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Co-trimoxazole

Class: Sulfonamides
VA Class: AM900
CAS Number: 8064-90-2
Brands: Bactrim, Bactrim DS, Septra, Septra DS, Sulfatrim

Introduction

Antibacterial; fixed combination of sulfamethoxazole (intermediate-acting sulfonamide) and trimethoprim; both sulfamethoxazole and trimethoprim are folate-antagonist anti-infectives.a

Uses for Co-trimoxazole

Acute Otitis Media

Treatment of acute otitis media (AOM) in adults and children caused by susceptible Streptococcus pneumoniae or Haemophilus influenzae186 272 273 274 278 a when the clinician makes the judgment that the drug offers some advantage over use of a single anti-infective.a 186

Not a drug of first choice; considered an alternative for treatment of AOM, especially for those with type I penicillin hypersensitivity.321 Because amoxicillin-resistant S. pneumoniae frequently are resistant to co-trimoxazole, the drug may not be effective in patients with AOM who fail to respond to amoxicillin.302 321

Data are limited regarding safety of repeated use of co-trimoxazole in pediatric patients <2 years of age; the drug should not be administered prophylactically or for prolonged periods for treatment of AOM in any age group.186 a

GI Infections

Treatment of travelers’ diarrhea caused by susceptible enterotoxigenic Escherichia coli.112 159 181 182 186 242 256 Replacement therapy with oral fluids and electrolytes may be sufficient for mild to moderate disease;115 159 180 181 242 256 257 those who develop diarrhea with ≥3 loose stools in an 8-hour period (especially if associated with nausea, vomiting, abdominal cramps, fever, or blood in the stools) may benefit from short-term anti-infectives.114 115 159 180 242 259 306 Fluoroquinolones (ciprofloxacin, levofloxacin, norfloxacin, ofloxacin) usually drugs of choice when treatment indicated;159 180 242 306 co-trimoxazole also has been recommended as an alternative when fluoroquinolones cannot be used (e.g., in children).159 242 306

Prevention of travelers’ diarrhea in individuals traveling forrelatively short periods to areas where enterotoxigenic E. coli and other causative bacterial pathogens (e.g., Shigella) are known to be susceptible to the drug.113 159 242 CDC and others do not recommend anti-infective prophylaxis in most individuals traveling to areas of risk;114 159 180 193 242 256 257 280 286 the principal preventive measures are prudent dietary practices.114 159 256 257 If prophylaxis is used (e.g., in immunocompromised individuals such as those with HIV infection), a fluoroquinolone (ciprofloxacin, levofloxacin, ofloxacin, norfloxacin) is preferred.159 180 Resistance to co-trimoxazole is common in many tropical areas.159

Treatment of enteritis caused by susceptible Shigella flexneri or S. sonnei when anti-infectives are indicated.121 135 186 286

Treatment of dysentery caused by enteroinvasive E. coli (EIEC).286 AAP suggests that an oral anti-infective (e.g., co-trimoxazole, azithromycin, ciprofloxacin) can be used if the causative organism is susceptible.286

Treatment of diarrhea caused by enterotoxigenic E. coli (ETEC) in travelers to resource-limited countries.286 Optimal therapy not established, but AAP suggests that use of co-trimoxazole, azithromycin, or ciprofloxacin be considered if diarrhea is severe or intractable and if in vitro testing indicates the causative organism is susceptible.286 A parenteral regimen should be used if systemic infection is suspected.286

Slideshow: The Shocking Truth About Antibiotic Resistance

Role of anti-infectives in treatment of hemorrhagic colitis caused by shiga toxin-producing E. coli (STEC; formerly known as enterohemorrhagic E. coli) is unclear; most experts would not recommend use of anti-infectives in children with enteritis caused by E. coli 0157:H7.286

Treatment of GI infections caused by Yersinia enterocolitica or Y. pseudotuberculosis.121 286 d These infections usually are self-limited, but IDSA, AAP, and others recommend anti-infectives for severe infections, when septicemia or other invasive disease occurs, and in immunocompromised patients.286 d Other than decreasing the duration of fecal excretion of the organism, a clinical benefit of anti-infectives in management of enterocolitis, pseudoappendicitis syndrome, or mesenteric adenitis caused by Yersinia has not been established.286

Respiratory Tract Infections

Treatment of acute exacerbation of chronic bronchitis caused by susceptible S. pneumoniae or H. influenzae135 when the clinician makes the judgment that the drug offers some advantage over use of a single anti-infective.186

A drug of choice for treatment of upper respiratory tract infections and bronchitis caused by H. influenzae;121 an alternative to penicillin G or penicillin V for treatment of respiratory tract infections caused by S. pneumoniae.121

Alternative for treatment of infections caused by Legionella micdadei (L. pittsburgensis) or L. pneumophila.121

Urinary Tract Infections (UTIs)

Treatment of UTIs caused by susceptible E. coli, Klebsiella, Enterobacter, Morganella morganii, Proteus mirabilis, or P. vulgaris.135 186 a A drug of choice for empiric treatment of acute uncomplicated UTIs.121 163

Brucellosis

Treatment of brucellosis; alternative when tetracyclines are contraindicated (e.g., children).121 286 Used alone or in conjunction with other anti-infectives (e.g., streptomycin or gentamicin and/or rifampin),121 286 especially for severe infections or when there are complications (e.g., endocarditis, meningitis, osteomyelitis).286

Burkholderia Infections

Treatment of infections caused by Burkholderia cepacia.121 Co-trimoxazole considered drug of choice; ceftazidime, chloramphenicol, or imipenem are alternatives.121

Treatment of melioidosis caused by susceptible B. pseudomallei; used in multiple-drug regimen with chloramphenicol and doxycycline.121 Ceftazidime or imipenem monotherapy may be preferred.121 B. pseudomallei is difficult to eradicate and relapse of melioidosis is common.

