Oral co-trimoxazole

Adult OPAT good practice prescribing guide for complex oral antibiotics

Co-trimoxazole is a combination of trimethoprim and sulfamethoxazole. Synergistic, bacteriostatic activity is observed for a variety of Gram-positive and Gram-negative bacteria. It is licensed for the treatment of urinary tract infections, otitis media, infective exacerbation of bronchitis, Pneumocystis jirovecii pneumonitis, toxoplasmosis and nocardia.

This guide shares practical experience of the use of co-trimoxazole in an OPAT setting. We took an evidence-based approach to create the guidance. We also used expert consensus and practical experience from across NHS Scotland.

This drug summary does not provide specific treatment guidance. Individual patient treatment should take into account the core principles of antimicrobial stewardship. This includes selection of the appropriate antimicrobial for the shortest duration with oral therapy being preferred, whenever possible.

For information on route and method of administration, contraindications, cautions and adverse effects and drug interactions please refer to the following approved resources:

These resources also have more information on licensed indication, use in pregnancy and use in breast feeding. When using an unlicensed medicine or a medicine off-label, follow local health board governance processes. 

It is strongly recommended that OPAT services in Scotland adhere to the Key performance indicators for the management of patients in an outpatient parenteral antimicrobial therapy (OPAT) setting.

Co-trimoxazole 

1. Indication and dose 

1a. Licensed indication(s) in the OPAT setting  Dose

Complicated urinary tract infection
Respiratory tract infection

 

 

960mg 12 hourly
(NB higher doses required if body mass index (BMI) over 30kg/m2. See ‘Dose adjustments and monitoring’ section below)

Pneumocystis jirovecii pneumonitis (PJP/ PCP)
Nocardiosis 

Requires higher dosing regimen 

 

1b. Off-label indications in the OPAT setting  Dose

Skin and soft tissue infection 
Bone and joint infection  
Moderate or severe diabetic foot infection 
Intra-abdominal infection

960mg 12 hourly
(NB higher doses required if BMI is over 30kg/m2. See ‘Dose adjustments and monitoring’ section below)
Infections associated with Stenotrophomonas and Serratia Requires higher initial dosing regimen 

 

2. Dose adjustments

These suggested dose adjustments are based on initial standard dosing 960mg 12 hourly.

Patient characteristic  Dosage advice 

Renal impairment 

 
Creatinine clearance (CrCl) Dose adjustment 
15 – 30ml/min  480mg 12 hourly 
Less than 15ml/min  Not recommended  
Hepatic impairment  No dose adjustment necessary. 

Obesity 

Consider higher dose (1440mg 12 hourly) in patients 100kg or more or with BMI of 30kg/m2 or more.

 

3. Monitoring requirements 

Frequency  Recommended monitoring 

Baseline 

Urea and Electrolytes (U&Es), liver function tests (LFTs), C-reactive protein (CRP) and full blood count (FBC).

Further monitoring 

 

 

 

 

Weekly U&Es, LFTs and FBC for at least two weeks after starting co-trimoxazole.

Monthly U&Es and FBC following initial weekly monitoring whilst patient remains with OPAT service.

CRP can be measured to monitor patient’s clinical progress.

Further monitoring once discharged from OPAT service is dependent upon patient and other clinical factors.
Therapeutic drug monitoring  No therapeutic drug monitoring required. 
Follow up  Ensure follow up is arranged with referring specialty, infection specialist or both as necessary.

 

4. Serious Drug/ Drug and Drug/ Food Interactions 

Please note that this is not an exhaustive list. Refer to the BNF or SPC for more information. 

Drug/ Food Recommendations


Other drugs known to increase risk of hyperkalaemia

(eg angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers and potassium sparing diuretics such as spironolactone)

Avoid co-administration where possible or perform increased weekly blood monitoring to assess for electrolyte imbalance.

