Trimethoprim-sulfamethoxazole (Co-trimoxazole, Bactrim, Septran) is a combination of two antibiotics that treats a variety of bacterial infections as discussed here.

Trimethoprim-sulfamethoxazole (Septran, Bactrim, Co-trimoxazole) Uses:

• Urinary tract infections:

  • It is used to treat urinary tract infections brought on by Proteus mirabilis, Proteus vulgaris, Morganella morganii, Klebsiella, and Enterobacter spp.

• Acute exacerbation of COPD:

  • It is approved for the prophylaxis and treatment of Pneumocystis pneumonia as well as acute COPD exacerbations caused by susceptible strains of Haemophilus influenzae or Streptococcus pneumoniae (PCP)

• Gastrointestinal infections:

  • It is used for traveler's diarrhea due to enterotoxigenic E. coli and treatment of shigellosis caused by Shigella flexneri or Shigella sonnei

• Acute otitis media:

  • It is used for the treatment of acute otitis media.

• Off Label Use of Trimethoprim-sulfamethoxazole in Adults:

  • For the prophylaxis or treatment of bite wound infection (animal or human bite);
  • Cyclosporiasis;
  • Cystoisosporiasis (Isosporiasis);
  • Diabetic foot infection;
  • Epididymitis;
  • Granuloma inguinale (Donovanosis);
  • Head lice (Pediculosis capitis);
  • Intracranial abscess 
  • Melioidosis (Burkholderia pseudomallei) infection;
  • Meningitis, bacterial;
  • Nocardiosis;
  • Osteomyelitis;
  • For the prevention of pontaneous bacterial Peritonitis;
  • Prostatitis;
  • Prosthetic joint infection;
  • Q fever (Coxiella burnetii);
  • Septic arthritis (methicillin-resistant Staphylococcus aureus);
  • Skin and soft tissue infections;
  • Stenotrophomonas maltophilia infections;
  • HIV-infected individuals' prophylaxis, treatment, and ongoing maintenance of Toxoplasma gondii encephalitis

Trimethoprim-sulfamethoxazole (Cotrimoxazole, Septran, Bactrim) dose in adults:

Note:

The trimethoprim (TMP) component is the basis for weight-based dosing recommendations. Each double-strength pill has a TMP content of 160 mg and an SMX content of 800 mg. TMP 80 mg and SMX 400 mg are both present in each single-strength tablet. TMP 16 mg and SMX 80 mg are both present in the undiluted IV solution.

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Trimethoprim-sulfamethoxazole General dosing guidelines:

• Every 12 to 24 hours, take 1 to 2 double-strength tablets by mouth.

Note:

Patients with high doses should be monitored for serum creatinine and potassium

• TMP component dosage of 8 to 20 mg/kg/day, split intravenously every 6 to 12 hours.

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Trimethoprim-sulfamethoxazole Dose as an alternative agent in the prophylaxis/ treatment of Bite wound infection (animal/human bite):

• Combining a suitable agent for anaerobic coverage with one double-strength pill per oral dose per day.
• Prophylaxis treatments normally last 3 to 5 days, while treatments for infections that have already taken hold last 5 to 14 days.

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Trimethoprim-sulfamethoxazole for the treatment of acute exacerbation of chronic obstructive pulmonary disease:

• For five to seven days, take one double-strength pill orally every 12 hours.

Note:

In uncomplicated COPD exacerbations ranging from mild to severe, sulfamethoxazole/trimethoprim is typically prescribed to patients who are under 65 years old, have no substantial comorbidities, have FEV > 50% expected, and experience exacerbations infrequently.

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Trimethoprim-sulfamethoxazole Dose in the treatment of Mild Diabetic foot infections (MRSA) (off label):

• Two double-strength tablets per oral b.i.d daily, usually for 7-14 days.

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Trimethoprim-sulfamethoxazole dose in the treatment of infectious Diarrhea:

• Cyclosporiasis (off-label use):

  • Immunocompromised (AIDS-associated):

    • One double-strength tablet per oral b.i.d. daily for 14 days, then one double-strength tablet three times per week for secondary prophylaxis.

  • Immunocompetent:

    • For 7 to 10 days, take one double-strength pill orally once a day.

• Cystoisosporiasis(off-label use):

  • Immunocompromised (AIDS-associated):

    • Oral, IV:
    • For 7 to 10 days, take 160 mg (TMP component) twice a day; if symptoms worsen or persist, take 160 mg (TMP component) four times a day and/or extend the course to 21 to 28 days.
    • Follow treatment with secondary prophylaxis of one double-strength pill taken orally three times per week in patients with CD4 counts below 200 cells/mm3.

  • Immunocompetent (usually self-limited; treatment not always indicated):

    • For 7 to 10 days, take one double-strength pill orally once a day.

• Shigellosis if susceptibility is documented:

  • • For five to seven days, take one double-strength pill orally every day.

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Trimethoprim-sulfamethoxazole (bactrim, septran) dose in the treatment of Intracranial abscess and spinal epidural abscess (as an alternative agent for MRSA) (off-label):

• Every 8 to 12 hours, provide 5 mg/kg/dose (TMP component) intravenously.
• For brain abscess, spinal epidural abscess, and intracranial epidural abscess, the period typically varies from 4 to 8 weeks and 6 to 8 weeks, respectively; however, some patients need a longer course of treatment.

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Trimethoprim-sulfamethoxazole dose in the treatment of Melioidosis (Burkholderia pseudomallei ) infection (off-label):

• In the case of localised disease affecting the CNS, prostate, bone, joint, skin, or soft tissues, initial intensive therapy as an adjunct to primary therapy [ceftazidime or a carbapenem]:

• Oral, IV:

  • 40 to 60 kg:

    • 240 mg (TMP component) b.i.d daily.

  • >60 kg:

    • 320 mg (TMP component) b.i.d daily.

• Eradication therapy (begin after completion of initial intensive therapy)

  • 40 to 60 kg:

    • 240 mg (TMP component) per oral b.i.d daily.