Cholera

Treatment of cholera caused by Vibrio cholerae.121 231 286 Alternative to tetracyclines; used as an adjunct to fluid and electrolyte replacement in moderate to severe disease.121 231 286

Cyclospora Infections

Treatment of infections caused by Cyclospora cayetanensis.119 159 286 320 The drug of choice.119 159 286

Granuloma Inguinale (Donovanosis)

Treatment of granuloma inguinale (donovanosis) caused by Calymmatobacterium granulomatis.116 121 286 CDC recommends doxycycline or co-trimoxazole.116

Isosporiasis

Treatment of isosporiasis caused by Isospora belli.119 120 The drug of choice.119

Listeria Infections

Treatment of infections caused by Listeria monocytogenes;121 232 233 234 235 236 237 a preferred alternative to ampicillin in penicillin-allergic patients.118 121 286

Mycobacterial Infections

Treatment of cutaneous infections caused by Mycobacterium marinum;121 e alternative to minocycline.121

Nocardia Infections

Treatment of infections caused by Nocardia, including N. asteroides, N. brasiliensis, and N. caviae.121 286 Drugs of choice are co-trimoxazole121 286 or a sulfonamide alone (e.g., sulfisoxazole, sulfamethoxazole).286

Pertussis

Treatment of the catarrhal stage of pertussis to potentially ameliorate the disease and reduce its communicability.121 164 165 166 168 169 286 Recommended by CDC, AAP, and others as an alternative to erythromycin.121 164 286

Prevention of pertussis in household and other close contacts (e.g., day-care facility attendees) of patients with the disease.164 165 166 167 168 255 Alternative to erythromycin.164 165 166 167 168 255

Plague

Has been used for postexposure prophylaxis of plague.159 283 286 Although recommended by CDC and others for such prophylaxis in infants and children <8 years of age,159 283 286 efficacy of the drug for prevention of plague is unknown.286 Most experts (e.g., CDC, AAP, the US Working Group on Civilian Biodefense, US Army Medical Research Institute of Infectious Diseases) recommend oral ciprofloxacin or doxycycline for postexposure prophylaxis in adults and most children.286 309 310 Postexposure prophylaxis recommended after high-risk exposures to plague, including close exposure to individuals with naturally occurring plague, during unprotected travel in active epizootic or epidemic areas, or laboratory exposure to viable Yersinia pestis.159 283 286 309 310

Has been used for treatment of plague, but appears to be less effective than other anti-infectives used for treatment of the disease (e.g., streptomycin, gentamicin, tetracycline, doxycycline, chloramphenicol).309 311 Because of lack of efficacy, some experts state that co-trimoxazole should not be used for the treatment of pneumonic plague.309

Pneumocystis jiroveci (Pneumocystis carinii) Pneumonia

Treatment of Pneumocystis jiroveci (formerly Pneumocystis carinii) pneumonia (PCP).119 135 186 286 a Initial drug of choice for most patients with PCP,119 170 286 including HIV-infected individuals.100 104 105 148 149 150 151 152 153 170 241

Prevention of initial episodes of PCP (primary prophylaxis) in immunocompromised individuals at increased risk, including HIV-infected individuals.119 151 155 156 157 186 199 202 203 227 228 240 241 261 262 280 286 a Drug of choice.119 261 262 286 up to 14

Long-term suppressive or chronic maintenance therapy (secondary prophylaxis) to prevent recurrence following an initial PCP episode in immunocompromised patients, including HIV-infected individuals.119 199 202 203 227 228 241 262 280 286 Drug of choice.119 280 286

Toxoplasmosis

Prevention of toxoplasmosis encephalitis (primary prophylaxis) in HIV-infected adults, adolescents, and children who are seropositive for Toxoplasma IgG antibody.119 280 Drug of choice.280

Not recommended for long-term suppressive or chronic maintenance therapy (secondary prophylaxis) to prevent recurrence of toxoplasmosis encephalitis; regimen of choice for secondary prophylaxis of toxoplasmosis is sulfadiazine and pyrimethamine (with leucovorin).280

Typhoid Fever and Other Salmonella Infections

Alternative for treatment of typhoid fever (enteric fever) caused by susceptible Salmonella typhi.121 286 Drugs of choice are fluoroquinolones and third generation cephalosporins (e.g., ceftriaxone, cefotaxime);121 286 consider that multidrug-resistant strains of S. typhi (strains resistant to ampicillin, amoxicillin, chloramphenicol, and/or co-trimoxazole) reported with increasing frequency.121 286

