CEFACLOR
DESCRIPTION:
Cefaclor, is a semisynthetic cephalosporin antibiotic for oral administration.
Cefaclor, USP, is chemically designated as 3-chloro-7-D- (2-phenylglycinamido)-
3- cephem-4-carboxylic acid monohydrate. Cefaclor monohydrate has a molecular formula of
C15H14ClN3O4S .H2O and a molecular weight of 385.82.
ACTIONS/CLINICAL PHARMACOLOGY:
Pharmacokinetics:
Absorption And Metabolism: The extent of absorption (AUC) and the maximum plasma
concentration (Cmax) of cefaclor from DISTACLOR CD are greater when the extended
release tablet is taken with food.
(NOTE: The extent of absorption (AUC) of cefaclor from DISTACLOR CAPS is
unaffected by food intake; however, when DISTACLOR CAPS are taken with food,
the Cmax is decreased.)
There is no evidence of metabolism of cefaclor in humans.
Comparative Serum Pharmacokinetics--Serum pharmacokinetic parameters for Ceclor
CD and DISTACLOR CAPS are shown in the following table.
-----------------------------------------------------------------------------------------------------------------------------------------------------
TABLE 1
COMPARATIVE PHARMACOKINETICS OF DISTACLOR CAPS VS
DISTACLOR CD IN FASTING AND FED STATES
------------------------------------------------------------------------------------------------------------------------------------------------------
Parameter DISTACLOR CD DISTACLOR CD DISTACLOR CAPS
----------------------------------------------------------------------------------------------------------------------------------------
375 mg 500 mg 2 X 250 mg
-----------------------------------------------------------------------------------------------------------------------------------------
fed fast fed fast fed fast
-----------------------------------------------------------------------------------------------------------------------------------------
n = 10 n = 16 n = 16 n = 15 n = 16
------------------------------------------------------------------------------------------------------------------------------------------------------
Cmax 3.7 (1.1) NA 8.2 (4.2) 5.4 (1.6) 9.3 (2.7) 16.8 (4.7)
------------------------------------------------------------------------------------------------------------------------------------------------------
Tmax 2.7 (1.0) NA 2.5 (0.8) 1.5 (0.7) 1.5 (0.6) 0.9 (0.4)
------------------------------------------------------------------------------------------------------------------------------------------------------
AUC 9.9 (2.2) NA 18.1 (4.2) 14.8 (4.0) 20.5 (2.8) 19.2 (5.0)
------------------------------------------------------------------------------------------------------------------------------------------------------
(+/- 1 standard deviation)
NA = data not available
No drug accumulation was noted when DISTACLOR CD was given twice daily.
The plasma half-life in healthy subjects is independent of dosage form and
averages approximately 1 hour.
Food Effect On Pharmacokinetics: When DISTACLOR CD is taken with food, the AUC is
10% lower while the Cmax is 12% lower and occurs 1 hour later compared to Ceclor
Pulvules. In contrast, when DISTACLOR CD is taken without food, the AUC is 23%
lower while the Cmax is 67% lower and occurs 0.6 hours later, using an
equivalent milligram dose of DISTACLOR CAPS as a reference. THEREFORE, CECLOR
CD SHOULD BE TAKEN WITH FOOD.
SPECIAL POPULATIONS:
Renal Insufficiency--In patients with reduced renal function, the serum half-
life of cefaclor is slightly prolonged. In those with complete absence of renal
function, the plasma half-life of the intact molecule is 2.3 to 2.8 hours.
Excretion pathways in patients with markedly impaired renal function have not
been determined. Hemodialysis shortens the half-life by 25% to 30%.
Geriatric Patients--In elderly subjects (over age 65) with normal serum
creatinine values, higher peak plasma concentrations and AUCs have been
observed. This is considered to be primarily a result of an age-related
decrement in renal function, and has no apparent clinical significance.
Therefore, dosage adjustment is not necessary in elderly subjects with normal
serum creatinine values.
