Clarithromycin
Encyclopedia
Clarithromycin is a macrolide
antibiotic
used to treat pharyngitis
, tonsillitis
, acute maxillary sinusitis
, acute bacterial exacerbation of chronic bronchitis
, pneumonia
(especially atypical pneumonias associated with Chlamydia pneumoniae or TWAR), skin and skin structure infections. In addition, it is sometimes used to treat Legionellosis
, Helicobacter pylori
, and lyme disease
.
Clarithromycin is available under several brand names, for example Crixan, Clarac, Biaxin, Klaricid, Klacid, Klaram, Klabax, Claripen, Clarem, Claridar, Fromilid, Clacid, Clacee, Vikrol, Infex and Clariwin, Resclar.
in the 1970s. The product emerged through efforts to develop a version of the antibiotic erythromycin
that did not experience acid instability in the digestive tract, causing side effects, such as nausea and stomach ache. Taisho filed for patent protection for the drug around 1980 and subsequently introduced a branded version of its drug, called Clarith, to the Japanese market in 1991. In 1985 Taisho partnered with the American company Abbott Laboratories
for the international rights, and Abbott also gained FDA approval for Biaxin in October 1991. The drug went generic
in Europe in 2004 and in the US in mid-2005.
Antibacterial spectrum is the same as erythromycin but it is active against Mycobacterium avium complex MAV , M. leprae and atypical mycobacteria.
from growing by interfering with their protein synthesis. Clarithromycin binds to the subunit 50S of the bacterial ribosome
and thus inhibits the translation of peptide
s. Clarithromycin has similar antimicrobial spectrum as erythromycin but is more effective against certain gram-negative bacteria, particularly Legionella pneumophila
. Besides this bacteriostatic effect, clarithromycin also has bactericidal effect on certain strains such as Haemophilus influenzae
, Streptococcus pneumoniae
and Neisseria gonorrhoeae
.
s. Due to the high concentration in phagocytes, clarithromycin is actively transported to the site of infection. During active phagocytosis, large concentrations of clarithromycin are released. The concentration of clarithromycin in the tissues can be over 10 times higher than in plasma. Highest concentrations were found in liver and lung tissue.
, nausea, extreme irritability, abdominal pain and vomiting, facial swelling. Less common side-effects include headaches, hallucinations (auditory and visual), dizziness/motion sickness, rashes, alteration in senses of smell and taste, including a metallic taste that lasts the entire time one takes it. Dry mouth, panic and / or anxiety attacks and nightmares have also been reported albeit less frequently. In more serious cases it has been known to cause jaundice
, cirrhosis
, and kidney problems including renal failure
. Uneven heartbeats, chest pain, and shortness of breath have also been reported while taking this drug.
Clarithromycin may cause false positives on urine drug screens for cocaine.
Adverse effects of clarithromycin in the central nervous system include dizziness, ototoxicity
and headaches, but delirium and mania are also uncommon side effects.
When taken along with some statins, drugs used to reduce blood serum cholesterol levels, muscle pain may occur.
There is also the risk of oral candidiasis
, due to the increased yeast
production in the body from the antibiotics.
or bradycardia
), or an electrolyte imbalance (e.g., low potassium or magnesium levels). Many other drugs can interact with clarithromycin, which is why the doctor should be informed of any other drugs the patient is taking concomitantly.
Clarithromycin is almost never used in HIV patients due to significant interaction with HIV drugs. Clarithromycin should not be used in pregnant patients.
Clarithromycin can also cause serotonin syndrome symptoms when taken in conjunction with buspirone
(Buspar).
Clarithromycin almost doubles the level of carbamazepine
in serum by reducing its clearance inducing toxic symptoms of Carbamazepine, including diplopia and nausea besides hyponatremia (reduced level of Sodium in serum). Research in many cases has shown a sharp increase in serum level of Carbamazepine in patients who were given Clarithromycin. Therefore, for epileptic patients taking carbamazepine, Clarithromycin should be better avoided.
, Roxane, Sandoz
, Teva
and Wockhardt. It is also used as part of a combination therapy to treat Helicobacter pylori. In the Middle East it is available as Claridar, produced by Dar Al Dawa. In India, Acnesol-CL gel, containing 1% w/w Clarithromycin, marketed by Systopic, is used to treat acne vulgaris
.
