Doxycycline Use and Adverse Events

Doxycycline use and adverse events search strategy:

MEDLINE/PubMed was searched for clinical studies that reported on adverse events with doxycycline use, specifically focusing on side-effects and metabolic effects of long-term use. Search terms included “doxycycline” AND (“adverse reaction” OR “adverse event” OR “side effect). Some studies prior to 2003 were included but the systematic review was focused on studies published subsequent to a prior systematic review published by Smith and Leyden (Smith K, Leyden JJ. Safety of doxycycline and minocycline: a systematic review. Clin Ther. 2005 Sep;27(9):1329-42.).

Inclusion criteria for initial screening included any retrospective or prospective clinical study with an average duration of 2 months (8 weeks) or more on doxycycline. No restrictions set regarding country, publication language, date or patient age, race, gender or sexuality. Exclusion criteria included: non-human subjects or in-vitro studies, unrelated papers, duplicates, unavailable full texts, abstract only papers, case reports and any papers that reported on doxycycline use in combination with other drugs since it would not be possible to identify side effects from doxycycline alone. After the initial screening, review articles from the initial search were reviewed to identify additional studies to include.

Characteristics of studies identified by the systematic literature review that assess longer-term1 doxycycline use and adverse events
First Author Publication Year Study Population Study Site Drug Duration (Days) Doxycycline (N) Mild*
Stopped (adverse events)
Akhyani (27) 2008 Rosacea Treatment 27-72 years old Iran Doxycycline 100mg once daily 91 30 NR NR NR 0
Alexis (28) 2012 Rosacea Treatment 18+ years old United States Doxycycline 40mg once daily (30 mg immediate release and 10 mg delayed release beads) once daily 84 1196 NR NR NR NR
Andersen (29)** 1998 Malaria Prophylaxis 18-55 years old Kenya Doxycycline 100mg once daily 70 55 NR NR NR 1
Angelakis (30) 2014 Q Fever Endocarditis Treatment 18+ years old France Doxycycline 100mg twice a day (and hydroxychloroquine) 540+ 48 NR NR NR NR
Arman (31) 2015 Rosacea Treatment Adults Turkey Doxycycline 100mg BID for one month then once daily for two months 90 19 NR NR NR NR
Babaeinejad (32) 2011 Acne Treatment 13+ years old Iran Doxycycline 100mg once daily 90 50 4 0 0 0
Baudon (33) 1999 Malaria Prophylaxis Adult soldiers Gabon and the Central African Republic Doxycycline 100mg once daily 120+ 171 NR NR NR 11
Baxter (34) 2002 Abdominal Aortic Aneurysm Treatment 54-84 years old United States (Multiple States) Doxycycline 100mg twice per day 90+ 36 NR NR NR 3
Berende (35) 2016 Lyme Disease Treatment Adults Netherlands Doxycycline 100mg twice a day 84 86 39 (Mild or Moderate) 39 (Mild or Moderate) 3 3
Brandt (36)** 2005 Osteoarthritis Treatment 45-64 years old United States (Indiana) Doxycycline 100mg twice a day 900 218 NR NR 31 25
Brill (37) 2015 COPD Treatment 45+ years old United Kingdom Doxycycline 100mg once daily 91 25 2 (Mild or Moderate) 2 (Mild or Moderate) 0 0
Caton (38)** 2000 Chronic Periodontitis 30-75 years old United States (Multiple) Doxycycline 20mg twice a day 274 93 NR NR 1 1
Del Rosso (39)** 2007 Rosacea Treatment 18+ years old United States and Puerto Rico Doxycycline monohydrate 40mg once daily (formulation: 30-mg immediate-release and 10-mg delayed-release beads) 112 269 133 (Mild or Moderate) 133 (Mild or Moderate) 16 19
Del Rosso (40)** 2022 Acne Treatment 12+ years old United States (Multiple Sites) Doxycycline 120mg once daily (with trifarotene cream) 84 133 3 (Mild or Moderate) 3 (Mild or Moderate) 0 0
Del Rosso (41)** 2022 Rosacea Treatment 18-80 years old United States (Multiple Sites) Doxycycline 40mg modified-release capsules once daily 84+ 300 12 (Mild or Moderate) 12 (Mild or Moderate) 0 0
Del Rosso (42) 2012 Rosacea Treatment Adults United States Doxycycline modified-release 40mg once daily (30mg immediate-release and 10 mg delayed-release) 84 1196 NR NR NR NR