Alternative for treatment of gastroenteritis caused by nontyphoidal Salmonella.121 286

Wegener’s Granulomatosis

Treatment of Wegener’s granulomatosis.122 123 133 146 147 207 c Effect on long-term morbidity and mortality unclear, but may prevent relapse and reduce need for cytotoxic (e.g., cyclophosphamide) and corticosteroid therapy in some patients.122 123 133 146 147 207 c

Whipple’s Disease

Treatment of Whipple’s disease caused by Tropheryma whippelii.121 Alternative or follow-up to penicillin G.121

Co-trimoxazole Dosage and Administration

Administration

Administer orallya or by IV infusion.135 Do not administer by rapid IV infusion or injection135 and do not administer IM.135

An adequate fluid intake should be maintained during co-trimoxazole therapy to prevent crystalluria and stone formation.135 a

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Dilution

Co-trimoxazole concentrate for injection must be diluted prior to IV infusion.135

Each 5 mL of the concentrate for injection containing 80 mg of trimethoprim should be added to 125 mL of 5% dextrose in water.135 In patients in whom fluid intake is restricted, each 5 mL of the concentrate may be added to 75 mL of 5% dextrose in water.135

Rate of Administration

IV solutions should be infused over a period of 60–90 minutes.135

Dosage

Available as fixed combination containing sulfamethoxazole and trimethoprim; dosage expressed as both the sulfamethoxazole and trimethoprim content or as the trimethoprim content.135 a b

Pediatric Patients

Acute Otitis Media
Oral

Children ≥2 months of age: 8 mg/kg of trimethoprim and 40 mg/kg of sulfamethoxazole daily in 2 divided doses every 12 hours.a Usual duration is 10 days.a

GI Infections
Shigella Infections
Oral

Children ≥2 months of age: 8 mg/kg of trimethoprim and 40 mg/kg of sulfamethoxazole daily in 2 divided doses every 12 hours.a Usual duration is 5 days.a

IV

Children ≥2 months of age: 8–10 mg/kg of trimethoprim daily (as co-trimoxazole) in 2–4 equally divided doses given for 5 days.135

Urinary Tract Infections (UTIs)
Oral

Children ≥2 months of age: 8 mg/kg of trimethoprim and 40 mg/kg of sulfamethoxazole daily in 2 divided doses every 12 hours.a Usual duration is 10 days.a

Severe UTIs
IV

Children ≥2 months of age: 8–10 mg/kg of trimethoprim daily (as co-trimoxazole) in 2–4 equally divided doses given for up to 14 days.135

Brucellosis
Oral

10 mg/kg daily (up to 480 mg daily) of trimethoprim (as co-trimoxazole) in 2 divided doses for 4–6 weeks.286

Cholera
Oral

4–5 mg/kg of trimethoprim (as co-trimoxazole) twice daily given for 3 days.283 286

Cyclospora Infections
Oral

5 mg/kg of trimethoprim and 25 mg/kg of sulfamethoxazole twice daily given for 7–10 days.119 HIV-infected patients may require higher dosage and longer treatment.119

Granuloma Inguinale (Donovanosis)
Oral

Adolescents: 160 mg of trimethoprim and 800 mg of sulfamethoxazole twice daily given for ≥3 weeks or until all lesions have healed completely;116 consider adding IV aminoglycoside (e.g., gentamicin) if improvement is not evident within the first few days of therapy and in HIV-infected patients.116

Relapse can occur 6–18 months after apparently effective treatment.116

Isosporiasis
Oral

5 mg/kg of trimethoprim and 25 mg/kg of sulfamethoxazole twice daily.119 Usual duration of treatment is 10 days; higher dosage or more prolonged treatment necessary in immunocompromised patients.119

Pertussis
Oral

8 mg/kg of trimethoprim and 40 mg/kg of sulfamethoxazole daily in 2 divided doses.164 286 Usual duration is 14 days for treatment or prevention.164 222 223 224 225 226 286

Plague
Postexposure Prophylaxis
Oral

Children ≥2 months of age: 320–640 mg of trimethoprim (as co-trimoxazole) daily in 2 divided doses given for 7 days.283 Alternatively, 8 mg/kg daily of trimethoprim (as co-trimoxazole) in 2 divided doses given for 7 days.283

Pneumocystis jiroveci (Pneumocystis carinii) Pneumonia
Treatment
Oral

Children ≥2 months of age: 15–20 mg/kg of trimethoprim and 75–100 mg/kg of sulfamethoxazole daily in 3 or 4 divided doses.119 286 a Usual duration is 14–21 days.119 286 a

IV

Children ≥2 months of age: 15–20 mg/kg of trimethoprim daily (as co-trimoxazole) in 3 or 4 equally divided doses.119 135 286 Usual duration is 14–21 days.119 286 a

Primary Prophylaxis in Infants and Children
Oral

150 mg/m2 of trimethoprim and 750 mg/m2 of sulfamethoxazole daily in 2 divided doses given on 3 consecutive days each week.119 186 280 286 a Total daily dose should not exceed 320 mg of trimethoprim and 1.6 g of sulfamethoxazole.a

