Investigating the relationship between lactose intolerance and doxycycline-induced gastrointestinal disturbances

Ashley Y. Hernandez-Gutierrez; Kenan Kherallah; Ivan Rodriguez; Scott D. Worswick

doi:10.18203/issn.2455-4529.IntJResDermatol20263733

Authors

Ashley Y. Hernandez-Gutierrez Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
Kenan Kherallah Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
Ivan Rodriguez Department of Dermatology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
Scott D. Worswick Department of Dermatology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

DOI:

https://doi.org/10.18203/issn.2455-4529.IntJResDermatol20263733

Keywords:

Doxycycline, Antibiotic, Drug side effects, Lactose intolerance

Abstract

Background: Doxycycline, a highly effective broad-spectrum antibiotic, is frequently prescribed for dermatological conditions due to its anti-inflammatory and anti-bacterial properties. The adverse effects (AE) doxycycline-induced gastrointestinal (GI) are well described in the literature and clinical practice. However, the use of lactose as an excipient in doxycycline formulations is not commonly known and may contribute to symptoms in patients with lactose intolerance.

Methods: We conducted a retrospective, phone-based survey of patients with documented doxycycline use. Participants reported lactose intolerance status and GI symptoms experienced during therapy. The association was assessed using odds ratios (OR) with 95% confidence intervals (CI) and statistical significance testing.

Results: Out of 98 participants, 46% experienced GI AE. We observed that individuals with lactose intolerance are 1.979 times more likely to experience any GI AE than those without (95% CI 0.598-6.547) with a p=0.257. With a threshold of p<0.05, we could not appreciate a statistically significant association between lactose intolerance and GI AE.

Conclusions: Although lactose intolerance was associated with increased odds of GI AE, the relationship was not statistically significant. However, findings noted in this study suggest a possible trend that warrants further investigation. Larger, prospective studies are needed to confirm our observation and clarify the clinical impact of lactose-containing doxycycline formulations.

References

Nelson ML, Levy SB. The history of the tetracyclines. Ann N Y Acad Sci. 2011;1241(1):17-32.

Navarro-Triviño FJ, Pérez-López I, Ruiz-Villaverde R. Doxiciclina, ¿antibiótico o antiinflamatorio? Usos más frecuentes en dermatología. Actas Dermo-Sifiliográficas. 2020;111(7):561-6.

Piacentini M, Borghetti RL, Zancanaro de Figueiredo MA, Cherubini K, Gonçalves Salum F. Doxycycline: An option in the treatment of ulcerated oral lesions? J Clin Pharm Ther. 2019;44(6):838-43.

Sapadin AN, Fleischmajer R. Tetracyclines: Nonantibiotic properties and their clinical implications. J Am Acad Dermatol. 2006;54(2):258-65.

Di Caprio R, Lembo S, Di Costanzo L, Balato A, Monfrecola G. Anti-Inflammatory Properties of Low and High Doxycycline Doses: An In Vitro Study. Mediators Inflamm. 2015;2015:329418.

Henehan M, Montuno M, De Benedetto A. Doxycycline as an anti-inflammatory agent: updates in dermatology. J Eur Acad Dermatol Venereol. 2017;31(11):1800-8.

Sloan B, Scheinfeld N. The use and safety of doxycycline hyclate and other second-generation tetracyclines. Expert Opin Drug Saf. 2008;7(5):571-7.

Smilack JD. The tetracyclines. Mayo Clin Proc. 1999;74(7):727-9.

Smith K, Leyden JJ. Safety of doxycycline and minocycline: a systematic review. Clin Ther. 2005;27(9):1329-42.

Jimenez Casado M. Doxycycline in Respiratory Tract Infections: Report of a Retrospective Study in Spain during the Winter 1972-1973. Chemotherapy. 2009;21(1):76-90.

Wormser GP, Ramanathan R, Nowakowski J, McKenna D, Holmgren D, Visintainer P, et al. Duration of antibiotic therapy for early Lyme disease. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2003;138(9):697-704.