Del Rosso (43) 2018 Acne Treatment 12+ years old United States Doxycycline hyclate delayed-release 100mg twice daily 84 175 26 (Mild or moderate) 26 (Mild or moderate) 1 4
Del Rosso (44) 2008 Rosacea Treatment 18+ years old United States Doxycycline 100mg daily or 40mg delayed-release daily (with topical metronidazole 1% gel) 112 91 16 18 6 9
Donta (45)** 2004 Gulf War Illness Treatment Adult veterans United States (Multiple sites) Doxycycline 200mg once daily 365 245 NR NR 12 7
Frenzel (46) 2008 Treatment of Brain Vascular Malformations 15-78 years old United States (California) Doxycycline 100mg twice a day 730 13 NR NR 1 2
Gollnick (47) 2010 Rosacea Treatment 19-91 years old Germany Doxycycline 100mg once daily for 14 days then 50mg once daily 84 143 NR NR NR NR
Golub (48) 2001 Chronic periodontitis treatment 18-75 years old United States Doxycycline 20mg once or twice daily 84 75 NR NR NR 3
Kaneshiro (49)** 2012 Prevention of Menstrual Bleeding 18-45 years old females United States Doxycycline 40mg once daily 84 32 NR NR NR 0
Kitchener (50) 2005 Malaria Prophylaxis Adult soldiers Australian soldiers settled in East Timor at risk for malaria Doxycycline (Dose not reported) 180+ 388 245* 78* 7* 1
Kus (51) 2005 Acne Treatment 18-30 years old Turkey Doxycycline 100mg BID for one month and then once daily for the next two months 90 26 NR NR NR NR
Layton (18) 1993 Acne Treatment 13-49 years old United Kingdom Doxycycline 150 or 200 mg/day 183 106 NR NR NR 37
Lee (52)** 2004 Chronic periodontitis treatment Adults South Korea Doxycycline hyclate 20mg twice daily 274 24 NR NR NR NR
Leijtens (53) 2019 Suppression of Prosthetic Joint Infection 40-88 years old Netherlands Doxycycline 100-200mg once daily 1157 14 NR NR NR 1
Leyden (54)** 2013 Acne Treatment 12-45 years old United States Doxycycline calcium 40-160mg (weight based) 84 190 NR NR NR 1
Lin (55) 2015 Graves Disease Treatment 18-60 years old China Doxycycline 50mg once daily 84 16 2 0 0 0
Makunde (56) 2006 Wuchereria Bancrofti Treatment 14-68 years old Tanzania Doxycycline 200mg once daily 60 19 7 0 0 0
Maleszka (57) 2011 Acne Treatment 14+ years old Poland and Croatia Doxycycline 100mg once daily 84 120 NR NR NR 0
Molina (3) 2017 STI Prophylaxis Adult Males France Single dose doxycycline 200mg within 24 hrs after sex and no later then 72 hrs 261+ 116 102 (Mild or Moderate) 102 (Mild or Moderate) 4 8
Moore (58)** 2015 Acne Treatment 12-59 years old United States Doxycycline 40-100mg once daily 112 440 NR NR 2 2
Naini (59) 2007 Diabetic Proteinuria Treatment 49-77 years old Iran Doxycycline 100mg once daily 61 35 NR NR 0 3
Novak (60) 2002 Chronic periodontitis treatment 29-45 years old United States Doxycycline hyclate 20mg twice daily 183 10 NR NR NR NR
Ohrt (61)** 1997 Malaria Prophylaxis Adult soldiers Indonesia Doxycycline 100mg once daily 91 67 NR NR NR 0
Pagès (62) 2002 Malaria Prophylaxis Adult soldiers French soldiers deployed in Gabon and Chad Doxycycline monohydrate 100mg once daily 120 275 NR NR NR 15
Pan (63)** 2022 Thyroid Disease Adults China Doxycycline 50mg once daily 84 50 1 0 0 0
Pang (64)** 1998 Malaria Prophylaxis 10-16 years old Thailand Doxycycline 25-100mg daily depending on weight 105 144 NR NR NR 0
Pang (65) 1987 Malaria Prophylaxis 10-15 years old Thailand Doxycycline 100mg once daily for those over 40kg;

Doxycycline 50mg once daily for those less than 40kg

63 95 NR 0 0 0
Parish (66) 2005 Acne Treatment 14-36 years old United States Doxycycline hyclate 100mg twice a day 56 12 NR NR NR NR
Park (67) 2015 Rosacea Treatment 18+ years old South Korea Doxycycline 100mg twice a day 770 15 NR NR NR 0
Pfeffer (68) 2011 Rosacea Treatment Adults Germany Doxycycline 40mg once daily (slow-release form) 60+ 7 0 0 0 0
Pimenta (69) 2011 Lymphangioleiomyomatosis Treatment Adult Females Brazil Doxycycline 100mg once daily 180 41 NR NR NR 0
Pimenta (70) 2013 Lymphangioleiomyomatosis Treatment Adults Brazil Doxycycline 100mg once daily 365 41 NR NR NR 3
Popa (71) 2022 Colorectal Cancer Treatment Adults Romania Doxycycline (Dose not reported) 56 10 NR NR NR NR
