Dosing & Uses
Dosage Forms & Strengths
trimethoprim/sulfamethoxazole
injected solution
- (16mg/80mg)/mL
oral suspension
- (40mg/200mg)/5mL
tablet
- 80mg/400mg
- 160mg/800mg
Dosing Guidelines for Infections
1-2 DS tablets PO q12-24hr
Chronic Bronchitis
Acute exacerbations of chronic bronchitis due to susceptible strains of Streptococcus pneumoniae or Haemophilus influenzae
DS tablet: 1 PO q12h for 10-14 days
Meningitis, Bacterial
10-20 mg TMP/kg/day IV divided q6-12hr
Pneumocystis (Carinii) Jiroveci Pneumonia
Documented Pneumocystis jiroveci pneumonia (PCP); also, prophylaxis against PCP in individuals who are immunosuppressed
Prophylaxis
- Tablet: 80-160 mg TMP PO qDay or 160 mg TMP 3 times/week on consecutive or alternate days
Treatment
Sepsis
20 mg TMP/kg/day IV divided q6hr
Shigellosis
Enteritis caused by susceptible strains of Shigella flexneri and S sonnei
DS tablet: 1 tab PO q12hr for 5 days
Alternatively, 8-10 mg TMP/kg/day IV divided q6-12hr for up to 5 days
Traveler's Diarrhea
Traveler's diarrhea due to susceptible strains of enterotoxigenic Escherichia coli
DS tablet: 1 tab PO q12hr for 5 days
Urinary Tract Infections
UTIs caused by susceptible strains of Escherichia coli, Klebsiella species, Enterobacter species, Morganella morganii, Proteus mirabilis, and Proteus vulgaris
Pyelonephritis: 1 DS tab or 2 regular-strength tabs PO q12hr x 14 days
Prostatitis: 1 DS tab or 2 regular-strength tabs PO q12hr x 14 days or 2-3 months if chronic infection
A 3 to 5 day course may be used for acute, uncomplicated cystitis
Prophylaxis (off-label): Various regimens exist; may use regular-strength tablet once/twice per week
Acne Vulgaris (Off-label)
1 DS tab or 1 regular-strength tab PO qDay or q12hr for up to 18 weeks
Community Acquired Pneumonia (Off-label)
1 DS tab PO q12hr for 10-14 days
Dosage Modifications
Renal impairment
- CrCl >30 mL/min: Dose adjustment not necessary
- CrCl 15-30 mL/min: Decrease dose by 50%
- CrCl <15 mL/min: Do not use
Renal impairment, off-label
- Administer doses PO/IV
- Dosing (Dose based on Total Body Weight(TBW) and trimethoprim component; use TBW in obese patients)
Pneumocystis jjirovecii pneumonia (PJP) prophylaxis
- CrCl < 30mL/min: 160 mg (1DS) q24hr or 80 mg (1 SS) q24hr or 160 mg (1DS) 3x week
- Hemodialysis (HD): 80 mg (1 SS) q24 hr or 160 mg (1DS) 3 x week; on hemodialysis days, administer dose post-HD
- Continuous renal replacement therapy (CRRT): 160 mg (1 DS) q24hr or 80 mg (1SS) q24hr or 160 mg (1DS) 3x week
Pneumocystis jjirovecii pneumonia (PJP) treatment
- CrCl < 30mL/min: 5 mg/kg q12hr
- HD: 10 mg/kg post-HD
- CRRT: 5 mg/kg q12hr
- Total daily dose: 15-20 mg/kg/day for Pneumocystis treatment
Skin and soft tissue infection
- CrCl < 30mL/min: 80-160 mg (1-2 SS) q12hr
- HD: 80 mg (1SS) q24hr; on hemodialysis days, administer dose post-HD
- CRRT: 80-160 mg (1-2SS) q12hr
Stenotrophomonas treatment
- CrCl<30mL/min: 4 mg/kg q12hr
- HD: 8 mg/kg post-HD
- CRRT: 4 mg/kg q12hr
- Total daily dose: 12-15 mg/kg/day for Stenotrophomonas treatment
Urinary tract infection
- CrCl < 30mL/min: 80 mg (1SS) q12hr
- HD: 80 mg (1SS) q12hr; on hemodialysis days, administer dose post-HD
- CRRT: 160 mg (1DS) q12hr
Other Infections
- CrCl < 30mL/min: 3 mg/kg q12hr
- HD: 6 mg/kg post-HD
- CRRT: 3 mg/kg q12hr
- Total daily dose: 8-12 mg/kg/day
Dosing Considerations
Susceptible organisms