MICROBIOLOGY:
Cefaclor has In Vitro activity against a broad range of gram-positive and gram-
negative bacteria. The bactericidal action of cefaclor results from inhibition
of cell-wall synthesis. Cefaclor is stable in the presence of some bacterial
beta-lactamases; consequently, some beta-lactamase-producing organisms may be
susceptible to cefaclor.
DISTACLOR CD 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:
GRAM-POSITIVE AEROBES:
Staphylococcus Aureus
Streptococcus Pneumoniae
Streptococcus Pyogenes
NOTE: Cefaclor is inactive against methicillin- resistant staphylococci.
GRAM-NEGATIVE AEROBES:
Haemophilus Influenzae (non-beta-lactamase- producing strains only)
Moraxella Catarrhalis (including beta-lactamase- producing strains)
The following In Vitro data are available, BUT THEIR CLINICAL SIGNIFICANCE IS
UNKNOWN. Cefaclor exhibits In Vitro minimum inhibitory concentrations (MICs) of
8 mcgm/mL or less (systemic susceptibility breakpoint) against most (>/= 90%)
strains of the following microorganisms; however, the safety and effectiveness
of DISTACLOR CD in treating clinical infections due to these microorganisms have
not been established in adequate and well-controlled trials.
GRAM-POSITIVE AEROBES:
Staphylococcus Epidermidis
GRAM-NEGATIVE AEROBES:
Haemophilus Parainfluenzae
Klebsiella Pneumoniae
ANAEROBIC BACTERIA:
Peptococcus Niger
Peptostreptococci
Propionibacterium Acnes
NOTE: Acinetobacter Calcoaceticus, Enterobacter spp., Entercoccus spp.,
Morganella Morganii, Proteus Vulgaris, Providencia spp., Pseudomonas spp., and
Serratia spp. are resistant to cefaclor.
Susceptibility Testing:
Dilution Techniques--Quantitative methods are used to determine antimicrobial
minimum inhibitory concentrations (MICs). These MICs provide estimates of the
susceptibility of bacteria to antimicrobial compounds. The MICs should be
determined using a standardized procedure. Standardized procedures are based on
a dilution method(Ref.1) (broth, agar, or microdilution) or equivalent with
standardized inoculum concentrations and standardized amounts of cefaclor
powder. The MIC values should be interpreted according to the following
criteria:
MIC (MCGM/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 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 cefaclor powder should provide the following MIC values:
MICROORGANISM MIC RANGE (MCGM/ML)
E. Coli ATCC 25922 1-4
E. Faecalis ATCC 29212 >32
S. Aureus ATCC 29213 1-4
H. Influenzae ATCC 49766* 1-4
*Broth microdilution tests performed using Haemophilus Test Medium (HTM)
(REF. 1)
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 procedure (REF. 2) requires
the use of standardized inoculum concentrations. This procedure uses paper disks
impregnated with 30-mcgm cefaclor to test the susceptibility of microorganisms
to cefaclor.
Reports from the laboratory providing results of the standard single-disk
susceptibility test with a 30-mcgm cefaclor disk should be interpreted according
to the following criteria:
ZONE DIAMETER (MM) INTERPRETATION
>/=18 Susceptible (S)
15-17 Intermediate (I)
=14 Resistant (R)
When testing* H. Influenzae, the following interpretive criteria should be used:
ZONE DIAMETER (MM) INTERPRETATION
>/=20 Susceptible (S)
17-19 Intermediate (I)
=16 Resistant (R)
*Disk susceptibility tests performed using Haemophilus Test Medium (HTM)
(REF. 2)
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 cefaclor.