  • >60 kg:

    • 320 mg (TMP component) per oral b.i.d daily.

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Trimethoprim-sulfamethoxazole dose in the treatment of Bacterial Meningitis (as an alternative agent for MRSA, L. monocytogenes, E. coli, and other Enterobacteriaceae) (off-label):

• 5 mg/kg/dose intravenous (TMP component) every 6 to 12 hours
• Note: Some professionals favour intravenous TMP doses of 5 mg/kg every 8 hours.

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Trimethoprim-sulfamethoxazole dose for the treatment of Nocardiosis (off-label):

• Cutaneous superficial infections (no other organ involvement):

  • TMP component dosage: 5–10 mg/kg/day orally, split into two doses.

• Mild to moderate Pulmonary infection:

  • Immunocompetent patients:

    • TMP component dosage: 5–10 mg/kg/day, split into 2 doses.

  • Immunocompromised patients:

    • 3 to 4 divided intravenous doses of 15 mg/kg/day (component of TMP).

• Severe Pulmonary infection, CNS, disseminated, or multi-site infection:

  • (TMP component) 3 to 4 divided intravenous dosages of 15 mg/kg/day.
  • Note: It must be combined with one or two more medications when used as empiric therapy.

• Duration of treatment:

  • It takes a long time to heal (between 3 months and 1 year [combined parenteral/oral therapy]).

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Trimethoprim-sulfamethoxazole dose in the treatment of Osteomyelitis due to MRSA (off-label):

• Oral, IV: 4 mg/kg/dose (TMP component) given with rifampin every 12 hours.

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Trimethoprim-sulfamethoxazole dose in the prevention of spontaneous bacterial Peritonitis (off-label):

• High-risk patients (eg, hospitalized patients with Child-Pugh class B or C cirrhosis and active GI bleeding):

  • One double-strength tablet per oral b.i.d daily.

• Long-term secondary SBP prophylaxis:

  • One double-strength tablet per oral once daily.

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Trimethoprim-sulfamethoxazole dose in the treatment of Pneumocystis pneumonia:

• Primary and Secondary Prophylaxis (off-label dose):

  • HIV-infected:

    • Oral:  One double-strength pill taken once a day, one single-strength tablet taken once a day, or one double-strength tablet taken three times a week are the recommended dosages (alternative regimen).

  • Note:

    • One double-strength pill should be used once a day in patients who also need toxoplasmosis prophylaxis.

  • Duration in HIV-infected patients receiving ART:

    • Continue until undetectable viral load and CD4 count >200 cells/mm for >3 months; some experts stop primary prophylaxis in patients on ART who have undetectable viral loads for 3 to 6 months and have CD4 counts between 100 and 200 cells/mm.

  • Immunocompromised host, HIV-uninfected (eg, transplant recipients, cancer-related, hematopoietic stem cell transplant (off-label dose):

    • One single-strength pill once day, one double-strength tablet once daily, or one double-strength tablet three times per week (recommended regimens).

  • Duration after a solid organ transplant (except lung):

    • During times of high immunosuppression, such as after receiving therapy for acute rejection, and for 6 to 12 months.

  • Duration after lung transplant:

    • Therapy should be regarded forever.

  • Duration for cancer-related patients at high risk for PCP infection:

    • Continue until there are no longer any risk factors for PCP infection, according to the opinion of an expert.

• Treatment (off-label dose)

  • Note:

    • Immediately after therapy is finished, secondary prophylaxis should start.

  • Moderate to severe infection:

    • 15 to 20 mg/kg/day (TMP component) intravenous in 3 or 4 divided doses for 21 days; after clinical improvement, the IV treatment may be changed to oral medication.
    • Note: Adjunctive glucocorticoids should be given to patients who have a moderate or severe infection (PaO2 70 mm Hg at room air or an alveolar-arterial oxygen gradient 35 mm Hg).

  • Mild to moderate infection:

    • Two double-strength tablets three times per day or 15 to 20 mg/kg/day (TMP component) per mouth in three evenly spaced doses for 21 days.

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Trimethoprim-sulfamethoxazole dose for the treatment of Prostatitis (off-label):

• Acute bacterial prostatitis:

  • For six weeks, take one double-strength tablet orally every day.

• Chronic bacterial prostatitis (alternative agent):

  • For around six weeks, use one double-strength tablet per oral b.i.d.

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Trimethoprim-sulfamethoxazole dose in the treatment of Prosthetic joint infection (off-label):

• In patients having a 1-stage exchange or debridement with retention of the prosthesis, the following treatment is administered after pathogen-specific IV therapy:

Note:

Depending on the individual patient, therapy may last anywhere from 3 months to an endless amount of time.

• Staphylococci (methicillin-resistant) and Enterobacteriaceae:

  • Every day, take one double-strength tablet orally. Combine with rifampin for the first 3 to 6 months of staphylococcal infection treatment.

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Treatment of Q fever (C. burnetii) with trimethoprim-sulfamethoxazole (recommended for pregnant women 32 weeks gestation; alternate for non-pregnant adults) (off-label):

• Acute illness:

  • When pregnant, but no later than 32 weeks gestation, take one double-strength tablet per oral b.i.d. every day. Also take folic acid supplements.

• Note:

  • Due to the possibility of hyperbilirubinemia, stop treatment during the last eight weeks of pregnancy.

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Patients with septic arthritis caused by MRSA and taking trimethoprim-sulfamethoxazole (without prosthetic material) (alternative agent following initial IV therapy with an appropriate antibiotic) (off-label):

• To complete a 3- to 4-week total treatment course, take two double-strength tablets or 4 mg/kg/dose (TMP component) twice day, maximum: 320 mg [TMP component]/dose (IV and oral).

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Trimethoprim-sulfamethoxazole Dose in the treatment of Sexually transmitted infections:

• Patients with epididymitis who are under 35 and have a low risk of STIs should consider an alternative treatment (off-label use):

  • For 10 days, take one double-strength pill orally, bi-daily.

• Granuloma inguinale (donovanosis) (alternative agent) (off-label use):

  • For at least three weeks and until the lesions have healed, take one double-strength pill orally every other day.

