Generic Name
Trimethoprim
Brand Names
Primsol
Trimpex
Proloprim
Monotrim
Polytrim (ophthalmic combination with polymyxin B)
Generic formulations available worldwide
Drug Class
Antibacterial agent
Dihydrofolate reductase (DHFR) inhibitor
Antimetabolite
Bacteriostatic antibiotic
Mechanism of Action
Trimethoprim selectively inhibits bacterial dihydrofolate reductase (DHFR)
DHFR is essential for the conversion of dihydrofolic acid to tetrahydrofolic acid
This inhibition blocks the synthesis of nucleotides (thymidine, purines) required for bacterial DNA replication and repair
By interfering with folic acid metabolism, trimethoprim halts bacterial growth
It acts synergistically with sulfamethoxazole (as in co-trimoxazole), which inhibits dihydropteroate synthase upstream in the folate pathway
Effective mainly against Gram-negative bacilli and some Gram-positive cocci
Indications
Used as monotherapy or in combination with sulfamethoxazole
Approved Uses for Trimethoprim Monotherapy
Uncomplicated urinary tract infections (UTIs)
Acute or chronic cystitis
Prostatitis
Prophylaxis of recurrent UTIs
Traveler’s diarrhea (limited role)
Off-label
Treatment of Pneumocystis jirovecii pneumonia (PCP) in sulfa-allergic patients
Treatment of nocardiosis (as alternative therapy)
Acne vulgaris (occasionally used off-label)
Trimethoprim-Sulfamethoxazole Combination (Co-trimoxazole)
Broad indications including
Pneumocystis jirovecii pneumonia (PCP)
Toxoplasmosis
MRSA skin infections
Otitis media
Shigellosis
Nocardiosis
Prophylaxis in immunocompromised patients (HIV, cancer, transplant)
Dosage and Administration
Oral Monotherapy (Adults)
Acute UTI
200 mg twice daily for 3 to 5 days
Prophylaxis
100 mg once daily at bedtime
Chronic or complicated UTI
100 mg to 200 mg twice daily for 7 to 14 days
Pediatric Dosage
6 months to 12 years
Trimethoprim 4 mgkg twice daily
Adjust dose by weight
Available as oral suspension in many markets
Renal Impairment
CrCl 15–30 mLmin reduce dose by 50 percent
CrCl <15 mLmin avoid or use alternative
Monitor creatinine and adjust dosing in elderly
Duration
Short courses for uncomplicated UTI
Longer duration for recurrent or complicated infections
Tailor to pathogen and clinical response
Pharmacokinetics
Absorption
Well absorbed orally (~90 to 100 percent)
Peak plasma levels in 1 to 4 hours
Distribution
Wide tissue distribution
Crosses placenta
Enters breast milk
Penetrates prostatic tissue and vaginal secretions
Low protein binding (~40 percent)
Metabolism
Hepatic metabolism (20 percent)
Elimination
Renal excretion (unchanged and metabolites)
Half-life 8 to 10 hours in normal renal function
Prolonged in renal impairment
Contraindications
Known hypersensitivity to trimethoprim or structurally related compounds
Severe renal impairment unless dose can be adjusted
Megaloblastic anemia due to folate deficiency
Use with caution in patients with hepatic impairment
Not recommended in neonates or during first trimester unless absolutely necessary
Warnings and Precautions
Monitor for hematologic toxicity especially in folate-deficient individuals or prolonged therapy
Risk of hyperkalemia, especially in elderly or those on potassium-sparing diuretics or ACE inhibitors
Caution in renal impairment due to drug accumulation
Risk of photosensitivity, advise sun protection
May mask symptoms of other infections
May rarely cause aseptic meningitis or cholestatic jaundice
Monitor complete blood count and renal function during extended therapy
Adverse Effects
Common
Nausea
Vomiting
Rash
Diarrhea
Headache
Glossitis
Loss of appetite
Less Common
Hyperkalemia
Pruritus
Photosensitivity
Elevated liver enzymes
Anemia
Leukopenia
Serious (Rare)
Aplastic anemia
Thrombocytopenia
Agranulocytosis
Stevens-Johnson syndrome (more common with combination therapy)
Toxic epidermal necrolysis
Hepatotoxicity
Interstitial nephritis
Crystalluria
Allergic pneumonitis
Overdose
Symptoms
Nausea
Vomiting
Dizziness
Confusion
Bone marrow suppression with prolonged excessive doses
Hyperkalemia
Management
Supportive therapy
Activated charcoal if early ingestion
Monitor electrolytes and renal function
Hemodialysis may help remove drug in severe cases
Drug Interactions
Pharmacodynamic Interactions
ACE inhibitors ARBs potassium-sparing diuretics
Increased risk of hyperkalemia
Methotrexate
Additive antifolate effect increases hematologic toxicity
Phenytoin
Trimethoprim may increase serum phenytoin levels
Digoxin
May increase digoxin levels in elderly
Warfarin
Potentiation of anticoagulant effect via interference with vitamin K metabolism
Cytotoxic drugs
Additive bone marrow suppression
Pharmacokinetic Interactions
May compete for renal tubular secretion
Inhibits renal excretion of creatinine leading to false rise in serum creatinine without real renal dysfunction
No major CYP450 involvement
Use in Special Populations
Pregnancy
Category C
Avoid in first trimester due to risk of neural tube defects from folate antagonism
Use only if benefit justifies risk
Supplemental folic acid recommended if use is unavoidable
Lactation
Excreted in breast milk
Use with caution especially in preterm infants or those with G6PD deficiency
Pediatrics
Approved in children >2 months
Avoid in neonates due to risk of kernicterus
Geriatrics
Increased risk of hyperkalemia
Monitor renal function and electrolytes closely
Renal Impairment
Dose adjustment required
Avoid in severe impairment
Hepatic Impairment
Use with caution
Monitor liver function during prolonged use
Monitoring Parameters
Renal function (baseline and during prolonged use)
Serum potassium especially in high-risk patients
Complete blood count in long-term therapy
Signs of skin rash or hypersensitivity
Liver function if clinical suspicion of hepatotoxicity
Urinalysis for crystalluria during high-dose treatment
Comparative Pharmacology
Trimethoprim monotherapy is less commonly used today compared to co-trimoxazole (TMP-SMX) due to broader spectrum of combination
Trimethoprim alone is effective against many E. coli strains in UTIs
Unlike fluoroquinolones it does not pose risk of tendon rupture or QT prolongation
Safer than sulfonamide combinations in sulfa-allergic patients
Nitrofurantoin is preferred in elderly women with uncomplicated UTI but less effective for upper UTI
Amoxicillin resistance in UTIs makes trimethoprim useful unless local resistance is high
Bacterial resistance to trimethoprim is increasing globally due to its extensive use in primary care
Formulations Available
Tablets 100 mg 200 mg
Oral suspension 50 mg/5 mL or 100 mg/5 mL
IV formulation rarely used in trimethoprim-only form
Combination with sulfamethoxazole available as co-trimoxazole
Regulatory and Legal Status
Prescription-only medicine
Available worldwide in generic and branded formulations
Included in WHO Model List of Essential Medicines
Not a controlled substance
Widespread use in primary and hospital care
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