Cephalexin

CEPHALEXIN- cephalexin capsule
Virtus Pharmaceuticals

To reduce the development of drug-resistant bacteria and maintain the effectiveness of cephalexin and other antibacterial drugs, cephalexin should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

DESCRIPTION

Cephalexin capsules, USP is a semisynthetic cephalosporin antibiotic intended for oral administration. It is 7-(D-α-Amino-α-phenylacetamido)-3-methyl-3-cephem-4- carboxylic acid monohydrate. Cephalexin has the molecular formula C16 H17 N3 O4 S∙H2 O and the molecular weight is 365.41.

Cephalexin has the following structural formula:

Chemical Structure

The nucleus of cephalexin is related to that of other cephalosporin antibiotics. The compound is a zwitterion; i.e., the molecule contains both a basic and an acidic group. The isoelectric point of cephalexin in water is approximately 4.5 to 5. The crystalline form of cephalexin which is available is a monohydrate. It is a white crystalline solid having a bitter taste. Solubility in water is low at room temperature; 1 or 2 mg/mL may be dissolved readily, but higher concentrations are obtained with increasing difficulty.

The cephalosporins differ from penicillins in the structure of the bicyclic ring system. Cephalexin has a D -phenylglycyl group as substituent at the 7-amino position and an unsubstituted methyl group at the 3-position.

Each capsule contains cephalexin monohydrate equivalent to 250 mg or 500 mg of cephalexin. The capsules also contain anhydrous lactose, gelatin, magnesium stearate, talc and titanium dioxide. The capsules are imprinted with edible ink containing black iron oxide.

CLINICAL PHARMACOLOGY

Human Pharmacology

Cephalexin is acid stable and may be given without regard to meals. It is rapidly absorbed after oral administration. Following doses of 250 mg, 500 mg, and 1 g, average peak serum levels of approximately 9, 18, and 32 µg/mL respectively were obtained at 1 hour. Measurable levels were present 6 hours after administration. Cephalexin is excreted in the urine by glomerular filtration and tubular secretion. Studies showed that over 90% of the drug was excreted unchanged in the urine within 8 hours. During this period, peak urine concentrations following the 250 mg, 500 mg, and 1g doses were approximately 1000, 2200, and 5000 µg/mL respectively.

Microbiology

In vitro tests demonstrate that the cephalosporins are bactericidal because of their inhibition of cell-wall synthesis. Cephalexin has been shown to be active against most strains of the following microorganisms both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section.

Aerobes, Gram-positive:

Staphylococcus aureus
(including penicillinase-producing strains)
Streptococcus pneumoniae
(penicillin-susceptible strains)
Streptococcus pyogenes

Aerobes, Gram-negative:

Escherichia coli
Haemophilus influenzae
Klebsiella pneumoniae
Moraxella (Branhamella) catarrhalis
Proteus mirabilis

Note: Methicillin-resistant staphylococci and most strains of enterococci (Enterococcus faecalis [formerly Streptococcus faecalis ]) are resistant to cephalosporins, including cephalexin. It is not active against most strains of Enterobacter spp., Morganella morganii , and Proteus vulgaris. It has no activity against Pseudomonas spp. or Acinetobacter calcoaceticus. Penicillin-resistant Streptococcus pneumoniae is usually cross-resistant to beta-lactam antibiotics.

Susceptibility Tests

Dilution techniques

Quantitative methods are used to determine antimicrobial minimal inhibitory concentrations (MIC’s). These MIC’s provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MIC’s should be determined using a standardized procedure. Standardized procedures are based on a dilution method1-3 (broth or agar) or equivalent with standardized inoculum concentrations and standardized concentrations of cephalothin powder. The MIC values should be interpreted according to the following criteria:

MIC (µg/mL) Interpretation

≤8

Susceptible (S)

16

Intermediate (I)

≥32

Resistant (R)

A report of “Susceptible” indicates that the pathogen is likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable. A report of “Intermediate” indicates that the result should be considered equivocal, and, if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where high dosage of drug can be used. This category also provides a buffer zone which prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of “Resistant” indicates that the pathogen is not likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable; other therapy should be selected.

Standardized susceptibility test procedures require the use of laboratory control microorganisms to control the technical aspects of the laboratory procedures. Standard cephalothin powder should provide the following MIC values:

Microorganism MIC (µg/mL)

E. coli

ATCC 25922

4 to 16

S. aureus

ATCC 29213

0.12 to 0.5

Diffusion techniques

Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure2,3 requires the use of standardized inoculum concentrations. This procedure uses paper disks impregnated with 30 µg cephalothin to test the susceptibility of microorganisms to cephalexin.

Reports from the laboratory providing results of the standard single-disk susceptibility test with a 30 µg cephalothin disk should be interpreted according to the following criteria:

Zone Diameter (mm) Interpretation

≥18

Susceptible (S)

15 to 17

Intermediate (I)

≤14

Resistant (R)

Interpretation should be as stated above for results using dilution techniques. Interpretation involves correlation of the diameter obtained in the disk test with the MIC for cephalexin. As with standard dilution techniques, diffusion methods require the use of laboratory control microorganisms that are used to control the technical aspects of the laboratory procedures. For the diffusion technique, the 30 µg cephalothin disk should provide the following zone diameters in these laboratory test quality control strains:

Microorganism Zone Diameter (mm)

E. coli

ATCC 25922

15 to 21

S. aureus

ATCC 25923

29 to 37

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