Note: Weight-based dosing recommendations are based on the trimethoprim (TMP) component. Each double-strength tablet contains TMP 160 mg and sulfamethoxazole (SMX) 800 mg. Each single-strength tablet contains TMP 80 mg and SMX 400 mg. The undiluted IV solution contains TMP 16 mg per mL and SMX 80 mg per mL. IV solutions must be diluted in D5W prior to use. Diluted IV solutions have limited stability and can precipitate unpredictably; refer to a detailed IV compatibility reference.
General dosing guidelines:
Oral: 1 to 2 double-strength tablets every 12 to 24 hours. Note: Serum creatinine and potassium concentrations should be monitored in outpatients receiving high-dose therapy (>5 mg/kg/day [TMP component]) (Ref).
IV: 8 to 20 mg/kg/day (TMP component) divided every 6 to 12 hours.
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 (TMP 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 (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 (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 (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 (methicillin-resistant Staphylococcus aureus) (off-label use): Oral: 2 double-strength tablets twice daily, usually for 1 to 2 weeks (Ref). Note: When used as empiric therapy, must be used in combination with other appropriate agents. Some experts also use this agent for selected moderate infections (Ref).
Diarrhea, infectious:
Cyclosporiasis (off-label use):
Immunocompromised (AIDS-associated): Limited data available: Oral: 1 double-strength tablet twice daily for 14 days, followed by secondary prophylaxis with 1 double-strength tablet 3 times weekly (Ref).
Immunocompetent: Oral: 1 double-strength tablet twice daily for 7 to 10 days (Ref).
Cystoisosporiasis (isosporiasis) (off-label use):
Immunocompromised (AIDS-associated): Oral, IV: 160 mg (TMP component) twice daily for 7 to 10 days; if symptoms worsen or persist, may increase dose to 160 mg (TMP component) 4 times daily and/or prolong duration to 21 to 28 days. In patients with CD4 <200 cells/mm3, follow treatment with secondary prophylaxis of one double-strength tablet orally 3 times weekly (Ref).
Immunocompetent (usually self-limited; treatment not always indicated): Oral: 1 double-strength tablet twice daily for 7 to 10 days (Ref).
Shigellosis (widespread resistance [alternative agent if susceptibility is documented]): Oral: 1 double-strength tablet twice daily for 5 to 7 days (Ref).
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 7 to 10 days (Ref).
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 (TMP 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 (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 ( Burkholderia pseudomallei ) infection (off-label use):
Initial intensive therapy (as a potential add-on to primary therapy [ceftazidime or a carbapenem] in focal disease of the CNS, prostate, bone, joint, skin, or soft tissue): Oral, IV:
40 to 60 kg: 240 mg (TMP component) twice daily (Ref).
>60 kg: 320 mg (TMP component) twice daily (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): Oral:
40 to 60 kg: 240 mg (TMP component) twice daily (Ref).
>60 kg: 320 mg (TMP component) twice daily (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).
Nocardiosis (off-label use): Limited data available to guide treatment. Due to concerns for resistance, susceptibility testing should be performed on isolates (Ref).
Cutaneous infections (superficial; no other organ involvement): Oral: 5 to 10 mg/kg/day (TMP component) in 2 divided doses (Ref).
Pulmonary infection (mild to moderate):
Immunocompetent patients: Oral: 5 to 10 mg/kg/day (TMP component) in 2 divided doses (Ref).
Immunocompromised patients: Oral: 15 mg/kg/day (TMP component) in 3 to 4 divided doses (Ref).
Pulmonary infection (severe), CNS, disseminated, or multi-site infection: IV: 15 mg/kg/day (TMP component) in 3 to 4 divided doses (Spelman 2021b). Note: When used as empiric therapy, must be used in combination with 1 to 2 additional agents. Consult an infectious diseases specialist for specific treatment recommendations.
Duration: Prolonged treatment is required (range: 3 months to ≥1 year [combined parenteral/oral therapy]) (Ref).
Osteomyelitis due to methicillin-resistant S. aureus (alternative agent) (off-label use): Oral, IV: 4 mg/kg/dose (TMP component) every 12 hours with rifampin (Ref).
Plague ( Yersinia pestis ) (alternative agent) (off-label use):
Note: Consult public health officials for event-specific recommendations.
Postexposure prophylaxis: Oral: 5 mg/kg/dose (TMP component) every 12 hours for 7 days (Ref).
Treatment: Oral, IV: 5 mg/kg/dose (TMP component) every 8 hours for 7 to 14 days and for at least a few days after clinical resolution (Ref).
