The effect of co‐trimoxazole on serum potassium concentration: safety evaluation of a randomized controlled trial

Chan, Wei Yee; Clark, Allan; Wilson, Andrew M.; Loke, Yoon K.

doi:10.1111/bcp.13263

Cited by 13 publications

(10 citation statements)

References 25 publications

(32 reference statements)

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“…There was no significantly increased incidence of hyperkalemia after co-trimoxazole compared to ceftriaxone therapy, but this may have been due to lack of power. The corrected rise of 0.28 mmol/l in serum potassium, when compared to ceftriaxone, is largely in line with previous literature, such as a recent randomized controlled trial by Chan et al, which showed an average rise of 0.21 mmol/l after 6 weeks of oral therapy [10]. Nonetheless, the observed average rise of 0.43 mmol/l (range − 0.6 to + 1.9 mmol/l) in hospitalized patients does suggest that many of these patients are at an increased risk of hyperkalemia.…”

Section: Discussionsupporting

confidence: 89%

Co-trimoxazole induced hyperkalemia and potassium monitoring in hospitalized patients

et al. 2020

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Background Co-trimoxazole is an antibiotic combination used for the treatment of Pneumocystis jirovecii pneumonia, amongst others. Co-trimoxazole is known to increase serum potassium. For this reason, Dutch guidelines advise serum potassium monitoring in high-risk patients. Objective This study aimed to determine average serum potassium rise after administration of intravenous co-trimoxazole in hospitalized patients, compared to intravenous ceftriaxone. This study also aimed to determine adherence to Dutch guidelines by measuring the incidence of serum potassium monitoring in these patients. Setting Five departments of the Canisius Wilhelmina Hospital, a teaching hospital in Nijmegen, the Netherlands. Method Data was collected and compared from patients that received intravenous co-trimoxazole (n = 66) and intravenous ceftriaxone (n = 132) in the period of November 2008-November 2017. For each patient using co-trimoxazole, two patients using ceftriaxone were included in a paired fashion. Baseline and follow-up potassium were collected, if available. Additionally, it was tested if serum potassium was measured around the initiation of antibiotic therapy. Main outcome measure Changes in serum potassium where obtainable in 30 patients using cotrimoxazole and 40 patients using ceftriaxone. When compared to ceftriaxone, administration of intravenous co-trimoxazole was associated with a significant mean increase in serum potassium (+ 0.55 mmol/l, 95% CI 0.29-0.80, p < 0.001). After correction for confounders (baseline potassium, estimated glomerular filtration rate 30 to < 60, the presence of haematological malignancies and the usage of corticosteroids), this effect shrunk noticeably, but remained significant (+ 0.28 mmol/l, 95% CI 0.03-0.53, p = 0.031). Results The incidence of hyperkalemia at follow-up was 20% in the cotrimoxazole group, compared to 5% in the ceftriaxone group. Despite this, serum potassium was often not measured in patients using intravenous cotrimoxazole, being 76% at baseline and 55% in the period of 48-120 h after antibiotic therapy initiation, compared to 87% and 34% in the ceftriaxone group respectively. Conclusion Adherence to Dutch guidelines was poor as serum potassium monitoring was often not performed. As intravenous co-trimoxazole usage is associated with a significant increase in mean serum potassium, monitoring is strongly recommended.

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Section: Discussionsupporting

confidence: 89%

Co-trimoxazole induced hyperkalemia and potassium monitoring in hospitalized patients

et al. 2020

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“…An association between both co-trimoxazole, or trimethoprim alone, with hyperkalaemia is well reported, particularly in association with renin-angiotensin system blockers. 3 7 8 30 31 32 33 Our results suggest that, regardless of other drug use (renin-angiotensin system blockers or potassium-sparing diuretics), trimethoprim (but not ciprofloxacin), is associated with a more than doubling of the odds of hyperkalaemia. There is an additional increase in the odds of hyperkalaemia after a UTI for those prescribed renin-angiotensin system blockers, and greater than sixfold increase in association with concomitant use of a potassium-sparing diuretic, regardless of antibiotic choice.…”

Section: Discussionmentioning

confidence: 73%

Trimethoprim use for urinary tract infection and risk of adverse outcomes in older patients: cohort study

