Brand name: Primsol
Drug class: Urinary Anti-infectives
VA class: AM900
CAS number: 738-70-5

Medically reviewed by Drugs.com on Jun 3, 2024. Written by ASHP.

Introduction

Antibacterial; dihydrofolate reductase inhibitor.^{106 124} Commercially available alone^{106 124} or in fixed combination with sulfamethoxazole.^{135 186}

Uses for Trimethoprim

Acute Otitis Media (AOM)

Has been used for treatment of AOM caused by Streptococcus pneumoniae and Haemophilus influenzae.¹²⁴

Do not use if Moraxella catarrhalis is suspected; this organism is resistant to trimethoprim.¹²⁴

Not indicated for AOM in adults or in children <6 months of age.¹²⁴

Do not use for prophylaxis of AOM or for prolonged periods in any age group.¹²⁴

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.³²¹ Although fixed combination containing trimethoprim and sulfamethoxazole (co-trimoxazole) has been used for treatment of AOM,^{186 321} substantial resistance to the drug reported in S. pneumoniae and AAP states do not use as an alternative to amoxicillin.³²¹

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).^{106 124}

Has been used alone for treatment of acute, uncomplicated cystitis;¹⁶³ however, value of trimethoprim alone for treatment of acute, uncomplicated UTIs has been questioned.^b Fixed combination containing trimethoprim and sulfamethoxazole (co-trimoxazole) is used for treatment of UTIs,^{135 186} and has been recommended as a good choice for empiric treatment of acute, uncomplicated cystitis.¹⁶³

Consider that uropathogens with resistance to trimethoprim (with or without sulfamethoxazole) reported with increasing frequency.¹⁶³

If using for treatment of acute, uncomplicated UTI, collect specimen for culture and in vitro susceptibility tests prior to initiating the drug.^{106 124} Some clinicians also recommend obtaining follow-up urine cultures after discontinuance of anti-infective therapy to determine whether the bacteria have been eliminated.^b

Pneumocystis jirovecii Pneumonia

Treatment of mild to moderate Pneumocystis jirovecii (formerly Pneumocystis carinii) pneumonia^{† [off-label]} (PCP); used in conjunction with dapsone.^{102 110 115 134 155 156}

Co-trimoxazole is drug of choice for treatment of mild, moderate, or severe PCP, including PCP in HIV-infected adults, adolescents, and children.^{134 155 156}

Dapsone in conjunction with trimethoprim is one of several alternatives recommended by CDC, NIH, and IDSA for treatment of mild or moderate PCP^{† [off-label]} in HIV-infected adults and adolescents when co-trimoxazole cannot be used.¹⁵⁵ Although efficacy and safety data limited regarding use for treatment of PCP in children,¹⁵⁶ some clinicians also recommend dapsone in conjunction with trimethoprim as an alternative for treatment of mild to moderate PCP in children^{† [off-label]}.¹³⁴ Not included in recommendations for treatment of more severe PCP infections.^{134 155 156}

Animal studies suggest trimethoprim alone is ineffective for treatment of PCP.¹⁰³

Trimethoprim Dosage and Administration

Administration

Oral Administration

Administer orally.^{106 124}

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.¹²⁴

Pneumocystis jirovecii Pneumonia (PCP)† [off-label]

Treatment of Mild to Moderate PCP† [off-label]

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).^{134 156}

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).^{134 155}

Adults

Urinary Tract Infections (UTIs)

Acute, Uncomplicated UTIs

Oral

100 mg every 12 hours or 200 mg once daily for 10 days.^{106 124}

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).^{134 155}

Special Populations

Renal Impairment

Urinary Tract Infections (UTIs)

Acute, Uncomplicated UTIs

Oral

Adults with Cl_cr 15–30 mL/minute: 50 mg every 12 hours.¹⁰⁶

Adults with Cl_cr <15 mL/minute: Not recommended.¹⁰⁶

Geriatric Patients

Cautious dosage selection because of age-related decreases in renal, hepatic, and/or cardiac function.¹⁰⁶ Initiate at lower end of dosing range.¹⁰⁶ (See Geriatric Precautions under Cautions.)

Cautions for Trimethoprim

Contraindications

• Hypersensitivity to trimethoprim.^{106 124}

• Documented megaloblastic anemia secondary to folate deficiency.^{106 124}

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.^{106 124}

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).^b

Clinical signs such as sore throat, fever, pallor, or purpura may be early indications of serious blood disorders.^{106 124} If such signs occur, perform CBC; discontinue trimethoprim if clinically important decrease in any formed blood element occurs.^{106 124}

Use with caution in patients with possible folate deficiency.^{106 124}

Folates, such as leucovorin (folinic acid), may be administered during trimethoprim therapy and will not interfere with the drug’s antibacterial effect.^{106 124} Hematologic abnormalities usually resolve following administration of leucovorin.^b

If signs of bone marrow depression occur, discontinue trimethoprim and administer leucovorin as required to restore normal hematopoiesis.^{106 124}

Sensitivity Reactions

Hypersensitivity Reactions

Most frequent adverse reactions are rash and pruritus.¹⁰⁶

Serious hypersensitivity reactions reported rarely, including anaphylaxis,¹⁰⁶ exfoliative dermatitis,¹⁰⁶ toxic epidermal necrolysis,^{106 107 108} erythema multiforme,¹⁰⁶ and Stevens-Johnson syndrome.^{106 105 106 107 108}

Photosensitivity

Photosensitivity (e.g., erythematous phototoxic eruptions with subsequent hyperpigmentation of sun-exposed skin) has been reported.^{105 106}