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 ART: Continue until undetectable viral load and CD4 count >200 cells/mm3 for >3 months (Ref); some experts discontinue primary prophylaxis in patients with CD4 counts between 100 and 200 cells/mm3 who are receiving ART and have had an undetectable viral load for ≥3 to 6 months (Ref).
Immunocompromised host, HIV-uninfected (eg, transplant recipients, cancer-related, hematopoietic stem cell transplant [HSCT]): 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 (except lung): ≥6 to 12 months and during periods of increased immunosuppression (eg, treatment for acute rejection) (Ref).
Duration after lung transplant: Lifelong therapy should be considered (Ref).
Duration for cancer-related (including HSCT) in patients at high risk for PCP infection: Based on expert opinion, continue until risk factor(s) for PCP infection are no longer present (Ref). Consult other specialized databases for more detailed information.
Treatment (Ref): Note: Secondary prophylaxis should be initiated immediately upon completion of therapy.
Moderate to severe infection: IV: 15 to 20 mg/kg/day (TMP 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.
Mild to moderate infection: Oral: 15 to 20 mg/kg/day (TMP component) in 3 divided doses for 21 days or two double-strength tablets 3 times daily.
Prosthetic joint infection (off-label use): 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):
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 (C. burnetii), acute symptomatic (off-label use): Note: Treatment is most effective if given within the first 3 days of symptoms (Ref).
Nonpregnant patients (alternative agent): Note: Reserve for patients unable to tolerate first-line agents and not at risk for complications (eg, patients without endocarditis or underlying valvular disease, negative antiphospholipid antibodies) (Ref).
Oral: 1 double-strength tablet twice daily for 14 days (Ref).
Pregnant patients: Oral: 1 double-strength tablet twice daily until 32 weeks' gestation; administer with folic acid supplementation. Note: Discontinue therapy for the final 8 weeks of pregnancy due to hyperbilirubinemia risk (Ref).
Septic arthritis (without prosthetic material) due to methicillin-resistant S. aureus (alternative agent following initial IV therapy with an appropriate antibiotic) (off-label use): Oral: 2 double-strength tablets twice daily or 4 mg/kg/dose (TMP component) twice daily (maximum: 320 mg [TMP component]/dose) for completion of 3- to 4-week total treatment course (IV and oral) (Ref).
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 (off-label use):
Cellulitis, nonpurulent with risk for methicillin-resistant S. aureus: Oral: 1 to 2 double-strength tablets twice daily (Ref). Some experts suggest adding an additional agent (eg, amoxicillin, cephalexin) for coverage of beta-hemolytic streptococci (Ref).
Cellulitis, purulent or abscess: Oral: 1 to 2 double-strength tablets twice daily (Ref). Note: Systemic antibiotics only indicated for abscess in certain instances (eg, immunocompromised patients, signs of systemic infection, large or multiple abscesses, indwelling device, high risk for adverse outcome with endocarditis). If at risk for gram-negative bacilli, use in combination with an appropriate agent (Ref).
Duration: 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 ≥3 episodes/year of known or presumed staphylococcal cellulitis when predisposing factors cannot be controlled (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 (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 infections (hospital-acquired or ventilator-associated pneumonia, bacteremia, or other sites) (off-label use): IV: 15 mg/kg/day (TMP component) in 3 or 4 divided doses. Duration depends on site of infection; 14 days for bacteremia and 7 days for pneumonia in an immunocompetent host with evidence of clinical improvement (Ref).
Surgical prophylaxis (off-label use):
Note: Reserve use for high-risk cystoscopy (eg, urine culture positive, 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 (AIDS associated) (off-label use):
Primary prophylaxis: 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-positive patients with CD4 count <100 cells/mm3. Continue primary prophylaxis following initiation of 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).
Treatment (alternative agent): Oral, IV: 10 mg/kg/day (TMP 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 or, alternatively, 1 double-strength tablet once daily (lower dose may be associated with increased relapse risk). Continue following initiation of ART until CD4 count >200 cells/mm3 for >6 months (Ref).
Urinary tract infection:
Cystitis, acute uncomplicated or acute simple cystitis (infection limited to the bladder without signs/symptoms of upper tract, prostate, or systemic infection), treatment: 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 women 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.
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 (TMP) component. Each double-strength (DS) tablet contains TMP 160 mg and sulfamethoxazole (SMX) 800 mg. Each single-strength (SS) tablet contains TMP 80 mg and SMX 400 mg.
|
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 |
|
Dose Adjustments for Kidney Impairmenta: IV | |||
|---|---|---|---|
|
CrCl (mL/minute) |
If usual recommended daily dose is 10 mg/kg/day (TMP component) |
If usual recommended daily dose is 8 to 12 mg/kg/day (TMP component) |
If usual recommended daily dose is 15 to 20 mg/kg/day (TMP 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 TMP 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 TMP 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).
