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| Clinical data | |
|---|---|
| Trade names | Biaxin, Klav, etc. |
| Other names | 6-O-Methylerythromycin A |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a692005 |
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| Routes of administration | By mouth,intravenous |
| Drug class | Macrolides |
| ATC code | |
| Legal status | |
| Legal status | |
| Pharmacokinetic data | |
| Bioavailability | 50% |
| Protein binding | Low binding |
| Metabolism | Liver |
| Eliminationhalf-life | 3–4 h |
| Identifiers | |
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| CAS Number | |
| PubChemCID | |
| DrugBank |
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| UNII | |
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| ChEMBL | |
| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.119.644 |
| Chemical and physical data | |
| Formula | C38H69NO13 |
| Molar mass | 747.964 g·mol−1 |
| 3D model (JSmol) | |
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Clarithromycin, sold under the brand nameBiaxin among others, is anantibiotic used to treat variousbacterial infections.[5] This includesstrep throat,pneumonia, skin infections,H. pylori infection, andLyme disease, among others.[5] Clarithromycin can be taken by mouth as a tablet or liquid or can be infused intravenously.[5]
Common side effects include nausea, vomiting, headaches, and diarrhea.[5] Severeallergic reactions are rare.[5] Liver problems have been reported.[5] It may cause harm if taken duringpregnancy.[5] It is in themacrolide class and works by slowing down bacterialprotein synthesis.[5] Clarithromycin resistance is already a major challenge to healthcare systems and such resistance is spreading, leading to recommendations to test the susceptibility of pathogenic organisms to the antibiotic before commencing clarithromycin therapy.[6]
Clarithromycin was developed in 1980 and approved for medical use in 1990.[7][8] It is on theWorld Health Organization's List of Essential Medicines.[9] Clarithromycin is available as a generic medication.[5] It is made fromerythromycin and is chemically known as 6-O-methylerythromycin.[10]
Clarithromycin is primarily used to treat a number of bacterial infections includingpneumonia,Helicobacter pylori, and as an alternative topenicillin instrep throat.[5] Other uses includecat scratch disease and other infections due toBartonella,cryptosporidiosis, as a second line agent inLyme disease andtoxoplasmosis.[5] It may also be used to preventbacterial endocarditis in those who cannot take penicillin.[5] It is effective against upper and lower respiratory tract infections, skin and soft tissue infections andhelicobacter pylori infections associated with duodenal ulcers.[citation needed]
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Aerobic Gram-positive bacteria
Aerobic Gram-negative bacteria
Helicobacter
Mycobacteria
Mycobacterium avium complex consisting of:
Other bacteria
Safety and effectiveness of clarithromycin in treating clinical infections due to the following bacteria have not been established in adequate and well-controlled clinical trials:[11]
Aerobic Gram-positive bacteria
Aerobic Gram-negative bacteria
Anaerobic Gram-positive bacteria
Anaerobic Gram-negative bacteria
Clarithromycin has been researched as a potential treatment foridiopathic hypersomnia (IH) in adults, but the evidence is limited. A 2021Cochrane study determined that the evidence is inadequate to definitively determine the efficacy of clarithromycin in the management of idiopathic hypersomnia.[12] TheAmerican Academy of Sleep Medicine's 2021 clinical practice guidelines conditionally suggested its use, especially for those who don't respond to other therapies.[13][14]
The most common side effects are gastrointestinal:diarrhea (3%),nausea (3%), abdominal pain (3%), andvomiting (6%). It also can cause headaches,insomnia, and abnormalliver function tests. Allergic reactions include rashes andanaphylaxis. Less common side effects (<1%) include extreme irritability, hallucinations (auditory and visual), dizziness/motion sickness, and alteration in senses of smell and taste, including a metallic taste. Dry mouth, panic attacks, and nightmares have also been reported, albeit less frequently.[15]
In February 2018, the USFood and Drug Administration (FDA) issued a safety communication warning with respect to an increased risk for heart problems or death with the use of clarithromycin, and has recommended that alternative antibiotics be considered in those with heart disease.[16]
Clarithromycin can lead to a prolongedQT interval. In patients withlong QT syndrome, cardiac disease, or patients taking other QT-prolonging medications, this can increase risk for life-threateningarrhythmias.[17]
In one trial, the use of short-term clarithromycin treatment was correlated with an increased incidence of deaths classified as sudden cardiac deaths in stable coronary heart disease patients not using statins.[18]
Clarithromycin has been known to causejaundice,cirrhosis, and kidney problems, includingkidney failure.[citation needed] Some case reports suspect it of causing liver disease.[19]
Common adverse effects of clarithromycin in the central nervous system include dizziness, headaches. Rarely, it can causeototoxicity, delirium and mania.[citation needed]
A risk oforal candidiasis andvaginal candidiasis, due to the elimination of theyeast's natural bacterial competitors by the antibiotic, has also been noted.[citation needed]
Clarithromycin should not be used in pregnant women except in situations where no alternative therapy is appropriate.[11] Clarithromycin can cause potential hazard to the fetus hence should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.[11] For lactating mothers it is not known whether clarithromycin is excreted in human milk.[11]
Clarithromycin inhibits a liver enzyme,CYP3A4, involved in the metabolism of many other commonly prescribed drugs. Taking clarithromycin with other medications that are metabolized by CYP3A4 may lead to unexpected increases or decreases indrug levels.[20][21]
A few of the common interactions are listed below.