Pradier (72) 2017 Suppression of Prosthetic Joint Infection Adults France Doxycycline 200mg once daily 508+ 39 NR NR NR 3
Pradier (73) 2018 Suppression of Prosthetic Joint Infection 18-91 years old France Doxycycline 200mg once daily 668 72 NR NR NR 6
Preshaw (74)** 2008 Chronic periodontitis treatment 24-81 years old United States Doxycycline monohydrate 40mg once daily (modified release) 274 133 79 (Mild or Moderate) 79 (Mild or Moderate) 9 7
Putschky (75) 2006 Reactive Arthritis Treatment 18-65 years old Germany Doxycycline 100mg twice a day 122 15 NR NR NR 0
Quarterman (76) 1997 Rosacea Treatment 31-66 years old Georgia Doxycycline 100mg once daily 84 39 NR NR NR NR
Sanchez (77)** 2005 Rosacea Treatment 18+ year old females United States and Puerto Rico Doxycycline hyclate 20mg twice daily for 12 weeks (with metronidazole 0.75% topical lotion) followed by 4 weeks of monotherapy with doxycycline hyclate 20mg 112 20 NR NR 0 0
Schlagenhauf (78) 2003 Malaria Prophylaxis 18-70 years old Travel clinics in Switzerland, Germany, and Israel Doxycycline monohydrate 100mg once daily 66 153 128 51 9 5
Sehgal (79) 2000 Leptospirosis prophylaxis 10+ years old India Doxycycline 200mg/week 84 386 NR NR NR 3
Smith (80) 2011 Rheumatoid Arthritis Treatment Adults United States Doxycycline 200mg once daily 90 484 31 53 26 35
Snijders (81)** 2011 Knee Osteoarthritis Treatment Adults Netherlands Doxycycline monohydrate 100mg twice a day 168 116 NR NR NR 19
Sonmez (82) 2005 Malaria Prophylaxis Adult soldiers Turkish soldiers in Kabul, Afghanistan Doxycycline 100mg once daily 84 506 395 32 0 NR
Tan (83) 2014 Acne Treatment 12-35 years old Canada Doxycycline hyclate 200mg once daily (with adapalene 0.1%/benzoyl peroxide 2.5% gel) 140 133 NR NR 0 6
Taylor (84)** 1999 Malaria Prophylaxis 18-55 years old Indonesia Doxycycline 100mg once daily 140 75 NR NR NR 1
Taylor (85) 2005 Wuchereria Bancrofti Treatment 15-68 year old males Tanzania Doxycycline 200mg once daily 56 34 8 NR NR 0
Thiboutot (86) 2005 Acne Treatment 12-36 years old United States (Multiple sites) Doxycycline 100mg once daily 84 467 NR NR 0 5
Thiboutot (87) 2009 Rosacea Treatment 19-83 years old United States Doxycycline monohydrate 100mg twice daily (with topical azelaic acid 15% gel) 28-84 172 19 8 4 12
Ullah (88) 2014 Acne Treatment 14-30 years old Pakistan Doxycycline 100mg once daily 90 193 NR NR NR 0
Ullah (89) 2022 Acne Treatment 12-24 years old Pakistan Doxycycline 100mg once daily 84 37 NR NR NR NR
van der Linden (90) 2016 Rosacea Treatment 18+ years old Netherlands Doxycycline 40mg once daily 112 40 23 (Mild or Moderate) 23 (Mild or Moderate) 0 3
Weiss (91) 1995 Malaria Prophylaxis 9-14 years old Kenya Doxycycline 50mg once daily 77 32 NR NR NR 2

NR=Not reported
1Longer term was defined as 8+ weeks
*Events (not individuals)
**Included in the meta-analysis (N=18)


  1. Sexually Transmitted Disease Surveillance 2021. Centers for Disease Control and Prevention;
  2. Luetkemeyer AF, Donnell D, Dombrowski JC, Cohen S, Grabow C, Brown CE, et al. Postexposure Doxycycline to Prevent Bacterial Sexually Transmitted Infections. N Engl J Med. 2023 Apr 6;388(14):1296–306.
  3. Molina JM, Charreau I, Chidiac C, Pialoux G, Cua E, Delaugerre C, et al. Post-exposure prophylaxis with doxycycline to prevent sexually transmitted infections in men who have sex with men: an open-label randomised substudy of the ANRS IPERGAY trial. Lancet Infect Dis. 2018 Mar;18(3):308–17.
  4. Jean-Michel Molina, Beatrice Bercot, Lambert Assoumou, Algarte-Genin Michele, Emma Rubenstein, Gilles Pialoux, et al. ANRS 174 DOXYVAC: An Open-Label Randomized Trial to Prevent STIs in MSM on PrEP. CROI [Internet]. 2023 Feb 19;Seattle, Washington. Available from:
  5. Bolan RK, Beymer MR, Weiss RE, Flynn RP, Leibowitz AA, Klausner JD. Doxycycline prophylaxis to reduce incident syphilis among HIV-infected men who have sex with men who continue to engage in high-risk sex: a randomized, controlled pilot study. Sex Transm Dis. 2015 Feb;42(2):98–103.
