TABLE 1:
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* (n) | Moderate* (n) | Severe* (n) | Stopped (adverse events) |
| Akhyani (56) | 2008 | Rosacea Treatment | 27–72 years old | Iran | Doxycycline 100mg once daily | 91 | 30 | NR | NR | NR | 0 |
| Alexis (57) | 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 (58)** | 1998 | Malaria Prophylaxis | 18–55 years old | Kenya | Doxycycline 100mg once daily | 70 | 55 | NR | NR | NR | 1 |
| Angelakis (44) | 2014 | Q Fever Endocarditis Treatment | 18+ years old | France | Doxycycline 100mg twice a day (and hydroxychloroquine) | 540+ | 48 | NR | NR | NR | NR |
| Arman (59) | 2015 | Rosacea Treatment | Adults | Turkey | Doxycycline 100mg BID for one month then once daily for two months | 90 | 19 | NR | NR | NR | NR |
| Babaeinejad (60) | 2011 | Acne Treatment | 13+ years old | Iran | Doxycycline 100mg once daily | 90 | 50 | 4 | 0 | 0 | 0 |
| Baudon (61) | 1999 | Malaria Prophylaxis | Adult soldiers | Gabon and the Central African Republic | Doxycycline 100mg once daily | 120+ | 171 | NR | NR | NR | 11 |
| Baxter (43) | 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 (27) | 2016 | Lyme Disease Treatment | Adults | Netherlands | Doxycycline 100mg twice a day | 84 | 86 | 39 (Mild or Moderate) | 39 (Mild or Moderate) | 3 | 3 |
| Brandt (26)** | 2005 | Osteoarthritis Treatment | 45–64 years old | United States (Indiana) | Doxycycline 100mg twice a day | 900 | 218 | NR | NR | 31 | 25 |
| Brill (52) | 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 (36)** | 2000 | Chronic Periodontitis | 30–75 years old | United States (Multiple) | Doxycycline 20mg twice a day | 274 | 93 | NR | NR | 1 | 1 |
| Del Rosso (28)** | 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 (62)** | 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 (63)** | 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 (64) | 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 (33) | 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 (65) | 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 (29)** | 2004 | Gulf War Illness Treatment | Adult veterans | United States (Multiple sites) | Doxycycline 200mg once daily | 365 | 245 | NR | NR | 12 | 7 |
| Frenzel (30) | 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 (48) | 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 (49) | 2001 | Chronic periodontitis treatment | 18–75 years old | United States | Doxycycline 20mg once or twice daily | 84 | 75 | NR | NR | NR | 3 |
| Kaneshiro (39)** | 2012 | Prevention of Menstrual Bleeding | 18–45 years old females | United States | Doxycycline 40mg once daily | 84 | 32 | NR | NR | NR | 0 |
| Kitchener (37) | 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 (66) | 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 (20) | 1993 | Acne Treatment | 13–49 years old | United Kingdom | Doxycycline 150 or 200 mg/day | 183 | 106 | NR | NR | NR | 37 |
| Lee (50)** | 2004 | Chronic periodontitis treatment | Adults | South Korea | Doxycycline hyclate 20mg twice daily | 274 | 24 | NR | NR | NR | NR |
| Leijtens (67) | 2019 | Suppression of Prosthetic Joint Infection | 40–88 years old | Netherlands | Doxycycline 100–200mg once daily | 1157 | 14 | NR | NR | NR | 1 |
| Leyden (42)** | 2013 | Acne Treatment | 12–45 years old | United States | Doxycycline calcium 40–160mg (weight based) | 84 | 190 | NR | NR | NR | 1 |
| Lin (45) | 2015 | Graves Disease Treatment | 18–60 years old | China | Doxycycline 50mg once daily | 84 | 16 | 2 | 0 | 0 | 0 |
| Makunde (46) | 2006 | Wuchereria Bancrofti Treatment | 14–68 years old | Tanzania | Doxycycline 200mg once daily | 60 | 19 | 7 | 0 | 0 | 0 |
| Maleszka (68) | 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 than 72 hrs | 261+ | 116 | 102 (Mild or Moderate) | 102 (Mild or Moderate) | 4 | 8 |
| Moore (32)** | 2015 | Acne Treatment | 12–59 years old | United States | Doxycycline 40–100mg once daily | 112 | 440 | NR | NR | 2 | 2 |
| Naini (69) | 2007 | Diabetic Proteinuria Treatment | 49–77 years old | Iran | Doxycycline 100mg once daily | 61 | 35 | NR | NR | 0 | 3 |
| Novak (70) | 2002 | Chronic periodontitis treatment | 29–45 years old | United States | Doxycycline hyclate 20mg twice daily | 183 | 10 | NR | NR | NR | NR |
| Ohrt (38)** | 1997 | Malaria Prophylaxis | Adult soldiers | Indonesia | Doxycycline 100mg once daily | 91 | 67 | NR | NR | NR | 0 |
| Pagès (71) | 2002 | Malaria Prophylaxis | Adult soldiers | French soldiers deployed in Gabon and Chad | Doxycycline monohydrate 100mg once daily | 120 | 275 | NR | NR | NR | 15 |
| Pan (72)** | 2022 | Thyroid Disease | Adults | China | Doxycycline 50mg once daily | 84 | 50 | 1 | 0 | 0 | 0 |
| Pang (73)** | 1998 | Malaria Prophylaxis | 10–16 years old | Thailand | Doxycycline 25–100mg daily depending on weight | 105 | 144 | NR | NR | NR | 0 |
| Pang (74) | 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 (75) | 2005 | Acne Treatment | 14–36 years old | United States | Doxycycline hyclate 100mg twice a day | 56 | 12 | NR | NR | NR | NR |
| Park (76) | 2015 | Rosacea Treatment | 18+ years old | South Korea | Doxycycline 100mg twice a day | 770 | 15 | NR | NR | NR | 0 |
| Pfeffer (77) | 2011 | Rosacea Treatment | Adults | Germany | Doxycycline 40mg once daily (slow-release form) | 60+ | 7 | 0 | 0 | 0 | 0 |
| Pimenta (78) | 2011 | Lymphangioleiomyomatosis Treatment | Adult Females | Brazil | Doxycycline 100mg once daily | 180 | 41 | NR | NR | NR | 0 |
| Pimenta (79) | 2013 | Lymphangioleiomyomatosis Treatment | Adults | Brazil | Doxycycline 100mg once daily | 365 | 41 | NR | NR | NR | 3 |
| Popa (51) | 2022 | Colorectal Cancer Treatment | Adults | Romania | Doxycycline (Dose not reported) | 56 | 10 | NR | NR | NR | NR |
| Pradier (80) | 2017 | Suppression of Prosthetic Joint Infection | Adults | France | Doxycycline 200mg once daily | 508+ | 39 | NR | NR | NR | 3 |
| Pradier (81) | 2018 | Suppression of Prosthetic Joint Infection | 18–91 years old | France | Doxycycline 200mg once daily | 668 | 72 | NR | NR | NR | 6 |
| Preshaw (31)** | 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 (82) | 2006 | Reactive Arthritis Treatment | 18–65 years old | Germany | Doxycycline 100mg twice a day | 122 | 15 | NR | NR | NR | 0 |
| Quarterman (83) | 1997 | Rosacea Treatment | 31–66 years old | Georgia | Doxycycline 100mg once daily | 84 | 39 | NR | NR | NR | NR |
| Sanchez (84)** | 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 (34) | 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 (85) | 2000 | Leptospirosis prophylaxis | 10+ years old | India | Doxycycline 200mg/week | 84 | 386 | NR | NR | NR | 3 |
| Smith (35) | 2011 | Rheumatoid Arthritis Treatment | Adults | United States | Doxycycline 200mg once daily | 90 | 484 | 31 | 53 | 26 | 35 |
| Snijders (86)** | 2011 | Knee Osteoarthritis Treatment | Adults | Netherlands | Doxycycline monohydrate 100mg twice a day | 168 | 116 | NR | NR | NR | 19 |
| Sonmez (87) | 2005 | Malaria Prophylaxis | Adult soldiers | Turkish soldiers in Kabul, Afghanistan | Doxycycline 100mg once daily | 84 | 506 | 395 | 32 | 0 | NR |
| Tan (47) | 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 (88)** | 1999 | Malaria Prophylaxis | 18–55 years old | Indonesia | Doxycycline 100mg once daily | 140 | 75 | NR | NR | NR | 1 |
| Taylor (89) | 2005 | Wuchereria Bancrofti Treatment | 15–68 year old males | Tanzania | Doxycycline 200mg once daily | 56 | 34 | 8 | NR | NR | 0 |
| Thiboutot (90) | 2005 | Acne Treatment | 12–36 years old | United States (Multiple sites) | Doxycycline 100mg once daily | 84 | 467 | NR | NR | 0 | 5 |
| Thiboutot (40) | 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 (91) | 2014 | Acne Treatment | 14–30 years old | Pakistan | Doxycycline 100mg once daily | 90 | 193 | NR | NR | NR | 0 |
| Ullah (92) | 2022 | Acne Treatment | 12–24 years old | Pakistan | Doxycycline 100mg once daily | 84 | 37 | NR | NR | NR | NR |
| van der Linden (41) | 2016 | Rosacea Treatment | 18+ years old | Netherlands | Doxycycline 40mg once daily | 112 | 40 | 23 (Mild or Moderate) | 23 (Mild or Moderate) | 0 | 3 |
| Weiss (93) | 1995 | Malaria Prophylaxis | 9–14 years old | Kenya | Doxycycline 50mg once daily | 77 | 32 | NR | NR | NR | 2 |
NR=Not reported
1
Longer term was defined as 8+ weeks
*
Events (not individuals)
**
Included in the meta-analysis (N=18)