Acne vulgaris (alternative agent) (off-label use): Oral: 100 mg 3 times daily or 300 mg twice daily (Amin 2007; Cunliffe 1999). The shortest possible duration should be used to minimize development of bacterial resistance; re-evaluate at 3 to 4 months (AAD [Zaenglein 2016]).
Pneumocystis pneumonia, treatment (mild to moderate infection) (alternative agent) (off-label use): Oral: 5 mg/kg every 8 hours in combination with dapsone for 21 days (HHS [adult] 2020).
Urinary tract infection:
Cystitis, acute uncomplicated or acute simple cystitis (infection limited to the bladder without signs/symptoms of upper tract, prostate, or systemic infection), treatment: Oral: 100 mg every 12 hours for 3 days (IDSA/ESCMID [Gupta 2011]; manufacturer's labeling).
Cystitis, prophylaxis for recurrent infection (alternative agent): Note: May be considered in nonpregnant women with bothersome, frequently recurrent cystitis despite nonantimicrobial preventive measures. The optimal duration has not been established; duration ranges from 3 to 12 months, with periodic reassessment (AUA/CUA/SUFU [Anger 2019]; Hooton 2021).
Continuous prophylaxis: Oral: 100 mg once daily (AUA/CUA/SUFU [Anger 2019]; Brumfitt 1983; Kasanen 1974; Stamm 1980).
Postcoital prophylaxis (females with cystitis temporally related to sexual intercourse): Oral: 100 mg as a single dose immediately before or after sexual intercourse (Hooton 2021).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Manufacturer's labeling:
CrCl >30 mL/minute: No dosage adjustments necessary; use with caution.
CrCl 15 to 30 mL/minute: Administer 50% of recommended dose.
CrCl <15 mL/minute: Use is not recommended.
Alternate recommendations:
Aronoff 2007: Note: The following dosage adjustments are based on a usual maintenance dose of 100 mg every 12 hours.
CrCl >30 mL/minute: No dosage adjustment necessary.
CrCl 10 to 30 mL/minute: 100 mg every 18 hours.
CrCl <10 mL/minute: 100 mg every 24 hours.
Intermittent Hemodialysis: Moderately dialyzable (20% to 59%). Dose after dialysis
Peritoneal dialysis: 100 mg every 24 hours.
HHS (OI adult 2020): Pneumocystis pneumonia, treatment: Note: The following dosage adjustments are based on a usual maintenance dose of 5 mg/kg every 8 hours. Renal function may be estimated using the Cockcroft-Gault formula for dosage adjustment purposes.
CrCl >30 mL/minute: No dosage adjustment necessary.
CrCl 10 to 30 mL/minute: 5 mg/kg every 12 hours.
CrCl <10 mL/minute: 5 mg/kg every 24 hours.
Intermittent Hemodialysis: Moderately dialyzable (20% to 59%). 5 mg/kg every 24 hours; dose after dialysis on dialysis day.
There are no dosage adjustments provided in the manufacturer’s labeling; use with caution.
(For additional information see "Trimethoprim: Pediatric drug information")
Otitis media, acute: Infants ≥6 months, Children, and Adolescents: Oral: 10 mg/kg/day in divided doses every 12 hours for 10 days; maximum daily dose: 400 mg/day
Urinary tract infection (uncomplicated), treatment: Infants ≥2 months, Children, and Adolescents: Oral: 4 to 6 mg/kg/day in divided doses every 12 hours (Kliegman 2011); Note: Preferred therapy is sulfamethoxazole and trimethoprim combined product (AAP 2011).
Pneumocystis jirovecii pneumonia (PCP), treatment: Children and Adolescents: Oral: 15 mg/kg/day in 3 divided doses for 21 days; in combination with dapsone; data in children is limited; preferred therapy is sulfamethoxazole and trimethoprim combined product (DHHS [adult and pediatric] 2013)
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Children and Adolescents:
CrCl 15 to 30 mL/minute: Administer 50% of recommended dose.
CrCl <15 mL/minute: Use is not recommended.
