Co-trimoxazole

Sulfonamide-trimethoprim combination

ATC code: J01EE01(J01EE01)

Brand names: Bactrim, Bactrim DS, Septra

Updated 24 Sep 2026 · Methodology

Indications

Pneumocystis pneumonia prophylaxis

First line

Co-trimoxazole is the first-line agent for Pneumocystis jirovecii prophylaxis in HIV patients with CD4 below 200 cells/uL, after HSCT, in solid organ transplant recipients, and in patients on prolonged high-dose glucocorticoids. CDC/NIH/ 2024 recommend co-trimoxazole 80/400 mg daily or 160/800 mg three times weekly. The 2014 Cochrane review confirms an 85% reduction in PJP incidence in non-HIV immunocompromised patients.

Prophylaxis continues until CD4 recovers above 200 cells/uL and viral load is suppressed. In transplant recipients, at least 6–12 months depending on protocol.

Sources

ICD-10: B59 · ICD-11: 1F2G

Pneumocystis pneumonia treatment

First line

Co-trimoxazole at 15–20 mg/kg/day by trimethoprim, divided into 3–4 doses, for 21 days is the first-line treatment of Pneumocystis pneumonia. CDC/NIH/ 2024 recommend this regimen for both HIV-associated PJP and non-HIV patients. With PaO2 below 70 mm Hg or alveolar-arterial gradient above 35 mm Hg, prednisolone 40 mg twice daily is added. Alternatives for intolerance include pentamidine and primaquine plus clindamycin.

Sources

ICD-10: B59 · ICD-11: 1F2G

MRSA skin and soft tissue infection

First line

For community-acquired MRSA skin and soft tissue infections of mild to moderate severity (furuncle, drained abscess, limited cellulitis), co-trimoxazole 1–2 DS tablets twice daily for 5–10 days is a first-line oral option. 2011 lists the drug alongside doxycycline and clindamycin. Co-trimoxazole is preferred when clindamycin is resistant or intolerable. Severe forms require parenteral vancomycin or linezolid.

Sources

ICD-10: L08.9 · ICD-11: 1B70.2

Uncomplicated acute cystitis in women

First line

Co-trimoxazole 160/800 mg twice daily for 3 days is one of the first-line options for acute uncomplicated cystitis in non-pregnant women in regions where local E. coli resistance is below 20%. /ESCMID 2011 lists the drug alongside nitrofurantoin and fosfomycin. In Russia, 2022 monitoring data show E. coli resistance to co-trimoxazole above 25%, so the drug is more often used as an alternative when susceptibility is confirmed.

Not used in pregnant women in the first and third trimesters. Dose adjustment is required at eGFR below 30 mL/min/1.73 m².

Sources

ICD-10: N30.0 · ICD-11: GC00.0

Marketing claims without evidence base

The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.

Common cold

Not recommended

For acute viral upper respiratory infection and uncomplicated common cold, co-trimoxazole is not prescribed. The antibiotic does not shorten symptom duration or prevent bacterial complications, while carrying risks of rash, hematologic complications, and selection of resistant strains. "Just-in-case" prescribing for URI is an example of irrational antibiotic use.

Sources

ICD-10: J00 · ICD-11: CA00

How to read tiers A–F

AStrong evidence – first or second line in international guidelines
BRecommended in selected cases
CStudy data contradict each other
DBenefit not proven, no documented harm
FDocumented harm, or risk without benefit

Mechanism of action

Sulfamethoxazole blocks dihydrofolate synthesis; trimethoprim blocks its reduction to tetrahydrofolate. Sequential blockade of folate pathway gives bactericidal effect. Used for UTI, Pneumocystis pneumonia, toxoplasmosis.

