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# Septran (Co-trimoxazole)
## Overview
Co-trimoxazole is a combination antibiotic of trimethoprim and sulfamethoxazole, which work synergistically to inhibit bacterial folic acid synthesis.
## Primary Indications
* Urinary tract infections (UTIs)
* Pneumocystis jirovecii pneumonia (PCP) prophylaxis and treatment
* Acute exacerbations of chronic bronchitis
* Shigellosis
* Traveler's diarrhea
* *Nocardia* infections
## Adult Dosing
* **UTIs:** 160 mg trimethoprim/800 mg sulfamethoxazole (1 DS tablet) every 12 hours for 3-7 days.
* **PCP Treatment:** 15 mg/kg/day trimethoprim (given in 2-4 divided doses) plus 75 mg/kg/day sulfamethoxazole (given in 2-4 divided doses), usually over 14-21 days.
* **PCP Prophylaxis:** 160 mg trimethoprim/800 mg sulfamethoxazole (1 DS tablet) daily, or 160 mg trimethoprim/800 mg sulfamethoxazole (1 DS tablet) three times weekly.
* **Shigellosis/Traveler's Diarrhea:** 160 mg trimethoprim/800 mg sulfamethoxazole (1 DS tablet) every 12 hours for 5 days.
* **Nocardiosis:** Higher doses may be required, typically 160 mg trimethoprim/800 mg sulfamethoxazole (1 DS tablet) every 6-8 hours. Duration varies based on infection site and severity.
Maximum daily dose for adults is generally 4 DS tablets (320 mg trimethoprim / 1600 mg sulfamethoxazole).
## Pediatric Dosing
Pediatric dosing is typically based on trimethoprim weight-based recommendations.
* **UTIs:** 8 mg/kg/day trimethoprim and 40 mg/kg/day sulfamethoxazole, divided into two doses every 12 hours.
* **PCP Treatment:** 15 mg/kg/day trimethoprim and 75 mg/kg/day sulfamethoxazole, divided into 2-4 doses every 24 hours.
* **PCP Prophylaxis:** 5 mg/kg/day trimethoprim and 25 mg/kg/day sulfamethoxazole, divided into two doses every 12 hours, given on 3 consecutive days per week or daily.
Specific dosing in neonates requires caution due to immature bilirubin conjugation.
## Dose Adjustments
* **Renal Impairment (CrCl < 15 mL/min):** Avoid use.
* **Renal Impairment (CrCl 15-30 mL/min):** Reduce dose by 50%.
* **Renal Impairment (CrCl 30-50 mL/min):** Reduce dose by 25%.
## Contraindications
* Known hypersensitivity to trimethoprim or sulfonamides.
* History of drug-induced thrombocytopenia with sulfonamides or trimethoprim.
* Megaloblastic anemia due to folate deficiency.
* Premature infants and infants < 2 months of age (risk of kernicterus).
* Severe renal or hepatic insufficiency when pharmacokinetic monitoring is not feasible.
## Adverse Effects
Common adverse effects include rash, nausea, vomiting, and diarrhea. Serious adverse effects include Stevens-Johnson syndrome, toxic epidermal necrolysis, aplastic anemia, agranulocytosis, hyperkalemia, and photosensitivity.
## Key Drug Interactions
* **Warfarin:** Increased INR. Monitor INR closely.
* **Methotrexate:** Increased methotrexate levels, leading to potential bone marrow suppression and stomatitis.
* **Potassium-sparing diuretics (e.g., spironolactone, amiloride):** Increased risk of hyperkalemia.
* **ACE inhibitors/ARBs:** Increased risk of hyperkalemia.
* **Cyclosporine:** Increased cyclosporine levels.
* **Potassium supplements:** Increased risk of hyperkalemia.
* **Certain oral hypoglycemics (sulfonylureas):** Increased risk of hypoglycemia.
## Monitoring
* **Renal function:** Monitor serum creatinine and electrolytes, especially in patients with renal impairment or those taking other nephrotoxic agents.
* **Complete blood counts (CBCs):** Monitor for hematologic toxicity (e.g., leukopenia, thrombocytopenia, anemia), particularly with prolonged therapy or in immunocompromised patients.
* **Liver function tests (LFTs):** Monitor periodically.
* **Potassium levels:** Especially in patients with renal impairment or those receiving other medications that affect potassium.
* **Therapeutic drug monitoring:** May be considered in certain situations (e.g., PCP treatment in HIV patients), though not routinely required.
## Clinical Pearls
* Instruct patients to drink plenty of fluids to prevent crystalluria.
* Advise patients to report any rash, sore throat, fever, or unusual bleeding/bruising immediately.
* Co-trimoxazole can inhibit CYP2C9, potentially increasing the levels of substrates like warfarin.
* Dosing for specific indications may vary based on local institutional protocols and emerging resistance patterns.
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*Disclaimer: This information is intended for clinical use and does not replace professional medical advice. Always consult the most current prescribing information and relevant clinical guidelines before making any treatment decisions.*
