Septran%2520%2528co-Trimoxazole%2529

# Septran (co-Trimoxazole) ## Overview Septran is a branded formulation of co-trimoxazole, a fixed-dose combination of **trimethoprim** and **sulfamethoxazole** (TMP-SMX) in a 1:5 ratio. It is a bactericidal antibiotic that inhibits sequential steps in bacterial folate synthesis. ## Primary Indications - **Urinary tract infections** (UTIs) – uncomplicated and complicated - **Pneumocystis jirovecii pneumonia (PJP)** – treatment and prophylaxis (especially in HIV) - **Acute exacerbations of chronic bronchitis** (AECB) - **Shigellosis** and traveler’s diarrhea - **Methicillin-resistant Staphylococcus aureus (MRSA)** skin infections (depending on local susceptibility) - **Otitis media** and **sinusitis** (when beta-lactam allergy or resistance present) ## Adult Dosing - **General infections (UTI, bronchitis):** - 1 double-strength tablet (160/800 mg) or 2 single-strength tablets (80/400 mg) **every 12 hours** - **PJP treatment:** - 15–20 mg/kg/day (trimethoprim component) in divided doses every 6–8 hours for 14–21 days. *Check local protocol for weight-based dosing.* - **PJP prophylaxis:** - 1 double-strength tablet daily **OR** 1 single-strength tablet daily - **Shigellosis:** - 1 double-strength tablet every 12 hours for 5 days ## Pediatric Dosing *Calculate based on trimethoprim component (TMP). Dosing per local guidelines is strongly recommended.* - **General infections (UTI, otitis media):** - 8 mg/kg/day TMP (plus 40 mg/kg/day SMX) in two divided doses every 12 hours - Maximum: 160 mg TMP per dose - **PJP treatment:** - 15–20 mg/kg/day TMP in divided doses every 6–8 hours - **PJP prophylaxis:** - 5–10 mg/kg/day TMP as a single daily dose (or divided twice daily) on 3 consecutive days per week (e.g., Monday/Wednesday/Friday) - **Dosing in neonates (≤2 months):** Use only if clearly indicated; avoid in neonates <2 weeks of age due to bilirubin displacement risk. ## Dose Adjustments - **Renal impairment (CrCl):** - CrCl >30 mL/min: Standard dosing - CrCl 15–30 mL/min: Reduce to 50% of standard dose; monitor for toxicity - CrCl <15 mL/min: Avoid unless hemodialysis; use half-dose post-dialysis if needed - **Hepatic impairment:** Avoid in severe liver disease; no adjustment for mild–moderate impairment but monitor. ## Contraindications - History of severe hypersensitivity to sulfonamides or trimethoprim - Severe hepatic impairment - Severe renal impairment (CrCl <15 mL/min) unless dialysis available - Megaloblastic anemia due to folate deficiency - Neonates <2 weeks of age (risk of kernicterus) - Porphyria (sulfonamides may trigger attacks) - Pregnancy (especially first trimester; avoid near term – risk of kernicterus) - Breastfeeding (avoid if infant is jaundiced, ill, or premature; sulfonamides displace bilirubin) ## Adverse Effects - **Common:** Nausea, vomiting, rash (photosensitivity), pruritus - **Serious (rare but important):** - Stevens-Johnson syndrome / toxic epidermal necrolysis (SJS/TEN) - Aplastic anemia, agranulocytosis, thrombocytopenia - Hyperkalemia (especially with high-dose TMP) - Acute kidney injury (crystalluria, interstitial nephritis) - Hepatotoxicity - Methemoglobinemia (rare) - **GI:** C. *difficile* colitis - **Metabolic:** Hypoglycemia (especially in renal impairment, elderly) ## Key Drug Interactions - **Warfarin:** Potentiated anticoagulation (inhibit CYP2C9 metabolism and displace) - **Methotrexate:** Increased methotrexate toxicity (displacement and reduced clearance) - **ACE inhibitors / ARBs / K-sparing diuretics:** Increased risk of hyperkalemia (TMP is a potassium-sparing diuretic) - **Phenytoin:** Increased phenytoin half-life - **Cyclosporine:** Nephrotoxicity risk increased; also may reduce cyclosporine levels - **Dapsone:** Increased risk of hemolysis and methemoglobinemia - **Repaglinide:** Sulfamethoxazole inhibits CYP2C8, increasing repaglinide hypoglycemia risk - **Anticoagulants (rivaroxaban):** Increased bleeding risk ## Monitoring - Renal function (BUN, creatinine) at baseline and periodically, especially in elderly or impaired - Serum potassium (especially with high doses, renal impairment, or concurrent K+ altering drugs) - CBC with differential at baseline and weekly during prolonged therapy (evidence of bone marrow suppression) - Bilirubin (in neonates/juvenile patients) - Signs of skin reactions (advise patient to stop drug at first sign of rash) - Culture and sensitivity before starting (documenting susceptibility) ## Clinical Pearls - **Hydration:** Advise patients to drink plenty of water (≥2–3 L/day if tolerated) to prevent crystalluria. - **Allergy cross-reactivity:** Sulfonamide antibacterials do *not* cross-react with non-antibacterial sulfonamides (e.g., hydrochlorothiazide, sulfonylureas) in most patients. However, if true hypersensitivity occurs, avoid all sulfonamides. - **Hyperkalemia:** TMP acts like a potassium-sparing diuretic. Monitor K+ in patients with renal failure, diabetes, or those on ARBs/ACEi. - **IV administration:** For severe infections (e.g., PJP), use IV formulation; infuse over 60–90 minutes. Must be given in dextrose-containing fluids (incompatible with saline in concentrated form). - **Folate supplementation:** Give folinic acid (not folic acid) to prevent megaloblastic anemia if therapy is prolonged (controversial; generally not needed in short courses). Do *not* give with PJP treatment—folate may reduce efficacy. - **Pediatric UTI:** Due to rising resistance in community *E. coli*, TMP-SMX is often **not** first-line empiric therapy unless local resistance is <20%. Check local antibiogram. - **Avoid in G6PD deficiency** (risk of hemolysis, especially with sulfamethoxazole component). --- **Disclaimer:** This summary is for educational reference only and does not replace professional judgment. Always verify the most current prescribing information, local protocols, susceptibility patterns, and patient-specific factors (age, weight, renal/hepatic function, allergies) before initiating therapy.