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Pronunciation
(sul fa meth OKS a zole & trye METH oh prim)
Generic Available (U.S.)
Yes
Index Terms
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Oral treatment of urinary tract infections due to E. coli, Klebsiella and Enterobacter sp, M. morganii, P. mirabilis and P. vulgaris; acute otitis media in children; acute exacerbations of chronic bronchitis in adults due to susceptible strains of H. influenzae or S. pneumoniae; treatment and prophylaxis of Pneumocystis jirovecii pneumonia (PCP); traveler's diarrhea due to enterotoxigenic E. coli; treatment of enteritis caused by Shigella flexneri or Shigella sonnei
I.V. treatment of severe or complicated infections when oral therapy is not feasible, for documented PCP, empiric treatment of PCP in immune compromised patients; treatment of documented or suspected shigellosis, typhoid fever, or other infections caused by susceptible bacteria
Use: Unlabeled
Cholera and Salmonella-type infections and nocardiosis; chronic prostatitis; as prophylaxis in neutropenic patients with P. jirovecii infections, in leukemia patients, and in patients following renal transplantation, to decrease incidence of PCP; treatment of Cyclospora infection, typhoid fever, Nocardia asteroides infection; prophylaxis against urinary tract infection; alternative treatment for MRSA infections
Pregnancy Risk Factor
C
Pregnancy Considerations
Adverse events have been observed in animal reproduction studies; therefore, the manufacturer classifies TMP-SMX as pregnancy category C. TMP-SMX crosses the placenta and distributes to amniotic fluid. Due to trimethoprim's potential effect on folic acid metabolism, TMP-SMX should only be used during pregnancy if the benefit justifies the potential risk. The use of dihydrofolate reductase inhibitors, including trimethoprim, during pregnancy may increase the risk of congenital anomalies including cardiovascular defects, oral clefts, urinary tract anomalies, and neural tube defects. Folic acid supplementation may decrease this risk. A few case reports have described additional congenital anomalies after TMP-SMX exposure, but none of these have proven causality. Most studies and case reports have failed to show an increased risk for congenital malformations after use of TMP-SMX. Per the manufacturer, TMP-SMX is contraindicated in late pregnancy because sulfonamides pass the placenta and may cause kernicterus in the newborn, but this has not been observed specifically with SMX. Neonatal healthcare providers should be informed if maternal sulfonamide therapy is used near the time of delivery. TMP-SMX may be used in pregnancy for prophylaxis or treatment of Pneumocystis jirovecii pneumonia (PCP), the prophylaxis of Toxoplasmic gondii encephalitis (TE), and may prevent fetal loss in patients with Q fever (Coxiella burnetii). The pharmacokinetics of TMP-SMX are similar to nonpregnant values in early pregnancy.
Lactation
Enters breast milk/contraindicated (AAP rates “compatible”; AAP 2001 update pending)
Breast-Feeding Considerations
Small amounts of TMP and SMX are transferred to breast milk. Per the manufacturer, TMP-SMX is contraindicated in nursing mothers since sulfonamides cross into the milk and may cause kernicterus in the newborn. Because TMP-SMX has therapeutic indications for infants ≥2 months of age, kernicterus after exposure via breast-feeding would not be expected in healthy infants of this age group; however, sulfonamides should not be used while nursing an infant with G6PD deficiency or hyperbilirubinemia. Nondose related effects could include modification of bowel flora.
Contraindications
Hypersensitivity to any sulfa drug, trimethoprim, or any component of the formulation; megaloblastic anemia due to folate deficiency; infants <2 months of age; marked hepatic damage or severe renal disease (if patient not monitored); pregnancy (at term); breast-feeding
Warnings/Precautions
Concerns related to adverse effects:
• Blood dyscrasias: Fatalities associated with severe reactions including agranulocytosis, aplastic anemia, and other blood dyscrasias have occurred; discontinue use at first sign of rash or signs of serious adverse reactions.
• Dermatologic reactions: Fatalities associated with severe reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis have occurred; discontinue use at first sign of rash.
• Hepatic necrosis: Fatalities associated with hepatic necrosis have occurred; discontinue use at first sign of rash or signs of serious adverse reactions.
• Hyperkalemia: May cause hyperkalemia (associated with high doses of trimethoprim).