There are no dosage adjustments provided in manufacturer’s labeling. Use with caution; use is contraindicated in cases of marked hepatic damage.
(For additional information see "Trimethoprim-sulfamethoxazole (co-trimoxazole): Pediatric drug information")
Note: 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: 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).
Catheter (peritoneal dialysis); exit-site or tunnel infection: 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).
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 (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).
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 (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 (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 (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 (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 (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 (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 (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 (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:
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.
Altered kidney function:
Infants, Children, and Adolescents: Oral, IV:
Note: Dosing is based on pharmacokinetic parameters, limited pediatric studies, adult studies, and expert opinion (Aronoff 2007; Golightly 2013; HHS [OI adult] 2020; Nahata 1995; Paap 1989; Veltri 2004; manufacturer's labeling):
|
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) (Nissenson 1987).
Children and Adolescents (Veltri 2004; expert opinion):
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 (Singlas 1982).
Infants, Children, and Adolescents: Oral, IV: Follow dosage recommendations for CrCl <15 mL/minute/1.73 m2; if used, monitor carefully (Aronoff 2007; Golightly 2013; Nemecek 2019; expert opinion).
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 (Brown 2014; Curkovic 2010; Kesner 2014).
There are no dosage adjustments provided in the manufacturer's labeling. Use with caution; use is contraindicated in cases of marked hepatic damage.
Refer to adult dosing.
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
Yes
The 5:1 ratio (SMX:TMP) remains constant in all dosage forms.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Septra: Sulfamethoxazole 80 mg and trimethoprim 16 mg per mL (5 mL) [contains alcohol, usp, propylene glycol, sodium metabisulfite]
Suspension, Oral:
Generic: Sulfamethoxazole 200 mg and trimethoprim 40 mg per 5 mL (100 mL, 400 mL)
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
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.
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)).
Oral: Treatment of urinary tract infection (UTI) due to Escherichia coli, Klebsiella and Enterobacter spp, Morganella morganii, Proteus mirabilis, and Proteus vulgaris; acute otitis media; acute exacerbations of chronic obstructive pulmonary disease due to susceptible strains of Haemophilus influenzae or Streptococcus pneumoniae; treatment and prophylaxis of Pneumocystis pneumonia (PCP); traveler's diarrhea due to enterotoxigenic E. coli; treatment of shigellosis caused by Shigella flexneri or Shigella sonnei.
IV: Treatment of PCP; treatment of shigellosis caused by S. flexneri or S. sonnei; treatment of severe or complicated UTIs due to E. coli, Klebsiella and Enterobacter spp, M. morganii, P. mirabilis, and P. vulgaris.
Bartonella spp. infection; Bite wound infection, prophylaxis or treatment (animal or human bite); Brucellosis; Cellulitis, long-term suppression of recurrent infection; Cellulitis, nonpurulent with risk for methicillin-resistant Staphylococcus aureus; Cellulitis, purulent or abscess; Cyclosporiasis; Cystoisosporiasis (Isosporiasis); Diabetic foot infection; Epididymitis; Granuloma inguinale (Donovanosis); Impetigo or ecthyma; Intra-abdominal infection; Intracranial abscess (brain abscess, intracranial epidural abscess) and spinal epidural abscess (methicillin-resistant Staphylococcus aureus); Mastitis, lactational; Melioidosis (Burkholderia pseudomallei) infection; Meningitis, bacterial; Nocardiosis; Osteomyelitis; Plague (Yersinia pestis); Prostatitis; Prosthetic joint infection; Q fever (Coxiella burnetii); Septic arthritis (methicillin-resistant Staphylococcus aureus); Spontaneous bacterial peritonitis, prophylaxis; Stenotrophomonas maltophilia infections; Surgical prophylaxis; Toxoplasma gondii encephalitis (prophylaxis/treatment/chronic maintenance) in patients with HIV
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
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 and older with decreased CrCl and on ACE inhibitors or ARBs due to increased risk of hyperkalemia (Beers Criteria [AGS 2019]).
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]).
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)
The most typical pattern of drug-induced liver injury (hepatotoxicity) observed with sulfamethoxazole/trimethoprim is a mixed hepatocellular cholestasis. Cholestasis without inflammation and hepatocellular necrosis (including fatalities) have also occurred (Ref). Some cases may be manifestations of drug reaction with eosinophilia and systemic symptoms (DRESS) (Ref). May also cause mild elevations in ALT that do not develop into more serious liver injury or jaundice (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)
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 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 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)
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)
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).
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).
