CEFADROXIL MONOHYDRATE
DESCRIPTION
DROXYL (cefadroxil monohydrate, USP) is a semi synthetic cephalosporin
antibiotic intended for oral administration. It is a white to yellowish-white
crystalline powder. It is soluble in water and it is acid-stable. It is
chemically designated as 5-Thia-1-azabicyclo(4.2.0)oct- 2-ene-2-carboxylic acid,
7-((amino(4-hydroxyphenyl)acetyl) amino)-3-methyl-8-oxo-, monohydrate, (6R-
(6(alpha),7(beta)(R*)))-. It has the formula C16H17N3O5S*H2O and the molecular
weight of 381.40.
DROXYL film-coated tablets, 1 g, contain the following inactive ingredients:
microcrystalline cellulose, hydroxypropyl methylcellulose, magnesium stearate,
polyethylene glycol, polysorbate 80, simethicone emulsion, and titanium dioxide.
DROXYL for Oral Suspension contains the following inactive ingredients: FD&C
Yellow No. 6, flavors (natural and artificial), polysorbate 80, sodium benzoate,
sucrose, and xanthan gum.
ACTIONS/CLINICAL PHARMACOLOGY:
DROXYL is rapidly absorbed after oral administration. Following single doses of
500 and 1000 mg, average peak serum concentrations were approximately 16 and 28
Mu-g/mL, respectively. Measurable levels were present 12 hours after
administration. Over 90% of the drug is excreted unchanged in the urine within
24 hours. Peak urine concentrations are approximately 1800 Mu- g/mL during the
period following a single 500-mg oral dose. Increases in dosage generally
produce a proportionate increase in DROXYL urinary concentration. The urine
antibiotic concentration, following a 1-g dose, was maintained well above the
MIC of susceptible urinary pathogens for 20 to 22 hours.
MICROBIOLOGY
In Vitro tests demonstrate that the cephalosporins are bactericidal because of
their inhibition of cell-wall synthesis. Cefadroxil has been shown to be active
against the following organisms both In Vitro and in clinical infections (see
INDICATIONS AND USAGE):
BETA-HEMOLYTIC STREPTOCOCCI
STAPHYLOCOCCI, including penicillinase-producing strains
STREPTOCOCCUS (DIPLOCOCCUS) PNEUMONIAE
ESCHERICHIA COLI
PROTEUS MIRABILIS
KLEBSIELLA species
MORAXELLA (BRANHAMELLA) CATARRHALIS
NOTE: Most strains of ENTEROCOCCUS FAECALIS (formerly STREPTOCOCCUS FAECALIS)
and ENTEROCOCCUS FAECIUM (formerly STREPTOCOCCUS FAECIUM) are resistant to
DROXYL (cefadroxil monohydrate, USP). It is not active against most strains of
ENTEROBACTER species, MORGANELLA MORGANII (formerly PROTEUS MORGANII), and P.
VULGARIS. It has no activity against PSEUDOMONAS SPECIES and ACINETOBACTER
CALCOACETICUS (formerly MIMA and HERELLEA species).
SUSCEPTIBILITY TESTS: DIFFUSION TECHNIQUES
The use of antibiotic disk susceptibility test methods which measure zone
diameter give an accurate estimation of antibiotic susceptibility. One such
standard procedure (REF.1) which has been recommended for use with disks to test
susceptibility of organisms to cefadroxil uses the cephalosporin class
(cephalothin) disk. Interpretation involves the correlation of the diameters
obtained in the disk test with the minimum inhibitory concentration (MIC) for
cefadroxil.
Reports from the laboratory giving results of the standard single-disk
susceptibility test with a 30 Mu-g 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 blood levels. A report of "Intermediate susceptibility"
suggests that the organism would be susceptible if high dosage is used or if the
infection is confined to tissue and fluids (eg, urine) in which high antibiotic
levels are attained. A report of "Resistant" indicates that achievable
concentrations of the antibiotic are unlikely to be inhibitory and other therapy
should be selected.
Standardized procedures require the use of laboratory control organisms. The 30
Mu-g cephalothin disk should give the following zone diameters:
ZONE
ORGANISM DIAMETER (MM)
STAPHYLOCOCCUS AUREUS ATCC 25923 29 -37
ESCHERICHIA COLI ATCC 25922 17- 22
DILUTION TECHNIQUES
When using the NCCLS agar dilution or broth dilution (including microdilution)
method (REF. 2) or equivalent, a bacterial isolate may be considered susceptible
if the MIC (minimum inhibitory concentration) value for cephalothin is 8 Mu-g/mL
or less. Organisms are considered resistant if the MIC is 32 Mu-g/mL or greater.
Organisms with an MIC value of less than 32 Mu- g/mL but greater than 8 Mu-g/mL
are intermediate.
