Trimethoprim and Co-Trimoxazole

This information on drug interactions with antimicrobials is intended for use as a guide and not as a complete reference source

Antimicrobials	Interacting Drug	Comment
Trimethoprim and Co-Trimoxazole	Warfarin	May increase anticoagulant effect of warfarin with increased risk of bleeding - monitor INR closely.
	Methotrexate	Alternative antibiotic recommended. Several cases of severe bone marrow depression (several fatal) have resulted from the concurrent use of low-dose methotrexate and co-trimoxazole or trimethoprim.
	Other bone marrow depressants e.g. azathioprine, mercaptopurine	With other bone marrow depressants, close monitoring of haematological toxicity is recommended.
	Tacrolimus, Ciclosporin	May cause additive nephrotoxicity. If combination required, more frequent monitoring of drug levels of the immunosuppressant advisable.
	Amiodarone	Possible increased risk of ventricular arrhythmias: consider ECG monitoring in the presence of other risk factors for QT prolongation such as increasing age, female sex, cardiac disease, and some metabolic disturbances (notably hypokalaemia).
	Potassium sparing diuretics e.g. eplenerone	Trimethoprim in combination with these agents or potassium salts may increase the risk of hyperkalaemia or hyponatraemia. Patients should be monitored closely particularly if receiving high-dose or long-term trimethoprim treatment.
	ACE inhibitors and angiotensin II receptor antagonists	In theory, concurrent use of trimethoprim with angiotensin II receptor antagonists or ACE inhibitors might increase the risk of hyperkalaemia and/or sudden death. Monitor potassium concentrations and avoid where possible in elderly patients with or without chronic renal impairment.
	Dapsone	Increased risk of methaemoglobinaemia with dapsone and trimethoprim co-administration.
	Clozapine	Contraindicated, risk of neutropenia. If concurrent use necessary, increase monitoring FBC, including absolute neutrophil count.
	Digoxin	Increase in exposure to digoxin. Monitor digoxin levels and signs of digoxin toxicity (e.g. bradycardia).
	Phenytoin	Co-trimoxazole prolongs the half-life of phenytoin. Close monitoring of the patients' conditions and serum phenytoin levels is advisable.
	Gliclazide and Glipizide	Risk of hypoglycaemia with co-trimoxazole: Increase blood glucose monitoring and adjust antidiabetic drug dose if necessary.
	Repaglinide	Risk of hypoglycaemia: Increase blood glucose monitoring and adjust antidiabetic drug dose if necessary.