Clarithromycin has been observed to have a dangerous interaction withcolchicine as the result of inhibition of CYP3A4 metabolism andP-glycoprotein transport. Combining these two drugs may lead to fatal colchicine toxicity, particularly in people withchronic kidney disease.[11]
Taking clarithromycin concurrently with certainstatins (a class of drugs used to reduce blood serumcholesterol levels) increases the risk of side effects, such as muscle aches and muscle break down (rhabdomyolysis).[22]
Concurrent therapy withcalcium channel blocker may increase risk oflow blood pressure,kidney failure, and death, compared to pairing calcium channel blockers withazithromycin, a drug similar to clarithromycin but without CYP3A4 inhibition.[23] Administration of clarithromycin in combination with verapamil have been observed to causelow blood pressure,low heart rate, andlactic acidosis.[11]
Clarithromycin may double the level ofcarbamazepine in the body by reducing its clearance, which may lead to toxic symptoms of carbamazepine, such asdouble vision,loss of voluntary body movement, and nausea, as well ashyponatremia.[24]
Depending on the combination of medications, clarithromycin therapy could be contraindicated, require changing doses of some medications, or be acceptable without dose adjustments.[25] For example, clarithromycin may lead to decreasedzidovudine concentrations.[26]
Clarithromycin preventsbacteria from multiplying by acting as aprotein synthesis inhibitor. It binds to 23S rRNA, a component of the 50S subunit of the bacterialribosome, thus inhibiting thetranslation ofpeptides.[citation needed]
In addition to its antibiotic activity, clarithromycin has been found to act as anegative allosteric modulator of theGABAA receptor.[27] In relation to this action, it may havewakefulness-promoting effects in people withhypersomnia.[27]
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Unlike erythromycin, clarithromycin is acid-stable, so can be taken orally without having to be protected from gastric acids. It is readily absorbed, and diffuses into most tissues andphagocytes. 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; its concentration in the tissues can be over 10 times higher than in plasma. Highest concentrations are found in liver, lung tissue, and stool.
Clarithromycin has a fairly rapidfirst-pass metabolism in the liver. Its major metabolites include an inactive metabolite, N-desmethylclarithromycin, and an active metabolite, 14-(R)-hydroxyclarithromycin. Compared to clarithromycin, 14-(R)-hydroxyclarithromycin is less potent against mycobacterial tuberculosis and theMycobacterium avium complex. Clarithromycin (20%-40%) and its active metabolite (10%-15%) are excreted in urine. Of all the drugs in its class, clarithromycin has the bestbioavailability at 50%, which makes it amenable to oral administration. Its elimination half-life is about 3 to 4 hours with 250 mg administered every 12 h, but increased to 5 to 7 h with 500 mg administered every 8 to 12 h. With any of these dosing regimens, the steady-state concentration of this metabolite is generally attained within 3 to 4 days.[28]
Clarithromycin was invented by researchers at the Japanese drug companyTaisho Pharmaceutical in 1980.[7] The product emerged through efforts to develop a version of the antibioticerythromycin 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 companyAbbott Laboratories for the international rights, and Abbott also gained FDA approval for Biaxin in October 1991. The drug wentgeneric in Europe in 2004 and in the US in mid-2005.[29]
Clarithromycin is available as a generic medication.[5] In the United States, clarithromycin is available as immediate-release tablets, extended-release tablets, and granules for oral suspension.[5]
Clarithromycin is available under several brand names in many different countries, including Biaxin, Crixan, Claritron, Clarihexal, Clacid, Claritt, Clacee, Clarac, Clariwin, Claripen, Clarem, Claridar, Cloff, Fromilid, Infex, Kalixocin, Karicin, Klaricid, Klaridex, Klacid, Klaram, Klabax, Klerimed, MegaKlar, Monoclar, Resclar, Rithmo, Truclar, Vikrol and Zeclar.[citation needed]
In the UK the drug product is manufactured in generic form by a number of manufacturers including Somex Pharma, Brown & Burk UK Ltd., Ranbaxy, Aptil and Sandoz.
Clarithromycin has been studied in aphase 2clinical trial in the treatment ofcentralhypersomnolence (i.e., idiopathic hypersomnolence andnarcolepsy withoutcataplexy).[27] There was no apparent improvement on an objective measure ofvigilance, but subjectivesleepiness was reduced with the drug compared toplacebo.[27] It is thought to work for this use as aGABAA receptornegative allosteric modulator.[27]
There is insufficient evidence to conclude whether clarithromycin is effective for the treatment of idiopathic hypersomnia.
Recommendation 9: We suggest that clinicians use clarithromycin (vs no treatment) for the treatment of idiopathic hypersomnia in adults. (CONDITIONAL)
