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 inf ...

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, ...

used in the treatment of infections caused by

bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were am ...

and certain

parasites Parasitism is a close relationship between species, where one organism, the parasite, lives on or inside another organism, the host, causing it some harm, and is adapted structurally to this way of life. The entomologist E. O. Wilson ha ...

. 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 pneumoni ...

acne Acne, also known as ''acne vulgaris'', is a long-term skin condition that occurs when dead skin cells and oil from the skin clog hair follicles. Typical features of the condition include blackheads or whiteheads, pimples, oily skin, and ...

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 we ...

Lyme disease Lyme disease, also known as Lyme borreliosis, is a vector-borne disease caused by the '' Borrelia'' bacterium, which is spread by ticks in the genus '' Ixodes''. The most common sign of infection is an expanding red rash, known as erythema ...

, cholera,

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 exposure. ...

, and syphilis. It is also used to prevent

malaria Malaria is a mosquito-borne infectious disease that affects humans and other animals. Malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or deat ...

in combination with

quinine Quinine is a medication used to treat malaria and babesiosis. This includes the treatment of malaria due to '' Plasmodium falciparum'' that is resistant to chloroquine when artesunate is not available. While sometimes used for nocturnal leg ...

. Doxycycline may be taken

by mouth Oral administration is a route of administration where a substance is taken through the mouth. Per os abbreviated to P.O. is sometimes used as a direction for medication to be taken orally. Many medications are taken orally because they are i ...

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 nutrie ...

. Common side effects include

diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin ...

, 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 animals include: red or reddish skin that i ...

. 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 c ...

. In 2020, it was the 79th most commonly prescribed medication in the United States, with more than 9million prescriptions.

Medical use

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. T ...

group, doxycycline is frequently used to treat

, chronic prostatitis,

sinusitis Sinusitis, also known as rhinosinusitis, is inflammation of the mucous membranes that line the sinuses resulting in symptoms that may include thick nasal mucus, a plugged nose, and facial pain. Other signs and symptoms may include fever, he ...

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

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, enlarg ...

, and rickettsial infections. 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 an 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 with

cefixime Cefixime, sold under the brand name Suprax among others, is an antibiotic medication used to treat a number of bacterial infections. These infections include otitis media, strep throat, pneumonia, urinary tract infections, gonorrhea, and Lyme d ...

for uncomplicated

gonorrhea 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. Infected men may experience pain or burning with ...

Antibacterial

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 i ...

'', ''

Brucella melitensis ''Brucella melitensis'' is a Gram-negative coccobacillus bacterium from the Brucellaceae family. The bacterium causes ovine brucellosis, along with ''Brucella ovis''. It affects primarily sheep and goats, but cases have also been observed ...

'', '' Chlamydia pneumoniae'', and '' Mycoplasma pneumoniae'' are generally susceptible to doxycycline, while some ''

Haemophilus ''Haemophilus'' is a genus of Gram-negative, pleomorphic, coccobacilli bacteria belonging to the family Pasteurellaceae. While ''Haemophilus'' bacteria are typically small coccobacilli, they are categorized as pleomorphic bacteria because of ...

'' spp., '' Mycoplasma hominis'', and ''

Pseudomonas aeruginosa ''Pseudomonas aeruginosa'' is a common encapsulated, gram-negative, aerobic– facultatively anaerobic, rod-shaped bacterium that can cause disease in plants and animals, including humans. A species of considerable medical importance, ''P. aer ...

'' have developed resistance to varying degrees. It is used in the treatment and

prophylaxis Preventive healthcare, or prophylaxis, consists of measures taken for the purposes of disease prevention.Hugh R. Leavell and E. Gurney Clark as "the science and art of preventing disease, prolonging life, and promoting physical and mental hea ...

anthrax Anthrax is an infection caused by the bacterium '' Bacillus anthracis''. It can occur in four forms: skin, lungs, intestinal, and injection. Symptom onset occurs between one day and more than two months after the infection is contracted. The s ...

and

Leptospirosis Leptospirosis is a blood infection caused by the bacteria '' Leptospira''. Signs and symptoms can range from none to mild (headaches, muscle pains, and fevers) to severe ( bleeding in the lungs or meningitis). Weil's disease, the acute, seve ...

. It is also effective against ''

Yersinia pestis ''Yersinia pestis'' (''Y. pestis''; formerly '' Pasteurella pestis'') is a gram-negative, non-motile, coccobacillus bacterium without spores that is related to both '' Yersinia pseudotuberculosis'' and '' Yersinia enterocolitica''. It is a facu ...

'' (the infectious agent of

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

), 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 made up of small spots of bleedin ...

