Doxycycline is a

broad-spectrum A broad-spectrum antibiotic is an antibiotic that acts on the two major bacterial groups, Gram-positive and Gram-negative, or any antibiotic that acts against a wide range of disease-causing bacteria. These medications are used when a bacterial in ...

antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...

of the tetracycline class used in the treatment of infections caused by

bacteria Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of Prokaryote, prokaryotic microorganisms. Typically a few micr ...

and certain

parasites Parasitism is a close relationship between species, where one organism, the parasite, lives (at least some of the time) on or inside another organism, the host, causing it some harm, and is adapted structurally to this way of life. The en ...

. It is used to treat

bacterial pneumonia Bacterial pneumonia is a type of pneumonia caused by bacterial infection. Types Gram-positive '' Streptococcus pneumoniae'' () is the most common bacterial cause of pneumonia in all age groups except newborn infants. ''Streptococcus pneumoniae ...

acne Acne ( ), also known as ''acne vulgaris'', is a long-term Cutaneous condition, skin condition that occurs when Keratinocyte, dead skin cells and Sebum, oil from the skin clog hair follicles. Typical features of the condition include comedo, ...

chlamydia infection Chlamydia, or more specifically a chlamydia infection, is a sexually transmitted infection caused by the bacterium ''Chlamydia trachomatis''. Most people who are infected have no symptoms. When symptoms do appear, they may occur only several w ...

Lyme disease Lyme disease, also known as Lyme borreliosis, is a tick-borne disease caused by species of ''Borrelia'' bacteria, Disease vector, transmitted by blood-feeding ticks in the genus ''Ixodes''. It is the most common disease spread by ticks in th ...

cholera Cholera () is an infection of the small intestine by some Strain (biology), strains of the Bacteria, bacterium ''Vibrio cholerae''. Symptoms may range from none, to mild, to severe. The classic symptom is large amounts of watery diarrhea last ...

typhus Typhus, also known as typhus fever, is a group of infectious diseases that include epidemic typhus, scrub typhus, and murine typhus. Common symptoms include fever, headache, and a rash. Typically these begin one to two weeks after exposu ...

, and

syphilis Syphilis () is a sexually transmitted infection caused by the bacterium ''Treponema pallidum'' subspecies ''pallidum''. The signs and symptoms depend on the stage it presents: primary, secondary, latent syphilis, latent or tertiary. The prim ...

. It is also used to prevent

malaria Malaria is a Mosquito-borne disease, mosquito-borne infectious disease that affects vertebrates and ''Anopheles'' mosquitoes. Human malaria causes Signs and symptoms, symptoms that typically include fever, Fatigue (medical), fatigue, vomitin ...

. Doxycycline may be taken

by mouth Oral administration is a route of administration whereby a substance is taken through the Human mouth, mouth, swallowed, and then processed via the digestive system. This is a common route of administration for many medications. Oral administ ...

or by

injection into a vein Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutr ...

. Common side effects include

diarrhea Diarrhea (American English), also spelled diarrhoea or diarrhœa (British English), is the condition of having at least three loose, liquid, or watery bowel movements in a day. It often lasts for a few days and can result in dehydration d ...

, nausea, vomiting, abdominal pain, and an increased risk of

sunburn Sunburn is a form of radiation burn that affects living tissue, such as skin, that results from an overexposure to ultraviolet (UV) radiation, usually from the Sun. Common symptoms in humans and other animals include red or reddish skin tha ...

. Use during pregnancy is not recommended. Like other agents of the tetracycline class, it either slows or kills bacteria by inhibiting protein production. It kills malaria by targeting a plastid organelle, the

apicoplast An apicoplast is a derived non-photosynthetic plastid found in most Apicomplexa, including ''Toxoplasma gondii'', and ''Plasmodium falciparum'' and other ''Plasmodium'' spp. (parasites causing malaria), but not in others such as ''Cryptosporidium' ...

Doxycycline was patented in 1957 and came into commercial use in 1967. It is on the

World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...

. Doxycycline is available as a

generic medicine A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ch ...

. In 2022, it was the 68th most commonly prescribed medication in the United States, with more than 9million prescriptions.

Medical uses

In addition to the general indications for all members of the

tetracycline antibiotics Tetracyclines are a group of broad-spectrum antibiotic compounds that have a common basic structure and are either isolated directly from several species of ''Streptomyces'' bacteria or produced semi-synthetically from those isolated compounds. ...

group, doxycycline is frequently used to treat

, chronic

prostatitis Prostatitis is an umbrella term for a variety of medical conditions that incorporate bacterial and non-bacterial origin illnesses in the pelvic region. In contrast with the plain meaning of the word (which means "inflammation of the prostate"), the ...

sinusitis Sinusitis, also known as rhinosinusitis, is an inflammation of the mucous membranes that line the sinuses resulting in symptoms that may include production of thick nasal mucus, nasal congestion, facial congestion, facial pain, facial pressure ...

pelvic inflammatory disease Pelvic inflammatory disease (PID), also known as pelvic inflammatory disorder, is an infection of the upper part of the female reproductive system, mainly the uterus, fallopian tubes, and ovaries, and inside of the pelvis. Often, there may be no ...

, severe

rosacea Rosacea is a long-term skin condition that typically affects the face. It results in redness, pimples, swelling, and small and superficial dilated blood vessels. Often, the nose, cheeks, forehead, and chin are most involved. A red, en ...

, and rickettsial infections. 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. In Canada, in 2004, doxycycline was considered a first-line treatment for

chlamydia Chlamydia, or more specifically a chlamydia infection, is a sexually transmitted infection caused by the bacterium ''Chlamydia trachomatis''. Most people who are infected have no symptoms. When symptoms do appear, they may occur only several w ...

and

non-gonococcal urethritis Nongonococcal urethritis (NGU) is inflammation of the urethra that is not caused by gonorrheal infection. For treatment purposes, doctors usually classify infectious urethritis in two categories: gonococcal urethritis, caused by gonorrhea, and ...

and with cefixime for uncomplicated

gonorrhea Gonorrhoea or gonorrhea, colloquially known as the clap, is a sexually transmitted infection (STI) caused by the bacterium ''Neisseria gonorrhoeae''. Infection may involve the genitals, mouth, or rectum. Gonorrhea is spread through sexual c ...

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 ''Moraxella catarrhalis'' is a fastidious, nonmotile, Gram-negative, aerobic, oxidase-positive diplococcus that can cause infections of the respiratory system, middle ear, eye, central nervous system, and joints of humans. It causes the in ...

'', '' Brucella melitensis'', ''

Chlamydia pneumoniae Chlamydia, or more specifically a chlamydia infection, is a sexually transmitted infection caused by the bacterium ''Chlamydia trachomatis''. Most people who are infected have no symptoms. When symptoms do appear, they may occur only several w ...