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
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: Crystalluria, diuresis, toxic nephrosis (with anuria and 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: 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)
Hypersensitivity: Anaphylaxis (Harle 1988; Kuyucu 2014), fixed drug eruption (Can 2014)
Renal: Acute kidney injury (Fraser 2012)
Respiratory: Acute respiratory distress syndrome (Miller 2019)
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
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; pregnancy; breastfeeding; premature infants; acute porphyria.
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.
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).
Refer to individual components.
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
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
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: Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors. Risk C: Monitor therapy
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: Monitor therapy
LamiVUDine: Trimethoprim may increase the serum concentration of LamiVUDine. Risk C: Monitor therapy
Leucovorin Calcium-Levoleucovorin: May diminish the therapeutic effect of Trimethoprim. Management: Avoid concurrent use of leucovorin or levoleucovorin with trimethoprim (plus sulfamethoxazole) for Pneumocystis jirovecii pneumonia. If trimethoprim is used for another indication, monitor closely for reduced efficacy. Risk X: Avoid combination
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: Trimethoprim may increase the serum concentration of RifAMPin. RifAMPin may decrease the serum concentration of Trimethoprim. Risk C: Monitor therapy
RifAMPin: Sulfamethoxazole may increase the serum concentration of RifAMPin. RifAMPin may decrease the serum concentration of Sulfamethoxazole. 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
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).
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 2020]); 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 2020]).
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 2020]).
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 2020]).
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]).
Sulfamethoxazole and trimethoprim are present in breast milk.
The manufacturer states that the exposure of sulfamethoxazole and trimethoprim to the breastfeeding infant would be 2% to 5% of the recommended daily dose for infants >2 months of age (maternal dose, milk concentration, and infant dose not specified).
Information related to the presence of sulfamethoxazole and trimethoprim in breast milk is also available from a study of breastfeeding women given sulfamethoxazole 400 mg and trimethoprim 80 mg as either 2 tablets (n = 40) or 3 tablets (n = 10) twice daily for a minimum of 5 days. All women were treated for a urinary tract infection and therapy started within 5 days of delivery. Breast milk samples were obtained 2, 6, and 12 hours after the morning dose on days 2 through 5, and more frequently over 24 hours the first day of dosing. The mean trimethoprim concentration in breast milk was not significantly different in women taking the lower dose (1.96 mcg/mL) compared to women using the higher dose (2 mcg/mL). The overall mean concentrations were 1.97 mcg/mL for trimethoprim (757 samples) and 4.71 mcg/mL for sulfamethoxazole (718 samples) (Miller 1974).
A prospective cohort study evaluated the outcomes of breastfed infants whose mothers were taking various medications. Within the study, 12 mother-infant pairs reported sulfamethoxazole/trimethoprim exposure (dose, duration, relationship to breastfeeding not provided). There were no cases of diarrhea, drowsiness, or irritability in the breastfed infants. Poor feeding was noted in 2 infants (Ito 1993). In general, antibiotics that are present in breast milk may cause nondose-related modification of bowel flora. Monitor infants for GI disturbances, such as thrush or diarrhea (WHO 2002).
The therapeutic use of sulfamethoxazole and trimethoprim is contraindicated in infants <2 months of age due to the possibility of bilirubin displacement resulting in kernicterus and hemolytic anemia caused by immature erythrocyte enzyme systems; theoretically, the risk of jaundice, kernicterus and hemolytic anemia is present in breastfed infants with G6PD deficiency exposed to sulfamethoxazole and trimethoprim via breast milk (Mitrano 2009). The manufacturer recommends that caution be used if administered to persons who are breastfeeding, especially if breastfeeding infants are ill, jaundiced, premature, or stressed due to the potential risk of bilirubin displacement and kernicterus. Avoid use of sulfamethoxazole in persons who are breastfeeding an infant with G6PD deficiency (WHO 2002) or hyperbilirubinemia (Della-Giustina 2003). The WHO considers sulfamethoxazole and trimethoprim compatible with breastfeeding in older, healthy, full-term infants with monitoring of the infant for jaundice and hemolysis (WHO 2002).
Sulfamethoxazole/trimethoprim is an alternative antibiotic for the empiric treatment of bacterial mastitis in patients who are breastfeeding. Antibiotic use may be considered when symptoms are present for >24 hours and have not responded to conservative measures, or the patient has symptoms such as fever or tachycardia. Consider a milk culture if symptoms do not improve after 48 hours of antibiotic therapy. The diagnosis of mastitis does not require interruption of breastfeeding. Use is not recommended if the breastfed child has G6PD deficiency, or if the infant is <30 days old, has hyperbilirubinemia, or was born premature (ABM [Mitchell 2022]; WHO 2000).
Should be taken with 8 oz of water. May be taken without regard to meals.
CBC, electrolytes, renal function.
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
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.
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.
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
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
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