Trimethoprim/sulfamethoxazole
Also called CO-Trimoxazole, Trimforte, Gantrim
Overview
Trimethoprim/sulfamethoxazole, sold under the trade names Bactrim, Cotrim (a short form of the British Approved Name, Co-trimoxazole) and Septra, among others, is a fixed-dose combination antibiotic medication used to treat a variety of bacterial infections. It consists of one part trimethoprim to five parts sulfamethoxazole. It is used to treat urinary tract infections, methicillin-resistant Staphylococcus aureus (MRSA) skin infections, travelers' diarrhea, respiratory tract infections, and cholera, among others. It is used both to treat and prevent Pneumocystis pneumonia and toxoplasmosis in people with HIV/AIDS and other causes of immunosuppression. It can be given orally (swallowed by mouth) or intravenous infusion (slowly injected into a vein with an IV).[1]
Trimethoprim/sulfamethoxazole is on the World Health Organization's List of Essential Medicines. It is available as a generic medication. In 2023, it was the 128th most commonly prescribed medication in the United States, with more than 4 million prescriptions.[2–6] WP
Uses, dosage and effects
Medical uses
Trimethoprim/sulfamethoxazole generally kills bacteria, by blocking the microorganisms' ability to make and to use folate.[1] WP
Pneumocystis jirovecii pneumonia
Trimethoprim/sulfamethoxazole (TMP/SMX) is the medicine most commonly used to prevent Pneumocystis jirovecii pneumonia (PCP) People who get Pneumocystis pneumonia have a medical condition that weakens their immune system, like HIV/AIDS, or take medicines (such as corticosteroid, monoclonal antibody and immunosuppressants) that reduce the body's ability to fight bacterial and viral infections. People with HIV/AIDS are less likely to get Pneumocystis pneumonia as a result of antiretroviral therapy (ART). However, Pneumocystis pneumonia is still a substantial public health problem. Most of what is scientifically known about Pneumocystis pneumonia and its treatment comes from studying people with HIV/AIDS.[7] WP
Susceptibility
Organisms against which trimethoprim/sulfamethoxazole can be effective include:[8]
- Acinetobacter spp.[8]
[9] WP - Aeromonas spp.[8]
[9] WP - Alcaligenes/Achromobacter spp.[8]
[9] WP - Bartonella henselae[8]
[9] WP - Bordetella pertussis (pertussis)[8]
[9] WP - Brucella spp.[8]
[9] WP - Burkholderia cepacia[8]
[9] WP - Burkholderia mallei (glanders)[8]
[9] WP - Burkholderia pseudomallei (melioidosis)[8]
[9] WP - Chlamydia spp.[8]
[9] WP - Chryseobacterium meningosepticum[8]
[9] WP - Citrobacter spp.[8]
[9] WP - Enterobacter spp.[8]
[9] WP - Enterococcus spp.[8]
[9] WP - Escherichia coli[8]
[9] WP - Haemophilus spp.[8]
[9] WP - Hafnia alvei[8]
[9] WP - Kingella spp.[8]
[9] WP - Klebsiella granulomatis[8]
[9] WP - Klebsiella pneumoniae[8]
[9] WP - Legionella spp.[8]
[9] WP - Listeria monocytogenes (listeriosis)[8]
[9] WP - Moraxella catarrhalis[8]
[9] WP - Morganella morganii[8]
[9] WP - Mycobacterium tuberculosis (tuberculosis)[8]
[9] WP - Neisseria gonorrhoeae (gonorrhoea)[8]
[9] WP - Neisseria meningitidis (meningococcal disease)[8]
[9] WP - Nocardia spp.[8]
[9] WP - Plesiomonas shigelloides[8]
[9] WP - Pneumocystis jirovecii[8]
[9] WP - Proteus mirabilis[8]
[9] WP - Proteus vulgaris[8]
[9] WP - Providencia rettgeri[8]
[9] WP - Providencia stuartii[8]
[9] WP - Salmonella typhi (typhoid fever)[8]
[9] WP - Non-typhi (food poisoning) Salmonella[8]
[9] WP - Serratia spp.[8]
[9] WP - Shigella spp.[8]
[9] WP - Staphylococcus aureus[8]
[9] WP - Staphylococcus epidermidis[8]
[9] WP - Staphylococcus saprophyticus[8]
[9] WP - Stenotrophomonas maltophilia[8]
[9] WP - Streptococcus agalactiae[8]
[9] WP - Streptococcus pneumoniae[8]
[9] WP - Streptococcus pyogenes[8]
