Common side effects include nausea, changes in taste, and rash.[1] Rarely it may result in blood problems such as not enough
platelets or
white blood cells.[1] Trimethoprim may cause sun sensitivity.[1] There is evidence of potential harm during
pregnancy in some animals but not humans.[3] It works by blocking
folate metabolism via
dihydrofolate reductase in some bacteria, preventing creation of bacterial
DNA and
RNA and leading to bacterial cell death.[1]
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.[19][20]
Pregnancy
Based on the 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.[21]
The trophoblasts in the early fetus are sensitive to changes in the folate cycle. A 2013 study found a doubling in the risk of miscarriage in women exposed to trimethoprim in the early pregnancy.[22]
Mechanism of action
Trimethoprim binds to
dihydrofolate reductase and inhibits the reduction of
dihydrofolic acid (DHF) to
tetrahydrofolic acid (THF).[24] THF is an essential precursor in the thymidine synthesis pathway and interference with this pathway inhibits bacterial DNA synthesis.[24] Trimethoprim's inhibitory activity for bacterial dihydrofolate reductase is sixty thousand times greater than for human dihydrofolate reductase.[25]Sulfamethoxazole inhibits
dihydropteroate synthase, an enzyme involved further upstream in the same pathway.[24]Trimethoprim and sulfamethoxazole are commonly used in combination due to possible synergistic effects, and reduced development of resistance.[24] This benefit has been questioned.[26]
History
Trimethoprim was first used in 1962.[4] In 1972, it was used as a prophylactic treatment for urinary tract infections in Finland.[4]
Its name is derived from trimethyloxy-
pyrimidine.
References
^
abcdefgh"Trimethoprim". The American Society of Health-System Pharmacists.
Archived from the original on 24 September 2015. Retrieved 1 August 2015.
^World Health Organization (2021). World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization.
hdl:10665/345533. WHO/MHP/HPS/EML/2021.02.
^Hamilton R (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 113.
ISBN978-1-284-05756-0.
^
abcRossi S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust.
ISBN978-0-9805790-9-3.
^Ellenhorn MJ, Schonwald S, Ordog G, Wasserberger J. American Hospital Formulary Service- Drug Information 2002. Baltimore, MD: Williams and Wilkins. p. 236.
^MICROMEDEX Thomson Health Care. USPDI (2002). Drug Information for the Health Care Professional. Vol. 1 (22nd ed.). Greenwood Village, CO.: Thomson Health Care. p. 2849.
^Brumfitt W, Hamilton-Miller JM (December 1993). "Reassessment of the rationale for the combinations of sulphonamides with diaminopyrimidines". Journal of Chemotherapy. 5 (6): 465–469.
doi:
10.1080/1120009X.1993.11741097.
PMID8195839.