Skip to main content

Trimethoprim

Class: Urinary Anti-infectives
VA Class: AM900
CAS Number: 738-70-5
Brands: Primsol

Medically reviewed by Drugs.com on Jun 2, 2021. Written by ASHP.

Introduction

Antibacterial; dihydrofolate reductase inhibitor. Commercially available alone or in fixed combination with sulfamethoxazole.

Uses for Trimethoprim

Acute Otitis Media (AOM)

Has been used for treatment of AOM caused by Streptococcus pneumoniae and Haemophilus influenzae.

Do not use if Moraxella catarrhalis is suspected; this organism is resistant to trimethoprim.

Not indicated for AOM in adults or in children <6 months of age.

Do not use for prophylaxis of AOM or for prolonged periods in any age group.

When anti-infectives indicated, AAP recommends high-dose amoxicillin or amoxicillin and clavulanate as drugs of first choice for initial treatment of AOM and certain cephalosporins (cefdinir, cefpodoxime, cefuroxime, ceftriaxone) as alternatives for initial treatment in penicillin-allergic patients without a history of severe and/or recent penicillin-allergic reactions. Although fixed combination containing trimethoprim and sulfamethoxazole (co-trimoxazole) has been used for treatment of AOM, substantial resistance to the drug reported in S. pneumoniae and AAP states do not use as an alternative to amoxicillin.

Urinary Tract Infections (UTIs)

Treatment of initial episodes of acute, uncomplicated UTIs caused by susceptible Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, Enterobacter, or coagulase-negative Staphylococcus (including S. saprophyticus).

Has been used alone for treatment of acute, uncomplicated cystitis; however, value of trimethoprim alone for treatment of acute, uncomplicated UTIs has been questioned. Fixed combination containing trimethoprim and sulfamethoxazole (co-trimoxazole) is used for treatment of UTIs, and has been recommended as a good choice for empiric treatment of acute, uncomplicated cystitis.

Consider that uropathogens with resistance to trimethoprim (with or without sulfamethoxazole) reported with increasing frequency.

If using for treatment of acute, uncomplicated UTI, collect specimen for culture and in vitro susceptibility tests prior to initiating the drug. Some clinicians also recommend obtaining follow-up urine cultures after discontinuance of anti-infective therapy to determine whether the bacteria have been eliminated.

Pneumocystis jirovecii Pneumonia

Treatment of mild to moderate Pneumocystis jirovecii (formerly Pneumocystis carinii) pneumonia (PCP); used in conjunction with dapsone.

Co-trimoxazole is drug of choice for treatment of mild, moderate, or severe PCP, including PCP in HIV-infected adults, adolescents, and children.

Dapsone in conjunction with trimethoprim is one of several alternatives recommended by CDC, NIH, and IDSA for treatment of mild or moderate PCP in HIV-infected adults and adolescents when co-trimoxazole cannot be used. Although efficacy and safety data limited regarding use for treatment of PCP in children, some clinicians also recommend dapsone in conjunction with trimethoprim as an alternative for treatment of mild to moderate PCP in children. Not included in recommendations for treatment of more severe PCP infections.

Animal studies suggest trimethoprim alone is ineffective for treatment of PCP.

Trimethoprim Dosage and Administration

Administration

Oral Administration

Administer orally.

Dosage

Pediatric Patients

Acute Otitis Media (AOM)
Oral

Children ≥6 months of age: 10 mg/kg daily in 2 divided doses every 12 hours given for 10 days.

Pneumocystis jirovecii Pneumonia (PCP)†
Treatment of Mild to Moderate PCP†
Oral

Children: 5 mg/kg 3 times daily for 21 days in conjunction with oral dapsone (2 mg/kg [up to 100 mg] once daily for 21 days).

Adolescents ≥13 years of age: 5 mg/kg 3 times daily for 21 days in conjunction with oral dapsone (100 mg once daily for 21 days).

Adults

Urinary Tract Infections (UTIs)
Acute, Uncomplicated UTIs
Oral

100 mg every 12 hours or 200 mg once daily for 10 days.

Pneumocystis jirovecii Pneumonia (PCP)†
Treatment of Mild to Moderate PCP†
Oral

5 mg/kg 3 times daily for 21 days in conjunction with oral dapsone (100 mg once daily for 21 days).

Special Populations

Renal Impairment

Urinary Tract Infections (UTIs)
Acute, Uncomplicated UTIs
Oral

Adults with Clcr 15–30 mL/minute: 50 mg every 12 hours.

