Sulfisoxazole

Pronunciation: sull-fih-SOX-uh-zole
Class: Sulfonamide

Trade Names:
Gantrisin Pediatric
- Suspension 500 mg per 5 mL

Pharmacology

Exerts bacteriostatic action by competing with PABA, an essential component in folic acid synthesis, thus preventing synthesis of folic acid, needed by bacteria for growth.

Pharmacokinetics

Absorption

Sulfisoxazole is rapidly and completely absorbed. The major site of absorption is the small intestine, but some drug is absorbed from the stomach. Steady-state plasma concentrations are about 49 to 89 mcg/mL. C max is approximately 169 mcg/mL.

Distribution

Sulfisoxazole is approximately 85% bound to plasma proteins and is only distributed in extracellular body fluids. The drug readily crosses the placental barrier and enters into fetal circulation. Sulfisoxazole crosses the blood-brain barrier.

Metabolism

N 1 -acetyl sulfisoxazole is metabolized to sulfisoxazole and is absorbed as sulfisoxazole.

Elimination

Sulfisoxazole is excreted primarily by the kidneys through glomerular filtration. Drug concentrations are higher in urine than in blood. Sulfisoxazole t ½ is 4.6 to 7.8 h after oral administration.

Special Populations

Elderly

Elimination has been shown to be slower in the elderly (63 to 75 years of age) with diminished renal function (CrCl 37 to 68 mL/min).

Indications and Usage

Oral

Treatment of UTI, chancroid, inclusion conjunctivitis, malaria, meningitis caused by Haemophilus influenzae or meningococci, nocardiosis, acute otitis media, toxoplasmosis, and trachoma.

Ophthalmic

Treatment of conjunctivitis, corneal ulcer, and superficial ocular infections, adjunct to systemic sulfonamide therapy of trachoma.

Unlabeled Uses

Oral

Treatment of recurrent otitis media.

Contraindications

Hypersensitivity to sulfonamides or chemically related drugs (eg, sulfonylureas, thiazide and loop diuretics, carbonic anhydrase inhibitors, sunscreens containing PABA, local anesthetics); hypersensitivity to salicylates; porphyria; children younger than 2 mo of age; pregnancy at term.

Dosage and Administration

Adults

PO 2 to 4 g initially, then 4 to 8 g/day in 4 to 6 divided doses. Ophthalmic Instill 1 to 2 drops into lower conjunctival sac every 1 to 3 h daily.

Children and Infants older than 2 mo of age

PO 75 mg/kg initially, then 120 to 150 mg/kg/day in 4 to 6 divided doses (max, 6 g/day).

Storage/Stability

Store oral suspension in refrigerator. Store at room temperature and protect from light.

Drug Interactions

Anticoagulants, oral

May enhance anticoagulant action.

Cyclosporine

Reduced concentration of cyclosporine and reduced efficacy; may have additive nephrotoxicity.

Hydantoins

May increase hydantoin serum levels.

Methotrexate

May enhance risk of methotrexate-induced bone marrow suppression.

Sulfonylureas

May increase sulfonylurea half-life and produce hypoglycemia.

Laboratory Test Interactions

May produce false-positive urinary glucose test results when performed by Benedict method; may interfere with Urobilistix test; may produce false-positive results with sulfosalicylic acid tests for urinary protein.

Adverse Reactions

CNS

Headache; peripheral neuropathy; depression; convulsions; dizziness; ataxia.

GI

Nausea; vomiting; abdominal pain; diarrhea; anorexia; pancreatitis; impaired folic acid absorption; pseudomembranous enterocolitis.

Genitourinary

Crystalluria; hematuria; proteinuria; elevated creatinine; nephrotic syndrome; toxic nephrosis with oliguria and anuria.

Hematologic

Agranulocytosis; aplastic anemia; thrombocytopenia; leukopenia; hemolytic anemia; purpura; hypoprothrombinemia; anemia; methemoglobinemia; megaloblastic (macrocytic) anemia.

Hepatic

Hepatitis; hepatocellular necrosis.

Ophthalmic

Browache; local irritation; transient epithelial keratitis; reactive hyperemia; conjunctival edema; burning; stinging; sensitivity to bright light.

Respiratory

Pulmonary infiltrates.

Miscellaneous

Drug fever; chills; pyrexia; arthralgia; myalgia; periarteritis nodosum; lupus erythematosus phenomenon. Hypersensitivity reactions may present as erythema multiforme of Stevens-Johnson type, generalized skin eruptions, allergic myocarditis, epidermal necrolysis with or without corneal damage, urticaria, serum sickness; pruritus, exfoliative dermatitis, anaphylactoid reactions, periorbital edema, photosensitization, arthralgia, and transient pulmonary changes with eosinophilia and decreased pulmonary function.

Precautions

Pregnancy

Category C . Sulfonamides cross placenta and can produce jaundice, hemolytic anemia, and kernicterus in newborn; therefore, they are contraindicated at term.

Lactation

Excreted in breast milk in low concentrations. Do not nurse premature infants or those with hyperbilirubinemia or G-6-PD deficiency.

Children

Contraindicated in infants younger than 2 mo of age.

Renal Function

Use drug with caution.

Hepatic Function

Use drug with caution.

Photosensitivity

Photosensitization may occur.

Allergy or asthma

Use drug with caution in patients with severe allergy or bronchial asthma.

Dry eye (ophthalmic)

Use with caution in patients with severe dry eye.

Group A beta-hemolytic streptococcal infections

Do not use drug for these infections.

Hemolytic anemia

May occur in G-6-PD-deficient individuals.

Porphyria

Drug may precipitate acute attack of porphyria.

Severe reactions

Reactions, including deaths, have been associated with hypersensitivity reactions, agranulocytosis, aplastic anemia, other blood dyscrasias, and renal and hepatic damage. Irreversible neuromuscular and CNS changes and fibrosing alveolitis may occur.

Sulfonamides

Have chemical similarities to some goitrogens, diuretics (acetazolamide and the thiazides), and oral hypoglycemic agents. Goiter production, diuresis, and hypoglycemia have occurred rarely in patients receiving sulfonamides. Cross-sensitivity may exist.

Overdosage

Symptoms

Anorexia, nausea, vomiting, abdominal cramping, dizziness, headache, drowsiness, coma.

Patient Information

  • Oral
  • Advise patient to administer medication around the clock.
  • Advise patient to notify other health care providers/dentists of this drug therapy prior to other treatments or surgery.
  • Instruct patient to report these symptoms to health care provider immediately: difficulty breathing, skin rash, fever, chills, mouth sores, sore throat, ringing in ears or unusual bleeding/bruising.
  • Caution patient to avoid exposure to sunlight and to use sunscreen or wear protective clothing to avoid photosensitivity reaction. Inform patient that photosensitivity may persist for several months after therapy is completed.
  • Advise patient not to take OTC medications without consulting health care provider.
  • Ophthalmic
  • Instruct patient/family in correct instillation of drops. Inform patient that stinging, burning, and blurred vision may occur after instillation of ophthalmic preparations. Advise patient to avoid hazardous activities until vision clears. Emphasize need for patient to contact health care provider immediately if patient notices a change in vision, eye pain, increased redness, itching, swelling, loss of sight, inability to breath, or flushing after ophthalmic application of this medication.
  • Advise patient to note color change or precipitate in container and to discard if these are present.
  • Tell patient to notify health care provider if improvement is not noted within 7 days.

Copyright © 2009 Wolters Kluwer Health.

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