Doxycycline

Template:Short description Template:Use American English Template:Use dmy dates Template:Cs1 config Template:Main other {{#invoke:Infobox|infobox}}Template:Template other{{#invoke:TemplatePar |check |template=Template:Infobox_drug |all= |opt= pronounce= pronounce_ref= pronounce_comment= ATC_prefix= ATC_suffix= ATC_supplemental= ATCvet= biosimilars= CAS_number_Ref= CAS_number= CAS_supplemental= ChEBI= ChEBI_Ref= ChEMBL_Ref= ChEMBL= ChemSpiderID= ChemSpiderID_Ref= chirality= class= container_only= DailyMedID= data_page= DrugBank_Ref= DrugBank= Drugs.com= duration_of_action= INN= INN_EMA= IUPAC_name= IUPHAR_ligand= KEGG_Ref= KEGG= MedlinePlus= NIAID_ChemDB= PDB_ligand= PubChemSubstance= PubChem= StdInChIKey_Ref= StdInChIKey= StdInChI_Ref= StdInChI_comment= StdInChI= UNII_Ref= UNII= DTXSID= Verifiedfields= Watchedfields= addiction_liability= alt2= altL= altR= alt= bioavailability= boiling_high= boiling_notes= boiling_point= captionLR= caption= caption2= charge= chemical_formula= chemical_formula_ref= chemical_formula_comment= class1= class2= class3= class4= class5= class6= component1= component2= component3= component4= component5= component6= density= density_notes= dependency_liability= drug_name= elimination_half-life= engvar= excretion= image2= imageL= imageR= image= image_class= image_class2= image_classL= image_classR= Jmol= legal_AU= legal_BR= legal_CA= legal_DE= legal_EU= legal_NZ= legal_UK= legal_UN= legal_US= legal_AU_comment= legal_BR_comment= legal_CA_comment= legal_DE_comment= legal_UK_comment= legal_NZ_comment= legal_US_comment= legal_UN_comment= legal_EU_comment= legal_status= licence_CA= licence_EU= licence_US= license_CA= license_EU= license_US= mab_type= melting_high= melting_notes= melting_point= metabolism= metabolites= molecular_weight= molecular_weight_round= molecular_weight_unit= molecular_weight_ref= molecular_weight_comment= onset= pregnancy_AU= pregnancy_AU_comment= pregnancy_category= protein_bound= routes_of_administration= SMILES= smiles= solubility= sol_units= source= specific_rotation= synonyms= target= tradename= type= vaccine_type= verifiedrevid= width2= widthL= widthR= width= AAN= BAN= JAN= USAN= source_tissues= target_tissues= receptors= agonists= antagonists= precursor= biosynthesis= gt_target_gene= gt_vector= gt_nucleic_acid_type= gt_editing_method= gt_delivery_method= sec_combustion= Ac=Ag=Al=Am=Ar=As=At=Au=B=Ba=Be=Bh=Bi=Bk=Br=C=Ca=Cd=Ce=Cf=Cl=Cm=Cn=Co=Cr=Cs=Cu= D=Db=Ds=Dy=Er=Es=Eu=F=Fe=Fl=Fm=Fr=Ga=Gd=Ge=H=He=Hf=Hg=Ho=Hs=I=In=Ir=K=Kr=La=Li=Lr=Lu=Lv= Mc=Md=Mg=Mn=Mo=Mt=N=Na=Nb=Nd=Ne=Nh=Ni=No=Np=O=Og=Os=P=Pa=Pb=Pd=Pm=Po=Pr=Pt=Pu=Ra=Rb=Re=Rf=Rg=Rh=Rn=Ru=S=Sb=Sc=Se=Sg=Si=Sm=Sn=Sr=Ta=Tb=Tc=Te=Th=Ti=Tl=Tm=Ts=U=V=W=Xe=Y=Yb=Zn=Zr= index_label= index2_label= index_comment= index2_comment= CAS_number2= CAS_supplemental2= ATC_prefix2= ATC_suffix2= ATC_supplemental2= PubChem2= PubChemSubstance2= IUPHAR_ligand2= DrugBank2= ChemSpiderID2= UNII2= KEGG2= ChEBI2= ChEMBL2= PDB_ligand2= NIAID_ChemDB2= SMILES2= smiles2= StdInChI2= StdInChIKey2= CAS_number2_Ref= ChEBI2_Ref= ChEMBL2_Ref= ChemSpiderID2_Ref= DrugBank2_Ref= KEGG2_Ref= StdInChI2_Ref= StdInChIKey2_Ref= UNII2_Ref= DTXSID2= QID= QID2=PLLR= pregnancy_US= pregnancy_US_comment= |cat=Pages using infobox drug with unknown parameters |format=0|errNS=0