Alternatively, 150 mg/m2 of trimethoprim and 750 mg/m2 of sulfamethoxazole can be administered as a single dose 3 times each week on consecutive days, in 2 divided doses daily 7 days each week, or in 2 divided daily doses given 3 times each week on alternate days.280 286

CDC, USPHS/IDSA, AAP, and others recommend that primary prophylaxis be initiated in all infants born to HIV-infected women starting at 4–6 weeks of age, regardless of their CD4+ T-cell count.280 282 286 Infants who are first identified as being HIV-exposed after 6 weeks of age should receive primary prophylaxis beginning at the time of identification.282

Primary prophylaxis should be continued until 12 months of age in all HIV-infected infants and infants whose infection status has not yet been determined;280 282 it can be discontinued in those found not to be HIV-infected.280 282

The need for subsequent prophylaxis should be based on age-specific CD4+ T-cell count thresholds.280 282 In HIV-infected children 1–5 years of age, primary prophylaxis should be initiated if CD4+ T-cell counts are <500/mm3 or CD4+ percentage is <15%.280 282 In HIV-infected children 6–12 years of age, primary prophylaxis should be initiated if CD4+ T-cell counts are <200/mm3 or CD4+ percentage is <15%.280 282

The safety of discontinuing prophylaxis in HIV-infected children receiving potent antiretroviral therapy has not been extensively studied.280

Prevention of Recurrence (Secondary Prophylaxis) in Infants and Children
Oral

150 mg/m2 of trimethoprim and 750 mg/m2 of sulfamethoxazole daily in 2 divided doses given on 3 consecutive days each week.119 186 280 a Total daily dose should not exceed 320 mg of trimethoprim and 1.6 g of sulfamethoxazole.a

Alternatively, 150 mg/m2 of trimethoprim and 750 mg/m2 of sulfamethoxazole can be administered as a single daily dose given for 3 consecutive days each week, in 2 divided doses daily, or in 2 divided daily doses given 3 times a week on alternate days.280

The safety of discontinuing secondary prophylaxis in HIV-infected children receiving potent antiretroviral therapy has not been extensively studied.280 Children who have a history of PCP should receive life-long suppressive therapy to prevent recurrence.280

Primary and Secondary Prophylaxis in Adolescents
Oral

Dosage for primary or secondary prophylaxis against P. jiroveci pneumonia in adolescents and criteria for initiation or discontinuance of such prophylaxis in this age group are the same as those recommended for adults.280 (See Adult Dosage under Dosage and Administration.)

Toxoplasmosis
Primary Prophylaxis in Infants and Children
Oral

150 mg/m2 of trimethoprim and 750 mg/m2 of sulfamethoxazole daily in 2 divided doses.280

The safety of discontinuing toxoplasmosis prophylaxis in HIV-infected children receiving potent antiretroviral therapy has not been extensively studied.280

Primary Prophylaxis in Adolescents
Oral

Dosage for primary prophylaxis against toxoplasmosis in adolescents and criteria for initiation or discontinuance of such prophylaxis in this age group are the same as those recommended for adults.280 (See Adult Dosage under Dosage and Administration.)

Adults

GI Infections
Treatment of Travelers’ Diarrhea
Oral

160 mg of trimethoprim and 800 mg of sulfamethoxazole every 12 hours given for 3–5 days.112 183 186 242 256 257 306 a A single 320-mg dose of trimethoprim (as co-trimoxazole) also has been used.242 306

Prevention of Travelers’ Diarrhea
Oral

160 mg of trimethoprim and 800 mg of sulfamethoxazole once daily during the period of risk.256 257 Use of anti-infectives for prevention of travelers’ diarrhea generally is discouraged.112 180 186 242 256 257 306

Shigella Infections
Oral

160 mg of trimethoprim and 800 mg of sulfamethoxazole every 12 hours given for 5 days.a

IV

8–10 mg/kg of trimethoprim daily (as co-trimoxazole) in 2–4 equally divided doses given for 5 days.135

Respiratory Tract Infections
Acute Exacerbations of Chronic Bronchitis
Oral

160 mg of trimethoprim and 800 mg of sulfamethoxazole every 12 hours given for 14 days.a

Urinary Tract Infections (UTIs)
Oral

160 mg of trimethoprim and 800 mg of sulfamethoxazole every 12 hours.a

Usual duration of treatment is 10–14 days.a A 3-day regimen may be effective for acute, uncomplicated cystitis in women.121 163

Severe UTIs
IV

8–10 mg/kg of trimethoprim daily (as co-trimoxazole) in 2–4 equally divided doses given for up to 14 days.135

Cholera
Oral

160 mg of trimethoprim and 800 mg of sulfamethoxazole every 12 hours given for 3 days.231

Cyclospora Infections
Oral

160 mg of trimethoprim and 800 mg of sulfamethoxazole twice daily given for 7–10 days.119 HIV-infected patients may require higher dosage and longer-term treatment.119

