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تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
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Trimethoprim-sulfamethoxazole (co-trimoxazole): Pediatric drug information

Trimethoprim-sulfamethoxazole (co-trimoxazole): Pediatric drug information
(For additional information see "Trimethoprim-sulfamethoxazole (co-trimoxazole): Drug information" and see "Trimethoprim-sulfamethoxazole (co-trimoxazole): Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Bactrim;
  • Bactrim DS;
  • Sulfatrim Pediatric
Brand Names: Canada
  • Septra;
  • Sulfatrim;
  • Sulfatrim DS;
  • Sulfatrim Pediatric;
  • TEVA-Trimel DS [DSC];
  • TEVA-Trimel [DSC]
Therapeutic Category
  • Antibiotic, Sulfonamide Derivative
Dosing: Pediatric

Dosage guidance:

Dosing: Dosage recommendations are based on the trimethoprim (TMP) component.

General dosing: Infants ≥2 months, Children, and Adolescents: Oral, IV: 8 to 12 mg TMP/kg/day in divided doses every 12 hours; maximum dose: 160 mg TMP/dose (Ref).

Brucellosis

Brucellosis: Limited data available: Note: Recommended in patients <8 years of age for whom prolonged use of doxycycline is not recommended or in older patients if tetracyclines are contraindicated (Ref).

Infants ≥2 months, Children, and Adolescents: Oral: 8 to 12 mg TMP/kg/day in divided doses every 12 hours in combination with rifampin for ≥6 weeks. Usual adult dose: 320 mg/day; however, doses up to 480 mg/day have been described. For serious infections, gentamicin should be added for the initial 1 to 2 weeks and therapy may be extended for up to 4 to 6 months (Ref).

Cyclosporiasis

Cyclosporiasis (Cyclospora infection): Limited data available: Infants ≥2 months, Children, and Adolescents: Oral, IV: 8 to 10 mg TMP/kg/day in divided doses every 12 hours; maximum dose: 160 mg TMP/dose. Typical treatment duration is 7 to 10 days, though longer durations may be required in immunocompromised patients (Ref).

Cystoisosporiasis

Cystoisosporiasis (Cystoisospora infection; formerly isosporiasis): Limited data available:

Treatment: Infants ≥2 months, Children, and Adolescents: Oral: 8 to 10 mg TMP/kg/day in divided doses every 12 hours for 7 to 10 days; maximum dose: 160 mg TMP/dose; immunocompromised patients may require longer courses of therapy (eg, 3 to 4 weeks). In patients with HIV, dose may be increased to 15 to 20 mg TMP/kg/day in divided doses every 6 to 8 hours if symptoms worsen or do not improve (Ref).

Chronic maintenance therapy (secondary prophylaxis): HIV-exposed/-infected: Note: Recommended in patients with HIV who are severely immunosuppressed (eg, adolescents with CD4 count <200 mm3); may consider discontinuation when immunologic status is improved in response to antiretroviral therapy (ART) for >6 months if no symptoms of active cystoisosporiasis are present (Ref).

Infants ≥2 months and Children: Oral: 5 mg TMP/kg/day in divided doses every 12 hours 3 days per week; maximum dose: 80 mg TMP/dose (Ref).

Adolescents: Oral: 160 mg TMP/dose 3 times weekly, or alternatively, 160 mg TMP/dose once daily, or 320 mg TMP/dose 3 times weekly (Ref).

Exit-site or tunnel infection, peritoneal dialysis catheter

Exit-site or tunnel infection, peritoneal dialysis catheter: Limited data available: Infants, Children, and Adolescents: Oral: 5 to 10 mg TMP/kg/dose once daily; maximum dose: 80 mg TMP/dose. Exit-site infection should be treated for ≥2 weeks and for at least 7 days after complete resolution, or for ≥3 weeks for Staphylococcus aureus; tunnel infection should be treated for 2 to 4 weeks (Ref).

Melioidosis

Melioidosis (Burkholderia pseudomallei infection): Limited data available:

Initial intensive therapy (as a potential add-on to primary therapy [eg, in focal disease of the CNS, bone, or joint]): Children and Adolescents: Oral, IV: 12 mg TMP/kg/day in divided doses every 12 hours; maximum dose: 320 mg TMP/dose. Duration is ≥14 days, though a longer duration may be necessary depending on disease severity and site of infection; should be followed by eradication therapy (Ref).

Eradication therapy (begin after completion of initial intensive therapy): Children and Adolescents: Oral: 12 mg TMP/kg/day in divided doses every 12 hours; maximum dose: 320 mg TMP/dose. Duration is ≥3 months, but may be longer (eg, 6 months) in some cases (Ref).

Meningitis, including health care-associated ventriculitis/meningitis

Meningitis, including health care-associated ventriculitis/meningitis (alternative agent):

Infants ≥2 months, Children, and Adolescents: IV: 10 to 20 mg TMP/kg/day in divided doses every 6 to 12 hours. Duration should be individualized based on pathogen, patient characteristics, and response; treatment duration for gram-negative bacilli and S. aureus is a minimum of 10 to 14 days, although some experts recommend ≥21 days for gram-negative bacilli; Listeria monocytogenes should be treated ≥21 days. With repeatedly positive cultures, therapy should be continued for at least 10 to 14 days after first negative cerebrospinal fluid culture (Ref).

Osteoarticular infection

Osteoarticular infection (step-down therapy following parenteral treatment): Very limited data available:

Infants ≥2 months, Children, and Adolescents: Oral: 6 to 20 mg TMP/kg/day in divided doses every 6 to 12 hours; maximum dose: 160 mg TMP/dose (Ref); in a retrospective evaluation of 20 patients (age 9 months to 17 years), the median dose was 16.4 mg/kg/day (Ref).

Otitis media, acute

Otitis media, acute (alternative agent): Note: Not considered appropriate empiric therapy for acute otitis media due to significant Streptococcus pneumoniae resistance (Ref). May be considered when a susceptible pathogen has been isolated.

Infants ≥2 months, Children, and Adolescents: Oral: 8 mg TMP/kg/day in divided doses every 12 hours for 10 days; maximum dose: 160 mg TMP/dose (Ref).

Pneumocystis jirovecii pneumonia

Pneumocystis jirovecii pneumonia (PCP):

Prophylaxis, primary and secondary:

HIV-infected:

Infants and Children: Oral: 5 to 10 mg TMP/kg/day or 150 mg TMP/m2/day; may be administered in divided doses every 12 hours 2 to 3 days per week on alternating or consecutive days, or as a single daily dose every day (ie, 7 days/week); maximum dose: 160 mg TMP/dose. In HIV-infected or indeterminate infants, continue until 12 months of age regardless of CD4 cell count/percentage. In children, continue until patient has been receiving ART for ≥6 months and achieves a CD4 percentage ≥15% or age-specific CD4 cell count targets (age <6 years: ≥500 cells/mm3; age ≥6 years: ≥200 cells/mm3) for >3 consecutive months (Ref).

Adolescents: Oral: 80 to 160 mg TMP daily or alternatively, 160 mg TMP 3 times weekly. Continue until CD4 cell count is ≥200 cells/mm3 for ≥3 months in response to ART; may also consider discontinuing when CD4 cell count is ≥100 cells/mm3 and viral load is undetectable for ≥3 to 6 months in response to ART (Ref).

Immunocompromised, HIV-uninfected (eg, solid organ or hematopoietic cell transplant recipients, patients with hematologic malignancies or primary immunodeficiencies):

Infants, Children, and Adolescents: Oral: 5 mg TMP/kg/day or 150 mg TMP/m2/day; may be administered in divided doses every 12 hours 2 to 3 days per week on alternating or consecutive days, or as a single daily dose given 7 days per week or 3 times weekly on consecutive days; maximum dose: 160 mg TMP/dose. Duration of prophylaxis varies based on underlying condition (eg, type of transplant) and presence of risk factors including continuing immunosuppression (Ref).

Treatment: Note: Patients with moderate or severe infection (PaO2 <70 mm Hg at room air or alveolar-arterial oxygen gradient ≥35 mm Hg) should receive adjunctive corticosteroids. Secondary prophylaxis should be initiated upon completion of therapy (Ref).

Infants and Children: IV, Oral: 15 to 20 mg TMP/kg/day in divided doses every 6 to 8 hours; in patients with mild to moderate disease and no diarrhea/malabsorption issues, may transition to oral therapy following clinical improvement; treat for a total of 21 days (Ref).

Adolescents (Ref):

Mild to moderate: Oral, IV: 15 to 20 mg TMP/kg/day in divided doses every 6 to 8 hours, or 320 mg TMP every 8 hours; treat for a total of 21 days.

Moderate to severe: IV, Oral: 15 to 20 mg TMP/kg/day in divided doses every 6 to 8 hours; may switch to oral after clinical improvement; treat for a total of 21 days.

Q-Fever, acute symptomatic

Q-Fever (Coxiella burnetii), acute symptomatic (alternative agent): Note: Treatment is most effective if given within the first 3 days of symptoms (Ref).

Children <8 years: Limited data available: Dose should be based on severity of illness: Oral: Usual dose range: 8 to 10 mg TMP/kg/day in divided doses twice daily for 14 days; a wider dose range of 4 to 20 mg TMP/kg/day divided twice daily has been suggested to address varying degrees of severity; however, reported pediatric efficacy experience is lacking; monitor patients receiving doses at the high and low end of the range closely for efficacy and possible adverse effects. Maximum dose: 160 mg TMP/dose (Ref).

Shigellosis

Shigellosis (alternative agent): Note: Not recommended as empiric therapy due to reported resistance; may be used for documented susceptible strains (Ref).

Infants ≥2 months, Children, and Adolescents: Oral, IV: 8 to 10 mg TMP/kg/day in divided doses every 12 hours for 3 to 5 days; maximum dose: 160 mg TMP/dose. May divide IV therapy up to every 6 hours. Longer treatment durations of 7 to 10 days have been suggested for immunocompromised patients (Ref).

Skin and soft tissue infection

Skin and soft tissue infection (SSTI): Limited data available:

Infants ≥2 months, Children, and Adolescents:

Cellulitis, purulent/fluctuant SSTI: Oral, IV: 8 to 12 mg TMP/kg/day in divided doses every 12 hours; may divide IV therapy every 6 hours; maximum dose: 320 mg TMP/dose (Ref). Typical duration is ≥5 days for uncomplicated infection but may be extended if clinical response is inadequate (Ref).

Impetigo, ecthyma: Oral: 8 to 12 mg TMP/kg/day in divided doses every 12 hours for 7 days. Shorter courses of 3 to 5 days have also been described (Ref).

Toxoplasma gondii encephalitis

Toxoplasma gondii encephalitis (toxoplasmosis):

Primary prophylaxis:

Patients with HIV: Note: Primary prophylaxis is indicated for T. gondii seropositive patients with CD4 cell percentage <15% if <6 years of age or CD4 count <100 cells/mm3 if ≥6 years of age (Ref).

Infants and Children: Oral: 150 mg TMP/m2/day; dose may be administered as a single daily dose (preferred) or in divided doses every 12 hours; alternatively, may also be given 3 times weekly for 3 consecutive or alternating days; maximum dose: 160 mg TMP/dose. In HIV-infected or indeterminate infants, continue until 12 months of age regardless of CD4 cell count. In children, continue until patient has been receiving ART for ≥6 months and achieves age-specific target CD4 count (age 1 to <6 years: ≥15%; age ≥6 years: >200 cells/mm3) for >3 consecutive months (Ref).

Adolescents: Oral: 160 mg TMP daily (preferred) or 160 mg TMP 3 times weekly or 80 mg TMP daily. Continue primary prophylaxis following initiation of ART until CD4 count >200 cells/mm3 for >3 months; can consider discontinuation in patients with a CD4 count between 100 to 200 cells/mm3 who are receiving ART and have had an undetectable viral load for ≥3 to 6 months (Ref).

Recipients of hematopoietic cell transplant (T. gondii seropositive): Infants ≥2 months, Children, and Adolescents: Oral: 150 mg TMP/m2/day or 5 mg/kg/day; dose may be administered as a single daily dose (preferred) or in divided doses every 12 hours; alternatively, may also be given 3 times weekly; maximum dose: 160 mg TMP/dose. Recommended to be used from engraftment until 6 months post-transplant (Ref).

Treatment (alternative agent): Note: Recommended only until first-line therapy is available or can be tolerated (Ref).

Infants, Children, and Adolescents: Oral, IV: 10 to 15 mg TMP/kg/day in divided doses every 8 to 12 hours for ≥6 weeks; longer duration may be needed if clinical or radiologic disease is extensive or response is incomplete at 6 weeks; following treatment, patients with HIV should receive chronic maintenance therapy (Ref).

Chronic maintenance therapy (secondary prophylaxis) (alternative agent):

Infants and Children: Oral: 150 mg TMP/m2/day once daily; maximum dose: 160 mg TMP/dose. For patients with HIV, continue until patient has been receiving ART for ≥6 months, has no toxoplasmosis symptoms, and achieves age-specific target CD4 count (age 1 to <6 years: ≥15%; age ≥6 years: >200 cells/mm3) for >6 consecutive months (Ref). Note: Only use when pyrimethamine is unavailable or not tolerated (Ref).

Adolescents: Oral: 160 mg TMP twice daily or, alternatively, 160 mg TMP once daily. For patients with HIV, continue following initiation of ART until CD4 count >200 cells/mm3 for >6 months (Ref). Note: Once-daily dosing may be associated with an increased risk of relapse; if used, a gradual transition (eg, follow acute treatment with 4 to 6 weeks of 160 mg TMP twice daily before lowering to once-daily dosing) may be beneficial (Ref).

Urinary tract infection

Urinary tract infection:

Treatment: Note: Duration of therapy should be individualized based on patient age, severity/extent of infection, and clinical response; typical duration is 7 to 14 days, though may be as short as 3 days in older children and adolescents with uncomplicated cystitis (Ref).

