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# Co-Trimoxazole (Sulfamethoxazole/Trimethoprim)
## Overview
Co-trimoxazole is a combination antibiotic of sulfamethoxazole (a sulfonamide) and trimethoprim. It is available in various formulations, including oral tablets, 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
* Shigellosis gastroenteritis
* Traveler's diarrhea
* Prophylaxis and treatment of *Staphylococcus aureus* infections in certain patients (e.g., nasal carriage)
## Adult Dosing
* **Urinary Tract Infections (Uncomplicated):** 1 double-strength (DS) tablet (160 mg trimethoprim/800 mg sulfamethoxazole) twice daily for 3 days.
* **Urinary Tract Infections (Complicated):** 1 DS tablet twice daily for 7-10 days.
* **Pneumocystis jirovecii Pneumonia (Treatment):** 15 mg/kg/day of trimethoprim component, divided into 3 or 4 doses, given intravenously or orally. Duration is typically 14-21 days.
* **Pneumocystis jirovecii Pneumonia (Prophylaxis):** 1 DS tablet once daily, or 1 DS tablet three times weekly.
* **Shigellosis:** 1 DS tablet twice daily for 5 days.
* **Traveler's Diarrhea:** 1 DS tablet twice daily for 3 days.
## Pediatric Dosing
Dosing is based on the trimethoprim component.
* **Urinary Tract Infections:** 8 mg/kg/day of trimethoprim component, given in two divided doses. Oral suspension is often preferred.
* **Pneumocystis jirovecii Pneumonia (Treatment):** 15 mg/kg/day of trimethoprim component, divided into 3 or 4 doses.
* **Pneumocystis jirovecii Pneumonia (Prophylaxis):** 5 mg/kg/day of trimethoprim component, given in two divided doses, on a daily or three times weekly schedule.
* **Acute Otitis Media:** 8 mg/kg/day of trimethoprim component, given in two divided doses.
## Dose Adjustments
* **Renal Impairment:**
* CrCl > 30 mL/min: No adjustment necessary.
* CrCl 15-30 mL/min: Half the usual dose.
* CrCl < 15 mL/min: Avoid use.
* **Hepatic Impairment:** Use with caution; no specific dosing adjustments are typically provided, but monitor liver function.
## Contraindications
* Known hypersensitivity to trimethoprim, sulfonamides, or any component of the formulation.
* Documented megaloblastic anemia due to folate deficiency.
* Infants less than 2 months of age (risk of kernicterus).
* Severe renal insufficiency or hepatic insufficiency when pharmacokinetic monitoring is not feasible.
* History of drug-induced thrombocytopenia with either agent or related drugs.
* Pregnancy at term and in breastfeeding mothers (risk of kernicterus).
## Adverse Effects
* **Common:** Nausea, vomiting, diarrhea, rash, pruritus.
* **Serious:** Severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis), hypersensitivity reactions (including anaphylaxis), blood dyscrasias (anemia, neutropenia, thrombocytopenia, leukopenia), hyperkalemia, crystalluria (ensure adequate hydration), liver injury, pseudomembranous colitis.
## Key Drug Interactions
* **Warfarin:** Increased INR. Monitor INR closely.
* **Methotrexate:** Increased risk of methotrexate toxicity.
* **Potassium-sparing diuretics (e.g., spironolactone, amiloride):** Increased risk of hyperkalemia.
* **ACE inhibitors / ARBs:** Increased risk of hyperkalemia.
* **Cyclosporine:** Increased cyclosporine levels.
* **Potassium supplements:** Increased risk of hyperkalemia.
* **Dapsone:** Increased levels of both drugs.
* **Oral hypoglycemics:** Increased risk of hypoglycemia.
* **Rifampin:** May decrease levels of co-trimoxazole.
* **Tricyclic antidepressants:** May decrease efficacy.
* **Amantadine:** Increased risk of CNS effects.
* **Procainamide:** Increased levels.
## Monitoring
* Complete blood count (CBC) with differential, particularly with prolonged therapy or in immunocompromised patients.
* Renal function (BUN, creatinine).
* Electrolytes, especially potassium.
* Liver function tests (LFTs).
* Signs and symptoms of hypersensitivity reactions and skin reactions.
* Monitor for diarrhea and signs of *Clostridioides difficile* infection.
* For pregnant patients, monitor for signs of kernicterus in neonates.
## Clinical Pearls
* Adequate fluid intake is crucial to prevent crystalluria.
* Co-trimoxazole can interfere with urine glucose and protein testing.
* Photosensitivity is a potential adverse effect; advise patients to avoid excessive sun exposure.
* Discontinue immediately if a rash develops; early recognition of severe skin reactions is critical.
* Due to the potential for kernicterus, co-trimoxazole is generally avoided in newborns and premature infants.
* For patients with a sulfa allergy, there is a significant risk of cross-reactivity.
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*Disclaimer: This information is intended for healthcare professionals and is not a substitute for professional medical advice. Always consult the current prescribing information and your institution's formulary for the most up-to-date and complete drug information.*