As with standardized 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-mcgm cefaclor
disk should provide the following zone diameters in these laboratory test
quality control strains:
MICROORGANISMS ZONE DIAMETER (MM)
E. Coli ATCC 25922 23-27
S. Aureus ATCC 25923 27-31
H. Influenzae* ATCC 49766 25-31
*Disk susceptibility tests performed using Haemophilus Test Medium (HTM)
(REF. 2)
INDICATIONS AND USAGE:
THE SAFETY AND EFFECTIVENESS OF DISTACLOR CD IN TREATING SOME OF THE INDICATIONS
AND PATHOGENS FOR WHICH OTHER FORMULATIONS OF CEFACLOR ARE APPROVED HAVE NOT
BEEN ESTABLISHED. When administered at the recommended dosages and durations of
therapy, DISTACLOR CD is indicated for the treatment of patients with the following
mild to moderate infections when caused by susceptible strains of the designated
organisms. (See DOSAGE AND ADMINISTRATION and CLINICAL STUDIES sections.)
ACUTE BACTERIAL EXACERBATIONS OF CHRONIC BRONCHITIS due to Haemophilus
Influenzae (non- beta-lactamase-producing strains only), Moraxella Catarrhalis
(including beta-lactamase-producing strains) or Streptococcus Pneumoniae.
NOTE: In view of the insufficient numbers of isolates of beta-lactamase-
producing strains of Haemophilus Influenzae that were obtained from clinical
trials with DISTACLOR CD for patients with acute bacterial exacerbations of chronic
bronchitis or secondary bacterial infections of acute bronchitis, it was not
possible to adequately evaluate the effectiveness of DISTACLOR CD for bronchitis
known, suspected, or considered potentially to be caused by beta-lactamase-
producing H. Influenzae.
SECONDARY BACTERIAL INFECTIONS OF ACUTE BRONCHITIS due to Haemophilus Influenzae
(non- beta-lactamase-producing strains only), Moraxella Catarrhalis (including
beta-lactamase-producing strains), or Streptococcus Pneumoniae. (See above
NOTE.)
PHARYNGITIS AND TONSILLITIS due to Streptococcus Pyogenes.
NOTE: Only penicillin by the intramuscular route of administration has been
shown to be effective in the prophylaxis of rheumatic fever. DISTACLOR CD is
generally effective in the eradication of S. Pyogenes from the oropharynx;
however, data establishing the efficacy of DISTACLOR CD for the prophylaxis of
subsequent rheumatic fever are not available.
UNCOMPLICATED SKIN AND SKIN AND STRUCTURE INFECTIONS due to Staphylococcus
Aureus (methicillin-susceptible).
NOTE: In view of the insufficient numbers of isolates of Streptococcus Pyogenes
that were obtained from clinical trials with DISTACLOR CD for patients with
uncomplicated skin and skin structure infections, it was not possible to
adequately evaluate the effectiveness of DISTACLOR CD for skin infections known,
suspected, or considered potentially to be caused by S. Pyogenes.
CONTRAINDICATIONS:
DISTACLOR CD is contraindicated in patients with known hypersensitivity to cefaclor
and other cephalosporins.
WARNINGS:
BEFORE THERAPY WITH DISTACLOR CD IS INSTITUTED, CAREFUL INQUIRY SHOULD BE MADE TO
DETERMINE WHETHER THE PATIENT HAS HAD PREVIOUS HYPERSENSITIVITY REACTIONS TO
CEFACLOR, 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 DISTACLOR CD 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 CEFACLOR, 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 by 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 clinically
effective against Clostridium Difficile.
PRECAUTIONS:
General: Superinfection (overgrowth by non- susceptible organisms) should always
be considered a possibility in a patient being treated with a broad-spectrum
antimicrobial. Careful observation of the patient is essential. If
superinfection occurs during therapy, appropriate measures should be taken.
Drug Interactions:
Antacids--The extent of absorption of DISTACLOR CD is diminished if magnesium or
aluminum hydroxide- containing antacids are taken within 1 hour of
administration; H2 blockers do not alter either the rate or the extent of
absorption of DISTACLOR CD.
Probenecid--The renal excretion of cefaclor is inhibited by probenecid.