. Doxycycline is indicated for treatment of:U.S. Food and Drug Administration. 14 December 2012
Doxycycline, ANDA no. 065055 Label.
U.S. Food and Drug Administration. 16 July 200
Doxycycline, ANDA no. 065454 Label
* Rocky Mountain spotted fever,

fever and the typhus group,

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, and tick fevers caused by ''Rickettsia'' * Respiratory tract infections caused by ''Mycoplasma pneumoniae'' * Lymphogranuloma venereum, trachoma, inclusion conjunctivitis, and uncomplicated urethral, endocervical, or rectal infections in adults caused by ''

Chlamydia trachomatis ''Chlamydia trachomatis'' (), commonly known as chlamydia, is a bacterium that causes chlamydia, which can manifest in various ways, including: trachoma, lymphogranuloma venereum, nongonococcal urethritis, cervicitis, salpingitis, pelvic infl ...

'' *

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 from ...

* Nongonococcal urethritis 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 or soft-bodied ticks (genus '' Ornithodoros''). Signs and symptoms Most people who a ...

due to ''Borrelia recurrentis'' * Chancroid caused by ''Haemophilus ducreyi'' * Plague due to ''

'' * Tularemia * Cholera * ''Campylobacter fetus'' infections * Brucellosis caused by ''Brucella'' species (in conjunction with streptomycin) *

Bartonellosis Bartonellosis is an infectious disease produced by bacteria of the genus ''Bartonella''. ''Bartonella'' species cause diseases such as Carrión's disease, trench fever, cat-scratch disease, bacillary angiomatosis, peliosis hepatis, chronic bacter ...

Granuloma inguinale Granuloma inguinale is a bacterial disease caused by '' Klebsiella granulomatis'' (formerly known as ''Calymmatobacterium granulomatis'') characterized by genital ulcers. It is endemic in many less-developed regions. It is also known as donova ...

(''Klebsiella'' species) *

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 do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wa ...

: * ''

Escherichia coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Esc ...

'' infections * '' Enterobacter aerogenes'' (formerly ''Aerobacter aerogenes'') infections * '' Shigella'' 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 importan ...

'' 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, non-motile, coccobacillary, facultatively anaerobic, capnophilic pathogenic bacterium of the family Pasteurellaceae. The bacte ...

'' * Respiratory tract and

urinary tract infection A urinary tract infection (UTI) is an infection that affects part of the urinary tract. When it affects the lower urinary tract it is known as a bladder infection (cystitis) and when it affects the upper urinary tract it is known as a kidne ...

s caused by ''

Klebsiella ''Klebsiella'' is a genus of Gram-negative, oxidase-negative, rod-shaped bacteria with a prominent polysaccharide-based capsule. ''Klebsiella'' species are found everywhere in nature. This is thought to be due to distinct sublineages developin ...

'' species 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. Gram-positive bact ...

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. 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, alpha-hemolytic (under aerobic conditions) or beta-hemolytic (under anaerobic conditions), aerotolerant anaerobic member of the genus Streptococcus. They a ...

'' (formerly ''Diplococcus pneumoniae'') * Skin and soft tissue infections caused by ''Staphylococcus aureus'', including methicillin-resistant ''Staphylococcus aureus'' infections * Anthrax caused by ''Bacillus anthracis'' infection When penicillin is contraindicated, doxycycline can be used to treat: * Syphilis caused by ''Treponema pallidum'' *

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 ul ...

caused by ''Treponema pertenue'' * Listeriosis due to ''Listeria monocytogenes'' * Vincent's infection caused by ''Fusobacterium fusiforme'' * Actinomycosis caused by ''Actinomyces israelii'' * Infections caused by ''Clostridium'' species Doxycycline may also be used as adjunctive therapy for severe

. The first-line treatment for

brucellosis Brucellosis is a highly contagious zoonosis caused by ingestion of unpasteurized milk or undercooked meat from infected animals, or close contact with their secretions. It is also known as undulant fever, Malta fever, and Mediterranean fever. T ...

is a combination of doxycycline and

streptomycin Streptomycin is an antibiotic medication used to treat a number of bacterial infections, including tuberculosis, ''Mycobacterium avium'' complex, endocarditis, brucellosis, ''Burkholderia'' infection, plague, tularemia, and rat bite fever ...

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 ...

(rifampin).

Antimalarial

Doxycycline is active against the erythrocytic stages of ''

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

'' 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. The

World Health Organization The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level o ...

(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 ''

Wolbachia ''Wolbachia'' is a genus of intracellular bacteria that infects mainly arthropod species, including a high proportion of insects, and also some nematodes. It is one of the most common parasitic microbes, and is possibly the most common repro ...

'' bacteria in the reproductive tracts of

parasitic Parasitism is a close relationship between species, where one organism, the parasite, lives on or inside another organism, the host, causing it some harm, and is adapted structurally to this way of life. The entomologist E. O. Wilson ha ...

filarial

nematodes The nematodes ( or grc-gre, Νηματώδη; la, Nematoda) or roundworms constitute the phylum Nematoda (also called Nemathelminthes), with plant-parasitic nematodes also known as eelworms. They are a diverse animal phylum inhabiting a broa ...