- Acinetobacter baumannii, Actinobacillus actinomycetemcomitans, Aeromonas hydrophila, Alcaligenes xylosoxidans, Bartonella henselae, Bordetella pertussis, Brucella spp, Burkholderia pseudomallei, Burkholderia cepacia, Chryseobacterium meningosepticum, Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli, Haemophilus aphrophilus, Haemophilus influenzae, Hafnia alvei, Kingella spp, Klebsiella pneumoniae, Klebsiella granulomatis, Legionella spp, Listeria monocytogenes, Moraxella catarrhalis, Morganella morganii, MRSA, MSSA, Nocardia asteroides, Plesiomonas shigelloides, Pneumocystis jiroveci (PCP), Proteus mirabilis, Proteus vulgaris, Providencia rettgeri, Providencia stuartii, Salmonella typhi, Serratia spp, Shigella spp, Staphylococcus saprophyticus, Stenotrophomonas maltophilia, Streptococcus pneumoniae, Tropheryma whippelii, Vibrio cholerae, Yersinia enterocolitica, Yersinia pseudotuberculosis, various Mycobacteria
Dosage Forms & Strengths
trimethoprim/sulfamethoxazole
injected solution
- (16mg/80mg)/mL
oral solution
- (40mg/200mg)/5mL
tablet
- 80mg/400mg
- 160mg/800mg
Mild to Moderate Infections
<2 months: Contraindicated
>2 months
Serious Infections
<2 months: Contraindicated
>2 months
Acute Otitis Media
Acute otitis media in pediatric patients due to susceptible strains of Streptococcus pneumoniae or Haemophilus influenzae
<2 months: Contraindicated
>2 months: 6-10 mg TMP/kg/day PO divided q12hr for 10 days
Pneumocystis (Carinii) Jiroveci Pneumonia
<2 months: Contraindicated
>2 months
- Treatment: 15-20 mg TMP/kg/day PO/IV divided q6-8hr for 21 days
- Prophylaxis: 150 mg TMP/m²/day PO divided q12 hr for 3 days/week on consecutive or alternate days
Shigellosis
<2 months: Contraindicated
>2 months
Urinary Tract Infection
<2 months: Contraindicated
>2 months
- 8 mg TMP/kg/day PO divided q12hr for 7-14 days if serious infection
- 8-10 mg TMP/kg/day IV divided q6-12hr for 14 days if serious infection
- Prophylaxis: 2 mg TMP/kg/dose PO qDay or 5 mg TMP/kg/dose twice weekly
Skin/soft Tissue Infection Due to Community Acquired MRSA (Off-label)
8-12 mg TMP/kg/day PO divided q12hr for 5-10 days; add beta-lactam antibiotic to regimen if beta-hemolytic Streptococcus spp also suspected
Interactions
Interaction Checker
No Results

Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor

Adverse Effects
Frequency Not Defined
Anorexia
Nausea
Vomiting
Vertigo
Seizure
Peripheral neuritis
Erythema multiforme
Hyperkalemia
Rash
Urticaria
Immune hypersensitivity reaction
Stevens-Johnson syndrome
Toxic epidermal necrolysis
Agranulocytosis
Aplastic anemia
Hyponatremia
Disorder of hematopoietic structure
Fulminant hepatic necrosis
Postmarketing Reports
Thrombotic thrombocytopenia purpura
Idiopathic thrombocytopenic purpura
QT prolongation resulting in ventricular tachycardia and torsade de pointes
Embryo-fetal toxicity
Hypersensitivity and other fatal reactions
Thrombocytopenia
Clostridium difficile-associated diarrhea
Sulfite sensitivity
Risk associated with concurrent use of leucovorin for
Pneumocystis jirovecii
Pneumonia
Infusion reactions
Hypoglycemia
Electrolyte abnormalities
Thrombophlebitis
Propylene glycol Toxicity
Metabolic acidosis
Drug reaction with eosinophilia and systemic symptoms (DRESS)
Acute generalized exanthematous pustulosis (AGEP)
Acute febrile neutrophilic dermatosis (AFND)
Warnings
Contraindications
Known hypersensitivity
Age <2 months
CrCl <15 mL/min when renal function status cannot be monitored
Documented megaloblastic or folate deficiency anemia
Significan hepatic impairment
Contraindicated in pregnant patients at term and in nursing mothers, because sulfonamides, which pass the placenta and are excreted in the milk, may cause kernicterus