  6. Binh VQ, Chinh NT, Thanh NX, Cuong BT, Quang NN, Dai B, et al. Sex affects the steady-state pharmacokinetics of primaquine but not doxycycline in healthy subjects. Am J Trop Med Hyg. 2009 Nov;81(5):747–53.
  7. Peyriere H, Makinson A, Marchandin H, Reynes J. Doxycycline in the management of sexually transmitted infections. J Antimicrob Chemother. 2018 Mar 1;73(3):553–63.
  8. Farrah G, Tan E. The use of oral antibiotics in treating acne vulgaris: a new approach. Dermatol Ther. 2016 Sep;29(5):377–84.
  9. Twartz JC, Shirai A, Selvaraju G, Saunders JP, Huxsoll DL, Groves MG. Doxycycline propylaxis for human scrub typhus. J Infect Dis. 1982 Dec;146(6):811–8.
  10. Nadelman RB, Nowakowski J, Fish D, Falco RC, Freeman K, McKenna D, et al. Prophylaxis with single-dose doxycycline for the prevention of Lyme disease after an Ixodes scapularis tick bite. N Engl J Med. 2001 Jul 12;345(2):79–84.
  11. Binenbaum Y, Ben-Ami R, Baneth G, Langford B, Negev Y, Friedlander E, et al. Single Dose of Doxycycline for the Prevention of Tick-borne Relapsing Fever. Clin Infect Dis. 2020 Oct 23;71(7):1768–71.
  12. Moran-Gilad J, Levine H, Schwartz E, Bartal C, Huerta-Hartal M, Schwaber MJ, et al. Postexposure prophylaxis of tick-borne relapsing fever: lessons learned from recent outbreaks in Israel. Vector Borne Zoonotic Dis. 2013 Nov;13(11):791–7.
  13. Schneider MC, Velasco-Hernandez J, Min KD, Leonel DG, Baca-Carrasco D, Gompper ME, et al. The Use of Chemoprophylaxis after Floods to Reduce the Occurrence and Impact of Leptospirosis Outbreaks. Int J Environ Res Public Health. 2017 Jun 3;14(6):E594.
  14. Takafuji ET, Kirkpatrick JW, Miller RN, Karwacki JJ, Kelley PW, Gray MR, et al. An efficacy trial of doxycycline chemoprophylaxis against leptospirosis. N Engl J Med. 1984 Feb 23;310(8):497–500.
  15. Wormser GP. Doxycycline for Prevention of Spirochetal Infections: Status Report. Clin Infect Dis. 2020 Nov 5;71(8):2014–7.
  16. Wormser GP, Warshafsky S, Visintainer P. Aggregation of data from 4 clinical studies demonstrating efficacy of single-dose doxycycline postexposure for prevention of the spirochetal infections: Lyme disease, syphilis, and tick-borne relapsing fever. Diagn Microbiol Infect Dis. 2021 Apr;99(4):115293.
  17. Tan KR, Magill AJ, Parise ME, Arguin PM, Centers for Disease Control and Prevention. Doxycycline for malaria chemoprophylaxis and treatment: report from the CDC expert meeting on malaria chemoprophylaxis. Am J Trop Med Hyg. 2011 Apr;84(4):517–31.
  18. Layton AM, Cunliffe WJ. Phototoxic eruptions due to doxycycline–a dose-related phenomenon. Clin Exp Dermatol. 1993 Sep;18(5):425–7.
  19. Sloan B, Scheinfeld N. The use and safety of doxycycline hyclate and other second-generation tetracyclines. Expert Opin Drug Saf. 2008 Sep;7(5):571–7.
  20. Smith K, Leyden JJ. Safety of doxycycline and minocycline: a systematic review. Clin Ther. 2005 Sep;27(9):1329–42.
  21. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JPA, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. Ann Intern Med. 2009 Aug 18;151(4):W65-94.
  22. Viechtbauer W. Conducting Meta-Analyses in R with the metafor Package. J Stat Soft [Internet]. 2010 [cited 2023 Jun 18];36(3). Available from:
  23. Borenstein M, Hedges LV, Higgins JPT, Rothstein HR. Introduction to MetaAnalysis [Internet]. 1st ed. Wiley; 2009 [cited 2023 Jun 18]. Available from:
  24. Thomas J, Walker C, Bradshaw M. Long-term use of subantimicrobial dose doxycycline does not lead to changes in antimicrobial susceptibility. J Periodontol. 2000 Sep;71(9):1472–83.
