Trimethoprimsulfamethoxazole induced hyperkalaemia in elderly patients receiving spironolactone: nested case-control study. In the primary analysis, co-trimoxazole was associated with a significantly increased risk of sudden death within seven days relative to amoxicillin (unadjusted odds ratio 1.83, 95% confidence interval 1.50 to 2.24), and this result persisted after adjustment using the disease risk index (1.38, 1.09 to 1.76). Interpretation: In contrast, we observed no increased risk of sudden death with the other antibiotics (table 3). If this example has you concerned, you may want to read more details in our chapter Drug Interactions Can Be Deadly. There are 11 tips for preventing dangerous drug interactions at the end of the section. In 2006, Long Island University awarded him an honorary doctorate as one of the country's leading drug experts for the consumer.. As a graduate student, she founded and directed the UNLV Maternal Health Lab, mentoring dozens of students while directing clinical and Internet-based research. Dr. Marrs received her BA in philosophy from the University of Redlands; MS in Clinical Psychology from California Lutheran University; and, MA and PhD in Experimental Psychology/ Neuroendocrinology from the University of Nevada, Las Vegas. And be honest; did you know trimethoprim blocks the epithelial sodium channel (ENaC) in the distal nephron, thereby impairing potassium elimination? Thank you for pointing out to your patients and readers that many conditions are better treated by lifestyle changes. Many people think trimethoprimsulfamethoxazole [co-trimoxazole] is a fairly innocuous drug with not a lot of side effects, says Tony Antoniou, lead author on the study and a pharmacist at St Michaels Hospital in Toronto, Canada. I am just so wary of medications these days. Sorry for going off on my tangent about FQs. Absent the ability to transport thiamine from diet into the cells, deficiency ensues. Our findings derive from patients aged 66 years and older, and the generalizability to younger patients is unknown. We did a population based nested case-control study of Ontario residents aged 66 years or older receiving an angiotensin converting enzyme inhibitor or angiotensin receptor blocker between 1 April 1994 and 1 January 2012, the last date for which the vital statistics database was updated. Canadian Institutes of Health Research/Canada, NCI CPTC Antibody Characterization Program. Neither trimethoprim nor sulfamethoxazole alone kill bacteria. Of these deaths, 1,110 occurred within seven days of a prescription for one of the study antibiotics. We will be forever grateful to all for the help they provided. The results were not appreciably different from our primary analyses (see web appendix). 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. Automated systems check on interactions before a doctor can finalize a prescription and before a pharmacist can dispense it. We're empowering you to make wise decisions about your own health, by providing you with essential health information about both medical and alternative treatment options. Control patients were required to be alive at the index date and, like cases, received one of the study antibiotics in the seven days preceding the index date. The antibiotic trimethoprim-sulfamethoxazole was associated with an increased risk of sudden death among older patients taking spironolactone. Most of the patients who died were. Although trimethoprim inhibits dihydrofolate reductase in bacteria, it is estimated that an approximately 50,000 times increased concentration of the drug is required to inhibit the human form of this enzyme.. They simply prevent bacterial replication. [Free open access link]Antoniou T, et al. Bookshelf These days, generic forms are dispensed as co-trimoxazole or the combination trimethoprim and sulfamethoxazole (abbreviated TMP-SMX or TMP-SMZ). The primary analysis examined the association between sudden death and receipt of a prescription for co-trimoxazole, norfloxacin, nitrofurantoin, or ciprofloxacin in the preceding seven days. Enthusiasm is brimming. BMJ 2014 Oct 30 A possible mechanism is trimethoprim-induced hyperkalemia in older patients taking angiotensin-converting-enzyme inhibitors or angiotensin-receptor blockers. The mTOR pathway regulates the balance between protein anabolism and catabolism critical for cell growth and division. The laws of nature no longer hold true. Maurer agreed that doctors should avoid this particular drug combination, especially since it mainly affects vulnerable seniors. If you experienced a negative reaction to Bactrim and would like to share your story, contact us. February 2, 2015 / 3:49 PM The study authors also found evidence of an interaction between spironolactone and the antibiotic ciprofloxacin (brand names Cetraxal, Cipro), which increased by half a person's risk of sudden death, Antoniou said. Of these deaths, 1,110 occurred within seven days of a prescription for one of the study antibiotics, GeriPal reports. Tradeoffs are truth. 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. Trimethoprimsulfamethoxazole and risk of sudden death among patients taking spironolactone. A recent study has shown an association between sudden death in those who were given the antibiotic trimethoprim-sulfamethoxazole (Bactrim) while already taking renin-angiotensin system blockers (ACE-inhibitors) or angiotensin receptor blockers (ARBs), heart medications. When appropriate, alternative antibiotics should be considered in such patients. and transmitted securely. 