Clarithromycin can cause liver disease.
Macrolide
The 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...
antibiotic
Antibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...
used to treat pharyngitis
Pharyngitis
Pharyngitis is an inflammation of the throat or pharynx. In most cases it is quite painful, and is the most common cause of a sore throat.Like many types of inflammation, pharyngitis can be acute – characterized by a rapid onset and typically a relatively short course – or chronic....
, tonsillitis
Tonsillitis
Tonsillitis is an inflammation of the tonsils most commonly caused by viral or bacterial infection. Symptoms of tonsillitis include sore throat and fever. While no treatment has been found to shorten the duration of viral tonsillitis, bacterial causes are treatable with antibiotics...
, acute maxillary sinusitis
Sinusitis
Sinusitis 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...
, acute bacterial exacerbation of chronic bronchitis
Bronchitis
Acute bronchitis is an inflammation of the large bronchi in the lungs that is usually caused by viruses or bacteria and may last several days or weeks. Characteristic symptoms include cough, sputum production, and shortness of breath and wheezing related to the obstruction of the inflamed airways...
, pneumonia
Pneumonia
Pneumonia 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...
(especially atypical pneumonias associated with Chlamydia pneumoniae or TWAR), skin and skin structure infections. In addition, it is sometimes used to treat Legionellosis
Legionellosis
Legionellosis is a potentially fatal infectious disease caused by gram negative, aerobic bacteria belonging to the genus Legionella. Over 90% of legionellosis cases are caused by Legionella pneumophila, a ubiquitous aquatic organism that thrives in temperatures between , with an optimum temperature...
, Helicobacter pylori
Helicobacter pylori
Helicobacter pylori , previously named Campylobacter pyloridis, is a Gram-negative, microaerophilic bacterium found in the stomach. It was identified in 1982 by Barry Marshall and Robin Warren, who found that it was present in patients with chronic gastritis and gastric ulcers, conditions that were...
, and lyme disease
Lyme disease
Lyme 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...
.
Clarithromycin is available under several brand names, for example Crixan, Clarac, Biaxin, Klaricid, Klacid, Klaram, Klabax, Claripen, Clarem, Claridar, Fromilid, Clacid, Clacee, Vikrol, Infex and Clariwin, Resclar.
History
Clarithromycin was invented by researchers at the Japanese drug company Taisho PharmaceuticalTaisho Pharmaceutical
is a Japanese pharmaceutical company based in Tokyo.-History:Taisho was established in 1912 to produce over-the-counter drugs. The company moved into prescription drug R&D in 1955.-Products:...
in the 1970s. The product emerged through efforts to develop a version of the antibiotic erythromycin
Erythromycin
Erythromycin 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...
that did not experience acid instability in the digestive tract, causing side effects, such as nausea and stomach ache. Taisho filed for patent protection for the drug around 1980 and subsequently introduced a branded version of its drug, called Clarith, to the Japanese market in 1991. In 1985 Taisho partnered with the American company Abbott Laboratories
Abbott Laboratories
Abbott Laboratories is an American-based global, diversified pharmaceuticals and health care products company. It has 90,000 employees and operates in over 130 countries. The company headquarters are in Abbott Park, North Chicago, Illinois. The company was founded by Chicago physician, Dr....
for the international rights, and Abbott also gained FDA approval for Biaxin in October 1991. The drug went generic
Generic drug
A generic drug is a drug defined as "a drug product that is comparable to brand/reference listed drug product in dosage form, strength, route of administration, quality and performance characteristics, and intended use." It has also been defined as a term referring to any drug marketed under its...
in Europe in 2004 and in the US in mid-2005.
Antibacterial spectrum is the same as erythromycin but it is active against Mycobacterium avium complex MAV , M. leprae and atypical mycobacteria.
Mechanism of action
Clarithromycin prevents bacteriaBacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
from growing by interfering with their protein synthesis. Clarithromycin binds to the subunit 50S of the bacterial ribosome
Ribosome
A 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 the translation of peptide
Peptide
Peptides are short polymers of amino acid monomers linked by peptide bonds. They are distinguished from proteins on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptides, consisting of two amino acids joined by a single peptide bond...
s. Clarithromycin has similar antimicrobial spectrum as erythromycin but is more effective against certain gram-negative bacteria, particularly Legionella pneumophila
Legionella pneumophila
Legionella pneumophila is a thin, ærobic, pleomorphic, flagellated, non-spore forming, Gram-negative bacterium of the genus Legionella. L. pneumophila is the primary human pathogenic bacterium in this group and is the causative agent of legionellosis or Legionnaires' disease.-Characterization:L...