'', and ''

Mycoplasma pneumoniae ''Mycoplasma pneumoniae'' is a species of very small-cell bacteria that lack a cell wall, in the class Mollicutes. ''M. pneumoniae'' is a human pathogen that causes the disease Mycoplasma pneumonia, a form of atypical bacterial pneumonia related ...

''. 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 ''Mycoplasma hominis'' (also known as ''Metamycoplasma hominis'') is a species of bacteria in the genus '' Mycoplasma''. ''M.hominis'' has the ability to penetrate the interior of human cells. Along with ureaplasmas, mycoplasmas are the smallest ...

'', and ''

Pseudomonas aeruginosa ''Pseudomonas aeruginosa'' is a common Bacterial capsule, encapsulated, Gram-negative bacteria, Gram-negative, Aerobic organism, aerobic–facultative anaerobe, facultatively anaerobic, Bacillus (shape), rod-shaped bacteria, bacterium that can c ...

'', have shown resistance to doxycycline. It is also effective against ''

Yersinia pestis ''Yersinia pestis'' (''Y. pestis''; formerly ''Pasteurella pestis'') is a Gram-negative bacteria, gram-negative, non-motile bacteria, non-motile, coccobacillus Bacteria, bacterium without Endospore, spores. It is related to pathogens ''Yer ...

'' (the infectious agent of

bubonic plague Bubonic plague is one of three types of Plague (disease), plague caused by the Bacteria, bacterium ''Yersinia pestis''. One to seven days after exposure to the bacteria, flu-like symptoms develop. These symptoms include fever, headaches, and ...

), and is prescribed for the treatment of

, ehrlichiosis, and

Rocky Mountain spotted fever Rocky Mountain spotted fever (RMSF) is a bacterial disease spread by ticks. It typically begins with a fever and headache, which is followed a few days later with the development of a rash. The rash is generally Petechial rash, made up of small s ...

. Specifically, doxycycline is indicated for treatment of the following diseases: *

fever and the typhus group,

scrub typhus Scrub typhus or bush typhus is a form of typhus caused by the intracellular parasite '' Orientia tsutsugamushi'', a Gram-negative α-proteobacterium of family Rickettsiaceae first isolated and identified in 1930 in Japan.

Q fever Q fever or query fever is a disease caused by infection with ''Coxiella burnetii'', a bacterium that affects humans and other animals. This organism is uncommon, but may be found in cattle, sheep, goats, and other domestic mammals, including ...

rickettsialpox Rickettsialpox is a mite-borne infectious illness caused by bacteria of the genus '' Rickettsia'' ('' Rickettsia akari''). Physician Robert Huebner and self-trained entomologist Charles Pomerantz played major roles in identifying the cause of ...

, and tick fevers caused by ''

Rickettsia ''Rickettsia'' is a genus of nonmotile, gram-negative, nonspore-forming, highly pleomorphic bacteria that may occur in the forms of cocci (0.1 μm in diameter), bacilli (1–4 μm long), or threads (up to about 10 μm long). The genus was n ...

'', * respiratory tract infections caused by ''

'', *

Lymphogranuloma venereum Lymphogranuloma venereum (LGV; also known as climatic bubo, Durand–Nicolas–Favre disease, poradenitis inguinale, lymphogranuloma inguinale, and strumous bubo) is a sexually transmitted infection caused by the invasive serovars L1, L2, L2a, ...

trachoma Trachoma is an infectious disease caused by bacterium '' Chlamydia trachomatis''. The infection causes a roughening of the inner surface of the eyelids. This roughening can lead to pain in the eyes, breakdown of the outer surface or cornea ...

, inclusion conjunctivitis, and uncomplicated urethral, endocervical, or rectal infections in adults caused by ''

Chlamydia trachomatis ''Chlamydia trachomatis'' () is a Gram-negative, Anaerobic organism, anaerobic bacterium responsible for Chlamydia infection, chlamydia and trachoma. ''C. trachomatis'' exists in two forms, an extracellular infectious elementary body (EB) and an ...

'', *

psittacosis Psittacosis—also known as parrot fever, and ornithosis—is a zoonotic infectious disease in humans caused by a bacterium called '' Chlamydia psittaci'' and contracted from infected parrots, such as macaws, cockatiels, and budgerigars, and ...

, *

caused by '' Ureaplasma urealyticum'', *

relapsing fever Relapsing fever is a vector-borne disease caused by infection with certain bacteria in the genus '' Borrelia'', which is transmitted through the bites of lice, soft-bodied ticks (genus '' Ornithodoros''), or hard-bodied ticks (Genus Ixodes). ...

due to ''

Borrelia recurrentis ''Borrelia recurrentis'' is a species of ''Borrelia'', a spirochaete bacterium associated with relapsing fever Relapsing fever is a vector-borne disease caused by infection with certain bacteria in the genus '' Borrelia'', which is transmitted t ...

'', *

chancroid Chancroid ( ) is a bacterial sexually transmitted infection characterized by painful sores on the genitalia. Chancroid is known to spread from one individual to another solely through sexual contact. However, there have been reports of accidenta ...

caused by '' Haemophilus ducreyi'', * plague due to ''

'', *

tularemia Tularemia, also known as rabbit fever, is an infectious disease caused by the bacterium '' Francisella tularensis''. Symptoms may include fever, skin ulcers, and enlarged lymph nodes. Occasionally, a form that results in pneumonia or a throat ...

, *

, * '' campylobacter fetus'' infections, *

brucellosis Brucellosis is a zoonosis spread primarily via ingestion of raw milk, unpasteurized milk from infected animals. It is also known as undulant fever, Malta fever, and Mediterranean fever. The bacteria causing this disease, ''Brucella'', are small ...

caused by ''

Brucella ''Brucella'' is a genus of Gram-negative bacterium, bacteria, named after David Bruce (microbiologist), David Bruce (1855–1931). They are small (0.5 to 0.7 by 0.6 to 1.5 μm), non-Bacterial capsule, encapsulated, non-motile, facultatively ...

'' species (in conjunction with

streptomycin Streptomycin is an antibiotic medication used to treat a number of bacterial infections, including tuberculosis, Mycobacterium avium complex, ''Mycobacterium avium'' complex, endocarditis, brucellosis, Burkholderia infection, ''Burkholderia'' i ...

), * bartonellosis, * granuloma inguinale (''

Klebsiella ''Klebsiella'' is a genus of Gram-negative, oxidase-negative, rod-shaped bacteria with a prominent polysaccharide-based capsule. ''Klebsiella'' is named after German-Swiss microbiologist Edwin Klebs (1834–1913). Carl Friedlander described ' ...

'' species), *

(''

Borrelia ''Borrelia'' is a genus of bacteria of the spirochete phylum. Several species cause Lyme disease, also called Lyme borreliosis, a zoonotic, vector-borne disease transmitted by ticks. Other species of ''Borrelia'' cause relapsing fever, and are ...