Oral: Infants ≥2 months, Children, and Adolescents: 6 to 12 mg TMP/kg/day in divided doses every 12 hours; maximum dose: 160 mg/dose (Ref).

IV: Infants ≥2 months, Children, and Adolescents: 8 to 10 mg TMP/kg/day in divided doses every 6 to 12 hours (Ref).

Prophylaxis: Infants ≥2 months, Children, and Adolescents: Oral: 2 to 3 mg TMP/kg/dose once daily (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

Altered kidney function:

Infants, Children, and Adolescents: Oral, IV:

Note: Dosing is based on pharmacokinetic parameters, limited pediatric studies, adult studies, and expert opinion (Ref):

Dose Adjustments for Kidney Impairment: Oral, IV

CrCl

If usual recommended dose is 5 to 12 mg TMP/kg/day in 1 or 2 divided doses

If usual recommended dose is 15 to 20 mg TMP/kg/day in 3 or 4 divided doses

If usual recommended dose is 80 mg to 160 mg TMP daily or 160 mg TMP 3 times a week

>30 mL/minute/1.73 m2

No dosage adjustment necessary.

No dosage adjustment necessary.

No dosage adjustment necessary.

15 to 30 mL/minute/1.73 m2

Use with caution and appropriate monitoring.

Administer 50% of daily dose for indication in 1 or 2 divided doses.

Use with caution and appropriate monitoring.

Administer 50% of daily dose for indication in 2 or 3 divided doses.

Use with caution and appropriate monitoring.

80 mg TMP once daily or 3 times a week.

<15 mL/minute/1.73 m2

Use not recommended; if used, monitor carefully.

Administer 25% to 50% of daily dose for indication in 1 or 2 divided doses.

Use not recommended; if used, monitor carefully.

Administer 25% to 50% of daily dose for indication in 1 or 2 divided doses.

Use not recommended; if used, monitor carefully.

80 mg TMP 3 times a week.

Hemodialysis, intermittent: Dialyzable (~44% of TMP and ~57% of SMX removed with low flux filter in adults) (Ref).

Children and Adolescents (Ref):

General infections: Oral, IV: 3 to 5 mg TMP/kg/dose every 24 hours; on dialysis days, administer after dialysis; consider administering an additional 2.5 mg TMP/kg dose after intermittent hemodialysis (IHD) sessions if daily dose administered prior to dialysis.

Pneumocystis pneumonia: Oral, IV: 5 mg TMP/kg/dose every 12 hours; on dialysis days, administer after dialysis; consider administering an additional 2.5 mg TMP/kg dose after IHD sessions if daily dose administered prior to dialysis.

Peritoneal dialysis: Pediatric data are lacking; however, based on adult information, not efficiently dialyzed (Ref).

Infants, Children, and Adolescents: Oral, IV: Follow dosage recommendations for CrCl <15 mL/minute/1.73 m2; if used, monitor carefully (Ref).

CRRT:

Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection) and consideration of initial loading doses. Close monitoring of response and adverse reactions due to drug accumulation is important.

CVVH/CVVHD/CVVHDF: Children and Adolescents: Oral, IV: Based on adult data, sulfamethoxazole and trimethoprim are substantially removed by CRRT. No dosage adjustment likely necessary (Ref).

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling. Use with caution; use is contraindicated in cases of marked hepatic damage.

Dosing: Adult

(For additional information see "Trimethoprim-sulfamethoxazole (co-trimoxazole): Drug information")

Dosage guidance:

Dosing: Weight-based dosing recommendations are based on the trimethoprim component.

Dosage form information: Each double-strength tablet contains trimethoprim 160 mg and sulfamethoxazole 800 mg. Each single-strength tablet contains trimethoprim 80 mg and sulfamethoxazole 400 mg. The undiluted IV solution contains trimethoprim 16 mg per mL and sulfamethoxazole 80 mg per mL.

Clinical considerations: For outpatients receiving high dose therapy (>5 mg/kg/day trimethoprim component]), monitor serum creatinine and potassium concentrations (Ref).

General dosing guidelines:

Oral: 1 to 2 double-strength tablets every 12 to 24 hours.

IV: 8 to 20 mg/kg/day (trimethoprim component) divided every 6 to 12 hours.

Bartonella spp. infection

Bartonella spp. infection (alternative agent) (off-label use):

Note: Not a recommended agent for patients with HIV (Ref).

Cat scratch disease, lymphadenitis: Oral: 1 double-strength tablet twice daily for 7 to 10 days (Ref).

Cat scratch disease, disseminated (CNS infection, neuroretinitis):

Note: Use in combination with rifampin (Ref).

IV: 160 mg (trimethoprim component) twice daily (Ref).

Oral: 1 double-strength tablet twice daily (Ref).

Duration of therapy: 10 to 14 days for CNS infection; 4 to 6 weeks for neuroretinitis (Ref).

Bite wound infection, prophylaxis or treatment

Bite wound infection, prophylaxis or treatment (animal or human bite) (alternative agent) (off-label use): Oral: 1 double-strength tablet twice daily; in combination with an appropriate agent for anaerobic coverage. Duration of therapy for prophylaxis is 3 to 5 days (Ref); duration of therapy for established infection is typically 5 to 14 days (Ref).

Brucellosis

Brucellosis (alternative agent) (off-label use):

Note: Alterative to preferred therapy; however, preferred in patients who are pregnant and <36 weeks' gestation (Ref).

Treatment:

Neurobrucellosis, endocarditis: Oral: One double-strength tablet twice daily for ≥12 weeks (may be needed for up to 6 months) as part of an appropriate combination regimen (Ref).

Uncomplicated (nonfocal): Oral: One double-strength tablet twice daily for 6 weeks as part of an appropriate combination regimen (Ref).

Postexposure prophylaxis (high-risk laboratory exposure): Oral: One double-strength tablet twice daily for 3 weeks as part of an appropriate combination regimen (Ref).

Chronic obstructive pulmonary disease, acute exacerbation

Chronic obstructive pulmonary disease, acute exacerbation (alternative agent): Note: Avoid use in patients with risk factors for Pseudomonas infection or poor outcomes (eg, ≥65 years of age with major comorbidities, FEV1 <50% predicted, frequent exacerbations) (Ref).

Oral: 1 double-strength tablet every 12 hours for 5 to 7 days (Ref).

Diabetic foot infection, mild to moderate

Diabetic foot infection, mild to moderate (off-label use):

Note: For empiric or directed coverage of methicillin-resistant S. aureus. When used as empiric therapy, give as part of an appropriate combination regimen (Ref).

Oral: 2 double-strength tablets twice daily, usually for 1 to 2 weeks (Ref).

Diarrhea, infectious

Diarrhea, infectious:

Cyclosporiasis (off-label use):

Treatment: Oral: 1 double-strength tablet twice daily for 7 to 10 days (Ref). A 10-day duration is preferred in solid organ transplant recipients (Ref) and 14 days for patients with HIV (Ref).

Secondary prophylaxis (patients who are immunocompromised): Oral: 1 double-strength tablet 3 times weekly, starting after completion of a treatment course (Ref).

Cystoisosporiasis (isosporiasis) (off-label use):

Patients who are immunocompetent (usually self-limited; treatment not always indicated): Oral: 1 double-strength tablet twice daily for 7 to 10 days (Ref).

Patients who are immunocompromised: Oral, IV: 160 mg (trimethoprim component) 4 times daily for 10 days (Ref) or 160 mg (trimethoprim component) twice daily for 7 to 10 days; if symptoms worsen or persist, may increase dose to 160 mg (trimethoprim component) 4 times daily and/or prolong duration to 21 to 28 days. In patients with HIV and CD4 <200 cells/mm3, follow treatment with secondary prophylaxis of one double-strength tablet orally 3 times weekly (Ref).

Shigellosis (alternative agent) : Note: Not recommended for empiric therapy due to widespread resistance: Oral: 1 double-strength tablet twice daily for 5 to 7 days (Ref).

Endocarditis, treatment, oral step-down therapy in patients who inject drugs

Endocarditis, treatment, oral step-down therapy in patients who inject drugs (alternative agent) (off-label use):

Note: Not first-line treatment; data are limited. Reserve use for patients who inject drugs who had initial clinical improvement with IV treatment for methicillin-resistant S. aureus or penicillin allergy for methicillin-susceptible S. aureus infection but cannot complete IV standard of care therapy (Ref).

Oral: 2 double-strength tablets twice daily for a total duration, including initial IV therapy, of 6 weeks (Ref).

Intra-abdominal infection

Intra-abdominal infection (off-label use) (alternative agent):

Diverticulitis, acute (for uncomplicated infection that meets criteria for outpatient therapy or as step-down therapy after clinical improvement on initial parenteral therapy):

Note: Some experts suggest deferring antibiotics in otherwise healthy immunocompetent patients with mild disease; however, data on this approach in outpatients are limited (Ref).

Oral: 1 double-strength tablet every 12 hours in combination with metronidazole for 10 to 14 days (Ref).

Intracranial abscess and spinal epidural abscess

Intracranial abscess (brain abscess, intracranial epidural abscess) and spinal epidural abscess (alternative agent for methicillin-resistant S. aureus) (off-label use): IV: 5 mg/kg/dose (trimethoprim component) every 8 to 12 hours (Ref). Duration generally ranges from 4 to 8 weeks for brain abscess and spinal epidural abscess and 6 to 8 weeks for intracranial epidural abscess (Ref).

Mastitis, lactational

Mastitis, lactational (alternative agent) (off-label use):

Note: Reserve for patients unable to use first-line agents or for patients at risk for methicillin-resistant S. aureus (Ref).

Oral: 1 double-strength tablet twice daily for 10 to 14 days; shorter courses (eg, 5 to 7 days) may be considered for patients with rapid clinical resolution (Ref).

Melioidosis

Melioidosis ( Burkholderia pseudomallei infection) (off-label use):

Initial intensive therapy: Note: For use as a potential add-on to primary therapy [ceftazidime or a carbapenem] in focal disease (eg, CNS, prostate) (Ref).

40 to 60 kg: Oral, IV: 240 mg (trimethoprim component) every 12 hours (Ref).

>60 kg: Oral, IV: 320 mg (trimethoprim component) every 12 hours (Ref).

Duration: ≥14 days; a longer duration may be necessary depending on disease severity and site of infection (Ref).

Eradication therapy (begin after completion of initial intensive therapy):

40 to 60 kg: Oral: 240 mg (trimethoprim component) every 12 hours (Ref).

>60 kg: Oral: 320 mg (trimethoprim component) every 12 hours (Ref).

Duration: ≥3 months; extend to 6 months for bone or CNS involvement. Longer duration may be necessary following vascular surgery with graft for mycotic aneurysm (Ref).

Meningitis, bacterial

Meningitis, bacterial (alternative agent for methicillin-resistant S. aureus, L. monocytogenes, E. coli, and other Enterobacteriaceae) (off-label use): IV: 5 mg/kg/dose (trimethoprim component) every 6 to 8 hours (Ref).

Nocardiosis

Nocardiosis (off-label use): Note: Due to concerns for resistance, susceptibility testing should be performed on isolates (Ref).

Cutaneous infection (superficial; no other organ involvement): Oral: 5 to 10 mg/kg/day (trimethoprim component) in 2 divided doses (Ref).

Pulmonary infection (mild to moderate):

Immunocompetent patients: Oral: 5 to 10 mg/kg/day (trimethoprim component) in 2 divided doses (Ref).

Immunocompromised patients: Oral: 15 mg/kg/day (trimethoprimcomponent) in 3 to 4 divided doses (Ref).

Pulmonary infection (severe), CNS, disseminated, or multi-site infection: IV: 15 mg/kg/day (trimethoprim component) in 3 to 4 divided doses as part of an appropriate combination regimen (Ref).

Duration: Prolonged treatment is required (range: 3 months to ≥1 year [combined parenteral/oral therapy]) (Ref).

Osteomyelitis due to methicillin-resistant S. aureus

Osteomyelitis due to methicillin-resistant S. aureus (alternative agent) (off-label use): Oral, IV: 4 mg/kg/dose (trimethoprim component) every 12 hours with rifampin (Ref).

Plague

Plague ( Yersinia pestis ) (alternative agent) (off-label use):

Note: Consult public health officials for event-specific recommendations.

Postexposure prophylaxis: Oral: 5 mg/kg/dose (trimethoprim component) every 12 hours for 7 days (Ref).

Treatment: Oral, IV: 5 mg/kg/dose (trimethoprim component) every 8 hours for 7 to 14 days and for at least a few days after clinical resolution (Ref).

Pneumocystis pneumonia

Pneumocystis pneumonia:

Prophylaxis, primary and secondary:

Patients with HIV: Oral: 1 double-strength tablet once daily or 1 single-strength tablet once daily (preferred regimens) or 1 double-strength tablet 3 times weekly (alternative regimen). Note: In patients also requiring prophylaxis for toxoplasmosis, 1 double-strength tablet once daily should be used (Ref).

Duration in patients with HIV receiving antiretroviral therapy: Continue until CD4 count >200 cells/mm3 for >3 months (Ref); may consider discontinuing primary prophylaxis in patients with CD4 counts between 100 and 200 cells/mm3 who are receiving antiretroviral therapy and have had an undetectable viral load for ≥3 to 6 months (Ref).

Immunocompromised host, HIV-uninfected (eg, transplant recipients, cancer-related, hematopoietic cell transplant [HCT]): Oral: 1 double-strength tablet once daily or 1 single-strength tablet once daily (preferred regimens); alternatively, 1 double-strength tablet 3 times weekly (Ref).

Duration after solid organ transplant: ≥6 to 12 months and during periods of increased immunosuppression (eg, treatment for acute rejection). Lifelong prophylaxis may be considered for high-risk recipients (eg, history of Pneumocystis, receipt of lung allograft) (Ref).

Duration for cancer-related (including HCT) in patients at high risk for Pneumocystis infection: Duration is at least through periods of significant immunosuppression and/or for ~6 months in allogeneic HCT recipients (Ref).

