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## Septra (Trimethoprim/Sulfamethoxazole)
### Overview
Septra is a combination antibiotic consisting of trimethoprim and sulfamethoxazole in a 1:5 ratio. It works by inhibiting sequential steps in the folic acid synthesis pathway, leading to bacterial cell death.
### Primary Indications
* Urinary tract infections (UTIs)
* Pneumocystis jirovecii pneumonia (PJP) prophylaxis and treatment
* Acute otitis media
* Traveler's diarrhea (enterotoxigenic E. coli)
* Shigellosis
* Bronchitis (acute exacerbations)
* Prophylaxis and treatment of other susceptible bacterial infections.
### Adult Dosing
* **Urinary Tract Infections and Shigellosis:** 1 double-strength (DS) tablet (160 mg trimethoprim/800 mg sulfamethoxazole) every 12 hours for 3-7 days (UTI) or 5 days (shigellosis).
* **Pneumocystis jirovecii Pneumonia (Treatment):** 15-20 mg/kg/day trimethoprim component, divided into 4 doses every 6 hours for 14-21 days. This is often administered as 2 double-strength tablets every 6 hours.
* **Pneumocystis jirovecii Pneumonia (Prophylaxis):** 1 double-strength tablet (160 mg trimethoprim/800 mg sulfamethoxazole) once daily, or 1 single-strength tablet (80 mg trimethoprim/400 mg sulfamethoxazole) twice daily. Other regimens exist.
* **Traveler's Diarrhea:** 1 double-strength tablet (160 mg trimethoprim/800 mg sulfamethoxazole) every 12 hours for 3-5 days.
* **Other Infections:** Dosing varies widely based on severity and site of infection. A common regimen is 1-2 double-strength tablets every 12 hours. Maximum daily dose is typically 4 double-strength tablets.
### Pediatric Dosing
Dosing is based on the trimethoprim component. Actual weight-based dosing should be confirmed with current guidelines or protocols.
* **Urinary Tract Infections and Shigellosis:** 8 mg/kg/day of the trimethoprim component, divided into 2 doses every 12 hours. For a 160/800 mg DS tablet, this is approximately 1/2 DS tablet per 33 lbs (15 kg) every 12 hours. Duration: 3-7 days (UTI), 5 days (shigellosis).
* **Pneumocystis jirovecii Pneumonia (Treatment):** 15-20 mg/kg/day of the trimethoprim component, divided into 4 doses every 6 hours for 14-21 days.
* **Pneumocystis jirovecii Pneumonia (Prophylaxis):** 5 mg/kg/day of the trimethoprim component, divided into 2 doses every 12 hours.
**Note:** For children under 2 months, trimethoprim/sulfamethoxazole is generally not recommended due to the risk of kernicterus.
### Dose Adjustments
* **Renal Impairment:**
* CrCl > 30 mL/min: No adjustment needed.
* CrCl 15-30 mL/min: Reduce maintenance dose by 25-50%.
* CrCl < 15 mL/min: Avoid use; if unavoidable, give usual loading dose then 1/4 of maintenance dose every 12 hours.
### Contraindications
* Known hypersensitivity to trimethoprim or sulfonamides.
* Infants younger than 2 months.
* Documented megaloblastic anemia due to folate deficiency.
* Severe renal or hepatic insufficiency.
* History of drug-induced immune thrombocytopenia with prior use of trimethoprim or sulfonamides.
### Adverse Effects
Common: Nausea, vomiting, diarrhea, rash.
Serious: Severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis), hematologic abnormalities (anemia, leukopenia, thrombocytopenia), hyperkalemia, interstitial nephritis, liver injury, crystalluria.
### Key Drug Interactions
* **Warfarin:** Increased INR. Monitor INR closely.
* **ACE Inhibitors/ARBs/Potassium-Sparing Diuretics:** Increased risk of hyperkalemia.
* **Methotrexate:** Increased risk of methotrexate toxicity (bone marrow suppression, renal toxicity).
* **Potassium Supplements:** Increased risk of hyperkalemia.
* **Diuretics (e.g., thiazides, furosemide):** Increased risk of thrombocytopenia, especially in elderly.
* **Potassium-rich foods/salt substitutes:** Increased risk of hyperkalemia.
### Monitoring
* Renal function (creatinine).
* Complete blood counts (CBC) with differential, especially with prolonged therapy or in immunocompromised patients.
* Electrolytes (especially potassium).
* Liver function tests.
* Signs and symptoms of hypersensitivity reactions and skin disorders.
### Clinical Pearls
* Encourage adequate fluid intake to prevent crystalluria.
* Sulfonamides can displace bilirubin from albumin; use with caution in neonates and patients with hyperbilirubinemia.
* Discontinue at the first sign of rash.
* Avoid concurrent use with other folate antagonists (e.g., methotrexate) unless folate supplementation is provided.
* Consider potential for cross-reactivity in patients with penicillin allergies, though data is conflicting.
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**Disclaimer:** This information is intended for healthcare professionals. Always consult the most current prescribing information, local protocols, and patient-specific factors before making clinical decisions.
