What are the indications and dosing guidelines for Cotrimoxazole (trimethoprim/sulfamethoxazole)?

Indications and Dosing Guidelines for Cotrimoxazole (Trimethoprim/Sulfamethoxazole)

Cotrimoxazole (trimethoprim/sulfamethoxazole) is indicated for urinary tract infections, shigellosis, acute exacerbations of chronic bronchitis, Pneumocystis carinii pneumonia treatment and prophylaxis, traveler's diarrhea, and as a second-line agent for certain respiratory and other infections. 1

Primary Indications

Urinary Tract Infections

• For adults: 1 double-strength tablet (160mg trimethoprim/800mg sulfamethoxazole) or 2 regular tablets (80mg/400mg) every 12 hours for 10-14 days 1
• For children: 8mg/kg trimethoprim and 40mg/kg sulfamethoxazole per 24 hours, divided into two doses every 12 hours for 10 days 1
• May be used as a second-line agent for complicated UTIs when first-line agents fail or are contraindicated 2

Respiratory Tract Infections

• Acute exacerbations of chronic bronchitis in adults: 1 double-strength tablet or 2 regular tablets every 12 hours for 14 days 1
• Acute otitis media in children: 8mg/kg trimethoprim and 40mg/kg sulfamethoxazole per 24 hours, divided into two doses every 12 hours for 10 days 1
• Second-line agent for non-severe pneumonia in children when amoxicillin is not suitable 2

Gastrointestinal Infections

• Shigellosis: Same dosage as for UTIs but for 5 days duration 1
• Traveler's diarrhea: 1 double-strength tablet or 2 regular tablets every 12 hours for 5 days 1
• Second-line agent for dysentery when quinolones are not suitable 2

Pneumocystis carinii Pneumonia (PCP)

• Treatment: 75-100mg/kg sulfamethoxazole and 15-20mg/kg trimethoprim per 24 hours in equally divided doses every 6 hours for 14-21 days 1
• Prophylaxis in adults: 1 double-strength tablet daily 1
• Prophylaxis in children: 750mg/m²/day sulfamethoxazole with 150mg/m²/day trimethoprim given in equally divided doses twice daily, on 3 consecutive days per week 1

Other Indications

• Prophylaxis for patients on prolonged corticosteroids, particularly with other risk factors: 960mg three times weekly or 480mg daily 2
• Non-tuberculous mycobacterial pulmonary disease as part of combination therapy 2
• Pharyngeal gonococcal infection in patients who cannot tolerate cephalosporins or quinolones: 720mg trimethoprim/3,600mg sulfamethoxazole once daily for 5 days 2

Special Populations and Dosing Adjustments

Renal Impairment

• Creatinine clearance >30 mL/min: Standard regimen
• Creatinine clearance 15-30 mL/min: Half the usual regimen
• Creatinine clearance <15 mL/min: Not recommended 1

Pediatric Patients

• Not recommended for infants less than 2 months of age due to risk of kernicterus 1
• For long-term prophylaxis in children with recurrent UTIs: 2mg trimethoprim and 10mg sulfamethoxazole per kg body weight daily 3

Contraindications

• Hypersensitivity to sulfonamides or trimethoprim 2
• Pregnancy (risk of teratogenicity) 2
• Severe renal impairment 2
• Liver parenchymal damage 2
• Infants under 2 months of age 2, 1
• Breast-feeding mothers if there's risk of infant developing hyperbilirubinaemia 2

Important Monitoring and Precautions

Adverse Effects to Monitor

• Dermatological: Rash, photosensitivity, Stevens-Johnson syndrome (rare but serious) 2
• Gastrointestinal: Nausea, vomiting, diarrhea 2
• Hematological: Monitor for blood disorders, particularly in elderly patients or those on prolonged therapy 2, 4
• Metabolic: Hyperkalaemia 2
• Neurological: Headache 2

Drug Interactions

• Anticoagulants: Potentiates warfarin activity 2
• Methotrexate: Increased levels and antifolate effects 2
• Phenytoin: Reduced metabolism, monitor serum levels 2
• Oral contraceptives: Risk of contraceptive failure 2
• Cyclosporine: Risk of renal function deterioration 2
• Diuretics (especially thiazides): Increased risk of thrombocytopenia 2

Clinical Pearls

• Cotrimoxazole is preferred over trimethoprim alone for specific infections including toxoplasmosis, brucellosis, nocardiosis, and Pneumocystis pneumonia due to synergistic effects 5
• For many common infections, particularly uncomplicated UTIs, trimethoprim alone may be equally effective with fewer side effects 5, 6
• Patient compliance is typically better with trimethoprim alone compared to cotrimoxazole due to simpler dosing regimen and fewer side effects 6
• Stevens-Johnson syndrome is a rare but devastating complication that should be discussed with patients when initiating therapy 2
• Increasing bacterial resistance may limit effectiveness for empiric therapy in some geographic regions; local resistance patterns should guide use 2
• For patients requiring pneumocystosis prophylaxis while on immunosuppression (such as during cancer treatment), cotrimoxazole is the preferred agent 2

Remember that dosing should be adjusted based on the specific indication, patient age, weight, and renal function, with close monitoring for adverse effects, particularly during prolonged therapy 2, 1.