Treatment:

Moderate to severe infection: IV: 15 to 20 mg/kg/day (trimethoprim component) in 3 or 4 divided doses for 21 days; may switch to oral therapy after clinical improvement. Note: Patients with moderate or severe infection (PaO2 <70 mm Hg at room air or alveolar-arterial oxygen gradient ≥35 mm Hg) should receive adjunctive glucocorticoids (Ref).

Mild to moderate infection: Oral: 15 to 20 mg/kg/day (trimethoprim component) in 3 divided doses for 21 days or two double-strength tablets 3 times daily (Ref).

Note: Some data suggest lower doses (~10 mg/kg/day [trimethoprim component]) may have similar efficacy (Ref). Secondary prophylaxis should be initiated immediately upon completion of therapy (Ref).

Prostatitis

Prostatitis (off-label use):

Acute bacterial prostatitis: Oral: 1 double-strength tablet twice daily for 4 to 6 weeks (Ref).

Chronic bacterial prostatitis (alternative agent): Oral: 1 double-strength tablet twice daily for ≥6 weeks (Ref).

Prosthetic joint infection

Prosthetic joint infection (off-label use): Note: For oral continuation therapy for methicillin-resistant S. aureus and Enterobacteriaceae (following pathogen-specific IV therapy in patients undergoing 1-stage exchange or debridement with retention of prosthesis) (Ref).

Oral: 1 double-strength tablet twice daily. For S. aureus infections, combine with rifampin (Ref). Duration is a minimum of 3 months, depending on patient-specific factors (Ref).

Q fever, acute symptomatic

Q fever (Coxiella burnetii), acute symptomatic (off-label use): Note: Treatment is most effective if given within the first 3 days of symptoms; alternative agent for patients who are not pregnant (Ref).

Oral: 1 double-strength tablet twice daily; duration is 14 days for patients who are not pregnant. For patients who are pregnant, consult an infectious diseases expert (Ref).

Septic arthritis due to methicillin-resistant S. aureus

Septic arthritis (without prosthetic material) due to methicillin-resistant S. aureus (following initial IV therapy with an appropriate antibiotic) (off-label use): Oral: 2 double-strength tablets twice daily or 4 mg/kg/dose (trimethoprim component) twice daily (maximum: 320 mg [trimethoprim component]/dose) for completion of 3- to 4-week total treatment course (IV and oral) (Ref).

Sexually transmitted infections

Sexually transmitted infections:

Epididymitis in patients ≥35 years of age and who are at low risk for sexually transmitted infections (ie, likely to be caused by enteric organisms) (alternative agent) (off-label use): Oral: 1 double-strength tablet twice daily for 10 days (Ref).

Granuloma inguinale (donovanosis) (alternative agent) (off-label use): Oral: 1 double-strength tablet every 12 hours for >3 weeks and until lesions have healed. Note: If symptoms do not improve within the first few days of therapy, another agent can be added (Ref).

Skin and soft tissue infection

Skin and soft tissue infection (off-label use):

Abscess:

Note: Systemic antibiotics may be reasonably withheld in healthy, immunocompetent patients with a single, small abscess that has been drained if they are clinically well and have no indwelling device, risk factors for endocarditis, or risk for methicillin-resistant S. aureus transmission (Ref).

Oral: 1 to 2 double-strength tablets twice daily (Ref). For patients who weigh >70 kg, some experts prefer the higher dose (Ref). Treat for ≥5 days but may extend up to 14 days depending on severity and clinical response (Ref).

Cellulitis, purulent or with risk for methicillin-resistant S. aureus: Oral: 1 to 2 double-strength tablets twice daily (Ref). For patients who weigh >70 kg, some experts prefer the higher dose (Ref). Some experts suggest adding an additional agent (eg, amoxicillin, cephalexin) for coverage of beta-hemolytic streptococci (Ref). Treat for ≥5 days but may extend up to 14 days depending on severity and clinical response (Ref).

Cellulitis, long-term suppression of recurrent infection: Note: For patients with recurrent presumptive staphylococcal cellulitis at the same anatomic site despite addressing predisposing factors (Ref).

Oral: 1 double-strength tablet twice daily after completion of treatment (Ref).

Impetigo or ecthyma if methicillin-resistant S. aureus is suspected or confirmed: Note: For impetigo, reserve systemic therapy for patients with numerous lesions or in outbreak settings to decrease transmission (Ref).

Oral: 1 to 2 double-strength tablets twice daily for 7 days (Ref).

Spontaneous bacterial peritonitis, prophylaxis

Spontaneous bacterial peritonitis, prophylaxis (off-label use):

Note: For secondary prophylaxis in patients with prior spontaneous bacterial peritonitis (SBP) and primary prophylaxis in patients at high risk for SBP (eg, low ascites protein [<1.5 g/dL] with advanced liver failure or impaired kidney function). Some experts also use for prophylaxis during hospitalization in patients with cirrhosis and either acute GI bleeding or ascites protein <1 g/dL (Ref).

Oral: 1 double-strength tablet once daily (Ref). For patients with cirrhosis and acute GI bleeding, some experts use 1 double-strength tablet twice daily following, or as an alternative to, parenteral prophylaxis, for a total antibiotic duration of 7 days (Ref).

Stenotrophomonas maltophilia infection

Stenotrophomonas maltophilia infection (off-label use):

Cystitis: IV, Oral: 160 mg (trimethoprim component) every 12 hours (Ref).

Hospital-acquired or ventilator-associated pneumonia, bacteremia: IV, Oral: 8 to 12 mg/kg/day (trimethoprim component) in 2 or 3 divided doses, as part of a combination regimen when appropriate; some experts suggest considering a maximum dose of 960 mg (trimethoprim component)/day (Ref).

Note: Duration depends on site of infection; some experts recommend 14 days for bacteremia (Ref).

Surgical prophylaxis

Surgical prophylaxis (off-label use):

Note: Reserve use for high-risk cystoscopy (eg, urine culture positive or unavailable, preoperative catheter, or placement of prosthetic material), cystoscopy with manipulation (eg, transrectal prostate biopsy), or upper GU tract instrumentation (Ref).

Oral: 1 double-strength tablet within 60 to 120 minutes prior to surgical incision (Ref).

Toxoplasma gondii encephalitis

Toxoplasma gondii encephalitis (off-label use):

Primary prophylaxis:

Patients with HIV: Oral: 1 double-strength tablet once daily (preferred) or 1 double-strength tablet 3 times weekly or 1 single-strength tablet once daily; primary prophylaxis is indicated for T. gondii IgG-seropositive patients with CD4 count <100 cells/mm3. Continue primary prophylaxis following initiation of antiretroviral therapy (ART) until CD4 count >200 cells/mm3 for >3 months; some experts discontinue primary prophylaxis in patients with a CD4 count between 100 to 200 cells/mm3 who are receiving ART and have had an undetectable viral load for ≥3 to 6 months (Ref).

Solid organ transplant recipients: Oral: 1 double-strength tablet 3 times weekly or 1 single-strength tablet once daily; primary prophylaxis is indicated for donor-seropositive/recipient-seronegative (D+/R−) cardiac recipients for at least 12 months; prophylaxis may be considered for D+/R− noncardiac recipients with duration dependent on patient-specific factors and/or institutional protocols (Ref).

Treatment (alternative agent): Oral, IV: 10 mg/kg/day (trimethoprim component) in 2 divided doses for at least 6 weeks; longer duration may be needed if clinical or radiologic disease is extensive or response is incomplete at 6 weeks (Ref).

Secondary prophylaxis (chronic maintenance therapy) (alternative agent): Oral: 1 double-strength tablet twice daily (Ref) or, alternatively, 1 double-strength tablet once daily (lower dose may be associated with increased relapse risk) (Ref). For patients with HIV, continue following initiation of ART until CD4 count >200 cells/mm3 for >6 months (Ref); for solid organ transplant recipients, continue lifelong (Ref).

Urinary tract infection

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: Note: Avoid use if resistance prevalence is >20% or if patient has risk factors for multidrug-resistant gram-negative infection (Ref):

Oral: 1 double-strength tablet twice daily; treat females for 3 days and males for 7 days (Ref).

Cystitis, prophylaxis for recurrent infection: 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: One-half of a single-strength tablet once daily or 3 times weekly (Ref).

Postcoital prophylaxis (females with cystitis temporally related to sexual intercourse): Oral: One-half to 1 single-strength tablet as a single dose immediately before or after sexual intercourse (Ref).

Urinary tract infection, complicated (including pyelonephritis) (outpatient targeted therapy [if the isolate is known to be susceptible]):

Oral: 1 double-strength tablet twice daily for 14 days (Ref); for patients who have a rapid response to treatment, some experts treat for 7 to 10 days (Ref). Note: Oral therapy should generally follow appropriate parenteral therapy (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

Note: Weight-based dosing recommendations are based on the trimethoprim component. Each double-strength (DS) tablet contains trimethoprim 160 mg and sulfamethoxazole 800 mg. Each single-strength (SS) tablet contains trimethoprim 80 mg and sulfamethoxazole 400 mg.

Sulfamethoxazole/Trimethoprim Dose Adjustments for Kidney Impairment - Oral

Dose Adjustments for Kidney Impairmenta: Oralb

CrCl (mL/minute)

If usual recommended dose is 1 DS tablet every 24 hours or 3 times per week

If usual recommended dose is 1 DS tablet every 12 hours

If usual recommended dose is 2 DS tablets every 12 hours

If usual recommended dose is 2 DS tablets every 8 hours

aExpert opinion derived from Golightly 2013, HHS (OI adult 2020), Nahata 1995, Nemecek 2019

bAbbreviations: DS: Double strength; SS: Single strength.

cFor severe infections, some experts recommend giving unadjusted doses for the first 1 to 2 days (Nahata 1995).

dRecommended by HHS (OI adult 2020) for treatment of Pneumocystis pneumonia in dialysis patients (administer once daily [on dialysis days administer post HD]).

>30

No dosage adjustment necessary.

No dosage adjustment necessary.

No dosage adjustment necessary.

No dosage adjustment necessary.

15 to 30c

Reduce dose to ~50% of usual dose.

Example: 1 SS tablet every 24 hours or 3 times per week

Reduce dose to ~50% of usual dose.

Example: 1 DS tablet once, followed by 1 SS tablet every 12 hours

Reduce dose to ~50% of usual dose.

Example: 1 DS tablet every 12 hours

Reduce dose to ~50% of usual dose.

Example: 2 DS tablets every 12 hours

<15

Reduce dose to ~25 to 50% of usual dose. Use with caution and appropriate monitoring.

Example: 1 SS tablet every 24 hours or 3 times per week

Reduce dose to ~25 to 50% of usual dose. Use with caution and appropriate monitoring.

Example: 1 DS tablet once, followed by 1 SS tablet every 12 or 24 hours

Reduce dose to ~25 to 50% of usual dose. Use with caution and appropriate monitoring.

Example: 1 DS tablet every 12 hours or 1 DS tablet once, followed by 1 SS tablet every 12 hours

Reduce dose to ~25 to 50% of usual dose. Use with caution and appropriate monitoring.

Example: 1 to 2 DS tablets every 12 hours or 2 DS tablets every 24 hoursd

Sulfamethoxazole/Trimethoprim Dose Adjustments for Kidney Impairment - IV

Dose Adjustments for Kidney Impairmenta: IV

CrCl (mL/minute)

If usual recommended daily dose is 10 mg/kg/day (trimethoprim component)

If usual recommended daily dose is 8 to 12 mg/kg/day (trimethoprim component)

If usual recommended daily dose is 15 to 20 mg/kg/day (trimethoprim component)

aExpert opinion derived from Golightly 2013, HHS (OI adult 2020), Nahata 1995, Nemecek 2019.

bIn severe infections, some experts recommend giving unadjusted doses for the first 1 to 2 days (Nahata 1995).

>30

No dosage adjustment necessary.

No dosage adjustment necessary.

No dosage adjustment necessary.

15 to 30b

Reduce dose to ~50% of usual dose.

Example: 5 mg/kg once daily

Reduce dose to ~50% of usual dose.

Example: 4 to 6 mg/kg/day in 2 divided doses

Reduce dose to ~50% of usual dose.

Example: 7.5 to 10 mg/kg/day in 2 to 4 divided doses

<15

Reduce dose to ~25 to 50% of usual dose. Use with caution and appropriate monitoring.

Example: 2.5 to 5 mg/kg once daily. Note: When treating toxoplasmosis encephalitis, use 5 mg/kg once daily or use alternative agent (HHS [OI Adult 2020]

Reduce dose to ~25 to 50% of usual dose. Use with caution and appropriate monitoring.

Example: 2 to 3 mg/kg once daily or 4 to 6 mg/kg every 24 to 48 hours

Reduce dose to ~25 to 50% of usual dose. Use with caution and appropriate monitoring.

Example: 4 to 5 mg/kg once daily or 7.5 to 10 mg/kg every 24 to 48 hours

Hemodialysis, intermittent (thrice weekly): Dialyzable (44% of trimethoprim and 57% sulfamethoxazole and its metabolites over 4 hours utilizing a low-flux filter (Ref)):

Oral, IV: Follow dose recommendations for patients with CrCl <15 mL/minute not on dialysis; doses due on dialysis days should be administered after hemodialysis (Ref).

Note: If treating Pneumocystis pneumonia, consider utilizing therapeutic drug monitoring to optimize therapy (target trimethoprim concentration: 5 to 8 mcg/mL) (Ref).

Peritoneal dialysis: Oral, IV: Not efficiently dialyzed (Ref). Follow dose recommendations for a patient with a CrCl <15 mL/minute (Ref).

Note: If treating Pneumocystis pneumonia, consider utilizing therapeutic drug monitoring to optimize therapy (target trimethoprim concentration: 5 to 8 mcg/mL) (Ref).

CRRT: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations assume high-flux dialyzers and flow rates of ~1,500 to 3,000 mL/hour, unless otherwise noted. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection). Close monitoring of response and adverse reactions due to drug accumulation is important.