Crellin

Mansfield

Leyrat

et al. 2018

BMJ

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ObjectiveTo determine if trimethoprim use for urinary tract infection (UTI) is associated with an increased risk of acute kidney injury, hyperkalaemia, or sudden death in the general population.DesignCohort study.SettingUK electronic primary care records from practices contributing to the Clinical Practice Research Datalink linked to the Hospital Episode Statistics database.ParticipantsAdults aged 65 and over with a prescription for trimethoprim, amoxicillin, cefalexin, ciprofloxacin, or nitrofurantoin prescribed up to three days after a primary care diagnosis of UTI between April 1997 and September 2015.Main outcome measuresThe outcomes were acute kidney injury, hyperkalaemia, and death within 14 days of a UTI treated with antibiotics.ResultsAmong a cohort of 1 191 905 patients aged 65 and over, 178 238 individuals were identified with at least one UTI treated with antibiotics, comprising a total of 422 514 episodes of UTIs treated with antibiotics. The odds of acute kidney injury in the 14 days following antibiotic initiation were higher following trimethoprim (adjusted odds ratio 1.72, 95% confidence interval 1.31 to 2.24) and ciprofloxacin (1.48, 1.03 to 2.13) compared with amoxicillin. The odds of hyperkalaemia in the 14 days following antibiotic initiation were only higher following trimethoprim (2.27, 1.49 to 3.45) compared with amoxicillin. However, the odds of death within the 14 days following antibiotic initiation were not higher with trimethoprim than with amoxicillin: in the whole population the adjusted odds ratio was 0.90 (95% confidence interval 0.76 to 1.07) while among users of renin-angiotensin system blockers the odds of death within 14 days of antibiotic initiation was 1.12 (0.80 to 1.57). The results suggest that, for 1000 UTIs treated with antibiotics among people 65 and over, treatment with trimethoprim instead of amoxicillin would result in one to two additional cases of hyperkalaemia and two admissions with acute kidney injury, regardless of renin-angiotensin system blockade. However, for people taking renin-angiotensin system blockers and spironolactone treatment with trimethoprim instead of amoxicillin there were 18 additional cases of hyperkalaemia and 11 admissions with acute kidney injury.ConclusionTrimethoprim is associated with a greater risk of acute kidney injury and hyperkalaemia compared with other antibiotics used to treat UTIs, but not a greater risk of death. The relative risk increase is similar across population groups, but the higher baseline risk among those taking renin-angiotensin system blockers and potassium-sparing diuretics translates into higher absolute risks of acute kidney injury and hyperkalaemia in these groups.

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“…Dextromethorphan/quinidine was added because of its limited efficacy, concerns for clinically significant drug interactions, and potentially increased risk of falls in older adults. TMP‐SMX was placed in the “use with caution table” because of increased risk of hyperkalemia when used concurrently with an ACEI or ARB in the presence of decreased creatinine clearance . Rivaroxaban was also added to the use with caution table for adults 75 years or older.…”

Section: Discussionmentioning

confidence: 99%

“…TMP-SMX was placed in the "use with caution table" because of increased risk of hyperkalemia when used concurrently with an ACEI or ARB in the presence of decreased creatinine clearance. 13,14 Rivaroxaban was also added to the use with caution table for adults 75 years or older. Other important changes in the use with caution table included lowering the age threshold in the aspirin for primary prevention recommendation from 80 years or younger to 70 years or younger on the basis of emerging evidence of a major increase in the risk of bleeding at a lower age.…”

Section: Strength Of Recommendationmentioning

confidence: 99%

American Geriatrics Society 2019 Updated AGS Beers Criteria® for Potentially Inappropriate Medication Use in Older Adults

2019

J American Geriatrics Society

2,391

1,043

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The American Geriatrics Society (AGS) Beers Criteria® (AGS Beers Criteria®) for Potentially Inappropriate Medication (PIM) Use in Older Adults are widely used by clinicians, educators, researchers, healthcare administrators, and regulators. Since 2011, the AGS has been the steward of the criteria and has produced updates on a 3‐year cycle. The AGS Beers Criteria® is an explicit list of PIMs that are typically best avoided by older adults in most circumstances or under specific situations, such as in certain diseases or conditions. For the 2019 update, an interdisciplinary expert panel reviewed the evidence published since the last update (2015) to determine if new criteria should be added or if existing criteria should be removed or undergo changes to their recommendation, rationale, level of evidence, or strength of recommendation. J Am Geriatr Soc 67:674–694, 2019.

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The effect of co‐trimoxazole on serum potassium concentration: safety evaluation of a randomized controlled trial

Abstract: Co-trimoxazole significantly increases serum potassium concentration, even in participants not using antikaliuretic drugs. While the magnitude of increase was often minor, a small proportion in our outpatient cohort developed hyperkalaemia of clinical importance.

Cited by 13 publications

References 25 publications

Co-trimoxazole induced hyperkalemia and potassium monitoring in hospitalized patients

Co-trimoxazole induced hyperkalemia and potassium monitoring in hospitalized patients

Trimethoprim use for urinary tract infection and risk of adverse outcomes in older patients: cohort study

American Geriatrics Society 2019 Updated AGS Beers Criteria® for Potentially Inappropriate Medication Use in Older Adults

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