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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 the following conditions (per product labeling): Chancroid, trachoma, inclusion conjunctivitis, nocardiosis, urinary tract infections, toxoplasmosis encephalitis, malaria, meningococcal meningitis, acute otitis media, rheumatic fever (prophylaxis), meningitis (adjunctive)
Refer to current guidelines for appropriate use.
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; children <2 months of age unless indicated for the treatment of congenital toxoplasmosis; pregnancy (at term); breast-feeding
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 or signs of serious adverse reactions.
• 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:
• Allergies/asthma: Use with caution in patients with allergies or asthma.
• Glucose 6-phosphate dehydrogenase (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. Maintain adequate hydration to prevent crystalluria.
Other warnings/precautions:
• Appropriate use: Not for the treatment of group A beta-hemolytic streptococcal infections.
Adverse Reactions
Frequency not defined.
Cardiovascular: Allergic myocarditis, periarteritis nodosa
Central nervous system: Ataxia, chills, convulsions, depression, fever, hallucinations, headache, insomnia, vertigo
Dermatologic: Epidermal necrolysis, erythema multiforme, exfoliative dermatitis, photosensitivity, pruritus, purpura, rash, skin eruptions, Stevens-Johnson syndrome, urticaria
Endocrine & metabolic: Hypoglycemia, thyroid function disturbance
Gastrointestinal: Abdominal pain, anorexia, diarrhea, nausea, pancreatitis, stomatitis, vomiting
Genitourinary: Crystalluria, stone formation, toxic nephrosis with oliguria and anuria
Hematologic: Agranulocytopenia, aplastic anemia, hemolytic anemia, hypoprothrombinemia, leukopenia, methemoglobinemia, thrombocytopenia
Hepatic: Hepatitis
Neuromuscular & skeletal: Arthralgia, peripheral neuritis
Ocular: Conjunctival/scleral injection, periorbital edema
Otic: Tinnitus
Renal: Diuresis
Miscellaneous: Anaphylactoid reactions, lupus erythematosus, serum sickness-like reactions
Metabolism/Transport Effects
Substrate of CYP2C9 (major), CYP2E1 (minor), CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; 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 (Low risk). Risk C: Monitor therapy
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 (Strong): May increase the metabolism of CYP2C9 Substrates. Risk C: Monitor therapy
CYP2C9 Inhibitors (Moderate): May decrease the metabolism of CYP2C9 Substrates. Risk C: Monitor therapy
CYP2C9 Inhibitors (Strong): May decrease the metabolism of CYP2C9 Substrates. Risk D: Consider therapy modification
CYP2C9 Substrates: CYP2C9 Inhibitors (Strong) may decrease the metabolism of CYP2C9 Substrates. Risk D: Consider therapy modification
Cyproterone: May decrease the serum concentration of CYP2E1 Substrates. Risk C: Monitor therapy
Diclofenac: CYP2C9 Inhibitors (Strong) may increase the serum concentration of Diclofenac. Risk C: Monitor therapy
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. Risk C: Monitor therapy
Phenytoin: Sulfonamide Derivatives may increase the serum concentration of Phenytoin. Risk C: Monitor therapy
Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Risk C: Monitor therapy
Potassium P-Aminobenzoate: May diminish the therapeutic effect of Sulfonamide Derivatives. Risk X: Avoid combination
Prilocaine: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Prilocaine. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Management: Monitor patients for signs of methemoglobinemia (e.g., hypoxia, cyanosis) when prilocaine is used in combination with other agents associated with development of methemoglobinemia. Avoid lidocaine/prilocaine in infants receiving such agents. Risk C: Monitor therapy
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
Store at controlled room temperature of 20°C to 25°C (68°F to 77°F). Protect from light.
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:
General dosing guidelines:
Children >2 months of age: Initial: 75 mg/kg; Maintenance: 150 mg/kg/day in 4-6 divided doses (maximum: 6 g/24 hours)
Adults: 2-4 g/day in 3-6 divided doses
Rheumatic fever prophylaxis: Children and Adults:
<30 kg: 0.5 g/day
≥30 kg: 1 g/day
Toxoplasmosis (HIV-exposed/-positive patients) (CDC, 2009):
Congenital toxoplasmosis: Infants: 100 mg/kg/day in divided doses every 12 hours for 12 months in combination with pyrimethamine plus leucovorin calcium
Acquired toxoplasmosis: Infants and Children:
Acute induction therapy: 25-50 mg/kg/dose given 4 times/day (maximum: 1-1.5 g/dose) in combination with pyrimethamine and leucovorin calcium. Continue acute induction therapy for ≥6 weeks, then follow with chronic suppressive therapy.
Prophylaxis to prevent recurrence (prior to encephalitis): 85-120 mg/kg/day divided every 6-12 hours (maximum: 2-4 g/day) in combination with pyrimethamine plus leucovorin calcium
Toxoplasma gondii encephalitis: Adolescents and Adults:
Acute therapy (duration of therapy: ≥6 weeks): 1000 mg (<60 kg) or 1500 mg (≥60 kg) every 6 hours in combination with pyrimethamine plus leucovorin calcium (preferred) or alternatively, may give 1000-1500 mg every 6 hours in combination with atovaquone
Prophylaxis to prevent recurrence: 2000-4000 mg/day in 2-4 divided doses in combination with pyrimethamine and leucovorin calcium (preferred) or alternatively, may give 2000-4000 mg/day in 2-4 divided doses in combination with atovaquone
Administration: Oral
Administer with at least 8 ounces of water and around-the-clock to promote less variation in peak and trough serum levels. Oral sodium bicarbonate may be used to alkalinize the urine of patients unable to maintain adequate fluid intake (in order to prevent crystalluria, azotemia, oliguria) (Lerner, 1996).
Monitoring Parameters
Perform culture and sensitivity testing prior to initiating therapy; frequent CBC and urinalysis during therapy; signs of serious blood disorders (sore throat, fever, pallor, purpura, jaundice); CD4+ count in HIV-exposed/-positive patients treated for toxoplasmosis; sulfonamide blood concentrations may be monitored for severe infections (target: 12-15 mg/100 mL)
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. Maintain adequate hydration to prevent kidney damage, unless instructed to restrict fluid intake. May cause dizziness, headache, photosensitivity, nausea, vomiting, or loss of appetite. Notify prescriber of red, blistered, or swollen skin or red or purple patches under the skin; decreased urine or trouble urinating; persistent nausea; vomiting; diarrhea; opportunistic infection (sore throat, fever, vaginal itching or discharge, unusual bruising or bleeding, fatigue); dark urine; yellow skin or eyes; seizures; hallucinations; joint pain; 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
Gerber MA, Baltimore RS, Eaton CB, et al, "Prevention of Rheumatic Fever and Diagnosis and Treatment of Acute Streptococcal pharyngitis: A Scientific Statement From the American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young, the Interdisciplinary Council on Functional Genomics and Translational Biology, and the Interdisciplinary Council on Quality of Care and Outcomes Research: Endorsed by the American Academy of Pediatrics," Circulation, 2009, 119(11):1541-51.
Kaplan JE, Benson C, Holmes KH, et al, "Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents: Recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America," MMWR Recomm Rep, 2009, 58(RR-4):1-207.
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.
Lerner PI, "Nocardiosis," Clin Infect Dis, 1996, 22(6):891-903.
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 March 2012
Content last modified March 2012
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