  25. Walker C, Preshaw PM, Novak J, Hefti AF, Bradshaw M, Powala C. Long-term treatment with sub-antimicrobial dose doxycycline has no antibacterial effect on intestinal flora. J Clin Periodontol. 2005 Nov;32(11):1163–9.
  26. Turner RB, Smith CB, Martello JL, Slain D. Role of doxycycline in Clostridium difficile infection acquisition. Ann Pharmacother. 2014 Jun;48(6):772–6.
  27. Akhyani M, Ehsani AH, Ghiasi M, Jafari AK. Comparison of efficacy of azithromycin vs. doxycycline in the treatment of rosacea: a randomized open clinical trial. Int J Dermatol. 2008 Mar;47(3):284–8.
  28. Alexis AF, Webster G, Preston NJ, Caveney SW, Gottschalk RW. Effectiveness and safety of once-daily doxycycline capsules as monotherapy in patients with rosacea: an analysis by Fitzpatrick skin type. J Drugs Dermatol. 2012 Oct;11(10):1219–22.
  29. Andersen SL, Oloo AJ, Gordon DM, Ragama OB, Aleman GM, Berman JD, et al. Successful double-blinded, randomized, placebo-controlled field trial of azithromycin and doxycycline as prophylaxis for malaria in western Kenya. Clin Infect Dis. 1998 Jan;26(1):146–50.
  30. Angelakis E, Million M, Kankoe S, Lagier JC, Armougom F, Giorgi R, et al. Abnormal weight gain and gut microbiota modifications are side effects of long-term doxycycline and hydroxychloroquine treatment. Antimicrob Agents Chemother. 2014 Jun;58(6):3342–7.
  31. Arman A, Demirseren DD, Takmaz T. Treatment of ocular rosacea: comparative study of topical cyclosporine and oral doxycycline. Int J Ophthalmol. 2015;8(3):544–9.
  32. Babaeinejad S, Khodaeiani E, Fouladi RF. Comparison of therapeutic effects of oral doxycycline and azithromycin in patients with moderate acne vulgaris: What is the role of age? J Dermatolog Treat. 2011 Aug;22(4):206–10.
  33. Baudon D, Martet G, Pascal B, Bernard J, Keundjian A, Laroche R. Efficacy of daily antimalarial chemoprophylaxis in tropical Africa using either doxycycline or chloroquine-proguanil; a study conducted in 1996 in the French Army. Trans R Soc Trop Med Hyg. 1999;93(3):302–3.
  34. Baxter BT, Pearce WH, Waltke EA, Littooy FN, Hallett JW, Kent KC, et al. Prolonged administration of doxycycline in patients with small asymptomatic abdominal aortic aneurysms: report of a prospective (Phase II) multicenter study. J Vasc Surg. 2002 Jul;36(1):1–12.
  35. Berende A, ter Hofstede HJM, Vos FJ, van Middendorp H, Vogelaar ML, Tromp M, et al. Randomized Trial of Longer-Term Therapy for Symptoms Attributed to Lyme Disease. N Engl J Med. 2016 Mar 31;374(13):1209–20.
  36. Brandt KD, Mazzuca SA, Katz BP, Lane KA, Buckwalter KA, Yocum DE, et al. Effects of doxycycline on progression of osteoarthritis: results of a randomized, placebo-controlled, double-blind trial. Arthritis Rheum. 2005 Jul;52(7):2015–25.
  37. Brill SE, Law M, El-Emir E, Allinson JP, James P, Maddox V, et al. Effects of different antibiotic classes on airway bacteria in stable COPD using culture and molecular techniques: a randomised controlled trial. Thorax. 2015 Oct;70(10):930–8.
  38. Caton JG, Ciancio SG, Blieden TM, Bradshaw M, Crout RJ, Hefti AF, et al. Treatment with subantimicrobial dose doxycycline improves the efficacy of scaling and root planing in patients with adult periodontitis. J Periodontol. 2000 Apr;71(4):521–32.
  39. Del Rosso JQ, Webster GF, Jackson M, Rendon M, Rich P, Torok H, et al. Two randomized phase III clinical trials evaluating anti-inflammatory dose doxycycline (40-mg doxycycline, USP capsules) administered once daily for treatment of rosacea. J Am Acad Dermatol. 2007 May;56(5):791–802.
  40. Del Rosso JQ, Johnson SM, Schlesinger T, Green L, Sanchez N, Lain E, et al. A Randomized, Controlled Trial of Trifarotene Plus Doxycycline for Severe Acne Vulgaris. J Clin Aesthet Dermatol. 2022 Jul;15(7):E53–9.
  41. Del Rosso JQ, Brantman S, Baldwin H. Long-term inflammatory rosacea management with subantibiotic dose oral doxycycline 40 mg modified-release capsules once daily. Dermatol Ther. 2022 Jan;35(1):e15180.
