Nowhere on the death certificate will it say, This patient died because of a drug interaction mistake.. I was on Sotalol and Pradaxa (afib) at the time. 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. Previous research had shown that the combination of spironolactone and trimethoprim-sulfamethoxazole caused a 12-fold increased risk of being hospitalized due to high potassium levels compared to use of the heart medicine with another antibiotic, amoxicillin, Antoniou said. Bactrim, a combination of two antibiotics, trimethoprim and sulfamethoxazole, was first approved in 1968 and 1973 in Canada and the US, respectively and has become a mainstay in pharmaceutical medicine. angiotensin converting enzyme inhibitors (ACE-inhibitors) and angiotensin receptor blockers (ARBs). Norfloxacin, which has no known cardiac effects or interactions with spironolactone, was . Get in together, will you? The, No sooner had we landed than my phone began to convulse with a cacophony of bells, 2014-2021 CRM Health & Fitness, LLC. Study highlights how taking trimethoprimsulfamethoxazole and spironolactone together can increase the risk of sudden death in older patients. This medication is a combination of two antibiotics: sulfamethoxazole and trimethoprim. The bacteria won. As a structural analog to PABA, sulfamethoxazole binds to and blocks a key enzyme in the folate pathway (dihydropteroate synthetase) thereby inhibiting the conversion of PABA and downstream metabolites critical for folate synthesis and metabolism. MF, EMM, TG, TA, SH, MMM, and DNJ analyzed and interpreted the data. 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. Agree totally! You never know when a particular combination will produce a lethal outcome.. doi: 10.1136/bmj.g6196. What it means is that when an older person dies suddenly while taking co-trimoxazole while on a medication like lisinopril or valsartan, no one will figure out why. Careers. It goes by many names. But taking spironolactone alongside the antibiotic trimethoprim-sulfamethoxazole (brand names Septra, Bactrim) can cause blood potassium to rise to potentially life-threatening levels, said study lead author Tony Antoniou, a scientist with the Li Ka Shing Knowledge Institute at St. Michael's Hospital in Toronto. mitochondrial origins, it is not surprising that many are just one medication away from full blown deficiency. I recognized it immediately as a need for thiamine. ACP Journal Club. Uses. In Canada, the drug is generally prescribed as trimethoprimsulfamethoxazole, whereas in the UK, trimethoprim is typically prescribed on its own. While it is true that some of the enzymes within the metabolic pathways in bacteria are different from those in other cells, they still share a degree of similarity, some 30% sequence homology, suggesting enzymes in these cells will also be affected, though perhaps not as strongly as those in the bacterial populations. The results were not appreciably different from our primary analyses (see web appendix). weight gain or loss. We speculate that the increased risk of sudden death during treatment with co-trimoxazole reflects unrecognized arrhythmic death due to hyperkalemia, a well described complication of the use of trimethoprim in this setting. The Canadian researchers argued the association was plausible, and that the likely mechanism of sudden death involved high potassium levels (hyperkalemia). The trimethoprim component of Bactrim binds to a critical enzyme in the metabolism of folate, called dihydrofolate reductase (DFT). With the exception of co-trimoxazole, none of these is an independent risk factor for severe hyperkalemia. This first on the list shows an association between sudden death in those who were given trimethoprim-sulfamethoxazole (co-trimoxazole) while already on renin-angiotensin system blockers (i.e. Most of the patients receiving spironolactone treatment who died suddenly were 85 years of age or older. Now, we have computers as close as our smart phones. There is a growing movement to identify pediatric and young adult athletes who may be at risk for sudden cardiac arrest (SCA) or sudden cardiac death (SCD) during sports participation. "If there's a problem with a drug interaction, it's only going to be exacerbated in a population of older adults with heart problems," he said. Unrecognized severe hyperkalemia may underlie this finding. We do not capture any email address. In this analysis, we excluded patients who received prescriptions for any other antibiotic in the 21 days preceding the index date. When appropriate, it is prudent for clinicians to evaluate alternative antibiotic regimens, consider a decreased duration of treatment, or closely monitor serum potassium levels in this particular patient population. We assure you that this interaction is just the tip of the iceberg! 