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## Septra (Co-trimoxazole)
### Overview
Septra is a combination antibiotic containing sulfamethoxazole and trimethoprim.
### Primary Indications
* Treatment of urinary tract infections (UTIs).
* Treatment of Pneumocystis jirovecii pneumonia (PCP).
* Treatment of *Shigella* gastroenteritis.
* Prophylaxis and treatment of *Pneumocystis jirovecii* pneumonia (PCP) in immunocompromised patients.
* Treatment of *Stenotrophomonas maltophilia* infections.
### Adult Dosing
* **Urinary Tract Infections (UTIs):** 1 double-strength (DS) tablet (800 mg sulfamethoxazole/160 mg trimethoprim) every 12 hours for 3-14 days.
* **Pneumocystis jirovecii pneumonia (PCP):**
* **Treatment:** 15 mg/kg/day (based on trimethoprim component) in 3-4 divided doses every 12-6 hours for 14-21 days. This is typically administered as 2 DS tablets every 6 hours.
* **Prophylaxis:** 1 DS tablet once daily, or 1 DS tablet three times weekly.
* **Shigellosis:** 1 DS tablet every 12 hours for 5-7 days.
* **Stenotrophomonas maltophilia:** Dosing varies by severity and susceptibility; often 15-20 mg/kg/day (based on trimethoprim component) divided every 6-8 hours.
### Pediatric Dosing
* Dosing is based on the trimethoprim component, generally 8-10 mg/kg/day divided every 12 hours for UTIs and other infections.
* For PCP treatment: 15 mg/kg/day (based on trimethoprim component) in 3-4 divided doses.
* For PCP prophylaxis: 5 mg/kg/day (based on trimethoprim component) divided into 2 doses daily, or 150 mg/m^2/day (trimethoprim) divided into 2 doses daily.
* **Note:** Specific tablet strengths for pediatric dosing are crucial. Co-trimoxazole is available as single-strength (400 mg sulfamethoxazole/80 mg trimethoprim) and double-strength (800 mg sulfamethoxazole/160 mg trimethoprim) tablets, as well as oral suspension (40 mg trimethoprim/200 mg sulfamethoxazole per 5 mL). Always calculate doses carefully, especially in young children and infants, considering renal function.
### Dose Adjustments
* **Renal Impairment:** Dose adjustment is necessary based on creatinine clearance (CrCl).
* CrCl > 30 mL/min: Usual dose.
* CrCl 15-30 mL/min: Half the usual dose.
* CrCl < 15 mL/min: Avoid use or administer only with caution and frequent monitoring.
### 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 term infants during the first 2 months of life (risk of kernicterus).
* Severe renal insufficiency where urine output cannot be monitored.
* Severe hepatic insufficiency.
### Adverse Effects
* **Hematologic:** Agranulocytosis, aplastic anemia, megaloblastic anemia, thrombocytopenia, leukopenia, hemolytic anemia.
* **Dermatologic:** Rash (including Stevens-Johnson syndrome and toxic epidermal necrolysis), pruritus, urticaria.
* **Gastrointestinal:** Nausea, vomiting, diarrhea, stomatitis.
* **Hepatic:** Elevated liver enzymes, hepatitis, cholestatic jaundice.
* **Renal:** Increased serum creatinine, BUN.
* **Metabolic:** Hyperkalemia.
* **Other:** Fever, drug-induced lupus.
### Key Drug Interactions
* **Warfarin:** Increased INR. Monitor INR closely and adjust warfarin dose.
* **Methotrexate:** Increased risk of bone marrow suppression.
* **Potassium-sparing diuretics (e.g., spironolactone, amiloride):** Increased risk of hyperkalemia.
* **ACE inhibitors/ARBs:** Increased risk of hyperkalemia.
* **Oral hypoglycemics:** Increased risk of hypoglycemia.
* **Digoxin:** Increased digoxin levels, particularly in patients with renal impairment.
* **Tricyclic Antidepressants (TCAs):** Trimethoprim may inhibit the metabolism of TCAs, potentially increasing TCA levels.
### Monitoring
* Complete blood counts (CBC) with differential and platelet count, especially with prolonged therapy or in immunocompromised patients.
* Renal function (serum creatinine, BUN).
* Electrolytes (especially potassium).
* Liver function tests.
* For patients on warfarin, INR.
* Monitor for signs of hypersensitivity reactions.
### Clinical Pearls
* Co-trimoxazole can crystallize in the renal tubules; ensure adequate fluid intake to prevent crystalluria.
* Sulfonamides can potentiate the effects of oral hypoglycemics.
* Co-trimoxazole is a potent inhibitor of CYP2C8 and CYP2C9, which can affect the metabolism of other drugs.
* The risk of hypersensitivity reactions, including severe skin reactions, is increased in patients with HIV/AIDS, though this does not preclude its use for PCP treatment or prophylaxis.
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*This information is intended for healthcare professionals. Please consult the full prescribing information and local protocols for complete details. Always verify current drug information before making clinical decisions.*
