CEFADROXIL Capsules, hard (2018)
Pharmacotherapeutic group: Other beta-lactam antibacterials. First generation cephalosporins.
Mode of action
Cefadroxil is a cephalosporin for oral administration which inhibits bacterial wall synthesis of actively dividing cells by binding to one or more penicillin-binding proteins. The result is formation of a defective cell wall that is osmotically unstable, and bacterial cell lysis.
Mechanisms of resistance
Cefadroxil may be active against organisms producing some types of beta-lactamase, for example TEM-1, in low to moderate quantities. However, it is inactivated by beta-lactamases that can efficiently hydrolyse cephalosporins, such as many of the extended-spectrum beta-lactamases and chromosomal cephalosporinases, such as AmpC type enzymes.
Cefadroxil cannot be expected to be active against bacteria with penicillin-binding proteins that have reduced affinity for beta-lactam drugs. Resistance may also be mediated by bacterial impermeability or by bacterial drug efflux pumps. More than one of these four means of resistance may be present in the same organism.
In vitro, oral first generation cephalosporins are less active than penicillins G and V on Gram-positive microorganisms and are less active than aminopenicillins on H. influenzae.
The following breakpoint recommendations for cefadroxil according to the European Committee on Antimicrobial Susceptibly Testing (EUCAST) have been defined (Breakpoint tables for interpretation of MICs and zone diameters, Version 1.0, December 2009):
|Cefadroxil (EUCAST Clinical Breakpoint Table)||MIC breakpoints|
|S ≤||R >|
|Enterobacteriaceae (uncomplicated UTI only)||16||16|
|Streptococcus groups A, B, C, and G||Note2||Note2|
|Non-species related breakpoints||IE||IE|
Note1: Susceptibility of staphylococci to cephalosporins is inferred from the methicillin susceptibility except for ceftazidime and cefixime and ceftibuten, which do not have breakpoints and should not be used for staphylococcal infections.
Note2: The beta-lactam susceptibility of beta-haemolytic streptococci groups A, B, C and G is inferred from the penicillin susceptibility.
IE: indicates that there is insufficient evidence that the species in question is a good target for therapy with the drug.
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. As necessary, expert advice should be sought when the local prevalence of resistance is such, that the utility of the agent in at least some types of infections is questionable.
Commonly susceptible species
Streptococci Group B, C and G
Species for which acquired resistance may be a problem
Staphylococcus aureus (methicillin-susceptible)*
Inherently resistant species
Staphylococcus aureus (methicillin-resistant)
Staphylococcus epidermidis (methicillin-resistant)
Streptococcus pneumoniae (penicillin-resistant)
* Clinical efficacy has been demonstrated for susceptible isolates in approved clinical indications
$ Species with natural intermediate susceptibility
After oral administration cefadroxil is practically completely absorbed. Simultaneous intake of food has practically no effect on absorption (AUC).
After oral doses of 500 mg (1000 mg) peak plasma concentrations of about 16 (30) μg/ml are obtained after 1-1,3 hours. Between 18 and 20% of cefadroxil is bound to plasma proteins. Cephalosporins do not penetrate in the CSF and should not be used for treatment of meningitis (see section 4.1)
Cefadroxil is not metabolised.
Address WWW Cefadroxil is eliminated far more slowly than comparable oral cephalosporins (half life: about 1,4 h to 2,6 h) so that intervals between doses can be prolonged to 12-24 hours. Roughly 90% of the substance is eliminated in unchanged form through the kidneys within 24 hours. Cefadroxil may be eliminated from the organism through haemodialysis.
Characteristics in patients with reduced creatinine clearance, a sign for renal functional impairment
Elimination is retarded, so that interval between doses must be prolonged (see section 4.2).
Preclinical safety data
Pre-clinical data reveal no special hazard for humans based on conventional studies of repeated dose toxicity, genotoxicity and toxicity to reproduction.