Co-trimoxazole

Drug class: Antineoplastic Agents

Usage of Co-trimoxazole

Acute Otitis Media

Treatment of acute otitis media (AOM) in adults† [off-label] and children caused by susceptible Streptococcus pneumoniae or Haemophilus influenzae when the clinician makes the judgment that the drug offers some advantage over use of a single anti-infective.

Not a drug of first choice; considered an alternative for treatment of AOM, especially for those with type I penicillin hypersensitivity. 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.

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.

GI Infections

Treatment of travelers’ diarrhea caused by susceptible enterotoxigenic Escherichia coli. Replacement therapy with oral fluids and electrolytes may be sufficient for mild to moderate disease; 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. Fluoroquinolones (ciprofloxacin, levofloxacin, norfloxacin, ofloxacin) usually drugs of choice when treatment indicated; co-trimoxazole also has been recommended as an alternative when fluoroquinolones cannot be used (e.g., in children).

Prevention of travelers’ diarrhea† [off-label] 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. CDC and others do not recommend anti-infective prophylaxis in most individuals traveling to areas of risk; the principal preventive measures are prudent dietary practices. If prophylaxis is used (e.g., in immunocompromised individuals such as those with HIV infection), a fluoroquinolone (ciprofloxacin, levofloxacin, ofloxacin, norfloxacin) is preferred. Resistance to co-trimoxazole is common in many tropical areas.

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

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

Treatment of diarrhea caused by enterotoxigenic E. coli† [off-label] (ETEC) in travelers to resource-limited countries. 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. A parenteral regimen should be used if systemic infection is suspected.

Role of anti-infectives in treatment of hemorrhagic colitis caused by shiga toxin-producing E. coli† [off-label] (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.

Treatment of GI infections caused by Yersinia enterocolitica† or Y. pseudotuberculosis†. 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. 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.

Respiratory Tract Infections

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

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

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

Urinary Tract Infections (UTIs)

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

Brucellosis

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

Burkholderia Infections

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

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

Cholera

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

Cyclospora Infections

Treatment of infections caused by Cyclospora cayetanensis†. The drug of choice.

Granuloma Inguinale (Donovanosis)

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

Isosporiasis

Treatment of isosporiasis† caused by Isospora belli. The drug of choice.

Listeria Infections

Treatment of infections caused by Listeria monocytogenes†; a preferred alternative to ampicillin in penicillin-allergic patients.

Mycobacterial Infections

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

Nocardia Infections

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

Pertussis

Treatment of the catarrhal stage of pertussis† to potentially ameliorate the disease and reduce its communicability. Recommended by CDC, AAP, and others as an alternative to erythromycin.

Prevention of pertussis† in household and other close contacts (e.g., day-care facility attendees) of patients with the disease. Alternative to erythromycin.

Plague

Has been used for postexposure prophylaxis of plague†. Although recommended by CDC and others for such prophylaxis in infants and children <8 years of age, efficacy of the drug for prevention of plague is unknown. 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. 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.

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). Because of lack of efficacy, some experts state that co-trimoxazole should not be used for the treatment of pneumonic plague.

Pneumocystis jiroveci (Pneumocystis carinii) Pneumonia

Treatment of Pneumocystis jiroveci (formerly Pneumocystis carinii) pneumonia (PCP). Initial drug of choice for most patients with PCP, including HIV-infected individuals.

Prevention of initial episodes of PCP (primary prophylaxis) in immunocompromised individuals at increased risk, including HIV-infected individuals. Drug of choice. 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. Drug of choice.

Toxoplasmosis

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

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).

Typhoid Fever and Other Salmonella Infections

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

Alternative for treatment of gastroenteritis caused by nontyphoidal Salmonella†.

Wegener’s Granulomatosis

Treatment of Wegener’s granulomatosis†. 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.

Whipple’s Disease

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

Relate drugs

How to use Co-trimoxazole

Administration

Administer orally or by IV infusion. Do not administer by rapid IV infusion or injection and do not administer IM.

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

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.

Each 5 mL of the concentrate for injection containing 80 mg of trimethoprim should be added to 125 mL of 5% dextrose in water. 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.

Rate of Administration

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

Dosage

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

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. Usual duration is 10 days.

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. Usual duration is 5 days.

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.

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. Usual duration is 10 days.

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.

Brucellosis† Oral

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

Cholera† Oral

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

Cyclospora Infections† Oral

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

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; consider adding IV aminoglycoside (e.g., gentamicin) if improvement is not evident within the first few days of therapy and in HIV-infected patients.