As with standard diffusion methods, dilution procedures require the use of
laboratory control organisms. Standard cephalothin powder should give MIC values
in the range of 0.12 Mu-g/mL and 0.5 Mu-g/mL for STAPHYLOCOCCUS AUREUS ATCC
29213. For ESCHERICHIA COLI ATCC 25922, the MIC range should be between 4.0 Mu-
g/mL and 16.0 Mu-g/mL. For STREPTOCOCCUS FAECALIS ATCC 29212, the MIC range
should be between 8.0 and 32.0 Mu-g/mL.
INDICATIONS AND USAGE:
DROXYL (cefadroxil monohydrate, USP) is indicated for the treatment of
patients with infection caused by susceptible strains of the designated
organisms in the following diseases:
Urinary tract infections caused by E. COLI, P. MIRABILIS, and KLEBSIELLA
species.
Skin and skin structure infections caused by staphylococci and/or streptococci.
Pharyngitis and tonsillitis caused by Group A beta-hemolytic streptococci.
(Penicillin is the usual drug of choice in the treatment and prevention of
streptococcal infections, including the prophylaxis of rheumatic fever. DROXYL
is generally effective in the eradication of streptococci from the nasopharynx;
however, substantial data establishing the efficacy of DROXYL in the subsequent
prevention of rheumatic fever are not available at present.)
NOTE: Culture and susceptibility tests should be initiated prior to and during
therapy. Renal function studies should be performed when indicated.
CONTRAINDICATIONS:
DROXYL (cefadroxil monohydrate, USP) is contraindicated in patients with known
allergy to the cephalosporin group of antibiotics.
WARNINGS:
BEFORE THERAPY WITH DROXYL IS INSTITUTED, CAREFUL INQUIRY SHOULD BE MADE TO
DETERMINE WHETHER THE PATIENT HAS HAD PREVIOUS HYPERSENSITIVITY REACTIONS TO
CEFADROXIL, CEPHALOSPORINS, PENICILLINS OR OTHER DRUGS. IF THIS PRODUCT IS TO BE
GIVEN TO PENICILLIN- SENSITIVE PATIENTS, CAUTION SHOULD BE EXERCISED BECAUSE
CROSS-SENSITIVITY AMONG BETA-LACTAM ANTIBIOTICS HAS BEEN CLEARLY DOCUMENTED AND
MAY OCCUR IN UP TO 10% OF PATIENTS WITH A HISTORY OF PENICILLIN ALLERGY.
IF AN ALLERGIC REACTION TO DROXYL OCCURS, DISCONTINUE THE DRUG. SERIOUS ACUTE
HYPERSENSITIVITY REACTIONS MAY REQUIRE TREATMENT WITH EPINEPHRINE AND OTHER
EMERGENCY MEASURES, INCLUDING OXYGEN, INTRAVENOUS FLUIDS, INTRAVENOUS
ANTIHISTAMINES, CORTICOSTEROIDS, PRESSOR AMINES, AND AIRWAY MANAGEMENT, AS
CLINICALLY INDICATED.
PSEUDOMEMBRANOUS COLITIS HAS BEEN REPORTED WITH NEARLY ALL ANTIBACTERIAL AGENTS,
INCLUDING CEFADROXIL, AND MAY RANGE FROM MILD TO LIFE- THREATENING. THEREFORE,
IT IS IMPORTANT TO CONSIDER THIS DIAGNOSIS IN PATIENTS WHO PRESENT 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 a primary cause of "antibiotic-associated colitis."
After the diagnosis of pseudomembranous colitis has been established,
therapeutic measures should be initiated. Mild cases of pseudomembranous colitis
usually respond to discontinuation of the drug alone. In moderate to severe
cases, consideration should be given to management with fluids and electrolytes,
protein supplementation and treatment with an antibacterial drug effective
against CLOSTRIDIUM DIFFICILE.
PRECAUTIONS:
GENERAL
DROXYL should be used with caution in the presence of markedly impaired renal
function (creatinine clearance rate of less than 50 mL/min/1.73 M(squared)) (See
DOSAGE AND ADMINISTRATION)). In patients with known or suspected renal
impairment, careful clinical observation and appropriate laboratory studies
should be made prior to and during therapy.
Prolonged use of DROXYL 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.
DROXYL (cefadroxil monohydrate, USP) should be prescribed with caution in
individuals with history of gastrointestinal disease, particularly colitis.
DRUG/LABORATORY TEST INTERACTIONS
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.
CARCINOGENESIS, MUTAGENESIS, AND IMPAIRMENT OF FERTILITY:
No long-term studies have been performed to determine carcinogenic potential. No
genetic toxicity tests have been performed.
PREGNANCY:
Pregnancy Category B: Reproduction studies have been performed in mice and rats
at doses up to 11 times the human dose and have revealed no evidence of impaired
fertility or harm to the fetus due to cefadroxil monohydrate. 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.
LABOR AND DELIVERY:
DROXYL (cefadroxil monohydrate, USP) has not been studied for use during labor
and delivery. Treatment should only be given if clearly needed.
NURSING MOTHERS:
Caution should be exercised when cefadroxil monohydrate is administered to a
nursing mother.