|preview=

}}{{Infobox drug/maintenance categoriesTemplate:Yesno | drug_name = | INN = | _drugtype =

| _has_physiological_data= | _has_gene_therapy=

| vaccine_type= | mab_type= | _number_of_combo_chemicals={{#invoke:ParameterCount |main |component1 |component2 |component3 |component4|component5|component6 }} | _vaccine_data= | _mab_data= | _mab_vaccine_data= | _mab_other_data=222428CN(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]341S/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./s1XQTWDDCIUJNLTR-CVHRZJFOSA-NTemplate:StdinchiciteTemplate:Stdinchicite | _combo_data= | _physiological_data= | _clinical_data=Template:Drugs.coma682063Doxycycline DBy mouth, intravenous<ref name=AHFS2015/>Doxy, Doryx, Vibramycin, othersJ01Template:ATC | _legal_data=S4POMRx-only

| _other_data=(4S,4aR,5S,5aR,6R,12aS)-4-(Dimethylamino)-3,5,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydrotetracene-2-carboxamide

| _image_0_or_2 = Doxycycline structure.svgDoxycycline ball-and-stick model from xtal 2012.png | _image_LR =

| _datapage = Doxycycline (data page) | _vaccine_target={{#ifeq: | vaccine | | _type_not_vaccine }} | _legal_all=S4POMRx-only | _ATC_prefix_supplemental=J01Template:ATC | _has_EMA_link = | CAS_number=564-25-0 | PubChem=Doxycycline | ChemSpiderID=10482106 | ChEBI=60648 | ChEMBL=1433 | DrugBank=DB00254 | KEGG=D07876 | _hasInChI_or_Key={{#if: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./s1XQTWDDCIUJNLTR-CVHRZJFOSA-N |yes}} | UNII=334895S862 | _hasJmol02 = |_hasMultipleCASnumbers = |_hasMultiplePubChemCIDs = |_hasMultipleChEBIs =

| _countSecondIDs={{#invoke:ParameterCount |main |CAS_number2 |ATC_prefix2 |PubChem2 |PubChemStructure2 |IUPHAR_ligand2 |DrugBank2 |ChemSpiderID2 |UNII2 |KEGG2 |ChEBI2 |ChEMBL2 |PDB_ligand2 |NIAID_ChemDB2 |SMILES2 |smiles2 |StdInChI2 |StdInChIKey2 |DTXCID2}} | _countIndexlabels={{#invoke:ParameterCount |main |index_label |index2_label}} | _trackListSortletter= |QID = |QID2 = |Verifiedfields=changed |Watchedfields=changed |verifiedrevid=477166918}}

Doxycycline is a broad-spectrum antibiotic of the tetracycline class used in the treatment of infections caused by bacteria and certain parasites.<ref name=AHFS2015/> It is used to treat bacterial pneumonia, acne, chlamydia infections, Lyme disease, cholera, typhus, and syphilis.<ref name=AHFS2015/> It is also used to prevent malaria.<ref name="Fit for Travel">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="Centers for Disease Control and Prevention-2023">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Doxycycline may be taken by mouth or by injection into a vein.<ref name=AHFS2015>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

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">Template:Cite journal</ref><ref name="Schlagenhauf-Lawlor-2008">Template:Cite book</ref>

File:Doxycycline hyclate substance photo2.jpg

Doxycycline hyclate

Doxycycline was patented in 1957 and came into commercial use in 1967.<ref name="Fischer-2006">Template:Cite book</ref><ref name="Corey-2013">Template:Cite book</ref> It is on the World Health Organization's List of Essential Medicines.<ref name="WHO23rd">Template:Cite book</ref> Doxycycline is available as a generic medicine.<ref name=AHFS2015/><ref name="Hamilton-2011">Template:Cite book</ref> In 2022, it was the 68th most commonly prescribed medication in the United States, with more than 9Template:Nbspmillion prescriptions.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Medical uses

