CEFUROXIME AXETIL
DESCRIPTION:
Cefuroxime is a semisynthetic, broad-spectrum, cephalosporin antibiotic for
parenteral administration. It is the sodium salt of (6R, 7R)-3-
carbamoyloxymethyl-7-(Z-2-methoxyimino- 2-(fur-2-yl) acetamido)ceph-3-em-4-
carboxylate.
The empirical formula is C16H15N4NaO8S, representing a molecular weight of
446.4.
FORCEF contains approximately 54.2 mg (2.4 mEq) of sodium per gram of
Cefuroxime activity.
FORCEF in sterile crystalline form is supplied in vials equivalent to 750 mg,
1.5 g, or 7.5 g of cefuroxime as cefuroxime and in ADD-Vantage(R) vials
equivalent to 750 mg or 1.5 g of cefuroxime as cefuroxime. Solutions of FORCEF
range in color from light yellow to amber, depending on the concentration and
diluent used. The pH of freshly constituted solutions usually ranges from 6 to
8.5.
FORCEF is available as a frozen, iso-osmotic, sterile, nonpyrogenic solution
with 750 mg or 1.5g of cefuroxime as cefuroxime. Approximately 1.4 g of dextrose
hydrous, USP has been added to the 750- mg dose to adjust the osmolality. Sodium
citrate hydrous, USP has been added as a buffer (300 mg and 600 mg to the 750-mg
and 1.5-g doses, respectively). FORCEF contains approximately 111mg (4.8 mEq)
and 222 mg (9.7 mEq) of sodium in the 750-mg and 1.5-g doses, respectively. The
pH has been adjusted with hydrochloric acid and may have been adjusted with
sodium hydroxide. Solutions of premixed FORCEF range in color from light yellow
to amber. The solution is intended for intravenous (IV) use after thawing to
room temperature. The osmolality of the solution is approximately 300 mOsmol/kg,
and the pH of thawed solutions ranges from 5 to 7.5.
ACTIONS/CLINICAL PHARMACOLOGY:
After intramuscular (IM) injection of a 750-mg dose of cefuroxime to normal
volunteers, the mean peak serum concentration was 27 mcg/mL. The peak occurred
at approximately 45 minutes (range, 15 to 60 minutes). Following IV doses of 750
mg and 1.5 g, serum concentrations were approximately 50 and 100 mcg/mL,
respectively, at 15 minutes. Therapeutic serum concentrations of approximately 2
mcg/mL or more were maintained for 5.3 hours and 8 hours or more, respectively.
There was no evidence of accumulation of cefuroxime in the serum following IV
administration of 1.5-g doses every 8 hours to normal volunteers. The serum
half-life after either IM or IV injections is approximately 80 minutes.
Approximately 89% of a dose of cefuroxime is excreted by the kidneys over an 8-
hour period, resulting in high urinary concentrations.
Following the IM administration of a 750-mg single dose, urinary concentrations
averaged 1,300 mcg/mL during the first 8 hours. Intravenous doses of 750 mg and
1.5 g produced urinary levels averaging 1,150 and 2,500 mcg/mL, respectively,
during the first 8-hour period.
The concomitant oral administration of probenecid with cefuroxime slows tubular
secretion, decreases renal clearance by approximately 40%, increases the peak
serum level by approximately 30%, and increases the serum half-life by
approximately 30%. Cefuroxime is detectable in therapeutic concentrations in
pleural fluid, joint fluid, bile, sputum, bone, and aqueous humor.
Cefuroxime is detectable in therapeutic concentrations in cerebrospinal fluid
(CSF) of adults and pediatric patients with meningitis. The following table
shows the concentrations of cefuroxime achieved in cerebrospinal fluid during
multiple dosing of patients with meningitis.
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Mean (Range) CSF
Number Cefuroxime Concentrations
of (mcg/mL) Achieved Within
Patients Dose Patients 8 hours Post Dose
----------------------------------------------------------------------------------------------------------------------------------------------------------------
Pediatric patients 200 mg/kg/day, 6.6
(4 weeks to 6.5 years) divided q 6 hours 5 (0.9-17.3)
Pediatric patients 200 to 230 mg/kg/day, 8.3
(7 months to 9 years) divided q 8 hours 6 (<2-22.5)
5.2
Adults 1.5 grams q 8 hours 2 (2.7-8.9)
6.0
Adults 1.5 grams q 6 hours 10 (15-13.5)
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Cefuroxime is approximately 50% bound to serum protein.