Safety

Contraindications

Hypersensitivity to sulfonamides or trimethoprim
Glucose-6-phosphate dehydrogenase deficiency
Severe hepatic impairment with active hepatitis
eGFR below 15 mL/min/1.73 m² without monitoring capability
Folate deficiency-related megaloblastic anemia
First and third trimester of pregnancy
Children under 6 weeks
Concurrent use with high-dose methotrexate

Serious adverse effects

Stevens-Johnson syndrome, toxic epidermal necrolysis, DRESS
Fulminant hepatitis, hepatic failure
Agranulocytosis, aplastic anemia
Severe hyperkalemia in elderly patients on ACEi/ARB and spironolactone

Common adverse effects

Nausea, vomiting, diarrhea
Skin rash, pruritus
Hyperkalemia due to inhibition of collecting duct secretion
Creatinine rise due to competition with trimethoprim tubular secretion (does not reflect true GFR drop)

Uncommon adverse effects

Drug-induced hepatitis, cholestasis
Leukopenia, thrombocytopenia, megaloblastic anemia (especially in the elderly and folate-deficient)
Crystalluria with inadequate urine output
Hyponatremia due to SIADH

Pregnancy: can you take Co-trimoxazole?

AEMPS summary of product characteristics (section 4.6): trimethoprim and sulfamethoxazole cross the placenta, their safety in pregnant women has not been established, and both substances caused fetal malformations in animal studies. Trimethoprim is a folate antagonist, and case-control studies in humans suggest a possible association between exposure to folate antagonists and birth defects. Co-trimoxazole should be avoided in pregnancy unless the potential benefit to the mother outweighs the potential risk to the fetus; if it is used, high-dose folate supplementation (up to 4 or 5 mg/day) may be considered. If the mother takes it before delivery, sulfamethoxazole, which competes with bilirubin for binding to plasma albumin, may precipitate or worsen neonatal hyperbilirubinaemia, with a theoretical risk of kernicterus, because significant drug levels of maternal origin persist in the newborn for several days. This risk is particularly relevant in premature infants and infants with glucose-6-phosphate dehydrogenase deficiency, so co-trimoxazole should be avoided in late pregnancy.

Breastfeeding: can you take Co-trimoxazole?

In healthy term infants older than 1 month, breastfeeding is compatible with maternal co-trimoxazole use. In neonates with hyperbilirubinemia, prematurity, or G6PD deficiency, concurrent use is avoided.

Calculate RID

Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.

Practical notes

Timing and administration

Taken with meals or immediately after, washed down with a full glass of water (200–250 mL). Good hydration (at least 1.5–2 L/day) reduces crystalluria risk. Dosing is twice daily with a 12-hour interval. Combined with folic acid 5 mg/day in the elderly and during prolonged therapy to reduce cytopenia risk.

Dose titration

Standard doses by indication: UTI and travelers' diarrhea – 160/800 mg twice daily; MRSA skin infections – 160/800 mg twice daily; PJP treatment – 15–20 mg/kg/day by trimethoprim in 3–4 doses; PJP prophylaxis – 80/400 mg daily or 160/800 mg three times weekly. At eGFR 15–30 mL/min/1.73 m², the dose is halved. At eGFR below 15 mL/min/1.73 m², the drug is not used except in monitored hemodialysis patients.

Monitoring

Before starting therapy, check CBC, creatinine, eGFR, potassium, and liver enzymes. By day 7–10 of prolonged therapy and every 2 weeks thereafter, repeat CBC, creatinine, and potassium. In the elderly, with concomitant ACEi/ARB or potassium-sparing diuretics, monitor potassium every 3–5 days during the first 2 weeks of therapy. Rash is an indication to stop the drug immediately and assess severity (Stevens-Johnson risk).

Special situations

With concomitant warfarin, INR rises – check every 3 days and reduce warfarin dose by 25–50%. With concomitant methotrexate, myelosuppression risk increases; co-trimoxazole is contraindicated with high-dose methotrexate. In HIV patients tolerance is worse: rash occurs in 30–60%, and desensitization protocols are considered to continue PJP therapy.

Common myths

Myth: "biseptol is old and safe, can be used for any URI". Fact: useless in viral infections, while carrying rare but severe adverse effects (Stevens-Johnson, agranulocytosis). "Prophylactic" prescribing for URI is unjustified.

Myth: "creatinine rise on co-trimoxazole means renal failure". Fact: trimethoprim blocks tubular creatinine secretion, so creatinine rises by 10–20% without a true eGFR drop. Use cystatin C or repeat eGFR 7 days after discontinuation to assess kidney function.

Myth: "can be taken during partner's pregnancy". Fact: contraindicated in the first and third trimesters because of malformation and kernicterus risks.