Adults with Clcr <15 mL/minute: Not recommended.

Geriatric Patients

Cautious dosage selection because of age-related decreases in renal, hepatic, and/or cardiac function. Initiate at lower end of dosing range. (See Geriatric Precautions under Cautions.)

Cautions for Trimethoprim

Contraindications

  • Hypersensitivity to trimethoprim.

  • Documented megaloblastic anemia secondary to folate deficiency.

Warnings/Precautions

Warnings

Hematologic Effects

Hematologic toxicity (as the result of trimethoprim-induced inhibition of dihydrofolate reductase) has resulted in thrombocytopenia, leukopenia, neutropenia, megaloblastic anemia, and methemoglobinemia.

Hematologic toxicity occurs more frequently in folate-depleted patients including geriatric, malnourished, alcoholic, pregnant, or debilitated patients; in patients receiving folate antimetabolites (e.g., phenytoin); in patients with hemolysis or impaired renal function; and in patients receiving high trimethoprim dosage for prolonged periods (e.g., >6 months).

Clinical signs such as sore throat, fever, pallor, or purpura may be early indications of serious blood disorders. If such signs occur, perform CBC; discontinue trimethoprim if clinically important decrease in any formed blood element occurs.

Use with caution in patients with possible folate deficiency.

Folates, such as leucovorin (folinic acid), may be administered during trimethoprim therapy and will not interfere with the drug’s antibacterial effect. Hematologic abnormalities usually resolve following administration of leucovorin.

If signs of bone marrow depression occur, discontinue trimethoprim and administer leucovorin as required to restore normal hematopoiesis.

Sensitivity Reactions

Hypersensitivity Reactions

Most frequent adverse reactions are rash and pruritus.

Serious hypersensitivity reactions reported rarely, including anaphylaxis, exfoliative dermatitis, toxic epidermal necrolysis, erythema multiforme, and Stevens-Johnson syndrome.

Photosensitivity

Photosensitivity (e.g., erythematous phototoxic eruptions with subsequent hyperpigmentation of sun-exposed skin) has been reported.

General Precautions

Selection and Use of Anti-infectives

To reduce development of drug-resistant bacteria and maintain effectiveness of trimethoprim and other antibacterials, use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.

Specific Populations

Pregnancy

Category C.

Because trimethoprim may interfere with folic acid metabolism, use during pregnancy only if potential benefits justify risk to fetus.

Lactation

Distributed into milk. Because trimethoprim may interfere with folic acid metabolism, use caution in nursing women.

Pediatric Use

Safety and efficacy of oral solution and tablets not established in infants <2 months of age.

Efficacy of oral solution for treatment of AOM not established in children <6 months of age.

Efficacy of tablets when used as a single agent for treatment of acute, uncomplicated UTIs not established in children <12 years of age.

It has been suggested that trimethoprim be used with caution in children who have fragile X chromosome associated with mental retardation, because folate depletion may worsen psychomotor regression associated with the disorder.

Geriatric Use

Experience in those ≥65 years of age insufficient to determine whether they respond differently than younger adults.

Hyperkalemia reported in geriatric patients receiving fixed combination of trimethoprim and sulfamethoxazole (co-trimoxazole).

Substantially eliminated by kidneys; risk of adverse effects increased in patients with renal impairment. Consider monitoring potassium concentrations and renal function (e.g., Clcr) since geriatric patients more likely to have decreased renal function.

Caution advised; start at lower end of dosing range due to greater frequency of decreased renal, hepatic, and/or cardiac function and of concomitant disease and drug therapy observed in the elderly.

Hepatic Impairment

Use with caution.

Renal Impairment

Use with caution.

Not recommended in patients with Clcr <15 mL/minute; decrease dosage in those with Clcr 15–30 mL/minute. (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Hypersensitivity (rash, pruritus), GI effects (epigastric discomfort, nausea, diarrhea, vomiting, glossitis, abnormal taste sensation).