Moderately dialyzable (20% to 50%)
There are no dosage adjustments are provided in the manufacturer's labeling.
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Oral [strength expressed as base]:
Primsol: 50 mg/5 mL (473 mL) [alcohol free, dye free; contains methylparaben, propylene glycol, propylparaben, saccharin sodium, sodium benzoate; bubble-gum flavor]
Trimpex: 50 mg/5 mL (473 mL [DSC]) [alcohol free, dye free; contains methylparaben, propylene glycol, propylparaben, saccharin sodium, sodium benzoate, sorbitol]
Tablet, Oral:
Generic: 100 mg
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Generic: 100 mg, 200 mg
Oral: Administer without regard to food; may administer with milk or food if GI upset occurs.
Oral: Administer on an empty stomach; may administer with milk or food if GI upset occurs
Cystitis, acute uncomplicated (tablets, oral solution): Treatment of initial episodes of uncomplicated urinary tract infections due to susceptible strains of Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, Enterobacter species and coagulase-negative Staphylococcus species, including S. saprophyticus.
Otitis media, acute (oral solution): Treatment of acute otitis media in pediatric patients due to susceptible strains of Streptococcus pneumoniae and Haemophilus influenzae.
Acne vulgaris; Pneumocystis pneumonia, treatment (mild to moderate infection)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Frequency not always defined.
Dermatologic: Maculopapular rash (200 mg/day: 3% to 7%; incidence higher with larger daily doses), phototoxicity, pruritus (common)
Endocrine & metabolic: Hyperkalemia, hyponatremia
Gastrointestinal: Epigastric distress, glossitis, nausea, vomiting
Hematologic & oncologic: Leukopenia, megaloblastic anemia, methemoglobinemia, neutropenia, thrombocytopenia
Hepatic: Increased liver enzymes
Hypersensitivity: Anaphylaxis, hypersensitivity reaction
Renal: Increased blood urea nitrogen, increased serum creatinine
Miscellaneous: Fever
1%, postmarketing, and/or case reports: Aseptic meningitis, cholestatic jaundice, erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis
Hypersensitivity to trimethoprim or any component of the formulation; megaloblastic anemia due to folate deficiency
Concerns related to adverse effects:
• Hematologic effects: May rarely interfere with hematopoiesis, especially with large doses or long term therapy; monitor patients on long term therapy for signs/symptoms of hematologic disorders.
• Hyperkalemia: May cause hyperkalemia; potential risk factors include high dosage (20 mg/kg/day), renal impairment, older age, hypoaldosteronism, and concomitant use of medications causing or exacerbating hyperkalemia (Perazella 2000).
• Hypersensitivity: Serious hypersensitivity reactions have been reported (rarely).
• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns:
• Hepatic impairment: Use with caution in patients with hepatic impairment.
• Renal impairment: Use with caution in patients with renal impairment.
Special populations:
• Elderly: Elderly patients may be at risk for hyperkalemia with trimethoprim use and are at an increased risk for severe and potentially life-threatening hyperkalemia when trimethoprim is used concomitantly with medications known to cause or exacerbate hyperkalemia, such as spironolactone, ACE inhibitors, or ARBs (Antoniou 2010; Antoniou 2011; Antoniou 2015).
• Patients with potential for folate deficiency: Use with caution in patients with potential folate deficiency (malnourished, chronic antiseizure therapy, or elderly).
Dosage form specific issues:
• Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer’s labeling.
• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP ["Inactive" 1997]; Zar 2007).
Other warnings/precautions:
• Appropriate use: Otitis media: Not indicated for prophylactic or prolonged administration in otitis media at any age.
Due to resistance, should not be used for treatment of acute otitis media caused by Moraxella catarrhalis. Trimethoprim is not indicated for prolonged administration or prophylaxis of otitis media in any age.