Warfarin--There have been rare reports of increased prothrombin time with or
without clinical bleeding in patients receiving cefaclor and warfarin
concomitantly. No specific studies have been performed to rule in or rule out
this potential drug/drug interaction.
Laboratory Test Interactions: Administration of DISTACLOR CD may result in a false-
positive reaction for glucose in the urine. This phenomenon has been seen in
patients taking cephalosporin antibiotics when the test is performed using
Benedict's and Fehling's solutions and also with Clinitest(R)tablets.
Carcinogenesis, Mutagenesis, Impairment Of Fertility: Studies in animals have
not been performed to evaluate the carcinogenic or mutagenic potential for
cefaclor. Reproduction studies have revealed no evidence of impaired fertility.
Usage In Pregnancy: Teratogenic Effect: Pregnancy Category B: Reproduction
studies using cefaclor have been performed in mice, rats, and ferrets at doses
up to 3-5 times the maximum human dose (1500 mg/day) based on mg/M(squared).
These studies have revealed no harm to the fetus due to cefaclor. There are,
however, no adequate and well-controlled studies in pregnant women. Because
animal reproduction studies are not always predictive of human response. Ceclor
CD should be used during pregnancy only if clearly needed.
Labor And Delivery: DISTACLOR CD has not been studied for use during labor and
delivery. Treatment should be given only if clearly needed.
Nursing Mothers: No studies in lactating women have been performed with Ceclor
CD. Small amounts of cefaclor (=0.21 mcgm/mL) have been detected in human milk
following administration of single 500-mg doses of Ceclor. The effect on nursing
infants is not known. Caution should be exercised when DISTACLOR CD is administered
to a nursing woman.
Pediatric Use: Safety and effectiveness of DISTACLOR CD in pediatric patients less
than 16 years of age have not been established.
Geriatric Use: Healthy geriatric volunteers (>/=65 years old) who received a
single 750-mg dose of DISTACLOR CD had 40%-50% higher AUC and 20% lower renal
clearance values when compared to healthy adult volunteers less than 45 years of
age. These differences are considered to be primarily a result of age-related
decreases in renal function. In clinical studies when geriatric patients
received the usual recommended adult doses, clinical efficacy and safety were
comparable to results in non-geriatric adult patients. No dosage changes are
recommended for healthy geriatric patients.
DRUG INTERACTIONS:
Antacids--The extent of absorption of DISTACLOR CD is diminished if magnesium or
aluminum hydroxide- containing antacids are taken within 1 hour of
administration; H2 blockers do not alter either the rate or the extent of
absorption of DISTACLOR CD.
Probenecid--The renal excretion of cefaclor is inhibited by probenecid.
Warfarin--There have been rare reports of increased prothrombin time with or
without clinical bleeding in patients receiving cefaclor and warfarin
concomitantly. No specific studies have been performed to rule in or rule out
this potential drug/drug interaction.
Laboratory Test Interactions: Administration of DISTACLOR CD may result in a false-
positive reaction for glucose in the urine. This phenomenon has been seen in
patients taking cephalosporin antibiotics when the test is performed using
Benedict's and Fehling's solutions and also with Clinitest(R)tablets.
(See Also PRECAUTIONS section).
ADVERSE REACTIONS:
Clinical Trials: There were 3272 patients treated with multiple doses of Ceclor
CD in controlled clinical trials and an additional 211 subjects in pharmacology
studies. There were no deaths in these trials thought to be related to toxicity
from DISTACLOR CD. Treatment was discontinued in 1.7% of patients due to adverse
events thought to be possibly or probably drug-related.
The following adverse clinical and laboratory events were reported during the
DISTACLOR CD clinical trials conducted in North America at doses of 375 mg or 500
mg BID; however, relatedness of the adverse events to the drug was not assigned
by clinical investigations during the trials (See Tables 2 and 3).
