Human Pharmacology

Cephalexin Capsule, USP 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 mcg/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 1 g doses were approximately 1000, 2200, and 5000 mcg/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 to 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:

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:

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 mcg 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 mcg cephalothin disk should be interpreted according to the following criteria:

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 mcg cephalothin disk should provide the following zone diameters in these laboratory test quality control strains:

General

Prescribing cephalexin capsules, USP in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
 
Patients should be followed carefully so that any side effects or unusual manifestations of drug idiosyncrasy may be detected. If an allergic reaction to cephalexin capsules, USP occurs, the drug should be discontinued and the patient treated with the usual agents (e.g., epinephrine or other pressor amines, antihistamines, or corticosteroids).
 
Prolonged use of cephalexin capsules, USP may result in the overgrowth of nonsusceptible organisms. Careful observation of the patient is essential. If superinfection occurs during therapy, appropriate measures should be taken.
 
Positive direct Coombs’ tests have been reported during treatment with the cephalosporin antibiotics. In hematologic studies or in transfusion cross-matching procedures when antiglobulin tests are performed on the minor side or in Coombs’ testing of newborns whose mothers have received cephalosporin antibiotics before parturition, it should be recognized that a positive Coombs’ test may be due to the drug.
 
Cephalexin capsules, USP should be administered with caution in the presence of markedly impaired renal function. Under such conditions, careful clinical observation and laboratory studies should be made because safe dosage may be lower than that usually recommended.
 
Indicated surgical procedures should be performed in conjunction with antibiotic therapy.
 
Broad-spectrum antibiotics should be prescribed with caution in individuals with a history of gastrointestinal disease, particularly colitis.

Cephalosporins may be associated with a fall in prothrombin activity. Those at risk include patients with renal or hepatic impairment, or poor nutritional state, as well as patients receiving a protracted course of antimicrobial therapy, and patients previously stabilized on anticoagulant therapy. Prothrombin time should be monitored in patients at risk and exogenous vitamin K administered as indicated.

Information for Patients

Patients should be counseled that antibacterial drugs including cephalexin capsules, USP should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When cephalexin capsules, USP is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed.
 
Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by cephalexin capsules, USP or other antibacterial drugs in the future.
 
Diarrhea is a common problem caused by antibiotics which usually ends when the antibiotic is discontinued. Sometimes after starting treatment with antibiotics, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.

Drug Interactions

Metformin — In healthy subjects given single 500 mg doses of cephalexin and metformin, plasma metformin mean Cmax and AUC increased by an average of 34% and 24%, respectively, and metformin mean renal clearance decreased by 14%. No information is available about the interaction of cephalexin and metformin following multiple doses of either drug.
 
Although not observed in this study, adverse effects could potentially arise from co-administration of cephalexin and metformin by inhibition of tubular secretion via organic cationic transporter systems. Accordingly, careful patient monitoring and dose adjustment of metformin is recommended in patients concomitantly taking cephalexin and metformin.
 
Probenecid — As with other β‑lactams, the renal excretion of cephalexin is inhibited by probenecid.

Drug / Laboratory Test Interactions

As a result of administration of cephalexin capsules, USP, a false‑positive reaction for glucose in the urine may occur. This has been observed with Benedict’s and Fehling’s solutions and also with Clinitest® tablets.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Lifetime studies in animals have not been performed to evaluate the carcinogenic potential of cephalexin. Tests to determine the mutagenic potential of cephalexin have not been performed. In male and female rats, fertility and reproductive performance were not affected by cephalexin oral doses up to 1.5 times the highest recommended human dose based upon mg/m2.

Pregnancy

Teratogenic effects —  Pregnancy Category B — Reproduction studies have been performed on mice and rats using oral doses of cephalexin monohydrate 0.6 and 1.5 times the maximum daily human dose (66 mg/kg/day) based upon mg/m2, and have revealed no harm to the fetus. There are, however, no adequate and well‑controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers

The excretion of cephalexin in human milk increased up to 4 hours after a 500 mg dose; the drug reached a maximum level of 4 mcg/mL, then decreased gradually, and had disappeared 8 hours after administration. Caution should be exercised when cephalexin capsules, USP is administered to a nursing woman.

Pediatric Use

The safety and effectiveness of cephalexin capsules, USP in pediatric patients was established in clinical trials for the dosages described in the DOSAGE AND ADMINISTRATION section. In these trials, pediatric patients may have received cephalexin capsules. Cephalexin capsules should only be used in children and adolescents capable of ingesting the capsule.

Geriatric Use

Of the 701 subjects in 3 published clinical studies of cephalexin, 433 (62%) were 65 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
 
This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function (see PRECAUTIONS, General).