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. The prescribing of co-trimoxazole with angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) results in a sevenfold increase in the risk of hospital admission with hyperkalemia relative to amoxicillin, Case reports have shown that this drug interaction can cause life threatening hyperkalemia, In older patients receiving ACE inhibitors or ARBs, co-trimoxazole was associated with an increased risk of sudden death; this may reflect sudden death from unrecognized severe hyperkalemia, When patients receiving ACE inhibitors or ARBs require an antibiotic, clinicians should either select antibiotics that do not contain trimethoprim or limit the dose and duration of trimethoprim based therapies, while closely monitoring the serum potassium concentration. Bethesda, MD 20894, Web Policies CastBox The case story that compelled my investigation into Bactrim included clear symptoms of both wet and dry beriberi, marked by serious dysautonomic function. 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). (Those stakeholders are getting pissed I mean, dont trust computers? 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. Materially, the summated populations of simple organisms may in fact regulate the ultimate fate of our genetic material. Thank you. 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. Those who got the combo were almost seven times more likely to be hospitalized for problems due to high potassium compared to people taking different antibiotics (Archives of Internal Medicine, June 28, 2010). Interpretation: The antibiotic trimethoprim-sulfamethoxazole was associated with an increased risk of sudden death among older patients taking spironolactone. Contributors: MF, EMM, TG, MMM, and DNJ were responsible for study concept and design. MF, EMM, and SH acquired the data. Although, the spironolactone + Bactrim > sudden death relationship is studied typically only in the elderly, both drugs are increasingly common in adolescents and young women and may account for a good percentage of the adverse events in these populations that are considered idiopathic. More than one in ten had also received a prescription for the antibiotic in question. It is used to treat a wide variety of bacterial infections (such as middle ear, urine, respiratory . "For these patients, try if possible to avoid this particular combination," he said. Fralick M, et al. Please note: your email address is provided to the journal, which may use this information for marketing purposes. Hosted by Eric Widera and Alex Smith. Norfloxacin, which has no known cardiac effects or interactions with spironolactone, was . 1, 1994, and Dec. 31, 2011. If the goal of the computer is to capture every possible piece of billable data and alert us to every possible bad thing that could happen, the machine becomes part of the patient safety problem. After just a few days on Bactrim I started experiencing rapid heart rate, hyperventilation-type symptoms, numbness and insomnia. How can it hurt?. I didnt want to take Cipro because of possible side effects (including Achilles Tendon rupture), so the doc Rxed Bactrim instead. 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. Within the cohort of patients receiving an angiotensin converting enzyme inhibitor or angiotensin receptor blocker, we defined case patients as those who died suddenly by using an approach validated previously (positive predictive value 87%).25 This definition was validated using linked Medicaid databases and death certificates to identify international classification of disease (ICD) codes consistent with sudden death (that is, sudden death, conduction disorders, dysrhythmias). Antibiotic use and risk of sudden death within 14 days. We speculate that this association reflects sudden death from co-trimoxazole induced hyperkalemia in a vulnerable group of patients. 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. 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! Careers. It is estimated that roughly 20 million prescriptions are filled for this drug each year. This question is for testing whether or not you are a human visitor and to prevent automated spam submissions. None of which are true. Trimethoprim-sulfamethoxazole is frequently prescribed for urinary tract infections, with more than 20 million prescriptions written every year in the United States for a variety of infections, the researchers said in background information. Each case was matched with up to four controls on age, sex, presence of kidney disease, and diabetes. How can it hurt? goes the (fast) thinking. This site needs JavaScript to work properly. Thank you so much for this information. Sadly, there is not adequate awareness about the deadly consequences of this drug interaction. lung failure causing loss of breath. 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). Bactrim and Septra were the original brand names for this drug. The finding of a threefold increased risk of death with cotrimoxazole over amoxicillin in older patients taking ACE inhibitors or ARBs teaches us to consider other antibiotics in these patients. Whereas nitrofurantoin and norfloxacin are limited to the treatment of urinary tract infection, amoxicillin, co-trimoxazole, and ciprofloxacin are sometimes used for infections at other sites. That retrospective study used the administrative health records, spanning 18 years, of more than 200,000 patients prescribed spironolactone. Ciprofloxacin can prolong the QT interval and cause torsades de pointes in susceptible patients.27 28 35 36 37 Ciprofloxacin induced QT prolongation occurs early in the course of treatment and generally resolves when treatment is stopped;25 37 this may explain why the effect was attenuated in the 14 day analysis. FDA Approves Rizatriptan Benzoate Oral Film to Treat Acute Migraine, Pharmacy Focus - Global Vaccination Rates, Study Suggests C. Difficile May Be a Foodborne Illness, Public Health Matters - Harm Reduction, SUD Treatment, Study: COVID-19 Infection Spreads Through Households Via Common Surfaces, Hands, Overcoming Our Blind Spots: Pharmacists Can Help Address Human Trafficking. 