Granuloma Inguinale (Donovanosis)
Oral

160 mg of trimethoprim and 800 mg of sulfamethoxazole twice daily given for ≥3 weeks or until all lesions have healed completely;116 consider adding IV aminoglycoside (e.g., gentamicin) if improvement is not evident within the first few days of therapy and in HIV-infected patients.116

Relapse can occur 6–18 months after apparently effective treatment.116

Isosporiasis
Oral

160 mg of trimethoprim and 800 mg of sulfamethoxazole twice daily.119 Usual duration of treatment is 10 days; higher dosage or more prolonged treatment necessary in immunocompromised patients.119

Mycobacterial Infections
Mycobacterium marinum Infections
Oral

160 mg of trimethoprim and 800 mg of sulfamethoxazole twice daily given for ≥3 months recommended by ATS for treatment of cutaneous infections.c A minimum of 4–6 weeks of treatment usually is necessary to determine whether the infection is responding.c

Pertussis
Oral

320 mg of trimethoprim (as co-trimoxazole) daily in 2 divided doses.164 166 168 Usual duration is 14 days for treatment or prevention.164 222 223 224 225 226 286

Pneumocystis jiroveci (Pneumocystis carinii) Pneumonia
Treatment
Oral

15–20 mg/kg of trimethoprim and 75–100 mg/kg of sulfamethoxazole daily in 3 or 4 divided doses.119 170 186 a Usual duration is 14–21 days.119 a

IV

15–20 mg/kg of trimethoprim daily in 3 or 4 equally divided doses every 6 or 8 hours given for up to 14 days.135 Some clinicians recommend 15 mg/kg of trimethoprim and 75 mg/kg of sulfamethoxazole daily in 3 or 4 divided doses for 14–21 days.119

Primary Prophylaxis
Oral

160 mg of trimethoprim and 800 mg of sulfamethoxazole once daily.119 186 227 240 241 243 280 a Alternatively, 80 mg of trimethoprim and 400 mg of sulfamethoxazole can be given once daily.119 280

Initiate primary prophylaxis in patients with CD4+ T-cell counts <200/mm3 or a history of oropharyngeal candidiasis.280 Also consider primary prophylaxis if CD4+ T-cell percentage is <14% or there is a history of an AIDS-defining illness.280

Primary prophylaxis can be discontinued in adults and adolescents responding to potent antiretroviral therapy who have a sustained (≥3 months) increase in CD4+ T-cell counts from <200/mm3 to >200/mm3.199 280 281 287 312 313 314 315 316 However, it should be restarted if CD4+ T-cell count decreases to <200/mm3.280

Prevention of Recurrence (Secondary Prophylaxis)
Oral

160 mg of trimethoprim and 800 mg of sulfamethoxazole once daily.119 280 Alternatively, 80 mg of trimethoprim and 400 mg of sulfamethoxazole can be given once daily.119 280

Initiate long-term suppressive therapy or chronic maintenance therapy (secondary prophylaxis) in those with a history of P. jiroveci pneumonia to prevent recurrence.280

Discontinuance of secondary prophylaxis is recommended in those who have a sustained (≥3 months) increase in CD4+ T-cell counts to >200/mm3 since such prophylaxis appears to add little benefit in terms of disease prevention and discontinuance reduces the medication burden, the potential for toxicity, drug interactions, selection of drug-resistant pathogens, and cost.280

Reinitiate secondary prophylaxis if CD4+ T-cell count decreases to <200/mm3 or if P. jiroveci pneumonia recurs at a CD4+ T-cell >200/mm3.280 It probably is prudent to continue secondary prophylaxis for life in those who had P. jiroveci episodes when they had CD4+ T-cell counts >200/mm3.280

Toxoplasmosis
Primary Prophylaxis
Oral

160 mg of trimethoprim and 800 mg of sulfamethoxazole once daily.280 Alternatively, 80 mg of trimethoprim and 400 mg of sulfamethoxazole may be used.280

Initiate primary prophylaxis against toxoplasmosis in HIV-infected adults and adolescents who are seropositive for Toxoplasma IgG antibody and have CD4+ T-cell counts <100/mm3.280

Consideration can be given to discontinuing primary prophylaxis in adults and adolescents who have a sustained (≥3 months) increase in CD4+ T-cell counts to >200/mm3 since such prophylaxis appears to add little benefit in terms of disease prevention for toxoplasmosis, and discontinuance reduces the pill burden, the potential for toxicity, drug interactions, selection of drug-resistant pathogens, and cost.280

Reinitiate primary prophylaxis against toxoplasmosis if CD4+ T-cell count decreases to <100–200/mm3.280

Wegener’s Granulomatosis
Oral

160 mg of trimethoprim and 800 mg of sulfamethoxazole twice daily.c

Special Populations

Renal Impairment

In patients with Clcr 15–30 mL/minute, use 50% of usual dosage.135 a

Use not recommended in those with Clcr <15 mL/minute.135 a

Geriatric Patients

No dosage adjustments except those related to renal impairment.135 (See Renal Impairment under Dosage and Administration.)