Interactions for Trimethoprim

Specific Drugs and Laboratory Tests

Drug or Test

Interaction

Comments

Dapsone

Increased dapsone concentrations and increased risk of dapsone-associated adverse effects (e.g., methemoglobinemia); possible increased trimethoprim concentrations, but no evidence of increased risk of trimethoprim-associated adverse effects

Monitor periodically for potential toxicity (e.g., methemoglobinemia)

Phenytoin

May inhibit phenytoin metabolism resulting in increased half-life and decreased clearance of phenytoin

Monitor closely for signs of phenytoin toxicity; reduce phenytoin dosage if necessary

Tests for creatinine

Possible interference with Jaffe alkaline picrate assay resulting in falsely elevated creatinine concentrations

Tests for methotrexate

Possible interference with serum methotrexate assays if competitive binding protein technique (CBPA) is used with a bacterial dihydrofolate reductase as the binding protein; interference does not occur if methotrexate is measured using radioimmunoassay (RIA)

Trimethoprim Pharmacokinetics

Absorption

Bioavailability

Rapidly absorbed from GI tract.

Steady-state concentrations attained within 2–3 days. Peak serum concentrations attained within 1–4 hours after a dose.

Distribution

Extent

Widely distributed into body tissues and fluids, including aqueous humor, middle ear fluid, saliva, lung tissue, sputum, seminal fluid, prostatic tissue and fluid, vaginal secretions, bile, and bone.

Distributed into CSF. In patients with uninflamed meninges receiving oral trimethoprim, CSF concentrations are approximately 13–34% of concurrent serum concentrations. CSF concentrations somewhat higher if meninges are inflamed.

Readily crosses placenta; amniotic fluid concentrations are 80% of concurrent maternal serum concentrations.

Distributed into milk in concentrations approximately 125% those of concurrent maternal serum concentrations.

Plasma Protein Binding

42–46% bound to plasma proteins.

Elimination

Metabolism

10–20% of a dose is metabolized in the liver to oxide and hydroxylated metabolites.

Elimination Route

Eliminated in urine via glomerular filtration and tubular secretion. Only small amounts excreted in feces via biliary elimination.

In adults with normal renal function, approximately 50–60 and 56–70% of an oral dose is excreted in urine within 24 and 72 hours, respectively. Approximately 80% of amount recovered in urine is unchanged drug.

Hemodialysis is only moderately effective in removing trimethoprim; not removed by peritoneal dialysis.

Half-life

8–11 hours in adults with normal renal function.

7.7 hours in children <1 year of age and 5.5 hours in children 1–10 years of age.

Special Populations

Half-life is prolonged in patients with renal impairment. Half-life is 15 hours in adults with Clcr 10–30 mL/minute and may increase to >26 hours in those with Clcr ≤10 mL/minute.

Stability

Storage

Oral

Solution

15–25°C in tight, light-resistant container.

Tablets

20–25°C in tight, light-resistant container in a dry place.

Actions and Spectrum

  • A folate antagonist that inhibits formation of tetrahydrofolic acid (the metabolically active form of folic acid) in susceptible bacteria.

  • Inhibits reduction of dihydrofolic acid to tetrahydrofolic acid by binding to the enzyme dihydrofolate reductase and inhibits bacterial thymidine synthesis.

  • Usually slowly bactericidal.

  • Spectrum of activity includes some gram-positive aerobes and some gram-negative aerobes, including some Enterobacteriaceae. Inactive against most anaerobes and inactive against Mycobacterium and Chlamydia.

  • Gram-positive aerobes: Active against coagulase-negative staphylococci (including Staphylococcus saprophyticus) and Streptococcus pyogenes (group A β-hemolytic streptococci), and S. pneumoniae (penicillin-susceptible strains). May be active against some, but not all, strains of Enterococcus faecalis.

  • Gram-negative aerobes: Active against Acinetobacter, Citrobacter, Enterobacter, Escherichia coli, Haemophilus influenzae (except β-lactamase-negative, ampicillin-resistant strains), Klebsiella pneumoniae, Proteus mirabilis, Salmonella, and Shigella. Also active against some, but not all, strains of Providencia and Serratia. Inactive against Moraxella catarrhalis and Pseudomonas aeruginosa.

  • Moraxella catarrhalis is resistant to trimethoprim. Resistant strains of Enterobacteriaceae, especially E. coli, Klebsiella, and Proteus, have developed during trimethoprim therapy.

Advice to Patients

  • Importance of reporting clinical signs that may be early indications of serious blood disorders (e.g., sore throat, fever, pallor, purpura).

  • Importance of discontinuing use and contacting clinician if signs or symptoms of sensitization occur.

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Trimethoprim

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

100 mg*

Trimethoprim Tablets

Trimethoprim Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Solution

50 mg (of trimethoprim per 5 mL)

Primsol

FSC

AHFS DI Essentials™. © Copyright 2021, Selected Revisions June 12, 2017. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

Show article references

Frequently asked questions