• Hypoglycemia: May cause hypoglycemia, particularly in malnourished, or patients with renal or hepatic impairment.
• Sulfonamide allergy: Chemical similarities are present among sulfonamides, sulfonylureas, carbonic anhydrase inhibitors, thiazides, and loop diuretics (except ethacrynic acid). Use in patients with sulfonamide allergy is specifically contraindicated in product labeling, however, a risk of cross-reaction exists in patients with allergy to any of these compounds; avoid use when previous reaction has been severe.
• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns:
• Asthma/allergies: Use with caution in patients with allergies or asthma.
• Hepatic impairment: Use with caution in patients with hepatic impairment.
• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment recommended. Maintain adequate hydration to prevent crystalluria.
• Thyroid dysfunction: Use with caution in patients with thyroid dysfunction.
Special populations:
• AIDS patients: Incidence of adverse effects appears to be increased in patients with AIDS.
• Elderly: Use with caution in the elderly; greater risk for more severe adverse reactions.
• G6PD deficiency: Use with caution in patients with G6PD deficiency; hemolysis may occur (dose-related).
• Patients with potential for folate deficiency: Use with caution in patients with potential folate deficiency (malnourished, chronic anticonvulsant therapy, or elderly).
• Slow acetylators: May be more prone to adverse reactions.
Dosage form specific issues:
• Injection vehicle: May contain benzyl alcohol which has been associated with "gasping syndrome" in neonates and sodium metabisulfite.
Adverse Reactions
The most common adverse reactions include gastrointestinal upset (nausea, vomiting, anorexia) and dermatologic reactions (rash or urticaria). Rare, life-threatening reactions have been associated with co-trimoxazole, including severe dermatologic reactions, blood dyscrasias, and hepatotoxic reactions. Most other reactions listed are rare, however, frequency cannot be accurately estimated.
Cardiovascular: Allergic myocarditis
Central nervous system: Apathy, aseptic meningitis, ataxia, chills, depression, fatigue, fever, hallucinations, headache, insomnia, kernicterus (in neonates), nervousness, peripheral neuritis, seizure, vertigo
Dermatologic: Photosensitivity, pruritus, rash, skin eruptions, urticaria; rare reactions include erythema multiforme, exfoliative dermatitis, Henoch-Schönlein purpura, Stevens-Johnson syndrome, and toxic epidermal necrolysis
Endocrine & metabolic: Hyperkalemia (generally at high dosages), hypoglycemia (rare), hyponatremia
Gastrointestinal: Abdominal pain, anorexia, diarrhea, glottitis, nausea, pancreatitis, pseudomembranous colitis, stomatitis, vomiting
Hematologic: Agranulocytosis, aplastic anemia, eosinophilia, hemolysis (with G6PD deficiency), hemolytic anemia, hypoprothrombinemia, leukopenia, megaloblastic anemia, methemoglobinemia, neutropenia, thrombocytopenia
Hepatic: Hepatotoxicity (including hepatitis, cholestasis, and hepatic necrosis), hyperbilirubinemia, transaminases increased
Neuromuscular & skeletal: Arthralgia, myalgia, rhabdomyolysis, weakness
Otic: Tinnitus
Renal: BUN increased, crystalluria, diuresis (rare), interstitial nephritis, nephrotoxicity (in association with cyclosporine), renal failure, serum creatinine increased, toxic nephrosis (with anuria and oliguria)
Respiratory: Cough, dyspnea, pulmonary infiltrates
Miscellaneous: Allergic reaction, anaphylaxis, angioedema, periarteritis nodosa (rare), serum sickness, systemic lupus erythematosus (rare)
Metabolism/Transport Effects
Refer to individual components.