MICROBIOLOGY: Cefuroxime has In Vitro activity against a wide range of gram-
positive and gram- negative organisms, and it is highly stable in the presence
of beta-lactamases of certain gram- negative bacteria. The bactericidal action
of cefuroxime results from inhibition of cell-wall synthesis. Cefuroxime is
usually active against the following organisms In Vitro.
AEROBES, GRAM-POSITIVE: Staphylococcus Aureus, Staphylococcus Epidermidis,
Streptococcus Pneumoniae, and Streptococcus Pyogenes (and other streptococci).
NOTE: Most strains of enterococci, e.g., Enterococcus Faecalis (formerly
Streptococcus Faecalis), are resistant to cefuroxime. Methicillin-resistant
staphylococci and Listeria Monocytogenes are resistant to cefuroxime.
AEROBES, GRAM-NEGATIVE: Citrobacter spp., Enterobacter spp., Escherichia Coli,
Haemophilus Influenzae (including ampicillin-resistant strains), Haemophilus
Parainfluenzae, Klebsiella spp. (including Klebsiella Pneumoniae), Moraxella
(Branhamella) Catarrhalis (including ampicillin- and cephalothin-resistant
strains), Morganella Morganii (formerly Proteus Morganii), Neisseria Gonorrhoeae
(including penicillinase- and non- penicillinase-producing strains), Neisseria
Meningitidis, Proteus Mirabilis, Providencia Rettgeri (formerly Proteus
Rettgeri), Salmonella spp., and Shigella spp.
NOTE: Some strains of Morganella Morganii, Enterobacter Cloacae, and Citrobacter
spp. have been shown by In Vitro tests to be resistant to cefuroxime and other
cephalosporins. Pseudomonas and Campylobacter spp., Acinetobacter Calcoaceticus,
and most strains of Serratia spp. and Proteus Vulgaris are resistant to most
first- and second-generation cephalosporins.
ANAEROBES: Gram-positive and gram-negative cocci (including Peptococcus and
Peptostreptococcus spp.), gram-positive bacilli (including Clostridium spp.),
and gram-negative bacilli (including Bacteroides and Fusobacterium spp.).
NOTE: Clostridium Difficile and most strains of Bacteroides Fragilis are
resistant to cefuroxime.
SUSCEPTIBILITY TESTS: DIFFUSION TECHNIQUES: Quantitative methods that require
measurement of zone diameters give an estimate of antibiotic susceptibility. One
such standard procedure (REF. 1) that has been recommended for use with disks to
test susceptibility of organisms to cefuroxime uses the 30-mcg cefuroxime disk.
Interpretation involves the correlation of the diameters obtained in the disk
test with the minimum inhibitory concentration (MIC) for cefuroxime.
A report of "Susceptible" indicates that the pathogen is likely to be inhibited
by generally achievable blood levels. A report of "Moderately Susceptible"
suggests that the organism would be susceptible if high dosage is used or if the
infection is confined to tissues and fluids in which high antibiotic levels are
attained. A report of "Intermediate" suggests an equivocable or indeterminate
result. A report of "Resistant" indicates that achievable concentrations of the
antibiotic are unlikely to be inhibitory and other therapy should be selected.
Reports from the laboratory giving results of the standard single-disk
susceptibility test for organisms other than Haemophilus spp. and Neisseria
Gonorrhoeae with a 30-mcg cefuroxime disk should be interpreted according to the
following criteria:
ZONE DIAMETER (MM) INTERPRETATION
>/=18 (S) Susceptible
15-17 (MS) Moderately Susceptible
=14 (R) Resistant
Results for Haemophilus spp. should be interpreted according to the following
criteria:
ZONE DIAMETER (MM) INTERPRETATION
>/=24 (S) Susceptible
21-23 (I) Intermediate
=20 (R) Resistant
Results for Neisseria Gonorrhoeae should be interpreted according to the
following criteria:
ZONE DIAMETER (MM) INTERPRETATION
>/=31 (S) Susceptible
26-30 (MS) Moderately Susceptible
=25 (R) Resistant
Organisms should be tested with the cefuroxime disk since cefuroxime has been
shown by In Vitro tests to be active against certain strains found resistant
when other beta-lactam disks are used. The cefuroxime disk should not be used
for testing susceptibility to other cephalosporins.
Standardized procedures require the use of laboratory control organisms. The 30
mcg cefuroxime disk should give the following zone diameters.