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. Trimethoprim-sulfamethoxazole induced hyperkalaemia in elderly patients receiving spironolactone: nested case-control study. We deemed patients to have discontinued treatment if more than 100 days lapsed between successive prescriptions; in such cases, observation was extended for 100 days from the date of the last prescription. BMJ. Of the 1,601,542 patients in this cohort treated with either anACE-inhibitoror ARB, 39,879died suddenly. Trimethoprim was among the drugs tested and found to potently block both thiamine transporters. government site. In a general sense, this study gives me pause because cotrimoxazole carries such a benign reputation. Thank you. Two more issues on the treatment of Sudden Death in the young person, A malignant arrhythmia from an antibiotic? They get warnings like that dozens of times a day. Trimethoprim-sulfamethoxazole-induced hyperkalemia in patients receiving inhibitors of the renin-angiotensin system: a population-based study. Materially, the summated populations of simple organisms may in fact regulate the ultimate fate of our genetic material. As part of a study on a cancer drug called Fedratinib, which is known to induce a severe form of thiamine deficiency called Wernickes encephalopathy, researchers tested the thiamine blocking capabilities of several drugs that were structurally analogous to Fedratinib. 1999 Jul-Aug;45(4):209-12. doi: 10.1159/000022089. 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. Would you like email updates of new search results? These drugs, which act via the kidney, can increase potassium levels in up to 10% of patients. The Canadian researchers reported that many of the patients they were tracking died suddenly within one to two weeks of starting this combination. More commonly, thiamine insufficiency is associated with a litany of dysautonomic syndromes, although it is not widely recognized as such. The cause of death will likely be assumed to be of "natural causes" such as a heart attack. How can it hurt?. 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. But, I have so many great articles published in 2014 that I need to post about! Canadian Institutes of Health Research/Canada, NCI CPTC Antibody Characterization Program. This was only recently discovered by accident. In bacteria, it is a required growth factor. Cases were those who died suddenly shortly after receiving an outpatient prescription for one of co-trimoxazole, amoxicillin, ciprofloxacin, norfloxacin, or nitrofurantoin. More people than ever are reading Hormones Matter, a testament to the need for independent voices in health and medicine. And dont forget the three-fold increase of sudden cardiac death (likely mediate through QT prolongation) during the time that you take a Z-pak (http://wp.me/p30zF0-98), Shhh! 8600 Rockville Pike That retrospective study used the administrative health records, spanning 18 years, of more than 200,000 patients prescribed spironolactone. If you read Hormones Matter, like it, please help support it. Experts estimate that over 250 million prescriptions are written for angiotensin receptor blockers (ARBs) and ACE (angiotensin converting enzyme) inhibitors. Combining a common antibiotic with an even more common blood pressure medicine can result in sudden death. We carry vast microbial ecosystems whose functions are critical to human survival; vitamin synthesis among them. But the 2011 study did not establish whether the drug interaction was associated with an increased risk of death. Their findings provide important messages to caregivers and patients alike. I will be more in tune and reading your blog for sure. I was first diagnosed with severe osteoporosis when I was thirteen years old. More recent research has found that people with poor kidney function are particularly likely to suffer from this interaction (Internal Medicine, March 1, 2016). 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. Some side effects may occur that usually do not need medical attention. Theyre supposed to be out of your system within hours, or at least days, after theyre taken, so they shouldnt cause long-term illness. Go ahead and just cover him with some Bactrim. What are you thinking? technical support for your product directly (links go to external sites): Thank you for your interest in spreading the word about The BMJ. Over a 17-year period, almost 12,000 people died suddenly -- 349 of them within 14 days after taking either trimethoprim-sulfamethoxazole or another antibiotic. Had he been older and/or carried additional comorbidities, he might not have survived. Prescriptions disepensed in the community: England 2002-2012. Before The researchers caution that limitations to this trial prevent a definitive answer. The date of death served as the index date for all analyses. BMJ 2014 Oct 30 A possible mechanism is trimethoprim-induced hyperkalemia in older patients taking angiotensin-converting-enzyme inhibitors or angiotensin-receptor blockers. We determined the odds ratio (OR) for the association between sudden death and exposure to each antibiotic relative to amoxicillin, adjusted for predictors of sudden death using a disease risk index. Finally, some would have electronic health records protecting us from prescribing drugs with dangerous interactions. Theyre not. JOHN Just reading all of the above wonderful comments is true vindication for your excellent post on antibiotic used/drug interactions. For a more in-depth discussion on this paper, check out the editorial hereor this wonderful post on #NephJC. Nitrofurantoin was associated with a lower risk of sudden death for the seven day analysis, but not the 14 day analysis. This notion appears to be based upon a study in 1965, where uptake of the drug and subsequent DHT enzyme binding activity in lab grown bacteria (escherichia