Drug Interactions
ACE Inhibitors: Trimethoprim may enhance the hyperkalemic effect of ACE Inhibitors. Risk C: Monitor therapy
Amantadine: Trimethoprim may enhance the adverse/toxic effect of Amantadine. Specifically, the risk of myoclonus and/or delirium may be increased. Amantadine may increase the serum concentration of Trimethoprim. Trimethoprim may increase the serum concentration of Amantadine. Risk C: Monitor therapy
Angiotensin II Receptor Blockers: Trimethoprim may enhance the hyperkalemic effect of Angiotensin II Receptor Blockers. Risk C: Monitor therapy
Antidiabetic Agents (Thiazolidinedione): Trimethoprim may decrease the metabolism of Antidiabetic Agents (Thiazolidinedione). Risk C: Monitor therapy
AzaTHIOprine: Sulfamethoxazole may enhance the myelosuppressive effect of AzaTHIOprine. Risk C: Monitor therapy
AzaTHIOprine: Trimethoprim may enhance the myelosuppressive effect of AzaTHIOprine. Risk C: Monitor therapy
BCG: Antibiotics may diminish the therapeutic effect of BCG. Risk X: Avoid combination
Carvedilol: CYP2C9 Inhibitors (Moderate) may increase the serum concentration of Carvedilol. Specifically, concentrations of the S-carvedilol enantiomer may be increased. Risk C: Monitor therapy
Conivaptan: May increase the serum concentration of CYP3A4 Substrates (Low risk). Risk C: Monitor therapy
CycloSPORINE: Sulfonamide Derivatives may enhance the nephrotoxic effect of CycloSPORINE. Sulfonamide Derivatives may decrease the serum concentration of CycloSPORINE. Risk C: Monitor therapy
CycloSPORINE (Systemic): Sulfonamide Derivatives may enhance the nephrotoxic effect of CycloSPORINE (Systemic). Sulfonamide Derivatives may decrease the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy
CYP2C8 Substrates: CYP2C8 Inhibitors (Moderate) may decrease the metabolism of CYP2C8 Substrates. Risk C: Monitor therapy
CYP2C9 Inducers (Strong): May increase the metabolism of CYP2C9 Substrates. Risk C: Monitor therapy
CYP2C9 Inhibitors (Moderate): May decrease the metabolism of CYP2C9 Substrates. Risk C: Monitor therapy
CYP2C9 Inhibitors (Strong): May decrease the metabolism of CYP2C9 Substrates. Risk D: Consider therapy modification
CYP2C9 Substrates: CYP2C9 Inhibitors (Moderate) may decrease the metabolism of CYP2C9 Substrates. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
Dapsone: May increase the serum concentration of Trimethoprim. Trimethoprim may increase the serum concentration of Dapsone. Risk C: Monitor therapy
Dapsone (Systemic): May increase the serum concentration of Trimethoprim. Trimethoprim may increase the serum concentration of Dapsone (Systemic). Risk C: Monitor therapy
Dapsone (Topical): Trimethoprim may enhance the adverse/toxic effect of Dapsone (Topical). More specifically, trimethoprim may increase the risk for hemolysis Risk C: Monitor therapy
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Dofetilide: Trimethoprim may decrease the excretion of Dofetilide. Risk X: Avoid combination
Eplerenone: Trimethoprim may enhance the hyperkalemic effect of Eplerenone. Risk C: Monitor therapy
Fosphenytoin: Sulfonamide Derivatives may increase the serum concentration of Fosphenytoin. Risk C: Monitor therapy
Fosphenytoin: Trimethoprim may increase the serum concentration of Fosphenytoin. Risk C: Monitor therapy
Herbs (CYP3A4 Inducers): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
LamiVUDine: Trimethoprim may decrease the excretion of LamiVUDine. Risk C: Monitor therapy
Leucovorin Calcium-Levoleucovorin: May diminish the therapeutic effect of Trimethoprim. Risk C: Monitor therapy
Memantine: Trimethoprim may enhance the adverse/toxic effect of Memantine. Specifically, the risk of myoclonus and/or delirium may be increased. Memantine may increase the serum concentration of Trimethoprim. Trimethoprim may increase the serum concentration of Memantine. Risk C: Monitor therapy
Mercaptopurine: Sulfamethoxazole may enhance the myelosuppressive effect of Mercaptopurine. Risk C: Monitor therapy
Mercaptopurine: Trimethoprim may enhance the myelosuppressive effect of Mercaptopurine. Risk C: Monitor therapy
Methenamine: May enhance the adverse/toxic effect of Sulfonamide Derivatives. Specifically, the combination may result in the formation of an insoluble precipitate in the urine. Risk X: Avoid combination
