Drug Interactions for Trimethoprim/ Sulfamethoxazole Come to Light

In the population-based nested, case-control study, the researchers evaluated patients older than 66 and showed an increase in the incidence of sudden death due to this potential interaction. They evaluated 39,879 cases of sudden deaths in which patients were taking an ACEI or ARB. Of these cases, 1,027 deaths occurred within seven days of an antibiotic exposure. Each case was matched to four controls (n = 3,733 control cases) with respect to age, chronic kidney disease, diabetes and sex. Antibiotic courses included amoxicillin, ciprofloxacin, co-trimoxazole, nitrofurantoin or norfloxacin. Compared with amoxicillin, co-trimoxazole was associated with a significantly increased risk of sudden death corresponding to approximately three sudden deaths within 14 days per 1,000 co-trimoxazole prescriptions (adjusted odds ratio, 1.38). Ciprofloxacin was also associated with an increased risk of death likely due to its ability to cause QT interval prolongation (adjusted odds ratio 1.29). No increased risk of sudden death was observed with amoxicillin, nitrofurantoin or norfloxacin.

Any agent with the potential to induce hyperkalemia runs the risk of this potentially serious drug interaction with co-trimoxazole. If co-trimoxazole is needed in a patient with risk factors for cardiac disease or sudden death, another antibiotic should be considered. If not a choice, other medications with a lower propensity for inducing hyperkalemia should be sought. If neither is possible, patients should be closely monitored for the development of hyperkalemia to avert any untoward reactions.

Michele B. Kaufman, PharmD, CGP, RPh, is a freelance medical writer based in New York City and a pharmacist at New York Presbyterian Lower Manhattan Hospital.

References

1. New dosage strength of butrans launched. Monthly Prescribing Reference. 2014 Oct 9. http://www.empr.com/new-dosage-strength-of-butrans-launched/article/376279.
2. Department of Health and Human Services, U.S. Food and Drug Administration. NDA approval letter (NDA 022396) to Javelin Pharmaceuticals Inc. 2014 Dec 23. http://www.accessdata.fda.gov/drugsatfda_docs/appletter/2014/022396Orig1s000ltr.pdf.
3. Jeffrey S. FDA okays diclofenac injection (Dyloject) for pain. Medscape. 2014 Dec 30. http://www.medscape.com/viewarticle/837385.
4. Prescribing information: Dyloject. Hospira. http://www.hospira.com/Images/DYLOJECT-%28diclofenac_sodium%29-Injection-Package-Insert_81-95926_2.pdf.
5. Department of Health and Human Services, U.S. Food and Drug Administration. FDA approves new psoriasis drug Cosentyx (press release). 2015 Jan 21. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm430969.htm.
6. Barber J. Novartis’ psoriasis therapy Cosentyx bests Johnson & Johnson’s Stelara in late-stage study. First Word Pharma. 2014 Dec 12. http://www.firstwordpharma.com/node/1251438#axzz3NWufbtPT.
7. Fralick M, Macdonald EM, Gomes T, et al. Co-trimoxazole and sudden death in patients receiving inhibitors of renin-angiotensin system: Population based study. BMJ. 2014 Oct 30;349:g6196.