1.Testing for organisms other than Haemophilus spp. and Neisseria Gonorrhoeae:
ORGANISM ZONE DIAMETER (MM)
Staphylococcus Aureus ATCC 25923 27-35
Escherichia Coli ATCC 25922 20-26
2. Testing for Haemophilus spp.:
ORGANISM ZONE DIAMETER (MM)
Haemophilus Influenzae ATCC 49766 28-36
3. Testing for Neisseria Gonorrhoeae:
ORGANISM ZONE DIAMETER (MM)
Neisseria Gonorrhoeae ATCC 49226 33-41
Staphylococcus Aureus ATCC 25923 29-33
DILUTION TECHNIQUES: Use a standardized dilution method (REF. 1) (broth, agar,
microdilution) or equivalent with cefuroxime powder. The MIC values obtained for
bacterial isolates other than Haemophilus spp. and Neisseria Gonorrhoeae should
be interpreted according to the following criteria:
MIC (MCG/ML) INTERPRETATION
=8 (S) Susceptible
16 (MS) Moderately Susceptible
>/=32 (R) Resistant
MIC values obtained for Haemophilus spp. should be interpreted according to the
following criteria:
MIC (MCG/ML) INTERPRETATION
=4 (S) Susceptible
8 (I) Intermediate
>/=16 (R) Resistant
MIC values obtained for Neisseria Gonorrhoeae should be interpreted according to
the following criteria:
MIC (MCG/ML) INTERPRETATION
=1 (S) Susceptible
2 (MS) Moderately Susceptible
>/=4 (R) Resistant
As with standard diffusion techniques, dilution methods require the use of
laboratory control organisms. Standard cefuroxime powder should provide the
following MIC values.
1. For organisms other than Haemophilus spp. and Neisseria Gonorrhoeae:
ORGANISM MIC (MCG/ML)
Staphylococcus Aureus ATCC 29213 0.5-2.0
Escherichia Coli ATCC 25922 2.0-8.0
2. For Haemophilus spp.:
ORGANISM MIC (MCG/ML)
Haemophilus Influenzae ATCC 49766 0.25-1.0
3. For Neisseria Gonorrhoeae:
ORGANISM MIC (MCG/ML)
Neisseria Gonorrhoeae ATCC 49226 0.25-1.0
Staphylococcus Aureus ATCC 29213 0.25-1.0
INDICATIONS AND USAGE:
FORCEF is indicated for the treatment of patients with infections caused by
susceptible strains of the designated organisms in the following diseases:
1. LOWER RESPIRATORY TRACT INFECTIONS, including pneumonia, caused by
Streptococcus Pneumoniae, Haemophilus Influenzae (including ampicillin-
resistant strains), Klebsiella spp., Staphylococcus Aureus (penicillinase- and
non- penicillinase-producing strains), Streptococcus Pyogenes, and Escherichia
Coli.
2. URINARY TRACT INFECTIONS caused by Escherichia Coli and Klebsiella spp.
3. SKIN AND SKIN-STRUCTURE INFECTIONS caused by Staphylococcus Aureus
(penicillinase- and non- penicillinase-producing strains), Streptococcus
Pyogenes, Escherichia Coli, Klebsiella spp., and Enterobacter spp.
4. SEPTICEMIA caused by Staphylococcus Aureus (penicillinase- and non-
penicillinase-producing strains), Streptococcus Pneumoniae, Escherichia Coli,
Haemophilus Influenzae (including ampicillin-resistant strains), and Klebsiella
spp.
5. MENINGITIS caused by Streptococcus Pneumoniae, Haemophilus Influenzae
(including ampicillin- resistant strains), Neisseria Meningitidis, and
Staphylococcus Aureus (penicillinase- and non- penicillinase-producing strains).
6. GONORRHEA: Uncomplicated and disseminated gonococcal infections due to
Neisseria Gonorrhoeae (penicillinase- and non- penicillinase-producing strains)
in both males and females.
7. BONE AND JOINT INFECTIONS caused by Staphylococcus Aureus (penicillinase-and
non- penicillinase-producing strains).
Clinical microbiological studies in skin and skin-structure infections
frequently reveal the growth of susceptible strains of both aerobic and
anaerobic organisms. FORCEF has been used successfully in these mixed
infections in which several organisms have been isolated. Appropriate cultures
and susceptibility studies should be performed to determine the susceptibility
of the causative organisms to FORCEF.
Therapy may be started while awaiting the results of these studies; however,
once these results become available, the antibiotic treatment should be adjusted
accordingly. In certain cases of confirmed or suspected gram-positive or gram-
negative sepsis or in patients with other serious infections in which the
causative organism has not been identified, FORCEF may be used concomitantly
with an aminoglycoside (see PRECAUTIONS). The recommended doses of both
antibiotics may be given depending on the severity of the infection and the
patient's condition.
