Possible Interaction: Trimethoprim and Folate

“Serum folate concentration decreases during high-dose trimethoprim therapy were statistically significant.”

“Drugs interfering with folate metabolism in the tachyzoites include sulphon-amides (hydropteroate synthetase or HPS inhibitors) and the dihydrofolate reductase or DHFR inhibitors, trimethoprim and pyrimeth-amine.”

“ Trimethoprim antagonize the actions of folate by inhibition of dihydrofolate reductase.”

“It has been suggested that folate deficiency could develop in patients on doses of trimethoprim greater than 500 mg daily and that haematological monitoring is required in these patients.”

“Other drugs with influence on folate metabolism, such as trimethoprim , should not be given concomitantly.”

“The folate levels may well have been further compromised by the administration of trimethoprim.”

“Those drugs that interfere with folate metabolism include: 1) dehydrofolate reductase inhibitors such as methotrexate pyrimethane trianterene and trimethaprim ; 2) anticonvulsives; 3) oral contraceptives; 4) alcohol; and 5) antimicrobial drugs.”

“Evidence to date indicates that trimethoprim (TMP) reduces use of folate by normal human cells by the same mechanism as its action against invading organisms, i.e., by blocking dihydrofolate reductase.”

“How­ ever, it remained possible that patients with suboptimal folate nutrition might develop such deleterious effects if they were treated with TMP.”

“Kinetic flux profiling with (15)N-labeled ammonia in Escherichia coli reveals that trimethoprim leads to blockade not only of DHFR but also of another critical enzyme of folate metabolism: folylpoly-gamma-glutamate synthetase (FP-gamma-GS).”