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

Abstract

Objective To determine whether the prescription of co-trimoxazole with an angiotensin converting enzyme inhibitor or angiotensin receptor blocker is associated with sudden death. Design Population based nested case-control study. Setting Ontario, Canada, from 1 April 1994 to 1 January 2012. Participants Ontario residents aged 66 years or older treated with an angiotensin converting enzyme inhibitor or angiotensin receptor blocker. Cases were those who died suddenly shortly after receiving an outpatient prescription for one of co-trimoxazole, amoxicillin, ciprofloxacin, norfloxacin, or nitrofurantoin. Each case was matched with up to four controls on age, sex, chronic kidney disease, and diabetes. Main outcome measure Odds ratio for the association between sudden death and exposure to each antibiotic relative to amoxicillin, after adjustment for predictors of sudden death according to a disease risk index. Results Of 39 879 sudden deaths, 1027 occurred within seven days of exposure to an antibiotic and were matched to 3733 controls. Relative to amoxicillin, co-trimoxazole was associated with an increased risk of sudden death (adjusted odds ratio 1.38, 95% confidence interval 1.09 to 1.76). The risk was marginally higher at 14 days (adjusted odds ratio 1.54, 1.29 to 1.84). This corresponds to approximately three sudden deaths within 14 days per 1000 co-trimoxazole prescriptions. Ciprofloxacin (a known cause of QT interval prolongation) was also associated with an increased risk of sudden death (adjusted odds ratio 1.29, 1.03 to 1.62), but no such risk was observed with nitrofurantoin or norfloxacin. Conclusions In older patients receiving angiotensin converting enzyme inhibitors or angiotensin receptor blockers, co-trimoxazole is associated with an increased risk of sudden death. Unrecognized severe hyperkalemia may underlie this finding. When appropriate, alternative antibiotics should be considered in such patients.

Trimethoprim–sulfamethoxazole and risk of sudden death among patients taking spironolactone

“…9,[26][27][28][29] A similar interaction likely accounts for the increased risk of hyperkalemia and sudden death associated with trimethoprim-sulfamethoxazole among patients receiving renin-angiotensin inhibitors. 18,30 The mechanism by which trimethoprim can precipitate hyperkalemia in patients receiving spironolactone relates to an amiloride-like inhibition of sodium channels in the luminal membrane of the distal tubule, which results in impaired potassium secretion and sodium reabsorption. 31 Similarly, the heightened risk of sudden death with nitrofurantoin observed in our main analysis is consistent with our earlier findings of a more than twofold increased risk of hyperkalemia when the drug is combined with spironolactone.…”

2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death

“…Wykazano, że inne antybiotyki z grupy makrolidów, w tym erytromycyna i klarytromycyna (które są również metabolizowane przez izoenzym 3A4 cytochromu P450), zwiększają ryzyko wielokształtnego VT i zgonu z przyczyn sercowych, zwłaszcza u kobiet [748]. Ostatnio ze zwiększonym ryzykiem nagłego zgonu powiązano jednoczesne stosowanie inhibitorów układu renina-angiotensyna oraz takich antybiotyków, jak kotrimoksazol, które mogą się wiązać z nierozpoznaną hiperkaliemią [749].…”

A decade of outpatient antimicrobial use in older adults in Ontario: a descriptive study

“…This may reflect increasing recognition of its adverse effects, 52 particularly among older patients coprescribed common cardiovascular and renal medications. 37,53,54 Prescriptions for ciprofloxacin decreased as well, which may be owing to rising awareness of the risks associated with fluoroquinolones. [55][56][57][58] Cephalexin was consistently the most commonly prescribed antibiotic for skin/soft-tissue infections.…”

“…These databases are well validated and have been used in studies on antimicrobial prescribing. [34][35][36][37][38] The Ontario Drug Benefit Program database, which contains all publicly funded medications prescribed to Ontario residents aged 65 years or more, was used for information on antimicrobial prescribing. This database exhibits greater than 99% accuracy when compared against pharmacy dispensing data.…”