SULFATRIM

General Administration Information
For storage information, see the specific product information within the How Supplied section.

Route-Specific Administration

Oral Administration
-May be administered without regard to meals. Administer with food, water, or milk to minimize gastric irritation.
Oral Liquid Formulations
-Shake well before administration.



Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
-Do NOT administer intramuscularly.
Intravenous Administration
Dilution
-Dilute to a usual concentration of approximately 0.6 mg/mL trimethoprim (i.e., each 5 mL of the concentrate for injection in 125 mL of 5% Dextrose Injection). For fluid-restricted patients, a concentration up to 1 mg/mL trimethoprim may be used (i.e., each 5 mL of the concentrate for injection in 75 mL of 5% Dextrose Injection).
-Storage: If diluted to 0.6 mg/mL, use within 6 hours; if diluted to 0.8 mg/mL, use within 4 hours; if diluted to 1 mg/mL, use within 2 hours. Do not refrigerate after dilution.
-Multi-dose vial: Use within 48 hours of initial entry.

Intermittent IV Infusion
-Rapid or direct IV injection must be avoided.
-Infuse over a period of 60 to 90 minutes.

Sulfamethoxazole; trimethoprim has been associated with fatalities due to agranulocytosis, aplastic anemia and other blood dyscrasias. Thrombocytopenia may be an immune-mediated disorder; severe cases that are fatal or life-threatening have been reported. Thrombocytopenia usually resolves with a week upon treatment discontinuation. Discontinue sulfamethoxazole; trimethoprim at the first appearance of any sign of a serious adverse reaction. In glucose-6-phosphate dehydrogenase-deficient persons, hemolysis may occur and is frequently dose-related. Other hematologic adverse reactions associated with sulfamethoxazole; trimethoprim include leukopenia, neutropenia, hemolytic anemia, megaloblastic anemia, hypoprothrombinemia, methemoglobinemia, eosinophilia, thrombotic thrombocytopenic purpura (TTP), and idiopathic thrombocytopenic purpura. When used at high doses and/or for extended periods, sulfamethoxazole; trimethoprim may cause bone marrow suppression, manifested as thrombocytopenia, leukopenia, and/or megaloblastic anemia. If signs of bone marrow suppression occur, leucovorin use (except in persons with HIV with PCP pneumonia) has been recommended until normal hematopoiesis is restored.

Hypersensitivity is a more common reaction to sulfamethoxazole; trimethoprim and usually manifests as rash and urticaria. Sulfamethoxazole; trimethoprim has been associated with fatalities due to anaphylaxis, anaphylactic shock, and severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP), and acute febrile neutrophilic dermatosis (AFND). Clinical signs, such as rash, fever, pallor, and purpura, may be early indications of serious reactions. Discontinue sulfamethoxazole; trimethoprim at the first appearance of skin rash or any sign of a serious adverse reaction. Other hypersensitivity reactions reported include anaphylaxis (anaphylactoid reactions), erythema multiforme, exfoliative dermatitis, angioedema, drug fever, chills, Henoch-Schoenlein purpura, serum sickness-like syndrome, generalized allergic reactions, generalized skin eruptions, photosensitivity, conjunctival and scleral injection, pruritus, lupus-like symptoms, and periarteritis nodosa.

Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in patients with preexisting risk factors (e.g., renal disease). Hyperkalemia has been reported during high-dose sulfamethoxazole; trimethoprim therapy and can occur independently of a significant worsening of renal function. Hyperkalemia has also been observed after standard trimethoprim doses in patients with underlying disorders of potassium metabolism, renal insufficiency, or when administered with other drugs known to induce hyperkalemia. Other renal adverse effects include renal failure (unspecified), interstitial nephritis, BUN (azotemia) and serum creatinine elevations, renal insufficiency with oliguria and anuria, crystalluria, and nephrotoxicity associated with cyclosporine. Ensure adequate fluid intake and urinary output during treatment to prevent crystalluria.

CNS-related adverse reactions have been reported with sulfamethoxazole; trimethoprim and include headache, aseptic meningitis, ataxia, insomnia, peripheral neuritis, seizures, tinnitus, and vertigo. These adverse effects usually disappear or lessen with continued treatment. Psychiatric adverse reactions have included apathy, depression, hallucinations, and nervousness.

Musculoskeletal adverse reactions have been reported with sulfamethoxazole; trimethoprim and include arthralgia, fatigue, myalgia, and weakness. Isolated cases of rhabdomyolysis have occurred primarily in persons with AIDS.

Nausea, vomiting, and anorexia are the most common GI adverse effects caused by sulfamethoxazole; trimethoprim. These effects usually decrease with time, but medical attention may be needed if they persist. Other GI adverse effects include abdominal pain, diarrhea, glossitis, stomatitis, and pancreatitis.

Sulfonamides have chemical similarities to some goitrogens, diuretics (acetazolamide and thiazides), and oral hypoglycemic agents. It is possible that cross-sensitivity exists with these agents. Diuresis and hypoglycemia have occurred rarely in patients receiving sulfonamides. A study reported severe protracted hypoglycemia in a person with AIDS and renal impairment receiving sulfamethoxazole; trimethoprim. The study also reviewed 13 other cases of SMX-TMP-induced hypoglycemia reported in the literature. All cases had at least 1 predisposing factor for the development of hypoglycemia (e.g., renal impairment, hepatic disease, propoxyphene use) and required IV glucose administration.

A local injection site reaction, including pain and irritation, may infrequently occur with intravenous sulfamethoxazole; trimethoprim. Thrombophlebitis (phlebitis) has been rarely reported.

Severe hyponatremia has been reported with sulfamethoxazole; trimethoprim use. To prevent life-threatening complications, monitor for hyponatremia and implement corrective measure as necessary in symptomatic patients.

QT prolongation resulting in ventricular tachycardia and torsade de pointes has been reported with the use of sulfamethoxazole; trimethoprim. Sulfamethoxazole; trimethoprim has been associated with fatalities due to circulatory shock. Circulatory shock with fever, severe hypotension, and confusion requiring intravenous fluid resuscitation and vasopressors has occurred within minutes to hours of re-challenge with sulfamethoxazole; trimethoprim in patients with a history of recent (days to weeks) of previous exposure. Discontinue sulfamethoxazole; trimethoprim at the first appearance of any sign of a serious adverse reaction. Allergic myocarditis has also been reported with sulfamethoxazole; trimethoprim.

Uveitis has been reported with sulfamethoxazole; trimethoprim.

Metabolic acidosis has been noted in postmarketing reports with parenteral sulfamethoxazole; trimethoprim. Some formulations of injectable sulfamethoxazole; trimethoprim contain propylene glycol as a solvent. When administered in high doses or concomitantly with other products that contain propylene glycol, propylene glycol toxicity may occur, resulting in hyperosmolarity with anion gap metabolic acidosis, including lactic acidosis. Additionally, propylene glycol toxicity may result in acute kidney injury, CNS toxicity, and multi-organ failure. Monitor patients for the total daily intake of propylene glycol from all sources and for acid-base disturbances. Discontinue sulfamethoxazole; trimethoprim if propylene glycol toxicity is suspected.

Sulfamethoxazole; trimethoprim has been associated with fatalities due to fulminant hepatic necrosis. Jaundice may be an early indication of a serious reaction. Discontinue sulfamethoxazole; trimethoprim at the first sign of a serious adverse reaction. Hepatitis, elevated hepatic enzymes, elevated bilirubin (hyperbilirubinemia), and cholestatic jaundice have also been reported. Hepatotoxicity has been reported rarely with sulfamethoxazole; trimethoprim in pediatric patients.

Microbial overgrowth and superinfection can occur with antibiotic use. C. difficile-associated diarrhea (CDAD) or pseudomembranous colitis has been reported with sulfamethoxazole; trimethoprim. If pseudomembranous colitis is suspected or confirmed, ongoing antibacterial therapy not directed against C. difficile may need to be discontinued. Institute appropriate fluid and electrolyte management, protein supplementation, C. difficile-directed antibacterial therapy, and surgical evaluation as clinically appropriate.

Sulfamethoxazole; trimethoprim has been associated with fatalities due to acute and delayed lung injury. Cough, dyspnea, and pulmonary infiltrates potentially representing hypersensitivity reactions of the respiratory tract have been reported with sulfamethoxazole; trimethoprim. Other severe pulmonary reactions occurring within days to weeks of sulfamethoxazole; trimethoprim initiation and resulting in prolonged respiratory failure requiring mechanical ventilation or extracorporeal membrane oxygenation (ECMO), lung transplantation, or death have also been reported in patients and otherwise healthy individuals treated with sulfamethoxazole; trimethoprim. Clinical signs, such as pharyngitis, cough, chest pain (unspecified), and dyspnea may be early indications of serious reactions. Other adverse reactions reported include acute eosinophilic pneumonia, interstitial lung disease, and acute respiratory failure. Discontinue sulfamethoxazole; trimethoprim at the first appearance of any sign of a serious adverse reaction.
Sulfamethoxazole; trimethoprim can precipitate hypothyroidism. Additionally, thyroid dysfunction is uncommon long-term sequelae in persons with drug reaction with eosinophilia and systemic symptoms (DRESS), including due to sulfamethoxazole; trimethoprim. In a retrospective case review, sulfa-based medications were associated with thyroid dysfunction after DRESS (n = 14). Hypothyroidism associated with confirmed Hashimoto's thyroiditis (6 adults and 3 children) and possible Hashimoto's thyroiditis (3 adults) was noted along with hyperthyroidism associated with Graves' disease (2 adults). The onset of thyroid dysfunction was 0.3 to 26 months after DRESS in adults and 1 to 4 months after DRESS in children.