Drug–nutrient interactions

Folate

Trimethoprim is a dihydrofolate reductase inhibitor and impairs conversion of folic acid to its active form. In long therapy or in patients with baseline deficiency, megaloblastic anemia, leukopenia, and thrombocytopenia develop. Prevention: folic acid 5 mg daily for courses longer than 14 days, in the elderly, and with concurrent methotrexate, phenytoin, or antiepileptic drugs.

Source: AEMPS: Ficha técnica de Cotrimoxazol (trimetoprima + sulfametoxazol) (2024)

Drug–drug interactions

9 pairs found. Sorted from critical to minor.

CriticalAmiodaroneClass III antiarrhythmics (Vaughan Williams)

Mechanism

Amiodarone prolongs the QT interval. Co-trimoxazole (trimethoprim + sulfamethoxazole) also prolongs QT and amplifies the effect in combination. UK MHRA Cordarone X SmPC Section 4.3 specifically lists QT-prolonging drugs as contraindications. Co-trimoxazole additionally inhibits CYP2C9, a partial amiodarone clearance route.

Symptoms

QT prolongation on ECG, dizziness, syncope, palpitations. Severe cases progress to torsades de pointes with risk of ventricular fibrillation. Risk rises with hypokalaemia (which co-trimoxazole can worsen).

Management

The combination is not prescribed. For UTI in patients on amiodarone, use a cephalosporin, nitrofurantoin, or fosfomycin. For Pneumocystis infection (where co-trimoxazole is irreplaceable), continuous ECG monitoring and daily potassium and magnesium checks.

Sources

Pair details →Amiodarone →

CriticalMethotrexateAntimetabolites, folic acid analogues

Mechanism

Co-trimoxazole contains trimethoprim, a dihydrofolate reductase inhibitor. Methotrexate blocks the same enzyme system. Co-administration intensifies the antifolate effect and suppresses haematopoiesis. Fatal pancytopenia and severe mucositis have been reported, even at low rheumatological methotrexate doses.

Symptoms

Stomatitis, mouth ulcers, nausea. Then – falling leukocyte and platelet counts: increased infection susceptibility and bleeding. Severe cases progress to fatal pancytopenia. Symptoms appear after 1–2 weeks of combined dosing.

Management

The combination is not recommended. For urinary tract infections in a patient on methotrexate, use nitrofurantoin or fosfomycin. For Pneumocystis infection where co-trimoxazole cannot be replaced, hold methotrexate for the antibiotic course and check full blood count every 3–5 days. Folic acid supplementation is mandatory.

Sources

FDA: Methotrexate Sodium Tablets prescribing information (2016)

Pair details →Methotrexate →

MajorCaptoprilACE inhibitor

Mechanism

Trimethoprim (a co-trimoxazole component) blocks sodium channels in the collecting duct epithelium (amiloride-like mechanism) and reduces potassium secretion. Captopril (ACE-I) additionally retains potassium via aldosterone suppression.

Symptoms

Muscle weakness, paraesthesia in the limbs, slowed pulse, arrhythmias. ECG shows peaked T waves and widened QRS. Severe cases progress to cardiac arrest. Symptoms typically appear within 1–2 weeks of starting the combination.

Management

During co-trimoxazole therapy (usually 5–10 days), check potassium 3–5 days after start. In older patients and chronic kidney disease, prefer alternative antibiotics: nitrofurantoin or fosfomycin for urinary tract infection.

Sources

PubMed: Trimethoprim-sulfamethoxazole and risk of sudden death among patients taking spironolactone or ACE inhibitors (2014)

Pair details →Captopril →

MajorEnalaprilAngiotensin-converting enzyme inhibitors (ACEi)

Mechanism

Trimethoprim blocks collecting duct sodium channels (amiloride-like mechanism) and reduces potassium secretion. Enalapril (ACE-I) additionally retains potassium through aldosterone suppression.

Symptoms

Management

During co-trimoxazole therapy, check potassium 3–5 days after start. In older patients and chronic kidney disease, prefer alternative antibiotics: nitrofurantoin or fosfomycin.