'' species).

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 Gram-negative bacteria are bacteria that, unlike gram-positive bacteria, do not retain the Crystal violet, crystal violet stain used in the Gram staining method of bacterial differentiation. Their defining characteristic is that their cell envelo ...

: * ''

Escherichia coli ''Escherichia coli'' ( )Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. is a gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Escherichia'' that is commonly fo ...

'' infections, * '' Enterobacter aerogenes'' (formerly ''Aerobacter aerogenes'') infections, * ''

Shigella ''Shigella'' is a genus of bacteria that is Gram negative, facultatively anaerobic, non–spore-forming, nonmotile, rod shaped, and is genetically nested within ''Escherichia''. The genus is named after Kiyoshi Shiga, who discovered it in 1 ...

'' species infections, * ''

Acinetobacter ''Acinetobacter'' is a genus of Gram-negative bacteria belonging to the wider class of Gammaproteobacteria. ''Acinetobacter'' species are oxidase-negative, exhibit twitching motility, and occur in pairs under magnification. They are important ...

'' species (formerly ''Mima'' species and ''Herellea'' species) infections, * respiratory tract infections caused by ''

Haemophilus influenzae ''Haemophilus influenzae'' (formerly called Pfeiffer's bacillus or ''Bacillus influenzae'') is a Gram-negative, Motility, non-motile, Coccobacillus, coccobacillary, facultative anaerobic organism, facultatively anaerobic, Capnophile, capnophili ...

'', * respiratory tract and

urinary tract infection A urinary tract infection (UTI) is an infection that affects a part of the urinary tract. Lower urinary tract infections may involve the bladder (cystitis) or urethra (urethritis) while upper urinary tract infections affect the kidney (pyel ...

s caused by ''

'' species.

Gram-positive bacteria specific indications

Some

Gram-positive bacteria In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall. The Gram stain ...

have developed resistance to doxycycline. Up to 44% of ''

Streptococcus pyogenes ''Streptococcus pyogenes'' is a species of Gram-positive, aerotolerant bacteria in the genus '' Streptococcus''. These bacteria are extracellular, and made up of non-motile and non-sporing cocci (round cells) that tend to link in chains. They ...

'' 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. When bacteriologic testing indicates appropriate susceptibility to the drug, doxycycline may be used to treat these infections caused by

: * upper respiratory infections caused by ''

Streptococcus pneumoniae ''Streptococcus pneumoniae'', or pneumococcus, is a Gram-positive, spherical bacteria, hemolysis (microbiology), alpha-hemolytic member of the genus ''Streptococcus''. ''S. pneumoniae'' cells are usually found in pairs (diplococci) and do not f ...

'' (formerly ''Diplococcus pneumoniae''), * skin and soft tissue infections caused by ''

Staphylococcus aureus ''Staphylococcus aureus'' is a Gram-positive spherically shaped bacterium, a member of the Bacillota, and is a usual member of the microbiota of the body, frequently found in the upper respiratory tract and on the skin. It is often posi ...

'', including methicillin-resistant ''Staphylococcus aureus'' infections, *

anthrax Anthrax is an infection caused by the bacterium '' Bacillus anthracis'' or ''Bacillus cereus'' biovar ''anthracis''. Infection typically occurs by contact with the skin, inhalation, or intestinal absorption. Symptom onset occurs between one ...

caused by ''

Bacillus anthracis ''Bacillus anthracis'' is a gram-positive and rod-shaped bacterium that causes anthrax, a deadly disease to livestock and, occasionally, to humans. It is the only permanent (obligate) pathogen within the genus ''Bacillus''. Its infection is a ty ...

'' infection.

Specific applications of doxycycline when penicillin is contraindicated

When penicillin is contraindicated, doxycycline can be used to treat: *

caused by ''

Treponema pallidum ''Treponema pallidum'', formerly known as ''Spirochaeta pallida'', is a Microaerophile, microaerophilic, Gram-negative bacteria, gram-negative, spirochaete bacterium with subspecies that cause the diseases syphilis, bejel (also known as endemic ...

'', *

yaws Yaws is a tropical infection of the skin, bones, and joints caused by the spirochete bacterium ''Treponema pallidum pertenue''. The disease begins with a round, hard swelling of the skin, in diameter. The center may break open and form an ulc ...

caused by '' Treponema pertenue'', *

listeriosis Listeriosis is a bacterial infection most commonly caused by '' Listeria monocytogenes'', although '' L. ivanovii'' and '' L. grayi'' have been reported in certain cases. Listeriosis can cause severe illness, including severe sepsis, me ...

due to ''

Listeria monocytogenes ''Listeria monocytogenes'' is the species of pathogenic bacteria that causes the infection listeriosis. It is a facultative anaerobic bacterium, capable of surviving in the presence or absence of oxygen. It can grow and reproduce inside the ho ...

'', * Vincent's infection caused by ''

Fusobacterium ''Fusobacterium'' is a genus of obligate anaerobic, Gram-negative, non-sporeforming bacteria belonging to Gracilicutes. Individual cells are slender, rod-shaped bacilli with pointed ends. ''Fusobacterium'' was discovered in 1900 by Courmont an ...

fusiforme'', *

actinomycosis Actinomycosis is a rare infectious disease, infectious bacterial disease caused by the gram-positive ''Actinomyces'' species. The name refers to ray-like appearance of the organisms in the granules. About 70% of infections are due to either ''Acti ...

caused by '' Actinomyces israelii'', * infections caused by ''

Clostridium ''Clostridium'' is a genus of anaerobic, Gram-positive bacteria. Species of ''Clostridium'' inhabit soils and the intestinal tracts of animals, including humans. This genus includes several significant human pathogens, including the causative ...

'' species.

Use as adjunctive therapy

Doxycycline may also be used as adjunctive therapy for severe

. Subantimicrobial-dose doxycycline (SDD) is widely used as an adjunctive treatment to scaling and root planing for

periodontitis Periodontal disease, also known as gum disease, is a set of inflammatory conditions affecting the tissues surrounding the teeth. In its early stage, called gingivitis, the gums become swollen and red and may bleed. It is considered the main c ...

. 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 Meta-analysis is a method of synthesis of quantitative data from multiple independent studies addressing a common research question. An important part of this method involves computing a combined effect size across all of the studies. As such, th ...

published in 2011. SDD is also used to treat skin conditions such as acne and rosacea, including ocular rosacea. 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. Doxycycline is used as an adjunctive therapy for acute intestinal amebiasis. Doxycycline is also used as an adjunctive therapy for

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 ''Neisseria gonorrhoeae'', also known as ''gonococcus'' (singular) or ''gonococci'' (plural), is a species of Gram-negative diplococci bacteria first isolated by Albert Ludwig Sigesmund Neisser, Albert Neisser in 1879. An obligate human pathog ...