Some formulations of injectable sulfamethoxazole; trimethoprim contain propylene glycol as a solvent. When administered in high doses as for the treatment of P. jirovecii pneumonia and concomitantly with other products that contain propylene glycol, toxicity may occur. Propylene glycol toxicity may result in hyperosmolarity with anion gap metabolic acidosis, including lactic acidosis. Additionally, propylene glycol toxicity may result in acute kidney injury, CNS toxicity, and multi-organ failure. Monitor patients for the total daily intake of propylene glycol from all sources and for acid-base disturbances. Discontinue sulfamethoxazole; trimethoprim if propylene glycol toxicity is suspected.

Sulfamethoxazole; trimethoprim is contraindicated in patients with either sulfonamide hypersensitivity or trimethoprim hypersensitivity. Fatalities have been documented in patients with sulfonamide hypersensitivity who receive sulfonamides, usually secondary to Stevens-Johnson syndrome, toxic epidermal necrolysis, or hepatic necrosis. Because of structural similarity, sulfonamides should be used cautiously in patients with known thiazide diuretic hypersensitivity, sulfonylurea hypersensitivity, or carbonic anhydrase inhibitor hypersensitivity. Additionally, sulfamethoxazole; trimethoprim injection contains sodium metabisulfite and should not be used in patients with sulfite hypersensitivity. Patients with asthma may be at higher risk for sulfite sensitivity compared with non-asthmatic persons. Severe life-threatening anaphylactic reactions or less severe asthmatic episodes can develop in susceptible patients.

Sulfamethoxazole; trimethoprim is contraindicated in patients with folate deficiency megaloblastic anemia since either component could exacerbate this condition; the drug should be used with caution in patients with mild folate deficiency. Sulfamethoxazole; trimethoprim is also contraindicated for use in patients with a history of trimethoprim and/or sulfonamide-induced immune thrombocytopenia. Thrombocytopenia may be immune-mediated and usually subsides within a week of treatment discontinuation; however, severe/life-threatening cases have been reported. Caution is advised when administering the drug to patients with bone marrow suppression, as sulfonamides have been associated with fatalities resulting from agranulocytosis, aplastic anemia, and other blood dyscrasias. Do not administer to patients with G6PD deficiency; hemolysis and hemolytic anemia may occur if patients with G6PD deficiency receive sulfamethoxazole; trimethoprim; this reaction is frequently dose-related. Discontinue the drug at the first appearance of serious blood disorders.

Sulfamethoxazole; trimethoprim is contraindicated in patients with severe renal impairment or renal failure (creatinine clearance less than 15 mL/minute) when renal function status cannot be monitored. Use sulfamethoxazole; trimethoprim cautiously in patients with moderate renal impairment (i.e., creatinine clearance less than 30 mL/minute); dosage adjustments are recommended to avoid drug accumulation and potential toxicity. Trimethoprim has a potassium-sparing effect on the distal nephron and may induce hyperkalemia, especially in patients receiving high dosages or with preexisting risk factors (e.g., renal disease, disorders of potassium metabolism, receiving concurrent drugs known to significantly increase serum potassium). Monitor serum potassium concentrations closely in these patients. Sulfamethoxazole; trimethoprim has also been associated with severe cases of symptomatic hyponatremia, particularly in patients receiving high dosages for the treatment of Pneumocystis pneumonia (PCP). Monitor patients for the development of hyponatremia and implement appropriate corrective measures as needed in symptomatic patients.

Sulfamethoxazole; trimethoprim is contraindicated in patients with marked hepatic damage or hepatic disease. Because both sulfonamides and trimethoprim are metabolized in the liver, use caution when these drugs are given to patients with any degree of hepatic disease. Metabolism can be decreased, and as a result, toxicity may occur. Patients who are "slow acetylators" may be more prone to idiosyncratic reactions to sulfonamides.

Sulfonamides, such as sulfamethoxazole, can cause an acute attack of porphyria, and should not be used in patients with this condition.

Consider pseudomembranous colitis in patients presenting with diarrhea after antibacterial use. Careful medical history is necessary as pseudomembranous colitis has been reported to occur over 2 months after the administration of antibacterial agents. Almost all antibacterial agents, including sulfamethoxazole; trimethoprim, have been associated with pseudomembranous colitis or C. difficile-associated diarrhea (CDAD) which may range in severity from mild to life-threatening. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

Sulfamethoxazole; trimethoprim is contraindicated in neonates and infants younger than 2 months of age. Sulfonamides may cause bilirubin displacement and kernicterus in this age group. Additionally, sulfamethoxazole; trimethoprim injection contains benzyl alcohol as a preservative. There have been reports of fatal gasping syndrome in neonates after the administration of parenteral solutions containing the preservative benzyl alcohol at dosages of 99 mg/kg/day or more. Normal sulfamethoxazole; trimethoprim doses would deliver benzyl alcohol at amounts lower than those reported with gasping syndrome; however, the minimum amount of benzyl alcohol to cause toxicity is unknown. Consider the combined daily metabolic load of benzyl alcohol from all sources if using sulfamethoxazole; trimethoprim injection in infants. Sulfamethoxazole; trimethoprim injection contains 10 mg of benzyl alcohol per mL. Sulfamethoxazole; trimethoprim may be used for the prophylaxis of PCP in infants (1 month and older).

Photosensitivity can occur with sulfonamide treatment. Advise patients to avoid or limit sunlight (UV) exposure, including sunlamps and tanning booths. Sunscreens should be employed, but may provide limited protection for this reaction. Discontinue sulfamethoxazole; trimethoprim use at the first sign of erythema.

Laboratory test interference may occur with sulfamethoxazole; trimethoprim. Specifically, trimethoprim may interfere with serum methotrexate assays that are determined by the competitive binding protein technique (CBPA) when a bacterial dihydrofolate reductase is used as the binding protein. Methotrexate measurements by a radioimmunoassay are not affected. Sulfamethoxazole; trimethoprim may also interfere with creatinine assays that use the Jaffe alkaline picrate reaction, resulting in an overestimation of approximately 10% in the normal range of values.

Avoid the use of sulfamethoxazole; trimethoprim in persons with thyroid disease.

Use caution when administering sulfamethoxazole; trimethoprim to persons with human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS). Persons with AIDS may not tolerate or respond to treatment in the same manner as other persons. Persons with AIDS may experience more drug-related side effects, including rash, fever, leukopenia, elevated hepatic enzymes, and hyperkalemia. Reevaluate sulfamethoxazole; trimethoprim therapy or re-challenge in patients who develop rash, fever, leukopenia, or other treatment-related adverse reactions. If treatment is continued, closely monitor potassium concentrations and ensure adequate fluid intake during therapy. Additionally, avoid coadministration of sulfamethoxazole; trimethoprim with leucovorin in persons with HIV or AIDS for the treatment of pneumocystis pneumonia (PCP). During a clinical trial, persons with HIV with PCP receiving these drugs in combination experienced treatment failure and excess mortality.

Cases of hypoglycemia have been reported in non-diabetic patients receiving treatment with sulfamethoxazole; trimethoprim. This reaction is uncommon and usually develops after a few days of therapy. Risk factors include renal and hepatic dysfunction, malnutrition, and those patients receiving high drug doses.

Cases of QT prolongation resulting in ventricular tachycardia and torsade de pointes have been reported with the use of sulfamethoxazole; trimethoprim. Use sulfamethoxazole; trimethoprim with caution in patients with conditions that may increase the risk of QT prolongation including congenital long QT syndrome, bradycardia, AV block, heart failure, stress-related cardiomyopathy, myocardial infarction, stroke, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to prolong the QT interval or cause an electrolyte imbalance. Females, patients with sleep deprivation, pheochromocytoma, sickle cell disease, hypothyroidism, hyperparathyroidism, hypothermia, systemic inflammation (e.g., human immunodeficiency virus (HIV) infection, fever, and some autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus (SLE), and celiac disease) and patients undergoing apheresis procedures (e.g., plasmapheresis [plasma exchange], cytapheresis) may also be at increased risk for QT prolongation.

Fatalities and serious adverse reactions, including serious rash, including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia (DRESS), acute generalized exanthematous pustulosis (AGEP), and acute febrile neutrophilic dermatosis (AFND), have been reported with the use of sulfamethoxazole; trimethoprim.

Description: Sulfamethoxazole; trimethoprim (also known as co-trimoxazole or TMP-SMX) is a combination product of trimethoprim and sulfamethoxazole in a fixed 1:5 ratio. This dosage ratio produces serum concentrations of 1:20, which optimize antibacterial activity against some organisms. Both trimethoprim and sulfamethoxazole are synthetic folate antagonists that are effective antimicrobials as individual agents. Sulfamethoxazole; trimethoprim initially was used in the treatment of UTIs but has since proved to be a versatile agent and now is widely used in the prevention and treatment of Pneumocystis pneumonia (PCP) and for the treatment of gastrointestinal infections. Sulfamethoxazole; trimethoprim is FDA-approved for use in pediatric patients as young as 2 months of age. It is contraindicated in infants younger than 2 months of age; however, guidelines recommend that prophylaxis for PCP be considered in infants born to HIV-infected mothers beginning at 4 to 6 weeks of age.

Per the manufacturer, this drug has been shown to be active against most strains of the following microorganisms either in vitro and/or in clinical infections: Enterobacter sp., Escherichia coli, Haemophilus influenzae (beta-lactamase negative), Haemophilus influenzae (beta-lactamase positive), Klebsiella sp., Morganella morganii, Pneumocystis jirovecii (formerly Pneumocystis carinii), Proteus mirabilis, Proteus sp., Proteus vulgaris, Shigella flexneri, Shigella sonnei, Streptococcus pneumoniae
NOTE: The safety and effectiveness in treating clinical infections due to organisms with in vitro data only have not been established in adequate and well-controlled clinical trials.

