Article: Clarithromycin

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. weight	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 infections, and, in HIV and AIDS patients to prevent, and to treat, disseminated Mycobacterium avium complex or MAC. In addition, it is sometimes used to treat Legionellosis.

Clarithromycin is available under several brand names, for example Biaxin, Klacid, and Claripen.

History

Clarithromycin was invented by scientists at the Japanese drug company Taisho Pharmaceutical in the 1970s. The product had emerged through efforts to develop a version of the antibiotic erythromycin that did not experience acid instability in the digestive track 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.

Potential new uses

The Australian biotechnology company Giaconda is working on a new triple drug therapy for Crohn's disease that combines clarithromycin with rifabutin and and clofazimine.

Available forms

Clarithromycin is commonly administered in tablets (Biaxin®), extended-release tablets (Biaxin XL®), or oral suspension. In the United States generic clarithromycin is available from Andrx, Genpharm, Ivax, Ranbaxy Laboratories, Roxane, Sandoz, Teva and Wockhardt.

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 translocation of peptides. Clarithromycin has similar antimicrobial spectrum as erythromycin, but is more effective against certain gram-negative bacteria, particularly Legionella pneumophilae. 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 is 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, i.e 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.

Side effects

Most common side-effects are gastrointestinal; diarrhea, nausea, abdominal pain and vomiting. Less common side-effects include headaches, rashes, alteration in senses of smell and taste.

Special Precautions

Allergic reactions can occur with clarithromycin use. People with a history of allergy, asthma, hay fever or hives seem to be more susceptible to these reactions. The reaction can be immediate and severe.

Allergic symptoms include wheezing, hives, itching, swelling, spasms in the throat and breathing tubes, joint and muscle pain, difficulty breathing, fever and skin rashes. Nausea and vomiting are not symptoms of an allergic reaction.

Contraindications

Clarithromycin should be used with caution if the patient has liver or kidney disease, certain heart problems (e.g., QTc prolongation or bradycardia), or a mineral imbalance (e.g., low potassium or magnesium levels).