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

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

ATC code J01FA09

PubChem CID 5284534

DrugBank DB01211

ChemSpider 21112273 

UNII H1250JIK0A 

KEGG D00276 

ChEMBL CHEMBL143 

Chemical data

Formula C38H69NO13 

Mol. mass 747.953 g/mol

SMILES eMolecules & PubChem

  (what is this?)  [1]
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, Biaxin, Klaricid,
Klabax, Klacid, Claripen, Clarem, Claridar, Fromilid, Clacid, Clacee, Vikrol, Infex and
Clariwin.

Contents
[hide]

 1 History
 2 Mechanism of action
 3 Pharmacokinetics
 4 Metabolism
 5 Side effects
 6 Special uses
 7 Resistance
 8 Contraindications
 9 Drugs using clarithromycin
 10 Potential increased mortality using clarithromycin
 11 References
 12 External links

[edit] 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.

[edit] 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.

[edit] 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.

[edit] 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.

[edit] Side effects

Most common side-effects are gastrointestinal: diarrhoea, 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 increased yeast production in the body from
the antibiotics.
[edit] Special uses
According to a study performed by the Japanese manufacturer of clarithromycin, it was proved
that it can be used in the treatment of asthma as it has an anti-inflammatory effect.

In the clarithromycin study, researchers led by Hideaki Amayasu, MD, of the Yokohama Rosai
Hospital in Japan, randomized 17 subjects in double-blind fashion to 200 mg of clarithromycin
or placebo twice daily for eight weeks. After a washout period of at least four weeks, the two
groups of patients were then given the alternative treatment for eight weeks.

Before the study began, all patients had stable asthma, and all had been free from symptoms of
respiratory infection for at least six weeks. None were smokers. Patients were permitted to use an
inhaled ß-agonist for symptom control. However, those who used theophylline, antileukotriene
agents, clarithromycin, or an anti-inflammatory agent (including oral or inhaled corticosteroids)
were excluded from the study. During the study, the patients recorded their symptom severity
once a week, using a 0 to 3 scale (0 indicated that a patient was asymptomatic on at least four
days that week, and 3 indicated that a patient had had severe asthma attacks on more than four
days and/or nocturnal asthma symptoms almost daily; 1 and 2 indicated intermediate levels of
disease severity). In addition, they underwent laboratory testing as well as a methacholine
challenge for evaluation of bronchial responsiveness.

Neither forced expiratory volume in one second (FEV1) nor forced vital capacity were affected
by clarithromycin use. Thus, say the authors, it is unlikely that clarithromycin has a
bronchodilating effect. However, symptoms (i.e., nocturnal cough, wheezing, and severity and
frequency of asthma attacks) improved in 15 patients following clarithromycin use. "Overall, the
symptom score decreased significantly after treatment with clarithromycin," the authors added.
Blood and serum eosinophil counts and ECP levels also decreased; however, blood and sputum
neutrophil levels remained unchanged.

Methacholine challenge caused airway obstruction in all patients at baseline and during the
study. The amount of methacholine required to cause obstruction (PC20) was significantly
greater when the patients received clarithromycin, however, suggesting lower airway
hyperresponsiveness in this group. Yet no statistical association emerged between the increase in
PC20 and the decrease in ECP levels during clarithromycin administration. "Although [the
researchers] did not find a direct relationship between the changes in ECP concentrations and the
changes in airway hyperresponsiveness, their study suggests that prolonged treatment with a
macrolide may reduce the symptoms and bronchial hyperresponsiveness of asthma through an
anti-inflammatory action," wrote Pedro C. Avila, MD, and Homer A. Boushey, MD, in an
accompanying editorial.[3] Clarithromycin may also improve asthma symptoms by treating
airway infection. Indeed, some studies of asthma patients have found evidence of chronic
Chlamydia or Mycoplasma airway

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, and lips blistering / scabbing. Rashes can range in severity, the
most serious cases being toxic epidermal necrolysis and Stevens-Johnson syndrome.
Clarithromycin may also decrease the function of birth control pills and therefore an alternative
birth control should be used.

