cephalexin monohydrate
DESCRIPTION:
CEFF (Cephalexin, USP) is a semisynthetic cephalosporin antibiotic intended
for oral administration. It is 7-(D-alpha-Amino-alpha- phenylacetamido)-3-
methyl-3-cephem-4-carboxylic acid monohydrate. Cephalexin has the molecular
formula C16H17N3O4S.H2O and the molecular weight is 365.41.
The nucleus of cephalexin is related to that of other cephalosporin antibiotics.
The compound is a zwitterion; ie, 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 (720
micromol) or 500 mg (1,439 micromol) of cephalexin. The CAPSULEs also contain
cellulose, D & C Yellow No. 10, F D & C Blue No. 1, F D & C Yellow No. 6,
gelatin, magnesium stearate, silicone, titanium dioxide, and other inactive
ingredients.
After mixing, each 5 mL of CEFF, for Oral Suspension, will contain cephalexin
monohydrate equivalent to 125 mg (360 micromol) or 250 mg (720 micromol) of
cephalexin. The suspensions also contain flavors, methylcellulose, silicone,
sodium lauryl sulfate, and sucrose. The 125-mg suspension contains F D & C Red
No. 40, and the 250-mg suspension contains F D & C Yellow No. 6.
ACTIONS/CLINICAL PHARMACOLOGY:
Human Pharmacology--CEFF 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
mcgm/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
1,000, 2,200, and 5,000 mcgm/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)
Staphylococcus Epidermidis (penicillinase- producing strains)
Streptococcus Pneumoniae
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.
Susceptibility Tests--DIFFUSION TECHNIQUES: Quantitative methods that require
measurement of zone diameters provide reproducible estimates of the
susceptibility of bacteria to antimicrobial compounds. One such standardized
procedure (REF. 1) that has been recommended for use with disks to test
susceptibility of microorganisms to cephalexin, uses the 30-mcgm cephalothin
disk. Interpretation involves correlation of the diameter obtained in the disk
test with the minimal inhibitory concentration (MIC) for cephalexin.
Reports from the laboratory providing results of the standard single-disk
susceptibility test with a 30-mcgm cephalothin disk should be interpreted
according to the following criteria:
ZONE DIAMETER (MM) INTERPRETATION
>/=18 (S) Susceptible
15-17 (I) Intermediate
=14 (R) Resistant
A report of "Susceptible" indicates that the pathogen is likely to be inhibited
by generally achievable concentrations of the antimicrobial compound in blood. A
report of "Intermediate" indicates that the result should be considered
equivocal, and, if the microorganism is not fully susceptible to the
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 that prevents small
uncontrolled technical factors from causing major discrepancies in
interpretation. A report of "Resistant" indicates that usually achievable
concentrations of the antimicrobial compound in the blood are unlikely to be
inhibitory and that other therapy should be selected.
Measurement of MIC or MBC and achieved antimicrobial compound concentrations may
be appropriate to guide therapy in some infections. (See ACTIONS/CLINICAL
PHARMACOLOGY section for information on drug concentrations achieved in infected
body sites and other pharmacokinetic properties of this antimicrobial drug
product).
Standardized susceptibility test procedures require the use of laboratory
control microorganisms. The 30-mcgm cephalothin disk should provide the
following zone diameters in these laboratory test quality control strains:
MICROORGANISM ZONE DIAMETER (MM)
E. Coli ATCC 25922 15-21
S. Aureus ATCC 25923 29-37
DILUTION TECHNIQUES:
Quantitative methods that are used to determine MICs provide reproducible
estimates of the susceptibility of bacteria to antimicrobial compounds. One such
standardized procedure uses a standardized dilution method (Ref. 2) (broth,
agar, microdilution) or equivalent with cephalothin powder. The MIC values
obtained should be interpreted according to the following criteria:
MIC (MCGM/ML) INTERPRETATION
=8 (S) Susceptible
16 (I) Intermediate
>/=32 (R) Resistant
Interpretation should be as stated above for results using diffusion techniques.
As with standard diffusion techniques, dilution methods require the use of
laboratory control organisms. Standard cephalothin powder should provide the
following MIC values:
MICROORGANISM MIC (MCGM/ML)
E. Coli ATCC 25922 4-16
8-32
S. Aureus ATCC 29213 0.12-0.5
INDICATIONS AND USAGE:
CEFF is indicated for the treatment of the following infections when caused by
susceptible strains of the designated microorganisms:
Respiratory tract infections caused by S. Pneumoniae and S. Pyogenes (Penicillin
is the usual drug of choice in the treatment and prevention of streptococcal
infections, including the prophylaxis of rheumatic fever. CEFF is generally
effective in the eradication of streptococci from the nasopharynx; however,
substantial data establishing the efficacy of CEFF in the subsequent
prevention of rheumatic fever are not available at present.)
