Clarithromycin

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Clarithromycin

Systematic (IUPAC) name
(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
Clinical data
Trade names	Biaxin
AHFS/Drugs.com	monograph
MedlinePlus	a692005
Pregnancy cat.	C (USA) B3 (Aus)
Legal status	?
Routes	oral, intravenous
Pharmacokinetic data
Bioavailability	50%
Protein binding	low binding
Metabolism	hepatic
Half-life	3-4 hours
Identifiers
CAS number	81103-11-9 Y
ATC code	J01FA09
PubChem	CID 5284534
DrugBank	DB01211
ChemSpider	21112273 N
UNII	H1250JIK0A Y
KEGG	D00276 Y
ChEMBL	CHEMBL143 N
Chemical data
Formula	C38H69NO13
Mol. mass	747.953 g/mol
SMILES	eMolecules & PubChem
InChI 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 Y Key:AGOYDEPGAOXOCK-LERDGGEFSA-N Y
N(what is this?)  (verify)

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, Claritt,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 Pharmaceutical 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.

Mechanism of action

Clarithromycin prevents bacteria from growing by interfering with their protein synthesis. Clarithromycin binds to the subunit 50S of the bacterial ribosome and thus inhibits the translation of peptides. 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.

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 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. 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: diarrhea, 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 elimination of the yeast's natural bacterial competitors by the antibiotic.

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.^[1]

Contraindications

Clarithromycin should be used with caution if the patient has liver or kidney disease, certain heart problems (e.g., QT prolongation or bradycardia), or an electrolyte imbalance (e.g., low potassium or sodium 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 is not to 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 should avoid taking Clarithromycin.

Drugs using clarithromycin

In the United States generic clarithromycin is available from Andrx, Genpharm, Ivax, Ranbaxy Laboratories, 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.

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 deaths.^[2]

There have been case reports, suspecting that clarithromycin can cause liver disease.^[3]

References

External links

• "Biaxin XL (labeling)" (pdf). Abbott Laboratories. http://www.rxabbott.com/pdf/biapi.PDF. 
• US patent 4331803, Watanabe, Y.; Morimoto, S. & Omura, S., "Novel erythromycin compounds", issued 1981-05-19, assigned to Taisho Pharmaceutical