CVVH/CVVHD/CVVHDF: Oral, IV: Sulfamethoxazole and trimethoprim are substantially removed by CRRT (Ref). No dosage adjustment necessary (Ref).

PIRRT (eg, sustained low-efficiency diafiltration): Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection). Close monitoring of response and adverse reactions due to drug accumulation is important.

Oral, IV (blood and dialysate flow rates 170 mL/minute; 6- to 8-hour session): No dosage adjustment necessary (Ref).

Dosing: Hepatic Impairment: Adult

The hepatic dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Matt Harris, PharmD, MHS, BCPS, FAST; Jeong Park, PharmD, MS, BCTXP, FCCP, FAST; Arun Jesudian, MD; Sasan Sakiani, MD.

Note: The manufacturer's labeling states use is contraindicated in patients with marked hepatic damage (not defined); however, use in patients with any degree of hepatic dysfunction is generally considered appropriate (Ref). Additionally, it should be noted that use of prophylactic sulfamethoxazole/trimethoprim doses in patients with varying degrees of hepatic impairment may be associated with mild self-limiting adverse effects (eg, mild skin rash, epigastric pain, diarrhea) and renal dysfunction that resolved with discontinuation (Ref).

Hepatic impairment prior to treatment initiation:

Child-Turcotte-Pugh class A to C: No dosage adjustment necessary (Ref).

Dosage adjustment in patients with chronic, worsening hepatic function during treatment (eg, progression from Child-Turcotte-Pugh class A to B):

Progression from baseline to Child-Turcotte-Pugh class A to C: No dosage adjustment necessary; however, avoid use in patients with suspected or confirmed sulfamethoxazole-induced liver injury unless the benefits outweigh the risks (Ref).

Acute worsening of hepatic function (eg, requiring hospitalization): No dosage adjustment necessary; however, consider discontinuation of sulfamethoxazole/trimethoprim therapy in patients with suspected sulfamethoxazole-induced liver injury unless the benefits outweigh the risks (Ref).

Adverse Reactions (Significant): Considerations
Clostridioides difficile infection

Clostridioides difficile infection (CDI) has occurred with sulfamethoxazole/trimethoprim, specifically including diarrhea, abdominal pain, and Clostridioides difficile colitis (Ref).

Onset: Varied; may start on the first day of antibiotic therapy or up to 3 months postantibiotic (Ref).

Risk factors:

• Antibiotic exposure (highest risk factor) (Ref)

• Long durations in a hospital or other health care setting (recent or current) (Ref)

• Older adults (Ref)

• Immunocompromised conditions (Ref)

• A serious underlying condition (Ref)

• GI surgery/manipulation (Ref)

• Antiulcer medications (eg, proton pump inhibitors and H2 blockers) (Ref)

• Chemotherapy (Ref)

Drug-induced liver injury

The most typical pattern of drug-induced liver injury (hepatotoxicity) observed with sulfamethoxazole/trimethoprim is a mixed hepatocellular cholestasis. Cholestasis without inflammation, hepatocellular necrosis (including fatalities), and hepatic failure have also been reported (Ref). Some cases may be manifestations of drug reaction with eosinophilia and systemic symptoms (DRESS) (Ref). May also cause mild symptoms with elevated aminotransferases (Ref).

Mechanism: Non-dose-related; immunologic. Delayed hypersensitivity reactions, including hepatotoxicity associated with DRESS, are mediated by T-cells which may be induced by the toxic hydroxylamine and nitroso metabolites of sulfonamide antimicrobials (Ref). Other immune mechanisms have been suggested, including action of complement within the immune complex disease or binding of complement activating antibodies to membranes of hepatocytes or bile ducts (Ref).

Onset: Intermediate; most cases occur 1 to 3 weeks after initiation (Ref). Upon rechallenge, symptoms may develop more rapidly, often within 3 days of initiation (Ref).

Risk factors:

• African Americans (Ref)

• Genetic risk factors (ie, HLA-B*35:01 in African Americans; HLA-B*14:01 in European Americans) (Ref)

• Patients with HIV (Ref)

Hematologic effects

Various blood dyscrasias (including fatalities) have been reported with sulfamethoxazole/trimethoprim, including agranulocytosis, hemolytic anemia, leukopenia, and thrombocytopenia (Ref). Some cases may be manifestations of a hypersensitivity drug reaction with eosinophilia and systemic symptoms (Ref). Thrombocytopenia usually resolves within 1 week following discontinuation of therapy.

Mechanism: Non-dose-related. Thrombocytopenia is an immune-mediated process caused by platelet destruction by drug-dependent platelet antibodies (Ref). Hemolytic anemia is also immune-related (Ref). The pathogenesis for agranulocytosis is unknown, although in some cases an immune-mediated mechanism may be responsible (Ref).

Onset: Varied; ranges from 6 days up to 5 weeks (Ref). Upon rechallenge, symptoms may develop within 1 hour (Ref).

Risk factors:

• HIV/AIDS (Ref)

• Glucose-6-phosphate dehydrogenase deficiency may be at risk for the development of hemolytic anemia (Ref); although, most patients are able to tolerate the drug (Ref).

Hyperkalemia

Hyperkalemia may occur with sulfamethoxazole/trimethoprim and be life threatening (Ref); usually reversible following discontinuation (Ref).

Mechanism: Dose-related; trimethoprim blocks sodium channels in the distal nephron, inhibiting potassium secretion. Results in decreased renal potassium excretion (Ref).

Onset: Variable; usually occurs within 5 to 10 days after sulfamethoxazole/trimethoprim is initiated (Ref).

Risk factors:

• High doses (trimethoprim 20 mg/kg/day) (Ref)

• Kidney impairment (Ref)

• Older patients (Ref)

• Hypoaldosteronism (Ref)

• Concomitant use of medications causing or exacerbating hyperkalemia (Ref)

Hypoglycemia

Hypoglycemia may occur with sulfamethoxazole/trimethoprim and be life threatening (Ref); usually reversible following discontinuation (Ref).

Mechanism: Proposed to be related to the sulfamethoxazole component binding to receptors on the pancreatic islet cells and causing the release of insulin (Ref).

Onset: Rapid; range from 1.5 hours to 5 days after initiation (Ref).

Risk factors:

• Kidney or hepatic impairment (Ref)

• Prolonged fasting conditions (Ref)

• Malnourished (Ref)

• Concomitant medications that decrease plasma glucose levels (Ref)

Hyponatremia

Severe and symptomatic hyponatremia may occur with sulfamethoxazole/trimethoprim and be life threatening (Ref); usually reversible following discontinuation of therapy (Ref).

Mechanism: Dose-related; large volume of fluid required for IV infusion and/or due to diuretic actions (blockade of epithelial sodium channels in the distal nephron) of trimethoprim (Ref).

Onset: Rapid; ~5 days after initiation of therapy (Ref).

Risk factors:

• Dose (trimethoprim >8 mg/kg/day) (Ref)

Hypersensitivity reactions (delayed)

Delayed hypersensitivity reactions may occur with sulfamethoxazole/trimethoprim, including maculopapular skin rash, fixed drug eruption, and severe cutaneous adverse reactions (SCARs) (Ref). SCARs include acute generalized exanthematous pustulosis, drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), Sweet’s syndrome, and toxic epidermal necrolysis (TEN) (Ref).

Mechanism: Non-dose-related; immunologic. T-cell mediated, which may be induced by the toxic hydroxylamine and nitroso metabolites of sulfonamide antimicrobials (Ref).

Onset: Variable; typically occur days to weeks after drug exposure but may occur more rapidly (usually within 1 to 4 days) upon reexposure (Ref). In patients with HIV/AIDS, a morbilliform reaction with fever usually occurs 1 to 2 weeks after initiation of therapy (Ref).

Risk factors:

• HIV/AIDS (most often a maculopapular rash, often associated with fever) (Ref)

Note: Cross-reactivity between antibiotic sulfonamides and nonantibiotic sulfonamides may not occur, or at the very least this potential is extremely low (Ref). Drugs that should be avoided in patients who develop hypersensitivity reactions to sulfamethoxazole-trimethoprim include other sulfonamide antimicrobials (regardless of route of administration), dapsone, fosamprenavir, darunavir, and sulfasalazine (Ref). In addition, trimethoprim should also be avoided, as it is unknown whether this drug may have contributed or been responsible for the initial reaction (Ref). In patients with serious reactions (eg, SJS/TEN, DRESS), some clinicians may elect to avoid all sulfonamide medications (Ref).

Hypersensitivity reactions (immediate)

Immediate hypersensitivity reactions may occur with sulfamethoxazole/trimethoprim, including urticaria, angioedema, and anaphylaxis (Ref). The sulfonamide component is often implicated as the causative agent, but some patients may be reacting to the trimethoprim component (Ref). An immediate hypersensitivity reaction (“anaphylactic-like”) can occur in patients with HIV/AIDS that may resemble sepsis, with fever and hypotension; in some of these patients, pulmonary infiltrates and rash may be present (Ref).

Mechanism: Non-dose-related; immunologic (ie, IgE-mediated with antibodies to sulfamethoxazole and trimethoprim) (Ref). The N1-substitute and not the sulfonamide group has been found to have direct specificity to IgE antibodies (Ref). The mechanism for anaphylactic-like reactions in patients with HIV/AIDS is not known (Ref), although it may be caused by higher levels of IgE and tumor necrosis factor in patients with AIDS (Ref).

Onset: Rapid; typically occur within 1 hour of administration but may occur up to 6 hours after exposure (Ref). Anaphylactic-like reactions usually occur within 4 hours of administration (Ref).

Risk factors:

• HIV/AIDS (Ref)

Note: Cross-reactivity between antibiotic sulfonamides and nonantibiotic sulfonamides may not occur, or at the very least this potential is extremely low (Ref). Cross-reactions due to antibody production (anaphylaxis) are unlikely to occur with nonantibiotic sulfonamides and antibiotic sulfonamides (Ref).

Kernicterus

Sulfa antibiotics have been shown to displace bilirubin from protein binding sites, which may potentially lead to hyperbilirubinemia and kernicterus in neonates and young infants. There are limited data with sulfamethoxazole; therefore, the risk for kernicterus is extrapolated from data with sulfisoxazole (Ref).

Mechanism: Displaces bilirubin from albumin, resulting in higher concentrations of free unconjugated bilirubin, leading to kernicterus (Ref).

Risk factors:

• Neonates and infants <2 month of age, especially those born premature

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

Frequency not defined:

Cardiovascular: Circulatory shock (Liu 2018), hypersensitivity myocarditis (Nayak 2013), polyarteritis nodosa, thrombophlebitis (migrans; Verne-Pignatelli 1989)

Dermatologic: Acute generalized exanthematous pustulosis (Anliker 2003), erythema multiforme, exfoliative dermatitis, skin photosensitivity, skin rash, Stevens-Johnson syndrome (Acharya 2020), Sweet’s syndrome (Azfar 2009), toxic epidermal necrolysis (Zhang 2019), urticaria

Endocrine & metabolic: Hyperkalemia (Alappan 1999), hyponatremia (Babyev 2013)

Gastrointestinal: Abdominal pain, anorexia, diarrhea, glossitis, nausea, pancreatitis, stomatitis, vomiting

Genitourinary: Anuria, diuresis, oliguria

Hematologic & oncologic: Agranulocytosis (Andres 2003), aplastic anemia (IAAAS 1989), eosinophilia, hemolysis (with G6PD deficiency) (Calabrò 1989), hemolytic anemia (Williams 2017), Henoch-Schönlein purpura, hypoprothrombinemia, leukopenia (Gordin 1984), megaloblastic anemia (Kobrinsky 1981), methemoglobinemia (Carroll 2016), neutropenia, thrombocytopenia (Mitta 2019)

Hepatic: Cholestatic jaundice (Ogilvie 1980), hepatotoxicity (including hepatitis, cholestasis, and hepatic necrosis) (Slim 2017), hyperbilirubinemia, increased serum transaminases

Hypersensitivity: Angioedema, serum sickness (Platt 1988)

Immunologic: Drug reaction with eosinophilia and systemic symptoms (Kardaun 2013)

Local: Inflammation at injection site, infusion site irritation, infusion-site pain

Nervous system: Apathy, aseptic meningitis (Bruner 2014), ataxia, chills, depression, fatigue, hallucination, headache, insomnia, kernicterus (neonates), nervousness, peripheral neuritis, seizure, vertigo

Neuromuscular & skeletal: Arthralgia, asthenia, myalgia, rhabdomyolysis, systemic lupus erythematosus (Mahmood 2020)

Ophthalmic: Conjunctival injection, injected sclera, uveitis

Otic: Tinnitus

Renal: Increased blood urea nitrogen, increased serum creatinine (may not be reflective of a true reduction in glomerular filtration rate [Masters 2003]), interstitial nephritis, renal insufficiency

Respiratory: Acute respiratory failure, cough, dyspnea, eosinophilic pneumonitis (acute), interstitial pulmonary disease (Yuzurio 2010), pulmonary infiltrates, pulmonary injury (acute and delayed)

Miscellaneous: Fever (Gordin 1984)

Postmarketing:

Cardiovascular: Prolonged QT interval on ECG (Lopez 1987), torsades de pointes (Lopez 1987)

Endocrine & metabolic: Hypoglycemia (Nunnari 2010; Strevel 2006), metabolic acidosis (Porras 1998)

Gastrointestinal: Clostridioides difficile colitis (Brown 2013; Gordin 1994; Hensgens 2012), dysgeusia (Syed 2016)

Hematologic & oncologic: Thrombotic thrombocytopenic purpura (Bapani 2013)

Hepatic: Hepatic failure (Abusin 2008)

Hypersensitivity: Anaphylaxis (Harle 1988; Kuyucu 2014), fixed drug eruption (Can 2014)

Renal: Acute kidney injury (Fraser 2012)

Respiratory: Acute respiratory distress syndrome (Miller 2019)

Contraindications

Hypersensitivity to any sulfa drug, trimethoprim, or any component of the formulation; history of drug induced-immune thrombocytopenia with use of sulfonamides or trimethoprim; megaloblastic anemia due to folate deficiency; infants <2 months (manufacturer's labeling), infants <4 weeks (CDC 2009); marked hepatic damage or severe renal disease (if patient not monitored); concomitant administration with dofetilide.

Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Note: Although the FDA-approved product labeling states this medication is contraindicated in patients with hypersensitivity to sulfonamide-containing drugs, the scientific basis of this cross-sensitivity has been challenged. See “Warnings/Precautions” for more detail.

Canadian labeling: Additional contraindications (not in US labeling): Blood dyscrasias; evidence of marked parenchymal damage; pregnancy; breastfeeding; premature infants; acute porphyria.

Warnings/Precautions

Concerns related to adverse effects:

• Superinfection: Prolonged use may result in fungal or bacterial superinfection.

Disease-related concerns:

• Asthma/Allergies: Use with caution in patients with allergies or asthma.

• Hepatic impairment: Use with caution in patients with hepatic impairment.

• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment recommended. Maintain adequate hydration to prevent crystalluria.

• Thyroid dysfunction: Use with caution in patients with thyroid dysfunction.

Special populations:

• Older adult: Use with caution in older adult patients; greater risk for more severe adverse reactions.

• Patients with potential for folate deficiency: Use with caution in patients with potential folate deficiency (malnourished, chronic antiseizure therapy, or elderly).

• Porphyria: Avoid use in patients with porphyria.

• Slow acetylators: May be more prone to adverse reactions.

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some dosage forms may contain 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 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).

• Sulfite sensitivity: Injection may contain sodium metabisulfite, a sulfite that may cause allergic-type reactions, including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible persons. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic persons.

Other warnings/precautions:

• Appropriate use: When used for uncomplicated urinary tract infections, this combination should not be used if a single agent is effective. Additionally, sulfonamides should not be used to treat group A beta-hemolytic streptococcal infections.

Warnings: Additional Pediatric Considerations

Sulfa antibiotics have been shown to displace bilirubin from protein binding sites which may potentially lead to hyperbilirubinemia and kernicterus in neonates and young infants; do not use in neonates; avoid use in infants <2 months unless other options are not available (eg, Pneumocystis).

Some dosage forms may contain propylene glycol; in neonates, large amounts of propylene glycol delivered orally, intravenously (eg, >3,000 mg/day), or topically have been associated with potentially fatal toxicities which can include metabolic acidosis, seizures, renal failure, and CNS depression; toxicities have also been reported in children and adults including hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Shehab 2009).

Dosage Forms Considerations

The 5:1 ratio (SMX:TMP) remains constant in all dosage forms.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous:

Generic: Sulfamethoxazole 80 mg and trimethoprim 16 mg per mL (5 mL, 10 mL, 30 mL)

Suspension, Oral:

Sulfatrim Pediatric: Sulfamethoxazole 200 mg and trimethoprim 40 mg per 5 mL (473 mL) [contains alcohol, usp, fd&c red #40 (allura red ac dye), fd&c yellow #6 (sunset yellow), methylparaben, polysorbate 80, propylene glycol, propylparaben, saccharin sodium]

Generic: Sulfamethoxazole 200 mg and trimethoprim 40 mg per 5 mL (20 mL, 473 mL)

Tablet, Oral:

Bactrim: Sulfamethoxazole 400 mg and trimethoprim 80 mg [scored; contains sodium benzoate]

Bactrim DS: Sulfamethoxazole 800 mg and trimethoprim 160 mg [scored; contains sodium benzoate]

Generic: Sulfamethoxazole 400 mg and trimethoprim 80 mg, Sulfamethoxazole 800 mg and trimethoprim 160 mg

Generic Equivalent Available: US

Yes

Pricing: US

Solution (Sulfamethoxazole-Trimethoprim Intravenous)

400-80 mg/5 mL (per mL): $1.51 - $1.52

Suspension (Sulfamethoxazole-Trimethoprim Oral)

200-40 mg/5 mL (per mL): $0.46 - $1.21

Suspension (Sulfatrim Pediatric Oral)

200-40 mg/5 mL (per mL): $0.24

Tablets (Bactrim DS Oral)

800-160 mg (per each): $3.12

Tablets (Bactrim Oral)

400-80 mg (per each): $1.73

Tablets (Sulfamethoxazole-Trimethoprim Oral)

400-80 mg (per each): $0.66 - $0.78

800-160 mg (per each): $0.37 - $1.40

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.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Intravenous:

Septra: Sulfamethoxazole 80 mg and trimethoprim 16 mg per mL (5 mL) [contains alcohol, usp, propylene glycol, sodium metabisulfite]

Generic: Sulfamethoxazole 80 mg and trimethoprim 16 mg per mL (5 mL, 10 mL, 30 mL)

Suspension, Oral:

Generic: Sulfamethoxazole 200 mg and trimethoprim 40 mg per 5 mL ([DSC])

Tablet, Oral:

Sulfatrim Pediatric: Sulfamethoxazole 100 mg and trimethoprim 20 mg

Generic: Sulfamethoxazole 400 mg and trimethoprim 80 mg, Sulfamethoxazole 800 mg and trimethoprim 160 mg

Administration: Pediatric

Oral: Administer without regard to meals. Shake suspension well before use. Patient should maintain adequate fluid intake during use.

Parenteral: IV infusion: Do not administer IM. Must be diluted in D5W prior to administration. Inspect solution for evidence of cloudiness or precipitation prior to administration; infuse diluted solution IV over 60 to 90 minutes (administration over 30 to 60 minutes has also been described (Ref)).

Administration: Adult

IV: Infuse diluted solution over 60 to 90 minutes (administration over 30 to 60 minutes has also been described (Ref)); not for IM injection.

Oral: Administer without regard to meals. Administer with at least 8 ounces of water.

Storage/Stability

Injection: Store intact vial at 20°C to 25°C (68°F to 77°F); do not refrigerate. Multiple-dose vials must be used within 48 hours after initial entry. Solutions diluted for infusion should be stored at room temperature; do not refrigerate. Manufacturer-recommended dilutions and stability of parenteral admixture at room temperature are as follows:

Each 5 mL of drug solution per 125 mL D5W - stable for 6 hours.

Each 5 mL of drug solution per 100 mL D5W - stable for 4 hours.

Each 5 mL of drug solution per 75 mL D5W - stable for 2 hours.

Note: Stability information when diluted in other infusion solutions (eg, NS) may be available; refer to compatibility database and/or manufacturer's product labeling for details.

Suspension, tablet: Store at controlled room temperature of 15°C to 25°C (59°F to 77°F). Protect from light.

Use

Oral: Treatment of urinary tract infections caused by susceptible Escherichia coli, Klebsiella and Enterobacter spp, Morganella morganii, Proteus mirabilis, and Proteus vulgaris (FDA approved in ages ≥2 months and adults); treatment of acute otitis media due to Haemophilus influenzae or Streptococcus pneumoniae (FDA approved in ages ≥2 months and adults); prophylaxis and treatment of Pneumocystis jirovecii pneumonitis (PCP) (FDA approved in pediatric patients [age not specified] and adults); treatment of enteritis caused by Shigella flexneri or Shigella sonnei (FDA approved in ages ≥2 months and adults); acute exacerbations of chronic bronchitis due to susceptible strains of H. influenzae or S. pneumoniae (FDA approved in adults); traveler's diarrhea due to enterotoxigenic E. coli (FDA approved in adults); has also been used for the treatment of skin and soft tissue infections, osteoarticular infections, exit-site or tunnel infections in patients with peritoneal dialysis catheters, brucellosis, cyclosporiasis, cystoisosporiasis, melioidosis, meningitis, Q fever, and for treatment or prophylaxis of toxoplasmosis.

Parenteral: Treatment of P. jirovecii pneumonitis (PCP), Shigella, and severe or complicated urinary tract infections due to E. coli, Klebsiella and Enterobacter spp, M. morganii, P. mirabilis, and P. vulgaris (FDA approved in ages ≥2 months and adults); has also been used in treatment of severe or complicated infections caused by susceptible bacteria when oral therapy is not feasible.

Medication Safety Issues
Sound-alike/look-alike issues:

Bactrim may be confused with bacitracin, Bactine, Bactroban

Co-trimoxazole may be confused with clotrimazole

Septra may be confused with Ceptaz, Sectral

Septra DS may be confused with Semprex-D

Older Adult: High-Risk Medication:

Beers Criteria: Sulfamethoxazole and Trimethoprim is identified in the Beers Criteria as a potentially inappropriate medication to be used with caution in patients ≥65 years of age with decreased CrCl and on ACE inhibitors, angiotensin receptor-neprilysin inhibitors, or ARBs due to increased risk of hyperkalemia (Beers Criteria [AGS 2023]).

Pediatric patients: High-risk medication:

KIDs List: Sulfonamides, when used in neonates, are identified on the Key Potentially Inappropriate Drugs in Pediatrics (KIDs) list and should be avoided due to risk of kernicterus (weak recommendation; very low quality of evidence) (PPA [Meyers 2020]).

Metabolism/Transport Effects

Refer to individual components.

Drug Interactions

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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Ajmaline: Sulfonamides may enhance the adverse/toxic effect of Ajmaline. Specifically, the risk for cholestasis may be increased. Risk C: Monitor therapy

Amantadine: Trimethoprim may enhance the adverse/toxic effect of Amantadine. Specifically, the risk of myoclonus or delirium may be increased. Trimethoprim may increase the serum concentration of Amantadine. Risk C: Monitor therapy

Aminolevulinic Acid (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic). Risk X: Avoid combination

Aminolevulinic Acid (Topical): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Topical). Risk C: Monitor therapy

Amodiaquine: Sulfamethoxazole may enhance the neutropenic effect 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

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

Androgens: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

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

Antidiabetic Agents: May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Risk C: Monitor therapy

AzaTHIOprine: Sulfamethoxazole may enhance the myelosuppressive effect of AzaTHIOprine. Risk C: Monitor therapy

AzaTHIOprine: Trimethoprim may enhance the myelosuppressive effect of AzaTHIOprine. Risk C: Monitor therapy

Bacillus clausii: Antibiotics may diminish the therapeutic effect 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 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

Chloroprocaine (Systemic): May diminish the therapeutic effect of Sulfonamide Antibiotics. Management: Avoid concurrent use of chloroprocaine and systemic sulfonamide-based antimicrobials whenever possible. Risk D: Consider therapy modification

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

Clofarabine: OCT2 Inhibitors may increase the serum concentration of Clofarabine. Risk C: Monitor therapy

CycloSPORINE (Systemic): Sulfonamide Antibiotics may enhance the nephrotoxic effect of CycloSPORINE (Systemic). Sulfonamide Antibiotics may decrease the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy

Dalfampridine: OCT2 Inhibitors may increase the 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 the serum concentration of Daprodustat. Risk C: Monitor therapy

Dapsone (Systemic): Trimethoprim may increase the serum concentration of Dapsone (Systemic). Dapsone (Systemic) may increase the serum concentration of Trimethoprim. Risk C: Monitor therapy

Dapsone (Topical): May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Risk C: Monitor therapy

Dexketoprofen: May enhance the adverse/toxic effect of Sulfonamides. 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

Fecal Microbiota (Live) (Oral): May diminish the therapeutic effect of Antibiotics. Risk X: Avoid combination

Fecal Microbiota (Live) (Rectal): Antibiotics may diminish the therapeutic effect of Fecal Microbiota (Live) (Rectal). Risk X: Avoid combination

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

Herbal Products with Glucose Lowering Effects: May enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Risk C: Monitor therapy

Hypoglycemia-Associated Agents: May enhance the hypoglycemic effect of other Hypoglycemia-Associated Agents. Risk C: Monitor therapy

Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies): Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). 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

Local Anesthetics: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Local Anesthetics. Specifically, the risk for methemoglobinemia may be increased. Risk C: Monitor therapy

Maitake: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

Mecamylamine: Sulfonamides may enhance the adverse/toxic effect of Mecamylamine. 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. Risk C: Monitor therapy

Mercaptopurine: Sulfamethoxazole may enhance the myelosuppressive effect of Mercaptopurine. Risk C: Monitor therapy

Mercaptopurine: Trimethoprim may enhance the myelosuppressive effect of Mercaptopurine. Risk C: Monitor therapy

MetFORMIN: MATE1/2-K Inhibitors may increase the serum concentration of MetFORMIN. Risk C: Monitor therapy

Methenamine: May enhance the adverse/toxic effect of Sulfonamide Antibiotics. Specifically, the combination may result in the formation of an insoluble precipitate in the urine. Risk X: Avoid combination

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

Methoxsalen (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Methoxsalen (Systemic). Risk C: Monitor therapy

MetroNIDAZOLE (Systemic): May enhance the adverse/toxic effect of Products Containing Propylene Glycol. A disulfiram-like reaction may occur. Risk X: Avoid combination

Monoamine Oxidase Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

Nitric Oxide: May enhance the adverse/toxic effect of Methemoglobinemia Associated Agents. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Risk C: Monitor therapy

Ornidazole: May enhance the adverse/toxic effect of Products Containing Propylene Glycol. Specifically, a disulfiram-like reaction may occur. Risk X: Avoid combination

Pegvisomant: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

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

Phenytoin: Sulfamethoxazole may increase the serum concentration of Phenytoin. Management: Avoid coadministration of phenytoin and sulfamethoxazole. If coadministered, monitor phenytoin concentrations and for evidence of phenytoin toxicity. Risk of toxicity is increased with sulfamethoxazole/trimethoprim combination product. Risk D: Consider therapy modification

Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Risk C: Monitor therapy

Potassium P-Aminobenzoate: May diminish the therapeutic effect of Sulfonamide Antibiotics. Risk X: Avoid combination

PRALAtrexate: Trimethoprim may increase the serum concentration of PRALAtrexate. More specifically, trimethoprim may decrease excretion of pralatrexate. Risk C: Monitor therapy