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. In other words, an awful lot of people are vulnerable to this potentially deadly drug combination. Although I would argue, deficiencies in these two nutrients would exacerbate Bactrims effects on sodium-potassium balance. For example, the cases and controls were very different (the cases were more likely to have heart failure, renal failure, and all together more co-morbidities). So is the QT prolonging potential of Bactrim caused by its ability to promote hyperkalemia? Youre starting to sound like a doctor. Recently, research released by the British Medical Journal implicated trimethoprim/sulfamethoxazole as a cause for increased risk of sudden death in specific populations. 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. IMS Institute for Healthcare Informatics. I have tolerated Z-paks following dental surgery, but I keep my fingers crossed when I take it. We will strive to make that page accessible. document.getElementById( "ak_js_1" ).setAttribute( "value", ( new Date() ).getTime() ); This site uses Akismet to reduce spam. The BMJ 2011; 343:d5228. 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. 2007b). For each patient, we defined a period of continuous drug use beginning with the first prescription after their 66th birthday and ending with death, discontinuation of treatment, or the end of the study period, whichever occurred first. Methods: "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. Hello,thank you for the information.40 years ago just one Bactrim put me in hospital.All over mucuos membranes were red,open sores and painful.I was student in the university,went to hospital,internal med.dr saw me and called for a consultation from other departmans,they realize it was Bactrim allergy and said I should be in the literature.For one week I could only take water with pipet, going to bathroom was really really painfully was crying. Declaration of transparency: The lead author (study guarantor) affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained. 27299 Riverview Center Boulevard, Suite 108. Yes, I would like to support Hormones Matter. I would guess most caregivers who prescribe cotrimoxazole do not have a working knowledge of epithelial cells in the distal nephron. 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). 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. More than 250 million prescriptions are dispensed in the US each year. angiotensin converting enzyme inhibitors (ACE-inhibitors) and angiotensin receptor blockers (ARBs). Most people do not need to worry about high potassium levels, says Antoniou. 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. 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. We carry vast microbial ecosystems whose functions are critical to human survival; vitamin synthesis among them. 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. 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. Stitcher Trimethoprim-induced hyperkalemia: An analysis of reported cases. So, based upon the blockage of the DFT>THF pathway in bacteria, trimethoprim was deemed strongly antibacterial. Design Population based nested case-control study. Instead of putting this in the Avoid or Caution category, it merely listed this interaction as one that should be monitored because of a possible risk of hyperkalemia. 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. To avoid the potential confounding effects of changes in antibiotic selection and prescribing practices over time, controls were assigned exactly the same index date as cases. Please enter valid email address to continue. Each of the two drugs that make up Bactrim block microbial folate synthesis precipitating complete folate deprivation in bacteria, capable of resulting in folate deficiency non-bacterial cells. We used administrative data and did not have access to serum potassium or creatinine concentrations, adherence to treatment, non-prescription drug use, and other risk factors for sudden death. 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. Sign up to get our weekly updates directly to your inbox: Apple Podcasts Nowhere on the death certificate will it say, This patient died because of a drug interaction mistake.. Methods: We conducted a population-based nested case-control study involving Ontario residents aged 66 years or older who received spironolactone . This had been only recently and accidently discovered and is clearly not common knowledge. They noted then that: These findings support the notion of a potentially life-threatening drug interaction between trimethoprim and inhibitors of the renin-angiotensin aldosterone system.. Taken together, however, the combination yields potent bactericidal effects. Thats the easy lesson. Of course, with each passing year I have become incrementally more cautious with everyone from infants to the elderly in hospitals or in public health settings. HHS Vulnerability Disclosure, Help Be careful out there. The site is secure. Antoniou T, Gomes T, Mamdani MM, Yao Z, Hellings C, Garg AX, Weir MA, Juurlink DN. 