Patients who were prescribed trimethoprim-sulfamethoxazole had more than twice (adjusted odds ratio [OR], 2.46; 95% confidence interval [CI], 1.55 - 3.90) the risk for sudden death compared with . 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. I had never taken ACE/ARBs. The bradycardia, chaotic heart rhythm and blood pressure changes were the most acutely dangerous for this individual, particularly if this was accompanied by disrupted sodium and potassium balance, as we can suspect was the case. We excluded cases that could not be matched to at least one control. and transmitted securely. Legalization is. Contribute now. So now you can see the problem. The large study, conducted over a 17-year period, involved 206 319 patients aged 66 years or older who were treated with spironolactone. Spotify I do not understand why this is not more well known. This particular study gathered data for more than 17 years, from 1994 through 2012, and included patients aged 66 years or older who were being treated with either an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) and then suddenly died within 7 or 14 days of starting treatment as an outpatient with an oral antibiotic. Maurer agreed that doctors should avoid this particular drug combination, especially since it mainly affects vulnerable seniors. The authors of that prior study theorized that such increased risk of sudden death in the cohort was associated with the quick and clinically significant rise in potassium, which then caused an unrecognized arrhythmic death. National Library of Medicine 1950) self-taught practitioners of geriatric medicine. After some digging, I found that at least one of the antibiotics, Bactrim, likely does indeed induce thiamine deficiency by potently blocking both thiamine transporters. of sudden death using a disease risk index. 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. I also wonder how best to disseminate details of drug interactions and adverse effects to practicing physicians as Ive noticed several instances of recently publicized interactions (e.g., thiazide diuretics depressive effect on insulin secretion with resulting increased blood glucose) that are well-described in much older editions of medical physiology and pharmacology texts. PMC More importantly, however, and this speaks to the fallacy of separateness that medicine holds dear, at any given time, we carry with 36 pounds of commensal bacteria that are responsible for a myriad of functions, including protective responses that prevent colonization and invasion by pathogens, the inhibition of growth of respiratory pathogens by producing antimicrobial products/signals and competing for nutrients and adhesion sites and importantly, for our purposes, the synthesis and metabolism of vitamins to be used by the host; the very pathways blocked by these antibiotics. But short-sighted physicians (and others), who dont look at multi-symptom, chronic illness as a possible effect of a class of antibiotics (FQs are chemo drugs masquerading as antibiotics) think that they have a better safety record than sulfa drugs. I believe these aspects of the drug may underlie many its adverse reactions in addition to, and perhaps compounding, those associated with its propensity to induce hyperkalemia. Bethesda, MD 20894, Web Policies Thank you for bringing attention to the dangers of cotrimoxazole. Unrecognized severe hyperkalemia may underlie this finding. Although the study found an association between combined use of spironolactone and trimethoprim-sulfamethoxazole and sudden death in seniors, it did not prove a cause-and-effect relationship. Unauthorized use of these marks is strictly prohibited. Ann Intern Med. We used SAS version 9.3 for all analyses and a two sided type 1 error rate of 0.05 as the threshold for statistical significance. Its down-regulation shifts towards catabolism resulting in muscle wasting. 9 However, we did not examine whether the drug interaction was associated with an increased risk of sudden cardiac death, a . We closely follow guidance from the World Wide Web Consortium. Contributions support operations but are not tax deductible. Now and again, a study comes along that changes how health care professionals think about prescribing. Copyright 2023 CBS Interactive Inc. All rights reserved. Health and Social Care Information Centre. inflammation . We found no such risk with norfloxacin (adjusted odds ratio 0.74, 0.53 to 1.02) and a lower risk with nitrofurantoin (0.64, 0.46 to 0.88) (table 2). We obtained physicians claims data from the Ontario health insurance plan database and identified patients with diabetes by using the Ontario diabetes database.21 We used the Ontario congestive heart failure database to identify people with heart failure.22 We identified sudden death from the vital statistics database, which contains the cause of death listed on individual death certificates.23 In Ontario, all death certificates are completed by the physician who last provided care to the patient, the patients family physician, or a coroner. Now, following second ablation, I am on Tikosyn and Pradaxa. Dear Doctor, I would like to express the deepest gratitude to you for writing and updating this website. On average, there have been between 6-7 million prescriptions of this drug written annually from 2007-2017, except for in 2015, where almost 12 million prescriptions were written. World Health Organization. It has been shown that specific transporters in the colon actively absorb folate (Said 2013) and as such contribute to folate levels in peripheral tissues and the