Cephalexin

Sharon S. Castle VA Medical Center, Huntington, USA

ã 2007 Elsevier Inc. All rights reserved.

Introduction

Cephalexin is an orally active, first-generation cephalosporin antibiotic. It is effective against

gram-positive organisms, while having limited gram-negative coverage. Cephalexin is used
in the treatment of pharyngitis, tonsillitis, urinary tract infections, and uncomplicated skin
infections.

Nomenclature
Name of the Clinical Cephalexin
Form
Related Names 5-Thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylicacid,7-
Source: EMTREE [(aminophenylacetyl)amino]-3-methyl-8-oxo-,monohydrate,
[6R-(6alpha,7beta,(R*)]-; 7 (alpha aminophenylacetamido) 3
methyl 3 cephem 4 carboxylic acid; alsporin; apo cephalex;
cefalex; cefalexine; cefalexin glaxo; cefalexin monohydrate;
cefaseptin; cefaxin; cepexin; cephalexcin monohydrate;
cephalexine; cephalexine monohydrate; cephalexin hydrate;
cephalexin monohydrate; cephalexinum; cephaloxin; cepo
1000; ceporex; ceporexin; ceporexine; ceporexsyrup; d 7(2
amino 2 fenylacetamido) 3 methyl 8 oxo 5 thia 1 azabicyclo
[4.2.0]oct2 ene 2 carbonic acid; hi 89; keflet; keflex; keforal;
larixin; madlexin; novolexin; oracef; ospexin; palitrex;
pyasan; pyassan; s 6437; salitex; sencephalin; sigmacef;
syncl; cefalexin; 5-Thia-1-azabicyclo[4.2.0]oct-2-ene-2-
carboxylic acid,7-[(aminophenylacetyl)amino]-3-methyl-8-
oxo-,monohydrate,[6R-(6alpha,7beta,(R*)]-; (6R,7R)-7-((R)-
2-Amino-2-phenyl-acetylamino)-3-methyl-8-oxo-5-thia-1-
aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid; (6R,7R)-7-
((R)-2-Amino-2-phenyl-acetylamino)-3-methyl-8-oxo-5-thia-
1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid; ceporex
syrup; d 7(2 amino 2 fenylacetamido) 3 methyl 8 oxo 5 thia 1
azabicyclo[4.2.0]oct 2 ene 2 carbonic acid
Chemical Names (7R)-3-Methyl-7-(alpha-D-phenylglycylamino)-3-cephem-4-
carboxylicacid monohydrate Sweetman (2003).
CAS Number 23325-78-2

1
2 Cephalexin

Basic Chemistry
Chemical Structure
Structure

Chemical Formula C16 H17 N3 O4 S

Properties
Physical Properties 1.16 g of cephalexin hydrochloride monograph substance is
approximately equivalent to 1 g of anhydrous cefalexin
Sweetman (2003).
Molecular Weight 347.393
Solubility Cepalexin is a white to off-white, crystalline powder. It is slightly
soluble in water, practically insoluble in alcohol, in chloroform,
and in ether. The pH of a 5% aqueous suspension is between
3.0 and 5.5. It is soluble 1 in 100 in water, in acetone, in
acetonitrile, in alcohol, in dimethylformamide, and in methyl
alcohol. The hydrochloride is practically insoluble in
chloroform, in ether, in ethyl acetate, and in isopropyl alcohol.
The pH of a 1% aqueous solution of the hydrochloride salt is
between 1.5 and 3.0 Sweetman (2003).
Ionization Constant
Value Salt Conditions Reference Comments
pKa 3.2 Williams (2002) HA

Human Pharmacokinetics

Cephalexin, like other oral first-generation cephalosporins, is well-absorbed following

oral administration and is widely distributed to body fluids and tissues. It is excreted
unchanged in urine.

Pharmacokinetic Properties

Prep. and
Value Units Route of Admin. Reference Comments

Absorption Cephalexin hydrochloride appears to be more rapidly absorbed than the

free base. While peak concentrations of the drug are affected by food, the
extent of absorption is not altered AHFS (2001).
 Cephalexin 3

Bioavailability 90 % p.o. Spyker et al

(1978)
Distribution Cephalexin is widely distributed to body fluids and tissues.
Volume of Distribution 0.23 l/kg Poisindex
(2003)
Plasma Protein Binding 15 % Sweetman
(2003)
Metabolism
Plasma Half-Life 0.5–1.2 Hrs AHFS (2001) Plasma half-life is
prolonged in those
with impaired renal
function.
Bio Half-Life
Clearance 4.3 ml/min/ Spyker et al Clearance is
kg (1978) decreased in those
with compromised
renal function.
Routes of Elimination Cephalexin is excreted unchanged in urine by glomerular filtration and
tubular secretion AHFS (2001).

Targets-Pharmacodynamics

Cephalexin is a bactericidal antibiotic that inhibits bacterial cell wall synthesis by binding
to one or more penicillin binding proteins of actively dividing cells. It is also proposed that
cephalosporins decrease the availability of an inhibitor to murein hydrolase (autolysin), an
enzyme involved in cell division.