TABLE 2
ADVERSE CLINICAL EVENTS
DISTACLOR CD MULTIPLE DOSE DOSING REGIMENS
CLINICAL TRIALS--NORTH AMERICA
(n = 1400)
-------------------------------------------------------------------------------------------------------------------------------------
EVENT INCIDENCE
------------------------------------------------------------------------------------------------------------------------------------
Headache 4.9%
Rhinitis 3.9%
Diarrhea 3.8%
Incidence Equal Nausea 3.4%
to or Greater Vaginitis* 2.4%
Than 1% Vaginal Moniliasis* 2.2%
Abdominal Pain 1.6%
Cough Increased 1.5%
Pharyngitis 1.4%
Pruritus 1.4%
Back Pain 1.0%
----------------------------------------------------------------------------------------------------------------------------------
*n=934 for these events (subset of female participants).
Adverse reactions occurring during the clinical trials with cefaclor extended
release tablets with an incidence of less than 1% but greater than 0.1% included
the following (listed alphabetically):
Accidental injury, anorexia, anxiety, arthralgia, asthma, bronchitis, chest
pain, chills, congestive heart failure, conjunctivitis, constipation, dizziness,
dysmenorrhea, dyspepsia, dysuria, ear pain, edema, fever, flatulence, flu
syndrome, gastritis, infection, insomnia, leukorrhea, lung disorder,
maculopapular rash, malaise, menstrual disorder, myalgia, nausea and vomiting,
neck pain, nervousness, nocturia, otitis media, pain, palpitation, peripheral
edema, rash, respiratory disorder, sinusitis, somnolence, surgical procedure,
sweating, tremor, urticaria, vomiting.
NOTE: One case of SERUM-SICKNESS-LIKE reaction was reported among the 3272 adult
patients treated with DISTACLOR CD during the controlled clinical trials. These
reactions have also been reported with the use of cefaclor in other oral
formulations and are seen more frequently in pediatric patients than in adults.
These reactions are characterized by findings of erythema multiforme, rash, and
other skin manifestations accompanied by arthritis/arthralgia, with or without
fever, and differ from classic serum sickness in that there is infrequently
associated lymphadenopathy and proteinuria, no circulating immune complexes and
no evidence to date of sequelae of the reaction. While further investigation is
ongoing, SERUM- SICKNESS-LIKE reactions appear to be due to hypersensitivity and
more often occur during or following a second (or subsequent) course of therapy
with cefaclor. Such reactions have been reported with overall occurrence ranging
from 1 in 200 (0.5%) in one focused trial; to 2 in 8346 (0.024%) in overall
clinical trials (with an incidence in pediatric patients in clinical trials of
0.055%); to 1 in 38,000 (0.003%) in spontaneous event reports. Signs and
symptoms usually occur a few days after initiation of therapy and subside within
a few days after cessation of therapy. Occasionally these reactions have
resulted in hospitalization, usually of short duration (median hospitalization =
2 to 3 days, based on postmarketing surveillance studies). In those patients
requiring hospitalization, the symptoms have ranged from mild to severe at the
time of admission with more of the severe reactions occurring in pediatric
patients.
TABLE 3
ADVERSE CLINICAL LABORATORY EVENTS
DISTACLOR CD MULTIPLE DOSE DOSING REGIMENS
CLINICAL TRIALS--NORTH AMERICA
----------------------------------------------------------------------------------------------------------------------------------------
EVENT INCIDENCE
----------------------------------------------------------------------------------------------------------------------------------------
Albumin decreased 0.3%
Alkaline phosphatase increased 0.3%
ALT/SGPT increased 0.3%
Bilirubin total increased 0.3%
Blood urea nitrogen (BUN) increased 0.2%
Calcium decreased 0.7%
Incidence Less Creatine phosphokinase increased 0.7%
Than 1%, But Creatinine increased 0.5%
Greater Than Eosinophils increased 0.3%
0.1% Erythrocyte count decreased 0.3%
GGT increased 0.2%
Hemoglobin decreased 0.2%
Lymphocytes decreased 0.3%
Mean Cell Volume (MCV) increased 0.7%
Neutrophils segmented decreased 0.3%
Phosphorus increased 0.7%
Platelet count decreased 0.3%
Potassium increased 0.4%
Sodium decreased 0.3%
Sodium increased 0.4%
In Postmarketing Experience: In addition to the events reported during clinical
trials with DISTACLOR CD, the following adverse experiences are among those that
have been reported during worldwide postmarketing surveillance: allergic
reaction, anaphylactoid reaction, angioedema, face edema, hypotension, Stevens-
Johnson syndrome, syncope, paresthesia, vasodilatation, and vertigo.
