Azithromycin is an
azalideAzalides are a class of macrolide antibiotics which contain a nitrogen in the macrolide ring. This imparts different pharmacokinetic properties and is associated with greater stability of the molecule. One such azalide is the antibiotic azithromycin....
, a subclass of
macrolideThe macrolides are a group of drugs whose activity stems from the presence of a macrolide ring, a large macrocyclic lactone ring to which one or more deoxy sugars, usually cladinose and desosamine, may be attached. The lactone rings are usually 14-, 15-, or 16-membered...
antibiotics. Azithromycin is one of the world's best-selling antibiotics. It is derived from
erythromycinErythromycin is a macrolide antibiotic that has an antimicrobial spectrum similar to or slightly wider than that of penicillin, and is often used for people who have an allergy to penicillins. For respiratory tract infections, it has better coverage of atypical organisms, including mycoplasma and...
, with a methyl-substituted
nitrogenNitrogen is a chemical element that has the symbol N, atomic number of 7 and atomic mass 14.00674 u. Elemental nitrogen is a colorless, odorless, tasteless, and mostly inert diatomic gas at standard conditions, constituting 78.08% by volume of Earth's atmosphere...
atomThe atom is a basic unit of matter that consists of a dense central nucleus surrounded by a cloud of negatively charged electrons. The atomic nucleus contains a mix of positively charged protons and electrically neutral neutrons...
incorporated into the
lactoneIn chemistry, a lactone is a cyclic ester which can be seen as the condensation product of an alcohol group -OH and a carboxylic acid group -COOH in the same molecule...
ring, thus making the lactone ring 15-membered.
Azithromycin is used to treat or prevent certain bacterial infections, most often those causing
middle ear infectionsOtitis media is inflammation of the middle ear, or a middle ear infection.It occurs in the area between the tympanic membrane and the inner ear, including a duct known as the eustachian tube. It is one of the two categories of ear inflammation that can underlie what is commonly called an earache,...
,
strep throatStreptococcal pharyngitis, streptococcal tonsillitis, or streptococcal sore throat is a type of pharyngitis caused by a group A streptococcal infection. It affects the pharynx including the tonsils and possibly the larynx. Common symptoms include fever, sore throat, and enlarged lymph nodes...
,
pneumoniaPneumonia is an inflammatory condition of the lung—especially affecting the microscopic air sacs —associated with fever, chest symptoms, and a lack of air space on a chest X-ray. Pneumonia is typically caused by an infection but there are a number of other causes...
, typhoid, and
sinusitisSinusitis is inflammation of the paranasal sinuses, which may be due to infection, allergy, or autoimmune issues. Most cases are due to a viral infection and resolve over the course of 10 days...
. In recent years, it has been used primarily to prevent bacterial infections in infants and those with weaker immune systems. It is also effective against certain sexually transmitted infections, such as
non-gonococcal urethritisNongonococcal urethritis 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 nongonococcal urethritis .-Causes:There are many causes of...
, chlamydia, and
cervicitisCervicitis is inflammation of the uterine cervix. Cervicitis in women has many features in common with urethritis in men and many cases are caused by sexually transmitted infections...
. Recent studies have indicated it also to be effective against late-onset
asthmaAsthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...
, but these findings are controversial and not widely accepted.
Medical uses
Azithromycin is used to treat many different infections including acute otitis media, streptococcal pharyngitis, gastrointestinal infections such as
traveler's diarrheaTraveler's diarrhea , is the most common illness affecting travelers. An estimated 10 million people—20% to 50% of international travelers—develop it annually. TD is defined as three or more unformed stools in 24 hours passed by a traveler, commonly accompanied by abdominal cramps, nausea, and...
, respiratory tract infections such as
pneumoniaPneumonia is an inflammatory condition of the lung—especially affecting the microscopic air sacs —associated with fever, chest symptoms, and a lack of air space on a chest X-ray. Pneumonia is typically caused by an infection but there are a number of other causes...