Bryant SG, Fisher S, Kluge RM. Increased Frequency of Doxycycline Side Effects. Pharmacother J Hum Pharmacol Drug Ther. 1987;7(4):125-9.

Eljaaly K, Alghamdi H, Almehmadi H, Aljawi F, Hassan A, Thabit A. Long-term gastrointestinal adverse effects of doxycycline. J Infect Dev Ctries. 2023;17(2):281-5.

Affolter K, Samowitz W, Boynton K, Kelly ED. Doxycycline-induced gastrointestinal injury. Hum Pathol. 2017;66:212-5.

Panigrahi MK, Nayak HK, Samal SC. A recent surge of doxycycline-induced pill esophagitis during the corona virus disease 2019 (COVID-19) pandemic. Indian J Gastroenterol Off J Indian Soc Gastroenterol. 2022;41(2):206-7.

Doxycycline Hyclate Capsules, USP Doxycycline for Oral Suspension, USP Doxycycline Hyclate Tablets, USP. Available at: https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=3e7cf78f-3b48-4614-9fa4-c6d1e0c05a35&type=display. Accessed on 29 August 2026.

Hebbink GA, Dickhoff BHJ. Chapter 5-Application of lactose in the pharmaceutical industry. In: Paques M, Lindner C, eds. Lactose. Academic Press. 2019;175-229.

Shi C, Zhao H, Fang Y, Shen L, Zhao L. Lactose in tablets: Functionality, critical material attributes, applications, modifications and co-processed excipients. Drug Discov Today. 2023;28(9):103696.

Catanzaro R, Sciuto M, Marotta F. Lactose intolerance: An update on its pathogenesis, diagnosis, and treatment. Nutr Res N Y N. 2021;89:23-34.

Barbieri JS, Bhate K, Hartnett KP, Fleming-Dutra KE, Margolis DJ. Trends in Oral Antibiotic Prescription in Dermatology, 2008 to 2016. JAMA Dermatol. 2019;155(3):290-7.

Monk E, Shalita A, Siegel DM. Clinical applications of non-antimicrobial tetracyclines in dermatology. Pharmacol Res. 2011;63(2):130-45.

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. J Am Coll Gastroenterol ACG. 2010;105(12):2610.

Cao Y, Wu K, Mehta R, Drew D, Song M, Lochhead P, et al. Long-term use of antibiotics and risk of colorectal adenoma. Gut. 2018;67(4):672-8.

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):919-26.

Gouda MA. Common Pitfalls in Reporting the Use of SPSS Software. Med Princ Pract Int J Kuwait Univ Health Sci Cent. 2015;24(3):300.

Del Rosso JQ, Leyden JJ, Thiboutot D, Webster GF. Antibiotic use in acne vulgaris and rosacea: clinical considerations and resistance issues of significance to dermatologists. Cutis. 2008;82(2-2):5-12.

Sardana K, Gupta T, Garg VK, Ghunawat S. Antibiotic resistance to Propionobacterium acnes: worldwide scenario, diagnosis and management. Expert Rev Anti Infect Ther. 2015;13(7):883-96.

Waitayangkoon P, Moon SJ, Tirupur Ponnusamy JJ, Zeng L, Driban J, McAlindon T. Long-Term Safety Profiles of Macrolides and Tetracyclines: A Systematic Review and Meta-Analysis. J Clin Pharmacol. 2024;64(2):164-77.

Doxycycline: Package Insert. Drugs.com. Available at: https://www.drugs.com/pro/doxycycline.html. Accessed on 15 August 2026.

Fernandopulle ANR, Navarathne NMM. Oesophageal injury suspected to be due to doxycycline ingestion. Ceylon Med J. 2011;56(4):162-63.

Epstein ME, Amodio-Groton M, Sadick NS. Antimicrobial agents for the dermatologist. II. Macrolides, fluoroquinolones, rifamycins, tetracyclines, trimethoprim-sulfamethoxazole, and clindamycin. J Am Acad Dermatol. 1997;37(3 Pt 1):365-81.

Meyer FP, Specht H, Quednow B, Walther H. Influence of milk on the bioavailability of doxycycline--new aspects. Infection. 1989;17(4):245-6.