. 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. Appropriate use of doxycycline for PEP is supported by guidelines from the US Centers for Disease Control and Prevention (CDC) and the Australasian Society for HIV Medicine.

Use in combination

The first-line treatment for

is a combination of doxycycline and

. The second-line is a combination of doxycycline and

rifampicin Rifampicin, also known as rifampin, is an ansamycin antibiotic used to treat several types of bacterial infections, including tuberculosis (TB), ''Mycobacterium avium'' complex, leprosy, and Legionnaires' disease. It is almost always used tog ...

(rifampin).

Antimalarial

Doxycycline is active against the erythrocytic stages of ''

Plasmodium falciparum ''Plasmodium falciparum'' is a Unicellular organism, unicellular protozoan parasite of humans and is the deadliest species of ''Plasmodium'' that causes malaria in humans. The parasite is transmitted through the bite of a female ''Anopheles'' mos ...

'' but not against the gametocytes of ''P. falciparum''. It is used to prevent

. 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. Doxycycline blocks protein production in

(an

organelle In cell biology, an organelle is a specialized subunit, usually within a cell (biology), cell, that has a specific function. The name ''organelle'' comes from the idea that these structures are parts of cells, as Organ (anatomy), organs are to th ...

) 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. 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. The

World Health Organization The World Health Organization (WHO) is a list of specialized agencies of the United Nations, specialized agency of the United Nations which coordinates responses to international public health issues and emergencies. It is headquartered in Gen ...

(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.

Antihelminthic

Doxycycline kills the

symbiotic Symbiosis (Ancient Greek : living with, companionship < : together; and ''bíōsis'': living) is any type of a close and long-term biolo ...

Wolbachia ''Wolbachia'' is a genus of gram-negative bacteria infecting many species of arthropods and filarial nematodes. The symbiotic relationship ranges from parasitism to obligate mutualism. It is one of the most common parasitic microbes of arthrop ...

'' bacteria in the reproductive tracts of

parasitic Parasitism is a close relationship between species, where one organism, the parasite, lives (at least some of the time) on or inside another organism, the host, causing it some harm, and is adapted structurally to this way of life. The ent ...

filarial

nematodes The nematodes ( or ; ; ), roundworms or eelworms constitute the phylum Nematoda. Species in the phylum inhabit a broad range of environments. Most species are free-living, feeding on microorganisms, but many are parasitic. Parasitic worms (he ...

, making the nematodes sterile, and thus reducing transmission of diseases such as

onchocerciasis Onchocerciasis, also known as river blindness, is a disease caused by infection with the parasitic worm ''Onchocerca volvulus''. Symptoms include severe itching, bumps under the skin, and blindness. It is the second-most common cause of blindne ...

and

elephantiasis Elephantiasis, often incorrectly called elephantitis, is the enlargement and hardening of limbs or body parts due to tissue swelling (edema). It is characterised by edema, hypertrophy, and fibrosis of skin and subcutaneous tissues, due to obstru ...

. Field trials in 2005 showed an eight-week course of doxycycline almost eliminates the release of microfilariae.

Spectrum of susceptibility

Doxycycline has been used successfully to treat sexually transmitted, respiratory, and ophthalmic infections. Representative pathogenic genera include ''

Chlamydia Chlamydia, or more specifically a chlamydia infection, is a sexually transmitted infection caused by the bacterium ''Chlamydia trachomatis''. Most people who are infected have no symptoms. When symptoms do appear, they may occur only several w ...

Streptococcus ''Streptococcus'' is a genus of gram-positive spherical bacteria that belongs to the family Streptococcaceae, within the order Lactobacillales (lactic acid bacteria), in the phylum Bacillota. Cell division in streptococci occurs along a sing ...

Ureaplasma ''Ureaplasma'' is a genus of bacteria belonging to the family Mycoplasmataceae. As the name implies, ''Ureaplasma'' is urease positive. Phylogeny The currently accepted taxonomy is based on the List of Prokaryotic names with Standing in No ...

Mycoplasma ''Mycoplasma'' is a genus of bacteria that, like the other members of the class ''Mollicutes'', lack a cell wall, and its peptidoglycan, around their cell membrane. The absence of peptidoglycan makes them naturally resistant to antibiotics ...

'', and others. The following represents

minimum inhibitory concentration In microbiology, the minimum inhibitory concentration (MIC) is the lowest concentration of a chemical, usually a drug, which prevents visible ''in vitro'' cell growth, growth of bacteria or Fungus, fungi. MIC testing is performed in both diagnosti ...

susceptibility data for a few medically significant microorganisms. * ''

Chlamydia psittaci ''Chlamydia psittaci'' is a lethal intracellular bacterial species that may cause endemic avian chlamydiosis, epizootic outbreaks in other mammals, and respiratory psittacosis in humans. Potential hosts include feral birds and domesticated po ...

'': 0.03 ''μ''g/mL * ''

'': 0.016–2 ''μ''g/mL * ''

'': 0.06–32 ''μ''g/mL

Sclerotherapy

Doxycycline is also used for

sclerotherapy Sclerotherapy (the word reflects the Greek ''skleros'', meaning ''hard'') is a procedure used to treat blood vessel malformations ( vascular malformations) and also malformations of the lymphatic system. A medication is injected into the vessels ...

in slow-flow vascular malformations, namely

venous Veins () are blood vessels in the circulatory system of humans and most other animals that carry blood towards the heart. Most veins carry deoxygenated blood from the tissues back to the heart; exceptions are those of the pulmonary and fetal c ...

and lymphatic malformations, as well as post-operative lymphoceles.

Off-label use

Doxycycline has found off-label use in the treatment of transthyretin amyloidosis (ATTR). Together with

tauroursodeoxycholic acid Ursodoxicoltaurine is the international nonproprietary name (INN) for the pharmaceutical form of tauroursodeoxycholic acid (TUDCA). It is also known as taurursodiol. Tauroursodeoxycholic acid is a naturally occurring hydrophilic bile acid which ...

, doxycycline appears to be a promising combination capable of disrupting transthyretin TTR fibrils in existing amyloid deposits of ATTR patients.

Routes of administration

Doxycycline can be administered via oral or intravenous routes. The combination of doxycycline with dairy, antacids, calcium supplements, iron products, laxatives containing magnesium, or

bile acid sequestrant The bile acid sequestrants are a group of resins used to bind certain components of bile in the gastrointestinal tract. They disrupt the enterohepatic circulation of bile acids by combining with bile constituents and preventing their reabsorption f ...

s is not inherently dangerous, but any of these foods and supplements may decrease absorption of doxycycline. Doxycycline has a high oral bioavailability, as it is almost completely absorbed in the stomach and proximal small intestine. Unlike other tetracyclines, its absorption is not significantly affected by food or dairy intake. However, co-administration of dairy products reduces the serum concentration of doxycycline by 20%. Doxycycline absorption is also inhibited by divalent and trivalent cations, such as iron, bismuth, aluminum, calcium and magnesium. 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.