• Note:

  • Another medication (such as an aminoglycoside) may be administered if symptoms do not subside within the first few days of treatment.

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Trimethoprim-sulfamethoxazole dose in the treatment of mild to moderate skin/soft tissue infection (off-label):

• Depending on the severity and clinical response, treat for 5 to 14 days using 1 to 2 double-strength tablets taken orally twice daily.

Note:

Co-trimoxazole monotherapy is appropriate for the empiric treatment of purulent cellulitis, while nonpurulent cellulitis requires an extra drug (such as amoxicillin or cephalexin) for beta-hemolytic streptococci.

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Patients with infections caused by Stenotrophomonas maltophilia should take trimethoprim-sulfamethoxazole (hospital-acquired pneumonia, ventilator-associated pneumonia, and bacteremia) (off-label):

• (TMP component) 3 or 4 divided intravenous dosages of 15 mg/kg/day.

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Trimethoprim-sulfamethoxazole dose in Toxoplasma gondii encephalitis (AIDS-associated) (off-label):

• Primary prophylaxis:

  • Primary prophylaxis is recommended for T. gondii IgG-positive individuals with CD4 counts under 100 cells/mm3 and one double-strength tablet per mouth once daily, one double-strength tablet three times per week, or one single-strength tablet once daily.
  • When ART is started, primary prophylaxis should be continued until the CD4 count is >200 cells/mm3 for >3 months. However, some specialists advise stopping primary prophylaxis in patients who are undergoing ART and have had an undetectable viral load for 3 to 6 months.

• Treatment (alternative agent):

  • Oral, IV:
    • 10 mg/kg/day (TMP component) in 2 split doses for at least 6 weeks; if clinical or radiologic illness is significant or response is not complete at 6 weeks, further duration may be required.

• Secondary prophylaxis (chronic maintenance therapy) (alternative agent):

  • One oral double-strength pill each day, or you can take one double-strength tablet once per day.
  • When ART is started, continue until the CD4 count is >200 cells/mm3 for >6 months.

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Trimethoprim-sulfamethoxazole dose in the treatment of Urinary tract infection (off-label dose):

• Acute uncomplicated or simple cystitis:

Note:

Avoid using if the patient has risk factors for multidrug-resistant gram-negative infections or if the resistance prevalence is known to be higher than 20%.

For three days, treat females with one double-strength tablet every day.

• Complicated Urinary tract infection (including pyelonephritis):

  • For women who respond quickly to treatment, one double-strength tablet taken orally once daily for two weeks, some experts recommend treating for seven to ten days.

Note:

Parenteral therapy should be properly followed with oral therapy. Before receiving oral medication, a single dose of an injectable is sufficient for treating minor infections. Parenteral therapy should be continued for severe infections until culture and susceptibility data are known.

Trimethoprim-sulfamethoxazole (Cotrimoxazole, Septran, Bactrim) dose in children:

Note: Trimethoprim (TMP) is the basis for dosage recommendations:

General dosing for susceptible infection:

• Infants ≥2 months, Children, and Adolescents:

  • Oral, IV:

    • Split doses of 6 to 12 mg TMP/kg/day given every 12 hours.
    • 60 mg TMP/dose is maximum single dose

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Trimethoprim-sulfamethoxazole dose for Catheter (peritoneal dialysis) and exit-site or tunnel infection: 

• 5–10 mg TMP/kg/dose administered orally once per day.
• 80 mg TMP/dose is maximum single dose

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Trimethoprim-sulfamethoxazole dose for Cyclosporiasis: 

• For seven to ten days, provide 8 to 10 mg TMP/kg orally twice daily in divided dosages.
• 160 mg TMP. is maximum single dose

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Trimethoprim-sulfamethoxazole dose in Meningitis:

• For 7 to 21 days, administer 10 to 20 mg TMP/kg intravenously divided every 6 to 12 hours; the time frame depends on the pathogen and the severity of the clinical condition.

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Mild to moderate skin/soft tissue infection caused by community-acquired MRSA:

• Alternatively, administration of 20 mg TMP/kg/day in divided doses every 6 hours has been recorded. 8 to 12 mg TMP/kg daily mouth in divided doses every 12 hours.
• Consider include group A streptococcal coverage when utilising empirically.

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Trimethoprim-sulfamethoxazole dose in children with acute Otitis media:

• For ten days, provide 6 to 10 mg TMP/kg orally in divided doses every 12 hours.

Note: S. pneumoniae should not be utilised in individuals who do not respond to first-line amoxicillin therapy due to its resistance.

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Trimethoprim-sulfamethoxazole dose in Pneumocystis jirovecii pneumonia (PCP) (HIV-exposed/-positive):

• Prophylaxis:

  • Infants (at least 4 weeks of age) and Children:

    • A single daily dose of 5 to 10 mg TMP/kg or 150 mg TMP/m/day may be administered, as may divided doses every
    • 12 hours spread over 2 to 3 days per week on similar days or alternate days.
    • TMP 320 mg/day is the highest daily dose.

  • Adolescents:

    • Oral TMP doses of 80 to 160 mg per day or 160 mg TMP three times per week are both acceptable.

• Treatment:

  • Infants >2 months and Children:

    • Initial regimen: 15 to 20 mg TMP/kg intravenously given in divided doses every six hours for 21 days. As acute pneumonitis subsides in patients with mild to moderate disease and no malabsorption problems or diarrhoea, oral therapy at the same daily dose (15 to 20 mg/kg/day TMP) given in divided doses three or four times per day may be started.

  • Adolescents

    • Mild to moderate:

      • 320 mg TMP three times day for 21 days, or 15 to 20 mg TMP/kg per mouth in three evenly spaced doses

    • Moderate to severe:

      • Initial: 15–20 mg TMP/kg intravenously given in 3–4 separate doses over 21 days; transition to oral if clinical results improve

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Q-Fever ( Coxiella burnetii ); mild infection (doxycycline therapeutic failure):

• Children <8 years: The dose should be based on the severity of illness:

  • A larger dose range of 4 to 20 mg TMP/kg/day divided twice daily has been suggested to address varied degrees of severity; nevertheless, patients should be monitored for efficacy and potential side effects. The usual dose range is 8 to 10 mg TMP/kg per day in divided doses twice daily for 14 days.

