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Trimethoprim Sulfamethoxazole

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Trimethoprim Sulfamethoxazole, SMX-TMP, TMP-SMZ, Bactrim, Sulfatrim, Co-trimoxazole, Septra

  • See Also
  1. Sulfonamide
  2. Sulfonamide Allergy
  • Indications
  1. Organisms
    1. Enteric Gram Negative Bacteria (esp. Urinary Tract Infections)
  2. Conditions
    1. Urinary Tract Infection
    2. Pneumocystis carinii prophylaxis and treatment
    3. MRSA Skin Infections
  • Contraindications
  1. Avoid in infant under age 2 months (Kernicterus risk)
  2. Sulfonamide Allergy
  3. G6PD Deficiency
  4. Avoid in Streptococcal Pharyngitis, Acute Otitis Media and Acute Sinusitis (high Antibiotic Resistance rates)
  5. Stage 5 Chronic Kidney Disease (eGFR <15 ml/min)
  • Mechanism
  1. See Sulfonamide
  • Precautions
  1. Prolonged use may cause very severe adverse reactions
  2. Follow Complete Blood Count (CBC) in prolonged use
  3. Hyperkalemia risk (especially in Renal Insufficiency, related to trimethoprim component)
  • Medications
  1. Double Strength (DS)
    1. Trimethoprim 160 mg
    2. Sulfamethoxazole 800 mg
  2. Single Strength (SS)
    1. Trimethoprim 80 mg
    2. Sulfamethoxazole 400 mg
  3. Pediatric Suspension (40/200 per 5 ml)
    1. Trimethoprim 40 mg per 5 ml
    2. Sulfamethoxazole 200 mg per 5 ml
  1. Take on an empty Stomach
  2. Take more than 1 hour before or two hours after food
  • Dosing
  • Adult (or child weight >40 kg)
  1. See Pneumocystis Prophylaxis
  2. See PCP Pneumonia
  3. Standard Dosing (e.g. Urinary Tract Infection)
    1. Take 1 DS tablet (160/800 mg) orally twice daily
  4. Higher Dosing (e.g. MRSA Cellulitis)
    1. Take 1-2 DS tablet orally twice daily
  • Dosing
  • Child (weight <40 kg)
  1. Avoid in age <2 months old (Kernicterus risk), G6PD or marked Hyperbilirubinemia (see above)
  2. Dosing uses 40/200 mg per 5 ml suspension
  3. Treatment (e.g. Urinary Tract Infection)
    1. Dose 1 ml/kg/day divided twice daily orally (40/200 per 5 ml suspension)
      1. Alternatively dose 8 mg/kg/day of TMP component orally divided twice daily
      2. Doses up to 1.5 ml/kg/day may be used in MRSA Skin Infections (see Cellulitis)
      3. Maximum: 20 ml (160/800 mg) orally twice daily
    2. For each 10 kg weight, dose 5 ml suspension twice daily (up to maximum of 20 ml/dose)
      1. Age 2 months (5 kg): 2.5 ml orally twice daily
      2. Age 1 year (10 kg): 5.0 ml orally twice daily
      3. Age 3 years (15 kg): 7.5 ml orally twice daily
      4. Age 5 years (20 kg): 10 ml orally twice daily
  4. Prophylaxis of Urinary Tract Infections
    1. Dose: 4 mg/kg/day of Trimethoprim dosed once daily
  • Dosing
  • Renal (eGFR <30 ml/min)
  1. eGFR 15 to 30 ml/min (Stage 4 Chronic Kidney Disease)
    1. Decrease Trimethoprim-Sulfamethoxazole dose by 50%
  2. eGFR <15 ml/min (Stage 5 Chronic Kidney Disease)
    1. Avoid the use of Trimethoprim Sulfamethoxazole
  • Dosing
  • HIV
  1. Pneumocystis Treatment
    1. Take 15 to 20 mg/kg/day of TMP component orally or IV divided every 8 hours for 21 days
    2. Adult with mild to moderate infections
      1. Take 2 DS tablets orally three times daily for 21 days
    3. Child
      1. Take 5 ml suspension (40/200 mg) per every 8 kg orally every 6 hours for 21 days