Other Adverse Reactions Associated With Other Formulations Of Cefaclor: In
addition to the above, the following other adverse reactions and altered
laboratory tests have been associated with cefaclor in other oral formulations:
Clinical: Severe hypersensitivity reactions, including Stevens-Johnson syndrome,
toxic epidermal necrolysis, and anaphylaxis, have been reported rarely.
Anaphylactoid events may be manifested by solitary symptoms, including
angioedema, edema (including face and limbs), parasthesias, syncope, or
vasodilatation. Anaphylaxis may be more common in patients with a history of
penicillin allergy. Rarely, hypersensitivity symptoms may persist for several
months.
Symptoms of pseudomembranous colitis may appear either during or after
antibiotic treatment. (See WARNINGS.)
Laboratory: Abnormal urinalysis, eosinophilia, leukopenia, neutropenia,
transient elevations in AST, and transient thrombocytopenia have been reported.
Cephalosporin-Class Reactions: In addition to the adverse reactions listed
above, the following adverse reactions and altered laboratory tests have been
reported for cephalosporin-class antibiotics:
Clinical: Confusion, erythema multiforme, genital pruritus, hepatic dysfunction
including cholestasis, hemolytic anemia, reversible hyperactivity, hypertonia,
and reversible interstitial nephritis.
Laboratory--Positive direct Coombs' test.
OVERDOSAGE:
The toxic symptoms following an overdose of cefaclor may include nausea,
vomiting, epigastric distress, and diarrhea. The severity of the epigastric
distress and the diarrhea are dose- related.
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.
Although cefaclor is considered dialyzable, neither forced diuresis, peritoneal
dialysis, hemodialysis, nor charcoal hemoperfusion have been demonstrated to be
beneficial in an overdose of cefaclor.
DOSAGE AND ADMINISTRATION:
The absorption of DISTACLOR CD is enhanced when it is administered with food. (See
ACTIONS/CLINICAL PHARMACOLOGY.) Therefore, DISTACLOR CD SHOULD BE ADMINISTERED WITH
MEALS (I.E., AT LEAST WITHIN ONE HOUR OF EATING). The extended release tablets
should not be cut, crushed, or chewed.
SEE INDICATIONS AND USAGE FOR INFORMATION ABOUT PATIENTS FOR WHOM DISTACLOR CD IS
INDICATED.
NOTE: 500 mg BID of DISTACLOR CD is clinically equivalent to 250 mg TID of cefaclor
as a pulvule in those indications listed in the INDICATIONS AND USAGE section of
this label. 500 MG BID OF DISTACLOR CD IS NOT EQUIVALENT TO 500 MG TID OF OTHER
CEFACLOR FORMULATIONS.
-----------------------------------------------------------------------------------------------------------------------------------
ADULTS (AGE 16 YEARS AND OLDER):
TYPE OF INFECTION TOTAL DOSE AND DURATION
(as qualified in the INDICATIONS DAILY DOSE FREQUENCY
AND USAGE section of this labeling)
------------------------------------------------------------------------------------------------------------------------------------
Acute Bacterial Exacerbations 1000 mg 500 mg q12 hours 7 days
of Chronic Bronchitis due to
H. Influenzae (non-beta-lactamase-
producing strains only),
Moraxella Catarrhalis (including
beta-lactamase-producing strains),
or Streptococcus Pneumoniae
(See INDICATIONS AND USAGE.)