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Trimethoprim-sulfamethoxazole dose for Shigellosis:

• Note:

  • Sulfamethoxazole and trimethoprim empiric therapy is not advised due to widespread resistance that has reportedly been identified.

• Manufacturer's labeling:

  • For five days, provide 8 mg TMP/kg orally in divided doses every 12 hours.
  • 160 mg TMP is maximum single dose

• Alternate dosing:

  • The IDSA advises the following for infectious diarrhoea: For immunocompetent individuals, take 10 mg TMP/kg orally in divided doses every 12 hours for 3 days, or take it for 7–10 days (for immunocompromised patients)
    greatest single dose: 160 mg TMP

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Trimethoprim-sulfamethoxazole dose for Toxoplasmosis (HIV-exposed/infected):

• Primary Prophylaxis:

  • Infants ≥2 months and Children:

    • 150 mg TMP/m per mouth; The dose may be given as a single dose per day or in divided doses every 12 hours; additionally, it may be given three times per week for three consecutive or alternating days.

  • Adolescents:

    • 80 mg TMP per day, 160 mg TMP three times per week, or 60 mg TMP each oral dose.

• Treatment of encephalitis:

  • Adolescents:

    • Oral, IV: 10 mg/kg/day TMP in two divided doses for at least 6 weeks; extended duration may be needed in some patients; chronic maintenance medication should be given to all patients every day after the treatment.

• Secondary prophylaxis (chronic suppressive therapy, alternative regimen):

  • Note:

    • Use only in cases where pyrimethamine is inaccessible or intolerable:

  • Infants and Children:

    • 50 mg TMP/m2 orally once per day.

  • Adolescents:

    • Treatment for postencephalitis maintenance therapy: 60 mg TMP orally once or twice daily.
    • When asymptomatic and responding to ART with a CD4 count >200 cells/mm3 for >6 months, it may be stopped.

Note:

If utilised, a gradual transition may be helpful (for example, after acute therapy with 4 to 6 weeks of 160 mg TMP twice daily before dropping to once-daily dosing). Once-daily dose may be linked to an increased risk of recurrence.

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Trimethoprim-sulfamethoxazole dose  in Urinary tract infection:

• Treatment:

  • Infants and Children 2 to 24 months:

    • For 7 to 14 days, provide 6 to 12 mg TMP/kg orally in divided doses every 12 hours.

  • Children >24 months and Adolescents:

    • For three days, take 8 mg TMP/kg orally in divided doses every 12 hours; for some patients, a longer period of time may be necessary.
    • 160 mg TMP is maximum single dose

  • Infants ≥2 months, Children, and Adolescents:

    • With severe infections, provide 8–10 mg TMP/kg intravenously in divided doses every 6–12 hours for up to 14 days.

• Prophylaxis:

  • Infants ≥2 months, Children, and Adolescents:

    • TMP dosage: 2 mg/kg orally, once daily.

Pregnancy Risk Factor D

 

• Trimethoprim and sulfamethoxazole can cross the placenta.
• Congenital abnormalities such mouth clefts, cardiovascular abnormalities, and anomalies of the neural tube are possible.
• Supplementation with Folic acid may reduce this risk.
• Cotrimoxazole is used to prophylaxis Pneumocystis jarovecii pneumonia and Toxoplasmic gondiiencephalitis.
• Additionally, it can be used to treat Q fever in pregnant women both acutely and chronically.

Trimethoprim-sulfamethoxazole use during breastfeeding:

• Breast milk contains cotrimoxazole, which can cause bowel flora changes. Therefore, infants should be monitored for GI problems.
• According to the manufacturer, cotrimoxazole would be administered to a breastfeeding infant at a rate of 2% to 5% of the daily recommended dose for infants aged >2 months.
• When the relative infant dose of breastmilk is less than 10%, breastfeeding is permitted.
• Cotrimoxazole contraindicated for infants under 2 months old due to the possibility of hemolytic anemia and kernicterus.
• Women who breastfeed infants with G6PD deficiency/hyperbilirubinemia should not take it.
• Breastfeeding infants who are preterm, jaundiced, or at high risk for bilirubin displacement, kernicterus, and premature should be avoided.

Trimethoprim-sulfamethoxazole Dose adjustment in renal disease:

• Manufacturer's labeling: Oral, IV:

  • CrCl >30 mL/minute:

    • No dosage adjustment necessary.

  • CrCl 15 to 30 mL/minute:

    • 50% dose reduction required

  • CrCl <15 mL/minute:

    • It is contraindicated per the manufacturer's labeling in severe renal disease.

• Alternative recommendations:

  • Oral:

  • Note: The following dosage adjustments are based on a usual maintenance dose of 1 double-strength tablet every 12 hours.

    • GFR 10 to 50 mL/minute:

      • One pill of double strength once, followed by one of single strength every 12 hours.

    • GFR <10 mL/minute:

      • Avoid using; in the event that it is required, take 1 double-strength tablet once, followed by 1 single-strength tablet every 24 hours.

    • Hemodialysis:

      • Once with a double-strength pill, then once every 24 hours with a single-strength tablet (dose after hemodialysis on dialysis days).

  • IV Septran, Bactrim:

  • Note: The following dosage adjustments are based on a usual maintenance dose of 4 to 5 mg/kg (TMP component) every 6 hours.

    • GFR 10 to 50 mL/minute:

      • 4 to 5 mg/kg (TMP component) every 12 hours.

    • GFR <10 mL/minute:

      • Avoid use; if necessary, 2.5 to 5 mg/kg (TMP component) every 24 hours.

    • Hemodialysis:

      • 5 to 5 mg/kg (TMP component) every 24 hours (dose after hemodialysis on dialysis days).