 

 

 

 

 

Ciclosporin

 

 

Reversible deterioration in renal function has been observed in patients co-administered co-trimoxazole and ciclosporin. The mechanism is not fully understood but if co-administration cannot be avoided then close observation of renal function and ciclosporin therapeutic drug monitoring (TDM) is advised.

Digoxin

 

 

 

Trimethoprim may reduce renal clearance of digoxin leading to increased plasma concentrations and possible toxicity. If co-administration cannot be avoided, then digoxin TDM is advised (baseline and steady state digoxin plasma concentrations) to assess interaction and to advise digoxin dose adjustment if necessary. Digoxin TDM should also be performed on when stopping co-trimoxazole.

Hormonal contraception

 

Additional precautions are no longer necessary when co-trimoxazole (non-enzyme inducing drug) is taken with combined or progestogen-only contraceptive preparation unless diarrhoea, vomiting, or both occur. See manufacturer guidance.

Methotrexate

 

Co-administration with co-trimoxazole may result in profound bone marrow toxicity. Avoid co-administration where possible. Methotrexate is likely to already have been withheld in acute infection.

Phenytoin

 

 

 

Sulfonamides may reduce hepatic metabolism of phenytoin leading to increase plasma concentrations and possible toxicity. If co-administration cannot be avoided, then phenytoin TDM is advised (baseline and steady state phenytoin plasma concentrations) to assess interaction and to advise phenytoin dose adjustment if necessary. Phenytoin TDM should also be performed on cessation of co-trimoxazole.

Rifampicin

 

Rifampicin may increase metabolism of co-trimoxazole and subsequently reduce plasma concentrations by up to 30%. Consider increasing the co-trimoxazole dose to 1440mg 12 hourly.

Warfarin

 

 

Co-trimoxazole may enhance anticoagulant effect. Ensure follow up with anticoagulant service for International Normalised Ratio (INR) monitoring and any necessary dosage adjustments. Patients should also be counselled on signs of over anticoagulation (eg bruising, bleeding).

Drug/ Food interaction

Take with food to reduce gastrointestinal side effects.

 

5. Rare or Serious Adverse effects 

Please note that this is not an exhaustive list. Refer to the BNF or SPC and advice below.

Adverse effects  Recommendations 

Renal impairment

 

 

 

 

 

 

 

 

Serum creatinine rise may be observed following competition of tubular creatinine excretion.

If isolated serum creatinine rise;

  • Repeat U&Es monitoring and review blood test trends.
  • Continue co-trimoxazole therapy.

If any of the following are observed; reduced renal output or oliguria, hyperkalaemia, uraemia or raised and increasing serum creatinine trend;

  • Consider suspending other nephrotoxic drugs including ACE inhibitors, angiotensin receptor blockers and potassium sparing diuretics.
  • Repeat U&Es monitoring and review blood test trends.
  • Consider stopping co-trimoxazole therapy.

Blood dyscrasias 

 

 

 

 

 

 

Discontinue immediately if:

  • Blood dyscrasias (including leucopenia, thrombocytopenia, megaloblastic anaemia, neutropenia, eosinophilia)
    or
  • Rash (including Stevens-Johnson syndrome, Toxic Epidermal Necrolysis or acute generalised exanthematous pustulosis
    or
  • Acute respiratory symptoms associated with acute respiratory distress syndrome develop.

Haematinics 

 

 

 

 

 

Trimethoprim inhibits the action of an enzyme which is necessary for folate synthesis. This can lead to the development of megaloblastic anaemia.

Haematinics bloods test (including folate, vitamin B12 and iron studies) should be performed if concerns of folate deficiency with or without confirmed anaemia, known malabsorption or autoimmune gastroenterological disorder.

Trimethoprim or co-trimoxazole may be administered if folate deficiency is being actively treated.

Scottish Antimicrobial Prescribing Group (SAPG)
Approved May 2026 for review May 2029
Content updated: July 2026