. Besides this bacteriostatic effect, clarithromycin also has bactericidal effect on certain strains such as Haemophilus influenzae
Haemophilus influenzae
Haemophilus 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...
, Streptococcus pneumoniae
Streptococcus pneumoniae
Streptococcus pneumoniae, or pneumococcus, is Gram-positive, alpha-hemolytic, aerotolerant anaerobic member of the genus Streptococcus. A significant human pathogenic bacterium, S...
and Neisseria gonorrhoeae
Neisseria gonorrhoeae
Neisseria gonorrhoeae, also known as gonococci , or gonococcus , is a species of Gram-negative coffee bean-shaped diplococci bacteria responsible for the sexually transmitted infection gonorrhea.N...
.
Pharmacokinetics
Unlike erythromycin, clarithromycin is acid-stable and can therefore be taken orally without being protected from gastric acids. It is readily absorbed, and diffused into most tissues and phagocytePhagocyte
Phagocytes are the white blood cells that protect the body by ingesting harmful foreign particles, bacteria, and dead or dying cells. Their name comes from the Greek phagein, "to eat" or "devour", and "-cyte", the suffix in biology denoting "cell", from the Greek kutos, "hollow vessel". They are...
s. Due to the high concentration in phagocytes, clarithromycin is actively transported to the site of infection. During active phagocytosis, large concentrations of clarithromycin are released. The concentration of clarithromycin in the tissues can be over 10 times higher than in plasma. Highest concentrations were found in liver and lung tissue.
Metabolism
Clarithromycin has a fairly rapid first-pass hepatic metabolism. However, 14-hydroxy clarithromycin, clarithromycin's metabolite, is almost twice as active and has a half life of 7 hours compared to clarithromycin's 5. Clarithromycin and its metabolites main routes of elimination are urinary and biliary excretion. Of all the drugs in its class, clarithromycin has the best bioavailability at 50%, which makes it amenable to oral administration.Side effects
Most common side-effects are gastrointestinal: DiarrheaDiarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
, nausea, extreme irritability, abdominal pain and vomiting, facial swelling. Less common side-effects include headaches, hallucinations (auditory and visual), dizziness/motion sickness, rashes, alteration in senses of smell and taste, including a metallic taste that lasts the entire time one takes it. Dry mouth, panic and / or anxiety attacks and nightmares have also been reported albeit less frequently. In more serious cases it has been known to cause jaundice
Jaundice
Jaundice is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...
, cirrhosis
Cirrhosis
Cirrhosis is a consequence of chronic liver disease characterized by replacement of liver tissue by fibrosis, scar tissue and regenerative nodules , leading to loss of liver function...
, and kidney problems including renal failure
Renal failure
Renal failure or kidney failure describes a medical condition in which the kidneys fail to adequately filter toxins and waste products from the blood...
. Uneven heartbeats, chest pain, and shortness of breath have also been reported while taking this drug.
Clarithromycin may cause false positives on urine drug screens for cocaine.
Adverse effects of clarithromycin in the central nervous system include dizziness, ototoxicity
Ototoxicity
Ototoxicity is damage to the ear , specifically the cochlea or auditory nerve and sometimes the vestibular system, by a toxin. It is commonly medication-induced; ototoxic drugs include antibiotics such as the aminoglycoside gentamicin, loop diuretics such as furosemide, and platinum-based...
and headaches, but delirium and mania are also uncommon side effects.
When taken along with some statins, drugs used to reduce blood serum cholesterol levels, muscle pain may occur.
There is also the risk of oral candidiasis
Oral candidiasis
Oral candidiasis is an infection of yeast fungi of the genus Candida on the mucous membranes of the mouth. It is frequently caused by Candida albicans, or less commonly by Candida glabrata or Candida tropicalis...
, due to the increased yeast
Yeast
Yeasts are eukaryotic micro-organisms classified in the kingdom Fungi, with 1,500 species currently described estimated to be only 1% of all fungal species. Most reproduce asexually by mitosis, and many do so by an asymmetric division process called budding...
production in the body from the antibiotics.