PREVENTION: The preoperative prophylactic administration of FORCEF may prevent
the growth of susceptible disease-causing bacteria and thereby may reduce the
incidence of certain postoperative infections in patients undergoing surgical
procedures (e.g., vaginal hysterectomy) that are classified as clean-
contaminated or potentially contaminated procedures. Effective prophylactic use
of antibiotics in surgery depends on the time of administration. FORCEF should
usually be given one-half to 1 hour before the operation to allow sufficient
time to achieve effective antibiotic concentrations in the wound tissues during
the procedure. The dose should be repeated intraoperatively if the surgical
procedure is lengthy.
Prophylactic administration is usually not required after the surgical procedure
ends and should be stopped within 24 hours. In the majority of surgical
procedures, continuing prophylactic administration of any antibiotic does not
reduce the incidence of subsequent infections but will increase the possibility
of adverse reactions and the development of bacterial resistance.
The perioperative use of FORCEF has also been effective during open heart
surgery for surgical patients in whom infections at the operative site would
present a serious risk. For these patients it is recommended that FORCEF
therapy be continued for at least 48 hours after the surgical procedure ends. If
an infection is present, specimens for culture should be obtained for the
identification of the causative organism, and appropriate antimicrobial therapy
should be instituted.
CONTRAINDICATIONS:
FORCEF is contraindicated in patients with known allergy to the cephalosporin
group of antibiotics.
WARNINGS:
BEFORE THERAPY WITH FORCEF IS INSTITUTED, CAREFUL INQUIRY SHOULD BE MADE TO
DETERMINE WHETHER THE PATIENT HAS HAD PREVIOUS HYPERSENSITIVITY REACTIONS TO
CEPHALOSPORINS, PENICILLINS, OR OTHER DRUGS. THIS PRODUCT SHOULD BE GIVEN
CAUTIOUSLY TO PENICILLIN-SENSITIVE PATIENTS. ANTIBIOTICS SHOULD BE ADMINISTERED
WITH CAUTION TO ANY PATIENT WHO HAS DEMONSTRATED SOME FORM OF ALLERGY,
PARTICULARLY TO DRUGS. IF AN ALLERGIC REACTION TO FORCEF OCCURS, DISCONTINUE
THE DRUG. SERIOUS ACUTE HYPERSENSITIVITY REACTIONS MAY REQUIRE EPINEPHRINE AND
OTHER EMERGENCY MEASURES.
PSEUDOMEMBRANOUS COLITIS HAS BEEN REPORTED WITH NEARLY ALL ANTIBACTERIAL AGENTS,
INCLUDING CEFUROXIME, AND MAY RANGE IN SEVERITY 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 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.
When the colitis is not relieved by drug discontinuation or when it is severe,
oral vancomycin is the treatment of choice for antibiotic-associated
pseudomembranous colitis produced by Clostridium Difficile. Other causes of
colitis should also be considered.
PRECAUTIONS:
Although FORCEF rarely produces alterations in kidney function, evaluation of
renal status during therapy is recommended, especially in seriously ill patients
receiving the maximum doses. Cephalosporins should be given with caution to
patients receiving concurrent treatment with potent diuretics as these regimens
are suspected of adversely affecting renal function.
The total daily dose of FORCEF should be reduced in patients with transient or
persistent renal insufficiency (see DOSAGE AND ADMINISTRATION), because high and
prolonged serum antibiotic concentrations can occur in such individuals from
usual doses.
As with other antibiotics, prolonged use of FORCEF may result in overgrowth of
nonsusceptible organisms. Careful observation of the patient is essential. If
superinfection occurs during therapy, appropriate measures should be taken.
Broad-spectrum antibiotics should be prescribed with caution in individuals with
a history of gastrointestinal disease, particularly colitis.
Nephrotoxicity has been reported following concomitant administration of
aminoglycoside antibiotics and cephalosporins.
As with other therapeutic regimens used in the treatment of meningitis, mild-to-
moderate hearing loss has been reported in a few pediatric patients treated with
cefuroxime. Persistence of positive CSF (cerebrospinal fluid) cultures at 18 to
36 hours, has also been noted with cefuroxime injection, as well as with other
antibiotic therapies; however, the precise relevance of this is unknown.
DRUG/LABORATORY TEST INTERACTIONS: A false- positive reaction for glucose in the
urine may occur with copper reduction tests (Benedict's or Fehling's solution or
with CLINITEST(R) tablets) but not with enzyme-based tests for glycosuria (e.g.,
TES-TAPE(R)). As a false-negative result may occur in the ferricyanide test, it
is recommended that either the glucose oxidase or hexokinase method be used to
determine blood plasma glucose levels in patients receiving FORCEF.
