CLARITHROMYCIN Powder for concentrate for solution for infusion Ref.[6722] Active ingredients: Clarithromycin

Source: Medicines & Healthcare Products Regulatory Agency (GB)  Revision Year: 2018  Publisher: hameln pharma plus gmbh, Langes Feld 13, 31789, Hameln, Germany

Pharmacodynamic properties

Pharmacotherapeutic group: Antibacterial for systemic use, macrolide
ATC code: J01FA09

Mechanism of action

Clarithromycin is an antibiotic belonging to the macrolide antibiotic group. It exerts its antibacterial action by selectively binding to the 50s ribosomal sub-unit of susceptible bacteria preventing translocation of activated amino acids. It inhibits the intracellular protein synthesis of susceptible bacteria.

The 14-hydroxy metabolite of clarithromycin, a product of parent drug metabolism also has anti-microbial activity. The metabolite is less active than the parent compound for most organisms, including mycobacterium spp. An exception is Haemophilus influenza where the 14-hydroxy metabolite is two-fold more active than the parent compound.

Breakpoints

The following breakpoints have been established by the European Committee for Antimicrobial Susceptibility Testing (EUCAST):

Breakpoints (MIC, mg/l)
MicroorganismSusceptible (≤) Resistant (>)
Staphylococcus spp.11 mg/l2 mg/l
Streptococcus (A, B, C and G)10.25 mg/l0.5 mg/l
Streptococcus pneumoniae10.25 mg/l0.5 mg/l
Haemophilus influenzae.NoteNote
Moraxella catarrhalis10.25 mg/l0.5 mg/l

1 Erythromycin can be used to determine susceptibility to clarithromycin
Note: Clinical evidence for the efficacy of macrolides in H. influenzae respiratory infections is conflicting due to high spontaneous cure rates. Should there be a need to test clarithromycin against this species, an epidemiological cut-off (ECOFF) of 32 mg/l should be used to detect strains with acquired resistance.

Susceptibility

The prevalence of resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. This information gives only an appropriate guidance on the probabilities whether micro-organisms will be susceptible to clarithromycin or not.

Commonly susceptible species

Aerobic, Gram-positive microorganisms:

Streptococcus agalactiae
Streptococcus pyogenes (Group A beta-hemolytic streptococci)
Streptococcus viridans
Streptococcus (Diplococcus) pneumoniae
Staphylococcus aureus (methicillin susceptible)
Listeria monocytogenes

Aerobic, Gram-negative microorganisms:

Bordetella pertusis
Haemophilus influenzae
Haemophilus parainfluenzae
Helicobacter pylori
Campylobacter jejuni
Moraxella (Branhamella) catarrhalis
Neisseria gonorrhoeae
Legionella spp.

Anaerobic microorganisms:

Clostridium perfrigens
Bacterioides fragilis
Peptococcus/Peptostreptococcus spp.
Propionibacterium acnes

Other microorganisms:

Mycoplasma pneumoniae
Chlamydia trachomatis
Chlamydia pneumoniae
Ureaplasma urealyticum
Mycobacterium spp.

Other information

Susceptibility and resistance of Streptococcus pneumoniae and Streptococcus spp. to clarithromycin can be predicted by testing erythromycin.

The mechanisms of acquired resistance in macrolides are: efflux of drug by an active pump mechanism, inducible or constitutive production of a methylase enzyme that modifies the ribosomal target, hydrolysis of macrolides by esterases, chromosomal mutations that alter a 50 S ribosomal protein. Cross-resistance between clarithromycin and other macrolides and clindamycin and lincomycin may therefore occur. Methicillin-resistant and oxacillin-resistant staphylococci (MRSA) and penicillin-resistant Streptococcus pneumoniae are resistant to all currently available Beta- lactam antibiotics and macrolides such as clarithromycin.

Pharmacokinetic properties

Distribution

Following IV administration, the blood levels of clarithromycin achieved are well in excess of the MIC 90s for the common pathogens and the levels of 14-hydroxyclarithromycin exceed the necessary concentrations for important pathogens, e.g. H. influenzae. The microbiologically active metabolite 14-hydroxyclarithromycin is formed by first pass metabolism as indicated by lower biovailability of the metabolite following IV administration.

Clarithromycin gives good penetration into different compartments. Clarithromycin provides tissue concentrations that are several times higher than the circulating drug levels. Increased levels have been found in both tonsillar and lung tissue. Clarithromycin also penetrates the gastric mucus.

Clarithromycin is 80% bound to plasma proteins at therapeutic levels.

Serum half-life

The serum half-life of the active 14-®-hydroxy metabolite ranges between 5 to 6 hours.

Biotransformation and elimination

Clarithromycin is rapidly and extensively metabolised in the liver. Metabolism involves mainly N-dealkylation, oxidation and stereospecific hydroxylation at position C 14.

Linearity

The pharmacokinetics of clarithromycin and the 14-hydroxy metabolite are non-linear; steady state is achieved by day 3 of IV dosing. Following a single 500 mg IV dose over 60 minutes, about 33% clarithromycin and 11% 14-hydroxyclarithromycin is excreted in the urine at 24 hours.

Clarithromycin 500 mg powder for concentrate for solution for infusion does not contain tartrazine or other azo dyes, lactose or gluten.

Preclinical safety data

There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SmPC.

© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.