• Treatment of Pneumocystis pneumonia (PCP):

  • Note: Renal function may be estimated using the Cockcroft-Gault formula for dosage adjustment purposes.

  • Oral Septran, bactrim:

  • Note: The following dosage adjustments are based on a usual maintenance dose of 2 double-strength tablets every 8 hours.

    • CrCl 10 to 30 mL/minute:

      • Two double-strength tablets every 12 hours.

    • CrCl <10 mL/minute:

      • One double-strength tablet every 12 hours or 2 double-strength tablets every 24 hours.

    • Hemodialysis:

      • Two double-strength tablets once daily (dose after hemodialysis on dialysis days); consider therapeutic drug monitoring to optimize therapy.

    • IV Septran, Bactrim:

    • Note: The following dosage adjustments are based on a usual maintenance dose of 5 mg/kg (TMP component) every 8 hours.

      • CrCl 10 to 30 mL/minute:

        • 5 mg/kg (TMP component) every 12 hours.

      • CrCl <10 mL/minute:

        • 5 mg/kg (TMP component) every 24 hours.

      • Hemodialysis:

        • 5 mg/kg (TMP component) once daily (dose after hemodialysis on dialysis days); consider therapeutic drug monitoring to optimize therapy.

    • CRRT:

      • Drug clearance depends on the flow rate, filter type and on the method of renal replacement.
      • Monitoring of pharmacologic response, side effects of drug accumulation is required.
      • The following are general recommendations only (based on dialysate flow/ultrafiltration rates of 1 to 2 L/hour and minimal residual renal function) and should not supersede clinical judgment:

    • CVVH/CVVHD/CVVHDF:

      • Oral, IV: Every 12 hours, 2.5 to 7.5 mg/kg (TMP component).
      • Note: The dosage schedule is determined by the clinical indication. Patients receiving CVVHDF for P. jirovecii pneumonia who are critically unwell may need up to 10 mg/kg (TMP component) every 12 hours.

Septran Dose adjustment in liver disease:

The manufacturer's labelling does not mention dosage changes, and use is not advised in cases of severe liver damage.

Side effects of Trimethoprim-sulfamethoxazole (Septran, Bactrim):

• Cardiovascular:

  • Allergic Myocarditis
  • Periarteritis Nodosa (Rare)

• Central Nervous System:

  • Apathy
  • Aseptic Meningitis
  • Ataxia
  • Chills
  • Depression
  • Fatigue
  • Hallucination
  • Headache
  • Insomnia
  • Nervousness
  • Peripheral Neuritis
  • Seizure
  • Vertigo

• Dermatologic:

  • Erythema Multiforme (Rare)
  • Exfoliative Dermatitis (Rare)
  • Pruritus
  • Skin Photosensitivity
  • Skin Rash
  • Stevens-Johnson Syndrome (Rare)
  • Toxic Epidermal Necrolysis (Rare)
  • Urticaria

• Endocrine & Metabolic:

  • Hyperkalemia (Generally At High Dosages)
  • Hypoglycemia (Rare)
  • Hyponatremia

• Gastrointestinal:

  • Abdominal Pain
  • Anorexia
  • Diarrhea
  • Glottis Edema
  • Kernicterus (In Neonates)
  • Nausea
  • Pancreatitis
  • Pseudomembranous Colitis
  • Stomatitis
  • Vomiting

• Genitourinary:

  • Crystalluria
  • Diuresis (Rare)
  • Nephrotoxicity (In Association With Cyclosporine)
  • Toxic Nephrosis (With Anuria And Oliguria)

• Hematologic & Oncologic:

  • Agranulocytosis
  • Anaphylactoid Purpura (Iga Vasculitis; Rare)
  • Aplastic Anemia
  • Eosinophilia
  • Hemolysis (With G6PD Deficiency)
  • Hemolytic Anemia
  • Hypoprothrombinemia
  • Leukopenia
  • Megaloblastic Anemia
  • Methemoglobinemia
  • Neutropenia
  • Thrombocytopenia

• Hepatic:

  • Cholestatic Jaundice
  • Hepatotoxicity (Including Hepatitis
  • Cholestasis
  • And Hepatic Necrosis)
  • Hyperbilirubinemia
  • Increased Transaminases

• Hypersensitivity:

  • Anaphylaxis
  • Angioedema
  • Hypersensitivity Reaction
  • Serum Sickness

• Neuromuscular & Skeletal:

  • Arthralgia
  • Myalgia
  • Rhabdomyolysis (Mainly In AIDS Patients)
  • Systemic Lupus Erythematosus (Rare)
  • Weakness

• Ophthalmic:

  • Conjunctival Injection
  • Injected Sclera
  • Uveitis

• Otic:

  • Tinnitus

• Renal:

  • Increased Blood Urea Nitrogen
  • Increased Serum Creatinine
  • Interstitial Nephritis
  • Renal Failure

• Respiratory:

  • Cough
  • Dyspnea
  • Pulmonary Infiltrates

• Miscellaneous:

  • Fever

Contraindication to Trimethoprim-sulfamethoxazole (Septran, Bactrim):

• Hypersensitivity to trimethoprim, sulfa drugs, or any other component of the formulation
• Infants under 2 months (manufacturer’s labeling).
• Grave liver disease or renal disease
• Use of trimethoprim or sulfonamides has previously resulted in immunological thrombocytopenia brought on by medication.
• megaloblastic anemia due to folate deficiency
• Combination therapy with dofetilide
• Pregnancy/breastfeeding
• Blood dyscrasias