Cefuroxime does not interfere with the assay of serum and urine creatinine by
the alkaline picrate method.
CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY: Although no long-term
studies in animals have been performed to evaluate carcinogenic potential, no
mutagenic potential of cefuroxime was found in standard laboratory tests.
Reproductive studies revealed no impairment of fertility in animals.
PREGNANCY: TERATOGENIC EFFECTS: PREGNANCY CATEGORY B: Reproduction studies have
been performed in mice and rabbits at doses up to 60 times the human dose and
have revealed no evidence of impaired fertility or harm to the fetus due to
cefuroxime. 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: Since cefuroxime is excreted in human milk, caution should be
exercised when FORCEF is administered to a nursing woman.
PEDIATRIC USE: Safety and effectiveness in pediatric patients below 3 months of
age have not been established. Accumulation of other members of the
cephalosporin class in newborn infants (with resulting prolongation of drug
half-life) has been reported.
DRUG INTERACTIONS:
SEE PRECAUTIONS
ADVERSE REACTIONS:
FORCEF is generally well tolerated. The most common adverse effects have been
local reactions following IV administration. Other adverse reactions have been
encountered only rarely.
LOCAL REACTIONS: Thrombophlebitis has occurred with IV administration in 1 in 60
patients.
GASTROINTESTINAL: Gastrointestinal symptoms occurred in 1 in 150 patients and
included diarrhea (1 in 220 patients) and nausea (1 in 440 patients). The onset
of pseudomembranous colitis may occur during or after antibacterial treatment
(see WARNINGS).
HYPERSENSITIVITY REACTIONS: Hypersensitivity reactions have been reported in
fewer than 1% of the patients treated with FORCEF and include rash (1 in 125).
Pruritus, urticaria, and positive Coombs' test each occurred in fewer than 1 in
250 patients, and, as with other cephalosporins, rare cases of anaphylaxis, drug
fever, erythema multiforme, interstitial nephritis, toxic epidermal necrolysis,
and Stevens-Johnson syndrome have occurred.
BLOOD: A decrease in hemoglobin and hematocrit has been observed in 1 in 10
patients and transient eosinophilia in 1 in 14 patients. Less common reactions
seen were transient neutropenia (fewer than 1 in 100 patients) and leukopenia (1
in 750 patients). A similar pattern and incidence were seen with other
cephalosporins used in controlled studies. As with other cephalosporins, there
have been rare reports of thrombocytopenia.
HEPATIC: Transient rise in SGOT and SGPT (1 in 25 patients), alkaline
phosphatase (1 in 50 patients), LDH (1 in 75 patients), and bilirubin (1 in 500
patients) levels has been noted.
KIDNEY: Elevations in serum creatinine and/or blood urea nitrogen and a
decreased creatinine clearance have been observed, but their relationship to
cefuroxime is unknown.
In addition to the adverse reactions listed above that have been observed in
patients treated with cefuroxime, the following adverse reactions and altered
laboratory tests have been reported for cephalosporin-class antibiotics:
ADVERSE REACTIONS: Vomiting, abdominal pain, colitis, vaginitis including
vaginal candidiasis, toxic nephropathy, hepatic dysfunction including
cholestasis, aplastic anemia, hemolytic anemia, hemorrhage.
Several cephalosporins have been implicated in triggering seizures, particularly
in patients with renal impairment when the dosage was not reduced (see DOSAGE
AND ADMINISTRATION). If seizures associated with drug therapy should occur, the
drug should be discontinued. Anticonvulsant therapy can be given if clinically
indicated.
ALTERED LABORATORY TESTS: Prolonged prothrombin time, pancytopenia,
agranulocytosis.
OBSERVED DURING CLINICAL PRACTICE: In addition to adverse events reported from
clinical trials, the following events have been identified during post-approval
use of FORCEF. Because they are reported voluntarily from a population of
unknown size, estimates of frequency cannot be made. These events have been
chosen for inclusion due to combination of their seriousness, frequency of
reporting, or potential causal connection to FORCEF.
NEUROLOGIC: Seizure.
NON-SITE SPECIFIC: Angioedema.
OVERDOSAGE:
Overdosage of cephalosporins can cause cerebral irritation leading to
convulsions. Serum levels of cefuroxime can be reduced by hemodialysis and
peritoneal dialysis.