Methotrexate: Sulfonamide Derivatives may enhance the adverse/toxic effect of Methotrexate. Management: Consider avoiding concomitant use of methotrexate and either sulfamethoxazole or trimethoprim. If used concomitantly, monitor for the development of signs and symptoms of methotrexate toxicity (eg, bone marrow suppression). Risk D: Consider therapy modification
Methotrexate: Trimethoprim may enhance the adverse/toxic effect of Methotrexate. Management: Consider avoiding concomitant use of methotrexate and either sulfamethoxazole or trimethoprim. If used concomitantly, monitor for the development of signs and symptoms of methotrexate toxicity (e.g., bone marrow suppression). Risk D: Consider therapy modification
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2C9 Substrates. Risk C: Monitor therapy
Phenytoin: Sulfonamide Derivatives may increase the serum concentration of Phenytoin. Risk C: Monitor therapy
Phenytoin: Trimethoprim may increase the serum concentration of Phenytoin. Risk C: Monitor therapy
Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Risk C: Monitor therapy
Potassium P-Aminobenzoate: May diminish the therapeutic effect of Sulfonamide Derivatives. Risk X: Avoid combination
PRALAtrexate: Trimethoprim may increase the serum concentration of PRALAtrexate. More specifically, trimethoprim may decrease excretion of pralatrexate. Management: Closely monitor for increased pralatrexate serum level and/or possible toxicity with concomitant use of trimethoprim. Monitor for decreased pralatrexate levels with discontinuation of trimethoprim. Risk C: Monitor therapy
PRALAtrexate: Sulfamethoxazole may increase the serum concentration of PRALAtrexate. More specifically, sulfamethoxazole may decrease excretion of pralatrexate. Management: Closely monitor for increased pralatrexate serum level and/or possible toxicity with concomitant use of sulfamethoxazole. Monitor for decreased pralatrexate levels with discontinuation of sulfamethoxazole. Risk C: Monitor therapy
Prilocaine: Methemoglobinemia Associated Agents may enhance the adverse/toxic effect of Prilocaine. Combinations of these agents may increase the likelihood of significant methemoglobinemia. Management: Monitor patients for signs of methemoglobinemia (e.g., hypoxia, cyanosis) when prilocaine is used in combination with other agents associated with development of methemoglobinemia. Avoid lidocaine/prilocaine in infants receiving such agents. Risk C: Monitor therapy
Procainamide: Trimethoprim may increase serum concentrations of the active metabolite(s) of Procainamide. Trimethoprim may increase the serum concentration of Procainamide. Risk D: Consider therapy modification
Procaine: May diminish the therapeutic effect of Sulfonamide Derivatives. Risk X: Avoid combination
Repaglinide: Trimethoprim may decrease the metabolism of Repaglinide. Risk C: Monitor therapy
Spironolactone: Trimethoprim may enhance the hyperkalemic effect of Spironolactone. Risk C: Monitor therapy
Sulfonylureas: Sulfonamide Derivatives may enhance the hypoglycemic effect of Sulfonylureas. Risk C: Monitor therapy
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 24 hours after cessation of antibacterial agents. Risk D: Consider therapy modification
Varenicline: Trimethoprim may increase the serum concentration of Varenicline. Management: Monitor for increased varenicline adverse effects with concomitant use of trimethoprim, particulary in patients with severe renal impairment. International product labeling recommendations vary. Consult appropriate labeling. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Sulfonamide Derivatives may enhance the anticoagulant effect of Vitamin K Antagonists. Risk D: Consider therapy modification
Ethanol/Nutrition/Herb Interactions
Herb/Nutraceutical: Avoid dong quai; St John's wort (may diminish effects and also cause photosensitization).
Storage
Injection: Store at room temperature; do not refrigerate. Less soluble in more alkaline pH. Protect from light. Solution must be diluted prior to administration. Following dilution, store at room temperature; do not refrigerate. Manufacturer recommended dilutions and stability of parenteral admixture at room temperature (25°C):
5 mL/125 mL D5W; stable for 6 hours.
5 mL/100 mL D5W; stable for 4 hours.
5 mL/75 mL D5W; stable for 2 hours.
Studies have also confirmed limited stability in NS; detailed references should be consulted.
Suspension, tablet: Store at controlled room temperature of 15°C to 25°C (59°F to 77°F). Protect from light.