[edit] 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]

[edit] 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. Clarithromycin should not be used in pregnant patients.

Clarithromycin can also cause serotonin syndrome symptoms when taken in conjunction with
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, Clarithromycin should be better avoided.

[edit] 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.

[edit] 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], [3].

[edit] References
1. ^ 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 (9560): 482–90.
doi:10.1016/S0140-6736(07)60235-9. PMID 17292768.

Generic name: Clarithromycin

Generic name: Clarithromycin

Brand names: Biaxin®, Klacid® and Claripen®

Description
Clarithromycin is a semi-synthetic macrolide antibiotic. This antibiotic is
chemically related to erythromycin and works by fighting bacteria in your body .
The medicine is effective against a wide variety of bacteria organisms, like
Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, Staphylococcus aureus, and many
others. It works by killing or stopping the growth of sensitive bacteria by reducing the production of proteins needed
by the bacteria to survive.
Available in tablet and suspension form

Uses

It is used to treat the following:

 Pharyngitis
 Acute maxillary sinusitis
 Acute bacterial exacerbation of chronic bronchitis
 Tonsillitis
 Pneumonia
 Skin and skin structure infections
 Used in HIV and AIDS patients to prevent, and treat, disseminated
mycobacterium avium complex or MAC.
 It is used in combination with Prilosec® in treating H. Pylori bacteria that leads
to stomach ulcers.

How to use

Take as directed by your doctor. Usually recommended to be taken twice daily with or without food. If stomach upset
occurs, you may take it with food or milk. Take this medicine at evenly spaced intervals.

Safety tips

 Do not use Clarithromycin if you are allergic to any ingredient in Clarithromycin

or any other medicine, foods or other substances .
  Safe use in pregnancy has not been established. So do not take this medicine
when you are pregnant or breast feeding.
 Tell your doctor if you have diarrhea, a blood disorder, a stomach infection,
severe kidney problems, or liver problems before taking this medicine.
 Clarithromycin should not be used in children younger than 6 months old.

Side effects

Certain mild effects might occur while taking this medicine such as :

 Abnormal taste
 Diarrhea
 Indigestion
 Headache
 Nausea
 Stomach discomfort
 Vomiting

Seek medical attention immediately if any of these severe side effects occur:

 Severe allergic reactions

 Bloody stools
 Decreased urination
 Depression
 Confusion Emotional or mood changes
 Severe diarrhea
 Severe stomach pain
 Trouble sleeping

Disclaimer:The above information is for general understanding of the visitor. Please consult a registered medical
practitioner before taking the aforesaid medicine.

FDA Information
Clarithromycin was approved by the FDA in February 1995.
In the United States generic clarithromycin is available from Andrx, Genpharm, Ivax, Ranbaxy Laboratories,
Roxane, Sandoz, Teva and Wockhardt.

Why is this medication prescribed?

Clarithromycin is a macrolide antibiotic, and acts by fighting bacteria in your body.

It is 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.
Clarithromycin has been used in combination with Prilosec® in treating H. Pylori bacteria that causes
stomach ulcers.

This medication is available under several brand names, including Biaxin®, Klacid® and Claripen®.

Other uses for this medicine

Clarithromycin is also used sometimes to treat Lyme disease and toxoplasmosis and legionellosis.

Additionally, it has also been administered to prevent heart infection in patients having dental surgery or
other similar procedures.

However, it is important that you talk to your doctor about the possible risks of using this drug for your
particular condition.

What is the dosage and how should it be

used?
Clarithromycin is commonly administered in tablets (Biaxin®), extended-release tablets (Biaxin XL®), or
oral suspension.
The regular tablet and liquid are usually taken with or without food every 12 hours (twice a day) for 7-14
days.

The long-acting tablet is usually taken with food every 24 hours (once a day) for 7-14 days.

