The trouble is, physicians and pharmacists often ignore and override drug interaction alerts, especially those they deem relatively unimportant. 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. Bactrim and Septra were the original brand names for this drug. 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. So now you can see the problem. 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. It was an impossible task. My phone calls were always returned quickly and all of my questions were answered in a thorough manner. 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. MF, EMM, and SH acquired the data. Well then, for my next series of posts Im going to do a quick round-up of articles published last year that we havent already talked about on GeriPal. When appropriate, alternative antibiotics should be considered in such patients. "We wanted to see if this translated into a higher risk for sudden death in these patients," he said. Heart rhythm disorders. If you ever feel like covering the dangers of fluoroquinolones, I know that everyone going through fluoroquinolone toxicity syndrome would appreciate the attention and acknowledgement. Long QT syndrome is a heart rhythm condition that can cause fast, chaotic heartbeats. In Canada, the drug is generally prescribed as trimethoprimsulfamethoxazole, whereas in the UK, trimethoprim is typically prescribed on its own. Interpretation: The antibiotic trimethoprim-sulfamethoxazole was associated with an increased risk of sudden death among older patients taking spironolactone. The findings are published Feb. 2 in CMAJ (Canadian Medical Association Journal). 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. No human can possibly remember all the dangerous drug combinations. Hormones Matter is run by CRM Health & Fitness, LLC. Sigh. x-ray results showing lung tissue changes. In addition to blocking folate metabolism, the trimethoprim component of Bactrim also blocks thiamine uptake. ACE inhibitors and ARBs are used a lot. Had he been older and/or carried additional comorbidities, he might not have survived. 2014 Oct 30;349:g6196. We examined whether this drug combination is associated with an increased risk of sudden death, a consequence of severe hyperkalemia. If ones diet is high in sugars, supplemented with coffee or tea, and/or if alcohol is consumed regularly, the path to thiamine deficiency is expedited. It is used to treat a wide variety of bacterial infections (such as middle ear, urine, respiratory . PMC Im typically somewhat deficient already due to hyperthyroidism and wondered why the sudden increase in symptoms. UTIs are one of the most common types of infections; at least one in two women and one in 10 men will experience a UTI in their lifetime. More often than not, health professionals relied upon memory to try to avoid such complications. Most of the patients who died were. After just a few days on Bactrim I started experiencing rapid heart rate, hyperventilation-type symptoms, numbness and insomnia. Combining a common antibiotic with an even more common blood pressure medicine can result in sudden death. 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. Theyre not supposed to do the same thing to GABA-A receptors as protracted benzodiazepine withdrawal. Doing such an analysis may have further strengthened the argument that hyperkalemia underlies our main observations. Antibiotic prescribing excluding topical antibiotic preparations. 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. 2015 Canadian Medical Association or its licensors. Sorry for going off on my tangent about FQs. Those results are significant when compared with the control cohort, which recorded only 1 sudden death per 1000 patients. Ill be more cautious when prescribing trimethoprim-sulfamethoxazole, especially in those taking ACE-inhibitors and ARBs. 2015 Canadian Medical Association or its licensors. Cotrimoxazole is also a commonly used antibiotic, with up to 50 million prescriptions written each year. The importance of our findings is underscored by the fact that co-trimoxazole is prescribed to millions of patients taking angiotensin converting enzyme inhibitors or angiotensin receptor blockers. Thank you. As far as I can tell, in the 50 years this drug has been on the market, its conformational similitude to thiamine was not considered. Methods: That retrospective study used the administrative health records, spanning 18 years, of more than 200,000 patients prescribed spironolactone. 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. But, I have so many great articles published in 2014 that I need to post about! It is a structural analog of the vitamin-like compound para-aminobenzoic acid (PABA) found in several foods and involved in the metabolism of folic acid. 