Sources

Pair details →Enalapril →

MajorLosartanAngiotensin II receptor blockers (sartans)

Mechanism

Trimethoprim blocks sodium channels via an amiloride-like mechanism, additively with an ARB (losartan) causing hyperkalaemia. In older patients, sudden death risk rises.

Symptoms

Muscle weakness, paraesthesia, slowed pulse, arrhythmias. ECG: peaked T waves, widened QRS. Severe cases progress to cardiac arrest.

Management

During co-trimoxazole therapy, check potassium 3 days after start. In older patients and chronic kidney disease, prefer alternative antibiotics (nitrofurantoin, fosfomycin).

Sources

PubMed: Trimethoprim-sulfamethoxazole and risk of sudden death among patients taking spironolactone or ACE inhibitors (2014)

Pair details →Losartan →

MajorSpironolactonePotassium-sparing diuretics (mineralocorticoid receptor antagonists)

Mechanism

Trimethoprim in co-trimoxazole blocks epithelial sodium channels in renal collecting ducts via the same mechanism as amiloride. Combined with spironolactone this produces dual potassium retention. In the elderly and in chronic kidney disease cohort studies show increased sudden death rates with the combination.

Symptoms

Hyperkalaemia within 1–2 weeks: weakness, paresthesia, arrhythmia. Detected on labs; symptoms appear late.

Management

Switch to an alternative antibiotic when possible (amoxicillin, cefalexin for urinary tract infection). If co-trimoxazole is required, check potassium and creatinine on days 3–5 and at end of course. Avoid the combination in patients over 65 with eGFR below 60 mL/min/1.73 m².

Sources

Pair details →Spironolactone →

MajorTelmisartanAngiotensin II receptor blocker (ARB)

Mechanism

Trimethoprim in co-trimoxazole blocks the epithelial sodium channel (ENaC) like amiloride – potassium retention. With an ARB (telmisartan): additive hyperkalaemia.

Symptoms

Muscle weakness, paraesthesia, slowed pulse, arrhythmias. ECG: peaked T waves, widened QRS. Severe cases progress to cardiac arrest.

Management

During co-trimoxazole therapy, check potassium 3 days after start. In older patients and chronic kidney disease, prefer alternative antibiotics (nitrofurantoin, fosfomycin).

Sources

BMJ: Co-trimoxazole, sudden death and RAS blockers — Fralick 2014 (2014)

Pair details →Telmisartan →

MajorValsartanAngiotensin II receptor blockers (ARBs)

Mechanism

Trimethoprim blocks collecting duct sodium channels (amiloride-like mechanism) and reduces potassium secretion. Valsartan (ARB) additionally retains potassium through aldosterone suppression.

Symptoms

Management

During co-trimoxazole therapy, check potassium 3–5 days after start. In older patients and chronic kidney disease, prefer alternative antibiotics: nitrofurantoin or fosfomycin.

Sources

PubMed: Trimethoprim-sulfamethoxazole and risk of sudden death among patients taking spironolactone or ACE inhibitors (2014)

Pair details →Valsartan →

MajorWarfarinVitamin K antagonist anticoagulants

Mechanism

Trimethoprim in co-trimoxazole inhibits CYP2C9. INR rises 50-100% within 3-5 days. High bleeding risk in elderly.

Symptoms

Gum and nose bleeding, petechiae, haematuria within 5-10 days.

Management

If possible – alternative antibiotic. If co-trimoxazole needed – cut warfarin by 30% and check INR on days 3 and 7.

