indication

For the treatment of severe, repeated, or long-lasting urinary tract infections, meningococcal meningitis, acute otitis media, trachoma, inclusion conjunctivitis, nocardiosis, chancroid, toxoplasmosis, malaria and other bacterial infections.

pharmacology

Sulfisoxazole 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

Sulfisoxazole is a competitive inhibitor of the enzyme dihydropteroate synthetase. It inhibits bacterial synthesis of dihydrofolic acid by preventing the condensation of the pteridine with para-aminobenzoic acid (PABA), a substrate of the enzyme dihydropteroate synthetase. The inhibited reaction is necessary in these organisms for the synthesis of folic acid.

toxicity

LD₅₀=6800 mg/kg (Orally in mice)

route of elimination

The mean urinary excretion recovery following oral administration of sulfisoxazole is 97% within 48 hours, of which 52% is intact drug, with the remaining as the N4-acetylated metabolite. It is excreted in human milk.

drug interactions

Chlorpropamide: Sulfonamide/sulfonylurea: possible hypoglycemia

Methotrexate: The sulfamide increases the toxicity of methotrexate

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

Tolbutamide: Tolbutamide and Sulfisoxazole 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: Sulfisoxazole, 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 Sulfisoxazole is initiated, discontinued or dose changed.

Trimethoprim: The strong CYP2C9 inhibitor, Sulfisoxazole, 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 Sulfisoxazole is initiated, discontinued or dose changed.

Voriconazole: Sulfisoxazole, a strong CYP2C9 inhibitor, may increase the serum concentration of voriconazole by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of voriconazole if sulfisoxazole is initiated, discontinued or dose changed.

Warfarin: Sulfisoxazole, 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 sulfisoxazole is initiated, discontinued or dose changed.

Zafirlukast: Sulfisoxazole, 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 sulfisoxazole is initiated, discontinued or dose changed.