This drug may also have activity against the following microorganisms: Actinomadura madurae, Actinomadura pelletierii, Bordetella pertussis, Brucella melitensis, Brucella sp., Burkholderia pseudomallei, Coxiella burnetii, Cyclospora cayetanensis, Cystoisospora belli, Haemophilus ducreyi, Klebsiella granulomatis, Legionella pneumophila, Listeria monocytogenes, Nocardia asteroides, Nocardia brasiliensis, Nocardia otitidiscaviarum, Pediculus capitis, Salmonella enterica serotype Typhi , Salmonella sp., Staphylococcus aureus (MRSA), Staphylococcus aureus (MSSA), Toxoplasma gondii, Vibrio cholerae
NOTE: Some organisms may not have been adequately studied during clinical trials; therefore, exclusion from this list does not necessarily negate the drug's activity against the organism.

For the treatment of urinary tract infection (UTI), including pyelonephritis and catheter-associated urinary tract infection:
-for the treatment of nonspecific UTI:
Oral dosage:
Infants, Children, and Adolescents 2 months to 17 years: 8 to 10 mg/kg/day (trimethoprim component) PO divided every 12 hours (Max: 320 mg trimethoprim/1,600 mg sulfamethoxazole/day) for 10 days.
-for the treatment of acute uncomplicated lower UTI:
Oral dosage:
Infants, Children, and Adolescents 2 months to 17 years: 8 to 10 mg/kg/day (trimethoprim component) PO divided every 12 hours (Max: 320 mg trimethoprim/1,600 mg sulfamethoxazole/day) for 3 to 5 days.
-for the treatment of severe urinary tract infections, including pyelonephritis:
Oral dosage:
Infants, Children, and Adolescents 2 months to 17 years: 8 to 10 mg/kg/day (trimethoprim component) PO divided every 12 hours (Max: 320 mg trimethoprim/1,600 mg sulfamethoxazole/day) for 7 to 14 days.
Intravenous dosage:
Infants, Children, and Adolescents 2 months to 17 years: 8 to 10 mg/kg/day (trimethoprim component) IV divided every 6 to 12 hours (Max: 960 mg trimethoprim/day). Treat for 24 to 48 hours or until patient is clinically stable and afebrile, followed by oral antibiotics for a total duration of 7 to 14 days.
-for the treatment of catheter-associated UTI:
Oral dosage:
Infants, Children, and Adolescents 2 months to 17 years: 8 to 10 mg/kg/day (trimethoprim component) PO divided every 12 hours (Max: 320 mg trimethoprim/1,600 mg sulfamethoxazole/day) for 7 to 14 days.
Intravenous dosage:
Infants, Children, and Adolescents 2 months to 17 years: 8 to 10 mg/kg/day (trimethoprim component) IV divided every 6 to 12 hours (Max: 960 mg trimethoprim/day) for 7 to 14 days.

For urinary tract infection (UTI) prophylaxis*:
-for continuous, long-term UTI prophylaxis* for recurrent infections:
Oral dosage:
Infants, Children, and Adolescents 2 months to 17 years: 2 mg/kg/dose (trimethoprim component) PO every 24 hours or 5 mg/kg/dose (trimethoprim component) PO 2 times weekly.
-for UTI prophylaxis* in infants with hydronephrosis or vesicoureteral reflux:
NOTE: Routine antimicrobial prophylaxis for patients aged 2 to 24 months with vesicoureteral reflux is not supported by currently available data; however, antimicrobial prophylaxis is still utilized and has biological plausibility.
Oral dosage:
Infants and Children 2 months to 2 years: 2 mg/kg/dose (trimethoprim component) PO every 24 hours or 5 mg/kg/dose (trimethoprim component) PO 2 times weekly. Prophylaxis is only recommended in high-risk patients, which includes infants and children with recurrent febrile UTI and infants and children with reflux grade of III or higher. Guidelines recommend antibiotic prophylaxis for all grades of vesicoureteral reflux in all patients younger than 1 year.

For the treatment of Pneumocystis pneumonia (PCP):
-for the treatment of PCP in persons living with HIV:
Oral dosage:
Infants and Children 2 months to 12 years: 15 to 20 mg/kg/day (trimethoprim component) PO divided every 6 hours (Max: 1,600 mg trimethoprim/day) for 21 days then chronic suppressive therapy.
Adolescents: 15 to 20 mg/kg/day (trimethoprim component) PO divided every 6 to 8 hours (Max: 1,600 mg trimethoprim/day) or 320 mg trimethoprim/1,600 mg sulfamethoxazole PO 3 times daily for 21 days then chronic suppressive therapy.
Intravenous dosage:
Infants, Children, and Adolescents 2 months to 17 years: 15 to 20 mg/kg/day (trimethoprim component) IV divided every 6 to 8 hours (Max: 960 mg trimethoprim/day) for 21 days then chronic suppressive therapy.
-for the treatment of PCP in solid organ transplant recipients:
Oral dosage:
Infants and Children 2 months to 12 years: 15 to 20 mg/kg/day (trimethoprim component) PO divided every 6 to 8 hours (Max: 1,600 mg trimethoprim/day) for 14 to 21 days.
Adolescents: 15 to 20 mg/kg/day (trimethoprim component) PO divided every 6 to 8 hours (Max: 1,600 mg trimethoprim/day) or 320 mg trimethoprim/1,600 mg sulfamethoxazole PO 3 times daily for 14 to 21 days.
Intravenous dosage:
Infants, Children, and Adolescents 2 months to 17 years: 15 to 20 mg/kg/day (trimethoprim component) IV divided every 6 to 8 hours (Max: 960 mg trimethoprim/day) for 14 to 21 days. May consider the addition of caspofungin for salvage therapy.
-for the treatment of PCP in patients with hematological malignancies, cancer, or autoimmune/inflammatory disease:
Oral dosage:
Infants, Children, and Adolescents 2 months to 17 years: 15 to 20 mg/kg/day (trimethoprim component) PO divided every 6 hours (Max: 1,600 mg trimethoprim/day) for 14 to 21 days.
Intravenous dosage:
Infants, Children, and Adolescents 2 months to 17 years: 15 to 20 mg/kg/day (trimethoprim component) IV divided every 6 to 8 hours (Max: 960 mg trimethoprim/day) for 14 to 21 days. May consider the addition of caspofungin for salvage therapy.

