Pneumocystis jirovecii pneumonia (mild to moderate) (alternative agent): Limited data available: Children and Adolescents: Oral: 5 mg/kg/dose every 8 hours for 21 days in combination with dapsone. After completion of treatment, patient should be transitioned to a regimen for secondary prophylaxis (Ref).
Urinary tract infection (uncomplicated): Note: Sulfamethoxazole and trimethoprim combined product is typically preferred over trimethoprim alone (Ref).
Treatment: Infants ≥2 months, Children, and Adolescents: Oral: 2.5 to 5 mg/kg/dose every 12 hours (Ref); maximum dose: 100 mg/dose (Ref). Duration of therapy should be individualized based on patient-specific factors such as age, severity/extent of infection, clinical response, etc; usual duration 5 to 10 days (Ref).
Prophylaxis: Infants, Children, and Adolescents ≤13 years: Oral: 1 to 3 mg/kg/dose once daily (Ref); usual adult dose: 100 mg/dose (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Altered kidney function:
Children and Adolescents (Ref):
CrCl >30 mL/minute: Oral: No dosage adjustment necessary.
CrCl 15 to 30 mL/minute: Oral: Administer 50% of recommended dose.
CrCl <15 mL/minute: Use is not recommended.
Intermittent hemodialysis: No dosage adjustment provided in manufacturer's labeling. Moderately dialyzable (20% to 59%).
There are no dosage adjustments provided in the manufacturer's labeling.
(For additional information see "Trimethoprim: Drug information")
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 (Ref).
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 (Ref).
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 (Ref).
Continuous prophylaxis: Oral: 100 mg once daily (Ref).
Postcoital prophylaxis (females with cystitis temporally related to sexual intercourse): Oral: 100 mg as a single dose immediately before or after sexual intercourse (Ref).
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.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in infants, children, adolescents, and adults.
1% to 10%:
Dermatologic: Skin rash (1% to 7%; including maculopapular rash, morbilliform rash, pruritic rash)
Gastrointestinal: Diarrhea (4%), vomiting (2%)
<1%: Gastrointestinal: Abdominal pain
Frequency not defined:
Dermatologic: Phototoxicity, pruritus
Endocrine & metabolic: Hyperkalemia, hyponatremia
Gastrointestinal: Epigastric discomfort, glossitis, nausea
Hematologic & oncologic: Eosinophilia, leukopenia, lymphocytosis, megaloblastic anemia, methemoglobinemia, neutropenia, thrombocytopenia
Hepatic: Increased liver enzymes, increased serum bilirubin
Renal: Increased blood urea nitrogen, increased serum creatinine
Miscellaneous: Fever
Postmarketing:
Dermatologic: Erythema multiforme, exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis (Sood 2021), vasculitis of the skin (Holt 1992)
Gastrointestinal: Clostridium difficile-associated diarrhea
Hepatic: Cholestatic jaundice (Singh 1991)
Hypersensitivity: Anaphylaxis (Nordstrand 2004), drug reaction with eosinophilia and systemic symptoms (Subhani 2020), severe hypersensitivity reaction
Nervous system: Aseptic meningitis (Mathanasenarajah 2017)
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:
• Older adult: 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.
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 [DSC]) [alcohol free, dye free; contains methylparaben, propylene glycol, propylparaben, saccharin sodium, sodium benzoate]
Tablet, Oral:
Generic: 100 mg
May be product dependent
Tablets (Trimethoprim Oral)
100 mg (per each): $2.33
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Generic: 100 mg, 200 mg
10 mg/mL Oral Suspension:
A 10 mg/mL oral suspension may be made with tablets. Crush ten 100 mg tablets in a mortar and reduce to a fine powder. Add 20 mL of a 1:1 mixture of Simple Syrup, NF, and Methylcellulose 1% and mix to a uniform paste; mix while adding the vehicle in incremental proportions to almost 100 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 100 mL. Label "shake well" and "refrigerate." Stable for 91 days.
Oral: May administer without regard to food, although absorption may be improved on an empty stomach (Ref).
Oral: Administer without regard to food; may administer with milk or food if GI upset occurs.
Solution: Store between 15°C to 25°C (59°F to 77°F). Protect from light.
Tablets: Store at 20°C to 25°C (68°F to 77°F). Protect from light.
Treatment of urinary tract infections caused by susceptible Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, Enterobacter spp, and coagulase-negative Staphylococcus (including S. saprophyticus) (FDA approved in adults). Has also been used for treatment of Pneumocystis jirovecii pneumonia.