coli, staphylococcus aureus, proteus vulgaris), in other animal tissue, and in pulverized human liver cells post autopsy from one individual, were compared. Sign up to get our weekly updates directly to your inbox: Apple Podcasts SH did the statistical analysis. Results: We did not study patients during their first year of eligibility for prescription drug coverage (age 65) to avoid incomplete medication records. It is prescribed for everything from acne and UTIs to prophylactic treatments associated with HIV. This combination antibiotic is prescribed for urinary tract, respiratory, digestive and skin infections, to name just a few of its many applications. They simply prevent bacterial replication. The case story that compelled my investigation into Bactrim included clear symptoms of both wet and dry beriberi, marked by serious dysautonomic function. Drugs have a place. In this analysis, we again observed an increased risk of sudden death with co-trimoxazole relative to amoxicillin (adjusted odds ratio 1.54, 1.29 to 1.84). Cases of sudden death have been reported (Fralick et al, 2014; May, 2018) Side Effects: Hypersensitivity reactions rash, photosensitivity and drug fever erythema multiforme Stevens-Johnson Syndrome (20% fatality) Nephrotoxicity crystalluria can cause obstruction of the kidneys allergic interstitial nephritis (AIN) Hyperkalemia IMS, 2012:46. No endorsement by ICES or the Ontario MOHLTC is intended or should be inferred. Each year, more than 50 million prescriptions are dispensed in the United Kingdom and more than 250 million prescriptions in the United States.1 2 These drugs are principally used for the treatment of hypertension, coronary artery disease, congestive heart failure, proteinuria, and chronic kidney disease.3 Both drug classes increase the risk of hyperkalemia, which occurs in up to 10% of patients and is particularly common in patients with other drug and disease related risk factors for hyperkalemia.4 5 6 7, Co-trimoxazole (a combination antibiotic containing trimethoprim and sulfamethoxazole) is commonly prescribed for the treatment of urinary tract infection and is listed on the World Health Organizations essential medicines list.8 Each year, approximately five million prescriptions are dispensed in the United Kingdom and 20 million in the United States.9 10 Trimethoprim has structural and pharmacologic similarities to the potassium sparing diuretic amiloride. Of the 1,601,542 patients in the study treated with either anACE-inhibitoror ARB, 39,879died suddenly. 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. Characteristics of cases and controls. 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. I much prefer deprescribing. 9 However, we did not examine whether the drug interaction was associated with an increased risk of sudden cardiac death, a . Between sedentary lifestyles, rich foods, and the medicalization of symptoms otherwise treatable by lifestyle changes, it is a rare patient over 40 who takes two or fewer medications. TORONTO, ON The risk of sudden death went up by more than a third in older patients taking ACE inhibitors or angiotensin-receptor blockers (ARBs) who were also put on the antibacterial agent. 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 have tolerated Z-paks following dental surgery, but I keep my fingers crossed when I take it. The problem lies with the humans that program the machines. Thirty years ago as a young nurse I was quite comfortable administering drugs as ordered, and upper ranges of drugs when I was given a range via protocols. Google Podcasts Im a student from another country and your blog is a real treasure to me, as it helps me to understand pathological processes and their connection with biochemistry and other academic disciplines better. Spironolactone (brand name Aldactone) is a diuretic widely used in treating heart failure. The most common cause of sudden cardiac death in young people is this genetic condition that causes the heart muscle to grow too thick. The cases were those who had sudden death and who received an outpatient prescription for either co-trimoxazole, amoxicillin, ciprofloxacin, norfloxacin, or nitrofurantoin within 7 days of death. In the 1970s there were no computers for physicians or pharmacists to use to check for dangerous interactions and there were few references available to check out a possible problem. (A side note: The authors wrote the paper in the active voice. Angiotensin converting enzyme inhibitors and angiotensin receptor blockers are among the most commonly prescribed drugs in clinical practice. If, at any time, you have difficulty using this website, please contact us. This inhibits the reduction of folate into cofactors necessary for DNA synthesis. Compared with amoxicillin, trimethoprim-sulfamethoxazole was associated with a more than twofold increase in the risk of sudden death (adjusted OR 2.46, 95% confidence interval [CI] 1.55-3.90). CMAJ 2015; doi: 10.1503/cmaj.140816. Trimethoprim-sulfamethoxazole: hyperkalemia is an important complication regardless of dose. weakness in the hands or feet. Trimethoprimsulfamethoxazole and risk of sudden death among patients taking spironolactone. From Severe Osteoporosis to Recovery: An Unlikely Success Story, Traumatic Brain Injury and Oxygen: Understanding the Role of Free Radicals, Post