Compatibility
Stable in D5W, D51/2NS, LR, 1/2NS; variable stability (consult detailed reference) in NS.
Y-site administration: Compatible: Acyclovir, aldesleukin, allopurinol, amifostine, Aminosyn® II, amphotericin B cholesteryl sulfate complex, anidulafungin, atracurium, aztreonam, bivalirudin, cefepime, cyclophosphamide, cyclosporine, dexmedetomidine, diltiazem, docetaxel, doxorubicin liposome, enalaprilat, esmolol, etoposide phosphate, fenoldopam, filgrastim, fludarabine, gallium nitrate, gemcitabine, granisetron, hetastarch in lactate electrolyte injection (Hextend®), hydromorphone, labetalol, linezolid, lorazepam, magnesium sulfate, melphalan, meperidine, morphine, nicardipine, oxytocin, pancuronium, pemetrexed, piperacillin/tazobactam, remifentanil, sargramostim, tacrolimus, teniposide, thiotepa, vecuronium, zidovudine. Incompatible: Caspofungin, fluconazole, midazolam, pantoprazole, vinorelbine. Variable (consult detailed reference): Cisatracurium, foscarnet.
Compatibility in syringe: Compatible: Dimenhydramine, heparin. Incompatible: Pantoprazole.
Mechanism of Action
Sulfamethoxazole interferes with bacterial folic acid synthesis and growth via inhibition of dihydrofolic acid formation from para-aminobenzoic acid; trimethoprim inhibits dihydrofolic acid reduction to tetrahydrofolate resulting in sequential inhibition of enzymes of the folic acid pathway
Pharmacodynamics/Kinetics
Absorption: Oral: Almost completely, 90% to 100%
Protein binding: SMX: 68%, TMP: 45%
Metabolism: SMX: N-acetylated and glucuronidated; TMP: Metabolized to oxide and hydroxylated metabolites
Half-life elimination: SMX: 9 hours, TMP: 6-17 hours; both are prolonged in renal failure
Time to peak, serum: Within 1-4 hours
Excretion: Both are excreted in urine as metabolites and unchanged drug
Effects of aging on the pharmacokinetics of both agents has been variable; increase in half-life and decreases in clearance have been associated with reduced creatinine clearance
Dosage
Dosage recommendations are based on the trimethoprim component. Double-strength tablets are equivalent to sulfamethoxazole 800 mg and trimethoprim 160 mg.
Usual dosage ranges:
Children >2 months: Manufacturer's labeling:
Mild-to-moderate infections: Oral: 8 mg TMP/kg/day in divided doses every 12 hours
Serious infection:
Oral: 15-20 mg TMP/kg/day in divided doses every 6 hours
I.V.: 8-12 mg TMP/kg/day in divided doses every 6-12 hours
Adults:
Oral: 1-2 double-strength tablets (sulfamethoxazole 800 mg; trimethoprim 160 mg) every 12-24 hours
I.V.: 8-20 mg TMP/kg/day divided every 6-12 hours
Indication-specific dosing:
Children >2 months:
Acute otitis media: Oral: 8 mg TMP/kg/day in divided doses every 12 hours for 10 days. Note: Recommended by the American Academy of Pediatrics as an alternative agent in penicillin-allergic patients at a dose of 6-10 mg TMP/kg/day (AOM guidelines, 2004).