File:Doxycycline 100mg capsules.jpg

Generic 100 mg doxycycline capsules

File:Doksiciklin 100 091208.jpg

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">Template:Cite journal</ref><ref name="pmid345730">Template:Cite journal</ref> severe acne, rosacea,<ref name="safety-2009">Template:Cite journal</ref><ref name="pmid16411105">Template:Cite journal</ref><ref name="pmid9006372">Template:Cite journal</ref> and rickettsial infections.<ref name="pmid19061755">Template:Cite journal</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">Template:Cite journal</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">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="Stoddard-2015">Template:Cite book</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">Template:Cite journal</ref><ref name="pmid7793869">Template:Cite journal</ref><ref name="pmid11450675">Template:Cite journal</ref><ref name="pmid8035916">Template:Cite journal</ref> ehrlichiosis,<ref name="pmid8900357">Template:Cite journal</ref><ref name="pmid11234985">Template:Cite journal</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">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="FDA oralsusp label">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

• Rocky Mountain spotted fever, typhus fever and the typhus group, scrub typhus,<ref name="pmid38110855">Template:Cite journal</ref> Q fever,<ref name="pmid23535757">Template:Cite journal</ref> rickettsialpox, and tick fevers caused by Rickettsia,<ref name="pmid27172113">Template:Cite journal</ref><ref name="Schutze-2010">Template:Cite news</ref><ref name="Spotted fever group rickettsial disease DermNet 2024">{{#invoke:citation/CS1|citation

|CitationClass=web }}</ref>

• respiratory tract infections caused by Mycoplasma pneumoniae,<ref name="pmid22972867">Template:Cite journal</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 infections 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 S. faecalis specimens have developed resistance to the tetracycline group of antibiotics. Up to 57% of P. acnes strains developed resistance to doxycycline.<ref name="pmid24721547">Template:Cite journal</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 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">Template:Cite journal</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 mg twice daily for three months in a meta-analysis published in 2011.<ref name="pmid21417590">Template:Cite journal</ref> SDD is also used to treat skin conditions such as acne and rosacea,<ref name="safety-2009"/><ref name="pmid25919144">Template:Cite journal</ref><ref name="pmid25597924">Template:Cite journal</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">Template:Cite journal</ref>

Doxycycline is used as an adjunctive therapy for acute intestinal amebiasis.<ref name="drugs-com">{{#invoke:citation/CS1|citation |CitationClass=web }}</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">Template:Cite journal</ref><ref name="Samuel-2023">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="pmid38118022">Template:Cite journal</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">Template:Cite journal</ref>

Appropriate use of doxycycline for PEP is supported by guidelines from the US Centers for Disease Control and Prevention (CDC)<ref name="CDC-2023-Gudelines-Post-Exposure">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> and the Australasian Society for HIV Medicine.<ref name="Australasian Society for HIV Medicine 2023">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="Highleyman-2024">{{#invoke:citation/CS1|citation |CitationClass=web }}</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">Template:Cite journal</ref>

Antimalarial

Doxycycline is active against the erythrocytic stages of Plasmodium falciparum but not against the gametocytes of P. falciparum.<ref name="DailyMed-2020">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> It is used to prevent malaria.<ref name="CDC">{{#invoke:citation/CS1|citation |CitationClass=web }}</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">Template:Cite journal</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">Template:Cite journal</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">Template:Cite journal</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 P. falciparum or following intravenous treatment of severe malaria.<ref name="World Health Organization-2015">Template:Cite book</ref>

Antihelminthic

Doxycycline kills the 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.<ref name="pmid12684759">Template:Cite journal</ref> Field trials in 2005 showed an eight-week course of doxycycline almost eliminates the release of microfilariae.<ref name="pmid15964448">Template:Cite journal</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">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

• Chlamydia psittaci: 0.03 μg/mL<ref name="toku-e.com"/>
• Mycoplasma pneumoniae: 0.016–2 μg/mL<ref name="toku-e.com"/>
• Streptococcus pneumoniae: 0.06–32 μg/mL<ref name="toku-e.com"/>

Sclerotherapy

Doxycycline is also used for sclerotherapy in slow-flow vascular malformations, namely venous and lymphatic malformations, as well as post-operative lymphoceles.<ref name="Kaufman-2013">Template:Cite book</ref>

Off-label use

Doxycycline has found off-label use in the treatment of transthyretin amyloidosis (ATTR). Together with tauroursodeoxycholic acid, doxycycline appears to be a promising combination capable of disrupting transthyretin TTR fibrils in existing amyloid deposits of ATTR patients.<ref name="Muller-2020">Template:Cite journal</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 sequestrants 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">{{#invoke:citation/CS1|citation |CitationClass=web }}</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 retinoids are contraindications, as both tetracyclines and retinoids can cause intracranial hypertension (increased pressure around the brain) in rare cases.<ref name="AC">Template:Cite book</ref>