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.¹⁰⁶

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.¹⁰⁶

Specific Populations

Pregnancy

Category C.^{106 124}

Because trimethoprim may interfere with folic acid metabolism, use during pregnancy only if potential benefits justify risk to fetus.^{106 124}

Lactation

Distributed into milk.^{106 124} Because trimethoprim may interfere with folic acid metabolism, use caution in nursing women.^{106 124}

Pediatric Use

Safety and efficacy of oral solution and tablets not established in infants <2 months of age.^{106 124}

Efficacy of oral solution for treatment of AOM not established in children <6 months of age.¹²⁴

Efficacy of tablets when used as a single agent for treatment of acute, uncomplicated UTIs not established in children <12 years of age.¹⁰⁶

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.^b

Geriatric Use

Experience in those ≥65 years of age insufficient to determine whether they respond differently than younger adults.¹⁰⁶

Hyperkalemia reported in geriatric patients receiving fixed combination of trimethoprim and sulfamethoxazole (co-trimoxazole).¹⁰⁶

Substantially eliminated by kidneys; risk of adverse effects increased in patients with renal impairment.¹⁰⁶ Consider monitoring potassium concentrations and renal function (e.g., Cl_cr) since geriatric patients more likely to have decreased renal function.¹⁰⁶

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.¹⁰⁶

Hepatic Impairment

Use with caution.^{106 124}

Renal Impairment

Use with caution.^{106 124}

Not recommended in patients with Cl_cr <15 mL/minute;^{106 124} decrease dosage in those with Cl_cr 15–30 mL/minute.¹⁰⁶ (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Hypersensitivity (rash, pruritus), GI effects (epigastric discomfort, nausea, diarrhea, vomiting, glossitis, abnormal taste sensation).^{106 124 b}

Drug Interactions

Specific Drugs and Laboratory Tests

Trimethoprim Pharmacokinetics

Absorption

Bioavailability

Rapidly absorbed from GI tract.^{106 124}

Steady-state concentrations attained within 2–3 days.¹²⁴ Peak serum concentrations attained within 1–4 hours after a dose.^{106 124 b}

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.^{106 124 b}

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

Readily crosses placenta;^{106 124 b} amniotic fluid concentrations are 80% of concurrent maternal serum concentrations.^b

Distributed into milk^{106 124 b} in concentrations approximately 125% those of concurrent maternal serum concentrations.^b

Plasma Protein Binding

42–46% bound to plasma proteins.^{106 124 b}

Elimination

Metabolism

10–20%¹⁰⁶ of a dose is metabolized in the liver to oxide and hydroxylated metabolites.^{106 124 b}

Elimination Route

Eliminated in urine via glomerular filtration and tubular secretion.^{106 124 b} Only small amounts excreted in feces via biliary elimination.^b

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.^{106 b} Approximately 80% of amount recovered in urine is unchanged drug.^{106 124 b}

Hemodialysis is only moderately effective in removing trimethoprim;¹⁰⁶ not removed by peritoneal dialysis.¹⁰⁶

Half-life

8–11 hours in adults with normal renal function.^{106 b}

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

Special Populations

Half-life is prolonged in patients with renal impairment.^{124 b} Half-life is 15 hours in adults with Cl_cr 10–30 mL/minute and may increase to >26 hours in those with Cl_cr ≤10 mL/minute.^b

Stability

Storage

Oral

Solution

15–25°C in tight, light-resistant container.¹²⁴

Tablets

20–25°C in tight, light-resistant container in a dry place.¹⁰⁶

Actions and Spectrum

• A folate antagonist that inhibits formation of tetrahydrofolic acid (the metabolically active form of folic acid) in susceptible bacteria.^{106 124 b}

• Inhibits reduction of dihydrofolic acid to tetrahydrofolic acid by binding to the enzyme dihydrofolate reductase^{106 124} and inhibits bacterial thymidine synthesis.^b

• Usually slowly bactericidal.^b

• Spectrum of activity includes some gram-positive aerobes and some gram-negative aerobes, including some Enterobacteriaceae.^{106 b} Inactive against most anaerobes and inactive against Mycobacterium and Chlamydia.^b

• Gram-positive aerobes: Active against coagulase-negative staphylococci (including Staphylococcus saprophyticus)^{106 124} and Streptococcus pyogenes (group A β-hemolytic streptococci),^b and S. pneumoniae (penicillin-susceptible strains).¹²⁴ May be active against some, but not all, strains of Enterococcus faecalis.^b

• Gram-negative aerobes: Active against Acinetobacter, Citrobacter, Enterobacter,^{106 124} Escherichia coli,^{106 124} Haemophilus influenzae (except β-lactamase-negative, ampicillin-resistant strains),¹²⁴ Klebsiella pneumoniae,^{106 124} Proteus mirabilis,^{106 124} Salmonella, and Shigella. Also active against some, but not all, strains of Providencia and Serratia.^b Inactive against Moraxella catarrhalis¹²⁴ and Pseudomonas aeruginosa.^{106 b}

• Moraxella catarrhalis is resistant to trimethoprim.¹²⁴ Resistant strains of Enterobacteriaceae, especially E. coli, Klebsiella, and Proteus, have developed during trimethoprim therapy.^b

• Importance of reporting clinical signs that may be early indications of serious blood disorders (e.g., sore throat, fever, pallor, purpura).¹⁰⁶

• Importance of discontinuing use and contacting clinician if signs or symptoms of sensitization occur.¹⁰⁶

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.¹⁰⁶

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹⁰⁶

• Importance of informing patients of other important precautionary information.¹⁰⁶ (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

Frequently asked questions

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