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## Trimethoprim/Sulfamethoxazole (TMP/SMX)
### Overview
Trimethoprim/sulfamethoxazole is a combination antibiotic that inhibits bacterial folic acid synthesis. It is available in various strengths, often as 80 mg TMP / 400 mg SMX (double strength) or 40 mg TMP / 200 mg SMX (single strength) tablets.
### Primary Indications
* Urinary tract infections (UTIs)
* *Pneumocystis jirovecii* pneumonia (PJP) prophylaxis and treatment
* Acute otitis media
* Acute exacerbations of chronic bronchitis
* Shigellosis gastroenteritis
* *Staphylococcus aureus* skin and soft tissue infections (including MRSA)
### Adult Dosing
* **UTIs and Shigellosis:** 160 mg TMP / 800 mg SMX (one DS tablet) every 12 hours for 3-7 days (UTI) or 5 days (shigellosis).
* **PJP Prophylaxis:** 160 mg TMP / 800 mg SMX (one DS tablet) daily or three times weekly.
* **PJP Treatment:** 15-20 mg TMP/kg/day divided into 2-4 doses, administered orally or IV, for 14-21 days. The SMX dose is typically 75-100 mg/kg/day.
* **Other Infections:** Dosing varies based on severity and site of infection. Common regimens include 160 mg TMP / 800 mg SMX every 8-12 hours.
### Pediatric Dosing
* Dosing is based on TMP component, typically 5-10 mg/kg/day divided every 12 hours for UTIs and other common infections.
* **PJP Prophylaxis:** 5 mg TMP/kg/day divided every 12 hours, administered three times weekly on alternate days.
* **PJP Treatment:** 15-20 mg TMP/kg/day divided into 2-4 doses, administered orally or IV, for 14-21 days. The SMX dose is typically 75-100 mg/kg/day.
* *Note: Specific pediatric dosing should be guided by weight and indication.*
### Dose Adjustments
* **Renal Impairment (Adults):**
* CrCl > 30 mL/min: Standard dosing.
* CrCl 15-30 mL/min: Reduce dose by 50%.
* CrCl < 15 mL/min: Use with caution or avoid.
* **Hepatic Impairment:** Use with caution; no specific dose adjustments are universally established.
### Contraindications
* Documented hypersensitivity to trimethoprim or sulfonamides.
* History of drug-induced thrombocytopenia with sulfonamides or trimethoprim.
* Marked hyperkalemia.
* Megaloblastic anemia due to folate deficiency.
* Premature infants and infants up to 2 months of age (risk of kernicterus).
* Severe renal or hepatic insufficiency where drug levels cannot be monitored.
### Adverse Effects
* **Common:** Nausea, vomiting, rash (including Stevens-Johnson syndrome/toxic epidermal necrolysis, especially with prolonged use or in HIV patients), hyperkalemia, elevated liver enzymes, pruritus.
* **Less Common:** Diarrhea, headache, dizziness, bone marrow suppression (leukopenia, thrombocytopenia, megaloblastic anemia), crystalluria (ensure adequate fluid intake).
### Key Drug Interactions
* **Warfarin:** TMP/SMX can potentiate INR. Monitor INR closely and adjust warfarin dose as needed.
* **Potassium-sparing diuretics (e.g., spironolactone, amiloride):** Increased risk of hyperkalemia.
* **ACE inhibitors and ARBs:** Increased risk of hyperkalemia.
* **Methotrexate:** TMP/SMX can increase methotrexate levels, leading to toxicity.
* **Digoxin:** Increased digoxin levels may occur.
* **Cyclosporine:** Increased cyclosporine levels can occur, especially in transplant patients.
* **Potassium supplements:** Increased risk of hyperkalemia.
### Monitoring
* **Renal function:** Baseline and periodically during therapy, especially in patients with impaired renal function.
* **Complete blood count (CBC):** Baseline and periodically during therapy, particularly with prolonged treatment or in immunocompromised patients. Monitor for signs of bone marrow suppression.
* **Electrolytes:** Especially potassium, particularly in patients with renal impairment or those taking other medications that affect potassium.
* **Liver function tests:** Periodically, especially in patients with hepatic impairment or those on prolonged therapy.
* **INR:** If co-administered with warfarin.
### Clinical Pearls
* Encourage adequate fluid intake to prevent crystalluria.
* Sulfonamides can precipitate in acidic urine; alkalinization of urine may be considered if crystalluria is a concern, though typically not necessary with adequate hydration.
* Photosensitivity reactions can occur; advise patients to use sun protection.
* TMP/SMX is renally eliminated; dose adjustments are crucial in renal impairment.
* The risk of severe rash is increased in patients with a history of sulfa allergy, HIV infection, and older adults.
*Disclaimer: This information is for educational purposes only and does not substitute for professional medical advice. Always consult the most current prescribing information and guidelines or a qualified healthcare provider for any health concerns or before making any treatment decisions.*