Pregnancy and lactation

Doxycycline is categorized by the FDA as a class D drug in pregnancy. Doxycycline crosses into breastmilk.<ref name="pmid12431134">Template:Cite journal</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">Template:Cite journal</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">Template:Cite journal</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 CDC recommends the use of doxycycline for treatment of Q fever and tick-borne rickettsial diseases in young children; others advocate for its use in malaria.<ref name="pmid28407772">Template:Cite journal</ref>

Adverse effects

Adverse effects are similar to those of other members of the tetracycline antibiotic group. Doxycycline can cause gastrointestinal upset.<ref name="Hitchings-2015">Template:Cite book</ref><ref name="pmid3055652">Template:Cite journal</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">Template:Cite journal</ref> Doxycycline is less likely than other antibiotic drugs to cause Clostridioides difficile colitis.<ref name="pmid27025622">Template:Cite journal</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">Template:Cite journal</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">Template:Cite journal</ref> In one large 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">Template:Cite journal</ref>

Interactions

Previously, doxycycline was believed to impair the effectiveness of many types of hormonal contraception due to 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">Template:Cite journal</ref><ref name="pmid12436822">Template:Cite journal</ref><ref name="pmid15564203">Template:Cite journalTemplate:Dead link</ref>

Pharmacology

Template:See also Doxycycline, like other tetracycline antibiotics, is bacteriostatic. It works by preventing bacteria from reproducing by inhibiting protein synthesis.<ref name="Flower-2012">Template:Cite book</ref>

Doxycycline is highly 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 elimination half-life. It is also prevented from accumulating in the kidneys of patients with kidney failure due to the compensatory excretion in faeces.<ref name="pmid3055652"/><ref name="pmid23966509">Template:Cite journal</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">Template:Cite journal</ref>

Mechanism of action

Doxycycline is a broad-spectrum 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 acids cannot be added to 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">{{#invoke:citation/CS1|citation |CitationClass=web }}</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 tissues and body fluids. 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">Template:Cite book</ref><ref name="Drugs.com">Doxycycline Template:Drugs.com. 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">Template:Cite book</ref>

Doxycycline metabolism is negligible. It is actively excreted into the gut (in part via the gallbladder, in part directly from blood vessels), where some of it is inactivated by forming chelates. 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 ± 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">Template:Cite book</ref><ref name="ReferenceA">Template:Cite book</ref> causing Fanconi syndrome.<ref name="ReferenceB">Template:Cite book</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 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> −110° cm³/dm·g in 0.01 N methanolic hydrochloric acid.<ref name="Arzneistoff-Profile" />

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 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 class of antibiotics.<ref name="pmid22191524">Template:Cite journal</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">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> that was not resolved until 1983; at the time it was the largest litigated patent case in US history.<ref name=LitigationEnd>{{#invoke:citation/CS1|citation |CitationClass=web }}</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">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Companies involved included an unnamed major generics manufacturer that ceased production in February 2013, Teva (which ceased production in May 2013), Mylan, Actavis, and Hikma Pharmaceuticals.<ref name="American Society of Health-System Pharmacists.-2014">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="American Society of Health-System Pharmacists.-2014-2">{{#invoke:citation/CS1|citation |CitationClass=web }}</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">{{#invoke:citation/CS1|citation |CitationClass=web }}</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">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="Rosenthal-2014">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="Palmer-2014">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> before decreasing again.<ref name="Costco Drug Information">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref name="GoodRx">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Society and culture

Doxycycline is available worldwide under many brand names.<ref name="drugs.com">{{#invoke:citation/CS1|citation |CitationClass=web }}</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">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Research

Medical conditions

Research areas on the application of doxycycline include the following medical conditions:

• macular degeneration;<ref name="pmid23971874">Template:Cite journal</ref>
• rheumatoid arthritis instead of minocycline (both of which have demonstrated modest efficacy for this disease).<ref name="pmid21723947">Template:Cite journal</ref>

File:Tet-ON inducible transgene expression cells.svg

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">{{#invoke:citation/CS1|citation |CitationClass=web }}</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">Template:Cite journal</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">Template:Cite journal</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 metalloproteinases (MMPs) while increasing the production of anti-inflammatory cytokines 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 (NF-κB) pathway, which is responsible for upregulating several inflammatory mediators in various cells, including neurons; therefore, it is studied as a potential agent for treating neuroinflammation.<ref name="pmid33568043">Template:Cite journal</ref><ref name="pmid28516469">Template:Cite journal</ref><ref name="pmid17315050">Template:Cite journal</ref>