Contraindications

Severe

liver disease Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common. Liver diseases File:Ground gla ...

or concomitant use of

isotretinoin Isotretinoin, also known as 13-''cis''-retinoic acid and sold under the brand name Accutane among others, is a medication used to treat skin diseases like harlequin-type ichthyosis, and lamellar ichthyosis, and severe cystic acne or moderat ...

or other

retinoid The retinoids are a class of chemical compounds that are natural derivatives of vitamin A or are chemically related to it. Synthetic retinoids are utilized in cosmetic formulations, clinical dermatology, and the treatment of some forms of cancer ...

s are contraindications, as both tetracyclines and retinoids can cause intracranial hypertension (increased pressure around the brain) in rare cases.

Pregnancy and lactation

Doxycycline is categorized by the

FDA The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

as a class D drug in pregnancy. Doxycycline crosses into breastmilk. Other tetracycline antibiotics are contraindicated in pregnancy and up to eight years of age, due to the potential for disrupting bone and tooth development. 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. 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 The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency under the Department of Health and Human Services (HHS), and is headquartered in Atlanta, ...

recommends the use of doxycycline for treatment of

and tick-borne rickettsial diseases in young children; others advocate for its use in malaria.

Adverse effects

Adverse effects are similar to those of other members of the

tetracycline Tetracycline, sold under various brand names, is an antibiotic in the tetracyclines family of medications, used to treat a number of infections, including acne, cholera, brucellosis, plague, malaria, and syphilis. It is available in oral an ...

antibiotic group. Doxycycline can cause gastrointestinal upset. Oral doxycycline can cause pill

esophagitis Esophagitis, also spelled oesophagitis, is a disease characterized by inflammation of the esophagus. The esophagus is a tube composed of a mucosal lining, and longitudinal and circular smooth muscle fibers. It connects the pharynx to the stoma ...

, particularly when it is swallowed without adequate fluid, or by persons with difficulty swallowing or impaired mobility. Doxycycline is less likely than other antibiotic drugs to cause ''

Clostridioides difficile ''Clostridioides difficile'' ( syn. ''Clostridium difficile'') is a bacterium known for causing serious diarrheal infections, and may also cause colon cancer. It is known also as ''C. difficile'', or ''C. diff'' (), and is a Gram-positive spec ...

colitis Colitis is swelling or inflammation Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and ...

''.'' 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. Unlike some other members of the tetracycline group, it may be used in those with renal impairment. Doxycycline use has been associated with increased risk of

inflammatory bowel disease Inflammatory bowel disease (IBD) is a group of inflammatory conditions of the colon and small intestine, with Crohn's disease and ulcerative colitis (UC) being the principal types. Crohn's disease affects the small intestine and large intestine ...

. In one large

retrospective study A retrospective cohort study, also called a historic cohort study, is a longitudinal cohort study used in medical and psychological research. A cohort of individuals that share a common exposure factor is compared with another group of equival ...

, patients who were prescribed doxycycline for their acne had a 2.25-fold greater risk of developing

Crohn's disease Crohn's disease is a type of inflammatory bowel disease (IBD) that may affect any segment of the gastrointestinal tract. Symptoms often include abdominal pain, diarrhea, fever, abdominal distension, and weight loss. Complications outside of the ...

Interactions

Previously, doxycycline was believed to impair the effectiveness of many types of

hormonal contraception Hormonal contraception refers to birth control methods that act on the endocrine system. Almost all methods are composed of steroid hormones, although in India one selective estrogen receptor modulator is marketed as a contraceptive. The original ...

due to

CYP450 Cytochromes P450 (P450s or CYPs) are a superfamily of enzymes containing heme as a cofactor that mostly, but not exclusively, function as monooxygenases. However, they are not omnipresent; for example, they have not been found in ''Escherichi ...

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.

Pharmacology

Doxycycline, like other tetracycline antibiotics, is

bacteriostatic A bacteriostatic agent or bacteriostat, abbreviated Bstatic, is a biological or chemical agent that stops bacteria from reproducing, while not necessarily killing them otherwise. Depending on their application, bacteriostatic antibiotics, disinfec ...

. It works by preventing bacteria from reproducing by inhibiting

protein synthesis Protein biosynthesis, or protein synthesis, is a core biological process, occurring inside cells, balancing the loss of cellular proteins (via degradation or export) through the production of new proteins. Proteins perform a number of critica ...

. Doxycycline is highly

lipophilic Lipophilicity (from Greek language, Greek λίπος "fat" and :wikt:φίλος, φίλος "friendly") is the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene. Such compounds are c ...

, so it can easily enter cells, meaning the drug is easily absorbed after oral administration and has a large

volume of distribution In pharmacology, the volume of distribution (VD, also known as apparent volume of distribution, literally, ''volume of dilution'') is the theoretical volume that would be necessary to contain the total amount of an administered drug at the same c ...

. It can also be re-absorbed in the

renal tubules The nephron is the minute or microscopic structural and functional unit of the kidney. It is composed of a renal corpuscle and a renal tubule. The renal corpuscle consists of a tuft of capillaries called a glomerulus and a cup-shaped structure ...

and

gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the Digestion, digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascula ...

due to its high lipophilicity, giving it a long

elimination half-life Biological half-life (elimination half-life, pharmacological half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the blood plasma. ...

. It is also prevented from accumulating in the kidneys of patients with

kidney failure Kidney failure, also known as renal failure or end-stage renal disease (ESRD), is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney fa ...

due to the compensatory excretion in

faeces Feces (also known as faeces American and British English spelling differences#ae and oe, or fæces; : faex) are the solid or semi-solid remains of food that was not digested in the small intestine, and has been broken down by bacteria in the ...

. 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.

Mechanism of action

Doxycycline is a broad-spectrum

antibiotic. It inhibits the synthesis of bacterial proteins by binding to the 30S ribosomal subunit, which is only found in bacteria. This prevents the binding of

transfer RNA Transfer ribonucleic acid (tRNA), formerly referred to as soluble ribonucleic acid (sRNA), is an adaptor molecule composed of RNA, typically 76 to 90 nucleotides in length (in eukaryotes). In a cell, it provides the physical link between the gene ...

messenger RNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of synthesizing a protein. mRNA is created during the ...

at the ribosomal subunit, meaning

amino acids Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the Proteinogenic amino acid, 22 α-amino acids incorporated into p ...

cannot be added to polypeptide chains and new proteins cannot be made. This stops bacterial growth, giving the

immune system The immune system is a network of biological systems that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to bacteria, as well as Tumor immunology, cancer cells, Parasitic worm, parasitic ...

time to kill and remove the bacteria. In rosacea treatment, doxycycline inhibits neutrophil chemotaxis and oxidative bursts (common mechanisms of inflammation and

reactive oxygen species In chemistry and biology, reactive oxygen species (ROS) are highly Reactivity (chemistry), reactive chemicals formed from diatomic oxygen (), water, and hydrogen peroxide. Some prominent ROS are hydroperoxide (H2O2), superoxide (O2−), hydroxyl ...

activity in rosacea), and it also suppresses matrix metalloproteases and kallikrein 5 which in turn reduce the expression of the human cathelicidin antimicrobial peptide (LL-37) and limit downstream inflammatory cascades.

