Clarithromycin
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| Systematic (IUPAC) name |
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(3R,4S,5S,6R,7R,9R,11S,12R,13S,14S)-6-{[(2S,3R,4S,6R) -4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy} -14-ethyl-12,13-dihydroxy-4-{[(2R,4S,5S,6S)-5-hydroxy -4-methoxy-4,6-dimethyloxan-2-yl]oxy}-7 -methoxy-3,5,7,9,11,13-hexamethyl -1-oxacyclotetradecane-2,10-dione
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| Clinical data |
| Trade names |
Biaxin |
| AHFS/Drugs.com |
monograph |
| MedlinePlus |
a692005 |
Pregnancy
category |
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Routes of
administration |
oral, intravenous |
| Legal status |
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| Pharmacokinetic data |
| Bioavailability |
50% |
| Protein binding |
low binding |
| Metabolism |
hepatic |
| Biological half-life |
3–4 h |
| Identifiers |
| CAS Number |
81103-11-9 Y |
| ATC code |
J01FA09 (WHO) |
| PubChem |
CID 5284534 |
| DrugBank |
DB01211 Y |
| ChemSpider |
10342604 |
| UNII |
H1250JIK0A Y |
| KEGG |
D00276 Y |
| ChEMBL |
CHEMBL1741 N |
| Chemical data |
| Formula |
C38H69NO13 |
| Molar mass |
747.953 g/mol |
SMILES
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CC[C@@H]1[C@@]([C@@H]([C@H](C(=O)[C@@H](C[C@@]([C@@H]([C@H]([C@@H]([C@H](C(=O)O1)C)O[C@H]2C[C@@]([C@H]([C@@H](O2)C)O)(C)OC)C)O[C@H]3[C@@H]([C@H](C[C@H](O3)C)N(C)C)O)(C)OC)C)C)O)(C)O
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InChI
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InChI=1S/C38H69NO13/c1-15-26-38(10,45)31(42)21(4)28(40)19(2)17-37(9,47-14)33(52-35-29(41)25(39(11)12)16-20(3)48-35)22(5)30(23(6)34(44)50-26)51-27-18-36(8,46-13)32(43)24(7)49-27/h19-27,29-33,35,41-43,45H,15-18H2,1-14H3/t19-,20-,21+,22+,23-,24+,25+,26-,27+,29-,30+,31-,32+,33-,35+,36-,37-,38-/m1/s1
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Key:AGOYDEPGAOXOCK-KCBOHYOISA-N
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| NY (what is this?) (verify) |
Clarithromycin, sold under the brand name Biaxin, is an antibiotic used to treat various bacterial infections.[1] 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.[1]
Common side effects include nausea, vomiting, headaches, and diarrhea. Severe allergic reactions are rare. Liver problems have been reported. It may cause harm if taken during pregnancy. It is in the macrolide class and works by stopping the making of protein by some bacteria.[1]
Clarithromycin was developed in 1980.[2] It is on the World Health Organization's List of Essential Medicines the most important medications needed in a basic health system.[3] Clarithromycin is available as a generic medication.[1] The wholesale cost is between 0.13 and 0.79 USD per dose.[4] In the United States it is moderately expensive at 50 to 100 USD for a course of treatment.[5] It is made from erythromycin and is chemically known as 6-O-methylerythromycin.[6]
Contents
- 1 Medical uses
- 1.1 Spectrum of bacterial susceptibility
- 2 Contraindications
- 3 Side effects
- 3.1 Cardiac
- 3.2 Liver and kidney
- 3.3 Central nervous system
- 3.4 Infection
- 3.5 Pregnancy and breastfeeding
- 4 Interactions
- 4.1 Colchicine
- 4.2 Statins
- 4.3 Calcium channel blockers
- 4.4 Carbamazepine
- 4.5 HIV medications
- 5 Mechanism of action
- 6 Pharmacokinetics
- 7 Metabolism
- 8 History
- 9 Society and culture
- 9.1 Cost
- 9.2 Available forms
- 9.3 Brand names
- 9.4 Manufacturers
- 10 References
- 11 External links
Medical uses
Clarithromycin is primarily used to treat a number of bacterial infections including: pneumonia, Helicobacter pylori and as an alternative to penicillin in strep throat.[1] Other uses include: cat scratch disease and other infections due to bartonella, cryptosporidiosis, as a second line agent in Lyme disease and toxoplasmosis.[1] It may also be used to prevent bacterial endocarditis in those who cannot take penicillin.[1] It is effective against upper and lower respiratory tract infections, skin and soft tissue infections and helicobacter pylori infections associated with duodenal ulcers.