For Pneumocystis pneumonia (PCP) prophylaxis:
-for primary PCP prophylaxis in persons living with HIV:
Oral dosage:
Infants 2 to 11 months: 5 to 10 mg/kg/day (trimethoprim component) PO divided every 12 hours 2 or 3 times weekly or as a single dose once daily. Recommended for all infants younger than 12 months that are HIV-positive or HIV-indeterminate regardless of CD4 count or percentage. Consider prophylaxis for infants born to mothers living with HIV beginning at 4 to 6 weeks. Discontinue prophylaxis in infants with indeterminate HIV infection status when they are determined to be definitively or presumptively HIV-uninfected. Do not discontinue prophylaxis in HIV-positive infants younger than 12 months.
Children 1 to 5 years: 5 to 10 mg/kg/day (trimethoprim component) PO divided every 12 hours 2 or 3 times weekly or as a single dose once daily. Recommended for patients with CD4 count less than 500 cells/mm3 or CD4 less than 15%. May discontinue after 6 months or more of antiretroviral therapy if the CD4 count is 500 cells/mm3 or more or CD4 is 15% or more for more than 3 consecutive months. Restart prophylaxis if CD4 count is less than 500 cells/mm3 or CD4 is less than 15%.
Children 6 to 12 years: 5 to 10 mg/kg/day (trimethoprim component) PO divided every 12 hours 2 or 3 times weekly or as a single dose once daily (Max: 320 mg trimethoprim/1,600 mg sulfamethoxazole/day). Recommended for patients with CD4 count less than 200 cells/mm3 or CD4 less than 15%. May discontinue after 6 months or more of antiretroviral therapy if the CD4 count is 200 cells/mm3 or more or CD4 is 15% or more for more than 3 consecutive months. Restart prophylaxis if CD4 count is less than 200 cells/mm3 or CD4 is less than 15%.
Adolescents: 160 mg trimethoprim/800 mg sulfamethoxazole PO once daily or 80 mg trimethoprim/400 mg sulfamethoxazole PO once daily. Alternatively, 160 mg trimethoprim/800 mg sulfamethoxazole PO 3 times weekly. Recommended for patients with CD4 count less than 200 cells/mm3, CD4 less than 14%, or CD4 count of 200 to 250 cells/mm3 if antiretroviral therapy (ART) initiation must be delayed and if CD4 count monitoring every 3 months is not possible. May discontinue if the CD4 count is 200 cells/mm3 or more for more than 3 months in response to ART or if the CD4 count is 100 to 200 cells/mm3 and HIV RNA remains below the limit of detection for 3 to 6 months. Restart prophylaxis if CD4 count is less than 100 cells/mm3 or CD4 count is 100 to 200 cells/mm3 and HIV RNA is above detection limit.
-for secondary PCP prophylaxis (i.e., long-term suppressive therapy) in persons living with HIV:
Oral dosage:
Infants 2 to 11 months: 5 to 10 mg/kg/day (trimethoprim component) PO divided every 12 hours 2 or 3 times weekly or as a single dose once daily. Do not discontinue prophylaxis in HIV-positive infants younger than 12 months.
Children 1 to 5 years: 5 to 10 mg/kg/day (trimethoprim component) PO divided every 12 hours 2 or 3 times weekly or as a single dose once daily. May discontinue after 6 months or more of antiretroviral therapy if the CD4 count is 500 cells/mm3 or more or CD4 is 15% or more for more than 3 consecutive months. Restart prophylaxis if CD4 count is less than 500 cells/mm3 or CD4 is less than 15%.
Children 6 to 12 years: 5 to 10 mg/kg/day (trimethoprim component) PO divided every 12 hours 2 or 3 times weekly or as a single dose once daily (Max: 320 mg trimethoprim/1,600 mg sulfamethoxazole/day). May discontinue after 6 months or more of antiretroviral therapy if the CD4 count is 200 cells/mm3 or more or CD4 is 15% or more for more than 3 consecutive months. Restart prophylaxis if CD4 count is less than 200 cells/mm3 or CD4 is less than 15%.
Adolescents: 160 mg trimethoprim/800 mg sulfamethoxazole PO once daily or 80 mg trimethoprim/400 mg sulfamethoxazole PO once daily. Alternatively, 160 mg trimethoprim/800 mg sulfamethoxazole PO 3 times weekly. May discontinue if the CD4 count is more than 200 cells/mm3 for more than 3 months in response to antiretroviral therapy (ART) or if the CD4 count is 100 to 200 cells/mm3 and HIV RNA remains below the limit of detection for 3 to 6 months. Restart prophylaxis if CD4 count is less than 100 cells/mm3 or CD4 count is 100 to 200 cells/mm3 and HIV RNA is above detection limit. If PCP is diagnosed or recurs at a CD4 count of more than 200 cells/mm3, lifelong prophylaxis is necessary.
-for PCP prophylaxis in solid organ transplant recipients:
Oral dosage:
Infants and Children 2 months to 12 years: 5 to 10 mg/kg/day (trimethoprim component) PO once daily 7 days/week or divided twice daily on 2 or 3 days/week (Max: 320 mg trimethoprim/day) for 3 to 6 months after kidney transplant, for at least 6 to 12 months after other transplants, as well as for at least 6 weeks during and after antirejection therapy in kidney transplant recipients. Lifelong prophylaxis is recommended for lung and small bowel transplant recipients, as well as patients with a history of prior PCP or chronic cytomegalovirus disease.
Adolescents: 160 mg trimethoprim/800 mg sulfamethoxazole PO once daily or 3 times weekly or 80 mg trimethoprim/400 mg sulfamethoxazole PO once daily for 3 to 6 months after kidney transplant, for at least 6 to 12 months after other transplants, as well as for at least 6 weeks during and after antirejection therapy in kidney transplant recipients. Lifelong prophylaxis is recommended for lung and small bowel transplant recipients, as well as patients with a history of prior PCP or chronic cytomegalovirus disease.
-for primary PCP prophylaxis in hematopoietic stem cell transplantation (HSCT) recipients:
Oral dosage:
Infants and Children 2 months to 12 years: 150 mg/m2/day (trimethoprim component) PO once daily on 3 consecutive days/week or divided twice daily on 3 or 7 days/week (Max: 320 mg trimethoprim/day) starting at engraftment or 1 to 2 weeks before HSCT and continuing for at least 6 months after HSCT. Recommended for all allogenic HSCT recipients and autologous HSCT recipients with underlying hematologic malignancies, those receiving intense conditioning therapy or graft manipulation, or those who have received purine analogs. Longer-term prophylaxis is recommended for the duration of immunosuppression for all patients who are receiving immunosuppressive therapy or have chronic graft-versus-host disease.
Adolescents: 160 mg trimethoprim/800 mg sulfamethoxazole PO once daily or 3 times weekly or 80 mg trimethoprim/400 mg sulfamethoxazole PO once daily starting at engraftment or 1 to 2 weeks before HSCT and continuing for at least 6 months after HSCT. Recommended for all allogenic HSCT recipients and autologous HSCT recipients with underlying hematologic malignancies, those receiving intense conditioning therapy or graft manipulation, or those who have received purine analogs. Longer-term prophylaxis is recommended for the duration of immunosuppression for all patients who are receiving immunosuppressive therapy or have chronic graft-versus-host disease.
-for primary PCP prophylaxis in patients with cancer-related immunosuppression and hematological malignancies:
Oral dosage:
Infants, Children, and Adolescents 2 months to 17 years: 150 mg/m2/day (trimethoprim component) PO once or twice daily, 2 or 3 times weekly, or once weekly (Max: 320 mg trimethoprim/day). Recommended for patients receiving alemtuzumab or corticosteroids at doses equivalent to more than 0.4 mg/kg/day or 16 mg/day of prednisone for 1 month or more as well as patients with acute lymphoblastic leukemia (ALL), severe combined immunodeficiency (SCID), Wiskott-Aldrich syndrome (WAS), X-linked agammaglobulinemia, human leukocyte antigen (HLA) II combined immunodeficiency, acute myeloid leukemia (AML), and solid tumors. Duration of prophylaxis for ALL is from induction to the end of maintenance. Patients receiving corticosteroids or with SCID, WAS, X-linked agammaglobulinemia, or HLA II combined immunodeficiency require lifelong prophylaxis or until restoration of the underlying defect. Prophylaxis is recommended for patients with AML and solid tumors for the duration of chemotherapy.

For bacterial infection prophylaxis* in HIV-infected infants and children:
-for primary prophylaxis* to reduce opportunistic infection in HIV-infected children (regardless of CD4 count):
Oral dosage:
Infants and Children 2 months to 12 years: 150 mg/m2/day (trimethoprim component) PO divided every 12 hours may be considered an alternative treatment to decrease the rate of serious bacterial infections in HIV-infected infants and children unable to take antiretroviral therapy; however, guidelines do not recommend routine primary prophylaxis of bacterial infections, when not indicated for PCP or MAC prophylaxis or other specific reasons. A randomized, double-blind, placebo-controlled study in Zambian children aged 1 to 14 years (n = 541) with clinical features of HIV-infection evaluated the efficacy of sulfamethoxazole; trimethoprim (SMX-TMP) in reducing opportunistic infections in an area with high levels of in vitro bacterial resistance to SMX-TMP. Children younger than 5 years received 240 mg (5 mL of suspension) PO daily and those 5 years and older received 480 mg (10 mL suspension) PO daily or matching placebo. SMX-TMP reduced mortality by 43% and hospitalization by 23% compared to placebo. It was concluded that children of all ages with clinical features of HIV infection receive SMX-TMP prophylaxis in resource-poor areas, regardless of local resistance to the antibiotic.
-for secondary prophylaxis* in HIV-infected children with recurrent, severe bacterial infections:
Oral dosage:
Infants and Children 2 months to 12 years: 150 mg/m2/day (trimethoprim component) PO divided every 12 hours. Secondary prophylaxis is only recommended for infants and children with more than 2 serious bacterial infections in a 1-year period who are unable to take antiretroviral therapy. Secondary prophylaxis may be discontinued for sustained (3 months or more) immune reconstitution (CD4 at least 25% if 6 years or younger; CD4 at least 20% or CD4 count more than 350 cells/mm3 if older than 6 years). Secondary prophylaxis should be restarted for more than 2 serious bacterial infections in a 1-year period despite antiretroviral therapy.

For the treatment of otitis media:
Oral dosage:
Infants, Children, and Adolescents 2 months to 17 years: 8 mg/kg/day (trimethoprim component) PO divided every 12 hours (Max: 320 mg trimethoprim/1,600 mg sulfamethoxazole/day) for 10 days is recommended in FDA-approved labeling. The American Academy of Pediatrics (AAP) does not recommend sulfamethoxazole; trimethoprim as a treatment option in patients with type I penicillin allergy due to the low rates of cross sensitivity between penicillin and second and third generation cephalosporins, which are the recommended alternative agents. Sulfamethoxazole; trimethoprim is also not recommended as second-line therapy for children who have failed amoxicillin therapy due to high rates of pneumococcal resistance.

For the treatment of toxoplasmic encephalitis* (TE) due to Toxoplasma gondii:
NOTE: Recommended as an alternative therapy to pyrimethamine plus sulfadiazine plus leucovorin. This regimen has not been studied in children.
Oral dosage:
Infants and Children 2 months to 12 years: 5 mg/kg/dose (trimethoprim component) PO every 12 hours has been used as an alternative regimen in adults; however, this regimen has not been evaluated in children.
Adolescents: 5 mg/kg/dose (trimethoprim component) PO every 12 hours as an alternative regimen, then chronic maintenance therapy. Treatment duration should be at least 6 weeks; however, a longer duration may be necessary if clinical or radiologic disease is extensive or if the response is incomplete at 6 weeks. Adjunctive corticosteroids may be administered when clinically indicated for the treatment of mass effect attributed to focal lesions or associated edema; however, discontinue as soon as possible. Anticonvulsants may be administered to patients with a seizure history during the acute treatment phase; however, they should not be used prophylactically.
Intravenous dosage:
Infants and Children 2 months to 12 years: 5 mg/kg/dose (trimethoprim component) IV every 12 hours has been used as an alternative regimen in adults; however, this regimen has not been evaluated in children.
Adolescents: 5 mg/kg/dose (trimethoprim component) IV every 12 hours as an alternative regimen, then chronic maintenance therapy. Treatment duration should be at least 6 weeks; however, a longer duration may be necessary if clinical or radiologic disease is extensive or if the response is incomplete at 6 weeks. Adjunctive corticosteroids may be administered when clinically indicated for the treatment of mass effect attributed to focal lesions or associated edema; however, discontinue as soon as possible. Anticonvulsants may be administered to patients with a seizure history during the acute treatment phase; however, they should not be used prophylactically.