[9] WP - Streptococcus viridans[8]
[9] WP - Toxoplasma gondii (toxoplasmosis)[8]
[9] WP - Tropheryma whippelii (Whipple's disease)[8]
[9] WP - Vibrio cholerae (cholera)[8]
[9] WP - Yersinia enterocolitica[8]
[9] WP - Yersinia pestis (bubonic plague)[8]
[9] WP - Yersinia pseudotuberculosis[8]
[9] WP
The only notable nonsusceptible organisms are Pseudomonas aeruginosa, the mycoplasmae and Francisella tularensis (the causative organism of tularaemia).[9]
Pregnancy and breast feeding
Its use during pregnancy is contraindicated, although it has been placed in Australian pregnancy category C. Its use during the first trimester (during organogenesis) and 12 weeks prior to pregnancy has been associated with an increased risk of congenital malformations, especially malformations associated with maternal folic acid deficiency (which is most likely related to the mechanism of action of co-trimoxazole) such as neural tube defects such as spina bifida, cardiovascular malformations (e.g. Ebstein's anomaly), urinary tract defects, oral clefts, and club foot in epidemiological studies. Its use later on during pregnancy also increases the risk of preterm labour (odds ratio: 1.51) and low birth weight (odds ratio: 1.67). Animal studies have yielded similarly discouraging results.[8]
It appears to be safe for use during breastfeeding as long as the baby is healthy.[15] WP
Infants
Its use in those less than 2 months of age is not recommended due to the risk of adverse side effects.[16] WP
Risks and side effects
Adverse effects
Common side effects include nausea, vomiting, rash, and diarrhea. Severe allergic reactions and Clostridioides difficile infection may occasionally occur. Its use in pregnancy is not recommended. It appears to be safe for use during breastfeeding as long as the baby is healthy.[1]
A recent study supported previous case reports that the treatment of teens or young adults with trimethoprim/sulfamethoxazole can cause serious adverse results. The study found that the 30-day risk of developing potentially lethal respiratory failure in patients aged 10 to 25 years who were treated with trimethoprim/sulfamethoxazole was significantly higher than those in this age group who were treated with either amoxicillin or a cephalosporin. These findings supported the FDA warning on using trimethoprim/sulfamethoxazole. Overall, the study suggested that this risk of respiratory failure should be carefully weighed against the benefits of using this trimethoprim/sulfamethoxazole drug combination in individuals 10 to 25 years old.[17] WP
Contraindications
Contraindications include the following:[8]
- Known hypersensitivity to trimethoprim, sulphonamides or any other ingredients in the formulations[8]
[18] WP - Pregnancy[8]
[18] WP - Severe liver failure, marked liver parenchymal damage, or jaundice.[8]
[18] WP - Serious haematological disorders and porphyria (due to the sulfonamide component of the preparation).[8]
[18] WP - Severe chronic kidney disease (CrCl <15 ml/min) where repeated measurements of the plasma concentration cannot be performed[8]
[18] WP
Overdose
Likely signs of toxicity include:[14] WP
- Nausea[14] WP
- Vomiting[14] WP
- Dizziness[14] WP
- Headache[14] WP
- Mental depression[14] WP
- Confusion[14] WP
- Thrombocytopenia[14] WP
- Uremia[14] WP
- Bone marrow depression[14] WP
- Loss of appetite[14] WP
- Colic[14] WP
- Drowsiness[14] WP
- Unconsciousness[14] WP
The recommended treatment for overdose includes:[14] WP
- Administration of activated charcoal[14] WP
- Stomach pumping[14] WP
- General supportive measures[14] WP
- Haemodialysis, which is moderately effective in clearing co-trimoxazole from the plasma.[14] WP
- Calcium folinate treatment in cases of blood dyscrasias[14] WP