Cautions for Co-trimoxazole

Contraindications

  • Known hypersensitivity to sulfonamides or trimethoprim.135 a

  • Documented megaloblastic anemia due to folate deficiency.135 a

  • Children <2 months of age, pregnant women at term, and nursing women.135 a

Warnings/Precautions

Warnings

Severe Reactions related to the Sulfonamide Component

Severe (sometimes fatal) reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias, have been reported with sulfonamides.135 a

Rash, sore throat, fever, arthralgia, pallor, purpura, or jaundice may be early indications of serious reactions.135 a Discontinue co-trimoxazole at the first appearance of rash or any sign of adverse reactions.135 a

Superinfection/Clostridium difficile-associated Colitis

Possible emergence and overgrowth of nonsusceptible bacteria or fungi.135 a Institute appropriate therapy if superinfection occurs.135 a

Treatment with anti-infectives may permit overgrowth of clostridia.135 a Consider Clostridium difficile-associated diarrhea and colitis (antibiotic-associated pseudomembranous colitis) if diarrhea develops and manage accordingly.135 a

Some mild cases of C. difficile-associated diarrhea and colitis may respond to discontinuance alone.135 a Manage moderate to severe cases with fluid, electrolyte, and protein supplementation; appropriate anti-infective therapy (e.g., oral metronidazole or vancomycin) recommended if colitis is severe.135 a

Sensitivity Reactions

Hypersensitivity Reactions

Cough, shortness of breath, and pulmonary infiltrates are hypersensitivity reactions of the respiratory tact that have been reported with sulfonamides.135 a

Use with caution in patients with severe allergy or bronchial asthma.a

Sulfite Sensitivity

Concentrate for injection contains a sulfite, which may cause allergic-type reactions (including anaphylaxis and life-threatening or less severe asthmatic episodes) in certain susceptible individuals.135

General Precautions

Patients with Folate Deficiency or G6PD Deficiency

Hemolysis may occur in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency; this effect may be dose-related.a

Use with caution in patient with possible folate deficiency (e.g., geriatric patients, chronic alcoholics, patients receiving anticonvulsant therapy, patients with malabsorption syndrome, patients with malnutrition).135 a

Patients with Pneumocystis jiroveci (Pneumocystis carinii) Pneumonia

HIV-infected patients with Pneumocystis jiroveci pneumonia may have an increased incidence of adverse effects during co-trimoxazole therapy (particularly rash, fever, leukopenia, increased liver enzymes) compared with HIV-seronegative patients.135 a The incidence of hyperkalemia and hyponatremia also may be increased in HIV-infected patients.135 a

Adverse effects generally are less severe in those receiving co-trimoxazole for prophylaxis rather than treatment.a

A history of mild intolerance to co-trimoxazole in HIV-infected patients does not appear to predict intolerance to subsequent use of the drug for secondary prophylaxis.a However, use of the drug should be reevaluated in patients who develop rash or any sign of adverse reaction.a

Concomitant use of leucovorin and co-trimoxazole for acute treatment of P. jiroveci pneumonia in HIV-infected patients has been associated with increased rates of treatment failure and morbidity.a

Laboratory Monitoring

Perform CBCs frequently during co-trimoxazole therapy; discontinue the drug if a significant reduction in any formed blood element occurs.135 a

Perform urinalysis with careful microscopic examination and renal function tests during co-trimoxazole therapy, especially in patients with impaired renal function.135 a

Selection and Use of Anti-infectives

To reduce development of drug-resistant bacteria and maintain effectiveness of co-trimoxazole and other antibacterials, use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.b

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.135

Because S. pyogenes (group A β-hemolytic streptococci) may not be eradicated by co-trimoxazole, do not use the drug for treatment of infections caused by this organism since it cannot prevent sequelae such as rheumatic fever.135 a

Specific Populations

Pregnancy

Category C.135 a

Because sulfonamides may cause kernicterus in neonates, co-trimoxazole is contraindicated in pregnant women at term.135 a

Lactation

Both sulfamethoxazole and trimethoprim distributed into milk.a Co-trimoxazole contraindicated in nursing women.135 a

Pediatric Use

Safety and efficacy not established in children <2 months of age.135 a

Geriatric Use

Geriatric patients may be at increased risk of severe adverse reactions, particularly if they have impaired hepatic and/or renal function or are receiving concomitant drug therapy.135 a

The most frequent adverse reactions in geriatric patients are severe skin reactions, generalized bone marrow suppression, or a specific decrease in platelets (with or without purpura).135 a Those receiving concurrent therapy with a diuretic (principally thiazides) are at increased risk of thrombocytopenia with purpura.135 a

Dosage adjustments are necessary based on age-related decreases in renal function.a

Hepatic Impairment

Use with caution in patients with impaired hepatic function.135 a

Renal Impairment

Use reduced dosage in patients with Clcr 15–30 mL/minute.135 a

Do not use in patients with Clcr <15 mL/minute.135 a

Common Adverse Effects

GI effects (nausea, vomiting, anorexia); dermatologic and sensitivity reactions (rash, urticaria).135 b

Interactions for Co-trimoxazole

Specific Drugs and Laboratory Tests

Drug or Test

Interaction

Comments

Amantadine

Toxic delirium reported in an individual who received amantadine and co-trimoxazole concomitantly186