Warnings and precautions

• Blood dyscrasias:
  • The discontinuation of therapy is necessary for severe reactions, such as agranulocytosis or aplastic anemia.
• Dermatologic reactions
  • Stop the drug immediately if Stevens-Johnson syndrome or toxic epidermal necrosis occurs
  • Hepatic necrosis
  • In the event of fatal liver necrosis, it is important to stop using the drug.
• Hyperkalemia:
  • Hyperkalemia can be caused by the following risk factors: elderly, renal impairment, high dose (20 mg/kg/day trimethoprim), hypoaldosteronism and combination of medications.
• Hypoglycemia:
  • Hypoglycemia can be caused by co-trimoxazole. Therefore, it is important to monitor your blood sugar carefully.
• Hyponatremia:
  • It can increase the chance of hyponatremia, especially when there are infections with PCP.
• Allergy to sulfonamide ("sulfa")
  • Cross-reactivity can be seen when compounds contain the sulfonamide structural (SO-NH).
  • Antibiotic sulfonamide sulfasalazine has an arylamine structure. It could react negatively with antibacterial sulfonamides.
  • Mild reactions, such as T-cell-mediated type IV reactions that include maculopapular or severe Stevens-Johnson syndromes or toxic epidermal necrotic can occur.
• Superinfection
  • Long-term therapy can be used to treat superinfections with C.difficile or pseudomembranous collitis.
• Thrombocytopenia:
  • Immune-mediated hemoglobinopathy can be fatal, or it resolves in one week after discontinuation of therapy.
• Allergies/Asthma:
  • Patients with asthma or allergies should be cautious.
• Hepatic impairment
  • Patients with hepatic impairment should be cautious.
• Renal impairment
  • Recommendations for dosage adjustment: To prevent crystalluria, it is important to hydrate properly.
• Thyroid dysfunction:
  • Patients with thyroid dysfunction should be cautious.

