Saturday, 7 February 2015
RISK OF SUDDEN DEATH IN TAKING A VERY COMMON ANTIBIOTIC AND DIURETIC
A very recent study exposes how taking trimethoprim-sufamethoxazole(co-trimoxazole) and spirinolactone can lead to sudden death in the elderly.
Spironolactone, a diuretic used to treat
heart failure with side effects
including hyperkalaemia (raised blood
potassium levels), is associated with an
increased risk of sudden death when
combined with the antibiotic
trimethoprim–sulfamethoxazole,
according to a study [1] published in
the Canadian Medical Association
Journal on 2 February 2015.
“Many people think trimethoprim–
sulfamethoxazole [co-trimoxazole] is a
fairly innocuous drug with not a lot of
side effects,” says Tony Antoniou, lead
author on the study and a pharmacist
at St Michael’s Hospital in Toronto,
Canada. But the trimethoprim — not
the sulfamethoxazole — can also elevate potassium levels and
cause an interaction, he says.
“However, many medical professionals are not aware of this
effect of trimethoprim,” Antoniou adds. In Canada, the drug
is generally prescribed as trimethoprim–sulfamethoxazole,
whereas in the UK, trimethoprim is typically prescribed on
its own.
Antoniou, who is also a clinical epidemiologist at the non-
profit Institute for Clinical Evaluative Sciences, was prompted
to conduct his research after reading reports of high
potassium levels associated with this particular drug
interaction. In 2011, his team published their first study[2]
demonstrating the risk of hospital admission resulting from
hyperkalaemia in elderly patients taking spironolactone
alongside trimethoprim–sulfamethoxazole. That retrospective
study used the administrative health records, spanning 18
years, of more than 200,000 patients prescribed
spironolactone.
But the 2011 study did not establish whether the drug
interaction was associated with an increased risk of death.
“This is important because sudden death in patients taking
spironolactone may erroneously be attributed to intrinsic
heart disease,” say the researchers.
Using the same data, they found that of the 11,968 patients
who died of sudden death while receiving potassium-
elevating spironolactone, 328 died within 14 days of exposure
to certain antibiotics: trimethoprim–sulfamethoxazole,
amoxicillin, ciprofloxacin, norfloxacin or nitrofurantoin.
Most of the patients receiving spironolactone treatment who
died suddenly were 85 years of age or older.
The researchers matched each case with up to four controls
and found that sudden death was more than twice as likely
for those taking trimethoprim–sulfamethoxazole as for those
taking amoxicillin (adjusted odds ratio [OR] 2.46, 95%
confidence interval [CI] 1.55–3.90). Ciprofloxacin and
nitrofurantoin were also associated with an increased risk of
death (adjusted OR 1.55, 95% CI 1.02-2.38; and adjusted OR
1.70, 95% CI 1.03-2.79, respectively), although the risk with
nitrofurantoin was not apparent in a sensitivity analysis.
Most people do not need to worry about high potassium
levels, says Antoniou. And the potassium level of patients
taking spironolactone is usually monitored by cardiologists to
make sure it stays in the appropriate range. “However, with
this new study, we wanted to bring awareness about a drug
interaction which causes dangerously high potassium levels
that some physicians and pharmacists may not be aware of,”
he says. “If pharmacists notice that a patient is being treated
with both spironolactone and trimethoprim–
sulfamethoxazole or trimethoprim, they can call the
prescriber to see if an alternative antibiotic can be
prescribed.”
The study’s conclusions are not surprising given that both
spironolactone and co-trimoxazole on their own can cause
hyperkalaemia, say the editors of Stockley’s Drug
Interactions, a reference book of drug-interaction
information. “This additive adverse effect would also be
expected with any other drug known to cause hyperkalaemia,
such as other potassium-sparing diuretics and angiotensin-
converting enzyme inhibitors,” they say.
References:
[1] Antoniou T, Hollands S, Macdonald EM et al .
Trimethoprim–sulfamethoxazole and risk of sudden death
among patients taking spironolactone. CMAJ 2015; doi:
10.1503/cmaj.140816.
[2] Antoniou T, Gomes T, Mamdani M et al. Trimethoprim–
sulfamethoxazole induced hyperkalaemia in elderly patients
receiving spironolactone: nested case-control study. The BMJ
2011; 343:d5228.
Citation: The Pharmaceutical Journal , 14 February 2015, Vol 294, No
7849, online | URI: 20067792
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