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Structural formula of trimethoprim
Ball-and-stick model of the trimethoprim molecule
Trade namesProloprim, Monotrim, Triprim, others
  • 5-(3,4,5-Trimethoxybenzyl)pyrimidine-2,4-diamine
Clinical data
WHO AWaReAccess
  • AU: B3
  • US: C (Risk not ruled out)
Routes of
Defined daily dose0.4 g (parenteral) or
0.4 g (by mouth) [1]
External links
License data
Legal status
Protein binding44%
Elimination half-life8–12 hours
ExcretionUrine (50–60%), faeces (4%)
Chemical and physical data
Molar mass290.323 g·mol−1
3D model (JSmol)
  • Nc1nc(N)ncc1Cc(cc2OC)cc(OC)c2OC
  • InChI=1S/C14H18N4O3/c1-19-10-5-8(6-11(20-2)12(10)21-3)4-9-7-17-14(16)18-13(9)15/h5-7H,4H2,1-3H3,(H4,15,16,17,18) checkY

Trimethoprim (TMP) is an antibiotic used mainly in the treatment of bladder infections.[2] Other uses include for middle ear infections and travelers' diarrhea.[2] With sulfamethoxazole or dapsone it may be used for Pneumocystis pneumonia in people with HIV/AIDS.[2][3] It is taken by mouth.[2]

Common side effects include nausea, changes in taste, and rash.[4][2] Rarely it may result in blood problems such as not enough platelets or white blood cells.[2] It may cause sun sensitivity.[2] There is evidence of potential harm during pregnancy in some animals but not humans.[5] It works by blocking folate metabolism via dihydrofolate reductase in some bacteria which results in their death.[2]

Trimethoprim was first used in 1962.[6] It is on the World Health Organization's List of Essential Medicines.[7] It is available as a generic medication and the tablet form is not very expensive.[8][9] In the United States, ten days of treatment costs about $21.[2]

Medical uses

It is primarily used in the treatment of urinary tract infections, although it may be used against any susceptible aerobic bacterial species.[10] It may also be used to treat and prevent Pneumocystis jirovecii pneumonia.[10] It is generally not recommended for the treatment of anaerobic infections such as Clostridium difficile colitis (the leading cause of antibiotic-induced diarrhea).[10] Trimethoprim has been used in trials to treat retinitis.[11]

Resistance to trimethoprim is increasing, but it is still a first line antibiotic in many countries.[12] It is in the 'access' group of the WHO AWaRe Classification.[13]

Spectrum of susceptibility

Cultures and susceptibility tests should be done to make sure bacteria are treated by trimethoprim.[14][15]


The defined daily dose is 0.4 g (parenteral) or 0.4 g (by mouth).[1] The dose in adults for a urinary tract infection is 100 mg twice per day for 10 days.[2]

Side effects


  • Nausea
  • Change in taste
  • Vomiting
  • Diarrhea
  • Rash
  • Sun sensitivity
  • Itchiness[16][17]



Liver and kidney problems

10–20% of trimethoprim is metabolized by the liver and the rest is excreted in the urine. Therefore, trimethoprim should be used with caution in individuals with kidney and liver impairments. Dosage adjustment is not needed for liver impairment but should be adjusted for kidney impairment.[23]


Based on studies that show that trimethoprim crosses the placenta and can affect folate metabolism, there has been growing evidence of the risk of structural birth defects associated with trimethoprim, especially during the first trimester of pregnancy.[24] It may be involved in a reaction similar to disulfiram when alcohol is consumed after it is used, in particular when used in combination with sulfamethoxazole.[25][26] The trophoblasts in the early fetus are sensitive to changes in the folate cycle. A recent study has found a doubling in the risk of miscarriage in women exposed to trimethoprim in the early pregnancy.[27]

Mechanism of action

Staphylococcus aureus DHFR in complex with NADPH and trimethoprim PDB entry 2W9G [28]

Trimethoprim binds to dihydrofolate reductase and inhibits the reduction of dihydrofolic acid (DHF) to tetrahydrofolic acid (THF).[29] THF is an essential precursor in the thymidine synthesis pathway and interference with this pathway inhibits bacterial DNA synthesis.[29] Trimethoprim's affinity for bacterial dihydrofolate reductase is several thousand times greater than its affinity for human dihydrofolate reductase.[29] Sulfamethoxazole inhibits dihydropteroate synthase, an enzyme involved further upstream in the same pathway.[29] Trimethoprim and sulfamethoxazole are commonly used in combination due to possible synergistic effects, and reduced development of resistance.[29] This benefit has been questioned.[30]

Tetrahydrofolate synthesis pathway


Trimethoprim was first used in 1962.[6] In 1972, it was used in Finland, to prevent urinary tract infections.[6]

Its name is derived from trimethyloxy-pyrimidine.

Social and cultural


It is available as a generic medication and is not very expensive.[8] The liquid form, however, is much more expensive.[8] 14 tablets of trimethoprim 200mg tablets costs the NHS in the UK less than a pound.[31]


  1. 1.0 1.1 "WHOCC - ATC/DDD Index". Archived from the original on 24 August 2019. Retrieved 22 September 2020.
  2. 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 2.9 "Trimethoprim". The American Society of Health-System Pharmacists. Archived from the original on 2015-09-24. Retrieved Aug 1, 2015.
  3. Masur, H; Brooks, JT; Benson, CA; Holmes, KK; Pau, AK; Kaplan, JE; National Institutes of, Health; Centers for Disease Control and, Prevention; HIV Medicine Association of the Infectious Diseases Society of, America (May 2014). "Prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: Updated Guidelines from the Centers for Disease Control and Prevention, National Institutes of Health, and HIV Medicine Association of the Infectious Diseases Society of America". Clinical Infectious Diseases. 58 (9): 1308–11. doi:10.1093/cid/ciu094. PMC 3982842. PMID 24585567.
  4. Ritter, James M.; Flower, Rod; Henderson, Graeme; Loke, Yoon Kong; Robinson, Emma; Fullerton, James (2024). "52. Antibacterial drugs". Rang & Dale's Pharmacology (10th ed.). Elsevier. pp. 706–707. ISBN 978-0-7020-7448-6. Archived from the original on 2024-02-12. Retrieved 2024-01-30.
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  8. 8.0 8.1 8.2 Hitchings, Andrew; Lonsdale, Dagan; Burrage, Daniel; Baker, Emma (2019). The Top 100 Drugs: Clinical Pharmacology and Practical Prescribing (2nd ed.). Elsevier. pp. 212–213. ISBN 978-0-7020-7442-4. Archived from the original on 2021-05-22. Retrieved 2021-11-09.
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  10. 10.0 10.1 10.2 Rossi, S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3.
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  13. Zanichelli, Veronica; Sharland, Michael; Cappello, Bernadette; Moja, Lorenzo; Getahun, Haileyesus; Pessoa-Silva, Carmem; Sati, Hatim; van Weezenbeek, Catharina; Balkhy, Hanan; Simão, Mariângela; Gandra, Sumanth; Huttner, Benedikt (1 April 2023). "The WHO AWaRe (Access, Watch, Reserve) antibiotic book and prevention of antimicrobial resistance". Bulletin of the World Health Organization. 101 (4): 290–296. doi:10.2471/BLT.22.288614. ISSN 0042-9686. Archived from the original on 7 May 2023. Retrieved 17 November 2023.
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