Sources

Pair details →Warfarin →

Label mentions10 mentions

Verbatim lines from the interaction sections, in the language of the label

From other drugs’ labels

CriticalAmiodarone
«Medicamentos que inducen Torsades de pointes: Eritromicina intravenosa, cotrimoxazol o pentamidina inyectable.»
AEMPS, section 4.5 · Open on CIMA
MajorAzathioprine
«Siempre que sea posible, se debe evitar la administración concomitante de agentes citostáticos o medicamentos que puedan tener un efecto mielosupresor, como la penicilamina. Existen informes clínicos…»
AEMPS, section 4.5 · Open on CIMA
MajorClozapine
«Comentarios: Supresores de la médula ósea (p.ej., carbamazepina, cloranfenicol, sulfonamidas (p.ej., cotrimoxazol), analgésicos pirazolónicos (p.ej., fenilbutazona), penicilamina, agentes citotóxicos…»
AEMPS, section 4.5 · Open on CIMA
MajorLisinopril
«Diuréticos: Los factores de riesgo para el desarrollo de hipercalemia son: insuficiencia renal, diabetes mellitus y el uso concomitante de diuréticos ahorradores de potasio (ej. espironolactona…»
AEMPS, section 4.5 · Open on CIMA
MajorTacrolimus
«Recomendaciones relativas a la a dministración simultánea: Debido a que el tratamiento con tacrólimus puede asociarse con hiperpotasemia, o puede elevar la hiperpotasemia previa, debe evitarse la…»
AEMPS, section 4.5 · Open on CIMA
ModerateCandesartan
«Hiperpotasemia: El uso concomitante de candesartán y diuréticos ahorradores de potasio, suplementos de potasio, sustitutos de la sal que contengan potasio u otros medicamentos que puedan incrementar…»
AEMPS, section 4.4 · Open on CIMA
ModerateEnalapril
«Bloqueo dual del sistema renina-angiotensina-aldosterona (SRAA): Los inhibidores de la ECA reducen la pérdida de potasio inducida por los diuréticos. Los diuréticos ahorradores de potasio (p. ej…»
AEMPS, section 4.5 · Open on CIMA
ModerateLithium
«Interacciones que aumentan los niveles de litio: Antibióticos (nitroimidazoles (ej. Metronidazol)): el uso concomitante puede aumentar las concentraciones séricas de litio debido a la reducción del…»
AEMPS, section 4.5 · Open on CIMA
Azathioprine
«DRUG INTERACTIONS: Use with Other Agents Affecting Myelopoesis: Drugs which may affect leukocyte production, including co-trimoxazole, may lead to exaggerated leukopenia, especially in renal…»
FDA, section 7 · Open on DailyMed
Theophylline
«Drug Interactions:: co-trimoxazole (trimethoprim and sulfamethoxazole) norfloxacin»
FDA, section 7 · Open on DailyMed

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Frequently asked

What is Co-trimoxazole used for?

Co-trimoxazole is evaluated for the following indications with varying evidence strength: Pneumocystis pneumonia prophylaxis (evidence tier A), Pneumocystis pneumonia treatment (evidence tier A), Uncomplicated acute cystitis in women (evidence tier B). See the full indication matrix with dosing and citations above on this page.

What are the side effects of Co-trimoxazole?

Common side effects of Co-trimoxazole (≥ 1 in 100): Nausea, vomiting, diarrhea, Skin rash, pruritus, Hyperkalemia due to inhibition of collecting duct secretion, Creatinine rise due to competition with trimethoprim tubular secretion (does not reflect true GFR drop). See the Safety section for uncommon and serious reactions.

Is Co-trimoxazole safe during pregnancy?

Is Co-trimoxazole compatible with breastfeeding?

Who should not take Co-trimoxazole?

Co-trimoxazole is contraindicated in: Hypersensitivity to sulfonamides or trimethoprim; Glucose-6-phosphate dehydrogenase deficiency; Severe hepatic impairment with active hepatitis; eGFR below 15 mL/min/1.73 m² without monitoring capability; Folate deficiency-related megaloblastic anemia. Full list in the Safety section.

biseptol is old and safe, can be used for any URI

useless in viral infections, while carrying rare but severe adverse effects (Stevens-Johnson, agranulocytosis). "Prophylactic" prescribing for URI is unjustified.

creatinine rise on co-trimoxazole means renal failure

trimethoprim blocks tubular creatinine secretion, so creatinine rises by 10–20% without a true eGFR drop. Use cystatin C or repeat eGFR 7 days after discontinuation to assess kidney function.

can be taken during partner's pregnancy

contraindicated in the first and third trimesters because of malformation and kernicterus risks.

Official sources

Direct links to regulator labels. Open in a new tab.

GRLS

Other drugs in this group

Daptomycin, Doxycycline, Erythromycin, Flucloxacillin, Fosfomycin, Metronidazole, Amoxicillin, Cefuroxime axetil