- Forcing oral fluids[14] WP
Alkalinisation of the urine may reduce the toxicity of sulfamethoxazole, but it may increase the toxic effects of trimethoprim.[14] WP
Median lethal dose (LD50) in animals
Quoted from PubChem's Non-Human Toxicity Values, which come from the Hazardous Substances Data Bank (HSDB). PubChem describes them as: “Quantitative non-human toxicity values (e.g., lethal dose) for this compound. The data shown here are mostly for lab animals (e.g., rat, mouse, guinea pig, and rabbit).” and defines the “LD50 (median lethal dose, the estimated amount of a chemical expected to kill 50% of test animals in a single dose)”. PC
| LD50 (as the source gives it) | Reference |
|---|---|
| LD50 Mouse oral 5513 mg/kg PC | Budavari, S. (ed.). The Merck Index - Encyclopedia of Chemicals, Drugs and Biologicals. Rahway, NJ: Merck and Co., Inc., 1989., p. 1407 (via HSDB record 6780) |
Interactions
Interactions
Its use is advised against in people being concomitantly treated with:[8]
- ACE inhibitors like captopril, enalapril, lisinopril, perindopril, and ramipril due to the potential for additive hyperkalaemic effects[18] WP
- Prilocaine — additive risk of methaemoglobinaemia[8]
[14] [18–21] WP - Antiarrhythmics like amiodarone (increased risk of ventricular arrhythmias) and dofetilide (increased risk of QT interval prolongation)[8]
[14] [18–21] WP - Antibacterials like dapsone (increases plasma levels of both drugs), methenamine (increased risk of crystalluria) and rifampicin (as it may lead to an increased plasma level of rifampicin and lower plasma levels of trimethoprim)[8]
[14] [18–21] WP - Anticoagulants like warfarin and acenocoumarol — anticoagulant effects of either drug is potentiated by this combination[8]
[14] [18–21] WP - Sulfonylureas — effects enhanced[8]
[14] [18–21] WP - Phenytoin, half-life of phenytoin is increased[8]
[14] [18–21] WP - Antifolates like pyrimethamine, proguanil and methotrexate increase the risk of associated side effects like bone marrow toxicity, folic acid supplementation should be considered. A significant risk of megaloblastic anaemia exists with doses of pyrimethamine in excess of 25 mg/wk.[8]
[14] [18–21] WP - Antivirals, more specifically, lamivudine (increased plasma concentrations of lamivudine), zalcitabine (increased plasma concentrations of zalcitabine) and zidovudine (increased risk of haematological reactions)[8]
[14] [18–21] WP - Procainamide and/or amantadine may have their plasma concentrations increased bilaterally or unilaterally.[8]
[14] [18–21] WP - Clozapine and other antipsychotics — increased risk of haematological side effects[8]
[14] [18–21] WP - Nucleoside analogue antineoplastics like azathioprine and mercaptopurine — increased risk of haematological toxicity[8]
[14] [18–21] WP - Digoxin — increase in digoxin levels in a proportion of elderly patients[8]
[14] [18–21] WP - Diuretics — elderly patients receiving thiazide diuretics are at a heightened risk for developing thrombocytopaenia while on co-trimoxazole[8]
[14] [18–21] WP - Ciclosporin — patients who have received a kidney transplant and are receiving co-trimoxazole and ciclosporin concomitantly are at an increased risk of having a reversible deterioration in their kidney function.[8]
[14] [18–21] WP - Spironolactone — concurrent use can increase the likelihood of hyperkalemia, especially in the elderly. The trimethoprim portion acts to prevent potassium excretion in the distal tubule of the nephron.[22] WP
- Potassium aminobenzoate — effects of sulfonamides (like Sulfamethoxazole) inhibited.[8]
[14] [18–21] WP - Laboratory tests — trimethoprim and sulfonamides have been reported to interfere with diagnostic tests, including serum-methotrexate and elevated serum creatinine levels, also urea, urinary glucose and urobilinogen tests.[23] WP