DOSAGE AND ADMINISTRATION:
DOSAGE: ADULTS: The usual adult dosage range for FORCEF is 750 mg to 1.5 grams
every 8 hours, usually for 5 to 10 days. In uncomplicated urinary tract
infections, skin and skin-structure infections, disseminated gonococcal
infections, and uncomplicated pneumonia, a 750-mg dose every 8 hours is
recommended. In severe or complicated infections, a 1.5-gram dose every 8 hours
is recommended.
In bone and joint infections, a 1.5-gram dose every 8 hours is recommended. In
clinical trials, surgical intervention was performed when indicated as an
adjunct to FORCEF therapy. A course of oral antibiotics was administered when
appropriate following the completion of parenteral administration of FORCEF.
In life-threatening infections or infections due to less susceptible organisms,
1.5 grams every 6 hours may be required. In bacterial meningitis, the dosage
should not exceed 3 grams every 8 hours. The recommended dosage for
uncomplicated gonococcal infection is 1.5 grams given intramuscularly as a
single dose at two different sites together with 1 gram of oral probenecid. For
preventive use for clean-contaminated or potentially contaminated surgical
procedures, a 1.5-gram dose administered intravenously just before surgery
(approximately one-half to 1 hour before the initial incision) is recommended.
Thereafter, give 750 mg intravenously or intramuscularly every 8 hours when the
procedure is prolonged.
For preventive use during open heart surgery, a 1.5-gram dose administered
intravenously at the induction of anesthesia and every 12 hours thereafter for a
total of 6 grams is recommended.
IMPAIRED RENAL FUNCTION: A reduced dosage must be employed when renal function
is impaired. Dosage should be determined by the degree of renal impairment and
the susceptibility of the causative organism (see Table 1).
TABLE 1: DOSAGE OF FORCEF IN ADULTS
WITH REDUCED RENAL FUNCTION
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Creatinine
Clearance
(mL/min) Dose Frequency
-----------------------------------------------------------------------------
>20 750 mg-1.5 grams q8h
10-20 750 mg q12h
<10 750 mg q24h*
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* Since FORCEF is dialyzable, patients on hemodialysis should be given a
further dose at the end of the dialysis.
When only serum creatinine is available, the following formula (REF. 2) (based
on sex, weight, and age of the patient) may be used to convert this value into
creatinine clearance. The serum creatinine should represent a steady state of
renal function.
Males: Creatinine Clearance (mL/min)=
Weight (kg) X (140-age)
------------------------------
72 X serum creatinine (mg/dL)
Females: 0.85 X male value
NOTE: As with antibiotic therapy in general, administration of FORCEF should be
continued for a minimum of 48 to 72 hours after the patient becomes asymptomatic
or after evidence of bacterial eradication has been obtained; a minimum of 10
days of treatment is recommended in infections caused by Streptococcus Pyogenes
in order to guard against the risk of rheumatic fever or glomerulonephritis;
frequent bacteriologic and clinical appraisal is necessary during therapy of
chronic urinary tract infection and may be required for several months after
therapy has been completed; persistent infections may require treatment for
several weeks; and doses smaller than those indicated above should not be used.
In staphylococcal and other infections involving a collection of pus, surgical
drainage should be carried out where indicated.
PEDIATRIC PATIENTS: Administration of 50 to 100 mg/kg per day in equally divided
doses every 6 to 8 hours has been successful for most infections susceptible to
cefuroxime. The higher dosage of 100 mg/kg per day (not to exceed the maximum
adult dosage) should be used for the more severe or serious infections.
In bone and joint infections, 150 mg/kg per day (not to exceed the maximum adult
dosage) is recommended in equally divided doses every 8 hours. In clinical
trials, a course of oral antibiotics was administered to pediatric patients
following the completion of parenteral administration of FORCEF.
In cases of bacterial meningitis, a larger dosage of FORCEF is recommended, 200
to 240 mg/kg per day intravenously in divided doses every 6 to 8 hours.
In pediatric patients with renal insufficiency, the frequency of dosing should
be modified consistent with the recommendations for adults.
PREPARATION OF SOLUTION AND SUSPENSION: The directions for preparing FORCEF for
both IV and IM use are summarized in Table 2.
FOR INTRAMUSCULAR USE: Each 750-mg vial of FORCEF should be constituted with
3.0 mL of sterile water for injection. Shake gently to disperse and withdraw
completely the resulting suspension for injection.
FOR INTRAVENOUS USE: Each 750-mg vial should be constituted with 8.0 mL of
sterile water for injection. Withdraw completely the resulting solution for
injection.
Each 1.5-gram vial should be constituted with 16.0 mL of sterile water for
injection, and the solution should be completely withdrawn for injection.
