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Brand Name, Dosage Format and Strength
Amoclav 400 mg/57 mg per 5 mL Powder for Suspension
Therapeutic Category
Anti-infectives (Systemic)
Class
Aminoglycoside, Cephalosporin, Chloramphenicol, Lincosamide, Macrolide, Penicillin, Penicillin + Beta lactamase Inhibitor , Penicillinase-resistant isoxazolylpenicillin, Penicillin; Beta-lactam + Beta-lactamase Inhibitor, Quinolone, Sulfonamide + Folate Inhibitor, Tetracycline, Triazole Antibiotic, Immunostimulant, Neuraminidase Inhibitor
CLINICAL PHARMACOLOGY
Pharmacodynamics
Amoxicillin (an aminopenicillin antibiotic) and potassium clavulanate (a b-lactamase inhibitor) [Co-amoxiclav] is usually bactericidal in action. Concurrent administration of clavulanic acid does not alter the mechanism of action of amoxicillin. However, because clavulanic acid has a high affinity for and binds to certain b-lactamases that generally inactivate amoxicillin by hydrolyzing its b-lactam ring, concurrent administration of the drug with amoxicillin results in synergistic bactericidal effect which expands amoxicillin`s spectrum of activity against many strains of b-lactamase-producing bacteria resistant to amoxicillin alone.
Antimicrobial Spectrum of Activity
In vitro and clinical studies have demonstrated the susceptibility of the following microorganisms to Co-amoxiclav:
|
Aerobic Gram-positive |
Aerobic Gram-negative |
|
Staphylococcus aureus* |
Haemophilus influenzae* |
|
Anaerobic Gram-positive |
Anaerobic Gram-negative |
|
Peptostreptococcus spp |
Bacteroides spp.* including B. fragilis
|
*including b-lactamase-producing and non-producing strain
Although most strains of Enterobacter species are resistant in vitro, clinical efficacy has been demonstrated with Co-amoxiclav in UTI caused by these organisms.
Co-amoxiclav has demonstrated in vitro activity against most strains of the following microorganisms; however, clinical significance is unknown:
|
Aerobic Gram-positive |
Aerobic Gram-negative |
|
Staphylococcus epidermidis*
|
Haemophilus ducreyi |
|
Anaerobic Gram-positive |
Other Microorganisms |
|
Clostridium spp.
|
Borrelia burgdorferi
|
*Including b-lactamase-producing and non-producing strains
Pharmacokinetics
Co-amoxiclav is stable in the presence of acidic gastric secretions and is well absorbed following oral administration.
In a single-dose study in healthy male and female subjects, 19 to 44 yrs old, oral administration of Co-amoxiclav 1 g tab resulted in mean peak serum amoxicillin and clavulanic acid concentrations Cmax of 7.787 and 3.078 mcg/mL, respectively. Peak serum concentrations of amoxicillin and of clavulanic acid were generally attained within 1 to 2.5 hrs after oral administration. The AUC0-t for amoxicillin and clavulanic acid were 30.533 and 7.184 mcg/mL•hr, respectively, while AUC0-∞ were 31.615 and 7.487 mcg/mL•hr, respectively.
When a single oral dose of Co-amoxiclav 625 mg tab was administered in adult subjects (fasted state), PK parameters reached were: Cmax 7.03 mcg/mL, AUC0-t 19.49 mcg/mL•hr, AUC0-∞ 20.91 mcg/mL•hr, and t1/2 1.04 hrs for amoxicillin, and 2.143 mcg/mL, 4.064 mcg/mL•hr, 4.722 mcg/mL•hr and 1.2 hrs, respectively, for clavulanic acid.
Studies in healthy adults using Co-amoxiclav indicate that presence of food in the GI tract does not affect oral absorption of either amoxicillin or clavulanic acid.
In a study in children 2 to 5 yrs old with UTI who received a single oral dose of 125 mg of amoxicillin and 31.75 mg of clavulanic acid suspension, the Cmax of amoxicillin were 9.4, 9.7, and 6.5 mcg/mL and of clavulanic acid were 2.1, 4.4, and 2.5 mcg/mL at 30, 60, and 90 mins, respectively, after the dose.
In a study in fasting children who received a single amoxicillin dose of 35 mg/kg given as Co-amoxiclav oral suspension, concentrations of amoxicillin and of clavulanic acid in middle ear effusions averaged 3 and 0.5 mcg/mL, respectively, 2 hrs after the dose.
When a single 5 mL oral dose of Co-amoxiclav 457 mg/5 mL suspension was administered in healthy male and female subjects (fasted state), PK parameters reached were: Cmax 5.789 mcg/mL, Tmax 1.164 hrs, AUC0-t 12.21 mcg/mL•hr and AUC0-∞12.855 mcg/mL•hr for amoxicillin, and 1.379 mcg/mL, 1.039 hrs, 2.492 mcg/mL•hr and 2.727 mcg/mL•hr, respectively, for clavulanic acid.
Therapeutic concentrations of both amoxicillin and clavulanic acid have been found in the gall bladder, abdominal tissue, skin, fat, and muscle tissues; the synovial and peritoneal fluids, bile and pus. Animal studies show no evidence that either component may accumulate in any organ.
Neither amoxicillin nor clavulanic acid is highly protein-bound; studies show that about 13- 25% of total plasma drug concentration of each compound is protein-bound.
Both Co-amoxiclav components readily cross the placenta. Only small amounts of amoxicillin and clavulanic acid are distributed in human milk.
Serum concentrations of amoxicillin and clavulanic acid both decline in a biphasic manner and their t1/2 are similar. Approximately 50-73% of amoxicillin and 25-45% of clavulanic acid are excreted unchanged in urine within 6 to 8 hrs following oral administration of a single dose of Co-amoxiclav in adults with normal renal function.
In a study in children 2 to 15 yrs old, the elimination t1/2 of amoxicillin and clavulanic acid averaged 1.2 and 0.8 hrs, respectively.