Trimethoprim-sulfamethoxazole increases the risk of hyperkalemia when used with spironolactone. 2013. 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. Cotrimoxazole is also a commonly used antibiotic, with up to 50 million prescriptions written each year. 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. For a more in-depth discussion on this paper, check out the editorial hereor this wonderful post on #NephJC. Co-trimoxazole and sudden death in patients receiving inhibitors of renin-angiotensin system: population-based study. 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. Youre starting to sound like a doctor. (Those stakeholders are getting pissed I mean, dont trust computers? We were helping patients with effective dose ranges. 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. "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. Two more issues on the treatment of Sudden Death in the young person, A malignant arrhythmia from an antibiotic? We obtained hospital admission data from the Canadian Institute for Health Informations discharge abstract database, which contains detailed demographic and clinical information on admissions, discharges, and same day surgical procedures for all hospitals in Ontario. How can it hurt? goes the (fast) thinking. Although we used a validated algorithm to define sudden death,25 some degree of outcome misclassification is likely. Now, we have computers as close as our smart phones. Years later I was giving Cipro.With Cipro I had Ulnar nerve entrapment and muscle atrophy. We have previously shown that the use of trimethoprim-sulfamethoxazole in patients receiving spironolactone increased the risk of hospital admission with hyperkalemia more than 12-fold relative to amoxicillin. Remember, in order to get to usable folate THF, we need the DFT enzyme to work. The authors have noted in previous work that cotrimoxazole combined with ACE/ARB drugs associated with a sevenfold increase in the risk of hospital admission for elevated potassium levels. Combining a common antibiotic with an even more common blood pressure medicine can result in sudden death. Youve written a wonderful piece. This was only recently discovered by accident. The researchers matched each case with up to four controls and found that sudden death was more than twice as likely for those taking trimethoprimsulfamethoxazole as for those taking amoxicillin (adjusted odds ratio [OR] 2.46, 95% confidence interval [CI] 1.553.90). We will strive to make that page accessible. So is the QT prolonging potential of Bactrim caused by its ability to promote hyperkalemia? Our Firm Brochure Video Vault FAQS Recently In The News Press Releases Locations New York Attorneys Long Island Attorneys Podcast Addict These findings indicate that intestinal bacteria contribute to folate metabolism and that colonic contents represent a substantial and natural source of folate. Co-trimoxazole is a widely used antibiotic. He did survive, however, but remains chronically symptomatic of thiamine deficiency 6 years later. I have tolerated Z-paks following dental surgery, but I keep my fingers crossed when I take it. Trimethoprim is given to kill bacteria but it also acts like amiloride, (a potassium-sparing diuretic) in the kidney. No matter, a potential antibiotic was born and no one was the wiser. Converging lines of evidence support the notion that terminal hyperkalemia may explain our findings. If you are unable to import citations, please contact In addition to blocking folate metabolism, the trimethoprim component of Bactrim also blocks thiamine uptake. Post graduate, she continued at UNLV as an adjunct faculty member, teaching advanced undergraduate psychopharmacology and health psychology (stress endocrinology). The otherness of potential drug targets holds true to this day. And be honest; did you know trimethoprim blocks the epithelial sodium channel (ENaC) in the distal nephron, thereby impairing potassium elimination? Home Sudden Death in Those Taking Bactrim Along with ACE Inhibitors or ARBs, Taking Bactrim with ACE/ARBs Inhibitors cause Death. Learn more, Credits: Folate and vitamin B12 share a particularly close relationship, where deficiency in one, creates a functional deficiency in the other via alterations in methionine pathway leading to megaloblastic anemia. 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 . We have been alarmed about incompatible drug combinations for more than 40 years. In this population based study spanning 17 years, we found that co-trimoxazole was associated with sudden death in outpatients receiving angiotensin converting enzyme inhibitors or angiotensin receptor blockers. Trimethoprim-sulfamethoxazole (TMP-SMX), also known as co-trimoxazole, is a combination of two antimicrobial agents that act synergistically against a wide variety of bacteria. More commonly, thiamine insufficiency is associated with a litany of dysautonomic syndromes, although it is not widely recognized as such. We found that use of co-trimoxazole was associated with an increased risk of sudden death in older patients taking angiotensin converting enzyme inhibitors or angiotensin receptor blockers. FOIA Canadian Drug Safety and Effectiveness Research Network. MMM and DNJ obtained funding. swelling of the face, hands, legs, and feet. weight gain or loss. That is, how are Bactrim and other thiamine depleting drugs capable of provoking such a rapid decline into fulminant deficiency? In other words, it was easier and more economically prudent not to question potential problems in the research or the assumptions driving said research than risk losing a useful and lucrative antibiotic. Within this cohort, 39 879 died suddenly; of these deaths, 1110 occurred within seven days of a prescription for one of the study antibiotics. Clipboard, Search History, and several other advanced features are temporarily unavailable. Our findings derive from patients aged 66 years and older, and the generalizability to younger patients is unknown. 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. Get browser notifications for breaking news, live events, and exclusive reporting. Lessons to be had. The cause of death will likely be assumed to be of natural causes such as a heart attack. Legalization is. 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. I can hardly eat ! I think that most people, doctors and patients alike, think that all antibiotics are as benign as amoxicillin. 2015 Canadian Medical Association or its licensors. We did not study patients during their first year of eligibility for prescription drug coverage (age 65) to avoid incomplete medication records. MF, EMM, and SH acquired the data. Bookshelf 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). 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. DNJ is the guarantor. 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. Contribute now. Nevertheless, it was well known that Bactrim blocked folate, that folate was critical to human health, and that its deficiency could wreak havoc on health. Youll laugh, learn and maybe sing along. 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). During the 17 year study period, we identified 1 601 542 patients treated with either an angiotensin converting enzyme inhibitor or angiotensin receptor blocker. Methods: We conducted a population-based nested case-control study involving Ontario residents aged 66 years or older who received spironolactone . 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. 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. His symptoms immediately reminded me of beriberi induced by an acute thiamine deficiency. Thank you for bringing attention to the dangers of cotrimoxazole. What? 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. Finally, we checked with two of the best drug interaction resources available on the web. "It's been well-known within the heart failure community that while spironolactone is a great drug, management and use of the drug has to be carefully monitored.". I just finished a five day course of 800mg bactrim DS for a uti. I recognized it immediately as a need for thiamine. I had the rapid heart rate, insomnia , indigestion, and the worst still after finishing is my red gums, red and sore tongue. 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