Pharmacology
Pharmacology
The synergy between trimethoprim and sulfamethoxazole was first described in the late 1960s. Trimethoprim and sulfamethoxazole have a greater effect when given together than when given separately, because they inhibit successive steps in the folate synthesis pathway. They are given in a one-to-five ratio in their tablet formulations so that when they enter the body their concentration in the blood and tissues is roughly one-to-twenty — the exact ratio required for a peak synergistic effect between the two.[9]
Sulfamethoxazole, a sulfonamide, induces its therapeutic effects by interfering with the de novo (that is, from within the cell) synthesis of folate inside microbial organisms such as protozoa, fungi and bacteria. It does this by competing with p-aminobenzoic acid (PABA) in the biosynthesis of dihydrofolate.[9] WP
Trimethoprim serves as a competitive inhibitor of dihydrofolate reductase (DHFR), hence inhibiting the de novo synthesis of tetrahydrofolate, the biologically active form of folate.[9] WP
Tetrahydrofolate is crucial in the synthesis of purines, thymidine, and methionine which are needed for the production of DNA and proteins during bacterial replication.[27] WP
The effects of trimethoprim causes a backlog of dihydrofolate (DHF) and this backlog can work against the inhibitory effect the drug has on tetrahydrofolate biosynthesis. This is where the sulfamethoxazole comes in; its role is in depleting the excess DHF by preventing it from being synthesised in the first place.[9] WP
Co-trimoxazole was claimed to be more effective than either of its components individually in treating bacterial infections, although this was later disputed.[28]
Legal status
Brand names
Trimethoprim/sulfamethoxazole may be abbreviated as SXT, SMZ-TMP, TMP-SMX, TMP-SMZ, or TMP-sulfa. The generic British Approved Name (BAN) Co-trimoxazole is used for trimethoprim/sulfamethoxazole manufactured and sold by many different companies.[30] WP⚠ Wikipedia itself has flagged this text: citation needed.
The following list of brand names is incomplete: WP
- Bactrim, Bactrimel (manufactured by Roche and distributed in Europe) WP
- Bactrom (Venezuela) WP
- Bibactin (manufactured by PPM and distributed in Cambodia and some African countries) WP
- Biseptol WP
- Sumetrolim WP
- Co-trimoxazole (used as generic UK name) WP
- Cotrim WP
- Deprim (AFT Pharmaceuticals) WP
- Diseptyl (Israel) WP
- Graprima Forte Kaplet (manufactured by PT Graha Farma and distributed in Indonesia) WP
- Infectrin, Bactrim (Brazil) WP
- Novo-Trimel[31] WP
- Primadex (manufactured by Dexa Medica and distributed in Indonesia) WP
- Primotren (Lek in Slovenia and other countries) WP
- Resprim WP
- Sanprima (manufactured by Sanbe Farma and distributed in Indonesia) WP
- Septra (Aspen Pharmacare and formerly GlaxoSmithKline) WP
- Septram (Panama) WP
- Septran (GlaxoSmithKline)[32] WP
- Septrin (Spain)[33] WP
- Sulfatrim WP
- Teva-Trimel WP
- Trisul WP
- Vactrim (manufactured and distributed in Laos) WP
Economics
Trimethoprim/sulfamethoxazole is relatively inexpensive as of 2019.[4] WP
Chemistry
- Formula
- C24H29N7O6S PC
- CAS number
- 8064-90-2 PC
- Molar mass (g/mol)
- 543.6 PC
- IUPAC name (computed by PubChem)
- 4-
amino- PCN- (5- methyl- 1, 2- oxazol- 3- yl) benzenesulfonamide;5- [(3, 4, 5- trimethoxyphenyl) methyl] pyrimidine- 2, 4- diamine - SMILES
- CC1=CC(=NO1)
NS(=O) PC(=O) C2=CC=C(C=C2) N.COC1=CC(=CC(=C1OC) OC) CC2=CN=C(N=C2N) N - InChIKey
- WZRJTRPJURQBRM-
UHFFFAOYSA- PCN - PubChem CID
- 358641
Harm reduction information
No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.