,
cellulitisCellulitis is a diffuse inflammation of connective tissue with severe inflammation of dermal and subcutaneous layers of the skin. Cellulitis can be caused by normal skin flora or by exogenous bacteria, and often occurs where the skin has previously been broken: cracks in the skin, cuts, blisters,...
,
babesiosisBabesiosis is a malaria-like parasitic disease caused by infection with Babesia, a genus of protozoal piroplasms. After trypanosomes, Babesia are thought to be the second most common blood parasites of mammals and they can have a major impact on health of domestic animals in areas without severe...
,
bartonellaBartonella is a genus of Gram-negative bacteria. Facultative intracellular parasites, Bartonella species can infect healthy people but are considered especially important as opportunistic pathogens. Bartonella are transmitted by insect vectors such as ticks, fleas, sand flies and mosquitoes...
,
chancroidChancroid is a sexually transmitted infection characterized by painful sores on the genitalia...
choleraCholera is an infection of the small intestine that is caused by the bacterium Vibrio cholerae. The main symptoms are profuse watery diarrhea and vomiting. Transmission occurs primarily by drinking or eating water or food that has been contaminated by the diarrhea of an infected person or the feces...
,
donovanosisGranuloma inguinale is a bacterial disease caused by K. granulomatis characterized by ulcerative genital lesions. It is endemic in many less developed regions...
,
leptospirosisLeptospirosis is caused by infection with bacteria of the genus Leptospira, and affects humans as well as other mammals, birds, amphibians, and reptiles.The...
,
lyme diseaseLyme disease, or Lyme borreliosis, is an emerging infectious disease caused by at least three species of bacteria belonging to the genus Borrelia. Borrelia burgdorferi sensu stricto is the main cause of Lyme disease in the United States, whereas Borrelia afzelii and Borrelia garinii cause most...
,
malariaMalaria is a mosquito-borne infectious disease of humans and other animals caused by eukaryotic protists of the genus Plasmodium. The disease results from the multiplication of Plasmodium parasites within red blood cells, causing symptoms that typically include fever and headache, in severe cases...
,
mycobacterium avium complexMycobacterium avium complex is a group of genetically related bacteria belonging to the genus Mycobacterium. It includes Mycobacterium avium and Mycobacterium intracellulare....
, neisseria meningitis,
pelvic inflammatory diseasePelvic inflammatory disease is a generic term for inflammation of the uterus, fallopian tubes, and/or ovaries as it progresses to scar formation with adhesions to nearby tissues and organs. This may lead to infections. PID is a vague term and can refer to viral, fungal, parasitic, though most...
,
pertussisPertussis, also known as whooping cough , is a highly contagious bacterial disease caused by Bordetella pertussis. Symptoms are initially mild, and then develop into severe coughing fits, which produce the namesake high-pitched "whoop" sound in infected babies and children when they inhale air...
,
scrub typhusScrub typhus or Bush typhus is a form of typhus caused by Orientia tsutsugamushi first isolated and identified in 1930 in Japan., accessdate: 16 October 2011...
,
toxoplasmosisToxoplasmosis is a parasitic disease caused by the protozoan Toxoplasma gondii. The parasite infects most genera of warm-blooded animals, including humans, but the primary host is the felid family. Animals are infected by eating infected meat, by ingestion of feces of a cat that has itself...
, and
salmonellaSalmonella is a genus of rod-shaped, Gram-negative, non-spore-forming, predominantly motile enterobacteria with diameters around 0.7 to 1.5 µm, lengths from 2 to 5 µm, and flagella which grade in all directions . They are chemoorganotrophs, obtaining their energy from oxidation and reduction...
. It is used to prevent bacterial endocarditis and some sexually transmitted illnesses post sexual assault.
It has a similar antimicrobial spectrum as
erythromycinErythromycin is a macrolide antibiotic that has an antimicrobial spectrum similar to or slightly wider than that of penicillin, and is often used for people who have an allergy to penicillins. For respiratory tract infections, it has better coverage of atypical organisms, including mycoplasma and...