PRALAtrexate: Sulfamethoxazole may increase the serum concentration of PRALAtrexate. More specifically, sulfamethoxazole may decrease excretion of pralatrexate. Risk C: Monitor therapy

Prilocaine: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Prilocaine. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Management: Monitor patients for signs of methemoglobinemia (e.g., hypoxia, cyanosis) when prilocaine is used in combination with other agents associated with development of methemoglobinemia. Avoid lidocaine/prilocaine in infants receiving such agents. 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

Procaine: May diminish the therapeutic effect of Sulfonamide Antibiotics. Risk X: Avoid combination

Prothionamide: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

Pyrimethamine: May enhance the adverse/toxic effect of Trimethoprim. Risk C: Monitor therapy

Quinolones: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Quinolones may diminish the therapeutic effect of Agents with Blood Glucose Lowering Effects. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Risk C: Monitor therapy

Repaglinide: CYP2C8 Inhibitors (Weak) may increase the serum concentration of Repaglinide. Risk C: Monitor therapy

RifAMPin: May decrease the serum concentration of Trimethoprim. Trimethoprim may increase the serum concentration of RifAMPin. Risk C: Monitor therapy

RifAMPin: May decrease the serum concentration of Sulfamethoxazole. Sulfamethoxazole may increase the serum concentration of RifAMPin. Risk C: Monitor therapy

Salicylates: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. 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

Secnidazole: Products Containing Propylene Glycol may enhance the adverse/toxic effect of Secnidazole. Risk X: Avoid combination

Selective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Risk C: Monitor therapy

Sodium Nitrite: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Sodium Nitrite. Combinations of these agents may increase the likelihood of significant methemoglobinemia. 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

Sulfonylureas: Sulfonamide Antibiotics may enhance the hypoglycemic effect of Sulfonylureas. 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

Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Risk C: Monitor therapy

Vitamin K Antagonists (eg, warfarin): Sulfonamide Antibiotics may enhance the anticoagulant effect of Vitamin K Antagonists. Management: Consider reducing the vitamin K antagonist dose by 10% to 20% prior to starting the sulfonamide antibiotic. Monitor INR closely to further guide dosing. 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

Dietary Considerations

Should be taken with 8 oz of water. May be taken without regard to meals.

Reproductive Considerations

Sulfamethoxazole/trimethoprim is recommended for the acute treatment of Q fever (C. burnetii) in pregnant patients; however, it is an alternative agent in nonpregnant adults. Patients should avoid pregnancy for ≥1 month after treatment. Pregnancy testing is recommended in patients who may become pregnant prior to therapy (CDC [Anderson 2013]).

Sulfamethoxazole/trimethoprim may be appropriate for the treatment of bacterial prostatitis, a condition associated with sexual dysfunction (Lipsky 2010). Treatment of prostatitis may or may not improve semen quality. Sulfamethoxazole/trimethoprim may also be associated with transient disruption of spermatogenesis, but effects on semen parameters are conflicting (Drobnis 2017; Samplaski 2015).

Pregnancy Considerations

Sulfamethoxazole and trimethoprim cross the placenta.

An increased risk of congenital malformations (neural tube defects, cardiovascular malformations, urinary tract defects, oral clefts, club foot) following maternal use of sulfamethoxazole and trimethoprim during pregnancy has been observed. Trimethoprim interferes with folic acid metabolism, decreasing maternal levels. Adequate maternal folic acid supplementation may decrease the risk of some birth defects (Crider 2009; Czeizel 2001; Hernandez-Diaz 2000; Hernandez-Diaz 2001; Matok 2009).

Due to theoretical concerns that sulfonamides cross the placenta and may cause kernicterus in the newborn, neonatal health care providers should be informed if maternal sulfonamide therapy is used near the time of delivery (HHS [OI adult] 2022); avoidance of sulfamethoxazole/trimethoprim during the third trimester is recommended by some guidelines (specific weeks of gestation may vary as noted below).

The pharmacokinetics of sulfamethoxazole and trimethoprim are similar to nonpregnant pharmacokinetic values in early pregnancy (Ylikorkala 1973).

Sulfamethoxazole/trimethoprim is recommended for the treatment and prophylaxis of Pneumocystis jirovecii pneumonia (PCP) in pregnant patients with HIV because of the considerable maternal benefits of therapy. However, due to the risk of birth defects, supplemental folic acid at high doses (>0.4 mg/day) may be considered during the first trimester only. When sulfamethoxazole/trimethoprim is used during the first trimester, a fetal ultrasound is recommended at 18 to 20 weeks' gestation to evaluate fetal anatomy (HHS [OI adult] 2022).

Sulfamethoxazole/trimethoprim is recommended for the primary treatment of symptomatic Isospora belli infection as well as secondary prophylaxis in pregnant patients with HIV. Treatment for secondary prophylaxis can be withheld during the first trimester due to concerns of birth defects associated with sulfamethoxazole/trimethoprim therapy (HHS [OI adult] 2022).

Sulfamethoxazole/trimethoprim is recommended for the acute treatment of Q fever (Coxiella burnetii) in pregnant patients (alternative agent in nonpregnant adults). Untreated first trimester maternal infection may lead to miscarriage; premature delivery may occur when infection occurs later in pregnancy. Acute infection during pregnancy also increases the risk of chronic maternal infection. Treatment decreases the risk of adverse pregnancy outcomes and adverse events in subsequent pregnancies. Treatment with sulfamethoxazole/trimethoprim is recommended throughout pregnancy up to 32 weeks' gestation (withhold sulfamethoxazole/trimethoprim during the last 8 weeks of gestation due to the risk of kernicterus). Monitoring should continue for 24 months after delivery to evaluate possible progression to chronic disease (CDC [Anderson 2013]).

Sulfamethoxazole/trimethoprim is recommended for the primary prophylaxis of Toxoplasma gondii encephalitis (TE) in pregnant patients with HIV. The risks of fetal exposure to sulfamethoxazole/trimethoprim during the first trimester should be balanced with the risk TE (HHS [OI adult] 2022).

Sulfamethoxazole/trimethoprim is approved for the treatment of urinary tract infections (UTIs) in adults. Some guidelines prefer alternative antibiotics for UTIs in pregnancy as well as avoiding use in the third trimester (Betschart 2020).

Sulfamethoxazole/trimethoprim is not recommended for the treatment of granuloma inguinale during pregnancy (recommended as an alternative therapy in nonpregnant patients) (CDC [Workowski 2021]).

Sulfamethoxazole/trimethoprim may be used as part of a treatment regimen when brucellosis is diagnosed during pregnancy (not the preferred treatment in nonpregnant patients). Untreated maternal brucellosis infection may cause adverse pregnancy outcomes including spontaneous abortion or transmission to the infant. Treatment with sulfamethoxazole/trimethoprim is not recommended after 36 weeks' gestation due to the risk of kernicterus (Bosilkovski 2020; CDC brucellosis reference guide 2017).

Sulfamethoxazole/trimethoprim is used in the management of plague (Yersinia pestis). Untreated infections in pregnant patients may result in hemorrhage (including postpartum hemorrhage), maternal and fetal death, preterm birth, and stillbirth. Limited data suggest maternal-fetal transmission of Y. pestis can occur if not treated. Pregnant patients should be treated for Y. pestis; parenteral antibiotics are preferred for initial treatment when otherwise appropriate. Sulfamethoxazole/trimethoprim may be used as an alternative antibiotic for treating pregnant patients with bubonic, pharyngeal, pneumonic, or septicemic plague. Sulfamethoxazole/trimethoprim may also be used as an alternative antibiotic for pre- and postexposure prophylaxis in pregnant patients exposed to Y. pestis. Treatment and prophylaxis for plague with sulfamethoxazole/trimethoprim can be used regardless of trimester (CDC [Nelson 2021]).

Monitoring Parameters

CBC, renal function, sodium, potassium, glucose; observe for change in bowel frequency. Liver function (with longer-term use); urinalysis (if clinical presentation indicates need).

Mechanism of Action

Sulfamethoxazole interferes with bacterial folic acid synthesis and growth via inhibition of dihydrofolic acid formation from para-aminobenzoic acid; trimethoprim inhibits dihydrofolic acid reduction to tetrahydrofolate resulting in sequential inhibition of enzymes of the folic acid pathway

Pharmacokinetics (Adult Data Unless Noted)

Absorption: Oral: Rapid; almost completely (90% to 100%).

Distribution: Both SMX and TMP distribute to middle ear fluid, sputum, vaginal fluid; TMP also distributes into bronchial secretions.

Vd: TMP:

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 1 to 10 years: 0.86 to 1 L/kg (Hoppu 1987).

Adults: ~1.3 L/kg (Hoppu 1987).

Protein binding: SMX: ~70%, TMP: ~44%.

Metabolism: Hepatic, both to multiple metabolites; SMX to hydroxy (via CYP2C9) and acetyl derivatives, and also conjugated with glucuronide; TMP to oxide and hydroxy derivatives; the free forms of both SMX and TMP are therapeutically active.

Half-life elimination:

TMP: Prolonged in renal failure.

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: 3.7 to 5.5 hours (Hoppu 1987).

Children and Adolescents >10 years: 8.19 hours.

Adults: 6 to 11 hours.

SMX: 9 to 12 hours, prolonged in renal failure.

Time to peak, serum: Oral: 1 to 4 hours.

Excretion: Both are excreted in urine as metabolites and unchanged drug.

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Altered kidney function: Patients with severely impaired renal function exhibit an increase in the half-lives of both components, requiring dosage adjustments.

Older adult: Total body clearance of trimethoprim was 19% lower in elderly patients.