circulation (Aufreiter et al. The decreased risk for the seven day analysis may be spurious, given the relatively small sample size, and may reflect selection of patients, as nitrofurantoin is generally reserved for uncomplicated urinary tract infections. Although I did not spend any time covering Keflex, the second drug prescribed to this individual, I would like to note that it too damages mitochondria, albeit by different mechanisms. Insufficient consumption and/or ingestion of pharmaceutical compounds that block intestinal thiamine transporters responsible for bringing thiamine into the cells, pose a serious health risk that includes death. The Canadian researchers reported that many of the patients they were tracking died suddenly within one to two weeks of starting this combination. Of these deaths, 1,110 occurred within seven days of a prescription for one of the study antibiotics. The answer to that question has to do in part to shoddy research and in part to an economically self-serving framework for understanding human physiology that has since become institutionalized into medical dogma. 2013. Some of the most common names are: These drugs are also included in many combination products. Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: support for the submitted work as described above; MMM has served on advisory boards and/or received honorariums from Astra Zeneca, Bristol-Myers Squibb, Eli Lilly and Company, GlaxoSmithKline, Hoffman La Roche, Novartis, Novo Nordisk, and Pfizer; no other relationships or activities that could appear to have influenced the submitted work. While most of the adverse effects of this drug are attributed to its induction of hyperkalemia high potassium levels via its blockage of the sodium channels in the kidneys, I think that is only part of the story. Across different research projects, estimates suggest from 30-70% may have insufficient thiamine intake to meet the demands of daily living and given the corresponding rise in chronic health issues of metabolic e.g. 27299 Riverview Center Boulevard, Suite 108. technical support for your product directly (links go to external sites): Thank you for your interest in spreading the word about The BMJ. Its already 2015. document.getElementById( "ak_js_1" ).setAttribute( "value", ( new Date() ).getTime() ); This site uses Akismet to reduce spam. Before Publication types Agree totally! Here is a link to the full article in the British Medical Journal. Trimethoprim-sulfamethoxazole increases the risk of hyperkalemia when used with spironolactone. Post graduate, she continued at UNLV as an adjunct faculty member, teaching advanced undergraduate psychopharmacology and health psychology (stress endocrinology). The cause of death will likely be assumed to be of natural causes such as a heart attack. In a supplementary analysis designed to test the robustness of our findings, we removed congestive heart failure (a known risk factor for sudden death) from the disease risk index and incorporated it as an independent term in the conditional logistic regression model. [1] Antoniou T, Hollands S, Macdonald EM et al. There is even a name for this situation: alert fatigue. It means that physicians and pharmacists override the computerized warnings because they get so darned many. Their findings provide important messages to caregivers and patients alike. Importantly, thiamine sits atop these processes, as a gatekeeper of sorts. Of the 1,601,542 patients in the study treated with either anACE-inhibitoror ARB, 39,879died suddenly. In other words, an awful lot of people are vulnerable to this potentially deadly drug combination. Among older patients treated with ACEIs or ARBs, the use of trimethoprim-sulfamethoxazole is associated with a major increase in the risk of hyperkalemia-associated hospitalization relative to other antibiotics. Neither trimethoprim nor sulfamethoxazole alone kill bacteria. Audio & Video Editing by Tim Stck of Aspire Digital Productions, Copyright 2023 - GeriPal - All Rights Reserved, Sudden death with trimethoprim-sulfamethoxazole while on ACE-inhibitor or ARBs, large nested case-control study published in the BMJ, The importance of social connection: Julianne Holt-Lunstad, Thomas Cudjoe, & Carla Perissinotto, RCT of Chaplaincy: Lexy Torke, Karen Steinhauser, LaVera Crawley, Storytelling in Medicine: A Podcast with Liz Salmi, Anne Kelly, and Preeti Malani, Psychedelics reasons for caution: Stacy Fischer, Brian Anderson, Theora Cimino. These days, generic forms are dispensed as co-trimoxazole or the combination trimethoprim and sulfamethoxazole (abbreviated TMP-SMX or TMP-SMZ). Like many human infections, UTIs are usually caused . One warned that potassium levels may increase and therefore should be monitored. Sign up to get our weekly updates directly to your inbox: Apple Podcasts His best-selling book, The Peoples Pharmacy, was published in 1976 and led to a syndicated newspaper column, syndicated public radio show and web site. They get warnings like that dozens of times a day. unsteadiness, trembling, or other problems with muscle control or coordination. Trimethoprimsulfamethoxazole induced hyperkalaemia in elderly patients receiving spironolactone: nested case-control study. sharing sensitive information, make sure youre on a federal Importantly, ciprofloxacin also tends to be used in patients with more severe or complicated urinary tract infections.38 Whether QT prolongation, severity of illness, or different indications explain the risk associated with ciprofloxacin is unclear. 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