, but is more effective against certain
Gram-negativeGram-negative bacteria are bacteria that do not retain crystal violet dye in the Gram staining protocol. In a Gram stain test, a counterstain is added after the crystal violet, coloring all Gram-negative bacteria with a red or pink color...
bacteria, in particular,
Haemophilus influenzaeHaemophilus influenzae, formerly called Pfeiffer's bacillus or Bacillus influenzae, Gram-negative, rod-shaped bacterium first described in 1892 by Richard Pfeiffer during an influenza pandemic. A member of the Pasteurellaceae family, it is generally aerobic, but can grow as a facultative anaerobe. H...
. Azithromycin resistance has been described and is
endemicIn epidemiology, an infection is said to be endemic in a population when that infection is maintained in the population without the need for external inputs. For example, chickenpox is endemic in the UK, but malaria is not...
in many areas. Long-term use in treating
Staphylococcus aureusStaphylococcus aureus is a facultative anaerobic Gram-positive coccal bacterium. It is frequently found as part of the normal skin flora on the skin and nasal passages. It is estimated that 20% of the human population are long-term carriers of S. aureus. S. aureus is the most common species of...
infections with azithromycin may increase bacterial resistance to this and other macrolide antibiotics.
Azithromycin has been shown to be effective against
malariaMalaria is a mosquito-borne infectious disease of humans and other animals caused by eukaryotic protists of the genus Plasmodium. The disease results from the multiplication of Plasmodium parasites within red blood cells, causing symptoms that typically include fever and headache, in severe cases...
when used in combination with
artesunateArtesunate is part of the artemisinin group of drugs that treat malaria. It is a semi-synthetic derivative of artemisinin that is water-soluble and may therefore be given by injection...
or
quinineQuinine is a natural white crystalline alkaloid having antipyretic , antimalarial, analgesic , anti-inflammatory properties and a bitter taste. It is a stereoisomer of quinidine which, unlike quinine, is an anti-arrhythmic...
; the optimal dose for this is not yet known.
Adverse effects
Most common side-effects are gastrointestinal: diarrhea (5%), nausea (3%), abdominal pain (3%), and vomiting. Fewer than 1% of patients stop taking the drug due to side-effects. Nervousness, dermatologic reactions, and
anaphylaxisAnaphylaxis is defined as "a serious allergic reaction that is rapid in onset and may cause death". It typically results in a number of symptoms including throat swelling, an itchy rash, and low blood pressure...
have been reported. As with all antimicrobial agents,
pseudomembranous colitisPseudomembranous colitis, a cause of antibiotic-associated diarrhea , is an infection of the colon. It is often, but not always, caused by the bacterium Clostridium difficile. Because of this, the informal name C. difficile colitis is also commonly used. The illness is characterized by...
can occur during and up to several weeks after azithromycin therapy. This drug may interfere with the effectiveness of birth control pills; other forms of contraception may be required during the treatment period. Azithromycin suspension has an objectionable taste, so can be difficult to administer to young children, i.e., 2–5 years, who may spit it out.
Occasional patients have developed cholestatic hepatitis or
deliriumDelirium or acute confusional state is a common and severe neuropsychiatric syndrome with core features of acute onset and fluctuating course, attentional deficits and generalized severe disorganization of behavior...
. Accidental intravenous overdosage in an infant caused severe heart block, resulting in residual encephalopathy.
Mechanism of action
Azithromycin prevents bacteria from growing by interfering with their protein synthesis. Azithromycin binds to the 50S subunit of the bacterial
ribosomeA ribosome is a component of cells that assembles the twenty specific amino acid molecules to form the particular protein molecule determined by the nucleotide sequence of an RNA molecule....
, and thus inhibits translation of mRNA. Nucleic acid synthesis is not affected.
Pharmacokinetics
Unlike erythromycin,azithromycin is acid-stable and can therefore be taken orally with no need of protection from gastric acids. It is readily absorbed, but its absorption is greater on an empty stomach. Time to peak concentration in adults is 2.1 to 3.2 hours for oral dosage forms and one to two hours after a dose. Due to the high concentration in phagocytes, azithromycin is actively transported to the site of infection. During active phagocytosis, large concentrations of azithromycin are released. The concentration of azithromycin in the tissues can be over 50 times higher than in plasma. This is due to
ion trappingThe term ion trapping is used to describe the build-up of a higher concentration of a chemical across a cell membrane due to the pKa value of the chemical and difference of pH across the cell membrane...
and the high lipid solubility (volume of distribution is too low).