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Bactrim | Balkatrin | Cotrim | Imexim | Lagatrim | Nopil | Nortrim | Notrime | Omsat | Oribact | Septazole | Septrin | Sulfoprima | Sulfotrim | Sutrim | System | Trimol | Urtium;
  • (AR) Argentina: Adrenol | Bacticel | Bactrim | Bactrim forte | Cotrimox | Cotrimoxazol | Cotrimoxazol richet forte | Cotrizol-g | Danferane | Dosulfin forte | Lescot | Netocur | Novidrine | Spectrex | Sulfagrand | Tritenk | Tritenk forte;
  • (AT) Austria: Bactrim | Cotribene | Cotrimoxazol genericon pharma | Eusaprim | Oecotrim;
  • (AU) Australia: Bactrim | Cm trimeth s/meth | Cosig | Resprim | Resprim forte | Sbpa trimeth smeth | Septrin | Trimethoprim sulfa | Trimethoprim sulfamethoxazole | Trimoxazole-bc | Tw trimeth s/meth;
  • (BD) Bangladesh: Actrim | Adtrim | Alcot | Antrim | Apcetrim | Aptrim | Avlotrin | Bactacin | Bactazol | Bactipront | Bactronil | Bioprim | Biotrim | Bitrim | Centrim | Chemotrim | Chemozole | Citrim | Colotrim | Cosat | Cotrazen | Cotrilin | Cotrim | Cotrizol | Cots | Deotrim | Ditrim | Doctrim | Editrim | Ethitrim | Fisat | G-cotrimoxazole | Gentrim | Getrim | Japtrim | Jasotrim | Litrim | M-trim | Maktrim | Meditrim | Megaset | Megatrim | Methoprim | Methotrin | Metrim | Micogyl | Motrim | Napatrim | Navatrim | Neoset | Neotrim | Octrim | Omnatrim | Orgastran | Patrim | Pharmatrim | Politrim | Primazol | Rasat | Regtin | Rematrim | Retrim | Ribatrim | Rimazole | Saltrim | Satrim | Seematrim | Seftrim | Septazol | Septrin | Servitrim | Sinatrim | Sitrim | Skytrin | Soma ds | Strim | Sulphatrim | Sulprim | Sultra | Sumetrolim | Suprim | Suptrim | Synac | Synotrim | Theratrim | Tricot | Trimeton | Trimetrin | Trimezol | Trimox | Tytrim | Unitrim | Utrin | Zaxol;
  • (BE) Belgium: Bactrim | Co-trimoxazole | Cotrim | Eusaprim;
  • (BF) Burkina Faso: Altrim | Berlocid | Bibactin | Captrim | Co-trimoxazole | Cotrex | Cotrim | Cotrimoxazole | Cotrimoxazole tm | Cotrimoxazole ubigen | Deptrin | Mortin forte | Philco cotri;
  • (BG) Bulgaria: Bactrim | Berlocid | Biseptol | Primotren | Septrin | Sulfaprim | Sumetrolim | Trimezol;
  • (BR) Brazil: Assepium | Bac-sulfitrin | Bacfar | Bacmetrin | Bacprotin | Bacris | Bacsulfaprim | Bacteracin | Bacteracin f | Bactricin | Bactrim | Bactrisan | Bactropin | Baczin | Baklinger | Batrox | Belfactrim | Belfactrin | Belfactrin f | Benectrin | Benectrin f | Biotrin | Dientrin | Ectrin | Espectrin | Espectroprima | Furp sulfametoxazol + trimetoprima | Gamactrin | Genoctrin | Ibtrim | Infectrin | Infectrin f | Katrim | Leotrim | Lifactrin | Lupectrin | Mapitrim | Medtrim | Metoprin | Neotrin | Pulkrin | Qiftrim | Qiftrin | Roytrin | Selectrim | Selectrin | Septiolan | Septoprin | Silpin | Subtrax | Sulfametosazol con trimetoprim | Sulfametoxazol + trimetoprima | Sulftrin | Teutrin | Tricban | Trimexazol | Trimezol | Uropol;
  • (CH) Switzerland: Bactrim | Cotrim | Escoprim | Helveprim | Nopil | Sigaprim | Supracombin;
  • (CI) Côte d'Ivoire: Altrim | Altrim forte | Apo sulfatrim | Bactrim | Bactrim forte | Bibactin | Bibactin fort | Captrim | Cotri care | Cotrimoxazole | Cotrimoxazole tm | Phartrim | Sulfran | Sulfran ds | Sultrim fort | Trimac | Trimoprim | Trimoxol;
  • (CL) Chile: Bacterol | Bactrimel | Co-trimoxazol | Cotrimoxazol | Infesin | Introcin | Irgagen | Micinovo | Normacol | Plurisul | Septrin | Septrin forte | Trelibec;
  • (CN) China: Compound sulfamethoxazole | Fu fang huang an jia e zuo fen san | Nuo da ming | Nuo de fei | Smz (co) | Sulfamethoxazole c;
  • (CO) Colombia: Bactigram F | Bactisol | Bactrim | Bactrim f | Baxul f | Cotrimoxazol | Decasulf forte | Mediprim | Mediprim f | Oxitoprim | Penivacs | Septrin | Sulfametoxazol + trimetoprima | Sulfametoxazol trimetoprima | Sulfinam | Sulfinam s | Sulmet | Sulthrim | Sulthrim-f | Sultrifar | Sultrifar f | Sultrivon-f | Sultropim | Supribac | Supribac f | Supribac simple | Terasulf | Trime rande f | Trimeran | Trimeril | Trimesulf | Trimesulf f | Trimesulf forte | Trimesulf-f | Trimetoprim + sulfametoxazol | Trimetoprim sulfa | Trimetoprim sulfametoxazol | Trimetoprim sulfametoxazol f | Trimetoprim sulfametoxazol mk | Trimetoprima sulfa f | Trimetoprima sulfametoxazol | Trimetoprin sulfa | Trimetropina sulfametoxazol | Trimex | Trimsul | Trisolvat | Trisulfa | Trisulfa f | Tritosul f | Trixid | Weiditrin | Xazotrim;
  • (CR) Costa Rica: SEPTRAN;
  • (CU) Cuba: Cotrimoxazol;
  • (CZ) Czech Republic: Apo sulfatrim | Bactrim | Biseptol | Bismoral | Cotrimoxazol | Cotrimoxazol al forte | Cotripharm | Oribact | Primotren | Sumetrolim;
  • (DE) Germany: Bactoreduct | Bactrim | Co-trimoxazole | Cotrim | Cotrim abz | Cotrim diolan | Cotrim e | Cotrim forte | Cotrim forte eu rho | Cotrim Forte-ratiopharm | Cotrim hefa | Cotrim hexal | Cotrim holsten saft | Cotrim tablinen | Cotrim-CT | Cotrim-ratiopharm | Cotrim-sandoz | Cotrimox wolff | Cotrimoxazol al | Cotrimoxazol al forte | Cotrimstada | Eusaprim | Eusaprim k | Microtrim | Sigaprim | Sulfotrimin | Tms;
  • (DK) Denmark: Sulfametoxazol med trimetoprim SAD;
  • (DO) Dominican Republic: Apotrinelax | Bacticel | Bactrilac | Bactrin | Bactrizole | Baxolex | Cladon | Cotrim | Justeprim | Lisaprin | Metomide | Metoprin | Polibatrin | Primasulf | Quisulyn | S.T. Forte | SEPTRAN | Sulfamer | Sulfatropim | Sulftran | Sulgotri | Sultrima | Teof | Trimesul | Trimetoprim & sulfametoxazol | Trimetoprim sulfametoxazol iberofarmaco | Trimetoprin sulfa | Trisul | Tritosul;
  • (EC) Ecuador: Bacterol | Bacticel | Bactoprim | Bactricida | Bactrim | Bitrim | Cotribac forte | Cotrimoxazol | Cotrimoxazol forte | Cotrimoxazol pediatrico | Danferane | Fametrim forte | Fametrim simple | Fametrim sulfa | Fametrin sulfa | H.g. sulfatrim | Krobactrol | Meprim | Nopil | Omsat | Suftrex | Sulfacif | Sulfaprim | Sulfatalpin | Sulfatrim | Supracombin | Trimetoprim sulfa | Trimetoprima | Trimetotal | Trimezol | Trimol | Zoltrim;
  • (EE) Estonia: Bactrim | Bactrim ds | Bactrim forte | Berlocid | Biseptol | Co-trimoxazol | Co-trimoxazole | Cotribene | Cotrimoxazol | Oriprim | Septrin | Sulfatrim | Sulfotrim | Trimesol;
  • (EG) Egypt: Bacticure | Chemotrim | Co-trimoxazole | Coprimasept | Cotrazim | Cotril | Cotril forte | Epitrim | Farcotrim | Septazole | Septrin | Sulfatrim | Sulfatrim ds | Sutaprim | Sutrim | Sutrim forte;
  • (ES) Spain: Abactrim | Eduprim | Gobens trim | Septrin;
  • (ET) Ethiopia: Astrim | Cadiprim | Co-trimoxazole | Cotri | Deprim | Ifitrim | Sulfamethoxazole and trimethoprim | Sulphamethoxazole + trimethoprim;
  • (FI) Finland: Bactrim | Cotrim | Eusaprim | Oribact | Sulfotrim | Trimetsol | Trimosulfa;
  • (FR) France: Bactrim | Cotrim | Cotrimoxazole dakota pharm | Cotrimoxazole Ratiopharm | Cotrimoxazole rpg | Eusaprim;
  • (GB) United Kingdom: Bactrim | Chemotrim | Co trimoxazol | Co trimoxazole | Co trimoxazole cox | Co trimoxazole knt | Comixco | Comox | Fectrim | Laratrim | Nodilon | Septrin;
  • (GH) Ghana: Cotrim paediatric | Escotrim;
  • (GR) Greece: Bactrimel | Cotrim e ratiopharm | Septrin | Solfoton;
  • (HK) Hong Kong: Chemoprim | Cobacide | Dhatrin | Eurotrim | Letus | Po Trim | Septol | Septrin | Sulphathoprim | Suprim | Synco-smzt | Trimetrin | Trimezol | Trimezole;
  • (HR) Croatia: Sinersul | Sulotrim;
  • (HU) Hungary: Bactrim | Cotripharm | Huma-trimel | Sumetrolim;
  • (ID) Indonesia: Abatrim | Abditri | Aditrim | Altrim | Bactoprim combi | Bactricid | Bactrim | Bactrizol | Bimactrim | Centrim | Co-trim | Co-trimoxazole | Coprim | Cotrim | Cotrimol | Cotrimoxazole | Decatrim | Dotrim | Dumotrim | Erphatrim | Fameprim | Fatibact | Graprima | Gunametrim | Hexaprim | Hufacid | Ikaprim | Inatrim | Infatrim | Kaftrim | Kemocid | Kentricid | Kotrimoksazol | Lapikot | Licoprima | Maxtrim | Meditrim | Megatrim | Meprotrin | Miratrim | Moxalas | Nufaprim | Omegtrim | Ottoprim | Pehatrim | Primadex | Primatrim | Primavon | Primazole | Primsulfon | Ratrim | Saltrim | Sanprima | Septrin | Sisoprim | Spectrem | Sulprim | Sultrimmix | System | Toxaprim | Trimeta | Trimezol | Triminex | Trimoxsul | Trixzol | Trizole | Ulfaprim | Wiatrim | Xepaprim | Yekaprim | Zecatrim | Zoltrim | Zultrop;
  • (IE) Ireland: Antrimox | Septrin | Septrin paediatric;
  • (IL) Israel: Diseptyl | Resprim | Septrin;
  • (IN) India: Alaxol | Alco | Alcorim-f | Anprim | Antrima | Bacitran | Bactoprim | Bactosain | Bactostab | Bactrim | Bioprim | Centrim | Chemotrin | Cidaprim | Ciplin | Co-trimoxa | Co-trimoxazole | Colizole | Combact | Coprime | Cosulf | Cotran | Cotribid | Cotrim | Cotrimax | Cotrimoxazole | Cotrizole | Creptrim | Erotrim | Fabrol | Gatrima | Hatrix | Isoprim | Klotrim | Kolibitor | Kombina | L trim | Larprim | Lykaprim | Macprim | Maxiprim | Moly | Mortin | Neuroprim | Okatrim | Oriprim | Otrim | Rancotrim | Rizol | Rolprim | Salgatran | Sepmax | Septabid | Septabid-2 | Septinix | SEPTRAN | Stan | Suprin | Synastat | Synetra | Tabrol | Torrid | Tprim | Trima | Trimco | Trimex | Trimex ds | Trimox | Trimozol | Trimzole ds | Trisolak forte | Trisulfose | Trisuprim | Unitran | Woktrin ds | Wypal | X-trim;
  • (IQ) Iraq: Dadprim | Furaprim | Hayprim | Kindiprim | Metheprim | Methoprim | Piotrim | Safaprim | Sulfatrime;
  • (IS) Iceland: Primazol | Primazol sterkar;
  • (IT) Italy: Bacterial | Bactrim | Bactrimel | Chemitrim | Eusaprim | System | Trimesulf;
  • (JO) Jordan: Bactrim | Balkatrin | Lagatrim | Notrim | Septrin | Sulprim | Trimidar m | Trimol | Urtium;
  • (JP) Japan: Bactramin | Baktar | Daiphen | Oxaprim | Septerin | Stopan | Urodown;
  • (KE) Kenya: Alcorim | Alprim | Astrim | Bactifenin | Bactrim | Bactrim forte | Bactron | Betrim | Biotrim | Biotrim ds | Bisepton | Ciplin | Ciplin ds | Co tri | Co trimoxazole | Cosatrim | Cosatrim ds | Cotreich | Cotrikant | Cotrim | Cotrimoxazole | Dacotri ds | Lagatrim | Lagatrim forte | Lecotrim | Lecotrim forte | Maxotrim | Megatrim | Mortin | Osstrim | Otrim ds | Primox | Septrin | Shalphatrim | Shetrim | Sulfamethoxazole and trimethoprim | Sulfatrim | Sulfatrim forte | Sulfran | Sulfran ds | Sulfran paediatric | Sulprim | Sultrim | Trimoprim | Trimoxol | Trimoxol ds | Trizole | Unitrim | Unitrim ds | Vircot | Zeetrim;
  • (KR) Korea, Republic of: Alltarim | Bactrim | Canprim | Cotoram | Cotrim | Madroxin | Metorim | Pentrin | Septrin | Sinotrim | Sinotrim F | Sulprim | Sultase | Sultorim | Sultrim | T-s | Triprim | Ts | U-prin | Uprina;
  • (KW) Kuwait: Bactrim | Nopil | Septrin | Theraprim | Trimol;
  • (LB) Lebanon: Bactekod | Bactrim | Co trimoxazole | Cotrimoxazole | Lagatrim | Mediprim | Septrin | Tms | Trimexazol | Trimoxazol;
  • (LT) Lithuania: Apo sulfatrim | Bactekod | Bactrim | Biseptol | Bitrim | Blexon | Ciplin | Cotrimoxazol | Cotripharm | Duo septol | Groseptol | Oribact | Oriprim | Primotren | Rancotrim | Septrin | Sinersul | Sulfaton | Sumetrolin | Trimetop duplo | Trimezol;
  • (LU) Luxembourg: Bactrim | Co-trimoxazole | Cotrim | Cotrimoxazole | Eusaprim;
  • (LV) Latvia: Antrima | Apo sulfatrim | Bactekod | Bactrim | Berlocid | Biseptol | Blexon | Ciplin | Cotrim | Cotrimoxazol | Cotripharm | Duo septol | Groseptol | Nopil | Oribact | Oriprim | Primotren | Septrin | Sulfaton | Sumetrolin | Trimesolphar | Trimetop duplo | Trimezol;
  • (MA) Morocco: Apo sulfatrim | Bactrim forte | Berlocid | Co-trim | Eusaprim | Microcetim | Sulfaprim | Tms | Trimox | Trisulfa | Trixazol | Trixazol fort;
