|Pronunciation|| / /|
|Trade names||Doryx, Doxyhexal, Doxylin among others|
| Routes of|
|By mouth, IV|
|Elimination half-life||15–25 hours|
|ECHA InfoCard|| 100.008.429 |
|Chemical and physical data|
|Molar mass||444.43 g/mol g·mol−1|
|3D model (JSmol)|
Doxycycline is an antibiotic that is used in the treatment of infections caused by bacteria and certain other parasites.It is used to treat bacterial pneumonia, acne, chlamydia infections, early Lyme disease, cholera, and syphilis. It is also used to prevent malaria and in combination with quinine, to treat malaria. Doxycycline can be used either by mouth or by injection into a vein.
An antibiotic is a type of antimicrobial substance active against bacteria and is the most important type of antibacterial agent for fighting bacterial infections. Antibiotic medications are widely used in the treatment and prevention of such infections. They may either kill or inhibit the growth of bacteria. A limited number of antibiotics also possess antiprotozoal activity. Antibiotics are not effective against viruses such as the common cold or influenza; drugs which inhibit viruses are termed antiviral drugs or antivirals rather than antibiotics.
Bacteria are a type of biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a number of shapes, ranging from spheres to rods and spirals. Bacteria were among the first life forms to appear on Earth, and are present in most of its habitats. Bacteria inhabit soil, water, acidic hot springs, radioactive waste, and the deep portions of Earth's crust. Bacteria also live in symbiotic and parasitic relationships with plants and animals. Most bacteria have not been characterised, and only about half of the bacterial phyla have species that can be grown in the laboratory. The study of bacteria is known as bacteriology, a branch of microbiology.
Pneumonia is an inflammatory condition of the lung affecting primarily the small air sacs known as alveoli. Typically symptoms include some combination of productive or dry cough, chest pain, fever, and trouble breathing. Severity is variable.
Common side effects include diarrhea, nausea, vomiting, and an increased risk of a sunburn.Use after the first trimester of pregnancy or in young children may result in permanent problems with the teeth including changes in their color. Its use during breastfeeding is probably safe. Doxycycline is a broad-spectrum antibiotic of the tetracycline class. Like other agents of this class, it either slows or kills bacteria by inhibiting protein production. It kills malaria by targeting a plastid organelle, the apicoplast.
Diarrhea 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 with loss of the normal stretchiness of the skin and irritable behaviour. This can progress to decreased urination, loss of skin color, a fast heart rate, and a decrease in responsiveness as it becomes more severe. Loose but non-watery stools in babies who are exclusively breastfed, however, are normal.
Sunburn is a form of radiation burn that affects living tissue, such as skin, that results from an overexposure to ultraviolet (UV) radiation, commonly from the sun. Common symptoms in humans and other animals include red or reddish skin that is hot to the touch, pain, general fatigue, and mild dizziness. An excess of UV radiation can be life-threatening in extreme cases. Excessive UV radiation is the leading cause of primarily non-malignant skin tumors.
Breastfeeding, also known as nursing, is the feeding of babies and young children with milk from a woman's breast. Health professionals recommend that breastfeeding begin within the first hour of a baby's life and continue as often and as much as the baby wants. During the first few weeks of life babies may nurse roughly every two to three hours and the duration of a feeding is usually ten to fifteen minutes on each breast. Older children feed less often. Mothers may pump milk so that it can be used later when breastfeeding is not possible. Breastfeeding has a number of benefits to both mother and baby, which infant formula lacks.
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 most effective and safe medicines needed in a health system. Doxycycline is available as a generic medicine and is generally inexpensive. The wholesale cost in the developing world is between US$0.01 and US$0.04 per pill. In the United States, ten days of treatment costs about US$14; however, some in 2014 were selling it for more than US$3.00–10.00 per pill. In 2016, it was the 110th most prescribed medication in the United States, with more than 6 million prescriptions.
A health system, also sometimes referred to as health care system or as healthcare system, is the organization of people, institutions, and resources that deliver health care services to meet the health needs of target populations.
In addition to the general indications for all members of the tetracycline antibiotics group, doxycycline is frequently used to treat Lyme disease, chronic prostatitis, sinusitis, pelvic inflammatory disease,acne, rosacea, and rickettsial infections.
