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Clarithromycin

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Clarithromycin

Systematic (IUPAC) name

6-(4-dimethylamino-3-hydroxy- 6-methyl-tetrahydropyran-2-yl) oxy-14-ethyl-12,13-dihydroxy-

4-(5-hydroxy-4-methoxy-4,6- dimethyl-tetrahydropyran-2-yl) oxy-7-methoxy-3,5,7,9,11, 13-hexamethyl-1- oxacyclotetradecane-2,10-dione

Identifiers

CAS number 81103-11-9

ATC code J01FA09

PubChem 84029

DrugBank APRD00181

Chemical data

Formula C38H69NO13

Mol. mass 747.953 g/mol

Pharmacokinetic data

Bioavailability 50%

Protein binding low binding

Metabolism hepatic

Half life 3-4 hours

Excretion ?

Therapeutic considerations

Pregnancy cat. C (USA)

B3 (Aus)

Legal status

Routes oral

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 infectionsi, and, in HIV and AIDS patients to prevent, and to treat, disseminated Mycobacterium avium complex (MAC). In addition, it is sometimes used to treat Legionellosis. Clarithromycin is available under several brand names, for example Biaxin, Klaricid, Klabax, Claripen, Claridar and Clacid.

Contents

1 History

2 Available forms

3 Mechanism of action

4 Pharmacokinetics

5 Metabolism

6 Special precautions

7 Resistance

8 Contraindications

9 Drugs using clarithromycin

10 References

History

Clarithromycin was invented by scientists 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 and thereby cause side effects, such as nausea and stomach ache. Taisho filed for patent protection over its new drug around 1980 and subsequently introduced a branded version of its drug, called Clarith, to the Japanese market in 1991. In 1985 Taisho had 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 U.S. in mid-2005. Side effects include bad taste on tongue.

Available forms

These clarithromycin caplets are stamped with "93" on one side and "7244" on the other.Clarithromycin is commonly administered in tablets (Biaxin), extended-release tablets (Biaxin XL), oral suspension, or in a gel/lotion based form for topical use.

Mechanism of action

Clarithromycin prevents bacteria from growing by interfering with their protein synthesis. Clarithromycin binds to the subunit 50S of the bacterial ribosomei 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, that is, it is metabolised by the liver. However, this metabolite, 14-hydroxy clarithromycin is almost twice as active as clarithromycin. The half-life of clarithromycin is about 5 hours and 14-hydroxy clarithromycin's about 7 hours. Clarithromycin's and its metabolites' main routes of elimination are urinary and biliary excretion.

Special precautions

Allergic reactions can occur with clarithromycin use. People with a history of allergy, asthmai, hay fever or hives seem to be more susceptible to these reactions, and it is normally recommended they avoid the use of Clarithromycin. The reaction can be immediate and severe.

Allergic symptoms include wheezing, hives, itching, swelling, spasms in the throat and breathing tubes, swelling of the face and neck, joint and muscle pain, difficulty breathing, fever and skin rashes. Rashes can range in severity, the most serious cases being toxic epidermal necrolysis and Stevens-Johnson syndrome. Nausea and vomiting are not symptoms of an allergic reaction.

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 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.

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.

References

Malhotra-Kumar S, Lammens C, Coenen S, et al. (2007). "Effect of azithromycin and clarithromycin therapy on pharyngeal carriage of macrolide-resistant streptococci in healthy volunteers: A randomised, double-blind, placebo-controlled study". Lancet 369: 482–90. doi:10.1016/S0140-6736(07)60235-9 . PMID 17292768.

Biaxin XL Official web site by Abbott Laboratories

U.S. Patent 4,331,803

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