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Spectrum of activity (1)

Gram Positive microorganisms: Staphylococcus aureus

Streptococcus pneumoniae

Streptococcus pyogenes

Gram Negative microorganisms: Haemophilus influenzae

Haemophilus parainfluenzae

Moraxella catarrhalis Neisseria gonorrhea

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Spectrum of activity (2)

Atypical microorganisms: Mycoplasma pneumoniae

Chlamydia pneumoniae

Chlamydia trachomatis Legionella pneumiphila

Mycobacterium:

Mycobacterium avium

Mycobacterium intracellulare

Helicobacter pylori

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Mechanism of action

Translocation Reaction

Clarithromycininterferes

Nascentpolypeptide chain

mRNA

50S

30S

tRNA Acceptor site

Donor Site

Binds

X

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Mechanism of Action

Inhibit protein synthesis

Binds to 50 S ribosomal subunit

30S

50S

Clarithromycin binds to 50S subunit ofribosome and inhibit protein synthesis

RIBOSOME

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Synergy

Clarithromycin and its 14-hydroxy

metabolite showed syngergistic activity,

against Moraxella catarrhalis,

Staphylococcus aureus, coagulase

negative Staphylococci and S.pyogenes,

Legionella species and Haemophillus

influenzae.

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H.influenzae Strep. Pn Staph. ar

Clarithromycin 97 99 100Roxithromycin 29 90 98

Cefaclor 67 54 100

Amoxicillin 92 23 100Ciprofloxacin 100 91 81

Bacteriological eradication Rate for

Key Pathogens

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Clarithromycin and the

immune system

Immuno-enhancer

Potentiation of neutrophil migration and

bactericidal action.

Anti-inflammatory

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Enhancement of T-Cell Activity

T-cell is lymphocyte produced in bone marrowand members of immune system. Destroys or

neutralises foreign substances, bacteria.

Clarithromycin - potentiates the activity of T-cells.

Clarithromycin - excellent penetration into the

polymorphonuclear leukocytes, macrophages, and

lymphocytes.

Clarithromycin - increases phagocytosis.

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Effect Pulmonary congestion

Improves the visco-elastic

properties of mucus andsputum, relieving pulmonary

congestion.

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Pharmacokinetic Properties

Absorption, Distribution, Metabolism.

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Absorption

Absorption - Clarithromycin 52-55%,

Erythromycin. 30-35%

Erythromycin is acid labile but Clarithromycin is stable in acidic

environment.

Clarithromycin at an alkaline PH in intestine is non-ionized, canpenetrate intestinal cell walls.

In presence of food, erythromycin bioavailability reduces by 20%

azithromycin bioavailability reduces by 43%

Roxithromycin has to be administered 15 minutes prior to food.

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Plasma Concentration

Mean area under the plasma

concentration curve (AUC) clarithromycin

3.82 to 4.7 mg/L. h

14-OH Clarithromycin 11.06 to 11.66

mg/L. h

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C max

500 mg. twice daily for upto 3.5 days

mean Cmax

Clarithromycin 2.4 to 3.5 mg/L

14-OH Clarithromycin 0.7 to 0.8 mg/L

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Distribution (Intracellular Reach)

LRT

Epithelial lining fluidBronchoscopy patients 500 bid x 7 doses 5.17 2.79

Alveolar macrophages

Bronchoscopy patients 500 bid x 7 doses 94.1 56.8

Bronchial secretions

AECB patients 250 bid x 3 days 3.1 2.5

Study participants Dosage (mg)Tissue : Plasma ratio

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Distribution (Intracellular Reach)

LRT

Epithelial lining fluid

Bronchoscopy patients 500 bid x 7 doses 5.17 2.79

Alveolar macrophages

Bronchoscopy patients 500 bid x 7 doses 94.1 56.8

Bronchial secretions

AECB patients 250 bid x 3 days 3.1 2.5

Study participants Dosage (mg)Tissue : Plasma ratio CLR 140H

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Distribution (Intracellular Reach)

Tonsils

Tonsillar resection patients 250 bid x 3 days 331 375

Nasal mucosa

Rhinoplasty patients 250 bid x 3 days 27.5 16

Middle ear fluid

Children with otitis media 7.5 mg/kg bid x 7 days 8.82 3.78

Study participants Dosage (mg)Tissue : Plasma ratio CLR 140H

URT

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A Laboratory study compared the intracellular

reach between clarithromycin, amoxicillin and

azithromycin against S. aureus and L.

pneumophila. Clarithromycin intra- and

extracellularly, proportion to its concentrations

(0.34 to 1.33 mg/L vs 0.15 to 0.66 and mg/L,

respectively)

Amoxicillin was found only extracellularly andAzithromycin primarily within cells.

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Metabolism and Elimination

Only one of the, 14-OH metabolite, isbiologically active.

Mean elimination half-life Clarithromycin 2.6

to 2.8 hours.

14-OH Clarithromycin 3.5 to 4.9 hours.

The terythromycin (1.3-3.4h)

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32% of the dose recovered in urine was

parent plus metabolite.

In elderly, dosage adjustment not

necessary unless impaired renal

function.

Dosage adjustment in hepatic disease

not required.

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Adverse Effects

Nausea (3%), diarrhoea (3%)

dyspepsia (2%), abdominal pain (2%)and headache (2%).

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Drug Interactions

Theophylline, cyclosporine, tacrolimus andcarbamazepine. Plasma concentrations of

these increased

Rifabutin and rifampicin induce metabolism oclarithromycin.

Inhibits metabolism of omeprazole.

Digoxin toxicity

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Dosage and Administration

Pharyngitis or tonsillitis :

250 mg every 12 hours for 10 days.

Acute exacerbation of chronic bronchitis(AECB).

Clarithromycin 250 mg every 12 hours for 7 to 14

days. A higher dosage (500 mg every 12 hours for 7 to 14

days) should be used for AECB caused by H.

influenzae.

Children 7.5 mg/kg every 12 hours for 10 days.