Antidepressants, tricyclics

Possible decreased efficacy of the tricyclic antidepressant186

Cyclosporine

Reversible nephrotoxicity reported in renal transplant recipients receiving cyclosporine and co-trimoxazole concomitantly186

Digoxin

Possible increased digoxin concentrations, especially in geriatric patients186

Monitor serum digoxin concentrations in patients receiving co-trimoxazole concomitantly186

Diuretics

Possible increased incidence of thrombocytopenia and purpura if certain diuretics (principally thiazides) are used concomitantly, especially in geriatric patients135 a

Hypoglycemic agents, oral

Possible potentiation of hypoglycemic effects186

Indomethacin

Possible increased sulfamethoxazole concentrations186

Methotrexate

Co-trimoxazole can displace methotrexate from plasma protein-binding sites resulting in increased free methotrexate concentrations135 a b

Possible interference with serum methotrexate assays if competitive protein binding technique is used with a bacterial dihydrofolate reductase as the binding protein; interference does not occur if methotrexate is measured using radioimmunoassay135 a

Use caution if methotrexate and co-trimoxazole used concomitantlyb

Phenytoin

Co-trimoxazole may inhibit metabolism and increase half-life of phenytoin135 186 a

Monitor for possible increased phenytoin effects135 186 a

Pyrimethamine

Megaloblastic anemia reported when co-trimoxazole used concomitantly with pyrimethamine dosages >25 mg weekly (for malaria prophylaxis)186

Tests for creatinine

Possible interference with Jaffe alkaline picrate assay resulting in falsely elevated creatinine concentrations135 a

Warfarin

Possible inhibition of warfarin clearance and prolonged PT135 a b

Monitor PT closely and adjust warfarin dosage if co-trimoxazole used concomitantly135 a b

Co-trimoxazole Pharmacokinetics

Absorption

Bioavailability

Sulfamethoxazole and trimethoprim are rapidly and well absorbed from the GI tract following oral administration of the fixed combination preparation (co-trimoxazole).a b Peak serum concentrations of both sulfamethoxazole and trimethoprim are attained within 1–4 hours.a b

Co-trimoxazole contains a 1:5 ratio of trimethoprim to sulfamethoxazole, but the trimethoprim:sulfamethoxazole ratio in serum after administration of the fixed-combination preparation is about 1:20 at steady-state.b

Distribution

Extent

Widely distributed into body tissues and fluids, including sputum, aqueous humor, middle ear fluid, bronchial secretions, prostatic fluid, vaginal fluid, and bile.a b

In patients with uninflamed meninges, trimethoprim and sulfamethoxazole concentrations in CSF are about 50 and 40%, respectively, of concurrent serum concentrations.b

Both sulfamethoxazole and trimethoprim readily cross the placenta and are distributed into milk.a b

Plasma Protein Binding

Sulfamethoxazole is approximately 70% and trimethoprim is approximately 44% bound to plasma proteins.a b Presence of sulfamethoxazole decreases protein binding of trimethoprim.a

Elimination

Metabolism

Both sulfamethoxazole and trimethoprim are metabolized in the liver.b

Elimination Route

Both sulfamethoxazole and trimethoprim are rapidly excreted in urine by glomerular filtration and active tubular secretion.a b In adults with normal renal function, approximately 45–85% of a sulfamethoxazole dose and 50–67% of a trimethoprim dose are excreted in urine.a b

Only small amounts of trimethoprim are excreted in feces via biliary elimination.b

Half-life

Serum half-lives of sulfamethoxazole and trimethoprim are approximately 10–13 and 8–11 hours, respectively, in adults with normal renal function.a b

Special Populations

Patients with impaired renal function: Half-lives of both sulfamethoxazole and trimethoprim may be prolonged.a b

In adults with Clcr≤10 mL/minute, serum half-life of trimethoprim may increase to >26 hours.b In adults with chronic renal failure, sulfamethoxazole half-life may be 3 times that in patients with normal renal function.b

Stability

Storage

Oral

Tablets

15–25°C;a protect from light.a

Suspension

15–25°C;a protect from light.a

Parenteral

Concentrate for Injection

5–25°C;135 do not refrigerate.135

Following dilution in 125 or 100 mL of 5% dextrose in water, use within 6 or 4 hours, respectively.135 If diluted in 75 mL of 5% dextrose in water, use within 2 hours.135

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution CompatibilityHID

Compatible

Dextrose 5% in sodium chloride 0.45%

Ringer’s injection, lactated

Sodium chloride 0.45%

Variable

Dextrose 5% in water

Sodium chloride 0.9%

Drug Compatibility
Admixture CompatibilityHID

Incompatible

Fluconazole

Linezolid

Verapamil HCl

Y-Site CompatibilityHID

Compatible

Acyclovir sodium

Aldesleukin

Allopurinol sodium

Amifostine

Amphotericin B cholesteryl sulfate complex

Anidulafungin

Atracurium besylate

Aztreonam

Bivalirudin

Ceftaroline fosamil

Cyclophosphamide

Dexmedetomidine HCl

Diltiazem HCl

Docetaxel

Doxorubicin HCl liposome injection

Enalaprilat

Esmolol HCl

Etoposide phosphate

Fenoldopam mesylate

Filgrastim

Fludarabine phosphate

Gallium nitrate

Gemcitabine HCl

Granisetron HCl

Hetastarch in lactated electrolyte injection (Hextend)