Otitis media due to S. Pneumoniae, H. Influenzae, staphylococci, streptococci,
and M. Catarrhalis
Skin and skin structure infections caused by staphylococci and/or streptococci
Bone infections caused by staphylococci and/or P. Mirabilis
Genitourinary tract infections, including acute prostatitis, caused by E. Coli,
P. Mirabilis, and K. Pneumoniae
Note--Culture and susceptibility tests should be initiated prior to and during
therapy. Renal function studies should be performed when indicated.
CONTRAINDICATIONS:
CEFF is contraindicated in patients with known allergy to the cephalosporin
group of antibiotics.
WARNINGS:
BEFORE CEPHALEXIN THERAPY IS INSTITUTED, CAREFUL INQUIRY SHOULD BE MADE
CONCERNING PREVIOUS HYPERSENSITIVITY REACTIONS TO CEPHALOSPORINS AND PENICILLIN.
CEPHALOSPORIN C DERIVATIVES SHOULD BE GIVEN CAUTIOUSLY TO PENICILLIN-SENSITIVE
PATIENTS.
SERIOUS ACUTE HYPERSENSITIVITY REACTIONS MAY REQUIRE EPINEPHRINE AND OTHER
EMERGENCY MEASURES.
There is some clinical and laboratory evidence of partial cross-allergenicity of
the penicillins and the cephalosporins. Patients have been reported to have had
severe reactions (including anaphylaxis) to both drugs.
Any patient who has demonstrated some form of allergy, particularly to drugs,
should receive antibiotics cautiously. No exception should be made with regard
to CEFF.
PSEUDOMEMBRANOUS COLITIS HAS BEEN REPORTED WITH NEARLY ALL ANTIBACTERIAL AGENTS,
INCLUDING CEPHALEXIN, AND MAY RANGE FROM MILD TO LIFE THREATENING. THEREFORE, IT
IS IMPORTANT TO CONSIDER THIS DIAGNOSIS IN PATIENTS WITH DIARRHEA SUBSEQUENT TO
THE ADMINISTRATION OF ANTIBACTERIAL AGENTS.
Treatment with antibacterial agents alters the normal flora of the colon and may
permit overgrowth of clostridia. Studies indicate that a toxin produced by
Clostridium Difficile is one primary cause of antibiotic-associated colitis.
After the diagnosis of pseudomembranous colitis has been established,
appropriate therapeutic measures should be initiated. Mild cases of
pseudomembranous colitis usually respond to drug discontinuation alone. In
moderate to severe cases, consideration should be given to management with
fluids and electrolytes, protein supplementation, and treatment with an
antibacterial drug clinically effective against Clostridium Difficile colitis.
Usage In Pregnancy--Safety of this product for use during pregnancy has not been
established.
PRECAUTIONS:
General--Patients should be followed carefully so that any side effects or
unusual manifestations of drug idiosyncrasy may be detected. If an allergic
reaction to CEFF occurs, the drug should be discontinued and the patient
treated with the usual agents (eg, epinephrine or other pressor amines,
antihistamines, or corticosteroids).
Prolonged use of CEFF 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.
CEFF 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.
As a result of administration of CEFF, 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(R) tablets.
As with other Beta-lactams, the renal excretion of cephalexin is inhibited by
probenecid.
Broad-spectrum antibiotics should be prescribed with caution in individuals with
a history of gastrointestinal disease, particularly colitis.
Usage In Pregnancy--Pregnancy Category B--The daily oral administration of
cephalexin to rats in doses of 250 or 500 mg/kg prior to and during pregnancy,
or to rats and mice during the period of organogenesis only, had no adverse
effect on fertility, fetal viability, fetal weight, or litter size. Note that
the safety of cephalexin during pregnancy in humans has not been established.
Cephalexin showed no enhanced toxicity in weanling and newborn rats as compared
with adult animals. Nevertheless, because the studies in humans cannot rule out
the possibility of harm, CEFF should be used during pregnancy only if clearly
needed.
Nursing Mothers--The excretion of cephalexin in the milk increased up to 4 hours
after a 500-mg dose; the drug reached a maximum level of 4 mcgm/mL, then
decreased gradually, and had disappeared 8 hours after administration. Caution
should be exercised when CEFF is administered to a nursing woman.
ADVERSE REACTIONS:
Gastrointestinal--Symptoms of pseudomembranous colitis may appear either during
or after antibiotic treatment. Nausea and vomiting have been reported rarely.