Trimethoprim-sulfamethoxazole (co-trimoxazole): Drug Interaction

Risk Factor C (Monitor therapy)
Ajmaline	Sulfonamides might make ajmaline more harmful or poisonous. In particular, there may be an elevated risk for cholestasis.
Amantadine	Trimethoprim might make Amantadine's harmful or hazardous effects worse. Particularly, there may be a higher chance of myoclonus and/or delirium.
Aminolevulinic Acid (Topical)	Trimethoprim's serum levels may rise when amantadine is used. Trimethoprim may raise the level of amantadine in the blood. Aminolevulinic Acid's photosensitizing impact may be enhanced by photosensitizing agents (Topical).
Androgens	Can make blood glucose lowering medications more effective at lowering blood sugar. Danazol is an exception.
Angiotensin II Receptor Blockers	Angiotensin II Receptor Blockers' hyperkalemic impact may be increased by trimethoprim.
Angiotensin-Converting Enzyme Inhibitors	Angiotensin-Converting Enzyme Inhibitors' hyperkalemic impact may be enhanced by trimethoprim.
Antidiabetic Agents	Possibly makes hypoglycemia-associated agents more effective.
AzaTHIOprine	Azathioprine's myelosuppressive action may be enhanced by sulfamethoxazole.
AzaTHIOprine	Azathioprine's myelosuppressive action may be strengthened by trimethoprim.
BCG Vaccine (Immunization)	Antibiotics may reduce the BCG vaccine's therapeutic effect (Immunization).
CycloSPORINE (Systemic)	Sulfonamide antibiotics may intensify CycloSPORINE's nephrotoxic effects (Systemic). Antibiotics containing sulfonamides may lower the level of cycloSPORINE in the serum (Systemic).
CYP2C9 Inhibitors (Moderate)	May slow down CYP2C9 substrate metabolism (High risk with Inhibitors).
Dapsone (Systemic)	The serum concentration of Dapsone may increase when taking trimethoprim (Systemic). The serum concentration of Trimethoprim may rise when Dapsone (Systemic) is used.
Dapsone (Topical)	Trimethoprim may intensify Dapsone's harmful or hazardous effects (Topical). More particular, trimethoprim might make hemolysis more likely.
Dexketoprofen	Sulfonamides' harmful or poisonous effects could be amplified.
Digoxin	The serum levels of Digoxin may rise when taking trimethoprim.
Eplerenone	Eplerenone's hyperkalemic impact may be enhanced by trimethoprim.
Herbs (Hypoglycemic Properties)	May intensify the hypoglycemic effects of agents associated with hypoglycemia.
Hypoglycemia-Associated Agents	May increase other hypoglycemia-associated agents' hypoglycemic effects.
Lactobacillus and Estriol	The therapeutic effects of Lactobacillus and Estriol may be reduced by antibiotics.
LamiVUDine	LamiVUDine's serum concentration may be raised by trimethoprim.
Local Anesthetics	The harmful or toxic effects of local anaesthetics may be increased by methemoglobinemia associated agents. In particular, there may be an elevated risk for methemoglobinemia.
Lumacaftor	May lower the serum level of CYP2C9 substrates (High Risk with Inhibitors or Inducers). The serum concentration of CYP2C9 Substrates may rise when taking lumacaftor (High Risk with Inhibitors or Inducers).
Maitake	Can make blood glucose lowering medications more effective at lowering blood sugar.
Memantine	Trimethoprim may intensify Memantine's harmful or hazardous effects. Particularly, there may be a higher chance of myoclonus and/or delirium.
Mercaptopurine	Memantine's serum levels may rise in response to trimethoprim. Trimethoprim's serum concentration could rise as a result of memantine.
Mercaptopurine	Mercaptopurine's myelosuppressive action may be strengthened by sulfamethoxazole. Mercaptopurine's myelosuppressive action may be strengthened by trimethoprim.
MetFORMIN	The serum concentration of MetFORMIN may rise when taking trimethoprim.
Monoamine Oxidase Inhibitors	Can make blood glucose lowering medications more effective at lowering blood sugar.
Pegvisomant	Can make blood glucose lowering medications more effective at lowering blood sugar.
Porfimer	The photosensitizing effect of Porfimer may be strengthened by photosensitizing agents.
PRALAtrexate	Trimethoprim may raise PRALAtrexate's serum levels. More specifically, trimethoprim may lessen pralatrexate excretion. Management: Keep a close eye out for elevated pralatrexate serum levels and/or potential toxicity when trimethoprim is also being used. When stopping trimethoprim, keep an eye out for dropping pralatrexate levels.
PRALAtrexate	The serum levels of PRALAtrexate might rise in response to sulfamethoxazole. More specifically, sulfamethoxazole may lessen pralatrexate excretion. Management: Keep a close eye out for elevated pralatrexate serum levels and/or potential toxicity when sulfamethoxazole is also being used. When stopping sulfamethoxazole, keep an eye out for dropping pralatrexate levels.
Prilocaine	The harmful or toxic effects of Prilocaine may be increased by methemoglobinemia associated agents. Combinations of these medications may make substantial methemoglobinemia more likely. Monitoring patients for methemoglobinemia symptoms (such as hypoxia and cyanosis) is necessary when prilocaine is used with other medications that can cause methemoglobinemia in patients. When giving these medicines to newborns, avoid using lidocaine or prilocaine.
Prothionamide	Can make blood glucose lowering medications more effective at lowering blood sugar.
Pyrimethamine	May intensify Trimethoprim's negative or hazardous effects.
Quinolones	Can make blood glucose lowering medications more effective at lowering blood sugar. Blood Glucose Lowering Agents' therapeutic impact may be lessened by quinolones. In particular, the use of quinolones may result in a loss of blood sugar control if an agent is being used to treat diabetes.
Repaglinide	The metabolism of Repaglinide may be slowed down by trimethoprim.
RifAMPin	May lower the level of trimethoprim in the serum.
RifAMPin	Sulfamethoxazole's serum concentration can drop.
Rifapentine	May lower the serum level of CYP2C9 substrates (High risk with Inducers).
Salicylates	Can make blood glucose lowering medications more effective at lowering blood sugar.
Selective Serotonin Reuptake Inhibitors	Can make blood glucose lowering medications more effective at lowering blood sugar.
Sodium Nitrite	The harmful or toxic effects of sodium nitrite may be amplified by methemoglobinemia-associated agents. Combinations of these medications may make substantial methemoglobinemia more likely.
Spironolactone	Spironolactone's hyperkalemic impact may be enhanced by trimethoprim.
Sulfonylureas	Antibiotics that contain sulfonamides may improve the hypoglycemic effects of sulfonylureas.
Thiazolidinediones	Thiazolidinediones may have reduced metabolism due to trimethoprim.
Varenicline	The serum concentration of Varenicline may rise when trimethoprim is used. Management: Keep an eye out for any heightened varenicline side effects when trimethoprim is also being used, especially in individuals with severe renal impairment. International guidelines for product labelling differ. Refer to the relevant labelling.
Verteporfin	The photosensitizing effect of verteporfin may be strengthened by photosensitizing agents.
Risk Factor D (Consider therapy modification)
Chloroprocaine	May reduce a sulfonamide antibiotic's therapeutic efficacy. Management: Whenever feasible, avoid using systemic sulfonamide-based antimicrobials at the same time as chloroprocaine.
Dabrafenib	Could lower the serum levels of CYP2C9 substrates (High risk with Inducers). Management: When possible, look for substitutes for the CYP2C9 substrate. Monitor the clinical effects of the substrate carefully if concurrent therapy cannot be avoided (particularly therapeutic effects).
Enzalutamide	May lower the serum level of CYP2C9 substrates (High risk with Inducers). Treatment: Enzalutamide should not be used concurrently with CYP2C9 substrates that have a limited therapeutic index. Enzalutamide use, like with the use of any other CYP2C9 substrate, should be done with caution and under close observation.
Fosphenytoin	May lower the level of trimethoprim in the serum. Fosphenytoin's serum levels may rise when using trimethoprim. In order to prevent potentially decreased trimethoprim efficacy and higher phenytoin concentrations/effects, consider alternatives to this combination whenever it is practical. For each of these potential side effects, cautiously monitor patients receiving this combination.
Methotrexate	Methotrexate's harmful or toxic effects may be exacerbated by trimethoprim. Management: Take into account avoiding the simultaneous use of trimethoprim or sulfamethoxazole with methotrexate. If administered concurrently, keep an eye out for the emergence of methotrexate toxicity symptoms
MiFEPRIStone	May elevate CYP2C9 substrates' serum levels (High risk with Inhibitors). Management: During and for two weeks after mifepristone treatment, use CYP2C9 substrates at the lowest dose advised and keep a close eye out for any negative effects.
Phenytoin	Trimethoprim may raise the level of phenytoin in the blood. Trimethoprim's serum levels may drop if you take phenytoin. In order to prevent potentially decreased trimethoprim efficacy and higher phenytoin concentrations/effects, consider alternatives to this combination whenever it is practical. For each of these potential side effects, cautiously monitor patients receiving this combination.
Phenytoin	The levels of phenytoin in the serum may rise when using sulfamethoxazole.
Procainamide	The active metabolite(s) of procainamide may be present at higher serum quantities when taking trimethoprim. Procainamide levels in the serum may rise when taking trimethoprim.
Sodium Picosulfate	Antibiotics may reduce Sodium Picosulfate's therapeutic impact. Management: If a patient previously used or is currently using an antibiotic, think about utilising an alternative product for bowel cleansing prior to a colonoscopy.
Typhoid Vaccine	The Typhoid Vaccine's therapeutic benefits may be reduced by antibiotics. The only strain impacted is the live attenuated Ty21a strain. Treatment: Patients receiving systemic antibacterial drugs should refrain from receiving the live attenuated typhoid vaccination (Ty21a). It is recommended to wait at least 3 days following the last dose of antibacterial medication before administering this vaccine.
Vitamin K Antagonists (eg, warfarin)	The anticoagulant action of vitamin K antagonists may be increased by sulfonamide antibiotics.
Risk Factor X (Avoid combination)
Aminolevulinic Acid (Systemic)	Aminolevulinic Acid's photosensitizing impact may be enhanced by photosensitizing agents (Systemic).
Amodiaquine	The neutropenic impact of amodiaquine may be strengthened by trimethoprim. Amodiaquine's serum levels may rise in response to trimethoprim.
BCG (Intravesical)	Antibiotics may lessen BCG's therapeutic effects (Intravesical).
Benznidazole	The negative or hazardous effects of products containing propylene glycol may be increased.
Cholera Vaccine	The therapeutic benefit of the cholera vaccine may be reduced by antibiotic use. Management: Cholera vaccine should not be administered to individuals taking systemic antibiotics or within 14 days after taking oral or parenteral antibiotics.
Dofetilide	Trimethoprim may raise Dofetilide's serum levels.
Leucovorin Calcium-Levoleucovorin	May lessen Trimethoprim's therapeutic impact. When treating Pneumocystis jirovecii pneumonia, avoid taking leucovorin or levoleucovorin at the same time as trimethoprim (with sulfamethoxazole). Keep a close eye out for diminished efficacy if trimethoprim is being used for another reason.
Mecamylamine	Sulfonamides may intensify Mecamylamine's harmful or hazardous effects.
Methenamine	Sulfonamide antibiotics' harmful or toxic effects could be exacerbated. To be more precise, the mixture may cause the production of a soluble precipitate in the urine.
MetroNIDAZOLE (Systemic)	The negative or hazardous effects of products containing propylene glycol may be increased. There could be a reaction like disulfiram.
Potassium P-Aminobenzoate	Sulfonamide antibiotics' therapeutic efficacy can be diminished.
Procaine	May diminish the therapeutic effect of Sulfonamide Antibiotics.