A potential explanation of doxycycline's anti-inflammatory properties is its inhibition of matrix metalloproteinases (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">Template:Cite book</ref><ref name="pmid29034777">Template:Cite journal</ref><ref name="pmid27619752">Template:Cite journal</ref><ref name="pmid36759188">Template:Cite journal</ref> Doxycycline has been shown to inhibit MMPs,<ref name="pmid38649625">Template:Cite journal</ref> including matrilysin (MMP7), by interacting with the structural zinc atom and/or calcium atoms within the structural metal center of the protein.<ref name="pmid14681644">Template:Cite journal</ref><ref name="pmid15665254">Template:Cite journal</ref><ref name="pmid28662828">Template:Cite journal</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 vulgaris and rosacea.<ref name="pmid34812859">Template:Cite journal</ref><ref name="pmid33133338">Template:Cite journal</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">Template:Cite journal</ref><ref name="pmid27538054">Template:Cite journal</ref> or "subantimicrobial",<ref name="pmid36407641">Template:Cite journal</ref><ref name="pmid34161892">Template:Cite journal</ref><ref name="pmid14673277">Template:Cite journal</ref><ref name="safety-2009"/> or whether doxycycline's anti-inflammatory effects, which reduce inflammation in acne vulgaris and rosacea, including ocular rosacea,<ref name="pmid38361192"/> contribute more to its therapeutic effectiveness against these skin conditions.<ref name="pmid32401726">Template:Cite journal</ref> Subantimicrobial-dose doxycycline (SDD) can still have a bacteriostatic effect, especially when taken for extended periods, such as several months in treating acne and rosacea.<ref name="pmid37521754">Template:Cite journal</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">Template:Cite journal</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 ROS by inflammatory cells; these ROS contribute toward exacerbating symptoms. Doxycycline may reduce ROS levels and induce antioxidant activity because it directly scavenges hydroxyl radicals and singlet oxygen, helping minimize tissue damage caused by highly oxidative and inflammatory conditions.<ref name="pmid1357852">Template:Cite journal</ref> Studies have shown that SDD can effectively improve acne and rosacea symptoms,<ref name="pmid26897386">Template:Cite journal</ref> probably without inducing antibiotic resistance.<ref name="pmid18004018">Template:Cite journal</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 periodontitis.<ref name="pmid12900822">Template:Cite journal</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">Template:Cite journal</ref><ref name="pmid37759467">Template:Cite journal</ref><ref name="pmid37751595">Template:Cite journal</ref> Doxycycline has been studied in various immunological disorders, including rheumatoid arthritis, lupus, and periodontitis.<ref name="pmid35742496">Template:Cite journal</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">Template:Cite journal</ref><ref name="pmid34899697">Template:Cite journal</ref><ref name="pmid35294307">Template:Cite journal</ref><ref name="pmid36869773">Template:Cite journal</ref>

Doxycycline is also studied for its neuroprotective properties which are associated with antioxidant, 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 axonal and synaptic proteins.<ref name="pmid30798507">Template:Cite journal</ref><ref name="pmid31879858">Template:Cite journal</ref> Axonal degeneration and synaptic loss are key events at the early stages of neurodegeneration and precede neuronal death in neurodegenerative diseases, including Parkinson's disease (PD). Therefore, the regeneration of the axonal and synaptic network might be beneficial in PD.<ref name="pmid36843128">Template:Cite journal</ref> It has been demonstrated that doxycycline mimics nerve growth factor (NGF) signaling in 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 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">Template:Cite journal</ref><ref name="pmid36343696">Template:Cite journal</ref>

After a large-scale trial showed no benefit of using doxycycline in treating [[COVID-19|COVIDTemplate:Nbhyph19]], the UK's National Institute for Health and Care Excellence (NICE) updated its guidance to not recommend the medication for the treatment of COVIDTemplate:Nbhyph19.<ref name="NIHR Evidence-2022">Template:Cite journal</ref><ref name="pmid34329624">Template:Cite journal</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">Template:Cite journal</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">Template:Cite journal</ref><ref name="pmid34584416">Template:Cite journal</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">Template:Cite journal</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 class of antibiotics are often used as research reagents 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">Template:Cite journal</ref><ref name="pmid26475870">Template:Cite journal</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 cultures.<ref name="pmid7792603">Template:Cite journal</ref> Doxycycline is more stable than tetracycline for this purpose.<ref name="pmid7792603" /> At subantimicrobial doses, doxycycline is an inhibitor of matrix metalloproteases, and has been used in various experimental systems for this purpose, such as for recalcitrant recurrent corneal erosions.<ref name="pmid11438047">Template:Cite journal</ref>