Trimethoprim

What is Trimethoprim?

Trimethoprim is an antibiotic medication that belongs to the class of folate antagonists or dihydrofolate reductase inhibitors. It is primarily used to treat bacterial infections, most commonly urinary tract infections, and is often prescribed either alone or in combination with sulfamethoxazole. This medication works by interfering with bacterial DNA synthesis, making it effective against a variety of gram-positive and gram-negative bacteria.

Uses

Trimethoprim is approved for several bacterial infections:

• Uncomplicated urinary tract infections (UTIs): The most common use, particularly effective against E. coli and other common urinary pathogens
• Acute otitis media: Middle ear infections in children when other antibiotics are not suitable
• Pneumocystis pneumonia prevention: Used in immunocompromised patients, especially when combined with sulfamethoxazole
• Traveler’s diarrhea: Treatment and prevention of bacterial diarrhea caused by susceptible organisms
• Shigellosis: Treatment of infections caused by Shigella bacteria

How it works

Trimethoprim works by blocking an enzyme called dihydrofolate reductase, which bacteria need to produce folate, an essential vitamin required for DNA synthesis and cell division. By inhibiting this enzyme, trimethoprim prevents bacteria from making new DNA and reproducing, effectively stopping the infection from spreading. This mechanism is selective for bacterial cells because human cells obtain folate through different pathways, making the drug relatively safe for human use.

Side effects

Common side effects include:

Submit Your Paper

• Nausea and vomiting
• Diarrhea
• Loss of appetite
• Skin rash
• Headache
• Dizziness
• Elevated potassium levels
• Mild stomach upset

Serious side effects requiring immediate medical attention:

• Severe allergic reactions with difficulty breathing or swelling
• Blood disorders including anemia or low white blood cell count
• Severe skin reactions such as Stevens-Johnson syndrome
• Kidney problems or changes in urination
• Severe diarrhea that may indicate C. difficile infection

Warnings and precautions

• Kidney and liver function: Patients with impaired kidney or liver function require dose adjustments and careful monitoring, as trimethoprim is primarily eliminated through the kidneys
• Pregnancy and breastfeeding: Generally avoided during pregnancy, especially in the first trimester, due to potential effects on fetal development; passes into breast milk
• Folate deficiency: Patients with existing folate deficiency, elderly individuals, or those with poor nutrition may be at higher risk for side effects
• Blood disorders: Should be used cautiously in patients with a history of blood disorders, and regular monitoring may be necessary during prolonged treatment
• Electrolyte imbalances: Can cause elevated potassium levels, particularly concerning for patients with kidney problems or those taking potassium supplements

Interactions

• Warfarin: May increase bleeding risk by enhancing warfarin’s anticoagulant effects
• Metformin: Combined use may increase risk of lactic acidosis, especially in patients with kidney problems
• ACE inhibitors and ARBs: May increase risk of elevated potassium levels when used together
• Digoxin: Trimethoprim may increase digoxin levels, potentially causing toxicity
• Phenytoin: May increase phenytoin levels and risk of side effects
• Cyclosporine: May increase risk of kidney problems when used concurrently
• Potassium supplements: Concurrent use may lead to dangerously high potassium levels
• Folate supplements: May reduce trimethoprim’s effectiveness by counteracting its mechanism of action

Check interactions with the GMJ Interaction Checker

Dosage

Typical adult dosages vary depending on the condition being treated. For uncomplicated urinary tract infections, the standard dose is usually 100-200mg twice daily for 3-14 days. For pneumocystis pneumonia prevention, lower doses of 160mg daily may be prescribed. In cases of more severe infections, higher doses may be necessary. Dosage adjustments are required for patients with kidney impairment, and elderly patients may need reduced doses. The duration of treatment typically ranges from 3 days for simple UTIs to several weeks for more complex infections. All dosing decisions should be made by a healthcare provider based on the specific infection, patient factors, and bacterial susceptibility testing when available.

Sources: FDA DailyMed drug labels (public domain), BNF, WHO Essential Medicines List. This article is for informational purposes only and does not constitute medical advice. Always consult your healthcare provider before starting or stopping any medication.

This work is licensed under Creative Commons Attribution 4.0 International (CC BY 4.0). You are free to share and adapt this content with attribution to GMJ News (news.gmj.ge).