Cyclosporiasis (unlabeled use): Oral, I.V.: 5 mg TMP/kg twice daily for 7-10 days (Red Book, 2009)
Pneumocystis jirovecii:
Treatment: Oral, I.V.: 15-20 mg TMP/kg/day in divided doses every 6-8 hours for 21 days
Prophylaxis: Oral, 150 mg TMP/m2/day in divided doses every 12 hours and administered for 3 days/week on consecutive or alternate days; an alternative dosing regimen allows for same dose to be administered in 2 divided doses daily (maximum: trimethoprim 320 mg and sulfamethoxazole 1600 mg daily) (CDC, 2009)
Shigellosis:
Oral: 8 mg TMP/kg/day in divided doses every 12 hours for 5 days
I.V.: 8-10 mg TMP/kg/day in divided doses every 6, 8, or 12 hours for up to 5 days
Skin/soft tissue infection due to community-acquired MRSA (unlabeled use): Oral: 4-6 mg TMP/kg/dose every 12 hours for 5-10 days (Liu, 2011); Note: If beta-hemolytic Streptococcus spp are also suspected, a beta-lactam antibiotic should be added to the regimen (Liu, 2011)
Toxoplasmosis primary prophylaxis in HIV-exposed/infected patients (unlabeled use; CDC, 2009): Oral: 150 mg TMP/m2/day in 2 divided doses (preferred) or 150 mg TMP/m2/day in a single dose 3 times/week on consecutive days; or 150 mg TMP/m2/day in 2 divided doses 3 times/week on alternate days
Urinary tract infection:
Treatment:
Oral: 8 mg TMP/kg/day in divided doses every 12 hours
I.V.: 8-10 mg TMP/kg/day in divided doses every 6, 8, or 12 hours for up to 14 days with serious infections
Prophylaxis: Oral: 2 mg TMP/kg/dose daily or 5 mg TMP/kg/dose twice weekly
Adults:
Chronic bronchitis (acute): Oral: One double-strength tablet every 12 hours for 10-14 days
Cyclosporiasis (unlabeled use): Oral, I.V.: 160 mg TMP twice daily for 7-10 days. Note: AIDS patients: Oral: One double-strength tablet 2-4 times/day for 10 days, then 1 double-strength tablet 3 times/week for 10 weeks (Pape, 1994; Verdier, 2000)
Granuloma inguinale (donovanosis) (unlabeled use): Oral: One double-strength tablet every 12 hours for at least 3 weeks and until lesions have healed (CDC, 2010)
Isosporiasis (Isospora belli infection) in HIV-positive patients (unlabeled use; CDC, 2009):
Treatment: Oral, I.V.: 160 mg TMP 4 times/day for 10 days or 160 mg TMP 2 times/day for 7-10 days. May increase dose and/or duration up to 3-4 weeks if symptoms worsen or persist
Secondary prophylaxis (in patients with CD4+ count <200 /microL): Oral: 160 mg TMP 3 times/week (preferred) or alternatively, 160 mg TMP daily or 320 mg TMP 3 times/week
Meningitis (bacterial): I.V.: 10-20 mg TMP/kg/day in divided doses every 6-12 hours
Nocardia
(unlabeled use): Oral, I.V.:
Cutaneous infections: 5-10 mg TMP/kg/day in 2-4 divided doses
Severe infections (pulmonary/cerebral): 15 mg TMP/kg/day in 2-4 divided doses for 3-4 weeks, then 10 mg TMP/kg/day in 2-4 divided doses. Treatment duration is controversial; an average of 7 months has been reported.
Note: Therapy for severe infection may be initiated I.V. and converted to oral therapy (frequently converted to approximate dosages of oral solid dosage forms: 2 DS tablets every 8-12 hours). Although not widely available, sulfonamide levels should be considered in patients with questionable absorption, at risk for dose-related toxicity, or those with poor therapeutic response.
Osteomyelitis due to MRSA (unlabeled use): Oral, I.V.: 3.5-4 mg TMP/kg/dose every 8-12 hours for a minimum of 8 weeks with rifampin 600 mg once daily (Liu, 2011)
Pneumocystis jirovecii pneumonia (PCP): Oral: Manufacturer's labeling:
Prophylaxis: 160 mg TMP daily
Treatment: 15-20 mg TMP/kg/day divided every 6 hours for 14-21 days
Pneumocystis jirovecii pneumonia (PCP) prophylaxis and treatment in HIV-positive patients (CDC, 2009): Note: Sulfamethoxazole and trimethoprim is the preferred regimen for this indication.