Spectrum of bacterial susceptibility
Aerobic Gram-positive bacteria
- Staphylococcus aureus
- Streptococcus pneumoniae
- Streptococcus pyogenes
Aerobic Gram-negative bacteria
- Haemophilus parainfluenzae
- Haemophilus influenzae
- Moraxella catarrhalis
Heliobacter
Mycobacteria
Mycobacterium avium complex consisting of:
- Mycobacterium avium avium
- Mycobacterium intracellulare
Other bacteria
- Chlamydia pneumoniae
- Mycoplasma pneumoniae
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:[7]
Aerobic Gram-Positive bacteria
- Streptococcus agalactiae
- Streptococcus (Groups C, F, G)
- Viridans group streptococci
Aerobic Gram-Negative bacteria
- Bordetella pertussis
- Legionella pneumophila
- Pasteurella multocida
Anaerobic Gram-Positive bacteria
- Clostridium perfringens
- Peptococcus niger
- Propionibacterium acnes
Anaerobic Gram-Negative bacteria
- Prevotella melaninogenica (formerly Bacteroides melaninogenicus)
Contraindications
- you should not take Clarithromycin if you are allergic to other macrolides or the ingredients in the tablets which include microcrystalline cellulose, croscarmelose sodium, magnesium stearate and povidon
- Clarithromycin should not be used in people with a history of cholestatic jaundice and/or liver dysfunction associated with prior clarithromycin use.[7]
- or if you have hypokalaemia (low blood potassium)
- Use of clarithromycin with the following medications: cisapride, pimozide, astemizole, terfenadine, ergotamine, ticagrelor, ranolazine or dihydroergotamine is not recommended.[7]
- It should not be used with colchicine in people with kidney or liver impairment.[7]
- Concomitant use with cholesterol medications such as lovastatin or simvastatin.[7]
- Hypersensitivity to clarithromycin or any component of the product, erythromycin, or any macrolide antibiotics.[7]
- QT prolongation or ventricular cardiac arrhythmias, including torsade de pointes.[7]
Side effects
The most common side effects are gastrointestinal: diarrhea (3%), nausea (3%), abdominal pain (3%), and vomiting (6%). It also can cause headaches, insomnia, and abnormal liver function tests. Allergic reactions include rashes and anaphylaxis. 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.[1]
Cardiac
Clarithromycin can lead to a prolonged QT interval. In patients with long QT syndrome, cardiac disease, or patients taking other QT-prolonging medications, this can increase risk for life-threatening arrhythmias.[8]
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.[9] Some case reports suspect it of causing liver disease.[10]
Liver and kidney
Clarithromycin has been known to cause jaundice, cirrhosis, and kidney problems, including renal failure.
Central nervous system
Common adverse effects of clarithromycin in the central nervous system include dizziness, headaches. Rarely, it can cause ototoxicity, delirium and mania.
Infection
A risk of oral candidiasis, due to the elimination of the yeast's natural bacterial competitors by the antibiotic, is also incurred.
Pregnancy and breastfeeding
Clarithromycin should not be used in pregnant women except in situations where no alternative therapy is appropriate.[7] 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.[7] For lactating mothers it is not known whether clarithromycin is excreted in human milk.[7]
Interactions
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 in drug levels.
A few of the common interactions are listed below.
Colchicine
Clarithromycin has been observed to have a dangerous interaction with colchicine as the result of inhibition of CYP3A4 metabolism and P-glycoprotein transport. Combining these two drugs may lead to fatal colchicine toxicity, particularly in patients with renal insufficiency.[7]
Statins
Taking clarithromycin concurrently with certain statins (a class of drugs used to reduce blood serum cholesterol levels), increases the risk of side effects, such as muscle aches and muscle break down (rhabdomyolysis).[11]
Calcium channel blockers
Concurrent therapy with calcium channel blocker may increase risk of low blood pressure, kidney failure, and death, compared to pairing calcium channel blockers with azithromycin, a drug similar to clarithromycin but without CYP3A4 inhibition.[12] Administration of clarithromycin in combination with verapamil have been observed to cause low blood pressure, low heart rate, and lactic acidosis.[7]
Carbamazepine
Clarithromycin may double the level of carbamazepine in the body by reducing its clearance, which may lead to toxic symptoms of carbamazepine, such as double vision, loss of body movement, nausea, as well as hyponatremia.[13]
HIV medications
Depending on the combination of medications, clarithromycin therapy could be contraindicated, require changing doses of some medications, or be acceptable without dose adjustments.[14] For example, clarithromycin may lead to decreased zidovudine concentrations.[15]
Mechanism of action
Clarithromycin prevents bacteria by acting as a protein synthesis inhibitor. It binds to 23S rRNA, a component of the 50S subunit of the bacterial ribosome, thus inhibiting the translation of peptides.