Azithromycin's half-life allows a large single dose to be administered and yet maintain bacteriostatic levels in the infected tissue for several days.
Metabolism
According to Davis' Drug Guide for Nurses, following a single 500 mg dose, the half-life of azithromycin is 11–14 hours. The longer half-life of 68 hours is achieved only when multiple doses are consumed, allowing a "steady state" of medication in the body.
BiliaryBilirubin is the yellow breakdown product of normal heme catabolism. Heme is found in hemoglobin, a principal component of red blood cells. Bilirubin is excreted in bile and urine, and elevated levels may indicate certain diseases...
excretion of azithromycin, predominantly unchanged, is a major route of elimination. Over the course of a week, approximately 6% of the administered dose appears as unchanged drug in
urineUrine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...
.
Etymology
Azithromycin's name is derived from the
azane-substituent and
ErythromycinErythromycin is a macrolide antibiotic that has an antimicrobial spectrum similar to or slightly wider than that of penicillin, and is often used for people who have an allergy to penicillins. For respiratory tract infections, it has better coverage of atypical organisms, including mycoplasma and...
.
History
A team of researchers at the
CroatiaCroatia , officially the Republic of Croatia , is a unitary democratic parliamentary republic in Europe at the crossroads of the Mitteleuropa, the Balkans, and the Mediterranean. Its capital and largest city is Zagreb. The country is divided into 20 counties and the city of Zagreb. Croatia covers ...
n pharmaceutical company
PlivaPliva d.d. is a Croatian pharmaceutical company, based in Zagreb, Croatia. One of the world's largest producers of generic Adderall, it has seen drastic increases in revenue with an increasing number of patients being diagnosed with Attention Deficit Disorder . It is the largest pharmaceutical...
— Gabrijela Kobrehel, Gorjana Radobolja-Lazarevski, Zrinka Tamburašev, led by Dr. Slobodan Đokić — discovered azithromycin in 1980. It was patented in 1981. In 1986, Pliva and
PfizerPfizer, Inc. is an American multinational pharmaceutical corporation. The company is based in New York City, New York with its research headquarters in Groton, Connecticut, United States...
signed a licensing agreement, which gave Pfizer exclusive rights for the sale of azithromycin in Western Europe and the United States. Pliva put its azithromycin on the market in Central and Eastern Europe under the brand name of Sumamed in 1988. Pfizer launched azithromycin under Pliva's licence in other markets under the brand name Zithromax in 1991.
After several years, the
U.S. Food and Drug AdministrationThe Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
approved AzaSite, an ophthalmic formulation of azithromycin, for the treatment of eye infections. AzaSite is marketed in the U.S. and Canada by Inspire Pharmaceuticals, a wholly owned subsidiary of
MerckMerck & Co., Inc. , also known as Merck Sharp & Dohme or MSD outside the United States and Canada, is one of the largest pharmaceutical companies in the world. The Merck headquarters is located in Whitehouse Station, New Jersey, an unincorporated area in Readington Township...
.
Available forms
Azithromycin is commonly administered in tablet or oral
suspensionIn chemistry, a suspension is a heterogeneous fluid containing solid particles that are sufficiently large for sedimentation. Usually they must be larger than 1 micrometer. The internal phase is dispersed throughout the external phase through mechanical agitation, with the use of certain...
(a one-dose version was made available in 2005). It is also available for
intravenousIntravenous therapy or IV therapy is the infusion of liquid substances directly into a vein. The word intravenous simply means "within a vein". Therapies administered intravenously are often called specialty pharmaceuticals...
injectionAn injection is an infusion method of putting fluid into the body, usually with a hollow needle and a syringe which is pierced through the skin to a sufficient depth for the material to be forced into the body...
and in a 1% ophthalmic solution. Tablets come in doses of 250 mg and 500 mg. Oral suspension comes in strengths of 100 mg/5 mL and 200 mg/5 mL. The 250 mg tablets are often dispensed in packages of six and commonly referred to as a "Z-Pak," whereas the 500 mg tablets are commonly available commercially in a pack of three tablets, or "Tri-Pak," intended as a three-day treatment. A common dose of oral azithromycin therapy consists of a "double dose" of medication on the first day of treatment and subsequent treatment for four or five additional days. With the "Z-Pak," this means two 250 mg tablets (a total of 500 mg) on the first day and one 250 mg tablet once daily for the next four days.