Hydromorphone HCl

Labetalol HCl

Lorazepam

Magnesium sulfate

Melphalan HCl

Meperidine HCl

Morphine sulfate

Nicardipine HCl

Pancuronium bromide

Pemetrexed disodium

Piperacillin sodium-tazobactam sodium

Remifentanil HCl

Sargramostim

Tacrolimus

Teniposide

Thiotepa

Vecuronium bromide

Zidovudine

Incompatible

Caspofungin acetate

Fluconazole

Midazolam HCl

Vinorelbine tartrate

Variable

Cisatracurium besylate

Foscarnet sodium

Actions and Spectrum

  • A fixed combination of sulfamethoxazole and trimethoprim; both drugs are folate-antagonists and sequentially inhibit enzymes of the folic acid pathway in susceptible bacteria.b

  • Sulfamethoxazole inhibits formation of dihydrofolic acid from p-aminobenzoic acid and trimethoprim inhibits formation of tetrahydrofolic acid (the metabolically active form of folic acid).b

  • Sulfamethoxazole is bacteriostatic and trimethoprim usually is bactericidal; the fixed combination generally is bactericidal when synergism is achieved.b

  • Susceptibility to trimethoprim is more critical to efficacy of co-trimoxazole than susceptibility to sulfamethoxazole.b Co-trimoxazole is active against many organisms resistant to sulfamethoxazole but susceptible to trimethoprim.b

  • Spectrum of activity includes many gram-positive and -negative aerobic bacteria and some protozoa.b Inactive against most anaerobic bacteria and inactive against fungi and viruses.b

  • Gram-positive aerobes: Active against Staphylococcus aureus (including penicillinase-producing strains), Streptococcus pneumoniae, S. pyogenes (group A β-hemolytic streptococci), and some strains of enterococci (e.g., Enterococcus faecalis).a b Also active against Nocardia,b but Bacillus anthracis may be resistant.307 308

  • Gram-negative aerobes: Active against Acinetobacter, Enterobacter, Escherichia coli, Klebsiella pneumoniae, Morganella morganii, Proteus mirabilis, Salmonella, and Shigella.a b Also active against Haemophilus influenzae (including ampicillin-resistant strains), H. ducreyi, and Neisseria gonorrhoeae.a b Pseudomonas aeruginosa is resistant.a

  • Other organisms: Active in vitro and in vivo against Pneumocystis jiroveci (Pneumocystis carinii).b Most anaerobes, including Bacteroides and Clostridium, are resistant.b

  • Resistance to co-trimoxazole has been reported in some Enterobacteriaceae and H. influenzae.b

Advice to Patients

  • Importance of completing full course of therapy, even if feeling better after a few days.a

  • Advise patients to maintain an adequate fluid intake to prevent crystalluria and stone formation.135 a

  • Importance of discontinuing drug and informing clinician if rash or any sign of adverse reaction (sore throat, fever, arthralgia, pallor, purpura, jaundice) occurs.135 a

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

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

  • Importance of advising patients of other important precautionary information.a (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Co-trimoxazole

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Suspension

Trimethoprim 40 mg/5 mL and Sulfamethoxazole 200 mg/5 mL*

Septra Suspension

Monarch

Septra Grape Suspension

Monarch

Sulfatrim Pediatric Suspension

Alpharma

Sulfatrim Suspension

Alpharma, United Research

Tablets

Trimethoprim 80 mg and Sulfamethoxazole 400 mg*

Bactrim (scored)

Women First HealthCare

Septra (scored)

Monarch

Sulfamethoxazole and Trimethoprim Tablets

Trimethoprim 160 mg and Sulfamethoxazole 800 mg*

Bactrim DS

Women First HealthCare

Septra DS (scored)

Monarch

Parenteral

For injection concentrate, for IV infusion

Trimethoprim 16 mg/mL and Sulfamethoxazole 80 mg/mL

Sulfamethoxazole and Trimethoprim Concentrate for Injection

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Bactrim 400-80MG Tablets (AR SCIENTIFIC): 30/$49.99 or 90/$142.97

Bactrim DS 800-160MG Tablets (AR SCIENTIFIC): 30/$89.99 or 90/$257.96

Septra DS 800-160MG Tablets (MONARCH PHARMACEUTICALS): 30/$72.79 or 90/$203.82

Sulfamethoxazole-TMP DS 800-160MG Tablets (QUALITEST): 30/$20.99 or 90/$43.97

Sulfamethoxazole-Trimethoprim 200-40MG/5ML Suspension (HI-TECH): 200/$18.99 or 400/$29.97

Sulfamethoxazole-Trimethoprim 400-80MG Tablets (QUALITEST): 30/$15.99 or 60/$22.98

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions September 4, 2013. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

Only references cited for selected revisions after 1984 are available electronically.

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