History of drug-induced immune thrombocytopenia with use of trimethoprim and/or sulfonamides
Concomitant administration with dofetilide
Cautions
Not for use in areas with resistance rates >10%
Treatment with recommended doses may cause hyperkalemia when trimethoprim is administered to patients with underlying disorders of potassium metabolism, with renal insufficiency, or if drugs known to induce hyperkalemia are given concomitantly; close monitoring of serum potassium recommended
Severe and symptomatic hyponatremia can occur in patients receiving sulfamethoxazole/ trimethoprim, particularly for treatment of P. jirovecii pneumonia; evaluation for hyponatremia and appropriate correction is necessary in symptomatic patients to prevent life-threatening complications; if patient treated for Pneumocystis jirovecii develops skin rash, fever, leukopenia, or any other sign of adverse reaction, therapy or re-challenge should be re-evaluated
Circulatory shock with fever, severe hypotension, and confusion requiring intravenous fluid resuscitation and vasopressors has occurred within minutes to hours of re-challenge with trimethoprim-sulfamethoxazole in patients with history of recent (days to weeks) exposure to sulfamethoxazole-trimethoprim
Fatalities associated with the administration of sulfonamides, although rare, have occurred due to severe reactions, including 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), fulminant hepatic necrosis, agranulocytosis, aplastic anemia and other blood dyscrasias; clinical signs, such as rash, sore throat, fever, arthralgia, pallor, purpura or jaundice may be early indications of serious reactions
Caution when used in elderly individuals; risk of bone marrow suppression
PCP prophylaxis with AIDS: Rash, fever, leukopenia, and elevated transaminase values reported; hyperkalemia and hyponatremia also appear to be increased
Severe cases (including fatalities) of immune-mediated thrombocytopenia reported; monitor patients for hematologic toxicity
Sulfonamides should not be used to treat group A beta-hemolytic streptococcal infections; they will not eradicate streptococcus or prevent rheumatic fever
Clostridium difficile-associated diarrhea reported
Coadministration with leucovorin for the treatment of HIV-positive patients with PCP resulted in treatment failure and excess mortality in a randomized, placebo-controlled trial; avoid coadministration
Development of drug-resistant bacteria may occur when prescribed in absence of strongly suspected bacterial infection or prophylactic indication
Prolonged use may result in fungal or bacterial superinfection
Caution with impaired renal or hepatic function, patients with possible folate deficiency (eg, the elderly, chronic alcoholics, patients receiving anticonvulsant therapy, patients with malabsorption syndrome, and patients in malnutrition states), and patients with severe allergies or bronchial asthma
Hemolysis may occur if administered to patients with G6PD deficiency
Hypoglycemia (rare) reported in nondiabetic patients; patients with renal dysfunction, liver disease, or malnutrition or those receiving high doses at particular risk
Trimethoprim may impair phenylalanine metabolism
Caution with porphyria or thyroid dysfunction; sulfonamides can precipitate porphyria crisis and hypothyroidism; avoid use in patients with porphyria or thyroid dysfunction
Complete blood counts should be done frequently in patients receiving therapy; discontinue therapy if a significant reduction in count of any formed blood element is noted’ perform urinalyses with careful microscopic examination and renal function tests during therapy, particularly for those patients with impaired renal function