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. Tetracycline molecules comprise a linear fused tetracyclic nucleus to which a variety of functional groups are attached. Tetracyclines are named for their four ("tetra-") hydrocarbon rings ("-cycl-") derivation ("-ine"). They are defined as a subclass of polyketides, having an octahydrotetracene-2-carboxamide skeleton and are known as derivatives of polycyclic naphthacene carboxamide. While all tetracyclines have a common structure, they differ from each other by the presence of chloride, methyl, and hydroxyl groups. These modifications do not change their broad antibacterial activity, but do affect pharmacological properties such as half-life and binding to proteins in serum.
Lyme disease, also known as Lyme borreliosis, is an infectious disease caused by a bacterium named Borrelia spread by ticks. The most common sign of infection is an expanding area of redness on the skin, known as erythema migrans, that appears at the site of the tick bite about a week after it occurred. The rash is typically neither itchy nor painful. Approximately 70–80% of infected people develop a rash. Other early symptoms may include fever, headache and tiredness. If untreated, symptoms may include loss of the ability to move one or both sides of the face, joint pains, severe headaches with neck stiffness, or heart palpitations, among others. Months to years later, repeated episodes of joint pain and swelling may occur. Occasionally, people develop shooting pains or tingling in their arms and legs. Despite appropriate treatment, about 10 to 20% of people develop joint pains, memory problems, and tiredness for at least six months.
Prostatitis is inflammation of the prostate gland. Prostatitis is classified into acute, chronic, asymptomatic inflammatory prostatitis, and chronic pelvic pain syndrome.
In Canada, in 2004, doxycycline was considered a first-line treatment for chlamydia and non-gonococcal urethritis and with cefixime for uncomplicated gonorrhea.
Nongonococcal urethritis (NGU) is an inflammation of the urethra that is not caused by gonorrheal infection.
Cefixime is an antibiotic useful to treat a number of bacterial infections. This includes otitis media, strep throat, pneumonia, urinary tract infections, gonorrhea, and Lyme disease. For gonorrhea typically only one dose is required. In the United States it is a second line treatment to ceftriaxone for gonorrhea. It is taken by mouth.
Gonorrhea, colloquially known as the clap, is a sexually transmitted infection (STI) caused by the bacterium Neisseria gonorrhoeae. Many of those infected have no symptoms. Men may have burning with urination, discharge from the penis, or testicular pain. Women may have burning with urination, vaginal discharge, vaginal bleeding between periods, or pelvic pain. Complications in women include pelvic inflammatory disease and in men include inflammation of the epididymis. If untreated, gonorrhea can spread to joints or heart valves.
Moraxella catarrhalis , Brucella melitensis , Chlamydia pneumoniae , and Mycoplasma pneumoniae are generally susceptible to doxycycline, while some Haemophilus spp., Mycoplasma hominis , and Pseudomonas aeruginosa have developed resistance to varying degrees.
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 infection of the host cell by sticking to the host cell using trimeric autotransporter adhesins.
Brucella melitensis is a Gram-negative coccobacillus bacterium from the Brucellaceae family. The bacterium causes ovine brucellosis, along with Brucella ovis. It can infect sheep, cattle, and sometimes humans, and it can be transmitted by the stable fly. It is zoonotic, unlike B. ovis, causing Malta fever or localized brucellosis in humans.
Mycoplasma pneumoniae is a very small bacterium in the class Mollicutes. It is a human pathogen that causes the disease mycoplasma pneumonia, a form of atypical bacterial pneumonia related to cold agglutinin disease. M. pneumoniae is characterized by the absence of a peptidoglycan cell wall and resulting resistance to many antibacterial agents. The persistence of M. pneumoniae infections even after treatment is associated with its ability to mimic host cell surface composition.
It is used in the treatment and prophylaxis of anthrax and Leptospirosis.It is also effective against Yersinia pestis (the infectious agent of bubonic plague), and is prescribed for the treatment of Lyme disease, ehrlichiosis, and Rocky Mountain spotted fever.
