AZO GANTRISIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for AZO GANTRISIN (AZO GANTRISIN).
Sulfamethoxazole is a competitive inhibitor of dihydropteroate synthase, blocking bacterial folic acid synthesis. Phenazopyridine is an azo dye with local analgesic effects on urinary tract mucosa.
| Metabolism | Sulfamethoxazole is metabolized primarily via N-acetylation in the liver; phenazopyridine undergoes hepatic metabolism. |
| Excretion | Renal: 70-100% (sulfamethoxazole and metabolites; 15-30% as unchanged drug; remainder as acetylated and glucuronide conjugates). Biliary/fecal: <3%. |
| Half-life | Sulfamethoxazole: 9-12 hours (adults with normal renal function), prolonged to 20-50 hours in renal impairment; trimethoprim component: 8-11 hours. Clinical context: dosing interval adjusted based on CrCl. |
| Protein binding | Sulfamethoxazole: 65-70% bound to albumin; trimethoprim: 40-45% bound to albumin. |
| Volume of Distribution | Sulfamethoxazole: 0.2-0.3 L/kg (reflects distribution into extracellular fluid, not extensively tissue-bound); trimethoprim: 1-2 L/kg (higher due to lipophilicity, penetrates tissues including prostate and CSF). Clinical meaning: higher Vd of trimethoprim contributes to effective tissue concentrations. |
| Bioavailability | Oral: 85-95% for both components (tablets); suspension: ~90%. |
| Onset of Action | Oral: 1-2 hours for detectable serum levels, 2-4 hours for clinical effect (urinary tract symptoms). |
| Duration of Action | Oral: 12 hours (due to twice-daily dosing for urinary tract infections; sustained above MIC for ~12 hours). Clinical note: continue for 2-3 days after symptom resolution. |
| Molecular Weight | Sulfamethoxazole: 253.28 Da; Trimethoprim: 290.32 Da (combination product; each component accounted separately). |
AZO GANTRISIN (phenazopyridine 100 mg / sulfisoxazole 500 mg): 2 tablets orally 4 times daily for 2 days, then 1 tablet 4 times daily for up to 5 days.
| Dosage form | TABLET |
| Renal impairment | CrCl 50-80 mL/min: 1 tablet 3-4 times daily; CrCl 10-49 mL/min: 1 tablet 2-3 times daily; CrCl <10 mL/min: contraindicated. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50% or extend interval; Child-Pugh C: contraindicated. |
| Pediatric use | Children 6-12 years: 0.5-1.5 teaspoons (2.5-7.5 mL) of suspension (equivalent to 75-225 mg sulfisoxazole and 15-45 mg phenazopyridine) orally 4 times daily; children >12 years: adult dose. |
| Geriatric use | Initiate at lower doses (e.g., 1 tablet 3 times daily) and monitor for renal function and CNS side effects; contraindicated if CrCl <50 mL/min. |
| 1st trimester | Avoid in the first trimester due to risk of teratogenicity (folate antagonism, neural tube defects). |
| 2nd trimester | Use only if clearly needed; risk of kernicterus in the fetus if used near term (competition with bilirubin for albumin binding). |
| 3rd trimester | Contraindicated in the third trimester (especially after 36 weeks) due to risk of kernicterus and hemolytic anemia in the neonate. |
Clinical note
Comprehensive clinical and safety monograph for AZO GANTRISIN (AZO GANTRISIN).
| Placental transfer | Both components cross the placenta readily, achieving fetal serum levels 50-100% of maternal levels. |
| Breastfeeding | Sulfamethoxazole and trimethoprim are excreted into breast milk in low amounts. Avoid in breastfeeding infants with G6PD deficiency or hyperbilirubinemia; theoretical risk of kernicterus. Use caution in premature or ill infants. |
■ FDA Black Box Warning
Sulfonamides have been associated with severe reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, agranulocytosis, aplastic anemia, and other blood dyscrasias. Fatalities have occurred.
| Serious Effects |
Known hypersensitivity to sulfonamides or trimethoprimMegaloblastic anemia due to folate deficiencySevere hepatic damageSevere renal impairment (CrCl <15 mL/min) unless dialysisInfants <2 months of age (sulfonamide competition for bilirubin binding)
| Precautions | Risk of severe hypersensitivity reactions, blood dyscrasias, hepatotoxicity, and renal impairment. Use caution in patients with G6PD deficiency, hepatic impairment, or renal insufficiency. Phenazopyridine may cause orange-red discoloration of urine. |
| Food/Dietary | Avoid acidic foods and beverages (e.g., citrus fruits, tomatoes, cola) as they may decrease the efficacy of sulfisoxazole by increasing urine acidity, which can reduce solubility and increase risk of crystalluria. Maintain adequate fluid intake; avoid alcohol. No other significant food interactions. |
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| Lactation Rating | L3 (Moderately Safe) - limited data, avoid in high-risk situations. |
| Teratogenic Risk | Pregnancy Category D. First trimester: Associated with neural tube defects, cardiovascular anomalies, and oral clefts due to antifolate effect of trimethoprim. Second and third trimesters: Risk of kernicterus in newborn due to sulfonamide displacement of bilirubin from albumin, especially near term. Avoid use during pregnancy unless benefit outweighs risk. |
| Fetal Monitoring | Monitor CBC, renal function, and liver function tests monthly during therapy. Assess for signs of hypersensitivity reactions or hemolytic anemia. Fetal ultrasound if exposure in first trimester to assess for neural tube defects. |
| Fertility Effects | No significant adverse effects on fertility reported. Trimethoprim may impair folate metabolism, but clinical impact on fertility is negligible. |
| Clinical Pearls | AZO GANTRISIN combines phenazopyridine (urinary analgesic) and sulfisoxazole (sulfonamide antibiotic). Phenazopyridine imparts a red-orange color to urine and may stain contact lenses. Sulfisoxazole is contraindicated in infants <2 months due to risk of kernicterus. Use with caution in patients with G6PD deficiency, sulfonamide allergy, or renal impairment. Monitor for crystalluria; ensure adequate hydration. Avoid concurrent use with methenamine due to increased risk of crystalluria. |
| Patient Advice | Take this medication with a full glass of water and drink plenty of fluids throughout the day to prevent kidney stones. · Your urine may turn red-orange; this is harmless but may stain clothing or contact lenses. · Do not use for longer than 2 days unless directed by your doctor, as it only treats symptoms of UTI, not the infection. · Complete the full course of the sulfisoxazole component even if you feel better. · Avoid prolonged sun exposure; sulfonamides may cause photosensitivity. Use sunscreen. · Seek immediate medical attention if you develop skin rash, sore throat, fever, unusual bleeding, or bruising. |