For toxoplasmosis prophylaxis*, specifically prevention of toxoplasmic encephalitis (TE) due to Toxoplasma gondii:
-for primary prophylaxis* in persons living with HIV:
Oral dosage:
Infants and Children 2 months to 12 years: 150 mg/m2 trimethoprim/750 mg/m2 sulfamethoxazole PO once daily (Max: 160 mg trimethoprim/800 mg sulfamethoxazole/day) in patients with an IgG antibody to Toxoplasma and severe immunosuppression (i.e., infants and children younger than 6 years of age with a CD4 percentage less than 15% or children 6 years and older with a CD4 count less than 100 cells/mm3). Acceptable alternative regimens include 150 mg/m2 trimethoprim/750 mg/m2 sulfamethoxazole PO once daily for 3 consecutive days each week, 150 mg/m2 trimethoprim/750 mg/m2 sulfamethoxazole PO per day in 2 divided doses given every day, or 150 mg/m2 trimethoprim/750 mg/m2 sulfamethoxazole PO per day in 2 divided doses given 3 times per week on alternate days (e.g., Monday, Wednesday, Friday). Prophylaxis should not be discontinued in infants younger than 1 year of age. For children 1 to 5 years of age, primary prophylaxis may be discontinued after at least 6 months of antiretroviral therapy if CD4 percentage is at least 15% for more than 3 consecutive months. For children 6 years and older, primary prophylaxis may be discontinued after at least 6 months of antiretroviral therapy if CD4 count is more than 200 cells/mm3 for more than 3 consecutive months. Primary prophylaxis should be restarted if CD4 counts fall below these thresholds.
Adolescents: 160 mg trimethoprim/800 mg sulfamethoxazole PO once daily in patients with an IgG antibody to Toxoplasma and a CD4+ count less than 100 cells/mm3. As an alternative, may give 160 mg trimethoprim/800 mg sulfamethoxazole PO 3 times per week or 80 mg trimethoprim/400 mg sulfamethoxazole PO daily. Primary prophylaxis for TE may be discontinued in patients who have responded to highly active antiretroviral therapy with an increase in CD4 count to more than 200 cells/mm3 for at least 3 months. Prophylaxis should be reintroduced if CD4 count decreases to less than 100 to 200 cells/mm3.
-for chronic maintenance therapy* (secondary prophylaxis*) after acute toxoplasmosis infection:
Oral dosage:
Infants and Children 2 months to 12 years: 150 mg/m2 trimethoprim/750 mg/m2 sulfamethoxazole PO once daily (Max: 160 mg trimethoprim/800 mg sulfamethoxazole/day) is recommended as an alternative by guidelines. There are very limited data for alternative regimens in children, and trimethoprim/sulfamethoxazole is only recommended in patients who are intolerant to other preferred regimens. Chronic maintenance therapy may be discontinued in patients who have received antiretroviral therapy for at least 6 months, have successfully completed initial therapy and remain free of signs and symptoms of encephalitis, and have a CD4 count of at least 15% (1 to 5 years of age) or more than 200 cells/mm3 (6 years and older) for more than 6 months. Restart chronic maintenance therapy if the CD4 count drops below these thresholds.
Adolescents: 160 mg trimethoprim/800 mg sulfamethoxazole PO once daily or twice daily is recommended as an alternative in the HIV guidelines. Once daily therapy may be associated with an increased risk of relapse; therefore, a gradual transition from acute therapy may be beneficial, utilizing the twice daily dose for 4 to 6 weeks before switching to once daily dosing. Chronic maintenance therapy may be discontinued if initial therapy is successfully completed, patient remains free of signs and symptoms of encephalitis, and has a CD4 count more than 200 cells/mm3 for more than 6 months in response to antiretroviral therapy. Restart chronic maintenance therapy if the CD4 count drops below 200 cells/mm3.
-for primary prophylaxis* in allogeneic hematopoietic stem cell transplantation (HSCT) recipients with IgG antibody to Toxoplasma:
NOTE: Prophylaxis should be started after engraftment and given as long as the patient remains on immunosuppressant therapy (i.e., usually until 6 months after HSCT).
Oral dosage:
Infants and Children 2 months to 12 years: 150 mg/m2 trimethoprim/750 mg/m2 sulfamethoxazole per day PO in 1 of the following regimens: 2 divided doses 3 times weekly on consecutive days, a single dose 3 times weekly on consecutive days, 2 divided doses daily, or 2 divided doses 3 times weekly on alternate days (Max: 160 mg trimethoprim/800 mg sulfamethoxazole/day).
Adolescents: 160 mg trimethoprim/800 mg sulfamethoxazole PO once daily; or 80 mg trimethoprim/400 mg sulfamethoxazole PO once daily; or 160 mg trimethoprim/800 mg sulfamethoxazole PO 3 times per week.

For the treatment of pertussis (whooping cough)*:
Oral dosage:
Infants, Children, and Adolescents 2 months to 17 years: 8 mg/kg/day (trimethoprim component) PO divided every 12 hours (Max: 320 mg trimethoprim/1,600 mg sulfamethoxazole/day) for 14 days.

For the treatment of skin and skin structure infections*, including impetigo*, cellulitis*, erysipelas*, skin abscesses*, furunculosis*, and carbuncle*:
-for the treatment of impetigo when methicillin-resistant S. aureus is suspected or confirmed*:
Oral dosage:
Infants, Children, and Adolescents 2 months to 17 years: 4 to 6 mg/kg/dose (trimethoprim component) (Max: 320 mg trimethoprim/1,600 mg sulfamethoxazole/dose) PO every 12 hours for 5 to 7 days.
-for the treatment of nonpurulent skin infections*, such as cellulitis* and erysipelas*:
Oral dosage:
Infants, Children, and Adolescents 2 months to 17 years: 4 to 6 mg/kg/dose (trimethoprim component) (Max: 320 mg trimethoprim/1,600 mg sulfamethoxazole/dose) PO every 12 hours for 5 to 14 days.
-for the treatment of purulent skin infections*, such as furunculosis*, carbuncle*, and skin abscesses*:
Oral dosage:
Infants, Children, and Adolescents 2 months to 17 years: 4 to 6 mg/kg/dose (trimethoprim component) (Max: 320 mg trimethoprim/1,600 mg sulfamethoxazole/dose) PO every 12 hours for 5 to 10 days plus incision and drainage.

For postexposure pertussis prophylaxis*:
Oral dosage:
Infants, Children, and Adolescents 2 months to 17 years: 8 mg/kg/day (trimethoprim component) PO divided every 12 hours (Max: 320 mg trimethoprim/1,600 mg sulfamethoxazole/day) for 14 days. Administer to close contacts within 3 weeks of exposure.

For the treatment of granuloma inguinale* (Donovanosis):
Oral dosage:
Adolescents: 160 mg trimethoprim/800 mg sulfamethoxazole PO twice daily as an alternative for at least 3 weeks and until all lesions have completely healed. Consider adding a second antibiotic if lesions do not respond within the first few days of therapy.

For the treatment of pediculosis* capitis (head lice infestation):
Oral dosage:
Children and Adolescents: 5 mg/kg/dose (trimethoprim component) PO every 12 hours for 10 days has been used. Oral sulfamethoxazole/trimethoprim either alone or combined with topical 1% permethrin was effective; however, it was recommended that combination therapy be reserved for cases of lice resistance or multiple treatment failures.

For the treatment of melioidosis* and for postexposure prophylaxis:
Oral dosage:
Infants, Children, and Adolescents 2 months to 17 years: 8 mg/kg/dose (trimethoprim component) PO every 12 hours (Max: 320 mg trimethoprim/1,600 mg sulfamethoxazole/dose) for 12 weeks for the oral eradication-phase of therapy after initial IV treatment and for 21 days as postexposure prophylaxis during a public health emergency. Consider adding sulfamethoxazole; trimethoprim to carbapenem therapy in the setting of persistent bacteremia.

For sulfonamide desensitization* in patients requiring sulfamethoxazole; trimethoprim therapy:
-rapid sulfonamide desensitization* protocol:
Oral dosage:
Infants, Children, and Adolescents 2 months to 17 years: Data on sulfonamide desensitization protocols are lacking in pediatric patients. In 1 rapid, 4-hour oral protocol in HIV-infected children (n = 5), sulfamethoxazole; trimethoprim suspension was diluted in sterile water, and doses were given every 15 minutes at the following proportions of the final dose: 1:10,000, 1:1,000, 1:500, 1:250, 1:125, 1:62, 1:30, 1:15, 1:7.5, 1:5, 1:2.5, and full strength. After desensitization, maintenance sulfamethoxazole; trimethoprim therapy was begun at a dosage of 150 mg/m2/day PO divided twice daily. The desensitization protocol was successful in 4 of the 5 patients. Another protocol in HIV-infected patients, 4 of whom were pediatric patients, used sulfamethoxazole; trimethoprim suspension administered orally every 8 hours beginning with 1:10,000 of the desired total daily dose and progressing through serial dilutions of 1:5,000, 1:1,000, 1:500, 1:100, 1:50, and 1:10. Subsequently, the desired dosage was administered orally twice per day. The desensitization protocol was successful in 6 of the 7 patients.
-ambulatory sulfonamide desensitization* protocol:
Oral dosage:
Infants, Children, and Adolescents 2 months to 17 years: Data on ambulatory sulfonamide desensitization protocols are lacking in pediatric patients. In 1 successful protocol in HIV-infected children (n = 4), 1 mL of sulfamethoxazole; trimethoprim oral suspension (8 mg/mL trimethoprim) was diluted with 19 mL of distilled water for a concentration of 0.4 mg/mL (used for Days 1 to 4 of the desensitization regimen). The following desensitization regimen was used (all doses represent trimethoprim component): Day 1: 0.4 mg; Day 2: 0.8 mg; Day 3: 1.6 mg; Day 4: 3.2 mg; Day 5: 4.8 mg; Day 6: 9.6 mg; Day 7: 20 mg; Day 8: 40 mg; Day 9: 80 mg; Days 10 to 17: 40 mg; Days 18 onward: dose increased every 3 days to 5 mg/kg/day PO.

For the treatment of bacteremia* and catheter-associated infections*:
Intravenous dosage:
Infants, Children, and Adolescents 2 months to 17 years: 6 to 12 mg/kg/day (trimethoprim component) IV divided every 12 hours (Max: 960 mg trimethoprim/day) for mild-to-moderate infections and 15 to 20 mg/kg/day (trimethoprim component) IV divided every 6 to 8 hours (Max: 960 mg trimethoprim/day) for certain serious catheter-associated infections.