Pharmacokinetics

The substance is almost completely absorbed from the upper part of the

small intestine The small intestine or small bowel is an organ (anatomy), organ in the human gastrointestinal tract, gastrointestinal tract where most of the #Absorption, absorption of nutrients from food takes place. It lies between the stomach and large intes ...

. It reaches highest concentrations in the

blood plasma Blood plasma is a light Amber (color), amber-colored liquid component of blood in which blood cells are absent, but which contains Blood protein, proteins and other constituents of whole blood in Suspension (chemistry), suspension. It makes up ...

after one to two hours and has a high

plasma protein Plasma proteins, sometimes referred to as blood proteins, are proteins present in blood plasma. They perform many different functions, including transport of hormones, vitamins and minerals in activity and functioning of the immune system. Other b ...

binding rate of about 80–90%. Doxycycline penetrates into almost all tissues and

body fluid Body fluids, bodily fluids, or biofluids, sometimes body liquids, are liquids within the Body (biology), body of an organism. In lean healthy adult men, the total body water is about 60% (60–67%) of the total Human body weight, body weight; it ...

s. Very high concentrations are found in the

gallbladder In vertebrates, the gallbladder, also known as the cholecyst, is a small hollow Organ (anatomy), organ where bile is stored and concentrated before it is released into the small intestine. In humans, the pear-shaped gallbladder lies beneath t ...

liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...

, kidneys, lungs, breast milk, bones, and genitals; low concentrations are found in

saliva Saliva (commonly referred as spit or drool) is an extracellular fluid produced and secreted by salivary glands in the mouth. In humans, saliva is around 99% water, plus electrolytes, mucus, white blood cells, epithelial cells (from which ...

aqueous humor The aqueous humour is a transparent water-like fluid similar to blood plasma, but containing low protein concentrations. It is secreted from the ciliary body, a structure supporting the lens of the eyeball. It fills both the anterior and the po ...

cerebrospinal fluid Cerebrospinal fluid (CSF) is a clear, colorless Extracellular fluid#Transcellular fluid, transcellular body fluid found within the meninges, meningeal tissue that surrounds the vertebrate brain and spinal cord, and in the ventricular system, ven ...

(CSF), and especially in inflamed

meninges In anatomy, the meninges (; meninx ; ) are the three membranes that envelop the brain and spinal cord. In mammals, the meninges are the dura mater, the arachnoid mater, and the pia mater. Cerebrospinal fluid is located in the subarachnoid spac ...

.Doxycycline . Accessed 5 August 2020. By comparison, the tetracycline antibiotic

minocycline Minocycline, sold under the brand name Minocin among others, is a tetracycline antibiotic medication used to treat a number of bacterial infections such as some occurring in certain forms of pneumonia. It is generally (but not always) less pre ...

penetrates significantly better into the CSF and meninges. Doxycycline

metabolism Metabolism (, from ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the co ...

is negligible. It is actively excreted into the gut (in part via the gallbladder, in part directly from

blood vessels Blood vessels are the tubular structures of a circulatory system that transport blood throughout many animals’ bodies. Blood vessels transport blood cells, nutrients, and oxygen to most of the tissues of a body. They also take waste an ...

), where some of it is inactivated by forming

chelate Chelation () is a type of bonding of ions and their molecules to metal ions. It involves the formation or presence of two or more separate coordinate bonds between a polydentate (multiple bonded) ligand and a single central metal atom. These l ...

s. About 40% are eliminated via the kidneys, much less in people with

end-stage kidney disease Chronic kidney disease (CKD) is a type of long-term kidney disease, defined by the sustained presence of abnormal kidney function and/or abnormal kidney structure. To meet criteria for CKD, the abnormalities must be present for at least three m ...

. The

biological half-life Biological half-life (elimination half-life, pharmacological half-life) is the time taken for concentration of a drug, biological substance (such as a medication) to decrease from its maximum concentration (chemistry), concentration (Cmax (pharm ...

is 18 to 22 hours (16 ± 6 hours according to another source) in healthy people, slightly longer in those with end-stage kidney disease, and significantly longer in those with

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 causing

Fanconi syndrome Fanconi syndrome or Fanconi's syndrome (, ) is a syndrome of inadequate reabsorption in the proximal renal tubules of the kidney. The syndrome can be caused by various underlying congenital or acquired diseases, by toxicity (for example, from t ...

. In the case of doxycycline, the absence of a hydroxyl group in C-6 prevents the formation of the nephrotoxic compound. Nevertheless, tetracyclines and doxycycline itself have to be taken with caution in patients with kidney injury, as they can worsen

azotemia Azotemia (), also spelled azotaemia, is a medical condition characterized by abnormally high levels of nitrogen-containing compounds (such as urea, creatinine, various body waste compounds, and other nitrogen-rich compounds) in the blood. It is ...

due to catabolic effects.

Chemical properties

Doxycycline, doxycycline monohydrate and doxycycline hyclate are yellow, crystalline powders with a bitter taste. The latter smells faintly of

ethanol Ethanol (also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound with the chemical formula . It is an Alcohol (chemistry), alcohol, with its formula also written as , or EtOH, where Et is the ps ...

, a 1%

aqueous An aqueous solution is a solution in which the solvent is water. It is mostly shown in chemical equations by appending (aq) to the relevant chemical formula. For example, a solution of table salt, also known as sodium chloride (NaCl), in wat ...

solution has a pH of 2–3, and the

specific rotation In chemistry, specific rotation ( �'') is a property of a chiral chemical compound. It is defined as the change in orientation of monochromatic plane-polarized light, per unit distance–concentration product, as the light passes through a sampl ...

alpha Alpha (uppercase , lowercase ) is the first letter of the Greek alphabet. In the system of Greek numerals, it has a value of one. Alpha is derived from the Phoenician letter ''aleph'' , whose name comes from the West Semitic word for ' ...

D^ −110° cm³/dm·g in 0.01 N

methanol Methanol (also called methyl alcohol and wood spirit, amongst other names) is an organic chemical compound and the simplest aliphatic Alcohol (chemistry), alcohol, with the chemical formula (a methyl group linked to a hydroxyl group, often ab ...

hydrochloric acid Hydrochloric acid, also known as muriatic acid or spirits of salt, is an aqueous solution of hydrogen chloride (HCl). It is a colorless solution with a distinctive pungency, pungent smell. It is classified as a acid strength, strong acid. It is ...