  2. Pneumocystis Prophylaxis
    1. Adult
      1. Take one tablet DS orally daily (per FDA labeling) OR
      2. Take one tablet SS orally daily (off label use)
    2. Child
      1. Take 150 mg/m2/day of TMP component orally divided twice daily on 3 consecutive days per week
  • Adverse Effects
  • General
  1. See Sulfonamide
  2. Allergic Reaction or Anaphylaxis
    1. See Sulfonamide Allergy
  3. Bone Marrow suppression (Agranulocytosis)
    1. Highest risk with prolonged use, or high dose IV use
  4. Steven's Johnson Syndrome
  5. Toxic Epidermal Necrolysis
  6. Hyperkalemia
    1. Related to trimethoprim component
    2. Higher risk with underlying Renal Insufficiency
    3. Exacerbated by ACE Inhibitor, Angiotensin Receptor Blocker, and Potassium supplements
  7. Neonatal Hyperbilirubinemia and Kernicterus
    1. Sulfonamides compete with Bilirubin for albumin binding
    2. Results in increased free Bilirubin, with risk of Neonatal Hyperbilirubinemia and Kernicterus
  8. Propylene glycol toxicity
    1. Associated with high dose IV use (e.g. PCP Pneumonia)
  • Adverse Effects
  • HIV patients (40-60% within 3 weeks)
  1. Hepatitis
  2. Neutropenia
  3. Anemia
  4. Hyponatremia
  5. Hyperkalemia (6% of patients, esp. elderly)
  6. Nausea or Vomiting
  7. Rash
  8. Fever
  • Safety
  1. Pregnancy
    1. Avoid in first and third trimesters (considered safe in second trimester)
  2. Lactation
    1. Avoid in first month of life (HyperbilirubinemiaKernicterus risk)
    2. Avoid in maternal or infant G6PD Deficiency
    3. Otherwise considered safe in Lactation after first month of life
  • Drug Interactions
  1. Other drugs decrease Trimethoprim Sulfamethoxazole levels
    1. Rifampin
  2. Trimethoprim Sulfamethoxazole increases other drug levels
    1. Phenytoin (Dilantin)
    2. Methotrexate
    3. Warfarin
      1. Trimethoprim Sulfamethoxazole increases Warfarin effects and may result in up to a 3 fold increase in INR
      2. Monitor INR and plan 25-50% Warfarin dose reduction while on Trimethoprim Sulfamethoxazole
  3. Hyperkalemia risk
    1. Increased risk with ACE Inhibitors, Angiotensin Receptor Blockers, Spironolactone
    2. Higher risk with age >65 years, Renal Insufficiency, Diabetes Mellitus and Heart Failure
    3. Significantly increased rate of hospitalization and sudden death
    4. Avoid Septra use for longer than three days with these agents and comorbidities in age >65 years
    5. Consider alternative Antibiotics, holding Antihypertensive or recheck Serum Potassium in 4-5 days
    6. Fralick (2014) BMJ 349:g6196 +PMID:25359996 [PubMed]
  4. References
    1. (2014) Presc lett 21(8): 47
  • Resources
  1. Trimethoprim Sulfamethoxazole Tablet (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f59d0c04-9c66-4d53-a0e1-cb55570deb62
  2. Trimethoprim Sulfamethoxazole Suspension (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=a6182855-6287-45e9-b6b4-7b57efc9c76e
  3. Trimethoprim Sulfamethoxazole Injection Solution (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b89b5502-ce87-45a6-a43c-9891da3cfca4
  • References
  1. Hamilton (2020) Tarascon Pocket Pharmacopoeia
  2. Kemnic (2023) Trimethoprim Sulfamethoxazole, StatPearls, Treasure Island, Florida
    1. https://www.ncbi.nlm.nih.gov/books/NBK513232/