, 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 blind ...

and elephantiasis. 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, Streptococcus, Ureaplasma, Mycoplasma'', and others. The following represents MIC susceptibility data for a few medically significant microorganisms. * ''Chlamydia psittaci'': 0.03 ''μ''g/mL * ''Mycoplasma pneumoniae'': 0.016 ''μ''g/mL—2 ''μ''g/mL * ''Streptococcus pneumoniae'': 0.06 ''μ''g/mL—32 ''μ''g/mL

Sclerotherapy

Doxycycline is also used for sclerotherapy in slow-flow vascular malformations, namely

venous Veins are blood vessels in 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 the pulmonary and umbilical veins, both of which carry oxygenate ...

and

lymphatic malformation A cystic hygroma is an abnormal growth that usually appears on a baby's neck or head. It consists of one or more cysts and tends to grow larger over time. The disorder usually develops while the fetus is still in the uterus, but can also appear ...

s, as well as post-operative lymphoceles.

Others

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 cau ...

. 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 A meta-analysis is a statistical analysis that combines the results of multiple scientific studies. Meta-analyses can be performed when there are multiple scientific studies addressing the same question, with each individual study reporting m ...

published in 2011.

Contraindications

Pregnancy and lactation

Doxycycline is categorized by the FDA 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 and the CDC recommends the use of doxycycline for treatment of Q fever and also for tick-borne rickettsial diseases in young children and others advocate for its use in malaria.

Other

Other contraindications are 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. Signs and symptoms Some of the s ...

and concomitant use of

isotretinoin Isotretinoin, also known as 13-''cis''-retinoic acid and sold under the brand name Accutane among others, is a medication primarily used to treat severe acne. It is also used to prevent certain skin cancers ( squamous-cell carcinoma), and in ...

or other

retinoid The retinoids are a class of chemical compounds that are vitamers of vitamin A or are chemically related to it. Retinoids have found use in medicine where they regulate epithelial cell growth. Retinoids have many important functions throughout ...

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

Adverse effects

Adverse effects are similar to those of other members of the

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

antibiotic group. Doxycycline can cause gastrointestinal upset. Oral doxycycline can cause pill esophagitis, 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 '' Clostridium difficile'' colitis. An erythematous rash in sun-exposed parts of the body has been reported to occur in 7.3–21.2% of persons taking doxycycline for malaria prophylaxis. 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, Crohn's disease and ulcerative colitis being the principal types. Crohn's disease affects the small intestine and large intestine, as wel ...

. 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 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 (which may be bloody if inflammation is severe), fever, abdominal distension, ...

Interactions

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 ...

s is not inherently dangerous, but any of these foods and supplements may decrease doxycycline's effectiveness. 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 origi ...

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.

Pharmacology

Doxycycline, like other tetracycline antibiotics, is bacteriostatic. It works by preventing bacteria from reproducing through the inhibition of protein synthesis. 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 lipophillicity, giving it a long elimination half life, and it is also prevented from accumulating in the kidneys of patients with

kidney failure Kidney failure, also known as end-stage kidney disease, 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 failure is classified as eit ...

due to the compensatory excretion in faeces. Doxycycline–metal ion complexes are unstable at acid pH, therefore more doxycycline enters the duodenum for absorption than the earlier tetracycline compounds. In addition, food has less effect on absorption than on 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 bacteriostatic 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 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.

Pharmacokinetics

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

small intestine The small intestine or small bowel is an organ in the gastrointestinal tract where most of the absorption of nutrients from food takes place. It lies between the stomach and large intestine, and receives bile and pancreatic juice through t ...

. It reaches highest concentrations in the

blood plasma Blood plasma is a light amber-colored liquid component of blood in which blood cells are absent, but contains proteins and other constituents of whole blood in suspension. It makes up about 55% of the body's total blood volume. It is the ...

after one to two hours and has a high

plasma protein Blood-proteins, also termed plasma proteins, are proteins present in blood plasma. They serve many different functions, including transport of lipids, hormones, vitamins and minerals in activity and functioning of the immune system. Other blood pr ...

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 human body. In lean healthy adult men, the total body water is about 60% (60–67%) of the total body weight; it is usually slightly lower in women (52-55%) ...

s. Very high concentrations are found in the

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

, liver, kidneys, lung, breast milk, bone and genitals; low ones in saliva,

aqueous humour The aqueous humour is a transparent water-like fluid similar to 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 posteri ...

cerebrospinal fluid Cerebrospinal fluid (CSF) is a clear, colorless body fluid found within the tissue that surrounds the brain and spinal cord of all vertebrates. CSF is produced by specialised ependymal cells in the choroid plexus of the ventricles of the bra ...