Prophylaxis: Oral: 80-160 mg TMP daily or alternatively, 160 mg TMP 3 times/week
Treatment:
Mild-to-moderate: Oral: 15-20 mg TMP/kg/day in 3 divided doses for 21 days or alternatively, 320 mg TMP 3 times/day for 21 days
Moderate-to-severe: Oral, I.V.: 15-20 mg TMP/kg/day in 3-4 divided doses for 21 days
Sepsis: I.V.: 20 TMP/kg/day divided every 6 hours
Septic arthritis due to MRSA (unlabeled use): Oral, I.V.: 3.5-4 mg TMP/kg/dose every 8-12 hours for 3-4 weeks (some experts combine with rifampin) (Liu, 2011)
Shigellosis:
Oral: One double-strength tablet every 12 hours for 5 days
I.V.: 8-10 mg TMP/kg/day in divided doses every 6, 8, or 12 hours for up to 5 days
Skin/soft tissue infection due to community-acquired MRSA (unlabeled use): Oral: 1-2 double-strength tablets every 12 hours for 5-10 days (Liu, 2011); Note: If beta-hemolytic Streptococcus spp are also suspected, a beta-lactam antibiotic should be added to the regimen (Liu, 2011)
Stenotrophomonas maltophilia
(ventilator-associated pneumonia): I.V.: Most clinicians have utilized 12-15 mg TMP/kg/day for the treatment of VAP caused by Stenotrophomonas maltophilia. Higher doses (up to 20 mg TMP/kg/day) have been mentioned for treatment of severe infection in patients with normal renal function (Looney, 2009; Vartivarian, 1989; Wood, 2010)
Toxoplasma gondii encephalitis (unlabeled use; CDC, 2009): Oral:
Primary prophylaxis: Oral: 160 mg TMP daily (preferred) or 160 mg TMP 3 times/week or 80 mg TMP daily
Treatment (alternative to sulfadiazine, pyrimethamine and leucovorin calcium): Oral, I.V.: 5 mg/kg TMP twice daily
Travelers' diarrhea: Oral: One double-strength tablet every 12 hours for 5 days
Urinary tract infection:
Oral: One double-strength tablet every 12 hours
Duration of therapy: Uncomplicated: 3-5 days; Complicated: 7-10 days
Pyelonephritis: 14 days
Prostatitis: Acute: 2 weeks; Chronic: 2-3 months
I.V.: 8-10 mg TMP/kg/day in divided doses every 6, 8, or 12 hours for up to 14 days with severe infections
Dosing adjustment in renal impairment: Oral, I.V.:
Manufacturer's recommendation: Children and Adults:
Clcr >30 mL/minute: No dosage adjustment required
Clcr 15-30 mL/minute: Administer 50% of recommended dose
Clcr <15 mL/minute: Use is not recommended
Alternate recommendations:
Clcr 15-30 mL/minute:
Treatment: Administer full daily dose (divided every 12 hours) for 24-48 hours, then decrease daily dose by 50% and administer every 24 hours (Note: For serious infections including Pneumocystis jirovecii pneumonia (PCP), full daily dose is given in divided doses every 6-8 hours for 2 days, followed by reduction to 50% daily dose divided every 12 hours) (Nahata, 1995).
PCP prophylaxis: One-half single-strength tablet (40 mg trimethoprim) daily or 1 single-strength tablet (80 mg trimethoprim) daily or 3 times weekly (Masur, 2002).
Clcr <15 mL/minute:
Treatment: Administer full daily dose every 48 hours (Nahata, 1995)
PCP prophylaxis: One-half single-strength tablet (40 mg trimethoprim) daily or 1 single-strength tablet (80 mg trimethoprim) 3 times weekly (Masur, 2002). While the guidelines do acknowledge the alternative of giving 1 single-strength tablet daily, this may be inadvisable in the uremic/ESRD patient.
Intermittent Hemodialysis (IHD) (administer after hemodialysis on dialysis days):
Treatment: Full daily dose before dialysis and 50% dose after dialysis (Nahata, 1995)
Children: GFR <10 mL/minute/1.73 m2: Not recommended, but if required 5-10 mg TMP/kg every 24 hours (Aronoff, 2007)
PCP prophylaxis: One single-strength tablet (80 mg trimethoprim) after each dialysis session (Masur, 2002)
Note: Dosing dependent on the assumption of 3 times/week, complete IHD sessions.