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. A hyperkalemic crisis can come on so suddenly that even if a conscientious doctor were monitoring serum potassium levels every few months that might not be frequently enough to catch a problem in time. How can it hurt?. Home Sudden Death in Those Taking Bactrim Along with ACE Inhibitors or ARBs, Taking Bactrim with ACE/ARBs Inhibitors cause Death. 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. This fall the Canadian researchers closed the loop on this deadly drug interaction (BMJ, Oct. 30, 2014). doi: 10.1136/bmj.d5228. 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. I use them everyday. Trimethoprim-sulfamethoxazole: hyperkalemia is an important complication regardless of dose. Experts estimate that over 250 million prescriptions are written for angiotensin receptor blockers (ARBs) and ACE (angiotensin converting enzyme) inhibitors. In fact, mixing medicines is very much like playing Russian roulette. Drugs are used too much. Doing such an analysis may have further strengthened the argument that hyperkalemia underlies our main observations. The cause of death will likely be assumed to be of "natural causes" such as a heart attack. 2015 HealthDay. Spironolactone, a diuretic used to treat heart failure with side effects including hyperkalaemia (raised blood potassium levels), is associated with an increased risk of sudden death when combined with the antibiotic trimethoprimsulfamethoxazole, according to a study[1] published in the Canadian Medical Association Journal on 2 February 2015. 1950) self-taught practitioners of geriatric medicine. Please enable it to take advantage of the complete set of features! Chandler Marrs MS, MA, PhD spent the last dozen years in womens health research with a focus on steroid neuroendocrinology and mental health. But thats the thing about drugs: they dont do just one thing. Ill be more cautious when prescribing trimethoprim-sulfamethoxazole, especially in those taking ACE-inhibitors and ARBs. Youve written a wonderful piece. This additive adverse effect would also be expected with any other drug known to cause hyperkalaemia, such as other potassium-sparing diuretics and angiotensin-converting enzyme inhibitors, they say. 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. In the primary analysis, trimethoprim/sulfamethoxazole was associated with a significantly increased risk of sudden death compared to amoxicillin (odds ratio1.38, 95% confidence interval 1.09 to 1.76 after adjustment). If you read Hormones Matter, like it, please help support it. This corresponds to approximately three sudden deaths with co-trimoxazole compared with one sudden death with amoxicillin per 1000 prescriptions dispensed (see web appendix). The fallacies upon which trimethoprim safety was based were that bacteria are completely separate from the humans in and on which they reside, that they are solely responsible for illness, and that pharmaceuticals designed to attack said bacteria would affect only their intended targets. Additional demographic information came from the registered persons database, a registry of all Ontario residents with publically funded health insurance. We identified prescription drug claims by using the Ontario drug benefit database, which includes prescriptions dispensed to all Ontarians aged 65 years or older. 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). This is magical thinking. 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-sulfamethoxazole increases the risk of hyperkalemia when used with spironolactone. In the primary analysis, trimethoprim/sulfamethoxazole was associated with a significantly increased risk of sudden death compared those who received of amoxicillin (odds ratio 1.38, 95% confidence interval 1.09 to 1.76 after adjustment). Elderly patients receiving spironolactone: nested case-control study, mixing medicines is very much like playing Russian roulette said... Ace-Inhibitors ) and angiotensin receptor blockers ( ARBs ), an awful lot of are...: they dont do just one thing of the section not need worry... Quot ; such as a heart attack persons database, a registry of Ontario. Loop on this deadly drug combination, especially since it mainly affects vulnerable seniors reported. 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Experienced a negative reaction to Bactrim and would like to support Hormones Matter disease! 2014 Oct 30 a possible mechanism is trimethoprim-induced hyperkalemia: an analysis may have further strengthened the argument that underlies... Institutes of health Research/Canada, NCI CPTC Antibody Characterization Program mixing medicines is very much like playing Russian.... Check on interactions before a pharmacist can dispense it Dec. 31, 2011 the combination trimethoprim and sulfamethoxazole abbreviated... In these two nutrients would exacerbate Bactrims effects on sodium-potassium balance stakeholders are getting I! Information came from the registered persons database, a registry of all Ontario residents with publically funded health.. Trimethoprim-Sulfamethoxazole increases the risk of sudden death within 14 days rapid heart rate, symptoms. Our chapter drug interactions at the end of the complete set of features anabolism catabolism... 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