To help you remember to take clarithromycin, take it around the same time every day.

Always take clarithromycin exactly as directed by your doctor. Do not take more or less of it or take it
more often than prescribed by your doctor.

Shake the liquid well before each use to mix the medication evenly.

The tablets should be taken with a full glass of water. Swallow the long-acting tablets whole and do not
split, chew, or crush them.

Take clarithromycin until you finish the prescription, even if you feel better. Stopping clarithromycin too
soon may cause bacteria to become resistant to antibiotics.
What special precautions should I follow?
Before taking Clarithromycin:
Tell your doctor if you have liver or kidney disease. You may not be able to take clarithromycin, or you may
require a lower dose and special monitoring during therapy.

Do not take clarithromycin if you are taking cisapride (Propulsid®), pimozide (Orap®), or terfenadine
(Seldane®). These medicines can interact, possibly leading to a dangerous irregular heartbeat pattern.

Clarithromycin is in the FDA pregnancy category C. This means that it is not known whether clarithromycin
will harm an unborn baby. Do not take clarithromycin without first talking to your doctor if you are
pregnant.

Furthermore, it is not known whether clarithromycin passes into breast milk. Do not take this medication
without first talking to your doctor if you are breast-feeding a baby.

hat side effects can this medication cause?

Possible side effects from clarithromycin may include:
nausea
vomiting
diarrhea
abdominal pain

Tell your doctor if any of these symptoms are severe or do not go away:
diarrhea
upset stomach
abnormal taste
stomach pain
headache

If you experience any of the following symptoms, call your doctor immediately:
severe skin rash
hives
itching
difficulty breathing or swallowing
swelling of the face, throat, tongue, lips, eyes, hands, feet, or ankles
yellowing of the skin or eyes
rapid pounding
irregular heartbeat

 
Clarithromycin may cause other side effects. Call your doctor if you have any unusual problems while taking
this medication.
What storage conditions are needed for this
medicine?
Keep this medication in the container it came in, tightly closed, and out of reach of children. Store the
tablets at room temperature and away from excess heat and moisture (not in the bathroom). Keep away
from light.

Keep liquid medicine at room temperature (do not refrigerate) and away from excess heat and moisture.
Throw away any medication that is outdated or no longer needed

Pictures of Clarithromycin pills

Below you will find images and specific information on the principal types of clarithromycin that exist,
including their respective brand name(s), strength, inscription codes and manufacturers. 
The information below includes general information and guidelines for patients taking this medication and
should never be used to substitute professional medical advice that can be provided by a qualified physician
or family doctor.
 

Name: BIAXIN®
Strength(s): 250 MG
Imprint: KT
Manufacturer: ABBOTT LABS.

Name: CLARITHROMYCIN
Strength(s): 250 MG
Imprint: RX 725
Manufacturer: RANBAXY

Name: CLARITHROMYCIN
Strength(s): 250 MG
Imprint: DAVA
Manufacturer: DAVA PHARMACEUTICALS
Name: CLARITHROMYCIN
Strength(s): 250 MG
Imprint: 93 | 7157
Manufacturer: TEVA USA

Name: BIAXIN®
Strength(s): 500 MG
Imprint: KJ
Manufacturer: ABBOTT LABS.

Name: CLARITHROMYCIN
Strength(s): 500 MG
Imprint: DV | D
Manufacturer: DAVA PHARMACEUTICALS

Name: CLARITHROMYCIN
Strength(s): 500 MG
Imprint: RX 726
Manufacturer: RANBAXY

Name: CLARITHROMYCIN
Strength(s): 500 MG
Imprint: 93 | 7158
Manufacturer: TEVA USA
Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Hepatic

Source: Drug Bank

Protein Binding

Low protein binding

Source: Drug Bank

Absorption

50%

Source: Drug Bank

Toxicity

Symptoms of toxicity include diarrhea, nausea, abnormal taste, dyspepsia, and abdominal discomfort.
Pseudomembraneous colitis has been reported with clarithromycin use, allergic reactions ranging from
urticaria and mild skin eruptions to rare cases of anaphylaxis and Stevens-Johnson syndrome have
occurred. Rare cases of severe hepatic dysfunctions also have been reported. Hepatic failure is usually
reversible, but fatalities have been reported.