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. Sudden death is found among people who take Bactrim ds, especially for people who are male, 60+ old, have been taking the drug for < 1 month. Trimethoprim was among the drugs tested and found to potently block both thiamine transporters. Clinical trials, case reports, and laboratory studies show that co-trimoxazole induced hyperkalemia can occur quickly and can cause life threatening arrhythmias, especially among patients receiving angiotensin converting enzyme inhibitors or angiotensin receptor blockers.13 15 16 19 33 34 Our previous research on this drug interaction showed a nearly sevenfold increased risk of hospital admission with hyperkalemia following co-trimoxazole treatment but no such risk with the same alternative antibiotics studied here.14 In the analysis presented here, we found no increased risk of sudden death with nitrofurantoin or norfloxacin. Considering that the vast number of medication adverse reactions are rarely identified much less published, almost 1000 papers published suggests something is going on with this medication. Fralick M, Macdonald EM, Gomes T, Antoniou T, Hollands S, Mamdani MM, Juurlink DN; Canadian Drug Safety and Effectiveness Research Network. Some limitations of our study merit emphasis. It is estimated that roughly 20 million prescriptions are filled for this drug each year. 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: trimethoprimsulfamethoxazole, amoxicillin, ciprofloxacin, norfloxacin or nitrofurantoin. Although other combinations of sulfonamides are available with trimethoprim, TMP-SMX is by far the most widely used. 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. Trimethoprim-sulfamethoxazole-induced hyperkalemia in patients receiving inhibitors of the renin-angiotensin system: a population-based study. "We want to make sure pharmacists and physicians are aware of this interaction, but I don't think it's on the radar that this is something that can happen.". Neither trimethoprim nor sulfamethoxazole alone kill bacteria. We used amoxicillin as the reference exposure because it is not an independent risk factor for hyperkalemia and is not associated with torsades de pointes. Bicycle, Scooter, and Electric Bike Accidents, Cerebral Palsy Malpractice Injury Lawsuits, Stevens Johnson Syndrome (SJS) Disease Injury Lawyers, Clergy Sexual Abuse Lawyers | Priest Abuse Attorneys, Pennsylvania Sexual Abuse Lawsuit Lawyers, Sudden Death in Those Taking Bactrim Along with ACE Inhibitors or ARBs, Bicycle, Scooter, and Electric Bike Accident, Stevens Johnson Syndrome (SJS) Disease Injury. Getting the dabigatran (Pradaxa) story right Correcting four common mistakes. The authors also implied that sudden death in those patients might be inappropriately attributed to something other than hyperkalemia, such as an underlying cardiovascular disease. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Participants Ontario residents aged 66 years or older treated with an angiotensin converting enzyme inhibitor or angiotensin receptor blocker. FOIA We thank Brogan Inc, Ottawa, for use of their Drug Product and Therapeutic Class Database. A Deadly Drug Interaction Often Ignored by Doctors and Pharm Joe Graedon is a pharmacologist who has dedicated his career to making drug information understandable to consumers. Characteristics of cases and controls. 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. These efforts are ongoing. The overall importance of these observations relates to an expanded mechanism of action, whereby bactericidal antibiotics promote complex redox alterations that contribute to cellular damage and death, while also underlining a common evolutionary and developmental linkage between primordial bacteria and mitochondria (56,57). They should only damage bacteria, while leaving eukaryotic cells unscathed, but they damage mitochondria too (of course they do, mitochondria are ancient bacterium Did anyone think that disrupting the process of DNA replication and reproduction in bacteria wouldnt mess up mitochondrial DNA?). Careers. The story here is not just about the specifics of an important drug-drug interaction. Youll laugh, learn and maybe sing along. Canadian Drug Safety and Effectiveness Research Network. 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 The default to pharmacologic treatment needs to change. The .gov means its official. 