For the treatment of CNS infections*, including meningitis*, ventriculitis*, brain abscess*, subdural empyema*, spinal epidural abscess*, and septic thrombosis of the cavernous or dural venous sinus*:
-for the treatment of meningitis due to L. monocytogenes*:
Intravenous dosage:
Infants, Children, and Adolescents 2 months to 17 years: 10 to 20 mg/kg/day (trimethoprim component) IV divided every 6 to 12 hours for at least 21 days.
-for the treatment of meningitis or ventriculitis due to gram-negative organisms*:
Intravenous dosage:
Infants, Children, and Adolescents 2 months to 17 years: 10 to 20 mg/kg/day (trimethoprim component) IV divided every 6 to 12 hours for 21 days.
-for the treatment of meningitis or ventriculitis due to methicillin-resistant S. aureus (MRSA)*:
Intravenous dosage:
Infants, Children, and Adolescents 2 months to 17 years: 10 to 20 mg/kg/day (trimethoprim component) IV divided every 6 to 12 hours for 10 to 14 days.
-for the treatment of brain abscess*, subdural empyema*, spinal epidural abscess*, and septic thrombosis of the cavernous or dural venous sinus* due to methicillin-resistant S. aureus (MRSA)*:
Intravenous dosage:
Infants, Children, and Adolescents 2 months to 17 years: 10 to 20 mg/kg/day (trimethoprim component) IV divided every 6 to 12 hours for 4 to 6 weeks; consider the addition of oral rifampin.

For the treatment of brucellosis*:
Oral dosage:
Infants, Children, and Adolescents 2 months to 17 years: 8 to 12 mg/kg/day (trimethoprim component) PO divided every 12 hours (Max: 320 mg trimethoprim/1,600 mg sulfamethoxazole/day) for 6 to 8 weeks. Give in combination with rifampin or doxycycline (pediatric patients older than 8 years) to reduce the incidence of relapse. For serious infections or complications (i.e., endocarditis, meningitis, and osteomyelitis), the addition of streptomycin or gentamicin for the first 14 to 21 days of therapy is recommended.

For the treatment of acute Q fever*:
Oral dosage:
Infants and Children 2 months to 7 years: 4 mg/kg/dose (trimethoprim component) PO every 12 hours (Max: 160 mg trimethoprim/800 mg sulfamethoxazole/dose) for 14 days. Trimethoprim/sulfamethoxazole may be considered as an alternative therapy to doxycycline in children with mild or uncomplicated illness or as an option in patients who remain febrile after a 5-day course of doxycycline. Children with high-risk criteria (e.g., hospitalized or who have severe illness, children with preexisting heart valvulopathy, immunocompromised children, or children with delayed Q fever diagnosis who have experienced illness for more than 14 days without resolution of symptoms) should receive doxycycline treatment for 14 days.
Children and Adolescents 8 to 17 years: Doxycycline is the treatment of choice.

For the treatment of infectious diarrhea and gastroenteritis, including cyclosporiasis*, cystoisosporiasis*, salmonellosis*, shigellosis, and yersiniosis*:
-for the treatment of cyclosporiasis*:
Oral dosage:
Infants, Children, and Adolescents 2 months to 17 years: 8 to 10 mg/kg/day (trimethoprim component) PO divided every 12 hours (Max: 320 mg trimethoprim/1,600 mg sulfamethoxazole/day) for 7 to 10 days.
-for the treatment of cystoisosporiasis* in persons without HIV:
Oral dosage:
Infants, Children, and Adolescents 2 months to 17 years: 8 to 10 mg/kg/day (trimethoprim component) PO divided every 12 hours (Max: 320 mg trimethoprim/1,600 mg sulfamethoxazole/day) for 7 to 10 days.
-for the treatment of cystoisosporiasis* in persons living with HIV:
Oral dosage:
Infants and Children 2 months to 12 years: 10 mg/kg/day (trimethoprim component) PO divided every 12 hours (Max: 320 mg trimethoprim/1,600 mg sulfamethoxazole/day) for 10 days; may increase dose to 20 mg/kg/day (trimethoprim component) PO divided every 12 hours (Max: 640 mg trimethoprim/3,200 mg sulfamethoxazole/day) and/or duration to 3 to 4 weeks if symptoms worsen or persist. Follow with long-term suppressive therapy in persons with severe immunosuppression.
Adolescents: 160 mg trimethoprim/800 mg sulfamethoxazole PO 4 times daily for 10 days or 160 mg trimethoprim/800 mg sulfamethoxazole PO twice daily for 7 to 10 days; may start with twice-daily dosing and increase dose and/or duration to 3 to 4 weeks if symptoms worsen or persist. Follow with long-term suppressive therapy in persons with a CD4 count less than 200/mm3.
Intravenous dosage:
Infants and Children 2 months to 12 years: 10 mg/kg/day (trimethoprim component) IV divided every 12 hours (Max: 320 mg trimethoprim/1,600 mg sulfamethoxazole/day) for 10 days; may increase dose to 20 mg/kg/day (trimethoprim component) IV divided every 12 hours (Max: 640 mg trimethoprim/3,200 mg sulfamethoxazole/day) and/or duration to 3 to 4 weeks if symptoms worsen or persist. Follow with long-term suppressive therapy in persons with severe immunosuppression.
Adolescents: 160 mg trimethoprim/800 mg sulfamethoxazole IV 4 times daily for 10 days or 160 mg trimethoprim/800 mg sulfamethoxazole IV twice daily for 7 to 10 days; may start with twice-daily dosing and increase dose and/or duration to 3 to 4 weeks if symptoms worsen or persist. Follow with long-term suppressive therapy in persons with a CD4 count less than 200/mm3.
-for the treatment of salmonellosis* in persons without HIV:
Oral dosage:
Infants, Children, and Adolescents 2 months to 17 years: 8 to 10 mg/kg/day (trimethoprim component) PO divided every 12 hours (Max: 320 mg trimethoprim/1,600 mg sulfamethoxazole/day) for 48 to 72 hours or until the patient becomes afebrile. Routine use is not recommended; reserve for patients at high risk for invasive infection.
-for the treatment of salmonellosis* in persons living with HIV:
Oral dosage:
Adolescents: 160 mg trimethoprim/800 mg sulfamethoxazole PO twice daily for 7 to 14 days as an alternative; treat for at least 14 days if concurrent bacteremia in persons with a CD4 count more than 200 cells/mm3. Treat for 2 to 6 weeks in persons with a CD4 count less than 200 cells/mm3. Follow with long-term suppressive therapy if recurrent bacteremia or gastroenteritis with a CD4 count less than 200 cells/mm3 and severe diarrhea.
Intravenous dosage:
Adolescents: 160 mg trimethoprim/800 mg sulfamethoxazole IV twice daily for 7 to 14 days as an alternative; treat for at least 14 days if concurrent bacteremia in persons with a CD4 count more than 200 cells/mm3. Treat for 2 to 6 weeks in persons with a CD4 count less than 200 cells/mm3. Follow with long-term suppressive therapy if recurrent bacteremia or gastroenteritis with a CD4 count less than 200 cells/mm3 and severe diarrhea.
-for the treatment of shigellosis in persons without HIV:
Oral dosage:
Infants, Children, and Adolescents 2 months to 17 years: 8 mg/kg/day (trimethoprim component) PO divided every 12 hours (Max: 320 mg trimethoprim/1,600 mg sulfamethoxazole/day) for 5 days.
Intravenous dosage:
Infants, Children, and Adolescents 2 months to 17 years: 8 to 10 mg/kg/day (trimethoprim component) IV divided every 6 to 12 hours for 5 days.
-for the treatment of shigellosis in persons living with HIV:
Oral dosage:
Adolescents: 160 mg trimethoprim/800 mg sulfamethoxazole PO twice daily for 7 to 10 days as an alternative; treat for at least 14 days if concurrent bacteremia. Treat for up to 6 weeks for recurrent infections.
Intravenous dosage:
Adolescents: 160 mg trimethoprim/800 mg sulfamethoxazole IV twice daily for 7 to 10 days as an alternative; treat for at least 14 days if concurrent bacteremia. Treat for up to 6 weeks for recurrent infections.
-for the treatment of yersiniosis*:
Oral dosage:
Infants, Children, and Adolescents 2 months to 17 years: 8 to 10 mg/kg/day (trimethoprim component) PO divided every 12 hours (Max: 320 mg trimethoprim/1,600 mg sulfamethoxazole/day) for 7 to 14 days as first-line therapy; treat for 14 days if concurrent bacteremia.

For the treatment of typhoid fever*:
-for the treatment of fully sensitive uncomplicated typhoid fever*:
Oral dosage:
Infants, Children, and Adolescents 2 months to 17 years: 8 to 12 mg/kg/day (trimethoprim component) PO divided 2 or 4 times daily (Max: 640 mg trimethoprim/day) for 14 days as an alternative.
-for the treatment of fully sensitive severe typhoid fever*:
Intravenous dosage:
Infants, Children, and Adolescents 2 months to 17 years: 8 to 12 mg/kg/day (trimethoprim component) IV divided 2 or 4 times daily (Max: 640 mg trimethoprim/day) for 14 days as an alternative.

For the treatment of peritoneal dialysis-related peritonitis* and peritoneal dialysis catheter-related infection*:
-for the treatment of peritoneal dialysis-related peritonitis*:
Oral dosage:
Infants, Children, and Adolescents 2 months to 17 years: 5 to 10 mg/kg/dose (trimethoprim component) PO every 24 hours (Max: 80 mg trimethoprim/400 mg sulfamethoxazole/day) for 21 days.
-for the treatment of peritoneal dialysis catheter-related infection*:
Oral dosage:
Infants, Children, and Adolescents 2 months to 17 years: 5 to 10 mg/kg/dose (trimethoprim component) PO every 24 hours (Max: 80 mg trimethoprim/400 mg sulfamethoxazole/day) for 14 to 28 days.

