Co-trimoxazole and sudden death in patients receiving inhibitors of renin-angiotensin system: population based study | The BMJ

This is an important study. We have known for some time that trimethoprim interferes with potassium excretion in the distal nephron at doses used in clinical practice.  80% of patients receiving trimethoprim (or cotrimoxazole)  develop increases in serum K by at least 0.36 mEq/L and 6% develop frank hyperkalaemia (> 5.4).  This state can occur quickly and be life-threatening.

This population-based nested case-control study from Ontario, demonstrates in a robust statistical manner that in older patients who receive ACE inhibitors or similar, cotrimoxazole is associated with an increased risk of sudden death (compared with amoxycillin, 3 additional cases per 1000 prescriptions). The increased risk extends out to 2 weeks after initiation of the prescription.

Co-prescription of ciprofloxacin (and not norflox) was also associated with a lesser significant increase in risk of sudden death, an expected finding, most probably related to prolonged QT arrhythmias.