supper time [2:<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 orally a or by IV infusion. 135 Do not administer by rapid IV infusion or injection 135 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/m 2 of trimethoprim and 750 mg/m 2 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/m 2 of trimethoprim and 750 mg/m 2 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/mm 3 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/mm 3 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/m 2 of trimethoprim and 750 mg/m 2 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/m 2 of trimethoprim and 750 mg/m 2 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/m 2 of trimethoprim and 750 mg/m 2 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/mm 3 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/mm 3 to> 200/mm 3 . 199 280 281 287 312 313 314 315 316 However, it should be restarted if CD4 + T-cell count decreases to <200/mm 3 . 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/mm 3 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/mm 3 or if P. jiroveci pneumonia recurs at a CD4 + T-cell> 200/mm 3 . 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/mm 3 . 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/mm 3 . 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/mm 3 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/mm 3 . 280 Wegener s Granulomatosis Oral 160 mg of trimethoprim and 800 mg of sulfamethoxazole twice daily. c Special Populations Renal Impairment In patients with Cl cr 15 30 mL/minute, use 50% of usual dosage. 135 a Use not recommended in those with Cl cr> <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 Cl cr 15 30 mL/minute. 135 a Do not use in patients with Cl cr> <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 concomitantly 186 Antidepressants, tricyclics Possible decreased efficacy of the tricyclic antidepressant 186 Cyclosporine Reversible nephrotoxicity reported in renal transplant recipients receiving cyclosporine and co-trimoxazole concomitantly 186 Digoxin Possible increased digoxin concentrations, especially in geriatric patients 186 Monitor serum digoxin concentrations in patients receiving co-trimoxazole concomitantly 186 Diuretics Possible increased incidence of thrombocytopenia and purpura if certain diuretics (principally thiazides) are used concomitantly, especially in geriatric patients 135 a Hypoglycemic agents, oral Possible potentiation of hypoglycemic effects 186 Indomethacin Possible increased sulfamethoxazole concentrations 186 Methotrexate Co-trimoxazole can displace methotrexate from plasma protein-binding sites resulting in increased free methotrexate concentrations 135 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 radioimmunoassay 135 a Use caution if methotrexate and co-trimoxazole used concomitantly b Phenytoin Co-trimoxazole may inhibit metabolism and increase half-life of phenytoin 135 186 a Monitor for possible increased phenytoin effects 135 186 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 concentrations 135 a Warfarin Possible inhibition of warfarin clearance and prolonged PT 135 a b Monitor PT closely and adjust warfarin dosage if co-trimoxazole used concomitantly 135 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 Cl cr 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 Compatibility HID 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. Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations. * 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 fo a terribly
geared toward Co-trimoxazole is incredibly
EmoticonEmoticon