For secondary cystoisosporiasis prophylaxis* (i.e., long-term suppressive therapy*) in persons with HIV:
Oral dosage:
Infants and Children 2 months to 12 years: 2.5 mg/kg/dose (trimethoprim component) PO twice daily 3 times weekly (Max: 160 mg trimethoprim/day) in patients with severe immunosuppression (CDC immunologic category 3). Discontinuation may be considered in patients without evidence of active infection who have sustained improvement in immunologic status (CDC immunologic category 1 or 2) for longer than 6 months in response to antiretroviral therapy.
Adolescents: 160 mg trimethoprim/800 mg sulfamethoxazole PO 3 times weekly, or alternatively, 160 mg trimethoprim/800 mg sulfamethoxazole PO once daily or 320 mg trimethoprim/1,600 mg sulfamethoxazole PO 3 times weekly in patients with CD4 count less than 200 cells/mm3. Discontinuation may be considered in patients without evidence of active infection who have sustained increase in CD4 count to more than 200 cells/mm3 for more than 6 months in response to antiretroviral therapy.

For the treatment of plague* infection:
-for the treatment of bubonic or pharyngeal plague*:
Oral dosage:
Infants, Children, and Adolescents 2 months to 17 years: 5 mg/kg/dose (trimethoprim component) PO every 8 hours for 10 to 14 days as an alternative therapy. Monotherapy is recommended for stable patients with naturally occurring plague, although dual therapy can be considered for patients with large buboes. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment in patients infected after intentional release of Y. pestis.
Intravenous dosage:
Infants, Children, and Adolescents 2 months to 17 years: 5 mg/kg/dose (trimethoprim component) IV every 8 hours for 10 to 14 days as an alternative therapy. Monotherapy is recommended for stable patients with naturally occurring plague, although dual therapy can be considered for patients with large buboes. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment in patients infected after intentional release of Y. pestis.
-for the treatment of pneumonic or septicemic plague*:
Oral dosage:
Infants, Children, and Adolescents 2 months to 17 years: 5 mg/kg/dose (trimethoprim component) PO every 8 hours for 10 to 14 days as an alternative therapy. Monotherapy can be considered for mild-to-moderate disease in patients with naturally occurring plague. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment in patients with severe disease and patients infected after intentional release of Y. pestis.
Intravenous dosage:
Infants, Children, and Adolescents 2 months to 17 years: 5 mg/kg/dose (trimethoprim component) IV every 8 hours for 10 to 14 days as an alternative therapy. Monotherapy can be considered for mild-to-moderate disease in patients with naturally occurring plague. Use dual therapy with 2 distinct classes of antimicrobials for initial treatment in patients with severe disease and patients infected after intentional release of Y. pestis.

For plague prophylaxis*:
-for pre-exposure prophylaxis*:
Oral dosage:
Infants, Children, and Adolescents 2 months to 17 years: 5 mg/kg/dose (trimethoprim component) PO every 12 hours until 48 hours after the last perceived exposure as an alternative therapy.
-for postexposure prophylaxis*:
Oral dosage:
Infants, Children, and Adolescents 2 months to 17 years: 5 mg/kg/dose (trimethoprim component) PO every 12 hours for 7 days as an alternative therapy.

For the treatment of bartonellosis*, including uncomplicated Oroya fever*:
Oral dosage:
Infants, Children, and Adolescents: 10 mg/kg/day (trimethoprim component) PO divided every 12 hours (Max: 320 mg trimethoprim/1,600 mg sulfamethoxazole/day) for 14 days as second-line therapy.

For secondary salmonellosis prophylaxis* (i.e., long-term suppressive therapy*) in persons living with HIV:
Oral dosage:
Adolescents: 160 mg trimethoprim/800 mg sulfamethoxazole PO every 12 hours in persons with recurrent bacteremia or gastroenteritis with a CD4 count of less than 200 cells/mm3 and severe diarrhea as an alternative. Discontinuation may be considered after resolution of infection in persons with a response to antiretroviral therapy with sustained viral suppression and CD4 count more than 200 cells/mm3.

For the treatment of invasive vibriosis*:
Oral dosage:
Infants, Children, and Adolescents 2 months to 17 years: 8 to 10 mg/kg/day (trimethoprim component) PO divided every 12 hours (Max: 320 mg trimethoprim/1,600 mg sulfamethoxazole/day) in combination with gentamicin for 7 to 14 days.
Intravenous dosage:
Infants, Children, and Adolescents 2 months to 17 years: 8 to 10 mg/kg/day (trimethoprim component) IV divided every 12 hours (Max: 320 mg trimethoprim/1,600 mg sulfamethoxazole/day) in combination with gentamicin for 7 to 14 days.

For the treatment of small intestinal bacterial overgrowth*:
Oral dosage:
Children and Adolescents: 8 to 10 mg/kg/day (trimethoprim component) PO divided every 12 hours (Max: 320 mg trimethoprim/1,600 mg sulfamethoxazole/day) for 7 to 10 days.

For the treatment of bone and joint infections*, including osteomyelitis*, infectious arthritis*, and infectious bursitis*:
-for the treatment of osteomyelitis*:
Intravenous dosage:
Infants 2 months: 8 to 20 mg/kg/day (trimethoprim component) IV divided every 6 to 12 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Infants, Children, and Adolescents 3 months to 17 years: 8 to 20 mg/kg/day (trimethoprim component) IV divided every 6 to 12 hours (Max: 640 mg trimethoprim/day). Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 3 to 4 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for severe or complicated infections.
Oral dosage:
Infants 2 months: 8 to 20 mg/kg/day (trimethoprim component) PO divided every 6 to 12 hours as step-down therapy after initial parenteral therapy. Treat for a total duration of 4 to 6 weeks (parenteral plus oral). A longer course (several months) may be needed for severe or complicated infections.
Infants, Children, and Adolescents 3 months to 17 years: 8 to 20 mg/kg/day (trimethoprim component) PO divided every 6 to 12 hours (Max: 640 mg trimethoprim/day) as step-down therapy after initial parenteral therapy. Treat for a total duration of 3 to 4 weeks (parenteral plus oral) for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for severe or complicated infections.
-for the treatment of infectious arthritis*:
Intravenous dosage:
Infants 2 months: 8 to 20 mg/kg/day (trimethoprim component) IV divided every 6 to 12 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Infants, Children, and Adolescents 3 months to 17 years: 8 to 20 mg/kg/day (trimethoprim component) IV divided every 6 to 12 hours (Max: 640 mg trimethoprim/day). Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 2 to 3 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for septic hip arthritis or severe or complicated infections.
Oral dosage:
Infants 2 months: 8 to 20 mg/kg/day (trimethoprim component) PO divided every 6 to 12 hours as step-down therapy after initial parenteral therapy. Treat for a total duration of 4 to 6 weeks (parenteral plus oral). A longer course (several months) may be needed for severe or complicated infections.
Infants, Children, and Adolescents 3 months to 17 years: 8 to 20 mg/kg/day (trimethoprim component) PO divided every 6 to 12 hours (Max: 640 mg trimethoprim/day) as step-down therapy after initial parenteral therapy. Treat for a total duration of 2 to 3 weeks (parenteral plus oral) for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for septic hip arthritis or severe or complicated infections.
-for the treatment of infectious bursitis*:
Intravenous dosage:
Children and Adolescents: 8 to 20 mg/kg/day (trimethoprim component) IV divided every 6 to 12 hours (Max: 640 mg trimethoprim/day) for 2 to 3 weeks. Generally, 2 weeks is appropriate for most patients; immunocompromised patients may require a longer duration.
Oral dosage:
Children and Adolescents: 8 to 20 mg/kg/day (trimethoprim component) PO divided every 6 to 12 hours (Max: 640 mg trimethoprim/day) for 2 to 3 weeks. Generally, 2 weeks is appropriate for most patients; immunocompromised patients may require a longer duration.

For the treatment of listeriosis*:
NOTE: For CNS disease, see meningitis indication.
-for the treatment of invasive listeriosis* with bacteremia:
Intravenous dosage:
Infants, Children, and Adolescents 2 months to 17 years: 8 to 20 mg/kg/day (trimethoprim component) IV divided every 6 to 12 hours for 14 days.
-for the treatment of gastroenteritis due L. monocytogenes* in persons at risk for invasive disease:
Oral dosage:
Infants, Children, and Adolescents 2 months to 17 years: 8 to 10 mg/kg/day (trimethoprim component) PO divided every 12 hours (Max: 320 mg trimethoprim/1,600 mg sulfamethoxazole/day) for 3 to 7 days.

Maximum Dosage Limits:
All doses are based on trimethoprim component.
-Neonates
Contraindicated in infants younger than 2 months of age; however, doses up to 10 mg/kg/day PO are used off-label for PCP prophylaxis in HIV-infected/exposed infants as young as 4 weeks of age.
-Infants
younger than 2 months: Contraindicated in infants younger than 2 months of age; however, doses up to 10 mg/kg/day PO are used off-label for PCP prophylaxis in HIV-infected/exposed infants as young as 4 weeks of age.
2 to 11 months: 20 mg/kg/day PO/IV.
-Children
20 mg/kg/day PO (Max: 1,600 mg/day); 20 mg/kg/day IV (Max: 960 mg/day).
-Adolescents
20 mg/kg/day PO (Max: 1,600 mg/day); 20 mg/kg/day IV (Max: 960 mg/day).

Patients with Hepatic Impairment Dosing
Both sulfamethoxazole and trimethoprim are metabolized by the liver. Dosage adjustments may be necessary in patients with hepatic impairment; however, specific dosage adjustment guidelines are not available.

