indication

For the treatment of rheumatic fever and meningococcal meningitis

pharmacology

Sulfadiazine is a sulfonamide antibiotic. The sulfonamides are synthetic bacteriostatic antibiotics with a wide spectrum against most gram-positive and many gram-negative organisms. However, many strains of an individual species may be resistant. Sulfonamides inhibit multiplication of bacteria by acting as competitive inhibitors of p-aminobenzoic acid in the folic acid metabolism cycle. Bacterial sensitivity is the same for the various sulfonamides, and resistance to one sulfonamide indicates resistance to all. Most sulfonamides are readily absorbed orally. However, parenteral administration is difficult, since the soluble sulfonamide salts are highly alkaline and irritating to the tissues. The sulfonamides are widely distributed throughout all tissues. High levels are achieved in pleural, peritoneal, synovial, and ocular fluids. Although these drugs are no longer used to treat meningitis, CSF levels are high in meningeal infections. Their antibacterial action is inhibited by pus.

mechanism of action

Sulfadiazine is a competitive inhibitor of the bacterial enzyme dihydropteroate synthetase. This enzyme is needed for the proper processing of para-aminobenzoic acid (PABA) which is essential for folic acid synthesis. The inhibited reaction is necessary in these organisms for the synthesis of folic acid.

toxicity

Oral LD₅₀ in mouse is 1500 mg/kg.

route of elimination

Sulfadiazine is excreted largely in the urine.

drug interactions

Chlorpropamide: Sulfonamide/sulfonylurea: possible hypoglycemia

Cyclosporine: The sulfonamide decreases the effect of cyclosporine

Fosphenytoin: The sulfonamide increases the effect of hydantoin

Methotrexate: The sulfamide increases the toxicity of methotrexate

Phenytoin: The sulfonamide increases the effect of hydantoin

Tamoxifen: Sulfadiazine may reduce clearance rate of Tamoxifen. Monitor for changes in therapeutic/adverse effects of Tamoxifen if Sulfadiazine is initiated, discontinued or dose changed.

Tolbutamide: Tolbutamide and Sulfadiazine are strong CYP2C9 inhibitors and substrates. Decreased metabolism and clearance of both agents may occur during concomitant therapy. Consider alternate therpy or monitor for changes in the therapeutic and adverse effects of both agents if concomitant therapy is initiated, discontinued or dose(s) changed.

Torasemide: Sulfadiazine, a strong CYP2C9 inhibitor, may increase the serum concentration of Torasemide, a CYP2C9 substrate, by decreasing Torasemide metabolism and clearance. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of Torasemide if Sulfadiazine is initiated, discontinued or dose changed.

Trimethoprim: The strong CYP2C9 inhibitor, Sulfadiazine, may decrease the metabolism and clearance of Trimethoprim, a CYP2C9 substrate. Consider alternate therapy or monitor for changes in therapeutic and adverse effects of Trimethoprim if Sulfadiazine is initiated, discontinued or dose changed.

Warfarin: Sulfadiazine, a strong CYP2C9 inhibitor, may decrease the metabolism of warfarin. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of warfarin if sulfadiazine is initiated, discontinued or dose changed.

Zafirlukast: Sulfadiazine, a strong CYP2C9 inhibitor, may decrease the metabolism and clearance of zafirlukast. Consider alternate therapy or monitor for changes in zafirlukast therapeutic and adverse effects if sulfadiazine is initiated, discontinued or dose changed.