History

After

penicillin Penicillins (P, PCN or PEN) are a group of beta-lactam antibiotic, β-lactam antibiotics originally obtained from ''Penicillium'' Mold (fungus), moulds, principally ''Penicillium chrysogenum, P. chrysogenum'' and ''Penicillium rubens, P. ru ...

revolutionized the treatment of bacterial infections in World War II, many chemical companies moved into the field of discovering antibiotics by

bioprospecting Bioprospecting (also known as biodiversity prospecting) is the exploration of natural sources for small molecules, macromolecules and biochemical and genetic information that could be developed into commercialization, commercially valuable prod ...

American Cyanamid American Cyanamid Company was an American manufacturing conglomerate. It began as a fertilizer company and added many additional lines of business before merging with American Home Products in 1994. The combined company sold off most of its di ...

was one of these, and in the late 1940s chemists there discovered chlortetracycline, the first member of the tetracycline class of antibiotics. 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

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. As its patent grew near to expiring in the early 1970s, the patent became the subject of lawsuit between Pfizer and International Rectifier that was not resolved until 1983; at the time it was the largest litigated patent case in US history. Instead of a cash payment for infringement, Pfizer took the veterinary and feed-additive businesses of International Rectifier's subsidiary, Rachelle Laboratories. In January 2013, the FDA reported shortages of some, but not all, forms of doxycycline "caused by increased demand and manufacturing issues". Companies involved included an unnamed major generics manufacturer that ceased production in February 2013, Teva (which ceased production in May 2013),

Mylan Mylan N.V. was a global generic and specialty pharmaceuticals company. In November 2020, Mylan merged with Upjohn, Pfizer's off-patent medicine division, to form Viatris. Previously, the company was domiciled in the Netherlands, with principa ...

Actavis Actavis Generics (formerly known as Watson Pharmaceuticals and Actavis plc, prior to the acquisition of Irish-based Allergan, Inc.) is a global pharmaceutical company focused on acquiring, developing, manufacturing and marketing branded pharmaceut ...

, and Hikma Pharmaceuticals. The shortage came at a particularly bad time, since there were also shortages of an alternative antibiotic, tetracycline, at the same time. 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), before decreasing again.

Society and culture

Doxycycline is available worldwide under many brand names. Doxycycline is available as a generic medicine. Doxycycline is also used in the prevention of certain sexually transmitted infections, particularly among

men who have sex with men Men who have sex with men (MSM) are men who engage in sexual activity with other men, regardless of their sexual orientation or sexual identity. The term was created by epidemiologists in the 1990s, to better study and communicate the spre ...

Research

Medical conditions

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

macular degeneration Macular degeneration, also known as age-related macular degeneration (AMD or ARMD), is a medical condition which may result in blurred vision, blurred or vision loss, no vision in the center of the visual field. Early on there are often no sym ...

; *

rheumatoid arthritis Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects synovial joint, joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and h ...

instead of

(both of which have demonstrated modest efficacy for this disease). Tet-ON inducible transgene expression cells

Dosing

Although doxycycline is approved to treat

, the optimal dosing and duration of treatment for this condition is a topic of ongoing research. 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. 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.

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 The Interleukin-1 family (IL-1 family) is a group of 11 cytokines that plays a central role in the regulation of immune and inflammatory responses to infections or sterile insults. Discovery Discovery of these cytokines began with studies on t ...

(IL-1),

interleukin-6 Interleukin 6 (IL-6) is an interleukin that acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine. In humans, it is encoded by the ''IL6'' gene. In addition, osteoblasts secrete IL-6 to stimulate osteoclast formation. Smoo ...

(IL-6),

tumor necrosis factor-alpha Tumor necrosis factor (TNF), formerly known as TNF-α, is a chemical messenger produced by the immune system that induces inflammation. TNF is produced primarily by activated macrophages, and induces inflammation by binding to its receptors o ...

(TNF-α), and

matrix metalloproteinase Matrix metalloproteinases (MMPs), also known as matrix metallopeptidases or matrixins, are metalloproteinases that are calcium-dependent zinc-containing endopeptidases; other family members are adamalysins, serralysins, and astacins. The MMPs be ...

s (MMPs) while increasing the production of anti-inflammatory

cytokine Cytokines () are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...

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 may refer to: Physics Relating to the nucleus of the atom: * Nuclear engineering * Nuclear physics * Nuclear power *Nuclear reactor *Nuclear weapon * Nuclear medicine *Radiation therapy *Nuclear warfare Mathematics * Nuclear space * Nu ...

(NF-κB) pathway, which is responsible for upregulating several inflammatory mediators in various cells, including

neuron A neuron (American English), neurone (British English), or nerve cell, is an membrane potential#Cell excitability, excitable cell (biology), cell that fires electric signals called action potentials across a neural network (biology), neural net ...

s; therefore, it is studied as a potential agent for treating

neuroinflammation Neuroinflammation is inflammation of the nervous tissue. It may be initiated in response to a variety of cues, including infection, traumatic brain injury,Ebert SE, Jensen P, Ozenne B, Armand S, Svarer C, Stenbaek DS ''et al.'' Molecular imaging of ...

. A potential explanation of doxycycline's anti-inflammatory properties is its inhibition of

s (MMPs), which are a group of proteases known to regulate the turnover of

extracellular matrix In biology, the extracellular matrix (ECM), also called intercellular matrix (ICM), is a network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide structural and bio ...

(ECM) and thus are suggested to be important in the process of several diseases associated with

tissue remodeling Tissue may refer to: Biology * Tissue (biology), an ensemble of similar (or dissimilar in structure but same in origin) cells that together carry out a specific function * '' Triphosa haesitata'', a species of geometer moth ("tissue moth") found ...

and inflammation. Doxycycline has been shown to inhibit MMPs, including matrilysin (MMP7), by interacting with the structural zinc atom and/or calcium atoms within the structural metal center of the protein. Doxycycline also inhibits allikrein-related peptidase 5 (KLK5). 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. Doxycycline is used to treat

acne vulgaris Acne ( ), also known as ''acne vulgaris'', is a long-term Cutaneous condition, skin condition that occurs when Keratinocyte, dead skin cells and Sebum, oil from the skin clog hair follicles. Typical features of the condition include comedo, ...

and

. However, there is no clear understanding of what contributes more: the bacteriostatic properties of doxycycline, which affect bacteria (such as Propionibacterium acnes) on the surface of sebaceous glands even in lower doses called "submicrobial" or "subantimicrobial", or whether doxycycline's anti-inflammatory effects, which reduce inflammation in

and

, including

ocular rosacea Ocular rosacea is a type of rosacea that affects the eyes. Signs and symptoms generally consist of redness, irritation or burning of the eyes. Affected individuals may also feel that there is something, such as an eyelash, in the eye and frequent ...

