Drug Profile – Trimethoprim

trimethoprim pharmacology

For the NAPLEX exam, it’s vital that you understand the fundamental pharmacology and clinical pharmacy of each medicine. Here, we review the essential facts about the antibacterial drug, trimethoprim, that you need to know; a drug first used as far back as 1962.


Trimethoprim is used in the treatment of the following conditions:

  • Urinary tract infections (UTIs): particularly for uncomplicated UTIs. Alternative medicines include nitrofurantoin and amoxicillin.
  • Pneumocystis pneumonia: trimethoprim is used alongside sulfamethoxazole (Co-trimoxazole) to treat/prevent immunocompromised patients at risk, or with, this infection.
  • Otitis media

Trimethoprim may also be used for purposes not listed in this guide.

Mechanism of action

Bacterial cells need folate to function. They cannot use external folate sources; they must make folate themselves.

The mechanism of action of trimethoprim involves disrupting this function – preventing bacterial cells from generating folate. What results is an inability by those bacterial cells to manufacture folate, and, as a result, it impairs DNA synthesis. This effect is bacteriostatic.

More specifically, trimethoprim works by binding to dihydrofolate reductase to inhibit the conversion of dihydrofolic acid (DHF) to tetrahydrofolic acid (THF); THF being an essential precursor to thymidine synthesis (essential to DNA synthesis).

Trimethoprim has broad-spectrum activity – active against both Gram-positive and Gram-negative organisms.

However, resistance is growing.

Noted above was the combination of trimethoprim with sulfamethoxazole – a combined medicine marketed as Co-trimoxazole. Sulfamethoxazole also inhibits bacterial folate synthesis, but at a different point along the pathway (inhibiting dihydropteroate synthase).

As a result, both drugs taken together have more synergistic activity to produce a bactericidal effect.


The standard adult dose for patients with urinary tract infections is:

  • UTI: 100mg orally every 12 hours for 10 days, or 200mg orally every 24 hours for 10 days.
  • Pneumocystis infection: a weight-based dose of 120mg/kg daily in 2-4 divide doses for 14-21 days.

Renal dose and liver dose adjustments may be required.

Lower doses are used for prophylaxis of either condition.

Side effects

Side effects associated with trimethoprim include:

  • Gastrointestinal upset – nausea, vomiting, diarrhea
  • Taste disturbances
  • Photosensitivity
  • Itch
  • Hyperkalemia
  • Skin rash
  • Hypersensitivity reactions
  • Hematological disruption – megaloblastic anemia, leucopenia etc.

Hyperkalemia results because trimethoprim antagonizes the epithelial sodium channel of the distal tubule (in a manner like amiloride).

Clinical Factors

Here are some of the essential factors to consider when prescribing trimethoprim:

  • Trimethoprim may be taken with food to reduce the risk of gastrointestinal disturbances.
  • Patients should be counselled to take the drug at the prescribed times and that, if they fail to take the medicine at those times, that it may impede the effectiveness of the drug.
  • Avoid in first trimester of pregnancy where, as a folate antagonist, it can cause birth defects.
  • Similarly, use with caution in patients with folate deficiency.
  • Dose should be reduced in patients with liver / renal damage.
  • Avoid with potassium-elevating drugs or supplements – ACE inhibitors, ARBs etc. Phenytoin increases risk of hematological effects.
  • Trimethoprim enhances effect of warfarin by laying waste to colonic gut flora that otherwise produce vitamin K.
  • It causes a small, reversible increase in serum creatinine concentration.

Trimethoprim has been around since the early 1960s. Even still, it remains an important medicine in the treatment of UTIs and other infections. Here, we’ve put together an effective, essential summary of the fundamental facts you need to know about this antibacterial drug.

NAPLEX Study Guide is the leading online resource to help pharmacy graduates pass their licensing exam. Check back to our pharmacy blog soon for even more great tips, tricks and tutorials to help you pass your next medicine exam!


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