Substrate of CYP2C9 (minor), CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP2C8 (weak)
Amantadine: Trimethoprim may enhance the adverse/toxic effect of Amantadine. Specifically, the risk of myoclonus and/or delirium may be increased. Amantadine may increase the serum concentration of Trimethoprim. Trimethoprim may increase the serum concentration of Amantadine. Risk C: Monitor therapy
Amodiaquine: Trimethoprim may enhance the neutropenic effect of Amodiaquine. Trimethoprim may increase the serum concentration of Amodiaquine. Management: Avoid coadministration of sulfamethoxazole/trimethoprim and amodiaquine in HIV-infected patients when possible due to the possible increased risk for neutropenia. If coadministration is required, monitor closely for neutropenia. Risk D: Consider therapy modification
Angiotensin II Receptor Blockers: Trimethoprim may enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Risk C: Monitor therapy
Angiotensin-Converting Enzyme Inhibitors: Trimethoprim may enhance the hyperkalemic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy
AzaTHIOprine: Trimethoprim may enhance the myelosuppressive effect of AzaTHIOprine. Risk C: Monitor therapy
BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Risk C: Monitor therapy
Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Risk X: Avoid combination
Dapsone (Systemic): Trimethoprim may increase the serum concentration of Dapsone (Systemic). Dapsone (Systemic) may increase the serum concentration of Trimethoprim. Risk C: Monitor therapy
Digoxin: Trimethoprim may increase the serum concentration of Digoxin. Risk C: Monitor therapy
Dofetilide: Trimethoprim may increase the serum concentration of Dofetilide. Risk X: Avoid combination
Eplerenone: Trimethoprim may enhance the hyperkalemic effect of Eplerenone. Risk C: Monitor therapy
Fosphenytoin: May decrease the serum concentration of Trimethoprim. Trimethoprim may increase the serum concentration of Fosphenytoin. Management: Consider alternatives to this combination when possible, to avoid potential decreased trimethoprim efficacy and increased phenytoin concentrations/effects. Monitor patients receiving this combination closely for both of these possible effects. Risk D: Consider therapy modification
Immune Checkpoint Inhibitors: Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors. Risk C: Monitor therapy
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: Monitor therapy
LamiVUDine: Trimethoprim may increase the serum concentration of LamiVUDine. Risk C: Monitor therapy
Leucovorin Calcium-Levoleucovorin: May diminish the therapeutic effect of Trimethoprim. Management: Avoid concurrent use of leucovorin or levoleucovorin with trimethoprim (plus sulfamethoxazole) for Pneumocystis jirovecii pneumonia. If trimethoprim is used for another indication, monitor closely for reduced efficacy. Risk X: Avoid combination
Memantine: Trimethoprim may enhance the adverse/toxic effect of Memantine. Specifically, the risk of myoclonus and/or delirium may be increased. Trimethoprim may increase the serum concentration of Memantine. Memantine may increase the serum concentration of Trimethoprim. Risk C: Monitor therapy
Mercaptopurine: Trimethoprim may enhance the myelosuppressive effect of Mercaptopurine. Risk C: Monitor therapy
MetFORMIN: Trimethoprim may increase the serum concentration of MetFORMIN. Risk C: Monitor therapy
Methotrexate: Trimethoprim may enhance the adverse/toxic effect of Methotrexate. Management: Consider avoiding concomitant use of methotrexate and either sulfamethoxazole or trimethoprim. If used concomitantly, monitor for the development of signs and symptoms of methotrexate toxicity (e.g., bone marrow suppression). Risk D: Consider therapy modification
Phenytoin: Trimethoprim may increase the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of Trimethoprim. Management: Consider alternatives to this combination when possible, to avoid potential decreased trimethoprim efficacy and increased phenytoin concentrations/effects. Monitor patients receiving this combination closely for both of these possible effects. Risk D: Consider therapy modification
PRALAtrexate: Trimethoprim may increase the serum concentration of PRALAtrexate. More specifically, trimethoprim may decrease excretion of pralatrexate. Risk C: Monitor therapy
Procainamide: Trimethoprim may increase serum concentrations of the active metabolite(s) of Procainamide. Trimethoprim may increase the serum concentration of Procainamide. Management: Consider alternatives to trimethoprim-containing regimens to avoid this interaction. If coadministered, monitor for increased procainamide adverse effects (increased QTc) if trimethoprim is initiated/dose increased. Risk D: Consider therapy modification
Pyrimethamine: May enhance the adverse/toxic effect of Trimethoprim. Risk C: Monitor therapy
Repaglinide: CYP2C8 Inhibitors (Weak) may increase the serum concentration of Repaglinide. Risk C: Monitor therapy
RifAMPin: Trimethoprim may increase the serum concentration of RifAMPin. RifAMPin may decrease the serum concentration of Trimethoprim. Risk C: Monitor therapy
Sapropterin: Trimethoprim may decrease the serum concentration of Sapropterin. Specifically, trimethoprim may decrease tissue concentrations of tetrahydrobiopterin. Risk C: Monitor therapy
Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Risk D: Consider therapy modification
Spironolactone: Trimethoprim may enhance the hyperkalemic effect of Spironolactone. Risk C: Monitor therapy
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: Consider therapy modification
Zidovudine: May enhance the neutropenic effect of Trimethoprim. Trimethoprim may increase the serum concentration of Zidovudine. Risk C: Monitor therapy
Trimethoprim crosses the placenta.