Pharmacokinetics
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 and phagocytes. 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.
Metabolism
Clarithromycin has a fairly rapid first-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 the Mycobacterium 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 best bioavailability 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.[16]
History
Clarithromycin was invented by researchers at the Japanese drug company Taisho Pharmaceutical in 1980.[2] 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 stomachache. 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.
Society and culture
Cost
Clarithromycin is available as a generic medication.[1] The wholesale cost is between 0.13 and 0.79 USD per dose.[4] In the United States it is moderately expensive at 50 to 100 USD for a course of treatment.[5]
Available forms
In the United States, clarithromycin is available as immediate release tablets, extended release tablets, and granules for oral suspension.[1]
Brand names
Clarithromycin is available under several brand names in many different countries, for example Binoclar, Biclar, Bioclar, Biaxin, Crixan, Claritron, Clarihexal, Clacid, Claritt, Clacee, Clarac, Clariwin, Claripen, Clarem, Claridar, Fromilid, Infex, Kalixocin, Karicin, Klaricid, Klacid, Klaram, Klabax, Monoclar, Resclar, Rithmo, Truclar, and Vikrol.
Manufacturers
In the UK it is manufactured in generic form by a number of manufacturers including Somex Pharma and Ranbaxy.
References
- ^ a b c d e f g h i "Clarithromycin". The American Society of Health-System Pharmacists. Retrieved September 4, 2015.
- ^ a b Greenwood, David (2008). Antimicrobial drugs : chronicle of a twentieth century medical triumph (1 ed.). Oxford: Oxford University Press. p. 239. ISBN 9780199534845.
- ^ "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014.
- ^ a b "Clarithromycin". International Drug Price Indicator Guide. Retrieved 7 September 2015.
- ^ a b Hamilton, Richart (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 92. ISBN 9781284057560.
- ^ Kirst, Herbert A. (2012). Macrolide Antibiotics (2 ed.). Basel: Birkhäuser Basel. p. 53. ISBN 9783034881050.
- ^ a b c d e f g h i j k l "BIAXIN® Filmtab® (clarithromycin tablets, USP) BIAXIN® XL Filmtab® (clarithromycin extended-release tablets) BIAXIN® Granules (clarithromycin for oral suspension, USP)" (PDF). November 2, 2015. Retrieved November 2, 2015.
- ^ Yamaguchi S, Kaneko Y, Yamagishi T, et al. [Clarithromycin-induced torsades de pointes]. Nippon Naika Gakkai Zasshi. 2003;92(1):143–5.
- ^ Winkel, P.; Hilden, J. R.; Fischer Hansen, J. R.; Hildebrandt, P.; Kastrup, J.; Kolmos, H. J. R.; Kjøller, E.; Jespersen, C. M.; Gluud, C.; Jensen, G. B.; Claricor Trial, G. (2011). "Excess Sudden Cardiac Deaths after Short-Term Clarithromycin Administration in the CLARICOR Trial: Why is This So, and Why Are Statins Protective". Cardiology 118 (1): 63–67. doi:10.1159/000324533. PMID 21447948.
- ^ Tietz, A.; Heim, M. H.; Eriksson, U.; Marsch, S.; Terracciano, L.; Krähenbühl, S. (2003). "Fulminant liver failure associated with clarithromycin". The Annals of Pharmacotherapy 37 (1): 57–60. doi:10.1345/1542-6270(2003)037<0057:flfawc>2.0.co;2. PMID 12503933.
- ^ Patel AM, Shariff S, Bailey DG, et al. Statin toxicity from macrolide antibiotic coprescription: a population-based cohort study. Ann Intern Med. 2013;158(12):869–76.
