2-8-2021 Should we fear the Doxy?

Traditionally, there has been an inherent fear in pediatrics around the routine use of doxycycline. Most of this stems from the FDA warning surrounding teeth discoloration. Thankfully, studies have shown that to be unfounded1, but can doxycycline cause other effects that we should be on the lookout for? This is an important question to answer as Doxycycline is about to get a big boost in its use. Recent changes in CDC recommendations indicate the use of Doxycycline over Azithromycin for the treatment of Gonorrhea with a known or possible co-infection with Chlamydia due increased resistance patterns.2 This is a heavily prescribed treatment regimen with over 550,000 Gonorrhea cases and 1.7 million Chlamydia cases in the United States in 2018 alone.3 As we look to prescribe this more as a medical community, let us take a moment to familiarize ourselves with some of the secondary effects our patients might see:

  1. Your standard antibiotic GI side effects hold true with Doxycycline.
  2. Pill Esophagitis
    • Antibiotics are one of the more common causes of pill esophagitis with Doxycycline being the top culprit4. Common presentations include retrosternal pain and pain with swallowing, and treatment consists of discontinuation of the offending agent. Endoscopy should be performed for severe symptoms or if symptoms are not improving 1 week after discontinuation. For prevention, patients should be counseled to take the medication upright, with plenty of water, and not immediately before sleep.
  3. Light Sensitivity
    • The majority of presentations include a sunburn-like sensation to areas exposed to sun, palpable or erythematous plaques, or blistering. There is even a case report of a patient developing a photosensitivity reaction in her hospital bed on the side of her body facing the window.5 To prevent, recommend avoidance of sun, protective clothing, and application of sunscreen, although we lack the data to say if sunscreen this is truly effective in prevention.6
  4. Association with depression and suicidal ideation?
    • The evidence for this is simply anecdotal, but there are multiple reports of patients and family associating doxycycline with new-onset thoughts of suicide or completion of suicide.  A case report is included for reference here7. While these reports are something to keep in mind, and a topic our patients and families might bring up after a google search, the FDA has reviewed some of these cases and feel the association of suicide events with doxycycline use is unlikely.8
  5. Irritable Bowel Syndrome (IBS) and Irritable Bowel Disease (IBD)
    • There are 2 large studies examining cohorts that took prolonged courses of doxycycline. These studies looked at patients with acne and antibiotic prophylaxis while traveling abroad9,10. The study comparing acne found an association with doxycycline use and development of IBD, Crohn’s in particular.9 In addition, one retrospective study looked at doxycycline use during deployment and found it to be associated with not only an increased likelihood of developing IBS but also IBD.10
  6. What about in overdose?
    • Not much has been reported in humans, but animal studies have shown doxycycline induced cardiomyopathy in rats and calves with mortality at 10x the standard dose.11

While some of these side effects can be considered quite alarming, most can be avoided with good counseling or should not come into play with short courses of the medication. With familiarizing ourselves with the side effects, we will be able to more easily recognize Doxycycline as the offending agent when presented with these symptoms. In conclusion, don’t fear the doxy, but do have a healthy respect for it.

Prepared by Baillie Lott, MD, Pediatric Emergency Medicine, LeBonheur Children’s Hospital

1.         Todd SR, Dahlgren FS, Traeger MS, et al. No visible dental staining in children treated with doxycycline for suspected Rocky Mountain Spotted Fever. J Pediatr. 2015;166(5):1246-1251.

2.         St Cyr S, Barbee L, Workowski KA, et al. Update to CDC's Treatment Guidelines for Gonococcal Infection, 2020. MMWR Morb Mortal Wkly Rep. 2020;69(50):1911-1916.

3.         Prevention CfDCa. Sexually Transmitted Disease Surveillance 2018. https://www.cdc.gov/std/stats18/chlamydia.htm. Published 2019. Accessed January 26, 2020.

4.         Saleem F, Sharma A. Drug Induced Esophagitis. In: StatPearls. Treasure Island (FL)2020.

5.         Randhawa A, Ngu I, Bilsland D. Doxycycline photosensitivity. QJM. 2018;111(4):259-260.

6.         Goetze S, Hiernickel C, Elsner P. Phototoxicity of Doxycycline: A Systematic Review on Clinical Manifestations, Frequency, Cofactors, and Prevention. Skin Pharmacol Physiol. 2017;30(2):76-80.

7.         Atigari OV, Hogan C, Healy D. Doxycycline and suicidality. BMJ Case Rep. 2013;2013.

8.         Administration USFaD. Pediatric Focused Safety Review Doryx (doxycycline hyclate) Pediatric Advisory Committee Meeting https://www.fda.gov/media/100459/download. Published 2016. Accessed.

9.         Margolis DJ, Fanelli M, Hoffstad O, Lewis JD. Potential association between the oral tetracycline class of antimicrobials used to treat acne and inflammatory bowel disease. Am J Gastroenterol. 2010;105(12):2610-2616.

10.       Lee TW, Russell L, Deng M, Gibson PR. Association of doxycycline use with the development of gastroenteritis, irritable bowel syndrome and inflammatory bowel disease in Australians deployed abroad. Intern Med J. 2013;43(8):919-926.

11.       El-Neweshy MS. Experimental doxycycline overdose in rats causes cardiomyopathy. Int J Exp Pathol. 2013;94(2):109-114.

I am interested in any questions you would like answered in the Question of the Week.  Please email me with any suggestion at donna.seger@vumc.org.

Donna Seger, MD

Executive Director

Tennessee Poison Center

www.tnpoisoncenter.org

Poison Help Hotline: 1-800-222-1222