Resistance
Many Gram positive microbes quickly develop resistance to clarithromycin after standard courses of treatment, most frequently via acquisition of the erm(B) gene, which confers high-level resistance to all macrolides.Contraindications
Clarithromycin should be used with caution if the patient has liver or kidney disease, certain heart problems (e.g., QT prolongationQT interval
In cardiology, the QT interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle. In general, the QT interval represents electrical depolarization and repolarization of the left and right ventricles...
or bradycardia
Bradycardia
Bradycardia , in the context of adult medicine, is the resting heart rate of under 60 beats per minute, though it is seldom symptomatic until the rate drops below 50 beat/min. It may cause cardiac arrest in some patients, because those with bradycardia may not be pumping enough oxygen to their heart...
), or an electrolyte imbalance (e.g., low potassium or magnesium levels). Many other drugs can interact with clarithromycin, which is why the doctor should be informed of any other drugs the patient is taking concomitantly.
Clarithromycin is almost never used in HIV patients due to significant interaction with HIV drugs. Clarithromycin should not be used in pregnant patients.
Clarithromycin can also cause serotonin syndrome symptoms when taken in conjunction with buspirone
Buspirone
Buspirone is an anxiolytic psychoactive drug of the azapirone chemical class, and is primarily used to treat generalized anxiety disorder Bristol-Myers Squibb gained FDA approval of buspirone in 1986 for treatment of GAD...
(Buspar).
Clarithromycin almost doubles the level of carbamazepine
Carbamazepine
Carbamazepine is an anticonvulsant and mood-stabilizing drug used primarily in the treatment of epilepsy and bipolar disorder, as well as trigeminal neuralgia...
in serum by reducing its clearance inducing toxic symptoms of Carbamazepine, including diplopia and nausea besides hyponatremia (reduced level of Sodium in serum). Research in many cases has shown a sharp increase in serum level of Carbamazepine in patients who were given Clarithromycin. Therefore, for epileptic patients taking carbamazepine, Clarithromycin should be better avoided.
Drugs using clarithromycin
In the United States generic clarithromycin is available from Andrx, Genpharm, Ivax, Ranbaxy LaboratoriesRanbaxy Laboratories
Ranbaxy Laboratories Limited is a pharmaceutical company that was incorporated in India in 1961. The company went public in 1973 and Japanese pharmaceutical company Daiichi Sankyo gained majority control in 2008...
, Roxane, Sandoz
Sandoz
Founded in 2003, Sandoz presently is the generic drug subsidiary of Novartis, a multinational pharmaceutical company. The company develops, manufactures and markets generic drugs as well as pharmaceutical and biotechnological active ingredients....
, Teva
Teva Pharmaceutical Industries
Teva Pharmaceutical Industries Ltd. , is an international pharmaceutical company headquartered in Petah Tikva, Israel. It specializes in generic and proprietary pharmaceuticals and active pharmaceutical ingredients...
and Wockhardt. It is also used as part of a combination therapy to treat Helicobacter pylori. In the Middle East it is available as Claridar, produced by Dar Al Dawa. In India, Acnesol-CL gel, containing 1% w/w Clarithromycin, marketed by Systopic, is used to treat acne vulgaris
Acne vulgaris
Acne vulgaris is a common human skin disease, characterized by areas of skin with seborrhea , comedones , papules , pustules , Nodules and possibly scarring...
.
Potential increased mortality using clarithromycin
In the CLARICOR Trial, the use of short-term clarithromycin treatment correlated with an increased incidence of deaths which were classified as sudden cardiac deathshttp://www.ntkinstitute.org/news/content.nsf/NTKPaperFrameSet?OpenForm&pp=1&id=DD265946C30AC73B85256DA4005C2980&newsid=852576140048867C85257865001C8B5F&locref=ntkwatch&u=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=21447948, http://content.karger.com/produktedb/produkte.asp?DOI=000324533&typ=pdf.Clarithromycin can cause liver disease.
External links
- Biaxin XL Official web site by Abbott LaboratoriesAbbott LaboratoriesAbbott Laboratories is an American-based global, diversified pharmaceuticals and health care products company. It has 90,000 employees and operates in over 130 countries. The company headquarters are in Abbott Park, North Chicago, Illinois. The company was founded by Chicago physician, Dr....
- U.S. Patent 4,331,803