Peritoneal dialysis (PD):
Use Clcr <15 mL/minute dosing recommendations. Not significantly removed by PD; supplemental dosing is not required (Aronoff, 2007):
Exit-site and tunnel infections: Oral: One single-strength tablet daily (Li, 2010)
Peritonitis: Oral: One double-strength tablet twice daily (Li, 2010)
Children: GFR <10 mL/minute/1.73 m2: Not recommended, but if required 5-10 mg TMP/kg every 24 hours. Intraperitoneal: Loading dose: TMP-SMX 320/1600 mg/L; Maintenance: TMP-SMX 80/400 mg/L (Aronoff, 2007; Warady, 2000)
Continuous renal replacement therapy (CRRT) (Heintz, 2009; Trotman, 2005): Drug clearance is highly dependent on the method of renal replacement, filter type, and flow rate. Appropriate dosing requires close monitoring of pharmacologic response, signs of adverse reactions due to drug accumulation, as well as drug concentrations in relation to target trough (if appropriate). The following are general recommendations only (based on dialysate flow/ultrafiltration rates of 1-2 L/hour and minimal residual renal function) and should not supersede clinical judgment:
CVVH/CVVHD/CVVHDF: 2.5-7.5 mg/kg of TMP every 12 hours. Note: Dosing regimen dependent on clinical indication. Critically-ill patients with P. jirovecii pneumonia receiving CVVHDF may require up to 10 mg/kg every 12 hours (Heintz, 2009).
Administration: Oral
Administer without regard to meals. Administer with at least 8 ounces of water.
Administration: I.V.
Infuse over 60-90 minutes, must dilute well before giving (ie, 1:15 to 1:25, which equates to 5 mL of drug solution diluted in 75-125 mL base solution).
Administration: I.V. Detail
Not for I.M. injection. Administer around-the-clock every 6-12 hours.
pH: 10
Monitoring Parameters
Perform culture and sensitivity testing prior to initiating therapy; CBC, serum potassium, creatinine, BUN
Test Interactions
Increased creatinine (Jaffé alkaline picrate reaction); increased serum methotrexate by dihydrofolate reductase method
Dietary Considerations
Should be taken with 8 oz of water. May be taken without regard to meals.
Patient Education
Maintain adequate hydration unless instructed to restrict fluid intake. May cause nausea, vomiting, or GI upset. Report skin rash, severe GI upset or diarrhea, dark urine, yellow skin or eyes, or unusual bleeding or bruising. May cause photosensitivity reactions; avoid sun, sunlamps, and tanning beds. Use sunscreen and wear clothing and eyewear that protects you from the sun.
Geriatric Considerations
Elderly patients appear at greater risk for more severe adverse reactions.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Stomatitis.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
Rarely may cause depression, hallucination, or confusion; sulfonamides may cause euphoria, restlessness, irritability, disorientation, panic, and delusions
Mental Health: Effects on Psychiatric Treatment
May rarely cause granulocytopenia; use caution with clozapine and carbamazepine
Nursing: Physical Assessment/Monitoring
Perform culture and sensitivity tests prior to initiating therapy. For empiric treatment be aware of suspected organisms and institution/region's sensitivity patterns.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. Note: The 5:1 ratio (SMX:TMP) remains constant in all dosage forms.
Injection, solution: Sulfamethoxazole 80 mg and trimethoprim 16 mg per mL (5 mL, 10 mL, 30 mL) [contains benzyl alcohol, ethanol 12.2%, propylene glycol 400 mg/mL, sodium metabisulfite]
Suspension, oral: Sulfamethoxazole 200 mg and trimethoprim 40 mg per 5 mL (480 mL)
Tablet: Sulfamethoxazole 400 mg and trimethoprim 80 mg
Bactrim™: Sulfamethoxazole 400 mg and trimethoprim 80 mg
Tablet, double-strength: Sulfamethoxazole 800 mg and trimethoprim 160 mg
Bactrim™ DS: Sulfamethoxazole 800 mg and trimethoprim 160 mg
Septra® DS: Sulfamethoxazole 800 mg and trimethoprim 160 mg
Pricing: U.S. (www.drugstore.com)
Suspension (Sulfamethoxazole-Trimethoprim)
200-40 mg/5 mL (200): $18.99
Tablets (Bactrim)
400-80 mg (30): $49.99
Tablets (Bactrim DS)
800-160 mg (30): $89.99
Tablets (Septra DS)
800-160 mg (30): $72.79
Tablets (Sulfamethoxazole-TMP DS)
800-160 mg (30): $20.99
Tablets (Sulfamethoxazole-Trimethoprim)
400-80 mg (30): $15.99
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International Brand Names
Lexi-Comp.com
Last full review/revision March 2012
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