(CSF), and especially in inflamed

meninges In anatomy, the meninges (, ''singular:'' meninx ( or ), ) 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 ...

.Doxycycline . Accessed 5 August 2020. By comparison, the tetracycline antibiotic minocycline penetrates significantly better into the CSF and meninges. Doxycycline

metabolism Metabolism (, from el, μεταβολή ''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 c ...

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

chelate Chelation is a type of bonding of ions and 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 ligands are ...

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 kidney disease in which a gradual loss of kidney function occurs over a period of months to years. Initially generally no symptoms are seen, but later symptoms may include leg swelling, feeling tired, v ...

. The

biological half-life Biological half-life (also known as elimination half-life, pharmacologic 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 bl ...

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-epitetracyclineFoye's Principles of Medicinal Chemistry; David A. Williams; William O. Foye, Thomas L. Lemke causing Fanconi syndrome.Goodman & Gilman's The Pharmacological Basis of Therapeutics, 12ed, Laurence L. Brunton, Bruce A. Chabner, Björn C. Knollmann 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 due to catabolic effects.

Chemical properties

Doxycycline, doxycycline

monohydrate In chemistry, a hydrate is a substance that contains water or its constituent elements. The chemical state of the water varies widely between different classes of hydrates, some of which were so labeled before their chemical structure was underst ...

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

ethanol Ethanol (abbr. EtOH; also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound. It is an alcohol with the chemical formula . Its formula can be also written as or (an ethyl group linked to a h ...

; 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, or sodium chloride (NaCl), in water would ...

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 sa ...

alpha D^

−110° cm³/dm·g in 0.01 N methanolic

hydrochloric acid Hydrochloric acid, also known as muriatic acid, is an aqueous solution of hydrogen chloride. It is a colorless solution with a distinctive pungent smell. It is classified as a strong acid. It is a component of the gastric acid in the dig ...

History

After

penicillin Penicillins (P, PCN or PEN) are a group of β-lactam antibiotics originally obtained from ''Penicillium'' moulds, principally '' P. chrysogenum'' and '' P. rubens''. Most penicillins in clinical use are synthesised by P. chrysogenum using ...

revolutionized the treatment of bacterial infections in WWII, 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 commercially valuable products for the agric ...

. American Cyanamid was one of these, and in the late 1940s chemists there discovered

chlortetracycline Chlortetracycline (trade name Aureomycin, Lederle Laboratories) is a tetracycline antibiotic, the first tetracycline to be identified. It was discovered in 1945 at Lederle Laboratories under the supervision of scientist Yellapragada Subbarow and ...

, the first member of the tetracycline class of antibiotics. Shortly thereafter, scientists at Pfizer discovered terramycin 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.The Associated Press, 6 July 198
"Pfizer to Get Rachelle Units"
''The New York Times''. 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 Teva is the Hebrew word for nature ( he, טבע, "nature"). Teva may refer to: Companies * Teva Footwear, American footwear manufacturer * Teva Naot, Israeli footwear manufacturer * Teva Pharmaceuticals, Israeli multinational pharmaceutical com ...

(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 princip ...

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 pharmaceuti ...

, 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),Rosenthal, Elisabeth
Officials Question the Rising Costs of Generic Drugs
, ''

The New York Times ''The New York Times'' (''the Times'', ''NYT'', or the Gray Lady) is a daily newspaper based in New York City with a worldwide readership reported in 2020 to comprise a declining 840,000 paid print subscribers, and a growing 6 million paid ...

'', 7 October 2014. before decreasing again.

Society and culture

Doxycycline is available worldwide under many brand names. Doxycycline is available as a generic medicine.

Research

Research areas have included: *

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

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 ...

instead of minocycline (both of which have demonstrated modest efficacy for this disease)

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

gene expression Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, protein or non-coding RNA, and ultimately affect a phenotype, as the final effect. ...

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 cultures. 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 erosion Recurrent corneal erosion is a disorder of the eyes characterized by the failure of the cornea's outermost layer of epithelial cells to attach to the underlying basement membrane (Bowman's layer). The condition is excruciatingly painful because t ...

COVID-19

After a large-scale trial showed no benefit of using doxycycline in treating

COVID19 Coronavirus disease 2019 (COVID-19) is a contagious disease caused by a virus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The first known case was COVID-19 pandemic in Hubei, identified in Wuhan, China, in December ...

, 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 in England that publishes guidelines in four areas: * the use of health technologies withi ...

(NICE) updated its guidance to not recommend the medication for the treatment of COVID19.

References

External links

* {{Portal bar, Medicine Anti-acne preparations Antimalarial agents Dimethylamino compounds AbbVie brands Tetracycline antibiotics World Health Organization essential medicines Wikipedia medicine articles ready to translate