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# Co-trimoxazole (Septra)
## Overview
Co-trimoxazole is a combination of trimethoprim and sulfamethoxazole, a synergistic antibacterial agent.
## Primary Indications
* Urinary tract infections (UTIs)
* Pneumocystis jirovecii pneumonia (PJP) prophylaxis and treatment
* Shigellosis
* Acute otitis media
* Acute exacerbations of chronic bronchitis
* Bacterial gastroenteritis
## Adult Dosing
* **UTIs and most other infections:** 1 double-strength (DS) tablet (800 mg sulfamethoxazole/160 mg trimethoprim) every 12 hours. Duration varies by indication.
* **PJP Prophylaxis:** 1 DS tablet daily.
* **PJP Treatment:** 15 mg/kg trimethoprim component per day, divided into 3 or 4 doses, given orally or IV for 14 to 21 days. This typically equates to 2 DS tablets every 6 hours.
## Pediatric Dosing
Dosing is based on the trimethoprim component.
* **General Infections:** 8 mg/kg trimethoprim component per day, divided into 2 doses, given every 12 hours.
* For children >12 years: Same as adult dosing.
* For children <12 years:
* Mild to moderate infections: 4 mg/kg per dose every 12 hours.
* Severe infections: 10 mg/kg per dose every 12 hours.
* **PJP Prophylaxis:** 5 mg/kg trimethoprim component per day, divided into 2 doses, given every 12 hours, 3 times per week.
* **PJP Treatment:** 15 mg/kg trimethoprim component per day, divided into 3 or 4 doses, given every 6 or 8 hours for 14 to 21 days.
## Dose Adjustments
* **Renal Impairment:**
* CrCl >30 mL/min: No adjustment needed.
* CrCl 15-30 mL/min: Administer 75% of the usual dose.
* CrCl <15 mL/min: Avoid use or administer 50% of the usual dose every 12 hours.
## Contraindications
* Known hypersensitivity to trimethoprim, sulfonamides, or any component of the formulation.
* Infants <2 months of age (due to risk of kernicterus).
* Documented megaloblastic anemia due to folate deficiency.
* Severe renal or hepatic insufficiency when pharmacokinetic monitoring is not feasible.
## Adverse Effects
Common: Rash, nausea, vomiting, diarrhea, hyperkalemia.
Serious: Stevens-Johnson syndrome/toxic epidermal necrolysis, severe rash (e.g., DRESS), blood dyscrasias (anemia, leukopenia, thrombocytopenia), hyperkalemia, hyponatremia, crystalluria, photosensitivity, hepatic injury.
## Key Drug Interactions
* **ACE inhibitors, ARBs, Potassium-sparing diuretics, Potassium supplements:** Increased risk of hyperkalemia.
* **Warfarin:** Increased INR; monitor INR closely.
* **Methotrexate:** Increased methotrexate levels; consider co-administration with leucovorin.
* **CYP2C8 inhibitors (e.g., repaglinide, pioglitazone):** May increase concentrations of co-administered drugs.
* **CYP2C9 inhibitors (e.g., warfarin):** May increase concentrations of co-administered drugs.
* **CYP2C9 inducers (e.g., rifampin):** May decrease concentrations of co-administered drugs.
* **Diuretics:** Increased risk of thrombocytopenia.
* **Potassium:** Increased risk of hyperkalemia.
* **Sulfonylureas (e.g., glyburide):** Increased risk of hypoglycemia.
## Monitoring
* **Renal function (BUN, creatinine).**
* **Electrolytes (especially potassium).**
* **Complete blood count (CBC) with differential:** Particularly in prolonged therapy, elderly patients, or those with G6PD deficiency.
* **Liver function tests.**
* **Signs of hypersensitivity reactions.**
## Clinical Pearls
* Encourage adequate fluid intake to prevent crystalluria.
* Advise patients to report any rash, fever, sore throat, or other signs of infection immediately.
* Co-trimoxazole is renally eliminated; dose adjust per CrCl.
* Co-trimoxazole can inhibit bacterial folic acid synthesis, but human cells utilize pre-formed folic acid. However, high doses or prolonged therapy can lead to folate deficiency.
* Use with caution in patients with G6PD deficiency, as it can precipitate hemolysis.
* The "DS" tablet refers to a double-strength tablet, containing 800 mg sulfamethoxazole and 160 mg trimethoprim. Standard strength tablets contain half this amount.
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*Disclaimer: This information is intended for clinical decision support and does not replace comprehensive drug information resources or professional judgment. Always verify current prescribing information with authoritative sources.*