---------------------------------------------------------------------------------------------------------------------------------------
Secondary Bacterial Infections of 1000 mg 500 mg q12 hours 7 days
Acute Bronchitis due to H.
Influenzae (non-beta-lactamase-
producing strains only),
M. Catarrhalis (including beta-
lactamase-producing strains),
or S. Pneumoniae
(See INDICATIONS AND USAGE.)
-----------------------------------------------------------------------------------------------------------------------------------------
Pharyngitis and/or tonsillitis Due To 750 375 mg q12 hours 10 days
mg
S. Pyogenes
----------------------------------------------------------------------------------------------------------------------------------------
Uncomplicated Skin and Skin Struc- 750 mg 375 mg q12 hours 7-10
ture infections due to S. Aureus days
(methicillin-susceptible strains)
(See INDICATIONS AND USAGE.)
----------------------------------------------------------------------------------------------------------------------------------------
Elderly patients with normal renal function do not require dosage adjustments.
CLINICAL STUDIES:
(See Also ADVERSE REACTIONS section).
ACUTE BACTERIAL EXACERBATIONS OF CHRONIC BRONCHITIS AND SECONDARY BACTERIAL
INFECTIONS OF ACUTE BRONCHITIS: In adequate and well-controlled clinical trials
of DISTACLOR CD in the treatment of acute bacterial exacerbations of chronic
bronchitis (ABECB) and secondary bacterial infections of acute bronchitis
(SBIAB), only 4 evaluable patients with ABECB and no evaluable patients with
SBIAB had infections caused by beta-lactamase-producing H. Influenzae. Four
patients do not provide adequate data upon which to judge clinical efficacy of
DISTACLOR CD against beta-lactamase-producing H. Influenzae.
UNCOMPLICATED SKIN AND SKIN STRUCTURE INFECTIONS: DISTACLOR CD (375 mg Q12H)
(n=115) was compared to DISTACLOR CAPS (250 mg TID) (n=106) for the treatment
of patients with uncomplicated skin and skin structure infections, including
cellulitis, pyoderma, abscess, and impetigo. Patients were treated for 7 to 10
days and were evaluated for clinical resolution and bacterial eradication
approximately one week after completing therapy. To be evaluable, all patients
had to have a recognized pathogen isolated from the skin infection just prior to
the initiation of therapy. The results of this randomized, double- blinded, U.S.
trial demonstrated:
(1) overall clinical cure rates were 72% (83 of 115 patients) and 75% (80 of
106 patients), respectively, for DISTACLOR CD and DISTACLOR CAPS (95% CI around
3% difference = -16% to +9%),
(2) overall bacteriologic eradication rates against Straphylococcus Aureus were
comparable (see Table 4).
TABLE 4
CLINICAL RESPONSE* IN PATIENTS
WITH SKIN AND SKIN STRUCTURE INFECTIONS
-----------------------------------------------------------------------------
Outcome by PATHOGEN DISTACLOR CD DISTACLOR CAPS
Staphylococcus 67/95 (71%) 58/81 (71%)
Aureus
Streptococcus 10/16 (63%) 8/9 (89%)
Pyogenes
Other streptococci 7/11 (64%) 5/6 (83%)
-------------------- --------------------
Total 84/122 (69%) 71/96 (74%)
-----------------------------------------------------------------------------
*Cure plus improvement
REFERENCES:
1. National Committee for Clinical Laboratory Standards. Methods for Dilution
Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically--Third
edition; Approved Standard NCCLS Document M7-A3, Vol 13, No 25, NCCLS,
Villanova, PA, December 1993
2. National Committee for Clinical Laboratory Standards. Performance Standards
for Antimicrobial Disk Susceptibility Tests--Fifth edition; Approved Standard
NCCLS Document M2-A5, Vol 13, No 24, NCCLS, Villanova, PA, December 1993
PV 2741 AMP : (082096)
************************************************************************