The 7.5-gram pharmacy bulk vial should be constituted with 77 mL of sterile
water for injection; each 8 mL of the resulting solution contains 750 mg of
cefuroxime.
Each 750-mg and 1.5-gram infusion pack should be constituted with 100 mL of
sterile water for injection, 5% dextrose injection, 0.9% sodium chloride
injection, or any of the solutions listed under the Intravenous portion of the
COMPATIBILITY AND STABILITY section.
TABLE 2: PREPARATION OF SOLUTION AND SUSPENSION
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Approximate
Cefuroxime
Amount of Diluent Volume to Be Concentration
Strength to Be Added (mL) Withdrawn (mg/mL)
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750-mg Vial 3.0(IM) Total* 220
750-mg Vial 8.0(IV) Total 90
1.5-gram Vial 16.0(IV) Total 90
750-mg Infusion pack 100(IV) -- 7.5
1.5-gram Infusion pack 100(IV) -- 15
7.5-gram Pharmacy
bulk package 77(IV) Amount Needed** 95
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*NOTE: FORCEF is a suspension at IM concentrations.
**8 mL of solution contains 750 mg of cefuroxime; 16 mL of solution contains
1.5 grams of cefuroxime.
ADMINISTRATION: After constitution, FORCEF may be given intravenously or by
deep IM injection into a large muscle mass (such as the gluteus or lateral part
of the thigh). Before injecting intramuscularly, aspiration is necessary to
avoid inadvertent injection into a blood vessel.
INTRAVENOUS ADMINISTRATION: The IV route may be preferable for patients with
bacterial septicemia or other severe or life-threatening infections or for
patients who may be poor risks because of lowered resistance, particularly if
shock is present or impending.
FOR DIRECT INTERMITTENT IV ADMINISTRATION, slowly inject the solution into a
vein over a period of 3 to 5 minutes or give it through the tubing system by
which the patient is also receiving other IV solutions.
FOR INTERMITTENT IV INFUSION WITH A Y-TYPE ADMINISTRATION SET, dosing can be
accomplished through the tubing system by which the patient may be receiving
other IV solutions. However, during infusion of the solution containing FORCEF,
it is advisable to temporarily discontinue administration of any other solutions
at the same site.
ADD-Vantage vials are to be constituted only with 50 or 100 mL of 5% dextrose
injection, 0.9% sodium chloride injection, or 0.45% sodium chloride injection in
Abbott ADD-Vantage flexible diluent containers (see Instructions for
Constitution section of the product package insert). ADD-Vantage vials that have
been joined to Abbott ADD-Vantage diluent containers and activated to dissolve
the drug are stable for 24 hours at room temperature or for 7 days under
refrigeration. Joined vials that have not been activated may be used within a
14-day period; this period corresponds to that for use of Abbott ADD-Vantage
containers following removal of the outer packaging (overwrap).
Freezing solutions of FORCEF in the ADD-Vantage system is not recommended.
FOR CONTINUOUS IV INFUSION, a solution of FORCEF may be added to an IV infusion
pack containing one of the following fluids: 0.9% sodium chloride injection; 5%
dextrose injection; 10% dextrose injection; 5% dextrose and 0.9% sodium chloride
injection; 5% dextrose and 0.45% sodium chloride injection; or 1/6 M sodium
lactate injection.
Solutions of FORCEF, like those of most beta- lactam antibiotics, should not be
added to solutions of aminoglycoside antibiotics because of potential
interaction.
However, if concurrent therapy with FORCEF and an aminoglycoside is indicated,
each of these antibiotics can be administered separately to the same patient.
DIRECTIONS FOR USE OF FORCEF FROZEN IN GALAXY(R) PLASTIC CONTAINERS: FORCEF
supplied as a frozen, sterile, iso- osmotic, nonpyrogenic solution in plastic
containers is to be administered after thawing either as a continuous or
intermittent IV infusion. The thawed solution of the premixed product is stable
for 28 days if stored under refrigeration (5 deg C) or for 24 hours if stored at
room temperature (25 deg C). DO NOT REFREEZE.
Thaw container at room temperature (25 deg C) or under refrigeration (5 deg C).
Do not force thaw by immersion in water baths or by microwave irradiation.
Components of the solution may precipitate in the frozen state and will dissolve
upon reaching room temperature with little or no agitation. Potency is not
affected. Mix after solution has reached room temperature. Check for minute
leaks by squeezing bag firmly. Discard bag if leaks are found as sterility may
be impaired. Do not add supplementary medication. Do not use unless solution is
clear and seal is intact.