The most frequent side effect has been diarrhea. It was very rarely severe
enough to warrant cessation of therapy. Dyspepsia, gastritis, and abdominal pain
have also occurred. As with some penicillins and some other cephalosporins,
transient hepatitis and cholestatic jaundice have been reported rarely.
Hypersensitivity--Allergic reactions in the form of rash, urticaria, angioedema,
and, rarely, erythema multiforme, Stevens-Johnson syndrome, or toxic epidermal
necrolysis have been observed. These reactions usually subsided upon
discontinuation of the drug. In some of these reactions, supportive therapy may
be necessary. Anaphylaxis has also been reported.
Other reactions have included genital and anal pruritus, genital moniliasis,
vaginitis and vaginal discharge, dizziness, fatigue, headache, agitation,
confusion, hallucinations, arthralgia, arthritis, and joint disorder. Reversible
interstitial nephritis has been reported rarely. Eosinophilia, neutropenia,
thrombocytopenia, and slight elevations in AST and ALT have been reported.
OVERDOSAGE:
Signs And Symptoms--Symptoms of oral overdose may include nausea, vomiting,
epigastric distress, diarrhea, and hematuria. If other symptoms are present, it
is probably secondary to an underlying disease state, an allergic reaction, or
toxicity due to ingestion of a second medication.
Treatment--To obtain up-to-date information about the treatment of overdose, a
good resource is your certified Regional Poison Control Center. Telephone
numbers of certified poison control centers are listed in the Physicians' Desk
Reference (PDR). In managing overdosage, consider the possibility of multiple
drug overdoses, interaction among drugs, and unusual drug kinetics in your
patient.
Unless 5 to 10 times the normal dose of cephalexin has been ingested,
gastrointestinal decontamination should not be necessary.
Protect the patient's airway and support ventilation and perfusion. Meticulously
monitor and maintain, within acceptable limits, the patient's vital signs, blood
gases, serum electrolytes, etc. Absorption of drugs from the gastrointestinal
tract may be decreased by giving activated charcoal, which, in many cases, is
more effective than emesis or lavage; consider charcoal instead of or in
addition to gastric emptying. Repeated doses of charcoal over time may hasten
elimination of some drugs that have been absorbed. Safeguard the patient's
airway when employing gastric emptying or charcoal.
Forced diuresis, peritoneal dialysis, hemodialysis, or charcoal hemoperfusion
have not been established as beneficial for an overdose of cephalexin; however,
it would be extremely unlikely that one of these procedures would be indicated.
The oral median lethal dose of cephalexin in rats is 5,000 mg/kg.
DOSAGE AND ADMINISTRATION:
CEFF is administered orally.
Adults--The adult dosage ranges from 1 to 4 g daily in divided doses. The usual
adult dose is 250 mg every 6 hours. For the following infections, a dosage of
500 mg may be administered every 12 hours: streptococcal pharyngitis, skin and
skin structure infections, and uncomplicated cystitis in patients over 15 years
of age. Cystitis therapy should be continued for 7 to 14 days. For more severe
infections or those caused by less susceptible organisms, larger doses may be
needed. If daily doses of CEFF greater than 4 g are required, parenteral
cephalosporins, in appropriate doses, should be considered.
Pediatric Patients--The usual recommended daily dosage for pediatric patients is
25 to 50 mg/kg in divided doses. For streptococcal pharyngitis in patients over
1 year of age and for skin and skin structure infections, the total daily dose
may be divided and administered every 12 hours.
CEFF SUSPENSION
CHILD'S WEIGHT 125 MG/5 ML 250 MG/5 ML
10 kg (22 lb) 1/2 to 1 tsp q.i.d. 1/4 to 1/2 tsp q.i.d.
20 kg (44 lb) 1 to 2 tsp q.i.d. 1/2 to 1 tsp q.i.d.
40 kg (88 lb) 2 to 4 tsp q.i.d. 1 to 2 tsp q.i.d.
OR
CHILD'S WEIGHT 125 MG/5 ML 250 MG/5 ML
10 kg (22 lb) 1 to 2 tsp b.i.d. 1/2 to 1 tsp b.i.d.
20 kg (44 lb) 2 to 4 tsp b.i.d. 1 to 2 tsp b.i.d.
40 kg (88 lb) 4 to 8 tsp b.i.d. 2 to 4 tsp b.i.d.
In severe infections, the dosage may be doubled.
In the therapy of otitis media, clinical studies have shown that a dosage of 75
to 100 mg/kg/day in 4 divided doses is required.
In the treatment of beta-hemolytic streptococcal infections, a therapeutic
dosage of CEFF should be administered for at least 10 days.
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