When administered at high doses as for the treatment of P. jirovecii pneumonia, monitor for total daily intake of propylene glycol from all sources and for acid-base disturbances; discontinue therapy if propylene glycol toxicity suspected
Treatment failure and excess mortality were observed when trimethoprim-sulfamethoxazole was used concomitantly with leucovorin for treatment of HIV positive patients with Pneumocystis jirovecii pneumonia; co-administration of trimethoprim-sulfamethoxazole and leucovorin during treatment of Pneumocystis jirovecii pneumonia should be avoided
During treatment, adequate fluid intake and urinary output should be ensured to prevent crystalluria; patients who are “slow acetylators” may be more prone to idiosyncratic reactions to sulfonamides
Pregnancy & Lactation
Pregnancy
Therapy may cause fetal harm if administered to pregnant woman; some epidemiologic studies suggest that exposure to drug during pregnancy may be associated with increased risk of congenital malformations, particularly neural tube defects, cardiovascular abnormalities, urinary tract defects, oral clefts, and club foot
Urinary tract infection in pregnancy is associated with adverse perinatal outcomes such as preterm birth, low birth weight, and pre-eclampsia, and increased mortality to pregnant woman
P. jirovecii pneumonia in pregnancy is associated with preterm birth and increased morbidity and mortality for the pregnant woman
Use during pregnancy only if potential benefit justifies potential risk to fetus
Lactation
Levels of drug in breast milk are approximately 2 to 5% of recommended daily dose for pediatric patients over two months of age; there is no information regarding effect of therapy on breastfed infant or effect on milk production; because of potential risk of bilirubin displacement and kernicterus on breastfed child, advise women to avoid breastfeeding during therapy
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Blocks 2 consecutive steps in the biosynthesis of nucleic acids and proteins essential to many bacteria
Trimethoprim: Inhibits dihydrofolate reductase, thereby blocking production of tetrahydrofolic acid from dihydrofolic acid
Sulfamethoxazole: Inhibits bacterial synthesis of dihydrofolic acid by competing with para-aminobenzoic acid
Absorption
Time to peak: 1-4 hours
Distribution
Protein bound: TMP (44%); SMX (70%)
Metabolism
Hepatic
Enzymes inhibited: Hepatic CYP2C9
Elimination
Half-life: TMP (8-10 hr); SMX (10 hr)
Excretion: Urine (as unchanged drug)
Administration
IV Incompatibilities
Additive: Fluconazole, linezolid, verapamil
Y-site: Cisatracurium (incompatible at 2 mg/mL cisatra; may be compatible at much lower concs), fluconazole, foscarnet (may be compatible at very low TMP/SMX concs), midazolam, vinorelbine
IV Preparation
Do not use NS as diluent
Injection vehicle contains benzyl alcohol and sodium metabisulfite
Stability of parenteral admixture at room temperature (25°C)
- 5 mL/125 mL D5W: 6 hr
- 5 mL/100 mL D5W: 4 hr
- 5 mL/75 mL D5W: 2 hr
IV Administration
Infuse over 60-90 min; give q6hr, 8hr, or 12hr
Must be diluted well
May be given less diluted in a central line
Not for IM
Maintain adequate fluid intake to prevent crystalluria
Storage
Do not refrigerate injection
Less soluble in more alkaline pH
Protect from light
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Formulary
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