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Sources
- Other Co-trimoxazole
- Other Hamilton R. Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. 2015
- Other The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). 2023
- Other Brown D, Edwards H, Buckley T, Aitken RL. Lewis's Medical-Surgical Nursing EBook: Assessment and Management of Clinical Problems. 2019
- Other Top 300 of 2023
- Other Sulfamethoxazole; Trimethoprim Drug Usage Statistics, United States, 2013–2023
- Journal / agency Pneumocystis pneumonia. 13 October 2021
- Other trimethoprim/sulfamethoxazole (Rx)
- Journal / agency Wormser GP, Keusch GT, Heel RC. Co-trimoxazole (trimethoprim-sulfamethoxazole): an updated review of its antibacterial activity and clinical efficacy. Drugs. December 1982. doi:10.2165/00003495-198224060-00002 · PMID 6759092
- Other Tularemia. 17 July 2011
- Journal / agency Harik NS. Tularemia: epidemiology, diagnosis, and treatment. Pediatric Annals. July 2013. doi:10.3928/00904481-20130619-13 · PMID 23805970
- Journal / agency Yang J, Xie RH, Krewski D, Wang YJ, Walker M, Wen SW. Exposure to trimethoprim/sulfamethoxazole but not other FDA category C and D anti-infectives is associated with increased risks of preterm birth and low birth weight. International Journal of Infectious Diseases. May 2011. doi:10.1016/j.ijid.2011.01.007 · PMID 21345707
- Journal / agency Santos F, Sheehy O, Perreault S, Ferreira E, Berard A. Exposure to anti-infective drugs during pregnancy and the risk of small-for-gestational-age newborns: a case-control study. BJOG. October 2011. doi:10.1111/j.1471-0528.2011.03041.x · PMID 21749628
- Other Bactrim DS tablet blister pack
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- Journal / agency Ahmadi F, McArthur E, Garcia-Bournissen F, Rieder MJ, Muanda FT. Trimethoprim-Sulfamethoxazole and Acute Respiratory Failure in Adolescents and Young Adults. JAMA Network Open. November 2025. doi:10.1001/jamanetworkopen.2025.45251 · PMID 41284296 · PMC12645330
- Other Co-Trimoxazole 80 mg/400 mg Tablets – Summary of Product Characteristics (SmPC). 1 August 2021
- Journal / agency Bactrim DS- sulfamethoxazole and trimethoprim tablet Bactrim- sulfamethoxazole and trimethoprim tablet
- Other Joint Formulary Committee. British National Formulary (BNF). 2013
- Other Australian Medicines Handbook. 2013
- Journal / agency Juvet T, Gourineni VC, Ravi S, Zarich SW. Life-threatening hyperkalemia: a potentially lethal drug combination. Connecticut Medicine. September 2013. PMID 24156179
- Journal / agency Gentry CA, Nguyen AT. An evaluation of hyperkalemia and serum creatinine elevation associated with different dosage levels of outpatient trimethoprim-sulfamethoxazole with and without concomitant medications. The Annals of Pharmacotherapy. December 2013. doi:10.1177/1060028013509973 · PMID 24259630
- Journal / agency Bushby SR, Hitchings GH. Trimethoprim, a sulphonamide potentiator. British Journal of Pharmacology and Chemotherapy. May 1968. doi:10.1111/j.1476-5381.1968.tb00475.x · PMID 5301731 · PMC1570262
- Journal / agency Böhni E. Comparative bacteriological investigations with the combination trimethoprim/sulfamethoxazole in vitro and in vivo. Chemotherapy. 1969. doi:10.1159/000220651 · PMID 4908562
- Journal / agency Böhni E. Chemotherapeutic activity of the combination of trimethoprim and sulphamethoxazole in infections of mice. Postgraduate Medical Journal. November 1969. PMID 4902845
- Journal / agency Tetrahydrofolic acid
- Journal / agency Trubiano JA, Grayson ML. Kucers' the Use of Antibiotics. 2017. doi:10.1201/9781498747967
- Journal / agency Brumfitt W, Hamilton-Miller JM. Reassessment of the rationale for the combinations of sulphonamides with diaminopyrimidines. Journal of Chemotherapy. December 1993. doi:10.1080/1120009X.1993.11741097 · PMID 8195839
- Other Co-trimoxazole Medicinal forms
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- Other Septran/Sepman Double Strength – Co-Trimoxazole Oral Formulations. 13 August 2017
- Other SEPTRIN FORTE Comp. 800/160 mg – Datos generales
Text and values on this page are quoted from Wikipedia (CC BY-SA 4.0), PubChem (public domain). Each value links to the exact revision it came from.