Trimethoprim may affect folic acid metabolism; adverse fetal events may be associated with maternal trimethoprim use immediately prior to or during pregnancy (Andersen 2013a; Andersen 2013b; Mølgaard-Nielsen 2012; Sun 2014).
Studies evaluating the effects of trimethoprim administration in pregnancy have also been conducted with Sulfamethoxazole and Trimethoprim (see sulfamethoxazole/trimethoprim monograph for details).
Trimethoprim is present in breast milk.
Milk concentrations of trimethoprim are similar to those in the maternal plasma (Reeves 1979). In general, antibiotics that are present in breast milk may cause nondose-related modification of bowel flora. Monitor infants for GI disturbances, such as thrush or diarrhea (WHO 2002).
The manufacturer recommends caution while using trimethoprim in a breastfeeding female because trimethoprim may interfere with folic acid metabolism. However, single agent trimethoprim is considered to be compatible with breastfeeding when used in usual recommended doses (WHO 2002).
Also see the sulfamethoxazole/trimethoprim monograph for additional information.
May cause folic acid deficiency, supplements may be needed.
CBC with differential, platelet count, liver enzyme tests, bilirubin, serum potassium, serum creatinine, and BUN periodically during long-term therapy
Inhibits folic acid reduction to tetrahydrofolate by reversible inhibition of dihydrofolate reductase, inhibiting bacterial synthesis of nucleic acids and proteins
Absorption: Oral: Readily and extensively absorbed
Distribution: Widely into body tissues and fluids (middle ear, prostate, bile, aqueous humor, CSF); mean peak middle ear fluid concentration in children 1 to 12 years of 2 mcg/mL after a single 4 mg/kg dose; Vd:
Newborns: 2.7 L/kg (range: 1.3 to 4.1 hours) (Springer 1982)
Infants: 1.5 L/kg (Hoppu 1989)
Children (Hoppu 1987):
1 to 3 years: 0.86 L/kg
8 to 10 years: 1 L/kg
Adults: ~1.3 L/kg (Hoppu 1987)
Protein binding: ~44%
Metabolism: Partially hepatic (10% to 20%) via demethylation, oxidation, and hydroxylation
Bioavailability: Similar for tablets and solution
Half-life elimination: Prolonged with renal impairment
Newborns: 19 hours; range: 11 to 27 hours (Springer 1982)
Infants 2 months to 1 year: 4.6 hours; range: 3 to 6 hours (Hoppu 1989)
Children (Hoppu 1987):
1 to 3 years: 3.7 hours
8 to 10 years: 5.4 hours
Adults, normal renal function: 8 to 10 hours
Time to peak, serum: 1 to 4 hours
Excretion: Primarily urine (50% to 60%; 80% as unchanged drug); feces
Renal function impairment: Half-life is prolonged.
Tablets (Trimethoprim Oral)
100 mg (per each): $2.33
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