PEDIATRIC USE:
(See DOSAGE AND ADMINISTRATION)
DRUG INTERACTIONS:
DRUG/LABORATORY TEST INTERACTIONS
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.
(See also PRECAUTIONS)
ADVERSE REACTIONS:
GASTROINTESTINAL
Onset of pseudomembranous colitis symptoms may occur during or after antibiotic
treatment (See WARNINGS). Dyspepsia, nausea and vomiting have been reported
rarely. Diarrhea has also occurred.
HYPERSENSITIVITY
Allergies (in the form of rash, urticaria, angioedema, and pruritis) have been
observed. These reactions usually subsided upon discontinuation of the drug.
Anaphylaxis has also been reported.
OTHER
Other reactions have included genital pruritus, genital moniliasis, vaginitis,
moderate transient neutropenia, fever, and minor elevations in serum
transaminase. Agranulocytosis, thrombocytopenia, erythema multiforme, Stevens-
Johnson syndrome, serum sickness, and arthralgia have been rarely reported.
In addition to the adverse reactions listed above which have been observed in
patients treated with cefadroxil, the following adverse reactions and altered
laboratory tests have been reported for cephalosporin-class antibiotics:
Toxic epidermal necrolysis, abdominal pain, superinfection, renal dysfunction,
toxic nephropathy, hepatic dysfunction including cholestasis, aplastic anemia,
hemolytic anemia, hemorrhage, prolonged prothrombin time, positive Coombs test,
increased BUN, increased creatinine, elevated alkaline phosphatase, elevated
aspartate aminotransferase (AST), elevated alanine aminotransferase (ALT),
elevated bilirubin, elevated LDH, eosinophilia, pancytopenia, neutropenia.
Several cephalosporins have been implicated in triggering seizures, particularly
in patients with renal impairment, when the dosage was not reduced (see DOSAGE
AND ADMINISTRATION and OVERDOSAGE). If seizures associated with drug therapy
occur, the drug should be discontinued. Anticonvulsant therapy can be given if
clinically indicated.
OVERDOSAGE:
A study of children under six years of age suggested that ingestion of less than
250 mg/kg of cephalosporins is not associated with significant outcomes. No
action is required other than general support and observation. For amounts
greater than 250 mg/kg, induce gastric emptying.
In five anuric patients, it was demonstrated that an average of 63% of a 1 g
oral dose is extracted from the body during a 6-8 hour hemodialysis session.
DOSAGE AND ADMINISTRATION:
DROXYL is acid-stable and may be administered orally without regard to meals.
Administration with food may be helpful in diminishing potential
gastrointestinal complaints occasionally associated with oral cephalosporin
therapy.
Adults
Urinary Tract Infections:
For uncomplicated lower urinary tract infections (ie, cystitis) the usual dosage
is 1 or 2 g per day in single (q.d.) or divided doses (b.i.d.).
For all other urinary tract infections the usual dosage is 2 g per day in
divided doses (b.i.d.).
Skin and Skin Structure Infections:
For skin and skin structure infections the usual dosage is 1 g per day in single
(q.d.) or divided doses (b.i.d.).
Pharyngitis and Tonsillitis:
Treatment of group A beta-hemolytic streptococcal pharyngitis and tonsillitis -
1 g per day in single (q.d.) or divided doses (b.i.d.) for 10 days.
Children
For urinary tract infections, the recommended daily dosage for children is 30
mg/kg/day in divided doses every 12 hours. For pharyngitis, tonsillitis, and
impetigo, the recommended daily dosage for children is 30 mg/kg/day in a single
dose or in equally divided doses every 12 hours. For other skin and skin
structure infections, the recommended daily dosage is 30 mg/kg/day in equally
divided doses every 12 hours. In the treatment of beta-hemolytic streptococcal
infections, a therapeutic dosage of DROXYL should be administered for at
least 10 days.
See chart for total daily dosage for children.
DAILY DOSAGE OF DROXYL SUSPENSION
Child' s Weight
lbs kg 125 mg/5 mL 250 mg/5 mL 500 mg/5 mL
10 4.5 1 tsp -
20 9.1 2 tsp 1 tsp
30 13.6 3 tsp 1 1/2 tsp
40 18.2 4 tsp 2 tsp 1 tsp
50 22.7 5 tsp 2 1/2 tsp 1 1/4 tsp
60 27.3 6 tsp 3 tsp 1 1/2 tsp
70 & above 31.8+ - - 2 tsp
In patients with renal impairment, the dosage of cefadroxil monohydrate should
be adjusted according to creatinine clearance rates to prevent drug
accumulation. The following schedule is suggested. In adults, the initial dose
is 1000mg of DROXYL (cefadroxil monohydrate, USP) and the maintenance dose
(based on the creatinine clearance rate (mL/min/1.73 M(squared))) is 500 mg at
the time intervals listed below.
Creatinine Clearances Dosage Interval
0-10 mL/min 36 hours
10-25 mL/min 24 hours
25-50 mL/min 12 hours
Patients with creatinine clearance rates over 50 mL/min may be treated as if
they were patients having normal renal function.
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