Patients with Renal Impairment Dosing
Off-label dose adjustments
The following dose adjustments are based on a usual recommended dose in pediatric patients of 5 to 20 mg/kg/day (trimethoprim component) divided every 6 to 12 hours :
CrCl more than 50 mL/minute/1.73 m2: No dosage adjustment needed.
CrCl 30 to 50 mL/minute/1.73 m2: 5 to 7.5 mg/kg/dose every 8 hours.
CrCl 10 to 29 mL/minute/1.73 m2: 5 to 10 mg/kg/dose every 12 hours.
CrCl less than 10 mL/minute/1.73 m2: Use not recommended; if used, 5 to 10 mg/kg/dose every 24 hours.

FDA-approved dose adjustments

CrCl more than 30 mL/minute: No dosage adjustment needed.
CrCl 15 to 30 mL/minute: Reduce the recommended dose by 50%.
CrCl less than 15 mL/minute: Use not recommended.

Intermittent hemodialysis
Generally, use is not recommended in patients receiving hemodialysis. If used, 5 to 10 mg/kg/dose of trimethoprim component every 24 hours.

Peritoneal dialysis
Generally, use is not recommended in patients receiving peritoneal dialysis. If used, 5 to 10 mg/kg/dose of trimethoprim component every 24 hours.

Continuous renal replacement therapy (CRRT)
5 mg/kg/dose of trimethoprim component every 8 hours.

*non-FDA-approved indication

Monograph content under development

Mechanism of Action: Sulfamethoxazole; trimethoprim is usually bactericidal and acts by inhibiting sequential enzymes of the folic acid synthesis pathway. Sulfamethoxazole is a structural analog of p-aminobenzoic acid (PABA), and it inhibits the formation of dihydrofolic acid by competing with PABA for binding to bacterial dihydropteroate synthase. This action interferes with the conversion of PABA into folic acid, an essential component of bacterial development. Trimethoprim binds to and reversibly inhibits the enzyme dihydrofolate reductase, which prevents the formation of tetrahydrofolic acid from dihydrofolic acid. Tetrahydrofolic acid, or THF, is the metabolically active form of folic acid. Without THF, bacteria cannot synthesize thymidine, which leads to interference with bacterial nucleic acid and protein formation. The combination of trimethoprim with sulfamethoxazole is synergistic against some bacteria.

The susceptibility interpretive criteria for sulfamethoxazole; trimethoprim are delineated by pathogen. The MICs are defined for Enterobacterales, B. cepacia complex, Acinetobacter sp., S. maltophilia, other non-Enterobacterales, Staphylococcus sp., B. pseudomallei, Y. pestis, Aerococcus sp., Aeromonas sp., Lactococcus sp., R. mucilaginosa, Bacillus sp. (excluding B. anthracis), Corynebacterium sp., and Vibrio sp. as susceptible at 2/38 mcg/mL or less and resistant at 4/76 mcg/mL or more. The MICs are defined for H. influenzae, H. parainfluenzae, S. pneumoniae, Aggregatibacter sp., Cardiobacterium sp., E. corrodens, Kingella sp., and M. catarrhalis as susceptible at 0.5/9.5 mcg/mL or less, intermediate at 1/19 to 2/38 mcg/mL, and resistant at 4/76 mcg/mL or more. The MICs are defined for N. meningitidis as susceptible at 0.12/2.4 mcg/mL or less, intermediate at 0.25/4.75 mcg/mL, and resistant at 0.5/9.5 mcg/mL or more; sulfamethoxazole; trimethoprim may only be appropriate for prophylaxis of meningococcal case contacts. The MICs are defined for L. monocytogenes and Pasteurella sp. as susceptible at 0.5/9.5 mcg/mL or less. The MICs are defined for Brucella sp. as susceptible at 2/38 mcg/mL or less.

Differences in toxicity between healthy individuals and certain patient populations have been documented with sulfonamides. Sulfonamides are metabolized mainly by acetylation. Patients who are slow acetylators (50% of the US population) metabolize more sulfonamide drug by the cytochrome P450 system than fast acetylators. Metabolism via the cytochrome P450 system produces reactive metabolites, usually detoxified by scavengers, such as glutathione. Some patient populations, however, have low amounts of glutathione (i.e., AIDS patients) and toxic metabolites accumulate, leading to a higher incidence of severe toxicities such as hypersensitivity reactions.

Pharmacokinetics: Sulfamethoxazole; trimethoprim is administered orally and intravenously. Both sulfamethoxazole and trimethoprim are widely distributed throughout all body tissues and fluids, including sputum, vaginal fluid, and middle ear fluid. CSF concentrations are 20% and 30% to 50% of serum concentrations, respectively, for sulfamethoxazole and trimethoprim. Trimethoprim also reaches high concentrations in the liver, kidney, pulmonary tissue, and prostatic fluid. Protein binding is 44% for trimethoprim and 70% for sulfamethoxazole. Only the free forms of sulfamethoxazole and trimethoprim are considered to be therapeutically active. The kidney and liver are both important in the elimination of trimethoprim and sulfamethoxazole. Sulfamethoxazole is metabolized to at least 5 metabolites, primarily by N4 acetylation; 1 glucuronide conjugate metabolite has been identified. Formation of the N4 hydroxy metabolite is mediated via CYP2C9. Trimethoprim is metabolized to 11 various metabolites; the major metabolites are 1- and 3-oxides and the 3- and 4-hydroxy derivatives. Approximately 80% of trimethoprim and 20% of sulfamethoxazole is eliminated unchanged in the urine. Both compounds are removed by glomerular filtration, with some tubular secretion. Small amounts of both trimethoprim and sulfamethoxazole are excreted in the bile. In pediatric patients with normal renal function, the mean serum half-lives of sulfamethoxazole and trimethoprim are approximately 10 and 6 to 10 hours, respectively.

Affected cytochrome P450 isoenzymes and drug transporter: CYP2C9, CYP2C8, P-gp, OCT1, OCT2
Sulfamethoxazole is a substrate and inhibitor of CYP2C9. In vitro data suggest trimethoprim is a substrate for the drug transporters P-glycoprotein (P-gp), OCT1, and OCT2. Trimethoprim also inhibits both OCT2 and the hepatic isoenzyme CYP2C8.


-Route-Specific Pharmacokinetics
Oral Route
Sulfamethoxazole; trimethoprim is rapidly absorbed after oral administration. Peak serum concentrations of 1 to 2 mcg/mL and 40 to 60 mcg/mL are achieved 1 to 4 hours after an oral dose of 160 mg trimethoprim and 800 mg sulfamethoxazole, respectively. At steady state, the serum ratio of trimethoprim to sulfamethoxazole is 1:20.

Intravenous Route
Peak concentrations are reached approximately 1 hour after IV administration. After an IV infusion of 160 mg trimethoprim and 800 mg sulfamethoxazole, peak steady-state serum concentrations are approximately 9 mcg/mL and 105 mcg/mL, and troughs are 6 mcg/mL and 70 mcg/mL, respectively.


-Special Populations
Pediatrics
Infants, Children, and Adolescents
The serum half-lives of sulfamethoxazole and trimethoprim increase with age. In a pharmacokinetic study that included children and adults, the mean elimination half-life of sulfamethoxazole and trimethoprim was approximately 9.9 (+/- 3.9) and 5.6 (+/- 1.9) hours, respectively, in infants and children 3 months to less than 10 years (n = 9). In 1 infant (2 months of age), the mean elimination half-life of sulfamethoxazole and trimethoprim was 7.5 and 11.4 hours, respectively. In patients who were 10 to 49 years of age (n = 14), the mean elimination half-life of sulfamethoxazole and trimethoprim was approximately 10.1 (+/- 4.6) and 9.5 (+/- 3.2) hours, respectively. A pharmacokinetic simulation study with data from 153 infants and children demonstrated that mean steady-state AUC and maximum plasma concentration of trimethoprim and sulfamethoxazole would be comparable between pediatric patients 2 months to 18 years receiving 8 mg/kg/day trimethoprim/40 mg/kg/day sulfamethoxazole divided every 12 hours and adult patients receiving 320 mg trimethoprim/1,600 mg sulfamethoxazole per day.

Hepatic Impairment
The pharmacokinetics of sulfamethoxazole; trimethoprim were not altered in patients with hepatic impairment in a study in children and adults.

Renal Impairment
Pharmacokinetic data in pediatric patients with renal impairment are not available; however, data in adult patients have shown that renal impairment can significantly affect the pharmacokinetics of sulfamethoxazole and trimethoprim. Protein binding of sulfamethoxazole, but not trimethoprim, appears to be affected by uremia and hypoalbuminemia; in 1 small study in adults, protein binding of sulfamethoxazole dropped from about 62.2% in patients without uremia (n = 8) to 38.3% in patients with uremia (n = 7) and 14.7% in patients with uremia and hypoalbuminemia (n = 4). The half-lives of both sulfamethoxazole and trimethoprim are increased in patients with renal impairment. The half-life of sulfamethoxazole is increased to 20 to 50 hours and the half-life of trimethoprim is increased to 20 to 49 hours in patients with renal failure. Non-renal clearance may compensate for reduced renal clearance somewhat, as a 90% reduction in CrCl has been associated with only a 62% and 80% reduction in total body clearance for trimethoprim and sulfamethoxazole, respectively. The metabolite, N-acetyl-sulfamethoxazole, may accumulate in patients with significant renal dysfunction. Trimethoprim and sulfamethoxazole are significantly removed during hemodialysis. A pharmacokinetic study in adults demonstrated that 44% of the administered trimethoprim and 57% of the administered sulfamethoxazole dose was removed during hemodialysis, suggesting that 50% of the normal dose be administered after the dialysis session. Another pharmacokinetic study in adults suggested that peritoneal dialysis does not substantially remove sulfamethoxazole; trimethoprim.