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# Co-trimoxazole (Trimethoprim/Sulfamethoxazole)
## Overview
Co-trimoxazole is a combination antibiotic of trimethoprim and sulfamethoxazole, which act sequentially to inhibit folic acid synthesis in bacteria. It is available in various formulations, including oral tablets (often labeled as 80 mg trimethoprim/400 mg sulfamethoxazole), oral suspension, and intravenous injection.
## Primary Indications
* Urinary tract infections (UTIs)
* *Pneumocystis jirovecii* pneumonia (PJP) prophylaxis and treatment
* Acute otitis media
* Acute exacerbations of chronic bronchitis
* Traveler's diarrhea
* Shigellosis
* *Staphylococcus aureus* infections (including some MRSA infections, depending on susceptibility)
## Adult Dosing
* **UTIs:** 1 double-strength (DS) tablet (160 mg trimethoprim/800 mg sulfamethoxazole) every 12 hours for 3-7 days.
* **PJP Treatment:** 15 mg/kg/day trimethoprim component, divided into 3-4 doses every 24 hours for 14-21 days.
* **PJP Prophylaxis:** 1 DS tablet (160 mg trimethoprim/800 mg sulfamethoxazole) daily, or 1 DS tablet three times weekly (alternative regimens may apply).
* **Other Infections:** Dosing varies significantly by indication and severity. Common regimens include 1-2 DS tablets every 12 hours.
## Pediatric Dosing
Dosing is generally based on the trimethoprim component (5 mg/kg/dose to 15 mg/kg/day) divided every 12 or 24 hours, depending on the indication and formulation. **Specific pediatric dosing should be guided by local protocols or specialized pediatric references.**
* **General Infections:** Typically 6-12 mg/kg/day of the trimethoprim component, divided every 12 hours.
* **PJP Prophylaxis:** 5 mg/kg/dose trimethoprim component, divided every 12 hours, given 3 times weekly on alternate days.
* **PJP Treatment:** 15 mg/kg/day trimethoprim component, divided every 6-8 hours for 14-21 days.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 30 mL/min: No adjustment needed.
* CrCl 15-30 mL/min: Administer at 75% of the usual dose.
* CrCl < 15 mL/min: Avoid use or administer at 50% of the usual dose and monitor drug levels closely.
* **Hepatic Impairment:** Use with caution.
## Contraindications
* Known hypersensitivity to trimethoprim, sulfamethoxazole, or sulfonamides.
* Documented severe adverse reactions to sulfonamides (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis).
* Infants less than 2 months of age (due to risk of kernicterus).
* Marked bone marrow depression or history of sulfonamide-induced thrombocytopenia.
* Severe renal insufficiency or hepatic insufficiency when pharmacokinetic monitoring is not feasible.
* Anuria or oliguria.
## Adverse Effects
* **Common:** Nausea, vomiting, rash (including photosensitivity), hyperkalemia.
* **Serious:** Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), aplastic anemia, agranulocytosis, thrombocytopenia, hepatotoxicity, acute kidney injury, hyperkalemia, diarrhea (including *Clostridioides difficile*-associated diarrhea), hyponatremia, hypoglycemia.
## Key Drug Interactions
* **Warfarin:** Co-trimoxazole can potentiate the anticoagulant effect. Monitor INR closely and consider dose adjustments for warfarin.
* **ACE Inhibitors/ARBs:** Increased risk of hyperkalemia.
* **Potassium Supplements:** Increased risk of hyperkalemia.
* **Methotrexate:** Co-trimoxazole can increase methotrexate levels, increasing risk of toxicity.
* **Cyclosporine:** Increased risk of nephrotoxicity.
* **Diuretics (especially thiazides in elderly):** Increased risk of hyperkalemia.
* **Oral Hypoglycemics:** Potentiation of hypoglycemic effect.
* **Procainamide/N-acetylprocainamide:** Increased plasma levels may occur.
## Monitoring
* **Renal function** (creatinine, BUN).
* **Electrolytes**, especially potassium.
* **Complete blood counts** (CBC) with differential and platelet count, particularly with prolonged therapy or in immunocompromised patients.
* **Liver function tests** (LFTs).
* **Skin examination** for rash.
* **Therapeutic drug monitoring** may be indicated in severe renal impairment or for PJP treatment.
## Clinical Pearls
* Always check for sulfa allergies.
* Ensure adequate hydration to minimize risk of crystalluria.
* Photosensitivity is common; advise patients to use sun protection.
* Co-trimoxazole is teratogenic, especially in the first trimester (folate antagonist); avoid if possible, particularly during pregnancy, or consider folate supplementation.
* In PJP treatment, trimethoprim is the active component and doses are calculated based on its weight-based dose.
* IV formulation should be infused slowly over 60-90 minutes to reduce risk of infusion-related reactions.
* For patients with a severe sulfa allergy, alternative antibiotic therapy is recommended.
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This information is intended for healthcare professionals. Always consult the most current prescribing information and relevant clinical guidelines for complete details and to verify dosing and safety information before use.