  • (MX) Mexico: Andoprim | Anitrim | Apotrinelax | Bactelan | Bacteric | Bactide | Bactiver | Bactrim | Bactrim f | Bactropin | Bateral | Bioprim | Bisultrim | Dertrin | Dertrin s | Ectaprim | Ectaprim f | Eutrim | Kaltrim f | Maxtrim | Maxtrim f | Maxtrim p | Metoxiprim | Neofatrim | Octiban | Odisulfan | Ormoprim | Pisatrina | Polibatrin | Polibatrin f | Pribac | Septrin | Septrin f | Servitrim | Servitrim-f | Soltrim | Soltrim f | Sulfawal-t | Sulfort | Sultiprim | Suxprim | Thriazol | Thriazol-s | Tribakin | Trimetoger | Trimetoprima con sulfametoxazol | Trimetoprima y sulfametoxazol | Trimetox | Trimexazol | Trimexazol f | Trimexole f | Ts bac | Vanadyl;
  • (MY) Malaysia: Apo sulfatrim | Bacin | Bactrim | Baserin | Chemix | Co primazol | Co primox | Co-trimoxa | Co-trimoxazole | Co-Trimoxazole Pharmaniaga | Comazole | Comazole n | Coprime | Cotrim | Cotrimoxazole | Dhatrin | Dynaprim | Primzole | Rancotrim | Resprim m | Septrin | Setrim | Sulfaprim | Sulfatrim | Suprim | Trimexazole | Trimezole | Trizole;
  • (NG) Nigeria: Acartrin | Albetrin | Bradtrim | Cika cotrim | Co trimoxazole | Co trox | Co-trimoxazole | Coptrine | Cotrikris | Emtrim | Emtrim forte | Esitrim | Faptrimox | Garytrim | Jawatrim | Kisitrim | Mopson co trimoxazole | Osworth cotrimoxazole | Paltrin | Pantrim | Pectrim | Pistrin | Rancotrim forte | Samtrim | Tecotrim | Trimac | Trimac forte | Tutrim | Unitrim | Vadis co trimoxazole;
  • (NL) Netherlands: Bactrimel | Co trimoxazol cf | Co trimoxazol forte cf | Co-trimoxazol | Co-Trimoxazol A | Co-trimoxazol flx | Cotrimoxazol | Cotrimoxazol aurobindo | Eusaprim;
  • (NO) Norway: Bactrim | Bactrim camp | Bactrimel | Bactrimel specifik | Cotrim | Cotrim-ratiopharm | Eusaprim | Trimesolphar macura | Trimetoprim sulfa gea;
  • (NZ) New Zealand: Apo sulfatrim | Bactrim | Cotrimoxazole | Septrin | Trimel | Trisul;
  • (PE) Peru: Apo-bactotrim | Bacsulfin | Bacsulfin forte | Bacterol | Bacteromycin forte | Bacticel | Bactraxole forte | Bactrim | Bactrim f | Bactrim forte | Bactriplus | Balcotrin forte | Beckatrim forte | Biotrim | Broncoflam | Cipaprim | Cotrimoxazol | Dientrin | Dolatrim | Drossul | Droxol | Eliprim | Exazol | Infectrim | Infesul | Lusaprim | Maflux forte | Maflux pediatrico | Massulf | Mebryn | Medibiot | Megabroncoflam | Myctrim | Novotrim plus | Paldix forte | Plurisul | Quibac forte | Ropsil | Roxtrim | Sanaprim | Sanaprim forte | Sanatrim forte | Sanatrim pediatrico | Septrin | Sulfa 100 + trim 20 | Sulfa 200 + trima 40 | Sulfa 400 + trima 80 | Sulfa 800 + trima 160 | Sulfa maxx forte | Sulfamethoxazole and trimethoprim | Sulfametoxazol + trimetoprima | Sulfametoxazol y trimetoprima mf | Sulfaquilab forte | Sulphax | Sulphytrim forte | Sulphytrim junior | Sultrima | Sumetoprim | Suprasulf | Suprim | Suprimass | Tribaxon | Trimesulfin | Trimetoprim sulfa | Trimetoprim sulfa genfar | Trimexasol | Trimfasul | Trimol | Zitrim | Zitrim forte;
  • (PH) Philippines: Abetrim | Alcotri | Allibac | Bacidal | Bactille-ts | Bactrex | Bactrim | Bactrinol | Bacxal | Baczole | Bantizol | Bestofens | Biogenerics cotrimoxazole | Boie cotrimoxazole | Chemoprim | Chromo-z | Ciplin | Ciplin ds | Colimox | Combi-methoxan | Combizole | Costazole | Cotrexel | Cotribase | Cotrimoxazol | Cotrimoxazole | Cozole | Ctr | Dhatrin | Diazole | Dli cotrimoxazole | Drilozole | Embatrim forte | Fedimed | Forteprim | Genoxzole | Genzaprim | Globaxol | Intrafort | Jenetrol | Jestrim | Kassemox | Kathrex | Katrim | Kindoprim | Lacreozole | Lafayette cotrimoxazole | Lagatrim | Leprim | Lictora | Macromed | Medic aid cotrimoxazole | Microbid | Microbid ds | Moxadden | Moxzole | Necorzole | Neotrim | Nuruzole | Onetrim | Penzole | Pharex co-trimoxazole | Primecotrix | Procor | Renatrim | Rimezone | Rotrace | Scribcin | Septrin | Septrol | Servitrim | Sigatrim | Suprex | Syltrifil | Syndal | Synermed | Synerzole | Thoprim | Timizol | Triforam | Trihexal | Trim-s | Trimephar | Trimocom | Trimoxavin | Trimoxis | Trimoxol | Triphimox | Trisulcom | Trizole | Trymerin | Urethrax | Xanazole | Zamboprim | Zerrprim | Zolbach | Zolmed | Zoltrijem;
  • (PK) Pakistan: Aksotran | Albrotran | Amoxazol | Amtran | Amtril | Antibac | Antrima | Aratran | Ascotran | Bactrim | Biotran | Biprim | Boschtrim | Btran | Caretran | Chemizol | Chemotran | Clinitran | Co trifa | Co trimoxazole | Co-trimoxazol | Colitran | Comax | Cotri | Cotrim | Cotrimax | Cotrimaxazole | Cotrimoxazole | Cotrisul | Cotrizole | Cozol | Dosatran | Dubac | Dutran | Eroprim | Fakzol | Flocot | Hicot | Infectran | Kaytran | Kotazol | Lifzol | Lobact | Longasal | Mactran | Martiprim | Maxol | Maxzol | Mazatrim | Meditran | Mexaprim | Mexazole | Naftran | Nicotrim | Novozole | Octil-s | Octran | Opiran | Orgastran | Ostrin forte | Pabtran | Pakzole | Penetrin | Pharmazol | Phartex | Polytran | Primox | Radisulf | Rascotran | Rexaprim | Santrix | Saptri | Saptrim | Semozol | Sepiran | Septazol | SEPTRAN | Septran ds | Septrawin | Siltran | Smartrim | Sosetran | Sulfarim | Sulforin | Sulphaprim | Sulphatran | Sulprim | Sumitran | Suptrex | Synbac | Therasept | Tricare | Trimex | Trimoxin | Triprim | Trisep | Trizol | Wiltran | Xa-zole | Zactron | Zantran | Zeptra | Zolebid;
  • (PL) Poland: Bactrim | Biseptol | Duo septol | Groseptol | Sumetrolin | Two septol;
  • (PR) Puerto Rico: Bactrim | Bactrim ds | Bethaprim | Septra | Septra ds | Sulfamethoxazole and trimethoprim | Sulfatrim | Sultrex;
  • (PT) Portugal: Bactrim | Cotrim forte | Cotrimoxazol | Cotrimoxazol teva | Cotrimoxazole Ratiopharm | Metomide | Septrin;
  • (PY) Paraguay: Bacterol | Bacterol forte | Bacterol pediatrico | Bactrim | Bactrim forte | Camex s | Camex s forte | Co trimoxazol caplin point | Meditrin | Septoprim | Septoprim forte | Sulamin | Sulamin forte | Sulditen | Sulditen forte | Sulfa sepsidin | Sulfa sepsidin forte | Sulfagrand | Sulfametoxazol + trimetoprim bilac | Sulfametoxazol + trimetoprim kirei | Sulfametoxazol + trimetoprima bilac | Sulfametozaxol trimetoprim dasanti | Sulfatrim | Teraprodil | Teraprodil forte | Trimetoprima sulfametoxazol cellofarm | Trimezol | Trimezol forte | Trimsul | Trimsul forte;
  • (QA) Qatar: Apo-Sulfatrim | Bactrim | Bactrim Forte | Chemotrim | Chemotrim Forte | Cotrimhexal Forte | Farcotrim | Septrin | Septrin DS | Trimol | Trimol DS;
  • (RO) Romania: Bactrim | Berlocid | Biseptol | Biseptrim | Bitrim | Blexon | Cotrim diolan | Cotrimoxazol | Resprim | Septrin;
  • (RU) Russian Federation: Apo sulfatrim | Bacteriof.klebs pn | Bactrim | Bactrim forte | Berlocid | Bi septin | Bicotrim | Biseptol | Brifeseptol | Ciplin | Co-trimoxazole | Co-trimoxazole akri | Co-trimoxazole sti | Cotrimol | Cotrimoxazol | Cotrimoxazol vatch | Cotripharm | Duo septol | Dvaseptol | Groseptol | Oriprim | Rancotrim | Septrin | Sulfaton | Sumetrolim | Trimezol | Trimosul;
  • (SA) Saudi Arabia: Apo sulfatrim | Bactrim | Balkatrin | Balkatrin forte | Chemotrim | Nortrime | Septazol | Septrin | Sutrim | Theraprim | Trimol;
  • (SE) Sweden: Bactrim | Bactrim forte | Eusaprim | Triferm sulfa | Trimetoprim sulfa | Trimetoprim sulfa gea;
  • (SG) Singapore: Bacin | Chemix | Chemoprim | Dhatrin | Mortin | Primzole | Resprim | Septrin | Sulfaprim | Suprim | Syntoprim | Trimaxazole;
  • (SI) Slovenia: Eusaprim | Primotren | Septrin pediatrico | Sinersul | Sulotrim;
  • (SK) Slovakia: Berlocid | Biseptol | Bismoral | Nopil | Oriprim | Primotren | Sinersul | Sumetrolim;
  • (SL) Sierra Leone: Co trimoxazole | Mihitrim | Welcotrim;
  • (SV) El Salvador: Trimetoprim sulfametoxazole cr;
  • (TH) Thailand: Actin | Bacin | Bacoprim | Bactoprim | Bactrim | Baczole | Basatin | Betam | Canamed | Chemoprim | Co tri | Co-tasian | Co-trimed | Co-trimed d/s | Co-trimoxazole | Cofatrim | Comox | Coprim | Cotri | Cotrim | Cotrim forte | Cotrimoxazole | Cotrixyl-L | G prim | Gaprim | K.B.Famate | Ko-kure | Lastrim | Lastrim C | Letus | M-Moxa | M-trim | Maxitrin | Maxitrin-C | Medcotrim | Metrim | Metrim-f | Metrim-h | Metxaprim | Microtrim | Motrim | Moxatrim | Panatrim | Po Trim | Rancotrim | Septra | Septrin | Septrin-s | Servitrim | Spectrim | Sulfamet | Sulfometh | Sulfotrim | Sulfotrim Ped | Sulprim | Sulprimed | Sultrim | Suntrim | Supim | Sutrim | Trimetrin | Trimexazole | Trimoxin | Trimytrim | Triprim | Trixzol | Win trim;
  • (TN) Tunisia: Altrim | Bactekod | Bactrim | Balkatrin | Berlocid | Cotrim | Cotrimox | Eusaprim | Sulfatrim | Sumetrolim;
  • (TR) Turkey: Bactrim | Bactrim forte | Bakton | Baktrisid DS | Baktrol | Bibakrim | Biotrin | Kemoprim | Kemoprim fort | Metoprim | Mikrosid | Septrin | Sulfaprim | Trifen | Trimoks;
  • (TW) Taiwan: Andcide | Bacdan | Bacidim | Bacin | Bactrim | Baktacin | Baktar | Baktsin | Beyliyan | Bicidium | Chemix | Co trimoxazol | Co-trimoxazole | Coyenlin | Euctrim | Nopil | Pantrim | Senfihu | Septrin | Shuo mai pei lin ding | Sigaprim | Sinotrim | Sinzuin | Sioclofen | Someprim | Sulfatrim | Sulfotrim | Sultrim | Sultrimerim | Suprin | Tonz | Trimazole | Trimerin | Trimesin | Trimezol | Trimezole | Trimox | Waribact ts;
  • (TZ) Tanzania, United Republic of: Septrin | Shetrim;
  • (UA) Ukraine: Bactiseptol | Bactrim | Berlocid | Bi sept farmak | Bicotrim | Biseptazol | Biseptol | Blexon | Co-trimoxazole | Cotrimoxazol | Duo septol | Groseptol | Oriprim | Rancotrim | Raseptol | Rivoprim | Septrin | Sinersul | Sulfaton | Sumetrolim | Trimosul | Tryseptolum;
  • (UG) Uganda: Alprim | Astrim | Betrim | Ciplin | Ciplin ds | Co trimoxazole | Cosatrim | Cosatrim ds | Cotramox | Cotrikant | Cotrim | Cotrimoxazole | Emtrim | Emtrim forte | K trim | Kam cotri | L trim | L trim ds | Lecotrim | Megatrim | Renetrim | Renetrim d.s | Septrin | Simtrim | Sulfamethoxazole and trimethoprim | Sulfran | Sulfran ds | Sulphatrim | Trimago | Unitrim | Zeptrin;
  • (UY) Uruguay: Bacteracin f | Bacticel | Bactrim | Bactrim forte | Cotrimoxazol | Danferane | Herixina | Sistrim | Sistrim forte | Spectrex | Sulfatrim | Sulphax | Ultrim;
  • (VE) Venezuela, Bolivarian Republic of: Bactrimel | Bactron | Baxolex | Co-sultrin | Cotrimoxazol | Forcrim | Novactil | Sulfametoxazol/trimetoprim | Sultrim fuerte | Trimesul forte | Trimetoprim + sulfametoxazol | Trimetoprim sulfa | Trimetoprim sulfametoxazol | Trimetoprim/sulfametoxazol | Trimetoprima sulfametoxazol | Trimetropim y sulfametoxazol | Tripur;
  • (VN) Viet Nam: Agi cotrim | Bidiseptol | Bisepthabi | Cotrimstada forte | Disulfa | Dutased | Pms cotrim | Sanseptol | Sulfatrim | Tanacotrimf | Tidacotrim | Trimeseptol | Vacotrim;
  • (ZA) South Africa: Adco-co-trimoxazole | Aspen Cotrimazole | Bactrim | Bencole | Co trimoxazole biotech | Co-trimoxazole | Cocydal | Cotrim | Cozole | Dino-Bac | Doctrim | Fabubac | Ilvitrim | Lagatrim | Meditrim | Merck-co-trimoxazol | Mezenol | Micro co-trimoxazole | Micro-cotrimoxazol | Norisep | Novatrim | Nucotrim | Purbac | Purbac Ds | Q-med co-trimoxazole | Rolab-co-trimoxazole | SEPTRAN | Spectrim | Trimethox | Trimzol | Xerazole | Xeroprim;
  • (ZM) Zambia: Astrim | Bacrizole | Bactrizole | Betrim | Cadiprim | Ciplin | Ciplin ds | Co trimoxazole | Combact | Cotrim | Cotrimoxazole | Cotrizole | Fortrim a | L trim | Lyseptol | Megatrim | Mezenol | Ml cotri | Purbac | Rancotrim | Shetrim | Sulfamethoxazole and trimethoprim | Sulfatrim | Sulfatrim forte | Sulfran | Sulfran ds | Suprim | Timizol | Tprim | Trim | Trimago;
  • (ZW) Zimbabwe: Bencole | Ciplin | Co-trimoxazole | Cotrimoxazole | Cotrizole | Cotrizole ds | Mezenol | Mortin | Novabact | Stritrim | Sulfamethoxazole and trimethoprim | Umoxazole
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