Doxycycline is indicated for treatment of:
When bacteriologic testing indicates appropriate susceptibility to the drug, doxycycline may be used to treat these infections caused by Gram-negative bacteria:
Some Gram-positive bacteria have developed resistance to doxycycline. Up to 44% of Streptococcus pyogenes and up to 74% of S. faecalis specimens have developed resistance to the tetracycline group of antibiotics. When bacteriologic testing indicates appropriate susceptibility to the drug, doxycycline may be used to treat these infections caused by Gram-positive bacteria:
When penicillin is contraindicated, doxycycline can be used to treat:
Doxycycline may also be used as adjunctive therapy for severe acne.
The first-line treatment for brucellosis is a combination of doxycycline and streptomycin and the second-line is a combination of doxycycline and rifampicin (rifampin).
Doxycycline is active against the erythrocytic stages of Plasmodium falciparum but not against the gametocytes of Plasmodium falciparum.It is used to prevent malaria. 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 Guidelines states that the combination of doxycycline with either artesunate or quinine may be used for the treatment of uncomplicated malaria due to Plasmodium falciparum or following intravenous treatment of severe malaria.
Doxycycline kills the symbiotic Wolbachia bacteria in the reproductive tracts of parasitic filarial nematodes, making the nematodes sterile, and thus reducing transmission of diseases such as onchocerciasis and elephantiasis.Field trials in 2005 showed an eight-week course of doxycycline almost completely eliminates the release of microfilariae.
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.
Adverse effects are similar to those of other members of the tetracycline 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.
The combination of doxycycline with dairy, antacids, calcium supplements, iron products, and laxatives containing magnesium is not inherently dangerous, but any of these foods and supplements may decrease doxycycline's effectiveness.
Breakfast was observed to reduce doxycycline absorption significantly. Absorption of tetracycline occurs in the stomach and the upper small intestine. Absorption of tetracyclines has been reported to be impaired by milk products, aluminum hydroxide gels, sodium bicarbonate, calcium and magnesium salts, laxatives containing magnesium and iron preparations. The mechanisms responsible for decreased absorption appear to be chelation and an increase in gastric pH. ... In view of these results, it is advisable to instruct the patients to take doxycycline on an empty stomach.
Previously, doxycycline was believed to impair the effectiveness of many types of hormonal contraception due to CYP450 induction. Recent 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.
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.
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 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 so has a long elimination half life, and does not accumulate in the kidneys of patients with renal failure 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.
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 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.
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-epitetracyclinecausing Fanconi syndrome. 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.
After penicillin revolutionized the treatment of bacterial infections in WWII, many chemical companies moved into the field of discovering antibiotics by bioprospecting. American Cyanamid was one of these, and in the late 1940s chemists there discovered chlortetracycline, the first member of the tetracycline class of antibiotics.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 tetracycline itself, the first semi-synthetic antibiotic. Charlie Stephens' group at Pfizer worked on further analogs and created one with greatly improved stability and pharmacological efficacy: doxycycline. It was clinically developed in the early 1960s and approved by the FDA in 1967.
As its patent grew near to expiring in the early 1970s, the patent became the subject of lawsuit between Pfizer and International Rectifierthat wasn't 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 doxycyline "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, Actavis, 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.
Doxycycline is available worldwide under many brand names.Doxycycline is available as a generic medicine and is generally inexpensive. The wholesale cost is between US$0.01 and $0.04 per pill.
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.
Doxycycline has been used successfully in the treatment of one patient with lymphangioleiomyomatosis, an otherwise progressive and fatal disease.It has also been shown to attenuate cardiac hypertrophy (in mice), a deadly consequence of prolonged hypertension. In chronic obstructive pulmonary disease, doxycycline has been shown to improve lung functions in patients with stable symptoms.
Doxycycline is also used in "tet-on" (gene expression activated by doxycycline) and "tet-off" (gene expression inactivated by doxycycline) tetracycline-controlled transcriptional activation to regulate transgene expression in organisms and cell cultures.Doxycycline is more stable than tetracycline for this purpose.
Other experimental applications include:
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 may have anticancer activity.
Amoxicillin is an antibiotic often used for the treatment of a number of bacterial infections. These include middle ear infection, strep throat, pneumonia, skin infections, and urinary tract infections among others. It is taken by mouth, or less commonly by injection.
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 symptoms. Signs and symptoms, when present, may include lower abdominal pain, vaginal discharge, fever, burning with urination, pain with sex, bleeding after sex, or irregular menstruation. Untreated PID can result in long-term complications including infertility, ectopic pregnancy, chronic pelvic pain, and cancer.