  42. Del Rosso JQ, Preston NJ, Caveney SW, Gottschalk RW. Effectiveness and safety of modified-release doxycycline capsules once daily for papulopustular rosacea monotherapy results from a large community-based trial in subgroups based on gender. J Drugs Dermatol. 2012 Jun;11(6):703–7.
  43. Del Rosso JQ, Stein Gold L, Johnson SM, Rueda MJ, Baldwin H, Lain EL, et al. Efficacy and Safety of Adapalene 0.3%/Benzoyl Peroxide 2.5% Gel Plus Oral Doxycycline in Subjects With Severe Inflammatory Acne Who Are Candidates for Oral Isotretinoin. J Drugs Dermatol. 2018 Mar 1;17(3):264–73.
  44. Del Rosso JQ, Schlessinger J, Werschler P. Comparison of anti-inflammatory dose doxycycline versus doxycycline 100 mg in the treatment of rosacea. J Drugs Dermatol. 2008 Jun;7(6):573–6.
  45. Donta ST, Engel CC, Collins JF, Baseman JB, Dever LL, Taylor T, et al. Benefits and harms of doxycycline treatment for Gulf War veterans’ illnesses: a randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2004 Jul 20;141(2):85–94.
  46. Frenzel T, Lee CZ, Kim H, Quinnine NJ, Hashimoto T, Lawton MT, et al. Feasibility of minocycline and doxycycline use as potential vasculostatic therapy for brain vascular malformations: pilot study of adverse events and tolerance. Cerebrovasc Dis. 2008;25(1–2):157–63.
  47. Gollnick H, Blume-Peytavi U, Szabó EL, Meyer KG, Hauptmann P, Popp G, et al. Systemic isotretinoin in the treatment of rosacea – doxycycline- and placebo-controlled, randomized clinical study. J Dtsch Dermatol Ges. 2010 Jul;8(7):505–15.
  48. Golub LM, McNamara TF, Ryan ME, Kohut B, Blieden T, Payonk G, et al. Adjunctive treatment with subantimicrobial doses of doxycycline: effects on gingival fluid collagenase activity and attachment loss in adult periodontitis. J Clin Periodontol. 2001 Feb;28(2):146–56.
  49. Kaneshiro B, Edelman A, Carlson NE, Nichols M, Forbes MM, Jensen J. A randomized controlled trial of subantimicrobial-dose doxycycline to prevent unscheduled bleeding with continuous oral contraceptive pill use. Contraception. 2012 Apr;85(4):351–8.
  50. Kitchener SJ, Nasveld PE, Gregory RM, Edstein MD. Mefloquine and doxycycline malaria prophylaxis in Australian soldiers in East Timor. Med J Aust. 2005 Feb 21;182(4):168–71.
  51. Kus S, Yucelten D, Aytug A. Comparison of efficacy of azithromycin vs. doxycycline in the treatment of acne vulgaris. Clin Exp Dermatol. 2005 May;30(3):215–20.
  52. Lee JY, Lee YM, Shin SY, Seol YJ, Ku Y, Rhyu IC, et al. Effect of subantimicrobial dose doxycycline as an effective adjunct to scaling and root planing. J Periodontol. 2004 Nov;75(11):1500–8.
  53. Leijtens B, Weerwag L, Schreurs BW, Kullberg BJ, Rijnen W. Clinical Outcome of Antibiotic Suppressive Therapy in Patients with a Prosthetic Joint Infection after Hip Replacement. J Bone Jt Infect. 2019;4(6):268–76.
  54. Leyden JJ, Bruce S, Lee CS, Ling M, Sheth PB, Stewart DM, et al. A randomized, phase 2, dose-ranging study in the treatment of moderate to severe inflammatory facial acne vulgaris with doxycycline calcium. J Drugs Dermatol. 2013 Jun 1;12(6):658–63.
  55. Lin M, Mao Y, Ai S, Liu G, Zhang J, Yan J, et al. Efficacy of Subantimicrobial Dose Doxycycline for Moderate-to-Severe and Active Graves’ Orbitopathy. Int J Endocrinol. 2015;2015:285698.
  56. Makunde WH, Kamugisha LM, Makunde RA, Malecela MN, Kitua AY. Hospital-based safety and tolerability study to assess efficacy of oral doxycycline in the treatment of Wuchereria bancrofti infection in north-eastern Tanzania. Tanzan Health Res Bull. 2006 Sep;8(3):128–33.
  57. Maleszka R, Turek-Urasinska K, Oremus M, Vukovic J, Barsic B. Pulsed azithromycin treatment is as effective and safe as 2-week-longer daily doxycycline treatment of acne vulgaris: a randomized, double-blind, noninferiority study. Skinmed. 2011;9(2):86–94.