Target Name(s):
Penicillin binding proteins

Therapeutics

Cephalexin is a first-generation cephalosporin that displays activity against Streptococcal

and Staphylcoccocal species. It has limited gram-negative activity against some strains of
Escherichia coli, Klebsiella pneumonia, and Proteus mirabilis.

Indications

Prep. and Route

Value Units of Admin. Reference Comments

Skin and Skin Structure Infections

Dosage 250 mg every 6 hrs AHFS (2001) Can be administered as 500 mg every
12 hrs. Severe infections may
require doses as high as 4 g daily.
Doses must be reduced in those
with renal insufficiency based on
creatinine clearance.
Streptococcal Pharyngitis
Dosage 250 mg every 6 hrs AHFS (2001) Can be administered as 500 mg every
12 hrs. Severe infections may
require doses as high as 4 g daily.
4 Cephalexin

A minimum of 10 days of therapy

are recommended for infections
caused by Streptococcus
pyogenes.
Doses must be reduced in those
with renal insufficiency based on
creatinine clearance.
Cystitis, Uncomplicated
Dosage 250 mg every 6 hrs AHFS (2001) Can be administered as 500 mg every
12 hrs. Length of therapy for cystitis
is 7–14 days. Severe infections may
require doses as high as 4 g daily.
Doses must be reduced in those
with renal insufficiency based on
creatinine clearance.
Infections Caused By Susceptible Organisms, Pediatrics
Dosage 25–50 mg/kg divided in 3–4 AHFS (2001) Minimum of 10 days of therapy
doses recommended for infections
caused by Streptococcus
pyogenes.
Dose may be divided every 12
hours for Streptococcal
pharyngitis.

Contraindications
Cephalexin is contraindicated in patients with a history of allergic reactions to cephalo-
sporin antibiotics. Cephalexin should be avoided in those with anaphylactic reactions to
penicillins and should be used with caution in patients with delayed hypersensitivity
reactions such as rash, fever, or eosinophilia AHFS (2001).

Adverse Effects
Hypersensitivity reactions occur in approximately 5% or less of patients receiving
cephalosporin antibiotics. These include urticaria, pruritis, rash, fever, eosinophilia,
angioedema, hypotension, Stevens-Johnson Syndrome, erythema multiforme, toxic epi-
dermal necrolysis, and exfoliative dermatitis. Positive direct and indirect antiglobulin
(Coombs’) test have been reported in 3% or more of patients receiving cephalosporins.
Rarely, cephalosporins cause neutropenia, thrombocytopenia, leukocytosis, granulocyto-
sis, monocytosis, lymphocytopenia, basophilia, reversible leukopenia, aplastic anemia,
pancytopenia, and hemolytic anemia. Transient increases in BUN and serum creatinine,
renal dysfunction, and nephrotoxicity have occurred with cephalosporin use, as have
transient increases in AST, ALT, GGT, and alkaline phosphotase. Nausea, vomiting, and
diarrhea are the most frequent adverse reaction to oral cephalsporins. Clostridium
difficile colitis can occur with cephalosporin use AHFS (2001).

Agent-Agent Interactions

Agent Name Mode of Interaction

Aminoglycoside Aminoglycoside antibiotics (e.g., gentamicin, tobramycin, amikacin). There is
antibiotics an increased risk of nephrotoxicity with concurrent use of cephalexin and
aminoglycoside antibiotics.
Probenecid By inhibiting renal tubular secretion, probenecid delays the excretion of
cephalexin.
 Cephalexin 5

Pre-Clinical Research
Pharmacokinetics

Potency

Value Units Organ/ Prep. and Cell Effects Exp. Reference Comments
Tissue Route of Line/ End
Admin. Type Point
Rat
LD50 5 g/kg p.o. AHFS
(2001)
LD50 >20 g/kg p.o. Poisindex
(2003)
Mouse
LD50 1495 mg/kg p.o. Poisindex
(2003)

Journal Citations

Spyker, D.A., Thomas, B.L., Sande, M.A., Bolton, W.K., 1978. Pharmacokinetics of cefaclor and
cephalexin: dosage nomograms for impaired renal function. Antimicrob. Agents Chemother., 14,
172–177.

Book Citations

Sweetman, S., 2003. Martindale: The Complete Drug Reference. Sweetman, S. (Ed.), Micromedex,
Electronic Version. Pharmaceutical Press, Greenwood Village, Colorado.
Williams, D., 2002. pKa Values for Some Drugs and Miscellaneous Organic Acids and Bases. Williams, D.A.,
Lemke, T.L. (Ed.), Foye’s Principles of Medicinal Chemistry, Edition 5, p. 1071, Lippincott Williams and
Wilkins, Philidelphia.
Poisindex 2003 Poisindex System. Toll, L.L., Hurlbut, K.M. (Ed.), Micromedex, Electronic Version.
Pharmaceutical Press, Greenwood Village, Colorado.
AHFS 2001 Drug Monographs. McEvoy, G. (Ed.), American Hospital Formulary System, pp. 128–253,
American Society of Health-System Pharmacists, Inc., Bethesda, Maryland.