Clarithromycin, sold under the brand name Biaxin among others, is an antibiotic used to treat various bacterial infections. This includes strep throat, pneumonia, skin infections, H. pylori infection, and Lyme disease, among others. Clarithromycin can be taken by mouth as a pill or liquid.
Minocycline, sold under the brand name Minocin among others, is a tetracycline antibiotic used to treat a number of bacterial infections such as pneumonia. It is generally less preferred than the tetracycline doxycycline. It is also used for the treatment of acne and rheumatoid arthritis. It is taken by mouth.
Atypical pneumonia, also known as walking pneumonia, is the type of pneumonia not caused by one of the pathogens most commonly associated with the disease. Its clinical presentation contrasts to that of "typical" pneumonia. A variety of microorganisms can cause it. When it develops independently from another disease it is called primary atypical pneumonia (PAP).
Chlamydia trachomatis, commonly known as chlamydia, is a bacterium that can replicate only in human cells. It causes chlamydia, which can manifest in various ways, including: trachoma, lymphogranuloma venereum, nongonococcal urethritis, cervicitis, salpingitis, pelvic inflammatory disease. C. trachomatis is the most common infectious cause of blindness and the most common sexually transmitted bacterium.
Oxytetracycline was the second of the broad-spectrum tetracycline group of antibiotics to be discovered.
Azithromycin is an antibiotic used for the treatment of a number of bacterial infections. This includes middle ear infections, strep throat, pneumonia, traveler's diarrhea, and certain other intestinal infections. It may also be used for a number of sexually transmitted infections, including chlamydia and gonorrhea infections. Along with other medications, it may also be used for malaria. It can be taken by mouth or intravenously with doses once per day.
Lower respiratory tract infection (LRTI), while often used as a synonym for pneumonia, can also be applied to other types of infection including lung abscess and acute bronchitis. Symptoms include shortness of breath, weakness, fever, coughing and fatigue.
Chlamydophila pneumoniae is a species of Chlamydophila, an obligate intracellular bacterium that infects humans and is a major cause of pneumonia. It was known as the Taiwan acute respiratory agent (TWAR) from the names of the two original isolates – Taiwan (TW-183) and an acute respiratory isolate designated AR-39. Until recently, it was known as Chlamydia pneumoniae, and that name is used as an alternate in some sources. In some cases, to avoid confusion, both names are given.
Tigecycline is an antibiotic for a number of bacterial infections. It is a glycylcycline administered intravenously. It was developed in response to the growing rate of antibiotic resistant bacteria such as Staphylococcus aureus, Acinetobacter baumannii, and E. coli. As a tetracycline derivative antibiotic, its structural modifications has expanded its therapeutic activity to include Gram-positive and Gram-negative organisms, including those of multi-drug resistance.
Cefotaxime is an antibiotic used to treat a number of bacterial infections. Specifically it is used to treat joint infections, pelvic inflammatory disease, meningitis, pneumonia, urinary tract infections, sepsis, gonorrhea, and cellulitis. It is given either by injection into a vein or muscle.
Gemifloxacin mesylate is an oral broad-spectrum quinolone antibacterial agent used in the treatment of acute bacterial exacerbation of chronic bronchitis and mild-to-moderate pneumonia. Vansen Pharma Inc. has licensed the active ingredient from LG Life Sciences of Korea.
Acute exacerbation of COPD is a sudden worsening of COPD symptoms that typically lasts for several days. It may be triggered by an infection with bacteria or viruses or by environmental pollutants. Typically, infections cause 75% or more of the exacerbations; bacteria can roughly be found in 25% of cases, viruses in another 25%, and both viruses and bacteria in another 25%. Airway inflammation is increased during the exacerbation resulting in increased hyperinflation, reduced expiratory air flow and decreased gas exchange.
Tubal factor infertility (TFI) is female infertility caused by diseases, obstructions, damage, scarring, congenital malformations or other factors which impede the descent of a fertilized or unfertilized ovum into the uterus through the Fallopian tubes and prevents a normal pregnancy and full term birth. Tubal factors cause 25-30% of infertility cases. Tubal factor is one complication of Chlamydia trachomatis infection in women.