II. 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

III. 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)

IV. Mechanism

V. 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)

VI. 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

VII. Dosing: Directions (regarding Sulfonamide component)

  1. Take on an empty Stomach
  2. Take more than 1 hour before or two hours after food

VIII. 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

IX. 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

X. 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

XI. 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

XII. 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)

XIII. 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

XIV. 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

XV. 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

XVII. 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/

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Related Studies

Cost: Medications

sulfatrim (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
SULFATRIM PEDIATRIC SUSPENSION Generic $0.06 per ml

Ontology: Trimethoprim-Sulfamethoxazole Combination (C0041044)

Definition (NCI_NCI-GLOSS) An antibiotic drug used to treat infection and prevent pneumocystis carinii pneumonia.
Definition (NCI) A synthetic combination of two antibacterial agents, trimethoprim and sulfamethoxazole. This synergistic combination, also known as Co-Trimoxazole, inhibits two sequential steps in the bacterial metabolism of folic acid. Trimethoprim is a pyrimidine inhibitor of dihydrofolate reductase; sulfamethoxazole is a sulfamide inhibitor of bacterial dihydrofolate synthase.
Definition (MSH) This drug combination has proved to be an effective therapeutic agent with broad-spectrum antibacterial activity against both gram-positive and gram-negative organisms. It is effective in the treatment of many infections, including PNEUMOCYSTIS PNEUMONIA in AIDS.
Definition (PDQ) A synthetic combination of two antibacterial agents, trimethoprim and sulfamethoxazole. This synergistic combination, also known as co-trimoxazole, inhibits two sequential steps in the bacterial metabolism of folic acid. Trimethoprim is a pyrimidine inhibitor of dihydrofolate reductase; sulfamethoxazole is a sulfamide inhibitor of bacterial dihydrofolate synthetase. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=39724&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=39724&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C909" NCI Thesaurus)
Concepts Organic Chemical (T109) , Pharmacologic Substance (T121)
MSH D015662
SnomedCT 13939004, 398731002, 324367007, 387079003, 324356006, 703745000
LNC LP16302-9, MTHU008494
English Centran, Centrin, Eslectin, Insozalin, Trimedin, Trimethoprim Sulfamethoxazole, Trimethoprim Sulfamethoxazole Combination, Trimethoprim-Sulfamethoxazole, Trimezole, Sulfamethoxazole-Trimethoprim Combination, Sulfamethoxazole Trimethoprim Combination, Benzenesulfonamide, 4-amino-N-(5-methyl-3-isoxazolyl)-, mixt. with 5-((3,4,5-trimethoxyphenyl)methyl)-2,4-pyrimidinediamine, Bactrimel, Co Trimoxazole, TMP SMX, TMP-SMX, trimethoprim-sulfamethoxazole, SULFAMETHOXAZOLE/TRIMETHOPRIM, Co-trimoxazole [generic], Co-trimoxazole [proprietary], Co-trimazole, trimethoprim + sulfamethoxazole, trimethoprim + sulfamethoxazole (medication), Sulfamethoxazole-Trimethoprim, sulfamethoxazole-trimethoprim, Trimethoprim-Sulfamethoxazole Combination [Chemical/Ingredient], Sulfamethoxazole / Trimethoprim, smx tmp, tmp smx, trimezole, cotrimoxazole, smz tmp, co-trimazole, smz-tmp, tmp-smx, trimethoprim sulfamethoxazole, trimethoprim-sulphamethoxazole, co trimoxazole, smx-tmp, centrin, sulfamethoxazole trimethoprim, Trimethoprim-Sulfamethoxazole Combination, sulfamethoxazole and trimethoprim, Co-trimoxazole [proprietary] (product), Trimethoprim-sulfamethoxazole, Sulphamethoxazole-trimethoprim, Co-trimoxazole (product), SMX-TMP, Trimethoprim-sulphamethoxazole, Sulfamethoxazole-trimethoprim, Co-trimoxazole [generic] (product), Co-trimoxazole (substance), Trimethoprim+Sulfamethoxazole, Co-trimoxazole, co-trimoxazole, Sulfamethoxazole + trimethoprim (substance), Sulfamethoxazole + trimethoprim (product), Sulfamethoxazole + trimethoprim, Sulphamethoxazole + trimethoprim, Co-trimoxazole [generic] (substance), Co-trimoxazole [proprietary] (substance), Co-Trimoxazole, Cotrimoxazole, SMZ-TMP, Sulfamethoxazole and Trimethoprim
German Trimezole, Eslectin, Centrin, Centran, Insozalin, Trimedin, TMP-SMX, Co-Trimoxazole, Trimethoprim-Sulfamethoxazol, Sulfamethoxazol-Trimethoprim-Kombination, Trimethoprim-Sulfamethoxazol-Kombination
Swedish Trimetoprim-sulfametoxazolkombination
Czech trimethoprim-sulfamethoxazol kombinace
Finnish Trimetopriimi-sulfametoksatsoliyhdistelmä
Russian TRIMETOPRIM-SUL'FAMETOKSAZOLA SOEDINENIE, ТРИМЕТОПРИМ-СУЛЬФАМЕТОКСАЗОЛА СОЕДИНЕНИЕ
Japanese トリメトプリム-スルファメトキサゾール配合製剤, スルファメトキサゾール-トリメトプリム配合製剤, ST合剤, TMP-SMX合剤
French TMPSMX, Association triméthoprime-sulfaméthoxazole, TMP-SMX
Italian TMP-SMX, Trimedin, Centrin, Trimezole, TMP SMX, Co-trimoxazolo, Cotrimoxazolo, Insozalin, Trimetoprim-sulfametossazolo, Eslectin, Centran, Combinazione di trimetoprim e sulfametazolo
Polish Połączenie trimetoprimu z sulfametoksazolem
Spanish cotrimoxazol [genérico] (producto), cotrimoxazol, trimetoprima-sulfametoxazol, cotrimoxazol [genérico], trimetoprima - sulfametoxazol [genérico], co - trimoxazol (sustancia), cotrimoxazol [marca registrada], cotrimoxazol [marca registrada] (producto), co - trimoxazol, cotrimoxazol (producto), Cotrimoxazol, co - trimoxazol [genérico] (producto), co - trimoxazol [genérico], co - trimoxazol [marca registrada] (producto), co - trimoxazol [marca registrada], cotrimazol (producto), cotrimazol (sustancia), cotrimazol, sulfametoxazol + trimetoprima (producto), sulfametoxazol + trimetoprima, sulfametoxazol-trimetoprima, Combinación Trimetoprim-Sulfametoxazol
Portuguese Cotrimoxazol, Combinação Trimetoprima-Sulfametoxazol

Ontology: Bactrim (C0591139)

Definition (CHV) brand name of an antibiotic
Definition (CHV) brand name of an antibiotic
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D015662
German Bactrim
English bactrim [brand name], bactrim, Bactrim

Ontology: Septra (C0699595)

Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH D015662
German Septra
English septra, Septra

Ontology: Sulfatrim (C0723514)

Concepts Organic Chemical (T109) , Pharmacologic Substance (T121)
English Sulfatrim, sulfatrim