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AVEXUS
COMPOSITION
Avexus Film-Coated Tablet 250 mg: Each tablet contains Clarithromycin 250 mg
Avexus Film-Coated Tablet 500 mg: Each tablet contains Clarithromycin 500 mg
ACTIONS AND MECHANISMS OF ACTION
Clarithromycin is a semi-synthetic macrolide derived from erythromycin.
It exhibits similar but has slightly greater activity than the parent compound. Clarithromycin exerts its
antibacterial activity by inhibiting the synthesis of proteins via binding to the 50S ribosomal subunit
of susceptible microorganisms. Highly potent against a wide variety of aerobic and anaerobic Grampositive
and Gram-negative organisms, the in vitro antibacterial spectrum of clarithromycin generally includes:
Staphylococci spp.; Streptococci spp.; Haemophilus influenzae and
Haemophilus parainfluenzae; Mycobacterium spp.; Neisseria gonorrheae;
Listeria monocytogenes; Legionela pneumophila; Pasteurella multocida;
Mycoplasma pneumoniae; Helicobacter pylori and Campylobacter jejuni;
Chlamydia trachomatis and Chlamydia pneumoniae (TWAR); Moraxella catarrhalis;
Bordetella pertussis; Borrelia burgdorferi; Clostridium perfringens;
Peptococcus niger; Propionibacterium acnes; Bacteroides melaninogenicus.
PHARMACOKINETICS
Clarithromycin is rapidly absorbed from the gastrointestinal
tract following oral administration. Clarithromycin undergoes first-pass metabolism; the bioavailability
of the parent drug is about 50%. Food slightly delays the onset of absorption of clarithromycin but the
extent of its bioavailability is unaffected. In addition, food does not affect the onset of formation nor
peak plasma concentration of its principal (anti-microbially) active metabolite, 14-hydroxyclarithromycin.
Therefore, clarithromycin may be given without regard to meals. Peak plasma concentrations of clarithromycin
and its principal metabolite are reported to be about 0.6 and 0.7 µg per mL respectively (following a single
250 µg dose by mouth). These are attained within 2 to 3 hours after oral dosing in nonfasting, healthy subjects.
Steady-state peak plasma concentrations (of the same dose administered every 12 hours), Cmax
attained within 3 days, were about 1 to 2 µg per mL; Cmax values of 3 to 4 µg per mL were
obtained with a 500 µg dose administered every 8 to 12 hours and 5 to 10 µg per mL with 1000 µg doses every 12 hours.
The pharmacokinetics of clarithromycin are non-linear and dose dependent; high doses may produce
disproportionate increases in peak concentration and prolongs elimination half-lives of the parent
drug and its principal metabolite, due to saturation of the metabolic pathways. For example,
the elimination half-lives, T½ of clarithromycin and 14-hydroxyclarithromycin were about 3 to 4 hours
and 5 to 6 hours, respectively with a 250 µg dose administered every 12 hours; the half-lives increased
to 5 to 7 hours and 7 to 9 hours, respectively with a 500 µg dose administered every 8 to 12 hours.
Half-lives are prolonged in renal failure. The drug and its principal metabolite are widely distributed,
and tissue concentrations exceed those in serum, in part because of intracellular uptake.
It is extensively metabolised in the liver, and excreted in faeces via the bile.
Renal clearance of clarithromycin is relatively independent of the dose size and approximates the
normal glomerular filtration rate. Substantial amounts of the unchanged drug are excreted in urine;
about 20% and 30% respectively of a 250 µg or 500 µg dose (both given every 12 hours).
14-Hydroxyclarithromycin as well as other metabolites are also excreted in the urine;
the former accounts for an additional 10% to 15% of the dose with either a 250 µg or 500
µg dose administered every 12 hours.
INDICATIONS
Avexus is indicated for treatment of infections due
to susceptible organisms in respiratory-tract infections; mild to moderate skin and soft
tissue infections; acute otitis media and (in triple-therapy regimens for)
Helicobacter pylori eradication.
DOSAGE AND ADMINISTRATION
Adults
250 mg every 12 hours for 7 days, increased in
severe infections to 500 mg every 12 hours for up to 14 days. 500 mg every 12 hours for 7 to
14 days in triple-therapy regimen for Helicobacter pylori eradication.
Children
Body-weight under 8 kg: 7.5 mg per kg twice daily
(7 - 9 years) 20 - 29 kg: 187.5 mg twice daily
(10 - 12 years) 30 - 40 kg: 250 mg twice daily
A course is usually for 10 days.
Triple Therapy
Clarithromycin 500 mg twice daily should be given
with amoxycillin 1000 mg twice daily and omeprazole 20 mg daily for 10 days.
Dosage adjustment in renal impairment:
Half the normal dose if creatinine clearance is less than 30 mL per minute.
Dosage adjustment in liver impairment
May not be necessary if there is normal renal function.
CONTRAINDICATIONS
Clarithromycin is contraindicated in patients with
a known hypersensitivity to any of the macrolide antibiotics and ergot derivatives.
Concomitant administration of clarithromycin with cisapride, pimozide, astemizole or terfenadine is contraindicated.
Cardiac arrhythmias and fatalities have been reported when clarithromycin is co-administered with these drugs.
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