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# Septran (Co-Trimoxazole)
## Overview
Co-trimoxazole is a combination antibiotic of trimethoprim and sulfamethoxazole.
## Primary Indications
* Urinary tract infections (UTIs)
* Pneumocystis jirovecii pneumonia (PJP) prophylaxis and treatment
* *Shigella* gastroenteritis
* *Haemophilus influenzae* otitis media
* Other susceptible bacterial infections
## Adult Dosing
* **Urinary Tract Infections (Uncomplicated):** 160 mg trimethoprim/800 mg sulfamethoxazole (1 DS tablet) twice daily for 3 days.
* **Urinary Tract Infections (Complicated) / UTIs with Prostatitis:** 160 mg trimethoprim/800 mg sulfamethoxazole (1 DS tablet) twice daily for 10-14 days.
* **Pneumocystis jirovecii pneumonia (PJP) Treatment:** 15-20 mg/kg/day trimethoprim component divided into 3-4 doses, usually for 14-21 days.
* **Pneumocystis jirovecii pneumonia (PJP) Prophylaxis:** 160 mg trimethoprim/800 mg sulfamethoxazole (1 DS tablet) daily, or 3 times weekly on alternate days.
* **Shigellosis:** 160 mg trimethoprim/800 mg sulfamethoxazole (1 DS tablet) twice daily for 5 days.
* **Maximum Daily Dose:** Generally limited to 160 mg trimethoprim/800 mg sulfamethoxazole (1 DS tablet) every 12 hours for uncomplicated UTIs, but higher doses may be used for severe infections under close supervision. For PJP treatment, the trimethoprim component can reach up to 20 mg/kg/day.
## Pediatric Dosing
Dosing is based on the trimethoprim component.
* **Urinary Tract Infections (Acute):** 8 mg/kg/day of trimethoprim and 40 mg/kg/day of sulfamethoxazole, given in two equally divided doses every 12 hours. Dosing is typically continued for 7 days.
* **Pneumocystis jirovecii pneumonia (PJP) Treatment:** 15-20 mg/kg/day of trimethoprim and 75-100 mg/kg/day of sulfamethoxazole, divided into 3-4 doses daily for 14-21 days.
* **Pneumocystis jirovecii pneumonia (PJP) Prophylaxis:** 5 mg/kg/day of trimethoprim and 25 mg/kg/day of sulfamethoxazole, given as a single dose daily, or in two divided doses three times weekly.
* **Maximum Pediatric Dose:** Refer to specific guidelines, but generally not to exceed the adult equivalent dose.
## Dose Adjustments
* **Renal Impairment:** Dose adjustment is required based on creatinine clearance (CrCl).
* CrCl > 30 mL/min: No adjustment needed.
* CrCl 15-30 mL/min: Administer 75% of the standard dose.
* CrCl < 15 mL/min: Contraindicated, or administer 50% of the standard dose with extreme caution and close monitoring.
* **Hepatic Impairment:** Use with caution; dose adjustment is not well-defined, but close monitoring is essential.
## Contraindications
* Known hypersensitivity to trimethoprim or sulfonamides.
* Documented severe adverse reaction (e.g., Stevens-Johnson syndrome) to a sulfonamide.
* Megaloblastic anemia due to folate deficiency.
* Infants less than 2 months of age (due to risk of kernicterus).
* Severe renal insufficiency where urine concentration is not possible.
* History of drug-induced thrombocytopenia with the use of trimethoprim or sulfamethoxazole.
## Adverse Effects
Common: Rash, nausea, vomiting, diarrhea, anorexia.
Serious: Stevens-Johnson syndrome, toxic epidermal necrolysis, hypersensitivity reactions, hematologic toxicity (aplastic anemia, leukopenia, thrombocytopenia, megaloblastic anemia), hyperkalemia, renal impairment, photosensitivity, crystalluria.
## Key Drug Interactions
* **Warfarin:** Increased INR. Monitor INR closely and adjust warfarin dose.
* **Methotrexate:** Increased methotrexate levels and toxicity. Avoid concurrent use or monitor methotrexate levels.
* **Potassium-sparing diuretics (e.g., spironolactone, amiloride):** Increased risk of hyperkalemia. Monitor potassium levels.
* **ACE inhibitors/ARBs:** Increased risk of hyperkalemia. Monitor potassium levels.
* **Oral hypoglycemics:** Potential for enhanced hypoglycemic effect. Monitor blood glucose.
* **Digoxin:** Potential for increased digoxin levels. Monitor digoxin levels.
* **Cyclosporine:** Potential for increased cyclosporine levels and nephrotoxicity.
* **Rifampin:** May decrease co-trimoxazole levels or increase trimethoprim levels. Monitor drug levels.
## Monitoring
* **Renal function (creatinine, CrCl).**
* **Complete blood counts (CBC) with differential and platelet count**, especially with prolonged therapy, in elderly patients, or in those with G6PD deficiency.
* **Electrolytes (especially potassium).**
* **Liver function tests (LFTs).**
* **Signs of hypersensitivity reactions and rash.**
* **Hydration and urine output** to prevent crystalluria.
## Clinical Pearls
* Encourage adequate fluid intake to prevent crystalluria.
* Advise patients to report any rash, sore throat, fever, or easy bruising/bleeding immediately.
* Sulfonamides can displace bilirubin from albumin; use with caution in jaundiced infants or those with low albumin.
* For PJP prophylaxis, daily dosing is generally preferred for better adherence.
* Dosing in neonates and premature infants requires careful consideration due to immature liver and kidney function.
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**Disclaimer:** This information is intended for healthcare professionals. Always consult the most current official prescribing information and institutional protocols for definitive guidance.