- ^ Gandhi, Sonja; Fleet, Jamie L.; Bailey, David G.; McArthur, Eric; Wald, Ron; Rehman, Faisal; Garg, Amit X. (2013-12-18). "Calcium-channel blocker-clarithromycin drug interactions and acute kidney injury". JAMA 310 (23): 2544–2553. doi:10.1001/jama.2013.282426. ISSN 1538-3598. PMID 24346990.
- ^ Gélisse, P.; Hillaire-Buys, D.; Halaili, E.; Jean-Pastor, M.-J.; Vespignan, H.; Coubes, P.; Crespel, A. (2007-11-01). "[Carbamazepine and clarithromycin: a clinically relevant drug interaction]". Revue Neurologique 163 (11): 1096–1099. ISSN 0035-3787. PMID 18033049.
- ^ Sekar VJ, Spinosa-guzman S, De paepe E, et al. Darunavir/ritonavir pharmacokinetics following coadministration with clarithromycin in healthy volunteers. J Clin Pharmacol. 2008;48(1):60–5.
- ^ Polis, M. A.; Piscitelli, S. C.; Vogel, S.; Witebsky, F. G.; Conville, P. S.; Petty, B.; Kovacs, J. A.; Davey, R. T.; Walker, R. E. (1997-08-01). "Clarithromycin lowers plasma zidovudine levels in persons with human immunodeficiency virus infection". Antimicrobial Agents and Chemotherapy 41 (8): 1709–1714. ISSN 0066-4804. PMC 163990. PMID 9257746.
- ^ Ferrero JL, Bopp BA, Marsh KC, et al. Metabolism and Disposition of Clarithromycin in Man. Drug Metab Dispos. 1990;18(4):441–446. [PubMed 1976065]
External links
- "Biaxin XL (labeling)" (pdf). Abbott Laboratories.
- US patent 4331803, Watanabe, Y.; Morimoto, S. & Omura, S., "Novel erythromycin compounds", issued 1981-05-19, assigned to Taisho Pharmaceutical
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Antibacterials: protein synthesis inhibitors (J01A, J01B, J01F, J01G, QJ01XQ)
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| 30S |
Aminoglycosides
(initiation inhibitors) |
| -mycin (Streptomyces) |
- Streptomycin#
- Dihydrostreptomycin
- Neomycin#
- Framycetin
- Paromomycin
- Ribostamycin
- Kanamycin#
- Amikacin
- Arbekacin
- Bekanamycin
- Dibekacin
- Tobramycin
- Spectinomycin#
- Hygromycin B
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| -micin (Micromonospora) |
- Gentamicin#
- Netilmicin
- Sisomicin
- Isepamicin
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Tetracycline antibiotics
(tRNA binding) |
| Tetracyclines |
- Doxycycline#
- Chlortetracycline
- Clomocycline
- Demeclocycline
- Lymecycline
- Meclocycline
- Metacycline
- Minocycline
- Oxytetracycline
- Penimepicycline
- Rolitetracycline
- Tetracycline
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| Glycylcyclines |
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| 50S |
Oxazolidinone
(initiation inhibitors) |
- Eperezolid
- Linezolid
- Posizolid
- Radezolid
- Ranbezolid
- Sutezolid
- Tedizolid
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| Peptidyl transferase |
| Amphenicols |
- Chloramphenicol#
- Azidamfenicol
- Thiamphenicol
- Florfenicol
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| Pleuromutilins |
- Retapamulin
- Tiamulin
- Valnemulin
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| MLS (transpeptidation/translocation) |
| Macrolides |
- Azithromycin#
- Clarithromycin
- Dirithromycin
- Erythromycin#
- Flurithromycin
- Josamycin
- Midecamycin
- Miocamycin
- Oleandomycin
- Rokitamycin
- Roxithromycin
- Spiramycin
- Troleandomycin
- Tylosin
- Ketolides
- Telithromycin
- Cethromycin
- Solithromycin†
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| Lincosamides |
- Clindamycin#
- Lincomycin
- Pirlimycin
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| Streptogramins |
- Pristinamycin
- Quinupristin/dalfopristin
- Virginiamycin
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| EF-G |
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- #WHO-EM
- ‡Withdrawn from market
- Clinical trials:
- †Phase III
- §Never to phase III
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