sulfadiazine
Brand: Sulfadiazine
Prototype: trimethoprim-sulfamethoxazole
Drug Class: sulfonamide antibiotic
Drug Family: antibiotic
Subclass: short-acting sulfonamide
Organ Systems: infectious-disease
Mechanism of Action
Competitively inhibits dihydropteroate synthase, blocking the incorporation of PABA into dihydrofolic acid; bacteriostatic. Primarily used for toxoplasmosis in combination with pyrimethamine.
dihydropteroate synthase (DHPS)
Indications
- toxoplasmosis (in combination with pyrimethamine and leucovorin — treatment and prophylaxis in HIV)
- nocardiosis (alternative)
- congenital toxoplasmosis
Contraindications
- sulfonamide hypersensitivity
- pregnancy (near term — neonatal jaundice risk)
- infants <2 months
- severe hepatic/renal impairment
Adverse Effects
Common
- GI upset
- crystalluria/urolithiasis (maintain adequate hydration)
- photosensitivity
- rash
Serious
- Stevens-Johnson syndrome/TEN
- agranulocytosis
- hemolytic anemia (G6PD deficiency)
- acute renal failure (crystalluria)
Pharmacokinetics (ADME)
| Absorption | rapidly absorbed orally; ~90% bioavailability |
| Distribution | widely distributed; crosses BBB and placenta |
| Metabolism | hepatic acetylation (slow vs. rapid acetylators affect toxicity) |
| Excretion | renal (important to maintain urine alkalinity to prevent crystalluria) |
| Half-life | 10 hours |
| Onset | 1–4 hours |
| Peak | 4 hours |
| Duration | 6 hours |
| Protein Binding | 38–48% |
| Vd | moderate |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| pyrimethamine | synergistic inhibition of folate synthesis; used therapeutically for toxoplasmosis | beneficial |
| warfarin | sulfonamides inhibit CYP2C9, increasing warfarin exposure | major |
| phenytoin | inhibits CYP2C9, increasing phenytoin levels; toxicity risk | major |
Nursing Considerations
- Maintain vigorous oral hydration (2–3 L/day) to prevent crystalluria and urolithiasis; alkalinizing the urine with sodium bicarbonate further reduces crystal formation.
- Monitor CBC weekly — sulfonamides can cause bone marrow suppression including agranulocytosis.
- Leucovorin (folinic acid) must be administered concurrently with pyrimethamine-sulfadiazine for toxoplasmosis to prevent pyrimethamine-induced folate deficiency.
- Monitor for rash; Stevens-Johnson syndrome/TEN, while rare, is life-threatening — stop the drug immediately if bullous or desquamating skin reactions occur.
Clinical Pearls
- Sulfadiazine-pyrimethamine-leucovorin is the standard of care for treatment and secondary prophylaxis of toxoplasma encephalitis in HIV-infected patients (CD4 <200 cells/mcL).
- The acetylation phenotype (slow vs. fast acetylator, determined by NAT2 genotype) affects the proportion of sulfonamide converted to the toxic hydroxylamine metabolite, with slow acetylators at higher risk for adverse reactions.
Safety Profile
Pregnancy avoid
Lactation avoid
Renal Adjustment Required
Hepatic Adjustment Required
TDM Not required
Concordance Terms
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