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

Isosporiasis† Oral

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

Pertussis† Oral

8 mg/kg of trimethoprim and 40 mg/kg of sulfamethoxazole daily in 2 divided doses. Usual duration is 14 days for treatment or prevention.

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. Alternatively, 8 mg/kg daily of trimethoprim (as co-trimoxazole) in 2 divided doses given for 7 days.

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. Usual duration is 14–21 days.

IV

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

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. Total daily dose should not exceed 320 mg of trimethoprim and 1.6 g of sulfamethoxazole.

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.

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. Infants who are first identified as being HIV-exposed after 6 weeks of age should receive primary prophylaxis beginning at the time of identification.

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; it can be discontinued in those found not to be HIV-infected.

The need for subsequent prophylaxis should be based on age-specific CD4+ T-cell count thresholds. 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%. 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%.

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

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. Total daily dose should not exceed 320 mg of trimethoprim and 1.6 g of sulfamethoxazole.

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.

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

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. (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.

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

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. (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. A single 320-mg dose of trimethoprim (as co-trimoxazole) also has been used.

Prevention of Travelers’ Diarrhea Oral

160 mg of trimethoprim and 800 mg of sulfamethoxazole once daily during the period of risk. Use of anti-infectives for prevention of travelers’ diarrhea generally is discouraged.

Shigella Infections Oral

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

IV

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

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.

Urinary Tract Infections (UTIs) Oral

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

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

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.

Cholera† Oral

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

Cyclospora Infections† Oral

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

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; consider adding IV aminoglycoside (e.g., gentamicin) if improvement is not evident within the first few days of therapy and in HIV-infected patients.

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

Isosporiasis† Oral

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

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. A minimum of 4–6 weeks of treatment usually is necessary to determine whether the infection is responding.

Pertussis† Oral

320 mg of trimethoprim (as co-trimoxazole) daily in 2 divided doses. Usual duration is 14 days for treatment or prevention.

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. Usual duration is 14–21 days.

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. 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.

Primary Prophylaxis Oral

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

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

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. However, it should be restarted if CD4+ T-cell count decreases to <200/mm3.

Prevention of Recurrence (Secondary Prophylaxis) Oral

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

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

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.

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. 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.

Toxoplasmosis† Primary Prophylaxis Oral

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

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.

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.

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

Wegener’s Granulomatosis† Oral

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

Special Populations

Renal Impairment

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

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

Geriatric Patients

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

Warnings

Contraindications

  • Known hypersensitivity to sulfonamides or trimethoprim.
  • Documented megaloblastic anemia due to folate deficiency.
  • Children <2 months of age, pregnant women at term, and nursing women.

    • 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.

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

    Superinfection/Clostridium difficile-associated Colitis

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

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

    Some mild cases of C. difficile-associated diarrhea and colitis may respond to discontinuance alone. 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.

    Sensitivity Reactions

    Hypersensitivity Reactions

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

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

    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.

    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.

    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).

    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. The incidence of hyperkalemia and hyponatremia also may be increased in HIV-infected patients.

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

    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. However, use of the drug should be reevaluated in patients who develop rash or any sign of adverse reaction.

    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.

    Laboratory Monitoring

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

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

    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.

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

    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.

    Specific Populations

    Pregnancy

    Category C.

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

    Lactation

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

    Pediatric Use

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

    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.

    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). Those receiving concurrent therapy with a diuretic (principally thiazides) are at increased risk of thrombocytopenia with purpura.

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

    Hepatic Impairment

    Use with caution in patients with impaired hepatic function.

    Renal Impairment

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

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

    Common Adverse Effects

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

    What other drugs will affect 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

    Antidepressants, tricyclics

    Possible decreased efficacy of the tricyclic antidepressant

    Cyclosporine

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

    Digoxin

    Possible increased digoxin concentrations, especially in geriatric patients

    Monitor serum digoxin concentrations in patients receiving co-trimoxazole concomitantly

    Diuretics

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

    Hypoglycemic agents, oral

    Possible potentiation of hypoglycemic effects

    Indomethacin

    Possible increased sulfamethoxazole concentrations

    Methotrexate

    Co-trimoxazole can displace methotrexate from plasma protein-binding sites resulting in increased free methotrexate concentrations

    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

    Use caution if methotrexate and co-trimoxazole used concomitantly

    Phenytoin

    Co-trimoxazole may inhibit metabolism and increase half-life of phenytoin

    Monitor for possible increased phenytoin effects

    Pyrimethamine

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

    Tests for creatinine

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

    Warfarin

    Possible inhibition of warfarin clearance and prolonged PT

    Monitor PT closely and adjust warfarin dosage if co-trimoxazole used concomitantly

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