Pfizer brand-name, i.e. Zithromax, azithromycin tablets are mottled pink, unscored, film-coated, modified-oval-shaped tablets containing azithromycin monohydrate and the following inactive ingredients:
butylated hydroxytolueneButylated hydroxytoluene , also known as butylhydroxytoluene, is a lipophilic organic compound that is primarily used as an antioxidant food additive as well as an antioxidant additive in cosmetics, pharmaceuticals, jet fuels, rubber, petroleum products, electrical transformer oil, and embalming...
,
calcium phosphateCalcium phosphate is the name given to a family of minerals containing calcium ions together with orthophosphates , metaphosphates or pyrophosphates and occasionally hydrogen or hydroxide ions ....
,
carmineCarmine , also called Crimson Lake, Cochineal, Natural Red #4, C.I. 75470, or E120, is a pigment of a bright-red color obtained from the aluminum salt of carminic acid, which is produced by some scale insects, such as the cochineal beetle and the Polish cochineal, and is used as a general term for...
, colloidal
silicon dioxideThe chemical compound silicon dioxide, also known as silica , is an oxide of silicon with the chemical formula '. It has been known for its hardness since antiquity...
, FD&C
red # 40Allura Red AC is a red azo dye that goes by several names including: Allura Red, Food Red 17, C.I. 16035, FD&C Red 40, 2-naphthalenesulfonic acid, 6-hydroxy-5--, disodium salt, and disodium 6-hydroxy-5--2-naphthalenesulfonate. It is used as a food dye and has the E number E129...
lake, FD&C
yellow # 6Sunset Yellow FCF is a synthetic yellow azo dye, manufactured from aromatic hydrocarbons from petroleum. When added to foods, it is denoted by E Number E110...
lake,
hypromelloseHypromellose , short for hydroxypropyl methylcellulose , is a semisynthetic, inert, viscoelastic polymer used as an ophthalmic lubricant, as well as an excipient and controlled-delivery component in oral medicaments, found in a variety of commercial products.As a food additive, hypromellose is an...
(2910, 15cP),
lactose monohydrateLactose is a disaccharide sugar that is found most notably in milk and is formed from galactose and glucose. Lactose makes up around 2~8% of milk , although the amount varies among species and individuals. It is extracted from sweet or sour whey. The name comes from or , the Latin word for milk,...
,
magnesium stearateMagnesium stearate, also called octadecanoic acid, magnesium salt, is a white substance which is solid at room temperature. It has the chemical formula . It is a salt containing two equivalents of stearate and one magnesium cation...
,
pregelatinized starchStarch or amylum is a carbohydrate consisting of a large number of glucose units joined together by glycosidic bonds. This polysaccharide is produced by all green plants as an energy store...
, sodium lauryl sulfate,
talcTalc is a mineral composed of hydrated magnesium silicate with the chemical formula H2Mg34 or Mg3Si4O102. In loose form, it is the widely-used substance known as talcum powder. It occurs as foliated to fibrous masses, its crystals being so rare as to be almost unknown...
,
titanium dioxideTitanium dioxide, also known as titanium oxide or titania, is the naturally occurring oxide of titanium, chemical formula . When used as a pigment, it is called titanium white, Pigment White 6, or CI 77891. Generally it comes in two different forms, rutile and anatase. It has a wide range of...
, and
triacetinThe triglyceride 1,2,3-triacetoxypropane is more generally known as triacetin and glycerin triacetate. It is the triester of glycerol and acetic acid....
. In Colombia (South America) it is marketed under
Zaret from Laboratorios Bussié.
External links