tablets; however, it is stable for only 2 days.
Pathmanathan U, Halgrain D, Chiadmi F, et al, "Stability of Sulfadiazine Oral Liquids Prepared From Tablets and Powder," J Pharm Pharm Sci, 2004, 7(1):84-7.
References
Centers for Disease Control and Prevention, “Guidelines for the Prevention and Treatment of Opportunistic Infections Among HIV-Exposed and HIV-Infected Children: Recommendations from CDC, the National Institutes of Health, the HIV Medicine Association of the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the American Academy of Pediatrics,” MMWR Recomm Rep, 2009, 58(RR-11):1-166. Available at http://aidsinfo.nih.gov/contentfiles/Pediatric_OI.pdf
Frenkel JK, “Toxoplasmosis,” Pediatr Clin North Am, 1985, 32(4):917-32.
Katlama C, De Wit S, O'Doherty E, et al, “Pyrimethamine-Clindamycin vs Pyrimethamine-Sulfadiazine as Acute and Long-Term Therapy for Toxoplasmic Encephalitis in Patients With AIDS,” Clin Infect Dis, 1996, 22(2):268-75.
Porter SB and Sande MA, “Toxoplasmosis of the Central Nervous System in the Acquired Immunodeficiency Syndrome,” N Engl J Med, 1992, 327(23):1643-8.
Torre D, Casari S, Speranza F, et al, “Randomized Trial of Trimethoprim-Sulfamethoxazole Versus Pyrimethamine-Sulfadiazine for Therapy of Toxoplasmic Encephalitis in Patients With AIDS. Italian Collaborative Study Group,” Antimicrob Agents Chemother, 1998, 42(6):1346-9.
International Brand Names
Lexi-Comp.com
Last full review/revision May 2011
Content last modified May 2011
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