Use sterile equipment.
CAUTION: Do not use plastic containers in series connections. Such use could
result in air embolism due to residual air being drawn from the primary
container before administration of the fluid from the secondary container is
complete.
PREPARATION FOR ADMINISTRATION:
1. Suspend container from eyelet support.
2. Remove protector from outlet port at bottom of container.
3. Attach administration set. Refer to complete directions accompanying set.
COMPATIBILITY AND STABILITY
INTRAMUSCULAR: When constituted as directed with sterile water for injection,
suspensions of FORCEF for IM injection maintain satisfactory potency for 24
hours at room temperature and for 48 hours under refrigeration (5 deg C).
After the periods mentioned above any unused suspensions should be discarded.
INTRAVENOUS: When the 750-mg, 1.5-g, and 7.5-g pharmacy bulk vials are
constituted as directed with sterile water for injection, the FORCEF solutions
for IV administration maintain satisfactory potency for 24 hours at room
temperature and for 48 hours (750-mg and 1.5-g vials) or for 7 days (7.5-g
pharmacy bulk vial) under refrigeration (5 deg C). More dilute solutions, such
as 750 mg or 1.5 g plus 100 mL of sterile water for injection, 5% dextrose
injection, or 0.9% sodium chloride injection, also maintain satisfactory potency
for 24 hours at room temperature and for 7 days under refrigeration.
These solutions may be further diluted to concentrations of between 1 and 30
mg/mL in the following solutions and will lose not more than 10% activity for 24
hours at room temperature or for at least 7 days under refrigeration: 0.9%
sodium chloride injection; 1/6 M sodium lactate injection; ringer's injection,
USP; lactated ringer's injection, USP; 5% dextrose and 0.9% sodium chloride
injection; 5% dextrose injection; 5% dextrose and 0.45% sodium chloride
injection; 5% dextrose and 0.225% sodium chloride injection; 10% dextrose
injection; and 10% invert sugar in water for injection.
Unused solutions should be discarded after the time periods mentioned above.
FORCEF has also been found compatible for 24 hours at room temperature when
admixed in IV infusion with heparin (10 and 50 U/mL) in 0.9% sodium chloride
injection and potassium chloride (10 and 40 mEq/L) in 0.9% sodium chloride
injection. Sodium bicarbonate injection, USP is not recommended for the dilution
of FORCEF.
The 750-mg and 1.5-g FORCEF ADD-Vantage vials, when diluted in 50 or 100 mL of
5% dextrose injection, 0.9% sodium chloride injection, or 0.45% sodium chloride
injection, may be stored for up to 24 hours at room temperature or for 7 days
under refrigeration.
FROZEN STABILITY: Constitute the 750-mg, 1.5-g, or 7.5-g vial as directed for IV
administration in Table 2. Immediately withdraw the total contents of the 750-mg
or 1.5-g vial or 8 or 16 mL from the 7.5-g bulk vial and add to a Baxter
VIAFLEX(R) MINI-BAG(TM) containing 50 or 100 mL of 0.9% sodium chloride
injection or 5% dextrose injection and freeze. Frozen solutions are stable for 6
months when stored at -20 deg C. Frozen solutions should be thawed at room
temperature and not refrozen. Do not force thaw by immersion in water baths or
by microwave irradiation. Thawed solutions may be stored for up to 24 hours at
room temperature or for 7 days in a refrigerator.
NOTE: Parenteral drug products should be inspected visually for particulate
matter and discoloration before administration whenever solution and container
permit.
As with other cephalosporins, FORCEF powder as well as solutions and
suspensions tend to darken, depending on storage conditions, without adversely
affecting product potency.
DIRECTIONS FOR DISPENSING: PHARMACY BULK PACKAGE- -NOT FOR DIRECT INFUSION: The
pharmacy bulk package is for use in a pharmacy admixture service only under a
laminar flow hood. Entry into the vial must be made with a sterile transfer set
or other sterile dispensing device, and the contents dispensed in aliquots using
aseptic technique. The use of syringe and needle is not recommended as it may
cause leakage (see DOSAGE AND ADMINISTRATION). AFTER INITIAL WITHDRAWAL USE
ENTIRE CONTENTS OF VIAL PROMPTLY. ANY UNUSED PORTION MUST BE DISCARDED WITHIN 24
HOURS.
REFERENCES:
1. National Committee for Clinical Laboratory Standards. Performance Standards
For Antimicrobial Susceptibility Testing. Third Informational Supplement. NCCLS
Document M100-S3, Vol. 11, No. 17. