View source for Doxycycline

{{Short description|Tetracycline-class antibiotic}}
{{Use American English|date=February 2024}}
{{Use dmy dates|date=September 2024}}
{{cs1 config |name-list-style=vanc |display-authors=6}}
{{Infobox drug
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 477166918
| image = Doxycycline structure.svg
| image_class = skin-invert-image
| width = 200
| alt =
| image2 = Doxycycline 3D ball.png
| alt2 =

<!-- Clinical data -->
| pronounce = {{IPAc-en|ˌ|d|ɒ|k|s|ɪ|ˈ|s|aɪ|k|l|iː|n}}<br />{{respell|DOKS|iss|EYE|kleen}}
| tradename = Doxy, Doryx, Vibramycin, others
| Drugs.com = {{drugs.com|monograph|doxycycline_calcium}}
| MedlinePlus = a682063
| DailyMedID = Doxycycline
| pregnancy_AU = D
| routes_of_administration = [[Oral administration|By mouth]], [[Intravenous therapy|intravenous]]<ref name=AHFS2015/>
| ATC_prefix = J01
| ATC_suffix = AA02
| ATC_supplemental = {{ATC|A01|AB22}}

| legal_AU = S4
| legal_UK = POM
| legal_US = Rx-only

<!-- Pharmacokinetic data -->
| bioavailability = ~100%
| protein_bound = 80–90%
| metabolism = Negligible
| elimination_half-life = 10–22 hours
| excretion = Mainly feces, 40% urine

<!-- Identifiers -->
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 564-25-0
| PubChem = Doxycycline
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00254
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 10482106
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 334895S862
| KEGG_Ref = {{keggcite|changed|kegg}}
| KEGG = D07876
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 60648
| ChEMBL_Ref = {{ebicite|changed|EBI}}
| ChEMBL = 1433

<!-- Chemical data -->
| IUPAC_name = (4''S'',4a''R'',5''S'',5a''R'',6''R'',12a''S'')-4-(Dimethylamino)-3,5,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydrotetracene-2-carboxamide
| C=22 | H=24 | N=2 | O=8
| smiles = CN(C)[C@@H]3C(\O)=C(\C(N)=O)C(=O)[C@@]4(O)C(/O)=C2/C(=O)c1c(cccc1O)[C@H](C)[C@H]2[C@H](O)[C@@H]34
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C22H24N2O8.H2O/c1-7-8-5-4-6-9(25)11(8)16(26)12-10(7)17(27)14-15(24(2)3)18(28)13(21(23)31)20(30)22(14,32)19(12)29;/h4-7,10,14-15,17,25,27-29,32H,1-3H3,(H2,23,31);1H2/t7-,10+,14+,15-,17-,22-;/m0./s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = XQTWDDCIUJNLTR-CVHRZJFOSA-N
}}

<!-- Definition and medical uses -->
'''Doxycycline''' is a [[Broad-spectrum antibiotic|broad-spectrum]] [[antibiotic]] of the [[Tetracycline antibiotics|tetracycline class]] used in the treatment of infections caused by [[bacteria]] and certain [[parasites]].<ref name=AHFS2015/> It is used to treat [[pneumonia|bacterial pneumonia]], [[acne vulgaris|acne]], [[chlamydia infection]]s, [[Lyme disease]], [[cholera]], [[typhus]], and [[syphilis]].<ref name=AHFS2015/> It is also used to prevent [[malaria]].<ref name="Fit for Travel">{{cite web |title=Malaria |url=https://www.fitfortravel.nhs.uk/advice/malaria |website=Fit for Travel |publisher=Public Health Scotland |access-date=4 December 2023 |at=Chemoprophylaxis |archive-date=4 December 2023 |archive-url=https://web.archive.org/web/20231204191640/https://www.fitfortravel.nhs.uk/advice/malaria |url-status=live }}</ref><ref name="Centers for Disease Control and Prevention-2023">{{cite web |title=Choosing a Drug to Prevent Malaria |date=February 2023 |url=https://www.cdc.gov/malaria/travelers/drugs.html |publisher=Centers for Disease Control and Prevention |access-date=4 December 2023 |at=Doxycycline |archive-date=13 November 2016 |archive-url=https://web.archive.org/web/20161113071230/http://www.cdc.gov/malaria/travelers/drugs.html |url-status=live }}</ref> Doxycycline may be taken [[Oral administration|by mouth]] or by [[intravenous|injection into a vein]].<ref name=AHFS2015>{{cite web|title=Doxycycline calcium|url=https://www.drugs.com/monograph/doxycycline-calcium.html|publisher=The American Society of Health-System Pharmacists|access-date=18 August 2015|url-status=live|archive-url=https://web.archive.org/web/20150923232739/http://www.drugs.com/monograph/doxycycline-calcium.html|archive-date=23 September 2015}}</ref>

<!-- Side effects and mechanisms -->
Common side effects include [[diarrhea]], nausea, vomiting, abdominal pain, and an increased risk of [[sunburn]].<ref name=AHFS2015/> Use during pregnancy is not recommended.<ref name=AHFS2015/> Like other agents of the tetracycline class, it either slows or kills bacteria by inhibiting protein production.<ref name=AHFS2015/><ref name="pmid22191524"/> It kills malaria by targeting a [[plastid organelle]], the [[apicoplast]].<ref name="pmid24698369">{{cite journal | vauthors = McFadden GI | title = Apicoplast | journal = Current Biology | volume = 24 | issue = 7 | pages = R262-3 | date = March 2014 | pmid = 24698369 | doi = 10.1016/j.cub.2014.01.024 | doi-access = free | title-link=doi | bibcode = 2014CBio...24.R262M }}</ref><ref name="Schlagenhauf-Lawlor-2008">{{cite book | vauthors = Schlagenhauf-Lawlor P |title=Travelers' Malaria |date=2008 |publisher=PMPH-USA |isbn=978-1-55009-336-0 |page=148 |url=https://books.google.com/books?id=54Dza0UHyngC&pg=PA148 }}</ref>

<!-- Society and culture -->
Doxycycline was patented in 1957 and came into commercial use in 1967.<ref name="Fischer-2006">{{cite book| vauthors = Fischer J, Ganellin CR |title=Analogue-based Drug Discovery|date=2006|publisher=John Wiley & Sons|isbn=978-3-527-60749-5|page=489|url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA489}}</ref><ref name="Corey-2013">{{cite book|vauthors=Corey EJ|title=Drug discovery practices, processes, and perspectives|date=2013|publisher=John Wiley & Sons|location=Hoboken, N.J.|isbn=978-1-118-35446-9|page=406|url=https://books.google.com/books?id=mIyxO5cLEAcC&pg=PA406|access-date=9 September 2017|archive-date=14 January 2023|archive-url=https://web.archive.org/web/20230114202231/https://books.google.com/books?id=mIyxO5cLEAcC&pg=PA406|url-status=live}}</ref> It is on the [[WHO Model List of Essential Medicines|World Health Organization's List of Essential Medicines]].<ref name="WHO23rd">{{cite book | vauthors = ((World Health Organization)) | title = The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023) | year = 2023 | hdl = 10665/371090 | author-link = World Health Organization | publisher = World Health Organization | location = Geneva | id = WHO/MHP/HPS/EML/2023.02 | hdl-access=free }}</ref> Doxycycline is available as a [[generic medicine]].<ref name=AHFS2015/><ref name="Hamilton-2011">{{cite book| vauthors = Hamilton RJ |title=Tarascon pharmacopoeia|date=2011|publisher=Jones & Bartlett Learning|location=Sudbury, MA|isbn=978-1-4496-0067-9|page=79|edition=12th|url=https://books.google.com/books?id=17euT63udIAC&pg=PA79}}</ref> In 2022, it was the 68th most commonly prescribed medication in the United States, with more than 9{{nbsp}}million prescriptions.<ref>{{cite web | title=The Top 300 of 2022 | url=https://clincalc.com/DrugStats/Top300Drugs.aspx | website=ClinCalc | access-date=30 August 2024 | archive-date=30 August 2024 | archive-url=https://web.archive.org/web/20240830202410/https://clincalc.com/DrugStats/Top300Drugs.aspx | url-status=live }}</ref><ref>{{cite web | title = Doxycycline Drug Usage Statistics, United States, 2013 - 2022 | website = ClinCalc | url = https://clincalc.com/DrugStats/Drugs/Doxycycline | access-date = 30 August 2024 | archive-date = 19 December 2024 | archive-url = https://web.archive.org/web/20241219020001/https://clincalc.com/DrugStats/Drugs/Doxycycline | url-status = live }}</ref>

== Medical uses ==
[[File:Doxycycline 100mg capsules.jpg|right|thumb|Generic 100&nbsp;mg doxycycline capsules]] [[File:Doksiciklin 100 091208.jpg|right|thumb|A package of generic doxycycline]]
In addition to the general indications for all members of the [[tetracycline antibiotics]] group, doxycycline is frequently used to treat [[Lyme disease]], chronic [[prostatitis]], [[sinusitis]], [[pelvic inflammatory disease]],<ref name="pmid3162653">{{cite journal | vauthors = Sweet RL, Schachter J, Landers DV, Ohm-Smith M, Robbie MO | title = Treatment of hospitalized patients with acute pelvic inflammatory disease: comparison of cefotetan plus doxycycline and cefoxitin plus doxycycline | journal = American Journal of Obstetrics and Gynecology | volume = 158 | issue = 3 Pt 2 | pages = 736–41 | date = March 1988 | pmid = 3162653 | doi = 10.1016/S0002-9378(16)44537-0 }}</ref><ref name="pmid345730">{{cite journal | vauthors = Gjønnaess H, Holten E | title = Doxycycline (Vibramycin) in pelvic inflammatory disease | journal = Acta Obstetricia et Gynecologica Scandinavica | volume = 57 | issue = 2 | pages = 137–9 | year = 1978 | pmid = 345730 | doi = 10.3109/00016347809155893 | s2cid = 28328073 }}</ref> severe [[Acne vulgaris|acne]], [[rosacea]],<ref name="safety-2009">{{Cite journal|title=Safety and Efficacy Review of Doxycycline| vauthors = Holmes NE, Charles PG |date=5 January 2009|journal=Clinical Medicine. Therapeutics|volume=1|pages=CMT.S2035|doi=10.4137/CMT.S2035|s2cid=58790579 }}</ref><ref name="pmid16411105">{{cite journal | vauthors = Määttä M, Kari O, Tervahartiala T, Peltonen S, Kari M, Saari M, Sorsa T | title = Tear fluid levels of MMP-8 are elevated in ocular rosacea--treatment effect of oral doxycycline | journal = Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht von Graefes Archiv für Klinische und Experimentelle Ophthalmologie | volume = 244 | issue = 8 | pages = 957–62 | date = August 2006 | pmid = 16411105 | doi = 10.1007/s00417-005-0212-3 | s2cid = 20540747 }}</ref><ref name="pmid9006372">{{cite journal | vauthors = Quarterman MJ, Johnson DW, Abele DC, Lesher JL, Hull DS, Davis LS | title = Ocular rosacea. Signs, symptoms, and tear studies before and after treatment with doxycycline | journal = Archives of Dermatology | volume = 133 | issue = 1 | pages = 49–54 | date = January 1997 | pmid = 9006372 | doi = 10.1001/archderm.133.1.49 | doi-broken-date = 5 December 2024 }}</ref> and [[rickettsial]] infections.<ref name="pmid19061755">{{cite journal | vauthors = Walker DH, Paddock CD, Dumler JS | title = Emerging and re-emerging tick-transmitted rickettsial and ehrlichial infections | journal = The Medical Clinics of North America | volume = 92 | issue = 6 | pages = 1345–61, x | date = November 2008 | pmid = 19061755 | doi = 10.1016/j.mcna.2008.06.002 }}</ref> The efficiency of oral doxycycline for treating papulopustular rosacea and adult acne is not solely based on its antibiotic properties, but also on its anti-inflammatory and [[anti-angiogenic]] properties.<ref name="pmid38649625"/>

In Canada, in 2004, doxycycline was considered a first-line treatment for [[chlamydia]] and [[non-gonococcal urethritis]] and with [[cefixime]] for uncomplicated [[gonorrhea]].<ref name="Rekart-2004">{{cite journal | vauthors = Rekart ML | title = Doxycycline:" New" treatment of choice for genital chlamydia infections. | journal = British Columbia Medical Journal | date = December 2004 | volume = 46 | issue = 10 | pages = 503 |url= http://www.bcmj.org/bc-centre-disease-control/doxycycline-new-treatment-choice-genital-chlamydia-infections |url-status=live |archive-url=https://web.archive.org/web/20170202025155/http://www.bcmj.org/bc-centre-disease-control/doxycycline-new-treatment-choice-genital-chlamydia-infections |archive-date=2 February 2017 }}</ref>

===Antibacterial===
==== General indications ====
Doxycycline is a broad-spectrum antibiotic that is employed in the treatment of numerous bacterial infections. It is effective against bacteria such as ''[[Moraxella catarrhalis]]'', ''[[Brucella melitensis]]'', ''[[Chlamydia pneumoniae]]'', and ''[[Mycoplasma pneumoniae]]''. Additionally, doxycycline is used in the prevention and treatment of serious conditions like anthrax, leptospirosis, bubonic plague, and Lyme disease. However, some bacteria, including ''[[Haemophilus]]'' spp., ''[[Mycoplasma hominis]]'', and ''[[Pseudomonas aeruginosa]]'', have shown resistance to doxycycline.<ref name="Doxycycline spectrum of bacterial susceptibility and Resistance">{{cite web|title=Doxycycline spectrum of bacterial susceptibility and Resistance|url=http://www.toku-e.com/Upload/Products/PDS/20120618002946.pdf|access-date=4 May 2012|url-status=dead|archive-url=https://web.archive.org/web/20140201153943/http://www.toku-e.com/Upload/Products/PDS/20120618002946.pdf|archive-date=1 February 2014}}</ref><ref name="Stoddard-2015">{{cite book | vauthors = Stoddard RA, Galloway RL, Guerra MA | chapter = Leptospirosis | chapter-url= https://wwwnc.cdc.gov/travel/yellowbook/2016/infectious-diseases-related-to-travel/leptospirosis | title = Yellow Book |publisher=Centers for Disease Control and Prevention|access-date=16 April 2017|location=Atlanta, GA|date=10 July 2015|url-status=live|archive-url=https://web.archive.org/web/20170409045310/https://wwwnc.cdc.gov/travel/yellowbook/2016/infectious-diseases-related-to-travel/leptospirosis|archive-date=9 April 2017}}</ref> It is also effective against ''[[Yersinia pestis]]'' (the infectious agent of [[bubonic plague]]), and is prescribed for the treatment of [[Lyme disease]],<ref name="pmid1637021">{{cite journal | vauthors = Nadelman RB, Luger SW, Frank E, Wisniewski M, Collins JJ, Wormser GP | title = Comparison of cefuroxime axetil and doxycycline in the treatment of early Lyme disease | journal = Annals of Internal Medicine | volume = 117 | issue = 4 | pages = 273–80 | date = August 1992 | pmid = 1637021 | doi = 10.7326/0003-4819-117-4-273 | s2cid = 23358315 }}</ref><ref name="pmid7793869">{{cite journal | vauthors = Luger SW, Paparone P, Wormser GP, Nadelman RB, Grunwaldt E, Gomez G, Wisniewski M, Collins JJ | title = Comparison of cefuroxime axetil and doxycycline in treatment of patients with early Lyme disease associated with erythema migrans | journal = Antimicrobial Agents and Chemotherapy | volume = 39 | issue = 3 | pages = 661–7 | date = March 1995 | pmid = 7793869 | pmc = 162601 | doi = 10.1128/AAC.39.3.661 }}</ref><ref name="pmid11450675">{{cite journal | vauthors = Nadelman RB, Nowakowski J, Fish D, Falco RC, Freeman K, McKenna D, Welch P, Marcus R, Agüero-Rosenfeld ME, Dennis DT, Wormser GP | title = Prophylaxis with single-dose doxycycline for the prevention of Lyme disease after an Ixodes scapularis tick bite | journal = The New England Journal of Medicine | volume = 345 | issue = 2 | pages = 79–84 | date = July 2001 | pmid = 11450675 | doi = 10.1056/NEJM200107123450201 | df = dmy-all | doi-access = free }}</ref><ref name="pmid8035916">{{cite journal | vauthors = Karlsson M, Hammers-Berggren S, Lindquist L, Stiernstedt G, Svenungsson B | title = Comparison of intravenous penicillin G and oral doxycycline for treatment of Lyme neuroborreliosis | journal = Neurology | volume = 44 | issue = 7 | pages = 1203–7 | date = July 1994 | pmid = 8035916 | doi = 10.1212/WNL.44.7.1203 | s2cid = 38661885 }}</ref> [[ehrlichiosis]],<ref name="pmid8900357">{{cite journal | vauthors = Weinstein RS | title = Human ehrlichiosis | journal = American Family Physician | volume = 54 | issue = 6 | pages = 1971–6 | date = November 1996 | pmid = 8900357 }}</ref><ref name="pmid11234985">{{cite journal | vauthors = Karlsson U, Bjöersdorff A, Massung RF, Christensson B | title = Human granulocytic ehrlichiosis--a clinical case in Scandinavia | journal = Scandinavian Journal of Infectious Diseases | volume = 33 | issue = 1 | pages = 73–4 | year = 2001 | pmid = 11234985 | doi = 10.1080/003655401750064130 | s2cid = 218880245 }}</ref> and [[Rocky Mountain spotted fever]].<ref name="FDA capsules label"/>

Specifically, doxycycline is indicated for treatment of the following diseases:<ref name="FDA capsules label">{{cite web | work = U.S. Food and Drug Administration | date = 14 December 2012 | url = http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/065055s012lbl.pdf | title = Doxycycline, ANDA no. 065055 Label. | archive-url = https://web.archive.org/web/20140419011523/http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/065055s012lbl.pdf | archive-date=19 April 2014 }}</ref><ref name="FDA oralsusp label">{{cite web | work = U.S. Food and Drug Administration | date = 16 July 2008 | url = http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/065454s000lbl.pdf | title = Doxycycline, ANDA no. 065454 Label | archive-url = https://web.archive.org/web/20131019104106/http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/065454s000lbl.pdf | archive-date=19 October 2013 }}</ref>
* [[Rocky Mountain spotted fever]], [[typhus]] fever and the typhus group, [[scrub typhus]],<ref name="pmid38110855">{{cite journal |vauthors=Gupta N, Boodman C, Jouego CG, Van Den Broucke S |title=Doxycycline vs azithromycin in patients with scrub typhus: a systematic review of literature and meta-analysis |journal=BMC Infect Dis |volume=23 |issue=1 |pages=884 |date=December 2023 |pmid=38110855 |pmc=10726538 |doi=10.1186/s12879-023-08893-7 |doi-access=free |url=}}</ref> [[Q fever]],<ref name="pmid23535757">{{cite journal | vauthors = Anderson A, Bijlmer H, Fournier PE, Graves S, Hartzell J, Kersh GJ, Limonard G, Marrie TJ, Massung RF, McQuiston JH, Nicholson WL, Paddock CD, Sexton DJ | title = Diagnosis and management of Q fever--United States, 2013: recommendations from CDC and the Q Fever Working Group | journal = MMWR. Recommendations and Reports | volume = 62 | issue = RR-03 | pages = 1–30 | date = March 2013 | pmid = 23535757 | url = https://www.cdc.gov/mmwr/preview/mmwrhtml/rr6203a1.htm | url-status = live | df = dmy-all | archive-url = https://web.archive.org/web/20140419233615/http://www.cdc.gov/mmwr/preview/mmwrhtml/rr6203a1.htm | archive-date = 19 April 2014 }}</ref> [[rickettsialpox]], and tick fevers caused by ''[[Rickettsia]]'',<ref name="pmid27172113">{{cite journal | url=https://www.cdc.gov/mmwr/volumes/65/rr/rr6502a1.htm | doi=10.15585/mmwr.rr6502a1 | title=Diagnosis and Management of Tickborne Rickettsial Diseases: Rocky Mountain Spotted Fever and Other Spotted Fever Group Rickettsioses, Ehrlichioses, and Anaplasmosis — United States | date=2016 | journal=MMWR. Recommendations and Reports | volume=65 | issue=2 | pages=1–44 | pmid=27172113 | vauthors=Biggs HM, Behravesh CB, Bradley KK, Dahlgren FS, Drexler NA, Dumler JS, Folk SM, Kato CY, Lash RR, Levin ML, Massung RF, Nadelman RB, Nicholson WL, Paddock CD, Pritt BS, Traeger MS | doi-access=free | access-date=5 February 2024 | archive-date=28 January 2023 | archive-url=https://web.archive.org/web/20230128234432/https://www.cdc.gov/mmwr/volumes/65/rr/rr6502a1.htm | url-status=live }}</ref><ref name="Schutze-2010">{{cite news|title=Use doxycycline as first-line treatment for rickettsial diseases|url=https://publications.aap.org/aapnews/article-abstract/31/7/14/8731/Use-doxycycline-as-first-line-treatment-for?redirectedFrom=fulltext|date=1 July 2010| vauthors = Schutze GE, Regan J, Bradley J |series=AAP News|issn=1556-3332|publisher=American Academy of Pediatrics|access-date=5 February 2024|archive-date=5 February 2024|archive-url=https://web.archive.org/web/20240205201657/https://publications.aap.org/aapnews/article-abstract/31/7/14/8731/Use-doxycycline-as-first-line-treatment-for?redirectedFrom=fulltext|url-status=live}}</ref><ref name="Spotted fever group rickettsial disease DermNet 2024">{{cite web | url=https://dermnetnz.org/topics/spotted-fever | title=Spotted fever group rickettsial disease &#124; DermNet | date=26 October 2023 | access-date=5 February 2024 | archive-date=5 February 2024 | archive-url=https://web.archive.org/web/20240205201658/https://dermnetnz.org/topics/spotted-fever | url-status=live }}</ref>
* respiratory tract infections caused by ''[[Mycoplasma pneumoniae]]'',<ref name="pmid22972867">{{cite journal | vauthors = Okada T, Morozumi M, Tajima T, Hasegawa M, Sakata H, Ohnari S, Chiba N, Iwata S, Ubukata K | title = Rapid effectiveness of minocycline or doxycycline against macrolide-resistant Mycoplasma pneumoniae infection in a 2011 outbreak among Japanese children | journal = Clinical Infectious Diseases | volume = 55 | issue = 12 | pages = 1642–9 | date = December 2012 | pmid = 22972867 | doi = 10.1093/cid/cis784 | doi-access =  }}</ref>
* [[Lymphogranuloma venereum]], [[trachoma]], [[inclusion conjunctivitis]], and uncomplicated urethral, endocervical, or rectal infections in adults caused by ''[[Chlamydia trachomatis]]'',<ref name="FDA capsules label"/><ref name="FDA oralsusp label"/>
* [[psittacosis]],<ref name="FDA capsules label"/><ref name="FDA oralsusp label"/>
* [[non-gonococcal urethritis]] caused by ''[[Ureaplasma urealyticum]]'',<ref name="FDA capsules label"/><ref name="FDA oralsusp label"/>
* [[relapsing fever]] due to ''[[Borrelia recurrentis]]'',<ref name="FDA capsules label"/><ref name="FDA oralsusp label"/>
* [[chancroid]] caused by ''[[Haemophilus ducreyi]]'',<ref name="FDA capsules label"/><ref name="FDA oralsusp label"/>
* plague due to ''[[Yersinia pestis]]'',<ref name="FDA capsules label"/><ref name="FDA oralsusp label"/>
* [[tularemia]],<ref name="FDA capsules label"/><ref name="FDA oralsusp label"/>
* [[cholera]],<ref name="FDA capsules label"/><ref name="FDA oralsusp label"/>
* ''[[campylobacter fetus]]'' infections,<ref name="FDA capsules label"/><ref name="FDA oralsusp label"/>
* [[brucellosis]] caused by ''[[Brucella]]'' species (in conjunction with [[streptomycin]]),<ref name="FDA capsules label"/><ref name="FDA oralsusp label"/>
* [[bartonellosis]],<ref name="FDA capsules label"/><ref name="FDA oralsusp label"/>
* [[granuloma inguinale]] (''[[Klebsiella]]'' species),<ref name="FDA capsules label"/><ref name="FDA oralsusp label"/>
* [[Lyme disease]] (''[[Borrelia]]'' species).<ref name="Lyme disease. Treatment-2018"/>

==== Gram-negative bacteria specific indications ====
When bacteriologic testing indicates appropriate susceptibility to the drug, doxycycline may be used to treat these infections caused by [[Gram-negative bacteria]]:<ref name="FDA capsules label"/><ref name="FDA oralsusp label"/>
* ''[[Escherichia coli]]'' infections,<ref name="FDA capsules label"/><ref name="FDA oralsusp label"/>
* ''[[Enterobacter aerogenes]]'' (formerly ''Aerobacter aerogenes'') infections,<ref name="FDA capsules label"/><ref name="FDA oralsusp label"/>
* ''[[Shigella]]'' species infections,<ref name="FDA capsules label"/><ref name="FDA oralsusp label"/>
* ''[[Acinetobacter]]'' species (formerly ''Mima'' species and ''Herellea'' species) infections,<ref name="FDA capsules label"/><ref name="FDA oralsusp label"/>
* [[respiratory tract infections]] caused by ''[[Haemophilus influenzae]]'',<ref name="FDA capsules label"/><ref name="FDA oralsusp label"/>
* respiratory tract and [[urinary tract infection]]s caused by ''[[Klebsiella]]'' species.<ref name="FDA capsules label"/><ref name="FDA oralsusp label"/>

==== Gram-positive bacteria specific indications ====
Some [[Gram-positive bacteria]] have developed resistance to doxycycline. Up to 44% of ''[[Streptococcus pyogenes]]'' and up to 74% of ''[[Streptococcus faecalis|S. faecalis]]'' specimens have developed resistance to the [[Tetracycline antibiotics|tetracycline group]] of antibiotics. Up to 57% of [[Cutibacterium acnes|''P. acnes'']] strains developed resistance to doxycycline.<ref name="pmid24721547">{{cite journal | vauthors = Dreno B, Thiboutot D, Gollnick H, Bettoli V, Kang S, Leyden JJ, Shalita A, Torres V | title = Antibiotic stewardship in dermatology: limiting antibiotic use in acne | journal = European Journal of Dermatology | volume = 24 | issue = 3 | pages = 330–4 | date = 2014 | pmid = 24721547 | doi = 10.1684/ejd.2014.2309 | s2cid = 28700961 }}</ref> When bacteriologic testing indicates appropriate susceptibility to the drug, doxycycline may be used to treat these infections caused by [[Gram-positive bacteria]]:<ref name="FDA capsules label"/><ref name="FDA oralsusp label"/>
* upper respiratory infections caused by ''[[Streptococcus pneumoniae]]'' (formerly ''Diplococcus pneumoniae''),<ref name="FDA capsules label"/><ref name="FDA oralsusp label"/>
* skin and soft tissue infections caused by ''[[Staphylococcus aureus]]'', including [[methicillin-resistant Staphylococcus aureus|methicillin-resistant ''Staphylococcus aureus'']] infections,<ref name="FDA capsules label"/><ref name="FDA oralsusp label"/>
* [[anthrax]] caused by ''[[Bacillus anthracis]]'' infection.<ref name="FDA capsules label"/><ref name="FDA oralsusp label"/>

==== Specific applications of doxycycline when penicillin is contraindicated ====
When penicillin is contraindicated, doxycycline can be used to treat:<ref name="FDA capsules label"/><ref name="FDA oralsusp label"/>
* [[syphilis]] caused by ''[[Treponema pallidum]]'',<ref name="FDA capsules label"/><ref name="FDA oralsusp label"/>
* [[yaws]] caused by ''[[Treponema pertenue]]'',<ref name="FDA capsules label"/><ref name="FDA oralsusp label"/>
* [[listeriosis]] due to ''[[Listeria monocytogenes]]'',<ref name="FDA capsules label"/><ref name="FDA oralsusp label"/>
* [[Vincent's infection]] caused by ''[[Fusobacterium]] fusiforme'',<ref name="FDA capsules label"/><ref name="FDA oralsusp label"/>
* [[actinomycosis]] caused by ''[[Actinomyces israelii]]'',<ref name="FDA capsules label"/><ref name="FDA oralsusp label"/>
* infections caused by ''[[Clostridium]]'' species.<ref name="FDA capsules label"/><ref name="FDA oralsusp label"/>

==== Use as adjunctive therapy ====
Doxycycline may also be used as adjunctive therapy for severe [[acne]].<ref name="pmid22895927">{{cite journal | vauthors = Garner SE, Eady A, Bennett C, Newton JN, Thomas K, Popescu CM | title = Minocycline for acne vulgaris: efficacy and safety | journal = The Cochrane Database of Systematic Reviews | volume = 2012 | issue = 8 | pages = CD002086 | date = August 2012 | pmid = 22895927 | pmc = 7017847 | doi = 10.1002/14651858.CD002086.pub2 | collaboration = Cochrane Skin Group }}</ref><ref name="FDA capsules label"/><ref name="FDA oralsusp label"/>

Subantimicrobial-dose doxycycline (SDD) is widely used as an adjunctive treatment to scaling and root planing for [[periodontitis]]. Significant differences were observed for all investigated clinical parameters of periodontitis in favor of the scaling and root planing + SDD group where SDD dosage regimens is 20&nbsp;mg twice daily for three months in a [[meta-analysis]] published in 2011.<ref name="pmid21417590">{{cite journal | vauthors = Sgolastra F, Petrucci A, Gatto R, Giannoni M, Monaco A | title = Long-term efficacy of subantimicrobial-dose doxycycline as an adjunctive treatment to scaling and root planing: a systematic review and meta-analysis | journal = Journal of Periodontology | volume = 82 | issue = 11 | pages = 1570–1581 | date = November 2011 | pmid = 21417590 | doi = 10.1902/jop.2011.110026 }}</ref> SDD is also used to treat skin conditions such as acne and rosacea,<ref name="safety-2009"/><ref name="pmid25919144">{{cite journal | vauthors = van Zuuren EJ, Fedorowicz Z, Carter B, van der Linden MM, Charland L | title = Interventions for rosacea | journal = The Cochrane Database of Systematic Reviews | volume = 2015 | issue = 4 | pages = CD003262 | date = April 2015 | pmid = 25919144 | pmc = 6481562 | doi = 10.1002/14651858.CD003262.pub5 | collaboration = Cochrane Skin Group }}</ref><ref name="pmid25597924">{{cite journal | vauthors = Cao H, Yang G, Wang Y, Liu JP, Smith CA, Luo H, Liu Y | title = Complementary therapies for acne vulgaris | journal = The Cochrane Database of Systematic Reviews | volume = 1 | issue = 1 | pages = CD009436 | date = January 2015 | pmid = 25597924 | pmc = 4486007 | doi = 10.1002/14651858.CD009436.pub2 | collaboration = Cochrane Skin Group }}</ref> including ocular rosacea.<ref name="pmid38361192"/> In ocular rosacea, treatment period is 2 to 3 months. After discontinuation of doxycycline, recurrences may occur within three months; therefore, many studies recommend either slow tapering or treatment with a lower dose over a longer period of time.<ref name="pmid38361192">{{cite journal |vauthors=Avraham S, Khaslavsky S, Kashetsky N, Starkey SY, Zaslavsky K, Lam JM, Mukovozov I |title=Therapie der okulären Rosazea: Eine systematische Literatur-Übersicht: Treatment of ocular rosacea: a systematic review |journal=J Dtsch Dermatol Ges |volume=22 |issue=2 |pages=167–176 |date=February 2024 |pmid=38361192 |doi=10.1111/ddg.15290_g |url=}}</ref>

Doxycycline is used as an adjunctive therapy for acute [[intestinal amebiasis]].<ref name="drugs-com">{{cite web | url=https://www.drugs.com/dosage/doxycycline.html | title=Doxycycline Dosage Guide + Max Dose, Adjustments | access-date=5 February 2024 | archive-date=5 February 2024 | archive-url=https://web.archive.org/web/20240205202304/https://www.drugs.com/dosage/doxycycline.html | url-status=live }}</ref>

Doxycycline is also used as an adjunctive therapy for [[chancroid]].<ref name="drugs-com"/>

==== As prophylaxis against sexually transmitted infections ====
Doxycycline is used for post-exposure prophylaxis (PEP) to reduce the incidence of sexually transmitted bacterial infections (STIs), but it has been associated with tetracycline resistance in associated species, in particular, in [[Neisseria gonorrhoeae]].<ref name="pmid38575877">{{cite journal |vauthors=Vanbaelen T, Manoharan-Basil SS, Kenyon C |title=45 years of tetracycline post exposure prophylaxis for STIs and the risk of tetracycline resistance: a systematic review and meta-analysis |journal=BMC Infect Dis |volume=24 |issue=1 |pages=376 |date=April 2024 |pmid=38575877 |pmc=10996150 |doi=10.1186/s12879-024-09275-3|doi-access=free }}</ref><ref name="Samuel-2023">{{cite web |vauthors=Samuel K |title=Using antibiotics to prevent STIs |url=https://www.aidsmap.com/about-hiv/using-antibiotics-prevent-stis |website=Aidsmap |date=26 May 2023 |access-date=10 March 2024 |archive-date=10 March 2024 |archive-url=https://web.archive.org/web/20240310162916/https://www.aidsmap.com/about-hiv/using-antibiotics-prevent-stis |url-status=live }}</ref><ref name="pmid38118022">{{cite journal |vauthors=Stewart J |title=Doxycycline Prophylaxis to Prevent Sexually Transmitted Infections in Women |journal=New England Journal of Medicine |date=21 December 2023 |volume=389 |issue=25 |pages=2331–2340 |doi=10.1056/NEJMoa2304007 |pmid=38118022 |pmc=10805625 }}</ref> For this reason, the Australian consensus statement mentions that doxycycline for PEP particularly in gay, bisexual, and other men who have sex with men (GBMSM) should be considered only for the prevention of syphilis in GBMSM, and that the risk of increasing antimicrobial resistance outweighed any potential benefit from reductions in other bacterial STIs in GBMSM.<ref name="pmid38479437">{{cite journal |vauthors=Cornelisse VJ, Riley B, Medland NA |title=Australian consensus statement on doxycycline post-exposure prophylaxis (doxy-PEP) for the prevention of syphilis, chlamydia and gonorrhoea among gay, bisexual and other men who have sex with men |journal=Med J Aust |volume=220 |issue=7 |pages=381–386 |date=April 2024 |pmid=38479437 |doi=10.5694/mja2.52258|doi-access=free }}</ref>

Appropriate use of doxycycline for PEP is supported by guidelines from the [[Centers for Disease Control and Prevention|US Centers for Disease Control and Prevention]] (CDC)<ref name="CDC-2023-Gudelines-Post-Exposure">{{cite web |title=Guidelines for the Use of Doxycycline Post-Exposure Prophylaxis for Bacterial STI Prevention |url=https://www.cdc.gov/std/treatment/guidelines-for-doxycycline.htm |website=CDC |date=29 September 2023 |access-date=10 March 2024 |archive-date=10 March 2024 |archive-url=https://web.archive.org/web/20240310162915/https://www.cdc.gov/std/treatment/guidelines-for-doxycycline.htm |url-status=live }}</ref> and the Australasian Society for HIV Medicine.<ref name="Australasian Society for HIV Medicine 2023">{{cite web |title=2023 Consensus Statement on doxycycline prophylaxis (Doxy-PEP) for the prevention of syphilis, chlamydia and gonorrhoea among gay, bisexual, and other men who have sex with men in Australia |url=https://ashm.org.au/about/news/doxy-pep-statement/ |website=Australasian Society for HIV Medicine |access-date=10 March 2024 |archive-date=10 March 2024 |archive-url=https://web.archive.org/web/20240310162917/https://ashm.org.au/about/news/doxy-pep-statement/ |url-status=live }}</ref><ref name="Highleyman-2024">{{cite web |vauthors=Highleyman L |title=Sexually transmitted infections in San Francisco have fallen since doxyPEP roll-out |url=https://www.aidsmap.com/news/mar-2024/sexually-transmitted-infections-san-francisco-have-fallen-doxypep-roll-out |website=Aidsmap |date=5 March 2024 |access-date=10 March 2024 |archive-date=10 March 2024 |archive-url=https://web.archive.org/web/20240310162916/https://www.aidsmap.com/news/mar-2024/sexually-transmitted-infections-san-francisco-have-fallen-doxypep-roll-out |url-status=live }}</ref>

==== Use in combination ====
The first-line treatment for [[brucellosis]] is a combination of doxycycline and [[streptomycin]]. The second-line is a combination of doxycycline and [[rifampicin]] (rifampin).<ref name="pmid22296864">{{cite journal | vauthors = Hashemi SH, Gachkar L, Keramat F, Mamani M, Hajilooi M, Janbakhsh A, Majzoobi MM, Mahjub H | title = Comparison of doxycycline-streptomycin, doxycycline-rifampin, and ofloxacin-rifampin in the treatment of brucellosis: a randomized clinical trial | journal = International Journal of Infectious Diseases | volume = 16 | issue = 4 | pages = e247–e251 | date = April 2012 | pmid = 22296864 | doi = 10.1016/j.ijid.2011.12.003 | url = http://www.ijidonline.com/article/S1201-9712(12)00015-X/abstract | access-date = 23 August 2014 | url-status = live | doi-access = free | archive-url = https://web.archive.org/web/20210828065145/https://www.ijidonline.com/article/S1201-9712%2812%2900015-X/fulltext | archive-date = 28 August 2021 }}</ref>

===Antimalarial===
Doxycycline is active against the erythrocytic stages of ''[[Plasmodium falciparum]]'' but not against the gametocytes of ''P. falciparum''.<ref name="DailyMed-2020">{{cite web | title=Doryx- doxycycline hyclate tablet, delayed release | website=DailyMed | date=23 October 2020 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=99cf2de6-e0a3-42f2-9929-d33e107af948 | access-date=5 March 2022 | archive-date=3 January 2022 | archive-url=https://web.archive.org/web/20220103004820/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=99cf2de6-e0a3-42f2-9929-d33e107af948 | url-status=live }}</ref> It is used to prevent [[malaria]].<ref name="CDC">{{cite web |title=Malaria - Chapter 3 - 2018 Yellow Book {{!}} Travelers' Health {{!}} CDC |url=https://wwwnc.cdc.gov/travel/yellowbook/2018/infectious-diseases-related-to-travel/malaria |website=CDC |access-date=4 December 2018 |archive-date=3 December 2018 |archive-url=https://web.archive.org/web/20181203193423/https://wwwnc.cdc.gov/travel/yellowbook/2018/infectious-diseases-related-to-travel/malaria |url-status=live }}</ref> It is not recommended alone for initial treatment of malaria, even when the parasite is doxycycline-sensitive, because the antimalarial effect of doxycycline is delayed.<ref name="pmid16940111">{{cite journal | vauthors = Dahl EL, Shock JL, Shenai BR, Gut J, DeRisi JL, Rosenthal PJ | title = Tetracyclines specifically target the apicoplast of the malaria parasite Plasmodium falciparum | journal = Antimicrobial Agents and Chemotherapy | volume = 50 | issue = 9 | pages = 3124–31 | date = September 2006 | pmid = 16940111 | pmc = 1563505 | doi = 10.1128/AAC.00394-06 }}</ref>

Doxycycline blocks protein production in [[apicoplast]] (an [[organelle]]) of ''P. falciparum''—such blocking leads to two main effects: it disrupts the parasite's ability to produce fatty acids, which are essential for its growth, and it impairs the production of heme, a cofactor. These effects occur late in the parasite's life cycle when it is in the blood stage, causing the symptoms of malaria.<ref name="Holmes-2009">{{cite journal|doi=10.4137/CMT.S2035 |title=Safety and Efficacy Review of Doxycycline |date=2009 |journal=Clinical Medicine. Therapeutics |volume=1 |pages=CMT.S2035 | vauthors = Holmes NE, Charles PG }}</ref> By blocking important processes in the parasite, doxycycline both inhibits the growth and prevents the multiplication of ''P. falciparum''. It does not directly kill the living organisms of ''P. falciparum'' but creates conditions that prevent their growth and replication.<ref name="pmid26555664">{{cite journal |vauthors=Gaillard T, Madamet M, Pradines B |title=Tetracyclines in malaria |journal=Malar J |volume=14 |pages=445 |date=November 2015 |pmid=26555664 |pmc=4641395 |doi=10.1186/s12936-015-0980-0 |doi-access=free |url=}}</ref>

The [[World Health Organization]] (WHO) guidelines state that the combination of doxycycline with either artesunate or quinine may be used for the treatment of uncomplicated malaria due to ''[[Plasmodium falciparum|P. falciparum]]'' or following intravenous treatment of severe malaria.<ref name="World Health Organization-2015">{{cite book | title = Guidelines for the treatment of malaria | publisher = World Health Organization | location = Geneva | year = 2015 | isbn = 978-92-4-154912-7|page = 246 }}</ref>

===Antihelminthic===
Doxycycline kills the [[symbiosis|symbiotic]] ''[[Wolbachia]]'' bacteria in the reproductive tracts of [[parasitic]] [[filarial]] [[nematodes]], making the nematodes sterile, and thus reducing transmission of diseases such as [[onchocerciasis]] and [[elephantiasis tropica|elephantiasis]].<ref name="pmid12684759">{{cite journal | vauthors = Hoerauf A, Mand S, Fischer K, Kruppa T, Marfo-Debrekyei Y, Debrah AY, Pfarr KM, Adjei O, Büttner DW | title = Doxycycline as a novel strategy against bancroftian filariasis-depletion of Wolbachia endosymbionts from Wuchereria bancrofti and stop of microfilaria production | journal = Medical Microbiology and Immunology | volume = 192 | issue = 4 | pages = 211–6 | date = November 2003 | pmid = 12684759 | doi = 10.1007/s00430-002-0174-6 | s2cid = 23349595 }}</ref> Field trials in 2005 showed an eight-week course of doxycycline almost eliminates the release of [[microfilariae]].<ref name="pmid15964448">{{cite journal | vauthors = Taylor MJ, Makunde WH, McGarry HF, Turner JD, Mand S, Hoerauf A | title = Macrofilaricidal activity after doxycycline treatment of Wuchereria bancrofti: a double-blind, randomised placebo-controlled trial | journal = Lancet | volume = 365 | issue = 9477 | pages = 2116–21 | year = 2005 | pmid = 15964448 | doi = 10.1016/S0140-6736(05)66591-9 | s2cid = 21382828 }}</ref>

===Spectrum of susceptibility===
Doxycycline has been used successfully to treat sexually transmitted, respiratory, and ophthalmic infections. Representative pathogenic genera include ''[[Chlamydia]], [[Streptococcus]], [[Ureaplasma]], [[Mycoplasma]]'', and others. The following represents [[minimum inhibitory concentration]] susceptibility data for a few medically significant microorganisms.<ref name="toku-e.com">{{cite web|title=Doxycycline hyclate Susceptibility and Minimum Inhibitory Concentration (MIC) Data|url=http://www.toku-e.com/Assets/MIC/Doxycycline%20hyclate.pdf|website=toku-e.com|access-date=16 April 2017|archive-date=24 February 2015|archive-url=https://web.archive.org/web/20150224063348/http://www.toku-e.com/Assets/MIC/Doxycycline%20hyclate.pdf|url-status=live}}</ref>
* ''[[Chlamydia psittaci]]'': 0.03&nbsp;''μ''g/mL<ref name="toku-e.com"/>
* ''[[Mycoplasma pneumoniae]]'': 0.016–2&nbsp;''μ''g/mL<ref name="toku-e.com"/>
* ''[[Streptococcus pneumoniae]]'': 0.06–32&nbsp;''μ''g/mL<ref name="toku-e.com"/>

=== Sclerotherapy ===
Doxycycline is also used for [[sclerotherapy]] in slow-flow vascular malformations, namely [[Venous malformation|venous]] and [[lymphatic malformation]]s, as well as post-operative [[lymphocele]]s.<ref name="Kaufman-2013">{{cite book| vauthors = Kaufman JA, Lee MJ |title=Vascular and interventional radiology|date=22 June 2013|isbn=978-0-323-07672-2|edition=2nd|location=Philadelphia, PA | publisher = Saunders |oclc=853455295}}</ref>

==Off-label use==
Doxycycline has found off-label use in the treatment of [[transthyretin amyloidosis]] (ATTR). Together with [[tauroursodeoxycholic acid]], doxycyclin appears to be a promising combination capable of disrupting transthyretin TTR fibrils in existing amyloid deposits of ATTR patients.<ref name="Muller-2020">{{cite journal| vauthors = Müller M, Butler J, Heidecker B|title=Emerging therapies in transthyretin amyloidosis – a new wave of hope after years of stagnancy?|journal=European Journal of Heart Failure |date=7 January 2020|volume=22 |issue=1 |pages=39–53 |publisher=Wiley|doi=10.1002/ejhf.1695 |doi-access=free|pmid=31912620 }}</ref>

==Routes of administration==
Doxycycline can be administered via oral or intravenous routes.<ref name=AHFS2015 />

The combination of doxycycline with dairy, antacids, calcium supplements, iron products, laxatives containing magnesium, or [[bile acid sequestrant]]s is not inherently dangerous, but any of these foods and supplements may decrease absorption of doxycycline.<ref name="AC" /><ref name="U.S. National Library of Medicine-2016">{{cite web|author=((PubMed Health))|title=Doxycycline (By mouth)|url=https://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0010039/?report=details|date=1 July 2016|publisher=[[U.S. National Library of Medicine]]|access-date=16 July 2016|url-status=dead|archive-url=https://web.archive.org/web/20131111164820/http://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0010039/?report=details|archive-date=11 November 2013}}</ref>

Doxycycline has a high oral bioavailability, as it is almost completely absorbed in the stomach and proximal small intestine.<ref name="safety-2009"/> Unlike other tetracyclines, its absorption is not significantly affected by food or dairy intake.<ref name="safety-2009"/> However, co-administration of dairy products reduces the serum concentration of doxycycline by 20%.<ref name="safety-2009"/> Doxycycline absorption is also inhibited by divalent and trivalent cations, such as iron, bismuth, aluminum, calcium and magnesium.<ref name="safety-2009"/> Doxycycline forms unstable complexes with metal ions in the acidic gastric environment, which dissociate in the small intestine, allowing the drug to be absorbed. However, some doxycycline remains complexed with metal ions in the duodenum, resulting in a slight decrease in absorption.<ref name="safety-2009"/>

==Contraindications==
Severe [[liver disease]] or concomitant use of [[isotretinoin]] or other [[retinoid]]s are contraindications, as both tetracyclines and retinoids can cause [[intracranial hypertension]] (increased pressure around the brain) in rare cases.<ref name="AC">{{cite book|title=Austria-Codex| veditors = Haberfeld H |at=Doxycyclin Genericon 200 mg lösliche Tabletten|publisher=Österreichischer Apothekerverlag|location=Vienna|year=2020|language=de}}</ref>

===Pregnancy and lactation===
Doxycycline is categorized by the [[Food and Drug Administration|FDA]] as a [[Pregnancy category#United States|class D drug]] in pregnancy. Doxycycline crosses into [[breastmilk]].<ref name="pmid12431134">{{cite journal | vauthors = Chung AM, Reed MD, Blumer JL | title = Antibiotics and breast-feeding: a critical review of the literature | journal = Paediatric Drugs | volume = 4 | issue = 12 | pages = 817–37 | year = 2002 | pmid = 12431134 | doi = 10.2165/00128072-200204120-00006 | s2cid = 8595370 }}</ref> Other tetracycline antibiotics are contraindicated in pregnancy and up to eight years of age, due to the potential for disrupting bone and tooth development.<ref name="pmid20814687">{{cite journal | vauthors = Mylonas I | title = Antibiotic chemotherapy during pregnancy and lactation period: aspects for consideration | journal = Archives of Gynecology and Obstetrics | volume = 283 | issue = 1 | pages = 7–18 | date = January 2011 | pmid = 20814687 | doi = 10.1007/s00404-010-1646-3 | s2cid = 25492353 }}</ref> They include a class warning about staining of teeth and decreased development of dental enamel in children exposed to tetracyclines in utero, during breastfeeding or during young childhood.<ref name="FDA-2018">{{cite journal |title=Bioterrorism and Drug Preparedness - Doxycycline Use by Pregnant and Lactating Women |url=https://www.fda.gov/drugs/emergencypreparedness/bioterrorismanddrugpreparedness/ucm131011.htm |journal=FDA |access-date=9 December 2018 |date=3 November 2018 |archive-date=8 February 2019 |archive-url=https://web.archive.org/web/20190208034744/https://www.fda.gov/Drugs/EmergencyPreparedness/BioterrorismandDrugPreparedness/ucm131011.htm |url-status=live }}</ref> However, the FDA has acknowledged that the actual risk of dental staining of primary teeth is undetermined for doxycycline specifically. The best available evidence indicates that doxycycline has little or no effect on hypoplasia of dental enamel or on staining of teeth. The [[Centers for Disease Control and Prevention|CDC]] recommends the use of doxycycline for treatment of [[Q fever]] and tick-borne [[Rickettsial disease|rickettsial]] diseases in young children; others advocate for its use in malaria.<ref name="pmid28407772">{{cite journal | vauthors = Gaillard T, Briolant S, Madamet M, Pradines B | title = The end of a dogma: the safety of doxycycline use in young children for malaria treatment | journal = Malaria Journal | volume = 16 | issue = 1 | pages = 148 | date = April 2017 | pmid = 28407772 | pmc = 5390373 | doi = 10.1186/s12936-017-1797-9 | doi-access = free }}</ref>

==Adverse effects==
Adverse effects are similar to those of other members of the [[Tetracycline antibiotics|tetracycline]] antibiotic group. Doxycycline can cause gastrointestinal upset.<ref name="Hitchings-2015">{{cite book | vauthors = Hitchings A, Lonsdale D, Burrage D, Baker E |title=Top 100 drugs: clinical pharmacology and practical prescribing |date=2015 |isbn=978-0-7020-5516-4 |pages=200–201|publisher=Churchill Livingstone }}</ref><ref name="pmid3055652">{{cite journal | vauthors = Riond JL, Riviere JE | title = Pharmacology and toxicology of doxycycline | journal = Veterinary and Human Toxicology | volume = 30 | issue = 5 | pages = 431–43 | date = October 1988 | pmid = 3055652 }}</ref> Oral doxycycline can cause pill [[esophagitis]], particularly when it is swallowed without adequate fluid, or by persons with difficulty swallowing or impaired mobility.<ref name="pmid28286288">{{cite journal | vauthors = Affolter K, Samowitz W, Boynton K, Kelly ED | title = Doxycycline-induced gastrointestinal injury | journal = Human Pathology | volume = 66 | pages = 212–215 | date = August 2017 | pmid = 28286288 | doi = 10.1016/j.humpath.2017.02.011 }}</ref> Doxycycline is less likely than other antibiotic drugs to cause ''[[Clostridioides difficile infection|Clostridioides difficile]]'' [[colitis]]''.<ref name="pmid27025622">{{cite journal | vauthors = Hung YP, Lee JC, Lin HJ, Liu HC, Wu YH, Tsai PJ, Ko WC | title = Doxycycline and Tigecycline: Two Friendly Drugs with a Low Association with Clostridium Difficile Infection | journal = Antibiotics | volume = 4 | issue = 2 | pages = 216–29 | date = June 2015 | pmid = 27025622 | pmc = 4790331 | doi = 10.3390/antibiotics4020216 | doi-access = free }}</ref>''

An [[erythematous]] rash in sun-exposed parts of the body has been reported to occur in 7.3–21.2% of persons taking doxycycline as prophylaxis against malaria. One study examined the tolerability of various malaria prophylactic regimens and found doxycycline did not cause a significantly higher percentage of all skin events (photosensitivity not specified) when compared with other antimalarials. The rash resolves upon discontinuation of the drug.<ref name="pmid21460003">{{cite journal | vauthors = Tan KR, Magill AJ, Parise ME, Arguin PM | title = Doxycycline for malaria chemoprophylaxis and treatment: report from the CDC expert meeting on malaria chemoprophylaxis | journal = The American Journal of Tropical Medicine and Hygiene | volume = 84 | issue = 4 | pages = 517–31 | date = April 2011 | pmid = 21460003 | pmc = 3062442 | doi = 10.4269/ajtmh.2011.10-0285 }}</ref>

Unlike some other members of the tetracycline group, it may be used in those with renal impairment.<ref name="pmid15564203"/>

Doxycycline use has been associated with increased risk of [[inflammatory bowel disease]].<ref name="pmid23656210">{{cite journal | vauthors = Lee TW, Russell L, Deng M, Gibson PR | title = Association of doxycycline use with the development of gastroenteritis, irritable bowel syndrome and inflammatory bowel disease in Australians deployed abroad | journal = Internal Medicine Journal | volume = 43 | issue = 8 | pages = 919–26 | date = August 2013 | pmid = 23656210 | doi = 10.1111/imj.12179 | s2cid = 9418654 }}</ref> In one large [[Retrospective cohort study|retrospective study]], patients who were prescribed doxycycline for their acne had a 2.25-fold greater risk of developing [[Crohn's disease]].<ref name="pmid20700115">{{cite journal | vauthors = Margolis DJ, Fanelli M, Hoffstad O, Lewis JD | title = Potential association between the oral tetracycline class of antimicrobials used to treat acne and inflammatory bowel disease | journal = The American Journal of Gastroenterology | volume = 105 | issue = 12 | pages = 2610–6 | date = December 2010 | pmid = 20700115 | doi = 10.1038/ajg.2010.303 | s2cid = 20085592 }}</ref>

== Interactions ==
Previously, doxycycline was believed to impair the effectiveness of many types of [[hormonal contraception]] due to [[Cytochrome P450|CYP450]] induction. Research has shown no significant loss of effectiveness in oral contraceptives while using most tetracycline antibiotics (including doxycycline), although many physicians still recommend the use of barrier contraception for people taking the drug to prevent unwanted pregnancy.<ref name="pmid12063491">{{cite journal | vauthors = Archer JS, Archer DF | title = Oral contraceptive efficacy and antibiotic interaction: a myth debunked | journal = Journal of the American Academy of Dermatology | volume = 46 | issue = 6 | pages = 917–23 | date = June 2002 | pmid = 12063491 | doi = 10.1067/mjd.2002.120448 }}</ref><ref name="pmid15564203">{{cite journal | vauthors = Dréno B, Bettoli V, Ochsendorf F, Layton A, Mobacken H, Degreef H | title = European recommendations on the use of oral antibiotics for acne | journal = European Journal of Dermatology | volume = 14 | issue = 6 | pages = 391–9 | date = November–December 2004 | pmid = 15564203 | url = http://www.jle.com/e-docs/00/04/07/1B/vers_alt/VersionPDF.pdf }}{{dead link|date=September 2017 |bot=Level C |fix-attempted=yes }}</ref><ref name="pmid12436822">{{cite journal | vauthors = DeRossi SS, Hersh EV | title = Antibiotics and oral contraceptives | journal = Dental Clinics of North America | volume = 46 | issue = 4 | pages = 653–64 | date = October 2002 | pmid = 12436822 | doi = 10.1016/S0011-8532(02)00017-4 | citeseerx = 10.1.1.620.9933 }}</ref>

==Pharmacology==
{{see also|Tetracycline antibiotics#Mechanism of action}}
Doxycycline, like other tetracycline antibiotics, is [[Bacteriostatic agent|bacteriostatic]]. It works by preventing bacteria from reproducing by inhibiting [[Protein biosynthesis|protein synthesis]].<ref name="Flower-2012">{{cite book | vauthors = Flower R, Rang HP, Dale MM, Ritter JM, Henderson G |title=Rang & Dale's Pharmacology |publisher=Churchill Livingstone |location=Edinburgh |year=2012 |isbn=978-0-7020-3471-8}}</ref>

Doxycycline is highly [[Lipophilicity|lipophilic]], so it can easily enter cells, meaning the drug is easily absorbed after oral administration and has a large [[volume of distribution]]. It can also be re-absorbed in the [[renal tubules]] and [[gastrointestinal tract]] due to its high lipophilicity, giving it a long [[Biological half-life|elimination half-life]]. It is also prevented from accumulating in the kidneys of patients with [[kidney failure]] due to the compensatory excretion in [[Feces|faeces]].<ref name="pmid3055652"/><ref name="pmid23966509">{{cite journal | vauthors = Maaland MG, Papich MG, Turnidge J, Guardabassi L | title = Pharmacodynamics of doxycycline and tetracycline against Staphylococcus pseudintermedius: proposal of canine-specific breakpoints for doxycycline | journal = Journal of Clinical Microbiology | volume = 51 | issue = 11 | pages = 3547–54 | date = November 2013 | pmid = 23966509 | pmc = 3889732 | doi = 10.1128/JCM.01498-13 }}</ref> Doxycycline–metal ion complexes are unstable at acidic pH, therefore more doxycycline enters the duodenum for absorption than the earlier tetracycline compounds. In addition, food has less effect on the absorption of doxycycline than on the absorption of earlier drugs, with doxycycline serum concentrations being reduced by about 20% by test meals compared with 50% for tetracycline.<ref name="pmid16816396">{{cite journal | vauthors = Agwuh KN, MacGowan A | title = Pharmacokinetics and pharmacodynamics of the tetracyclines including glycylcyclines | journal = The Journal of Antimicrobial Chemotherapy | volume = 58 | issue = 2 | pages = 256–65 | date = August 2006 | pmid = 16816396 | doi = 10.1093/jac/dkl224 | doi-access = free }}</ref>

===Mechanism of action===
Doxycycline is a broad-spectrum [[bacteriostatic agent|bacteriostatic]] antibiotic. It inhibits the synthesis of bacterial proteins by binding to the [[30S ribosomal subunit]], which is only found in bacteria.<ref name="Hitchings-2015"/><ref name="pmid23966509"/> This prevents the binding of [[transfer RNA]] to [[messenger RNA]] at the ribosomal subunit, meaning [[Amino acid|amino acids]] cannot be added to [[Peptide|polypeptide chains]] and new proteins cannot be made. This stops bacterial growth, giving the [[immune system]] time to kill and remove the bacteria.<ref name="www.drugbank.ca">{{cite web |title=Doxycycline |url=https://www.drugbank.ca/drugs/DB00254 |website=www.drugbank.ca |access-date=23 January 2019 |archive-date=10 November 2008 |archive-url=https://web.archive.org/web/20081110051903/https://www.drugbank.ca/drugs/DB00254 |url-status=live }}</ref>

===Pharmacokinetics===
The substance is almost completely absorbed from the upper part of the [[small intestine]]. It reaches highest concentrations in the [[blood plasma]] after one to two hours and has a high [[plasma protein]] binding rate of about 80–90%. Doxycycline penetrates into almost all [[Tissue (biology)|tissues]] and [[body fluid]]s. Very high concentrations are found in the [[gallbladder]], [[liver]], kidneys, lungs, breast milk, bones, and genitals; low concentrations are found in [[saliva]], [[aqueous humor]], [[cerebrospinal fluid]] (CSF), and especially in inflamed [[meninges]].<ref name="AC" /><ref name="Arzneistoff-Profile">{{cite book|title=Arzneistoff-Profile|editor=Dinnendahl, V |editor2=Fricke, U|publisher=Govi Pharmazeutischer Verlag|location=Eschborn, Germany|year=2010|edition=24|volume=4|at=Doxycyclin|isbn=978-3-7741-9846-3|language=de}}</ref><ref name="Drugs.com">Doxycycline {{drugs.com|PPA|doxycycline}}. Accessed 5 August 2020.</ref> By comparison, the tetracycline antibiotic [[minocycline]] penetrates significantly better into the CSF and meninges.<ref name="Österreichischer Apothekerverlag-2020-2">{{cite book|title=Austria-Codex| veditors = Haberfeld H |at=Minostad 50 mg-Kapseln|publisher=Österreichischer Apothekerverlag|location=Vienna|year=2020|language=de}}</ref>

Doxycycline [[metabolism]] is negligible. It is actively excreted into the gut (in part via the gallbladder, in part directly from [[Blood vessel|blood vessels]]), where some of it is inactivated by forming [[chelate]]s. About 40% are eliminated via the kidneys, much less in people with [[end-stage kidney disease]]. The [[biological half-life]] is 18 to 22 hours (16&nbsp;±&nbsp;6 hours according to another source<ref name="Arzneistoff-Profile" />) in healthy people, slightly longer in those with end-stage kidney disease, and significantly longer in those with [[liver disease]].<ref name="AC" /><ref name="Arzneistoff-Profile" /><ref name="Drugs.com" />

==Chemistry==
Expired tetracyclines or tetracyclines allowed to stand at a pH less than 2 are reported to be nephrotoxic due to the formation of a degradation product, anhydro-4-epitetracycline<ref name="World Health Organization (WHO)-1991">{{cite book | chapter-url = http://www.inchem.org/documents/ehc/ehc/ehc119.htm | chapter = Principles and methods for the assessment of nephrotoxicity associated with exposure to chemicals | archive-url = https://web.archive.org/web/20110510093944/http://www.inchem.org/documents/ehc/ehc/ehc119.htm | archive-date=10 May 2011 | isbn = 92-4-157119-5 | title = Environmental health criteria | volume = 119 | publisher = [[World Health Organization]] (WHO)| issn = 0250-863X | date = 1991 }}</ref><ref name="ReferenceA">{{cite book | title = Foye's Principles of Medicinal Chemistry | vauthors = Williams DA, Foye WO, Lemke TL | date = 2008 | edition = 6th | publisher = Lippincott Williams & Wilkins | isbn = 978-0-7817-6879-5 }}</ref> causing [[Fanconi syndrome]].<ref name="ReferenceB">{{cite book | title = Goodman & Gilman's The Pharmacological Basis of Therapeutics | edition = 12th | veditors = Brunton LL, Chabner BA, Knollmann BC }}</ref> In the case of doxycycline, the absence of a hydroxyl group in C-6 prevents the formation of the nephrotoxic compound.<ref name="ReferenceA"/> Nevertheless, tetracyclines and doxycycline itself have to be taken with caution in patients with kidney injury, as they can worsen [[azotemia]] due to catabolic effects.<ref name="ReferenceB"/>

===Chemical properties===
Doxycycline, doxycycline [[Water of crystallization|monohydrate]] and doxycycline [[hyclate]] are yellow, crystalline powders with a bitter taste. The latter smells faintly of [[ethanol]], a 1% [[aqueous]] solution has a [[pH]] of 2–3, and the [[specific rotation]] is <math>[\alpha]_D^{25}</math>&nbsp;−110°&nbsp;cm<sup>3</sup>/dm·g in 0.01&nbsp;[[Normality (chemistry)|N]] [[methanol]]ic [[hydrochloric acid]].<ref name="Arzneistoff-Profile" />
{| class="wikitable"
|+ [[Solubility]]<ref name="Arzneistoff-Profile" />
|-
! Solubility in !! Doxycycline !! Doxycycline monohydrate !! Doxycycline hyclate
|-
| Water || very slightly || very slightly || freely
|-
| Ethanol || very slightly || very slightly || sparingly
|-
| Aqueous acids || freely || freely ||
|-
| [[Alkali metal|Alkali]] hydroxyde solutions || freely || freely ||
|-
| [[Chloroform]] || very slightly || practically insoluble || practically insoluble
|-
| [[Diethyl ether]] || insoluble || practically insoluble || practically insoluble
|}

==History==
After [[penicillin]] revolutionized the treatment of bacterial infections in World War II, many chemical companies moved into the field of discovering antibiotics by [[bioprospecting]]. [[American Cyanamid]] was one of these, and in the late 1940s chemists there discovered [[chlortetracycline]], the first member of the [[tetracycline antibiotic|tetracycline class]] of antibiotics.<ref name="pmid22191524">{{cite journal | vauthors = Nelson ML, Levy SB | title = The history of the tetracyclines | journal = Annals of the New York Academy of Sciences | volume = 1241 | issue = 1 | pages = 17–32 | date = December 2011 | pmid = 22191524 | doi = 10.1111/j.1749-6632.2011.06354.x | s2cid = 34647314 | bibcode = 2011NYASA1241...17N }}</ref> Shortly thereafter, scientists at Pfizer discovered [[oxytetracycline]] and it was brought to market. Both compounds, like penicillin, were natural products and it was commonly believed that nature had perfected them, and further chemical changes could only degrade their effectiveness. Scientists at Pfizer led by [[Lloyd Conover]] modified these compounds, which led to the invention of [[tetracycline]] itself, the first semi-synthetic antibiotic. Charlie Stephens' group at Pfizer worked on further analogs and created one with greatly improved stability and pharmacological efficacy: doxycycline. It was clinically developed in the early 1960s and approved by the FDA in 1967.<ref name="pmid22191524"/>

As its patent grew near to expiring in the early 1970s, the patent became the subject of lawsuit between Pfizer and [[International Rectifier]]<ref name="Justia Law">{{cite web|url=https://law.justia.com/cases/federal/district-courts/FSupp/545/486/1432019/|archive-url=https://web.archive.org/web/20150224061035/http://law.justia.com/cases/federal/district-courts/FSupp/545/486/1432019/|url-status=dead|title=Pfizer, Inc. v. International Rectifier Corp., 545 F. Supp. 486 (C.D. Cal. 1980)|archive-date=24 February 2015|website=Justia Law}}</ref> that was not resolved until 1983; at the time it was the largest litigated patent case in US history.<ref name=LitigationEnd>{{cite web | agency = The Associated Press | date = 6 July 1983 | url = https://www.nytimes.com/1983/07/06/business/pfizer-to-get-rachelle-units.html | title = Pfizer to Get Rachelle Units | archive-url = https://web.archive.org/web/20160306165725/http://www.nytimes.com/1983/07/06/business/pfizer-to-get-rachelle-units.html | archive-date=6 March 2016 | work = The New York Times }}</ref> Instead of a cash payment for infringement, Pfizer took the veterinary and feed-additive businesses of International Rectifier's subsidiary, Rachelle Laboratories.<ref name=LitigationEnd/>

In January 2013, the FDA reported shortages of some, but not all, forms of doxycycline "caused by increased demand and manufacturing issues".<ref name="CDC Health Alert Network-2013">{{cite web | work = CDC Health Alert Network | date = 12 June 2013 | url = http://emergency.cdc.gov/han/han00349.asp | title = Nationwide Shortage of Doxycycline: Resources for Providers and Recommendations for Patient Care | archive-url = https://web.archive.org/web/20150215093954/http://emergency.cdc.gov/han/han00349.asp | archive-date=15 February 2015 }}</ref> Companies involved included an unnamed major generics manufacturer that ceased production in February 2013, [[Teva Pharmaceutical Industries|Teva]] (which ceased production in May 2013), [[Mylan]], [[Actavis]], and [[Hikma Pharmaceuticals]].<ref name="American Society of Health-System Pharmacists.-2014">{{cite web | work = American Society of Health-System Pharmacists. | date = 12 December 2014 | url = http://www.ashp.org/menu/DrugShortages/CurrentShortages/bulletin.aspx?id=977 | title = Doxycycline Capsules and Tablets | archive-url = https://web.archive.org/web/20150101010923/http://www.ashp.org/menu/DrugShortages/CurrentShortages/bulletin.aspx?id=977 | archive-date=1 January 2015 }}</ref><ref name="American Society of Health-System Pharmacists.-2014-2">{{cite web | work = American Society of Health-System Pharmacists. | date = 12 November 2014 | url = http://www.ashp.org/menu/DrugShortages/CurrentShortages/bulletin.aspx?id=431 | title = Doxycycline Hyclate Injection | archive-url = https://web.archive.org/web/20150101011224/http://www.ashp.org/menu/DrugShortages/CurrentShortages/bulletin.aspx?id=431 | archive-date=1 January 2015 }}</ref> The shortage came at a particularly bad time, since there were also shortages of an alternative antibiotic, tetracycline, at the same time.<ref name="Consumer Reports News-2013">{{cite web | work = Consumer Reports News| date = 4 February 2013 | url = http://www.consumerreports.org/cro/news/2013/02/fda-reports-shortage-of-doxycycline-antibiotic-what-are-your-options/index.htm | title = FDA reports shortage of doxycycline antibiotic. What are your options? | archive-url = https://web.archive.org/web/20150101012412/http://www.consumerreports.org/cro/news/2013/02/fda-reports-shortage-of-doxycycline-antibiotic-what-are-your-options/index.htm | archive-date=1 January 2015 }}</ref> The market price for doxycycline dramatically increased in the United States in 2013 and early 2014 (from $20 to over $1800 for a bottle of 500 tablets),<ref name="WSMV-TV-2013">{{cite web | url = http://www.wsmv.com/story/21616095/sudden-increase-in-cost-of-common-drug-concerns-many | title = Sudden increase in cost of common drug concerns many | archive-url = https://web.archive.org/web/20141231084623/http://www.wsmv.com/story/21616095/sudden-increase-in-cost-of-common-drug-concerns-many | archive-date=31 December 2014 | work = [[WSMV-TV]] | date = 12 March 2013 | vauthors = Frio A }}</ref><ref name="Rosenthal-2014">{{cite web | vauthors = Rosenthal E | url = https://www.nytimes.com/2014/10/08/business/officials-question-the-rising-costs-of-generic-drugs.html | title = Officials Question the Rising Costs of Generic Drugs | archive-url = https://web.archive.org/web/20170223043227/https://www.nytimes.com/2014/10/08/business/officials-question-the-rising-costs-of-generic-drugs.html | archive-date=23 February 2017 | work = [[The New York Times]] | date = 7 October 2014 }}</ref><ref name="Palmer-2014">{{cite web | vauthors = Palmer E | work = FiercePharmaManufacturing | date = 13 March 2014 | url = http://www.fiercepharmamanufacturing.com/story/hikma-hits-jackpot-doxycycline-shortage/2014-03-13 | title = Hikma hits the jackpot with doxycycline shortage | archive-url = https://web.archive.org/web/20150101012858/http://www.fiercepharmamanufacturing.com/story/hikma-hits-jackpot-doxycycline-shortage/2014-03-13 | archive-date=1 January 2015 }}</ref> before decreasing again.<ref name="Costco Drug Information">{{cite web|url=http://www.costco.com/Pharmacy/drug-results-details-price?storeId=10301&catalogId=10051&langId=-1&searchKeyword=Doxycycline&drugId=212&drugName=Doxycycline&drugSearch=headerDrugSearch&isPharmacy=true&encodedDrugName=Doxycycline|title=Costco Drug Information|access-date=31 July 2016|url-status=live|archive-url=https://web.archive.org/web/20160304053451/http://www.costco.com/Pharmacy/drug-results-details-price?storeId=10301&catalogId=10051&langId=-1&searchKeyword=Doxycycline&drugId=212&drugName=Doxycycline&drugSearch=headerDrugSearch&isPharmacy=true&encodedDrugName=Doxycycline|archive-date=4 March 2016}}</ref><ref name="GoodRx">{{cite web|url=http://www.goodrx.com/doxycycline-hyclate?drug-name=doxycycline+hyclate|title=Doxycycline Hyclate Prices and Doxycycline Hyclate Coupons|work=GoodRx|access-date=31 July 2016|url-status=live|archive-url=https://web.archive.org/web/20160728183159/http://www.goodrx.com/doxycycline-hyclate?drug-name=doxycycline+hyclate|archive-date=28 July 2016}}</ref>

==Society and culture==
Doxycycline is available worldwide under many brand names.<ref name="drugs.com">{{cite web | work = drugs.com  | url = https://www.drugs.com/international/doxycycline.html | title = International availability for doxycycline | archive-url = https://web.archive.org/web/20150516031523/http://www.drugs.com/international/doxycycline.html | archive-date=16 May 2015 | access-date = 29 April 2015 }}</ref> Doxycycline is available as a generic medicine.<ref name=AHFS2015/><ref name="Hamilton-2011"/> Doxycycline is also used in the prevention of certain sexually transmitted infections, particularly among [[men who have sex with men]].<ref name = "CDC-doxy-pep">{{cite web |  work = cdc.gov | url = https://www.cdc.gov/sti/prevention/doxy-pep.html | title = Preventing STIs with Doxy PEP | date = 5 December 2024 | access-date = 26 December 2024}}</ref>

==Research==
===Medical conditions===
Research areas on the application of doxycycline include the following medical conditions:
* [[macular degeneration]];<ref name="pmid23971874">{{cite journal | vauthors = Leung E, Landa G | title = Update on current and future novel therapies for dry age-related macular degeneration | journal = Expert Review of Clinical Pharmacology | volume = 6 | issue = 5 | pages = 565–79 | date = September 2013 | pmid = 23971874 | doi = 10.1586/17512433.2013.829645 | s2cid = 26680094 }}</ref>
* [[rheumatoid arthritis]] instead of [[minocycline]] (both of which have demonstrated modest efficacy for this disease).<ref name="pmid21723947">{{cite journal | vauthors = Greenwald RA | title = The road forward: the scientific basis for tetracycline treatment of arthritic disorders | journal = Pharmacological Research | volume = 64 | issue = 6 | pages = 610–3 | date = December 2011 | pmid = 21723947 | doi = 10.1016/j.phrs.2011.06.010 }}</ref>
[[File:Tet-ON inducible transgene expression cells.svg|thumbnail|200px|Tet-ON inducible shRNA system]]

===Dosing===
Although doxycycline is approved to treat [[Lyme disease]], the optimal dosing and duration of treatment for this condition is a topic of ongoing research.<ref name="pmid38493509"/><ref name="Lyme disease. Treatment-2018">{{cite web |title=Lyme disease. Treatment |url=https://www.cdc.gov/lyme/treatment/ |url-status=live |archive-url=https://web.archive.org/web/20160610140827/http://www.cdc.gov/lyme/treatment/ |archive-date=10 June 2016 |date=21 December 2018 }}</ref> it can be used in adults and children. For treatment or prophylaxis of Lyme disease in children, it can be used for a duration of up to 21 days in children of any age.<ref name="pmid38167816">{{cite journal |vauthors=Taylor-Salmon E, Shapiro ED |title=Tick-borne infections in children in North America |journal=Curr Opin Pediatr |volume=36 |issue=2 |pages=156–163 |date=April 2024 |pmid=38167816 |pmc=10932821 |pmc-embargo-date=1 April 2025 |doi=10.1097/MOP.0000000000001326}}</ref> Doxycycline is specifically indicated to treat Lyme disease for patients presenting with erythema migrans. As for the optimal duration of treatment of this disease, guidelines vary, with some recommending a 10-day course of doxycycline, while others suggest a 14-day course; still, recent data suggest that even a 7-day course of doxycycline can be effective. Compared to other drugs, there are no significant differences in treatment response across antibiotic agents, doses, or durations when comparing 14 days versus 21 days; as such, the optimal duration of treatment of Lyme disease remains uncertain, as prolonged antibiotic courses have drawbacks, including diminishing returns in terms of patient outcomes, heightened risks of adverse events, superinfections, increased healthcare costs, and the potential for development of antibiotic resistance. Therefore, the consensus remains to treat patients with the shortest effective duration of antibiotics, as is the case with doxycycline for Lyme disease as well.<ref name="pmid38493509">{{cite journal |vauthors=Roca Mora MM, Cunha LM, Godoi A, Donadon I, Clemente M, Marcolin P, Valenzuela SA, Wormser GP |title=Shorter versus longer duration of antimicrobial therapy for early Lyme disease: A systematic review and meta-analysis |journal=Diagn Microbiol Infect Dis |volume=109 |issue=2 |pages=116215 |date=June 2024 |pmid=38493509 |doi=10.1016/j.diagmicrobio.2024.116215 }}</ref>

===Anti-inflammatory agent===
Some studies show doxycycline as a potential agent to possess anti-inflammatory properties acting by inhibiting proinflammatory cytokines such as [[interleukin-1]] (IL-1), [[interleukin-6]] (IL-6), [[tumor necrosis factor-alpha]] (TNF-α), and [[matrix metalloproteinase]]s (MMPs) while increasing the production of anti-inflammatory [[cytokine]]s such as [[interleukin-10]] (IL-10). Cytokines are small proteins that are secreted by immune cells and play a key role in the immune response. Some studies suggest that doxycycline can suppress the activation of the [[Nuclear Factor-Kappa B|nuclear factor-kappa B]] (NF-κB) pathway, which is responsible for upregulating several inflammatory mediators in various cells, including [[neuron]]s; therefore, it is studied as a potential agent for treating [[neuroinflammation]].<ref name="pmid33568043">{{cite journal |vauthors=Singh S, Khanna D, Kalra S |title=Minocycline and Doxycycline: More Than Antibiotics |journal=Curr Mol Pharmacol |volume=14 |issue=6 |pages=1046–1065 |date=2021 |pmid=33568043 |doi=10.2174/1874467214666210210122628 |s2cid=231881758 |url=http://eurekaselect.com/article/download/191269 |access-date=2 February 2024 |archive-date=2 February 2024 |archive-url=https://web.archive.org/web/20240202135951/https://eurekaselect.com/article/download/191269 |url-status=live }}</ref><ref name="pmid28516469">{{cite journal |vauthors=Henehan M, Montuno M, De Benedetto A |title=Doxycycline as an anti-inflammatory agent: updates in dermatology |journal= Journal of the European Academy of Dermatology and Venereology|volume=31 |issue=11 |pages=1800–1808 |date=November 2017 |pmid=28516469 |doi=10.1111/jdv.14345 |s2cid=37723341 |url=}}</ref><ref name="pmid17315050">{{cite journal |vauthors=Berman B, Perez OA, Zell D |title= Update on rosacea and anti-inflammatory-dose doxycycline|journal= Drugs of Today|volume= 43|issue= 1|date=January 2007|pages= 27–34|pmid=17315050 |doi=10.1358/dot.2007.43.1.1025697 |url=}}</ref>

A potential explanation of doxycycline's anti-inflammatory properties is its inhibition of [[matrix metalloproteinase]]s (MMPs), which are a group of proteases known to regulate the turnover of [[extracellular matrix]] (ECM) and thus are suggested to be important in the process of several diseases associated with [[tissue remodeling]] and inflammation.<ref name="Lagente-2011">{{cite book|doi=10.1007/978-3-0348-0157-7_5 |chapter=Matrix Metalloproteinase Inhibitors as New Anti-inflammatory Drugs |title=Proteases and Their Receptors in Inflammation |date=2011 | vauthors = Lagente V, Victoni T, Boichot E |series=Progress in Inflammation Research |pages=101–122 |publisher=Springer |isbn=978-3-0348-0156-0 }}</ref><ref name="pmid29034777">{{cite journal |vauthors=Wang S, Liu C, Liu X, He Y, Shen D, Luo Q, Dong Y, Dong H, Pang Z |title=Effects of matrix metalloproteinase inhibitor doxycycline and CD147 antagonist peptide-9 on gallbladder carcinoma cell lines |journal=Tumour Biol |volume=39 |issue=10 |pages=1010428317718192 |date=October 2017 |pmid=29034777 |doi=10.1177/1010428317718192 |s2cid=206614670 |url=|doi-access=free }}</ref><ref name="pmid27619752">{{cite journal |vauthors=Jung JJ, Razavian M, Kim HY, Ye Y, Golestani R, Toczek J, Zhang J, Sadeghi MM |title=Matrix metalloproteinase inhibitor, doxycycline and progression of calcific aortic valve disease in hyperlipidemic mice |journal=Sci Rep |volume=6 |pages=32659 |date=September 2016 |pmid=27619752 |pmc=5020643 |doi=10.1038/srep32659 |bibcode=2016NatSR...632659J |url=}}</ref><ref name="pmid36759188">{{cite journal |vauthors=Wehrli JM, Xia Y, Offenhammer B, Kleim B, Müller D, Bach DR |title=Effect of the Matrix Metalloproteinase Inhibitor Doxycycline on Human Trace Fear Memory |journal=eNeuro |volume=10 |issue=2 |date=February 2023 |pmid=36759188 |pmc=9961363 |doi=10.1523/ENEURO.0243-22.2023 |url=}}</ref> Doxycycline has been shown to inhibit MMPs,<ref name="pmid38649625">{{cite journal |vauthors=Lee JJ, Chien AL |title=Rosacea in Older Adults and Pharmacologic Treatments |journal=Drugs Aging |date=April 2024 |volume=41 |issue=5 |pages=407–421 |pmid=38649625 |doi=10.1007/s40266-024-01115-y}}</ref> including [[MMP7|matrilysin]] (MMP7), by interacting with the structural zinc atom and/or calcium atoms within the structural metal center of the protein.<ref name="pmid14681644">{{cite journal |vauthors=Liu J, Xiong W, Baca-Regen L, Nagase H, Baxter BT |title=Mechanism of inhibition of matrix metalloproteinase-2 expression by doxycycline in human aortic smooth muscle cells |journal=J Vasc Surg |volume=38 |issue=6 |pages=1376–83 |date=December 2003 |pmid=14681644 |doi=10.1016/s0741-5214(03)01022-x |url=|doi-access=free }}</ref><ref name="pmid15665254">{{cite journal |vauthors=García RA, Pantazatos DP, Gessner CR, Go KV, Woods VL, Villarreal FJ |title=Molecular interactions between matrilysin and the matrix metalloproteinase inhibitor doxycycline investigated by deuterium exchange mass spectrometry |journal=Mol Pharmacol |volume=67 |issue=4 |pages=1128–36 |date=April 2005 |pmid=15665254 |doi=10.1124/mol.104.006346 |s2cid=23253029 |url=}}</ref><ref name="pmid28662828">{{cite journal |vauthors=Liu J, Khalil RA |title=Matrix Metalloproteinase Inhibitors as Investigational and Therapeutic Tools in Unrestrained Tissue Remodeling and Pathological Disorders |journal=Prog Mol Biol Transl Sci |series=Progress in Molecular Biology and Translational Science |volume=148 |pages=355–420 |date=2017 |pmid=28662828 |pmc=5548434 |doi=10.1016/bs.pmbts.2017.04.003 |isbn=978-0-12-812776-6 |url=}}</ref>

Doxycycline also inhibits allikrein-related peptidase 5 (KLK5).<ref name="pmid36759188"/> The inhibition of MMPs and KLK5 enzymes subsequently suppresses the expression of LL-37, a cathelicidin antimicrobial peptide that, when overexpressed, can trigger inflammatory cascades. By inhibiting LL-37 expression, doxycycline helps to mitigate these downstream inflammatory cascades, thereby reducing inflammation and the symptoms of inflammatory conditions.<ref name="pmid36759188"/>

Doxycycline is used to treat [[Acne|acne vulgaris]] and [[rosacea]].<ref name="pmid34812859">{{cite journal |vauthors=Eichenfield DZ, Sprague J, Eichenfield LF |title=Management of Acne Vulgaris: A Review |journal=JAMA |volume=326 |issue=20 |pages=2055–2067 |date=November 2021 |pmid=34812859 |doi=10.1001/jama.2021.17633 |s2cid=244490539 |url=}}</ref><ref name="pmid33133338">{{cite journal |vauthors=Baldwin H |title=Oral Antibiotic Treatment Options for Acne Vulgaris |journal=J Clin Aesthet Dermatol |volume=13 |issue=9 |pages=26–32 |date=September 2020 |pmid=33133338 |pmc=7577330}}</ref><ref name="safety-2009"/> However, there is no clear understanding of what contributes more: the bacteriostatic properties of doxycycline, which affect bacteria (such as Propionibacterium acnes<ref name="safety-2009"/>) on the surface of sebaceous glands even in lower doses called "submicrobial"<ref name="pmid16146617">{{cite journal |vauthors=Parish LC, Parish JL, Routh HB, Witkowski JA |title=The treatment of acne vulgaris with low dosage doxycycline |journal=Acta Dermatovenerol Croat |volume=13 |issue=3 |pages=156–9 |date=2005 |pmid=16146617}}</ref><ref name="pmid27538054">{{cite journal |vauthors=Stein Gold LF |title=Acne: What's New |journal=Semin Cutan Med Surg |volume=35 |issue=6 Suppl |pages=S114–6 |date=June 2016 |pmid=27538054 |doi=10.12788/j.sder.2016.036 |url=}}</ref> or "subantimicrobial",<ref name="pmid36407641">{{cite journal |vauthors=Kontochristopoulos G, Tsiogka A, Agiasofitou E, Kapsiocha A, Soulaidopoulos S, Liakou AI, Gregoriou S, Rigopoulos D |title=Efficacy of Subantimicrobial, Modified-Release Doxycycline Compared to Regular-Release Doxycycline for the Treatment of Hidradenitis Suppurativa |journal=Skin Appendage Disord |volume=8 |issue=6 |pages=476–481 |date=November 2022 |pmid=36407641 |doi=10.1159/000524762 |pmc=9672876 |url= }}</ref><ref name="pmid34161892">{{cite journal |vauthors=((Mello BSF)), ((Chaves Filho AJM)), Custódio CS, Rodrigues PA, Carletti JV, ((Vasconcelos SMM)), ((Sousa FCF)), ((Sanders LLO)), Macedo DS |title=Doxycycline at subantimicrobial dose combined with escitalopram reverses depressive-like behavior and neuroinflammatory hippocampal alterations in the lipopolysaccharide model of depression |journal=J Affect Disord |volume=292 |pages=733–745 |date=September 2021 |pmid=34161892 |doi=10.1016/j.jad.2021.05.083 |url=}}</ref><ref name="pmid14673277">{{cite journal |vauthors=Bikowski JB |title=Subantimicrobial dose doxycycline for acne and rosacea |journal=Skinmed |volume=2 |issue=4 |pages=234–45 |date=2003 |pmid=14673277 |doi=10.1111/j.1540-9740.2003.03014.x |url=}}</ref><ref name="safety-2009"/> or whether doxycycline's anti-inflammatory effects, which reduce inflammation in [[Acne|acne vulgaris]] and [[rosacea]], including [[ocular rosacea]],<ref name="pmid38361192"/> contribute more to its therapeutic effectiveness against these skin conditions.<ref name="pmid32401726">{{cite journal |vauthors=Navarro-Triviño FJ, Pérez-López I, Ruiz-Villaverde R |title=Doxycycline, an Antibiotic or an Anti-Inflammatory Agent? The Most Common Uses in Dermatology |journal=Actas Dermosifiliogr (Engl Ed) |volume=111 |issue=7 |pages=561–566 |date=September 2020 |pmid=32401726 |doi=10.1016/j.ad.2019.12.006 |s2cid=218635190 |url=|doi-access=free }}</ref> Subantimicrobial-dose doxycycline (SDD) can still have a [[Bacteriostatic agent|bacteriostatic]] effect, especially when taken for extended periods, such as several months in treating acne and rosacea.<ref name="pmid37521754">{{cite journal |vauthors=Zolotarev O, Khakimova A, Rahim F, Senel E, Zatsman I, Gu D |title=Scientometric analysis of trends in global research on acne treatment |journal=Int J Womens Dermatol |volume=9 |issue=3 |pages=e082 |date=October 2023 |pmid=37521754 |pmc=10378739 |doi=10.1097/JW9.0000000000000082 |url=}}</ref> While the SDD is believed to have anti-inflammatory effects rather than solely antibacterial effects, SDD was proven to work by reducing inflammation associated with acne and rosacea. Still, the exact mechanisms have yet to be fully discovered.<ref name="pmid37820334">{{cite journal |vauthors=Shields A, Barbieri JS |title=From Breakouts to Bargains: Strategies for Patient-Centered, Cost-effective Acne Care |journal=Cutis |volume=112 |issue=2 |pages=E24–E29 |date=August 2023 |pmid=37820334 |doi=10.12788/cutis.0844 |s2cid=261786019 |doi-access=free |pmc=10951614 }}</ref> One probable mechanism is doxycycline's ability to decrease the amount of [[reactive oxygen species]] (ROS). Inflammation in rosacea may be associated with increased production of [[Reactive oxygen species|ROS]] by inflammatory cells; these ROS contribute toward exacerbating symptoms. Doxycycline may reduce ROS levels and induce antioxidant activity because it directly scavenges [[hydroxyl radical]]s and [[singlet oxygen]], helping minimize tissue damage caused by highly oxidative and inflammatory conditions.<ref name="pmid1357852">{{cite journal |vauthors=Akamatsu H, Asada M, Komura J, Asada Y, Niwa Y |title=Effect of doxycycline on the generation of reactive oxygen species: a possible mechanism of action of acne therapy with doxycycline |journal=Acta Derm Venereol |volume=72 |issue=3 |pages=178–9 |date=1992 |pmid=1357852 |doi= 10.2340/0001555572178179|s2cid=45726787 |url=|doi-access=free }}</ref> Studies have shown that SDD can effectively improve acne and rosacea symptoms,<ref name="pmid26897386">{{cite journal |vauthors=Zaenglein AL, Pathy AL, Schlosser BJ, Alikhan A, Baldwin HE, Berson DS, Bowe WP, Graber EM, Harper JC, Kang S, Keri JE, Leyden JJ, Reynolds RV, Silverberg NB, Stein Gold LF, Tollefson MM, Weiss JS, Dolan NC, Sagan AA, Stern M, Boyer KM, Bhushan R |title=Guidelines of care for the management of acne vulgaris |journal=J Am Acad Dermatol |volume=74 |issue=5 |pages=945–73.e33 |date=May 2016 |pmid=26897386 |doi=10.1016/j.jaad.2015.12.037 |url=|doi-access=free }}</ref> probably without inducing [[Antimicrobial resistance|antibiotic resistance]].<ref name="pmid18004018">{{cite journal |vauthors=Wise RD |title=Submicrobial doxycycline and rosacea |journal=Compr Ther |volume=33 |issue=2 |pages=78–81 |date=2007 |pmid=18004018 |doi=10.1007/s12019-007-8003-x |s2cid=28262106 }}</ref> It is observed that doxycycline exerts its anti-inflammatory effects by inhibiting neutrophil chemotaxis and oxidative bursts, which are common mechanisms involved in inflammation and ROS activity in rosacea and acne.<ref name="pmid38649625"/>

Doxycycline's dual benefits as an antibacterial and anti-inflammatory make it a helpful treatment option for diseases involving inflammation not only of the [[skin]], such as rosacea and acne, but also in conditions such as [[osteoarthritis]] or [[Periodontal disease|periodontitis]].<ref name="pmid12900822">{{cite journal |vauthors=Ahuja TS |title=Doxycycline decreases proteinuria in glomerulonephritis |journal=Am J Kidney Dis |volume=42 |issue=2 |pages=376–80 |date=August 2003 |pmid=12900822 |doi=10.1016/s0272-6386(03)00662-0 |url=}}</ref> Nevertheless, current results are inconclusive, and evidence of doxycycline's anti-inflammatory properties needs to be improved, considering conflicting reports from animal models so far.<ref name="pmid31955291">{{cite journal |vauthors=Patel A, Khande H, Periasamy H, Mokale S |title=Immunomodulatory Effect of Doxycycline Ameliorates Systemic and Pulmonary Inflammation in a Murine Polymicrobial Sepsis Model |journal=Inflammation |volume=43 |issue=3 |pages=1035–1043 |date=June 2020 |pmid=31955291 |doi=10.1007/s10753-020-01188-y |pmc=7224120 |url=}}</ref><ref name="pmid37759467">{{cite journal |vauthors=Martin V, Bettencourt AF, Santos C, Fernandes MH, Gomes PS |title=Unveiling the Osteogenic Potential of Tetracyclines: A Comparative Study in Human Mesenchymal Stem Cells |journal=Cells |volume=12 |issue=18 |date=September 2023 |page=2244 |pmid=37759467 |pmc=10526833 |doi=10.3390/cells12182244 |doi-access=free }}</ref><ref name="pmid37751595">{{cite journal |vauthors=Waitayangkoon P, Moon SJ, Tirupur Ponnusamy JJ, Zeng L, Driban J, McAlindon T |title=Long-Term Safety Profiles Macrolides and Tetracyclines: A Systematic Review and Meta-analysis |journal=J Clin Pharmacol |volume= 64|issue= 2|pages= 164–177|date=September 2023 |pmid=37751595 |doi=10.1002/jcph.2358 |s2cid=263151406 |url=}}</ref> Doxycycline has been studied in various immunological disorders, including [[rheumatoid arthritis]], [[lupus]], and [[Periodontal disease|periodontitis]].<ref name="pmid35742496">{{cite journal |vauthors=Orylska-Ratynska M, Placek W, Owczarczyk-Saczonek A |title=Tetracyclines-An Important Therapeutic Tool for Dermatologists |journal=Int J Environ Res Public Health |volume=19 |issue=12 |date=June 2022 |page=7246 |pmid=35742496 |pmc=9224192 |doi=10.3390/ijerph19127246 |doi-access=free }}</ref> In these conditions, doxycycline has been researched to determine anti-inflammatory and immunomodulatory effects that could be beneficial in treating these conditions. However, a solid conclusion still needs to be provided.<ref name="pmid33611055">{{cite journal |vauthors=Santos M, Gonçalves-Santos E, Gonçalves R, Santos E, Campos C, Bastos D, Marques M, Souza R, Novaes R |title=Doxycycline aggravates granulomatous inflammation and lung microstructural remodeling induced by Schistosoma mansoni infection |journal=Int Immunopharmacol |volume=94 |pages=107462 |date=May 2021 |pmid=33611055 |doi=10.1016/j.intimp.2021.107462 |s2cid=231988574 |url=|doi-access=free }}</ref><ref name="pmid34899697">{{cite journal |vauthors=Florou DT, Mavropoulos A, Dardiotis E, Tsimourtou V, Siokas V, Aloizou AM, Liaskos C, Tsigalou C, Katsiari C, Sakkas LI, Hadjigeorgiou G, Bogdanos DP |title=Tetracyclines Diminish In Vitro IFN-γ and IL-17-Producing Adaptive and Innate Immune Cells in Multiple Sclerosis |journal=Front Immunol |volume=12 |pages=739186 |date=2021 |pmid=34899697 |pmc=8662812 |doi=10.3389/fimmu.2021.739186 |doi-access=free }}</ref><ref name="pmid35294307">{{cite journal |vauthors=Garrido-Mesa J, Adams K, Galvez J, Garrido-Mesa N |title=Repurposing tetracyclines for acute respiratory distress syndrome (ARDS) and severe COVID-19: a critical discussion of recent publications |journal=Expert Opin Investig Drugs |volume=31 |issue=5 |pages=475–482 |date=May 2022 |pmid=35294307 |pmc=9115781 |doi=10.1080/13543784.2022.2054325 |url=}}</ref><ref name="pmid36869773">{{cite journal |vauthors=de Witte LD, Munk Laursen T, Corcoran CM, Kahn RS, Birnbaum R, Munk-Olsen T, Bergink V |title=A Sex-Dependent Association Between Doxycycline Use and Development of Schizophrenia |journal=Schizophr Bull |volume=49 |issue=4 |pages=953–961 |date=July 2023 |pmid=36869773 |doi=10.1093/schbul/sbad008 |pmc=10318877 |url= }}</ref>

Doxycycline is also studied for its neuroprotective properties which are associated with [[antioxidant]], [[Apoptosis|anti-apoptotic]], and anti-inflammatory mechanisms. In this context, it is important to note that doxycycline is able to cross the [[blood–brain barrier]]. Several studies have shown that doxycycline inhibits [[dopaminergic]] neurodegeneration through the upregulation of [[axon]]al and [[Synapse|synaptic]] proteins.<ref name="pmid30798507">{{cite journal |vauthors=Santa-Cecília FV, Leite CA, Del-Bel E, Raisman-Vozari R |title=The Neuroprotective Effect of Doxycycline on Neurodegenerative Diseases |journal=Neurotox Res |volume=35 |issue=4 |pages=981–986 |date=May 2019 |pmid=30798507 |doi=10.1007/s12640-019-00015-z |s2cid=71147889 |url=|doi-access=free }}</ref><ref name="pmid31879858">{{cite journal |vauthors=Paldino E, Balducci C, La Vitola P, Artioli L, D'Angelo V, Giampà C, Artuso V, Forloni G, Fusco FR |title=Neuroprotective Effects of Doxycycline in the R6/2 Mouse Model of Huntington's Disease |journal=Mol Neurobiol |volume=57 |issue=4 |pages=1889–1903 |date=April 2020 |pmid=31879858 |pmc=7118056 |doi=10.1007/s12035-019-01847-8 |url=}}</ref> Axonal degeneration and synaptic loss are key events at the early stages of neurodegeneration and precede neuronal death in [[neurodegenerative disease]]s, including [[Parkinson's disease]] (PD). Therefore, the regeneration of the axonal and synaptic network might be beneficial in PD.<ref name="pmid36843128">{{cite journal |vauthors=do Amaral L, ((Dos Santos NAG)), Sisti FM, Del Bel E, Dos Santos AC |title=Doxycycline inhibits dopaminergic neurodegeneration through upregulation of axonal and synaptic proteins |journal=Naunyn-Schmiedeberg's Arch Pharmacol |volume=396 |issue=8 |pages=1787–1796 |date=August 2023 |pmid=36843128 |doi=10.1007/s00210-023-02435-3 |s2cid=257218181 |url=}}</ref> It has been demonstrated that doxycycline mimics [[nerve growth factor]] (NGF) signaling in [[PC12 cell line|PC12]] cells. However, the involvement of this mechanism in the neuroprotective effect of doxycycline is unknown. Doxycycline is also studied in reverting inflammatory changes related to [[Major depressive disorder|depression]].<ref name="pmid34161892"/> While there is some research on the use of doxycycline for treating [[major depressive disorder]], the results are mixed.<ref name="pmid34161892"/><ref name="pmid34711196">{{cite journal |vauthors=Lee JW, Lee H, Kang HY |title=Association between depression and antibiotic use: analysis of population-based National Health Insurance claims data |journal=BMC Psychiatry |volume=21 |issue=1 |pages=536 |date=October 2021 |pmid=34711196 |pmc=8554858 |doi=10.1186/s12888-021-03550-2 |doi-access=free }}</ref><ref name="pmid36343696">{{cite journal |vauthors=Leyder E, Suresh P, Jun R, Overbey K, Banerjee T, Melnikova T, Savonenko A |title=Depression-related phenotypes at early stages of Aβ and tau accumulation in inducible Alzheimer's disease mouse model: Task-oriented and concept-driven interpretations |journal=Behav Brain Res |volume=438 |pages=114187 |date=February 2023 |pmid=36343696 |doi=10.1016/j.bbr.2022.114187 |s2cid=253300844 |url=}}</ref>

After a large-scale trial showed no benefit of using doxycycline in treating [[COVID-19|COVID{{nbhyph}}19]], the UK's [[National Institute for Health and Care Excellence]] (NICE) updated its guidance to not recommend the medication for the treatment of COVID{{nbhyph}}19.<ref name="NIHR Evidence-2022">{{cite journal |date=31 May 2022 |title=Platform trial rules out treatments for COVID-19 |url=https://evidence.nihr.ac.uk/alert/platform-trial-rules-out-covid-treatments/ |journal=NIHR Evidence |doi=10.3310/nihrevidence_50873 |access-date=1 June 2022 |archive-date=1 June 2022 |archive-url=https://web.archive.org/web/20220601095141/https://evidence.nihr.ac.uk/alert/platform-trial-rules-out-covid-treatments/ |url-status=live |url-access=subscription }}</ref><ref name="pmid34329624">{{cite journal | vauthors = Butler CC, Yu LM, Dorward J, Gbinigie O, Hayward G, Saville BR, Van Hecke O, Berry N, Detry MA, Saunders C, Fitzgerald M, Harris V, Djukanovic R, Gadola S, Kirkpatrick J, de Lusignan S, Ogburn E, Evans PH, Thomas NP, Patel MG, Hobbs FD | title = Doxycycline for community treatment of suspected COVID-19 in people at high risk of adverse outcomes in the UK (PRINCIPLE): a randomised, controlled, open-label, adaptive platform trial | journal = The Lancet. Respiratory Medicine | volume = 9 | issue = 9 | pages = 1010–1020 | date = September 2021 | pmid = 34329624 | pmc = 8315758 | doi = 10.1016/S2213-2600(21)00310-6 }}</ref> Doxycycline was expected to possess anti-inflammatory properties that could lessen the [[cytokine storm]] associated with a [[SARS-CoV-2]] infection, but the trials did not demonstrate the expected benefit.<ref name="pmid35462191">{{cite journal |vauthors=Sharma S, Bhatt P, Asdaq S, Alshammari M, Alanazi A, Alrasheedi N, Alrashdi B, Alyami S, Alhazmi B, Alam P, Sharma P, Tomar R, Arora M, Imran M |title=Combined therapy with ivermectin and doxycycline can effectively alleviate the cytokine storm of COVID-19 infection amid vaccination drive: A narrative review |journal=J Infect Public Health |volume=15 |issue=5 |pages=566–572 |date=May 2022 |pmid=35462191 |pmc=8964533 |doi=10.1016/j.jiph.2022.03.014 |url=}}</ref> Researchers also believed that doxycycline possesses anti-inflammatory and immunomodulatory effects that could reduce the production of cytokines in COVID-19, but these supposed effects failed to improve the outcome of COVID-19 treatment.<ref name="pmid35227056">{{cite journal |vauthors=Ohe M |title=Multi-drug Treatment for COVID-19-induced Acute Respiratory Distress Syndrome |journal=Turk J Pharm Sci |volume=19 |issue=1 |pages=101–103 |date=February 2022 |pmid=35227056 |pmc=8892560 |doi=10.4274/tjps.galenos.2021.63060 |url=}}</ref><ref name="pmid34584416">{{cite journal |vauthors=Dorobisz K, Dorobisz T, Janczak D, Zatoński T |title=Doxycycline in the Coronavirus Disease 2019 Therapy |journal=Ther Clin Risk Manag |volume=17 |pages=1023–1026 |date=2021 |pmid=34584416 |pmc=8464303 |doi=10.2147/TCRM.S314923 |doi-access=free }}</ref>

===Wound healing===
Research on novel drug formulations for the delivery of doxycycline in wound treatment is expanding, focusing on overcoming stability limitations for long-term storage and developing consumer-friendly, parenteral antibiotic delivery systems. The most common and practical form of doxycycline delivery is through wound dressings, which have evolved from mono- to three-layered systems to maximize healing effectiveness.<ref name="pmid38185273">{{cite journal |vauthors=Saliy O, Popova M, Tarasenko H, Getalo O |title=Development strategy of novel drug formulations for the delivery of doxycycline in the treatment of wounds of various etiologies |journal=Eur J Pharm Sci |volume=195 |pages=106636 |date=April 2024 |pmid=38185273 |doi=10.1016/j.ejps.2023.106636|doi-access=free }}</ref>

Research directions on the use of doxycycline in wound healing include the continuous stabilization of doxycycline, scaling up technology and industrial production, and exploring non-contact wound treatment methods like sprays and aerosols for use in emergencies and when medical care is not readily accessible.<ref name="pmid38185273"/>

===Research reagent===
Doxycycline and other members of the [[Tetracycline antibiotics|tetracycline class]] of antibiotics are often used as research [[reagent]]s in ''in vitro'' and ''in vivo'' biomedical research experiments involving bacteria as well in experiments in eukaryotic cells and organisms with inducible protein expression systems using [[tetracycline-controlled transcriptional activation]]. The mechanism of action for the antibacterial effect of tetracyclines relies on disrupting protein translation in bacteria, thereby damaging the ability of microbes to grow and repair; however protein translation is also disrupted in eukaryotic [[mitochondria]] impairing metabolism and leading to effects that can [[confound]] experimental results.<ref name="pmid25772356">{{cite journal | vauthors = Moullan N, Mouchiroud L, Wang X, Ryu D, Williams EG, Mottis A, Jovaisaite V, Frochaux MV, Quiros PM, Deplancke B, Houtkooper RH, Auwerx J | title = Tetracyclines Disturb Mitochondrial Function across Eukaryotic Models: A Call for Caution in Biomedical Research | journal = Cell Reports | volume = 10 | issue = 10 | pages = 1681–1691 | date = March 2015 | pmid = 25772356 | pmc = 4565776 | doi = 10.1016/j.celrep.2015.02.034 }}</ref><ref name="pmid26475870">{{cite journal | vauthors = Chatzispyrou IA, Held NM, Mouchiroud L, Auwerx J, Houtkooper RH | title = Tetracycline antibiotics impair mitochondrial function and its experimental use confounds research | journal = Cancer Research | volume = 75 | issue = 21 | pages = 4446–9 | date = November 2015 | pmid = 26475870 | pmc = 4631686 | doi = 10.1158/0008-5472.CAN-15-1626 }}</ref> Doxycycline is also used in "tet-on" ([[gene expression]] activated by doxycycline) and "tet-off" (gene expression inactivated by doxycycline) [[tetracycline-controlled transcriptional activation]] to regulate [[transgene]] expression in organisms and [[cell culture]]s.<ref name="pmid7792603">{{cite journal | vauthors = Gossen M, Freundlieb S, Bender G, Müller G, Hillen W, Bujard H | title = Transcriptional activation by tetracyclines in mammalian cells | journal = Science | volume = 268 | issue = 5218 | pages = 1766–9 | date = June 1995 | pmid = 7792603 | doi = 10.1126/science.7792603 | bibcode = 1995Sci...268.1766G }}</ref> Doxycycline is more stable than tetracycline for this purpose.<ref name="pmid7792603" /> At subantimicrobial doses, doxycycline is an inhibitor of [[matrix metalloprotease]]s, and has been used in various experimental systems for this purpose, such as for recalcitrant [[recurrent corneal erosion]]s.<ref name="pmid11438047">{{cite journal | vauthors = Dursun D, Kim MC, Solomon A, Pflugfelder SC | title = Treatment of recalcitrant recurrent corneal erosions with inhibitors of matrix metalloproteinase-9, doxycycline and corticosteroids | journal = American Journal of Ophthalmology | volume = 132 | issue = 1 | pages = 8–13 | date = July 2001 | pmid = 11438047 | doi = 10.1016/S0002-9394(01)00913-8 }}</ref>

== References ==
{{Reflist}}

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