  58. Moore A, Ling M, Bucko A, Manna V, Rueda MJ. Efficacy and Safety of Subantimicrobial Dose, Modified-Release Doxycycline 40 mg Versus Doxycycline 100 mg Versus Placebo for the treatment of Inflammatory Lesions in Moderate and Severe Acne: A Randomized, Double-Blinded, Controlled Study. J Drugs Dermatol. 2015 Jun;14(6):581–6.
  59. Naini AE, Harandi AA, Moghtaderi J, Bastani B, Amiran A. Doxycycline: a pilot study to reduce diabetic proteinuria. Am J Nephrol. 2007;27(3):269–73.
  60. Novak MJ, Johns LP, Miller RC, Bradshaw MH. Adjunctive benefits of subantimicrobial dose doxycycline in the management of severe, generalized, chronic periodontitis. J Periodontol. 2002 Jul;73(7):762–9.
  61. Ohrt C, Richie TL, Widjaja H, Shanks GD, Fitriadi J, Fryauff DJ, et al. Mefloquine compared with doxycycline for the prophylaxis of malaria in Indonesian soldiers. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1997 Jun 15;126(12):963–72.
  62. Pagès F, Boutin JP, Meynard JB, Keundjian A, Ryfer S, Giurato L, et al. Tolerability of doxycycline monohydrate salt vs. chloroquine-proguanil in malaria chemoprophylaxis. Trop Med Int Health. 2002 Nov;7(11):919–24.
  63. Pan Y, Chen YX, Zhang J, Lin ML, Liu GM, Xu XL, et al. Doxycycline vs Placebo at 12 Weeks in Patients With Mild Thyroid-Associated Ophthalmopathy: A Randomized Clinical Trial. JAMA Ophthalmol. 2022 Nov 1;140(11):1076–83.
  64. Pang L, Limsomwong N, Singharaj P. Prophylactic treatment of vivax and falciparum malaria with low-dose doxycycline. J Infect Dis. 1988 Nov;158(5):1124–7.
  65. Pang LW, Limsomwong N, Boudreau EF, Singharaj P. Doxycycline prophylaxis for falciparum malaria. Lancet. 1987 May 23;1(8543):1161–4.
  66. Parish LC, Parish JL, Routh HB, Witkowski JA. The treatment of acne vulgaris with low dosage doxycycline. Acta Dermatovenerol Croat. 2005;13(3):156–9.
  67. Park JM, Mun JH, Song M, Kim HS, Kim BS, Kim MB, et al. Propranolol, doxycycline and combination therapy for the treatment of rosacea. J Dermatol. 2015 Jan;42(1):64–9.
  68. Pfeffer I, Borelli C, Zierhut M, Schaller M. Treatment of ocular rosacea with 40 mg doxycycline in a slow release form. J Dtsch Dermatol Ges. 2011 Nov;9(11):904–7.
  69. Pimenta SP, Baldi BG, Acencio MMP, Kairalla RA, Carvalho CRR. Doxycycline use in patients with lymphangioleiomyomatosis: safety and efficacy in metalloproteinase blockade. J Bras Pneumol. 2011;37(4):424–30.
  70. Pimenta SP, Baldi BG, Kairalla RA, Carvalho CRR. Doxycycline use in patients with lymphangioleiomyomatosis: biomarkers and pulmonary function response. J Bras Pneumol. 2013;39(1):5–15.
  71. Popa CM, Ianosi SL, Dorobantu SC, Saftoiu A. Gut Microbiota Imbalance in Metastatic Colorectal Patients Treated With EGFRI and Long-Term Antibiotic Therapy for Cutaneous Toxicity: A Pilot Study. Cureus. 2022 May;14(5):e25007.
  72. Pradier M, Nguyen S, Robineau O, Titecat M, Blondiaux N, Valette M, et al. Suppressive antibiotic therapy with oral doxycycline for Staphylococcus aureus prosthetic joint infection: a retrospective study of 39 patients. Int J Antimicrob Agents. 2017 Sep;50(3):447–52.
  73. Pradier M, Robineau O, Boucher A, Titecat M, Blondiaux N, Valette M, et al. Suppressive antibiotic therapy with oral tetracyclines for prosthetic joint infections: a retrospective study of 78 patients. Infection. 2018 Feb;46(1):39–47.
  74. Preshaw PM, Novak MJ, Mellonig J, Magnusson I, Polson A, Giannobile WV, et al. Modified-release subantimicrobial dose doxycycline enhances scaling and root planing in subjects with periodontal disease. J Periodontol. 2008 Mar;79(3):440–52.
  75. Putschky N, Pott HG, Kuipers JG, Zeidler H, Hammer M, Wollenhaupt J. Comparing 10-day and 4-month doxycycline courses for treatment of Chlamydia trachomatis-reactive arthritis: a prospective, double-blind trial. Ann Rheum Dis. 2006 Nov;65(11):1521–4.
  76. Quarterman MJ, Johnson DW, Abele DC, Lesher JL, Hull DS, Davis LS. Ocular rosacea. Signs, symptoms, and tear studies before and after treatment with doxycycline. Arch Dermatol. 1997 Jan;133(1):49–54.
