Cotrimoxazole

# Cotrimoxazole ## Overview - **Classification**: Sulfonamide antibiotic; dihydrofolate reductase inhibitor. - **Mechanism**: Synergistically inhibits bacterial folic acid synthesis by blocking two sequential steps in the metabolic pathway. ## Primary Indications 1. **Urinary Tract Infections (UTIs)** - Treatment of acute uncomplicated and complicated UTIs. 2. **Pneumocystis Pneumonia (PCP)** - Treatment and prophylaxis in immunocompromised patients (e.g., HIV). 3. **Acute Exacerbations of Chronic Bronchitis (AECB)** - For susceptible organisms. 4. **Traveler's Diarrhea** - Caused by enterotoxigenic E. coli. ## Adult Dosing ### Standard Dosing **Uncomplicated Urinary Tract Infection (UTI)** - **Dose**: **160 mg TMP / 800 mg SMX** - **Frequency**: Every 12 hours - **Route**: Oral - **Duration**: 3-10 days (e.g., 3 days for uncomplicated cystitis in women). **Pneumocystis Pneumonia (PCP) Treatment** - **Dose**: **15-20 mg/kg/day TMP** (based on TMP component) - **Frequency**: Divided every 6-8 hours - **Route**: Oral or IV - **Duration**: 14-21 days - **Maximum**: Up to **320 mg TMP / 1600 mg SMX** per dose for severe infections. **Pneumocystis Pneumonia (PCP) Prophylaxis** - **Dose**: **160 mg TMP / 800 mg SMX** - **Frequency**: Once daily, or 3 times per week on consecutive days - **Route**: Oral ### Dose Adjustments - **Renal Impairment**: * CrCl **15-30 mL/min**: Administer **50% of standard dose**. * CrCl **<15 mL/min**: **Not recommended**; if used (e.g., PCP), administer **50% of dose every 24 hours**. Consider alternative. - **Hepatic Impairment**: Use with caution. Avoid in severe hepatic impairment or acute porphyria. - **Elderly Patients**: Increased risk of adverse effects (renal impairment, hyperkalemia, myelosuppression). Monitor closely; consider lower initial doses. ## Pediatric Dosing *(Dosing is based on the Trimethoprim (TMP) component)* ### Neonates (0-28 days) - **Contraindicated**: Due to risk of kernicterus (displacement of bilirubin from albumin). ### Infants (2 months - 12 months) **General Bacterial Infections (e.g., UTI)** - **Dose**: **8 mg/kg/day TMP** (40 mg/kg/day SMX) - **Frequency**: Divided every 12 hours - **Maximum**: **160 mg TMP / 800 mg SMX** per dose. **Pneumocystis Pneumonia (PCP) Treatment** - **Dose**: **15-20 mg/kg/day TMP** (75-100 mg/kg/day SMX) - **Frequency**: Divided every 6-8 hours - **Maximum**: Based on adult maximum for severe infections. - **Special Notes**: Often initiated IV for severe cases. **Pneumocystis Pneumonia (PCP) Prophylaxis** - **Dose**: **5-10 mg/kg/day TMP** (25-50 mg/kg/day SMX) - **Frequency**: Once daily or divided every 12 hours (e.g., 3 consecutive days/week). - **Maximum**: **160 mg TMP / 800 mg SMX** per dose. ### Children (1-12 years) *Follow Infants (2 months - 12 months) dosing guidelines based on weight.* **General Bacterial Infections** - **Dose**: **8 mg/kg/day TMP** (40 mg/kg/day SMX) - **Frequency**: Divided every 12 hours - **Maximum**: **160 mg TMP / 800 mg SMX** per dose. **Pneumocystis Pneumonia (PCP) Treatment** - **Dose**: **15-20 mg/kg/day TMP** (75-100 mg/kg/day SMX) - **Frequency**: Divided every 6-8 hours - **Maximum**: Up to **320 mg TMP / 1600 mg SMX** per dose. **Pneumocystis Pneumonia (PCP) Prophylaxis** - **Dose**: **5-10 mg/kg/day TMP** (25-50 mg/kg/day SMX) - **Frequency**: Once daily or divided every 12 hours (e.g., 3 consecutive days/week). - **Maximum**: **160 mg TMP / 800 mg SMX** per dose. ### Adolescents (13-18 years) - **Dose**: Typically follows **adult dosing guidelines**. - **Maximum**: Adult maximum doses apply. ## Safety Information ### Contraindications - **Absolute**: Documented **hypersensitivity to sulfonamides or trimethoprim**. - **Absolute**: Infants **less than 2 months of age** (risk of kernicterus). - **Absolute**: Severe renal impairment (**CrCl <15 mL/min**) not manageable by dialysis. - **Absolute**: Severe hepatic impairment or acute porphyria. - **Absolute**: Documented **megaloblastic anemia due to folate deficiency**. - **Absolute**: History of drug-induced immune thrombocytopenia with sulfonamides. ### Common Adverse Effects - **Very Common (>10%)**: Nausea, vomiting, diarrhea, skin rash, pruritus. - **Common (1-10%)**: Hyperkalemia, increased serum creatinine, elevated liver enzymes, photosensitivity. - **Serious but Rare**: * **Severe cutaneous adverse reactions (SCARs)**: Stevens-Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN), DRESS. * **Hematologic toxicities**: Agranulocytosis, aplastic anemia, thrombocytopenia, leukopenia (especially prolonged use). * **Renal failure**: Acute interstitial nephritis, crystalluria. * **Anaphylaxis**. ### Key Drug Interactions - **Warfarin**: Significantly **potentiates anticoagulant effect**, increasing INR and bleeding risk. Monitor INR frequently. - **Methotrexate**: Increases methotrexate levels and toxicity (myelosuppression, nephrotoxicity). Avoid or monitor closely. - **Potassium-sparing diuretics/ACE inhibitors/ARBs**: Increased risk of **hyperkalemia**. Monitor potassium levels closely. - **Phenytoin**: Inhibits phenytoin metabolism, increasing phenytoin levels and risk of toxicity. Monitor phenytoin levels. - **Dofetilide**: Concomitant use **contraindicated** due to increased dofetilide levels and risk of arrhythmias. ## Monitoring & Follow-up - **Before Treatment**: * Assess renal function (SCr, CrCl) and hepatic function (LFTs). * Obtain complete blood count (CBC) with differential, especially for prolonged therapy. - **During Treatment**: * Monitor **renal function and potassium levels** (especially in high-risk patients). * Monitor **CBC with differential** weekly for prolonged therapy (e.g., PCP treatment/prophylaxis). * Monitor for **skin rash or other hypersensitivity reactions**. * Monitor **INR** frequently if on warfarin. - **Clinical Signs**: Watch for signs of skin rash, fever, sore throat, easy bruising/bleeding, jaundice, decreased urine output, severe diarrhea. ## Clinical Pearls - 💡 **Hydration is key**: Counsel patients to maintain adequate fluid intake to prevent crystalluria. - 💡 **Folic Acid Supplementation**: Consider for prolonged high-dose therapy (e.g., PCP treatment) or in patients at risk of folate deficiency to reduce myelosuppression. - 💡 **Photosensitivity**: Advise patients to use sunscreen and wear protective clothing to prevent sunburn. - 💡 **Take with food**: To minimize gastrointestinal upset. - 💡 **Allergy Clarification**: Distinguish true sulfa allergy (hypersensitivity reactions) from GI intolerance when assessing patient history. > **⚠️ Important**: This information is for educational purposes only. Always consult current prescribing information, local guidelines, and clinical judgment before prescribing.