Substrate of CYP2C9 (Minor), CYP3A4 (Minor), MATE1/2-K; Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP2C8 (Weak), MATE1/2-K, OCT1, OCT2;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program
Amantadine: Trimethoprim may increase adverse/toxic effects of Amantadine. Specifically, the risk of myoclonus or delirium may be increased. Trimethoprim may increase serum concentration of Amantadine. Risk C: Monitor
Amodiaquine: Trimethoprim may increase neutropenic effects of Amodiaquine. Trimethoprim may increase 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 increase hyperkalemic effects of Angiotensin II Receptor Blockers. Risk C: Monitor
Angiotensin-Converting Enzyme Inhibitors: Trimethoprim may increase hyperkalemic effects of Angiotensin-Converting Enzyme Inhibitors. Management: Consider avoiding coadministration if possible. If combined, monitor serum potassium closely, particularly for patients with other risk factors (eg, renal impairment, older age, and other medications that increase potassium. Risk X: Avoid
AzaTHIOprine: Trimethoprim may increase myelosuppressive effects of AzaTHIOprine. Risk C: Monitor
Bacillus clausii: Antibiotics may decrease therapeutic effects of Bacillus clausii. Management: Bacillus clausii should be taken in between antibiotic doses during concomitant therapy. Risk D: Consider Therapy Modification
BCG (Intravesical): Antibiotics may decrease therapeutic effects of BCG (Intravesical). Risk X: Avoid
BCG Vaccine (Immunization): Antibiotics may decrease therapeutic effects of BCG Vaccine (Immunization). Risk C: Monitor
Cholera Vaccine: Antibiotics may decrease therapeutic effects 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
Clofarabine: OCT2 Inhibitors may increase serum concentration of Clofarabine. Risk C: Monitor
CycloSPORINE (Systemic): Trimethoprim may increase nephrotoxic effects of CycloSPORINE (Systemic). Trimethoprim may increase hyperkalemic effects of CycloSPORINE (Systemic). Risk C: Monitor
Dalfampridine: OCT2 Inhibitors may increase serum concentration of Dalfampridine. Management: Consider alternatives to this combination. Carefully weigh the risk of seizures against the benefit of combining OCT2 inhibitors with dalfampridine. Risk D: Consider Therapy Modification
Daprodustat: CYP2C8 Inhibitors (Weak) may increase serum concentration of Daprodustat. Risk C: Monitor
Dapsone (Systemic): Trimethoprim may increase serum concentration of Dapsone (Systemic). Dapsone (Systemic) may increase serum concentration of Trimethoprim. Risk C: Monitor
Digoxin: Trimethoprim may increase serum concentration of Digoxin. Risk C: Monitor
Dofetilide: Trimethoprim may increase serum concentration of Dofetilide. Risk X: Avoid
Fecal Microbiota (Live) (Oral): May decrease therapeutic effects of Antibiotics. Risk X: Avoid
Fecal Microbiota (Live) (Rectal): Antibiotics may decrease therapeutic effects of Fecal Microbiota (Live) (Rectal). Risk X: Avoid
Fosphenytoin-Phenytoin: Trimethoprim may increase serum concentration of Fosphenytoin-Phenytoin. Risk C: Monitor
Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies): Antibiotics may decrease therapeutic effects of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor
Lactobacillus and Estriol: Antibiotics may decrease therapeutic effects of Lactobacillus and Estriol. Risk C: Monitor
LamiVUDine: Trimethoprim may increase serum concentration of LamiVUDine. Risk C: Monitor
Leucovorin Calcium-Levoleucovorin: May decrease therapeutic effects 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
Memantine: Trimethoprim may increase adverse/toxic effects of Memantine. Specifically, the risk of myoclonus and/or delirium may be increased. Trimethoprim may increase serum concentration of Memantine. Risk C: Monitor
Mercaptopurine: Trimethoprim may increase myelosuppressive effects of Mercaptopurine. Risk C: Monitor
MetFORMIN: MATE1/2-K Inhibitors may increase serum concentration of MetFORMIN. Risk C: Monitor
Methotrexate: Trimethoprim may increase adverse/toxic effects 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 (eg, bone marrow suppression). Risk D: Consider Therapy Modification
Mycophenolate: Antibiotics may decrease active metabolite exposure of Mycophenolate. Specifically, concentrations of mycophenolic acid (MPA) may be reduced. Risk C: Monitor
Potassium-Sparing Diuretics: Trimethoprim may increase hyperkalemic effects of Potassium-Sparing Diuretics. Risk C: Monitor
PRALAtrexate: Trimethoprim may increase serum concentration of PRALAtrexate. More specifically, trimethoprim may decrease excretion of pralatrexate. Risk C: Monitor
Procainamide: Trimethoprim may increase serum concentration of Procainamide. Trimethoprim may increase active metabolite exposure 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 increase adverse/toxic effects of Trimethoprim. Risk C: Monitor
Repaglinide: CYP2C8 Inhibitors (Weak) may increase serum concentration of Repaglinide. Risk C: Monitor
RifAMPin: May decrease serum concentration of Trimethoprim. Trimethoprim may increase serum concentration of RifAMPin. Risk C: Monitor
Sapropterin: Trimethoprim may decrease serum concentration of Sapropterin. Specifically, trimethoprim may decrease tissue concentrations of tetrahydrobiopterin. Risk C: Monitor
Sodium Picosulfate: Antibiotics may decrease therapeutic effects 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
Typhoid Vaccine: Antibiotics may decrease therapeutic effects 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 increase neutropenic effects of Trimethoprim. Trimethoprim may increase serum concentration of Zidovudine. Risk C: Monitor
May cause folic acid deficiency, supplements may be needed.