1996; Magnusdottir et al. All rights reserved, From Healthy to Barely Functioning After Taking Bactrim and Keflex, Thiamine Deficiency Causes Intracellular Potassium Wasting, by potently blocking both thiamine transporters, glucose-6-phosphate dehydrogenase (G6PD) deficiency, Delirium, gait disturbances and other CNS symptoms, Stephens Johnson Syndrome and toxic epidermal necrosis, lining of the skin and mucous membranes blisters and necrolyses, popular angiotensin enzyme inhibitors (ACE), potentially deadly interactions involving hyperkalemia, high potassium levels via its blockage of the sodium channels in the kidneys, The overall importance of these observations, metabolism of the branched chain amino acids, nor are our vitamin synthesis pathways sufficiently distinct from bacteria, large number of gut bacteria in comparison, regulates something called the mTOR receptor, downregulate mTOR and deregulate mitochondrial function. Importantly, bacterial synthesis of folate and other B vitamins, represents a critical pathway not only for nutrient availability of the human host, but for managing the vast microbial ecosystems in a manner favorable to host survival. KEEP UP the GREAT work John! 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. The primary efficacy outcome was the time to the first event of the primary composite endpoint, which consisted of cardiovascular death, resuscitated sudden death, non-fatal myocardial. Finally, we were unable to reliably determine the dose of trimethoprim, precluding a dose-response analysis. 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. February 2, 2015 / 3:49 PM In a secondary analysis examining sudden death within 14 days of antibiotic prescription, we identified 1827 patients who died suddenly and were matched to at least one control (n=6771 controls). Get browser notifications for breaking news, live events, and exclusive reporting. Ciprofloxacin (which can prolong the QT interval) and nitrofurantoin (which was associated with hyperkalemia in a prior study) were associated with excess sudden-death risks of borderline statistical significance (adjusted ORs, 1.6 and 1.7, respectively). Sign up to get our weekly updates directly to your inbox: Apple Podcasts mitochondrial origins, it is not surprising that many are just one medication away from full blown deficiency. In a previous publication by the authors of this study, there was a seven sevenfold increase in the risk of hyperkalemia induced hospital admissions inACE-inhibitors and ARBusers taking trimethoprim-sulfamethoxazole compared with those exposed toother antibiotics. These findings indicate that intestinal bacteria contribute to folate metabolism and that colonic contents represent a substantial and natural source of folate. It included residents of Ontario who were 66 years of age or older and were treated with an ACE-inhibitors or ARBs. 8600 Rockville Pike Post graduate, she continued at UNLV as an adjunct faculty member, teaching advanced undergraduate psychopharmacology and health psychology (stress endocrinology). 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. 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. Co-trimoxazole and sudden death in patients receiving inhibitors of renin-angiotensin system: population based study. Terms Of Use | Privacy Policy | Disclaimer | Accessibility Compliance Policy | Library | Diversity StatementWe are committed to making this website accessible, and as consistent with the Web Content Accessibility Guidelines (WCAG) 2.0 as possible. However, this applies equally to all the antibiotics we studied. What are you thinking? 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). 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. Trimethoprim-sulfamethoxazole: hyperkalemia is an important complication regardless of dose. One warned that potassium levels may increase and therefore should be monitored. Within this group, we identified cases as patients who died of sudden death within 14 days after receiving a prescription for trimethoprim-sulfamethoxazole or one of the other study antibiotics (amoxicillin, ciprofloxacin, norfloxacin or nitrofurantoin). weight gain or loss. I did not. Because of my allergies I took a Penicillin test and I reacted. No endorsement by ICES or the Ontario MOHLTC is intended or should be inferred. Absent outright thiamine starvation, most folks consume sufficient thiamine from food to avoid the more acute thiamine deficiencies, but not enough to prevent the more gradual and often chronic thiamine insufficiency syndromes that mark modern medicine and certainly not enough to offset the direct blockage of thiamine transporters from pharmaceuticals like Bactrim, the mitochondrial damage initiated by modern medications (here, here, here, here, and more), environmental chemical exposures and industrial food based toxicants to which we are all exposed. Pocket Casts The results showed that, in this specific patient population, 3 of every 1000 individuals taking either ACE inhibitors or ARBs who then begin treatment with trimethoprim/sulfamethoxazole will die suddenly within 7 to 14 days. angiotensin converting enzyme inhibitors (ACE-inhibitors) and angiotensin receptor blockers (ARBs).