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# Septran (Co-Trimoxazole)
## Overview
Co-trimoxazole is a combination 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
* *Shigella* and *Salmonella* gastroenteritis
* Certain respiratory tract infections
## Adult Dosing
* **Uncomplicated UTI:** 1 DS (double strength) tablet (800 mg sulfamethoxazole/160 mg trimethoprim) every 12 hours for 3-7 days.
* **PCP Treatment:** 15 mg/kg/day (based on trimethoprim component) divided every 6 hours (or 2 DS tablets every 6 hours) for 14-21 days.
* **PCP Prophylaxis:** 1 DS tablet once daily, or 1 DS tablet three times a week (e.g., Monday, Wednesday, Friday). Consult local guidelines for optimal prophylaxis regimens.
* **Other Infections:** Dosing varies significantly based on the type and severity of infection. Consult specific guidelines. Maximum dose generally should not exceed 160 mg trimethoprim and 800 mg sulfamethoxazole every 12 hours unless treating severe infections like PCP.
## Pediatric Dosing
Dosing is typically calculated based on the trimethoprim component (mg/kg/day).
* **UTI and *Shigella*:** 8 mg/kg/day of trimethoprim, divided every 12 hours. (Equivalent to 40 mg/kg/day of sulfamethoxazole). For example, a 20 kg child would receive 160 mg trimethoprim/day, typically dosed as 10 mL of a 40 mg/5 mL trimethoprim suspension every 12 hours.
* **PCP Treatment:** 15 mg/kg/day of trimethoprim, divided every 6 hours for 14-21 days.
* **PCP Prophylaxis:** 5 mg/kg/day of trimethoprim, divided every 12 hours (or 150 mg/m²/day of sulfamethoxazole, divided every 12 hours).
**Note:** Pediatric dosing for specific indications can vary. Always refer to reliable pediatric dosing resources or local protocols. Maximum daily dose for children should not exceed the adult maximum.
## Dose Adjustments
* **Renal Impairment (CrCl < 15 mL/min):** Avoid use.
* **Renal Impairment (CrCl 15-30 mL/min):** Reduce dose by 25-50%.
* **Renal Impairment (CrCl 30-50 mL/min):** Reduce dose by 25%.
* **Hepatic Impairment:** Use with caution; dose reduction may be necessary.
## Contraindications
* Hypersensitivity to trimethoprim or sulfonamides.
* Documented megaloblastic anemia due to folate deficiency.
* Infants less than 2 months of age (risk of kernicterus).
* Severe renal or hepatic insufficiency when drug concentration cannot be monitored.
* History of drug-induced thrombocytopenia with either component.
## Adverse Effects
Common: Rash, nausea, vomiting, diarrhea.
Serious: Severe rash (Stevens-Johnson syndrome, toxic epidermal necrolysis), hyperkalemia, bone marrow suppression (anemia, leukopenia, thrombocytopenia), interstitial nephritis, hepatotoxicity, photosensitivity, crystalluria.
## Key Drug Interactions
* **Warfarin:** Increased INR. Monitor INR closely and adjust warfarin dose as needed.
* **Methotrexate:** Increased methotrexate levels and toxicity. Avoid concurrent use or monitor closely for bone marrow suppression.
* **ACE Inhibitors/ARBs/Potassium-Sparing Diuretics:** Increased risk of hyperkalemia.
* **Dofetilide:** Increased risk of dofetilide-induced arrhythmias. Co-trimoxazole is contraindicated.
* **Cyclosporine:** Increased cyclosporine levels, potentially leading to nephrotoxicity.
* **Potassium:** Increased risk of hyperkalemia.
* **Diuretics (Thiazide):** Increased risk of thrombocytopenia in elderly patients.
## Monitoring
* Renal function (BUN, creatinine).
* Complete blood counts (CBC) with differential and platelets, especially with prolonged therapy or in elderly patients.
* Liver function tests (LFTs).
* Serum potassium.
* INR if patient is on warfarin.
* Hydration status to prevent crystalluria.
## Clinical Pearls
* Advise patients to drink plenty of fluids to prevent crystalluria.
* Monitor for rash, which can be a sign of severe hypersensitivity. Discontinue immediately if a rash develops.
* Trimethoprim can cause a reversible elevation in serum creatinine without affecting glomerular filtration rate; this is due to inhibition of tubular secretion.
* Concurrent folic acid supplementation (e.g., 1 mg daily) may be considered for patients on long-term co-trimoxazole therapy to prevent hematologic side effects, particularly in elderly patients or those with folate deficiency. However, this may reduce efficacy in certain indications like PCP treatment.
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*Please verify current prescribing information for the most up-to-date recommendations.*