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).
CBC with differential, platelet count, liver enzyme tests, bilirubin, serum potassium, serum creatinine and BUN.
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:
Neonates (GA: 28 to 40 weeks; PNA: <3 days): ~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.
Neonates (GA: 28 to 40 weeks; PNA: <3 days): ~19 hours; range: 11 to 27 hours (Springer 1982).
Infants: ~4.6 hours; range: 3 to 6 hours (Hoppu 1989).
Children 1 to 10 years of age: 3.7 to 5.5 hours (Hoppu 1987).
Children >10 years of age and adolescents: 8.19 hours.
Adults: 8 to 12 hours (Hoppu 1984; manufacturer’s labeling).
Time to peak, serum: 1 to 4 hours.
Excretion: Primarily urine (50% to 60%; 80% as unchanged drug); feces.
Altered kidney function: Patients with severely impaired kidney function exhibit an increase in the half-life, requiring dosage adjustment.
Older adult: Total body clearance of trimethoprim is 19% lower in older patients (Varoquaux 1985).
Anti-infective considerations:
Parameters associated with efficacy (in combination with sulfamethoxazole [SMX]): Limited data available; associated with free area under the curve (fAUC24)/minimum inhibitory concentration (MIC) in the context of 100% free time over MIC (fT>MIC) (Lasko 2022a; Lasko 2022b). Data in specific organisms indicate additional free concentration-dependent effect (Close 2002; Lasko 2022a).
Organism specific:
Stenotrophomonas maltophilia: fAUC24/MIC ≥67.4 (bacteriostatic); fCmax/MIC ≥4.2 (bacteriostatic) (Lasko 2022a).
E. coli: fAUC24/MIC ≥40.7 (bacteriostatic); fAUC24/MIC ≥59.5 (1-log reduction); fAUC24/MIC ≥86.3 (2-log reduction) (Lasko 2022b).
Expected drug exposure in patients with normal renal function (in combination with SMX):
Pediatric patients: AUC0- 24: Oral, steady state (simulated using PK model):
Infants and children <6 years of age:
4 mg/kg/dose every 12 hours: Median: ~38 mg•hour/L (Autmizguine 2017).
5 mg/kg/dose every 8 hours: Median: ~71 mg•hour/L (Autmizguine 2017).
5 mg/kg/dose every 6 hours: Median: ~95 mg•hour/L (Autmizguine 2017).
Children ≥6 years of age and adolescents:
4 mg/kg/dose every 12 hours: Median: ~46 mg•hour/L (Autmizguine 2017).
5 mg/kg/dose every 8 hours: Median: ~92 mg•hour/L (Autmizguine 2017).
5 mg/kg/dose every 6 hours: Median: ~123 mg•hour/L (Autmizguine 2017).
Adults:
Cmax (peak): Oral: Healthy volunteers: 160 mg, single dose: 1.57 ± 0.32 mg/L (Varoquaux 1985).
Parameters associated with toxicity: Increased incidence of anemia, neutropenia, and azotemia have been associated with increasing serum concentration, described as average serum trimethoprim concentrations (Cavg) (obtained within 8 hours of a dose on an 8-hour dosing interval). For Cavg <5 mg/L, 5 to 8 mg/L, and >8 mg/L, incidence of anemia was 6%, 16%, and 33%; incidence of neutropenia was 13%, 22%, and 37%; and incidence of azotemia was 0%, 0%, and 15% (Hughes 1995).