Clarithromycin

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
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 infections, 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 and lyme disease. Clarithromycin is available under several brand names, for example Crixan, Biaxin, Klaricid, Klabax, Claripen, Claridar, Fromilid, Clacid, Vikrol, and infex

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.

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.

Side effects

Most common side-effects are gastrointestinal: diarrhea, nausea, abdominal pain and vomiting, facial swelling. Less common side-effects include headaches, 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, anxiety, hallucinations, and nightmares have also been reported. In more serious cases it has been known to cause jaundice, other liver disorders, and kidney problems including kidney failure. Inform your doctor immediately if side effects are extremely bothersome or serious. 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.

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, and it is normally recommended they avoid the use of Clarithromycin.^{[citation needed]} The reaction can be immediate and severe.

Allergic symptoms include hallucinations, 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.

Clarithromycin may also decrease the function of birth control pills and therefore, should use alternative birth control.

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

External links

• Biaxin XL Official web site by Abbott Laboratories
• U.S. Patent 4,331,803