  77. Sanchez J, Somolinos AL, Almodóvar PI, Webster G, Bradshaw M, Powala C. A randomized, double-blind, placebo-controlled trial of the combined effect of doxycycline hyclate 20-mg tablets and metronidazole 0.75% topical lotion in the treatment of rosacea. J Am Acad Dermatol. 2005 Nov;53(5):791–7.
  78. Schlagenhauf P, Tschopp A, Johnson R, Nothdurft HD, Beck B, Schwartz E, et al. Tolerability of malaria chemoprophylaxis in non-immune travellers to sub-Saharan Africa: multicentre, randomised, double blind, four arm study. BMJ. 2003 Nov 8;327(7423):1078.
  79. Sehgal SC, Sugunan AP, Murhekar MV, Sharma S, Vijayachari P. Randomized controlled trial of doxycycline prophylaxis against leptospirosis in an endemic area. Int J Antimicrob Agents. 2000 Feb;13(4):249–55.
  80. Smith CJ, Sayles H, Mikuls TR, Michaud K. Minocycline and doxycycline therapy in community patients with rheumatoid arthritis: prescribing patterns, patient-level determinants of use, and patient-reported side effects. Arthritis Res Ther. 2011;13(5):R168.
  81. Snijders GF, van den Ende CHM, van Riel PLCM, van den Hoogen FHJ, den Broeder AA, NOAC study group. The effects of doxycycline on reducing symptoms in knee osteoarthritis: results from a triple-blinded randomised controlled trial. Ann Rheum Dis. 2011 Jul;70(7):1191–6.
  82. Sonmez A, Harlak A, Kilic S, Polat Z, Hayat L, Keskin O, et al. The efficacy and tolerability of doxycycline and mefloquine in malaria prophylaxis of the ISAF troops in Afghanistan. J Infect. 2005 Oct;51(3):253–8.
  83. Tan J, Humphrey S, Vender R, Barankin B, Gooderham M, Kerrouche N, et al. A treatment for severe nodular acne: a randomized investigator-blinded, controlled, noninferiority trial comparing fixed-dose adapalene/benzoyl peroxide plus doxycycline vs. oral isotretinoin. Br J Dermatol. 2014 Dec;171(6):1508–16.
  84. Taylor WR, Richie TL, Fryauff DJ, Picarima H, Ohrt C, Tang D, et al. Malaria prophylaxis using azithromycin: a double-blind, placebo-controlled trial in Irian Jaya, Indonesia. Clin Infect Dis. 1999 Jan;28(1):74–81.
  85. Taylor MJ, Makunde WH, McGarry HF, Turner JD, Mand S, Hoerauf A. Macrofilaricidal activity after doxycycline treatment of Wuchereria bancrofti: a double-blind, randomised placebo-controlled trial. Lancet. 2005 Jun 18;365(9477):2116–21.
  86. Thiboutot DM, Shalita AR, Yamauchi PS, Dawson C, Arsonnaud S, Kang S, et al. Combination therapy with adapalene gel 0.1% and doxycycline for severe acne vulgaris: a multicenter, investigator-blind, randomized, controlled study. Skinmed. 2005;4(3):138–46.
  87. Thiboutot DM, Fleischer AB, Del Rosso JQ, Rich P. A multicenter study of topical azelaic acid 15% gel in combination with oral doxycycline as initial therapy and azelaic acid 15% gel as maintenance monotherapy. J Drugs Dermatol. 2009 Jul;8(7):639–48.
  88. Ullah G, Noor SM, Bhatti Z, Ahmad M, Bangash AR. Comparison of oral azithromycin with oral doxycycline in the treatment of acne vulgaris. J Ayub Med Coll Abbottabad. 2014;26(1):64–7.
  89. Ullah G, Ali F, Paracha MM, Noor SM, Naeem J. Comparison Of Efficacy Of Topical Adapalene Plus Oral Azithromycin And Topical Adapalene Plus Oral Doxycycline In Treatment Of Acne Vulgaris. J Ayub Med Coll Abbottabad. 2022;34(4):782–5.
  90. van der Linden MMD, van Ratingen AR, van Rappard DC, Nieuwenburg SA, Spuls PI. DOMINO, doxycycline 40 mg vs. minocycline 100 mg in the treatment of rosacea: a randomized, single-blinded, noninferiority trial, comparing efficacy and safety. Br J Dermatol. 2017 Jun;176(6):1465–74.
  91. Weiss WR, Oloo AJ, Johnson A, Koech D, Hoffman SL. Daily primaquine is effective for prophylaxis against falciparum malaria in Kenya: comparison with mefloquine, doxycycline, and chloroquine plus proguanil. J Infect Dis. 1995 Jun;171(6):1569–75.