, contribute more to its therapeutic effectiveness against these skin conditions. Subantimicrobial-dose doxycycline (SDD) can still have a

effect, especially when taken for extended periods, such as several months in treating acne and rosacea. 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. One probable mechanism is doxycycline's ability to decrease the amount of

(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 radical The hydroxyl radical, •HO, is the neutral form of the hydroxide ion (HO–). Hydroxyl radicals are highly reactive and consequently short-lived; however, they form an important part of radical chemistry. Most notably hydroxyl radicals are pr ...

s and

singlet oxygen Singlet oxygen, systematically named dioxygen(singlet) and dioxidene, is a gaseous inorganic chemistry, inorganic chemical with the formula O=O (also written as or ), which is in a quantum state where all electrons are Radical (chemistry), spin p ...

, helping minimize tissue damage caused by highly oxidative and inflammatory conditions. Studies have shown that SDD can effectively improve acne and rosacea symptoms, probably without inducing

antibiotic resistance Antimicrobial resistance (AMR or AR) occurs when microbes evolve mechanisms that protect them from antimicrobials, which are drugs used to treat infections. This resistance affects all classes of microbes, including bacteria (antibiotic resis ...

. 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. 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 Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other animal coverings, such as the arthropod exoskeleton, have different ...

, such as rosacea and acne, but also in conditions such as

osteoarthritis Osteoarthritis is a type of degenerative joint disease that results from breakdown of articular cartilage, joint cartilage and underlying bone. A form of arthritis, it is believed to be the fourth leading cause of disability in the world, affect ...

. 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. Doxycycline has been studied in various immunological disorders, including

lupus Lupus, formally called systemic lupus erythematosus (SLE), is an autoimmune disease in which the body's immune system mistakenly attacks healthy tissue in many parts of the body. Symptoms vary among people and may be mild to severe. Common ...

, and

. 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. Doxycycline is also studied for its neuroprotective properties which are associated with

antioxidant Antioxidants are Chemical compound, compounds that inhibit Redox, oxidation, a chemical reaction that can produce Radical (chemistry), free radicals. Autoxidation leads to degradation of organic compounds, including living matter. Antioxidants ...

, anti-apoptotic, and anti-inflammatory mechanisms. In this context, it is important to note that doxycycline is able to cross the

blood–brain barrier The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that regulates the transfer of solutes and chemicals between the circulatory system and the central nervous system ...

. Several studies have shown that doxycycline inhibits

dopaminergic Dopaminergic means "related to dopamine" (literally, "working on dopamine"), a common neurotransmitter. Dopaminergic substances or actions increase dopamine-related activity in the brain. Dopaminergic pathways, Dopaminergic brain pathways facil ...

neurodegeneration through the upregulation of

axon An axon (from Greek ἄξων ''áxōn'', axis) or nerve fiber (or nerve fibre: see American and British English spelling differences#-re, -er, spelling differences) is a long, slender cellular extensions, projection of a nerve cell, or neuron, ...

al and synaptic proteins. Axonal degeneration and synaptic loss are key events at the early stages of neurodegeneration and precede neuronal death in

neurodegenerative disease A neurodegenerative disease is caused by the progressive loss of neurons, in the process known as neurodegeneration. Neuronal damage may also ultimately result in their death. Neurodegenerative diseases include amyotrophic lateral sclerosis, mul ...

s, including

Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a neurodegenerative disease primarily of the central nervous system, affecting both motor system, motor and non-motor systems. Symptoms typically develop gradually and non-motor issues become ...

(PD). Therefore, the regeneration of the axonal and synaptic network might be beneficial in PD. It has been demonstrated that doxycycline mimics

nerve growth factor Nerve growth factor (NGF) is a neurotrophic factor and neuropeptide primarily involved in the regulation of growth, maintenance, proliferation, and survival of certain target neurons. It is perhaps the prototypical growth factor, in that it was ...

(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. While there is some research on the use of doxycycline for treating

major depressive disorder Major depressive disorder (MDD), also known as clinical depression, is a mental disorder characterized by at least two weeks of pervasive depression (mood), low mood, low self-esteem, and anhedonia, loss of interest or pleasure in normally ...

, the results are mixed. After a large-scale trial showed no benefit of using doxycycline in treating COVID19, the UK's

National Institute for Health and Care Excellence The National Institute for Health and Care Excellence (NICE) is an executive non-departmental public body of the Department of Health and Social Care (United Kingdom), Department of Health and Social Care. As the national health technolog ...

(NICE) updated its guidance to not recommend the medication for the treatment of COVID19. Doxycycline was expected to possess anti-inflammatory properties that could lessen the

cytokine storm A cytokine storm, also called hypercytokinemia, is a pathological reaction in humans and other animals in which the innate immune system causes an uncontrolled and excessive release of pro-inflammatory signaling molecules called cytokines. Cytok ...

associated with a

SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) is a strain of coronavirus that causes COVID-19, the respiratory illness responsible for the COVID-19 pandemic. The virus previously had the Novel coronavirus, provisional nam ...

infection, but the trials did not demonstrate the expected benefit. 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.

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. 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.

Research reagent

Doxycycline and other members of the tetracycline class of antibiotics are often used as research

reagent In chemistry, a reagent ( ) or analytical reagent is a substance or compound added to a system to cause a chemical reaction, or test if one occurs. The terms ''reactant'' and ''reagent'' are often used interchangeably, but reactant specifies a ...

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 A mitochondrion () is an organelle found in the cells of most eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is us ...

impairing metabolism and leading to effects that can

confound In causal inference, a confounder is a variable that influences both the dependent variable and independent variable, causing a spurious association. Confounding is a causal concept, and as such, cannot be described in terms of correlatio ...

experimental results. Doxycycline is also used in "tet-on" (

gene expression Gene expression is the process (including its Regulation of gene expression, regulation) by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, proteins or non-coding RNA, ...

activated by doxycycline) and "tet-off" (gene expression inactivated by doxycycline) tetracycline-controlled transcriptional activation to regulate

transgene A transgene is a gene that has been transferred naturally, or by any of a number of genetic engineering techniques, from one organism to another. The introduction of a transgene, in a process known as transgenesis, has the potential to change the ...

expression in organisms and

cell culture Cell culture or tissue culture is the process by which cell (biology), cells are grown under controlled conditions, generally outside of their natural environment. After cells of interest have been Cell isolation, isolated from living tissue, ...

s. Doxycycline is more stable than tetracycline for this purpose. 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.

References

External links

{{Authority control Anti-acne preparations Antimalarial agents Dimethylamino compounds Drugs developed by AbbVie Drugs developed by Pfizer Tetracycline antibiotics World Health Organization essential medicines Wikipedia medicine articles ready to translate