Monitoring parameters:

• CBC
• serum electrolytes
• Renal function tests
• BUN

How to administer Trimethoprim-sulfamethoxazole (Septran)?

• It should be given as intravenous Infusion (diluted )over 60-90 minutes, not for IM injection
• It should be given orally with or without food with at least 8 ounces of water.

Mechanism of action of Trimethoprim-sulfamethoxazole (Septran):

• Sulfamethoxazole inhibits dihydrofolic acid formation from paraaminobenzoic acids, thereby interfering with bacterial growth and folic acid production.
• Trimethoprim inhibits the sequential inhibition of enzymes in the folic acids pathway by inhibiting the conversion of dihydrofolic acid to trihydrofolate.

Absorption:

• Oral: Rapid; almost completely (90% to 100%)

Distribution:

• Middle ear fluid, sputum, and vaginal fluid all receive SMX and TMP distribution, while bronchial secretions also receive TMP.

Protein binding:

• SMX: 70%, TMP: 44%

Metabolism:

• Occurs in the liver and is converted to several metabolites, including SMX to hydroxy (through CYP2C9) and acetyl derivatives as well as conjugated with TMP to oxide and hydroxy derivatives; both SMX and TMP are therapeutically effective in their free forms.

Half-life elimination:

• TMP:
  • Prolonged in renal failure Newborns: 19 hours
  • range: 11 to 27 hours Infants 2 months to 1 year: 4.6 hours
  • range: 3 to 6 hours Children 1 to 10 years: 3.7 to 5.5 hours
  • Children and Adolescents >10 years: 8.19 hours
  • Adults: 6 to 11 hours
  • SMX: 9 to 12 hours, prolonged in renal failure

Time to reach peak serum concentration:

• Oral: 1 to 4 hours

Excretion:

• Both are excreted in urine as metabolites and unchanged drug   

International Brands of Trimethoprim-sulfamethoxazole:

• Bactrim
• Bactrim DS
• Sulfatrim Pediatric
• APO-Sulfatrim
• Protrin DF
• Septra
• Sulfatrim
• Sulfatrim DS
• Sulfatrim Pediatric
• TEVA-Trimel
• TEVA-Trimel DS
• Abacin
• Acuco
• Alcorim-F
• Anitrim
• Avlotrin
• Bacdan
• Bacin
• Bactelan
• Bacteric
• Bacterol
• Bacterol Forte
• Bacticel
• Bactiver
• Bactoprim
• Bactramin
• Bactrim
• Bactrim DS
• Bactrim F
• Bactrim Forte
• Bactrimel
• Bactropin
• Biseptol
• Brogamax
• Chemotrim
• Co-Try
• Colizole
• Colizole DS
• Comazole
• Comex
• Cotriinol
• Cotrim
• Cotrim DS
• Cotrimel
• Cotrix
• Cotrizol
• Cotrizole
• Deprim
• Dhatrim
• Dibaprim
• Diseptyl
• Duocide
• Duratrimet
• Ectaprim
• Epitrim
• Escoprim
• Espectrin
• Eusaprim
• Eusaprim Forte
• Farcotrim
• Fectrim
• Gantaprim
• Gantrim
• Ikaprim
• Infectrim
• Introcin
• Isotrim
• Kepinol
• Lagatrim
• Lagatrim Forte
• Lidaprim
• Lidaprim Forte
• Mano-Trim
• Mano-Trim Forte
• Medixin
• Metoxiprim
• Metrim
• Mezenol
• Mezenol DS
• Microtrim
• Morbifurb
• Mortin
• Nopil
• Novabact
• Octex
• Omsat
• Oriprim
• Oriprim DS
• Oxaprim
• Politrim
• Primzole
• Purbal
• Resprim
• Resprim Forte
• Sanprima
• Sanprima Forte
• Septran
• Septran Forte
• Septrin
• Septrin D.S.
• Septrin DS
• Septrin Forte
• Servitrim
• Sevatrim
• Sigaprim
• Sinersul
• Soltrim
• Suftrex
• Sulfacet
• Sulfoid Trimetho
• Sulfotrimin
• Sulotrim
• Suntrim
• Suntrim Forte
• Suprim
• Suprin
• Tagremin
• Timexole
• TMS
• Trim
• Trimaxazole
• Trimetoger
• Trimexan
• Trimexazol
• Trimexazole
• Trimezol
• Trimol
• Trimol D.S.
• Trimoprim
• Trimox
• Trimoxis
• Triomax
• Trisolvat
• Trisul
• Trizole
• Tryseptol
• Umoxazole
• Xepaprim
• Xepaprim Forte
• Zoltrim
• Zultrop
• Zultrop Forte

Trimethoprim-sulfamethoxazole Brand Names in Pakistan:

Brands will be updated later. Septran and Septran DS is easily available