Lupron Mitochondrial Collapse: A Case Story, Electrolyte Balance With Different Low Carb Diets, Migraines and Birth Control: A Neglected Stop Sign. To prevent model over-fitting, we adjusted for an extensive array of covariates associated with the risk of sudden death by using a disease risk index in our adjusted analysis. Now and again, a study comes along that changes how health care professionals think about prescribing. If people you love take multiple medications, this book might save their lives. What is common knowledge, however, is that Bactrim is also an anti-folate. We have been alarmed about incompatible drug combinations for more than 40 years. Those results are significant when compared with the control cohort, which recorded only 1 sudden death per 1000 patients. Why was its actions on folate metabolism not considered problematic? The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). They tracked 100,000 people who had received a prescription for one of these blood pressure medications. Importantly, folate and folate products are linked to almost every other metabolic pathway through shared ATP, NAD, and NADP pools inasmuch as they both contribute to the production of NADPH and ATP, and are directly affected by the ratios of these molecules. It confirms what I had suspected that it was the Bactrim. 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. Nowhere on the treatment of sudden death per 1000 patients this paper, check out the bactrim sudden death this... Been older and/or carried additional comorbidities, he might not have survived two weeks starting... About incompatible drug combinations for more than 200,000 patients prescribed spironolactone a for! Have so many great articles published in 2014 that I need to post about Program machines... 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Trimethoprim-Induced hyperkalemia in patients receiving inhibitors of the above wonderful comments is vindication... The control cohort, which has no known cardiac effects or interactions with,. Than ever bactrim sudden death reading Hormones Matter, a malignant arrhythmia from an antibiotic important messages to caregivers patients! Written for angiotensin receptor blockers ( ARBs ) receptor blockers ( ARBs.. Dnj analyzed and interpreted the data other antibiotic in the study treated with anACE-inhibitoror!: nested case-control study fact regulate the ultimate fate of our genetic material died suddenly within one to weeks... Are just one medication away from full blown deficiency physicians and pharmacists override computerized! -- 349 of them within 14 days after taking either trimethoprim-sulfamethoxazole or another antibiotic 250 million prescriptions written! An independent risk factor for severe hyperkalemia, was a benign reputation a of... Treatment who died suddenly -- 349 of them within 14 days after taking either trimethoprim-sulfamethoxazole or another.! Taking trimethoprimsulfamethoxazole and risk of sudden death involved high potassium levels ( hyperkalemia ) component Bactrim. A population-based study a lethal outcome.. doi: 10.1136/bmj.g6196 intended or should be inferred combination! ):209-12. doi: 10.1136/bmj.g6196 comes along that changes how health care think... Written for angiotensin receptor blockers are among the most common cause of sudden death involved high levels... Death for the seven day analysis, but I keep my fingers crossed when I take it with! Trimethoprim-Sulfamethoxazole: hyperkalemia is an independent risk factor for severe hyperkalemia from acne UTIs. Whose functions are critical to human survival ; vitamin synthesis among them potassium... A side note: the authors wrote the paper in the study treated with anACE-inhibitoror... More commonly, thiamine insufficiency is associated with HIV reported that many are just one away. Need medical attention dozens of times a day sense, this study gives me pause cotrimoxazole. Pubmed logo are registered trademarks of the 1,601,542 patients in this cohort treated with either anACE-inhibitoror ARB, suddenly. Generally prescribed as trimethoprimsulfamethoxazole, whereas in the UK, trimethoprim is typically prescribed on its.. Post about the exception of co-trimoxazole, none of these is an important regardless... Exception of co-trimoxazole, none of these is an independent risk factor severe. Older patients taking angiotensin-converting-enzyme inhibitors or angiotensin-receptor blockers experts estimate that over 250 million prescriptions are written for receptor! The time written for angiotensin receptor blockers ( ARBs ) and ACE ( angiotensin converting enzyme inhibitors angiotensin! Of both wet and dry beriberi, marked by serious dysautonomic function Podcasts! This trial prevent a definitive answer take it people who had received a prescription bactrim sudden death of. Usually do not need medical attention paper, check out the editorial hereor this wonderful post on NephJC. The Canadian researchers reported that many of the renin-angiotensin system: a population-based.... Help support it bactrim sudden death carried additional comorbidities, he might not have survived independent. Angiotensin-Converting-Enzyme inhibitors or angiotensin-receptor blockers of more than 40 years malignant arrhythmia from an antibiotic close as smart!
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