Source: Drug Bank

alprazolam The macrolide increases the effect of the benzodiazepine (source: Drug
Bank)

amiodarone Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)

astemizole Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)

atazanavir Atazanavir increases levels of clarithromycin (source: Drug Bank)

atorvastatin The macrolide possibly increases the statin toxicity (source: Drug Bank)

bretylium Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)

buspirone Increases the effect and toxicity of buspirone (source: Drug Bank)

carbamazepine The macrolide increases the effect of carbamazepine (source: Drug Bank)

cerivastatin The macrolide possibly increases the statin toxicity (source: Drug Bank)

cisapride Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)

citalopram Possible serotoninergic syndrome with this combination (source: Drug Bank)

colchicine Severe colchicine toxicity can occur (source: Drug Bank)

cyclosporine The macrolide increases the effect of cyclosporine (source: Drug Bank)

darunavir Increased levels of clarithromycin (source: Drug Bank)

diazepam The macrolide increases the effect of the benzodiazepine (source: Drug
Bank)

dicumarol The macrolide increases anticoagulant effect (source: Drug Bank)

digoxin The macrolide increases the effect of digoxin in 10% of patients (source:
Drug Bank)

disopyramide Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)

dofetilide Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)

efavirenz Efavirenz decreases levels of clarithromycin (source: Drug Bank)

eletriptan This macrolide increases the effect and toxicity of eletriptan (source: Drug
Bank)

erlotinib This CYP3A4 inhibitor increases levels/toxicity of erlotinib (source: Drug

Bank)

fluoxetine Possible serotoninergic syndrome with this combination (source: Drug Bank)

gefitinib This CYP3A4 inhibitor increases levels/toxicity of gefitinib (source: Drug

Bank)

imatinib The macrolide increases levels of imatinib (source: Drug Bank)

indinavir Increases the effect and toxicity of indinavir (source: Drug Bank)

itraconazole The macrolide increases the effect and toxicity of itraconazole (source:
Drug Bank)

lovastatin The macrolide possibly increases the statin toxicity (source: Drug Bank)

methylprednisolon The macrolide increases the effect of corticosteroid (source: Drug Bank)
e
midazolam The macrolide increases the effect of the benzodiazepine (source: Drug
Bank)

phenytoin Increases the effect and toxicity of phenytoin (source: Drug Bank)

pimozide Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)

quetiapine This macrolide increases the effect/toxicity of quetiapine (source: Drug Bank)

quinidine Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)

repaglinide Increases the effect of repaglinide (source: Drug Bank)

rifabutin The rifamycin decreases the effect of the macrolide (source: Drug Bank)

rifampin The rifamycin decreases the effect of the macrolide (source: Drug Bank)

sertraline Possible serotoninergic syndrome with this combination (source: Drug Bank)

sildenafil Increases the effect and toxicity of sildenafil (source: Drug Bank)

simvastatin The macrolide possibly increases the statin toxicity (source: Drug Bank)

sirolimus The macrolide increases sirolimus levels (source: Drug Bank)

sotalol Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)

sunitinib Possible increase in sunitinib levels (source: Drug Bank)

tacrolimus This antibiotic increases the effect and toxicity of tacrolimus (source: Drug
Bank)

terfenadine Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)

theophylline Increases the effect and toxicity of theophylline (source: Drug Bank)

triazolam The macrolide increases the effect of the benzodiazepine (source: Drug
Bank)

vardenafil Increases the effect and toxicity of vardenafil (source: Drug Bank)

warfarin The macrolide increases anticoagulant effect (source: Drug Bank)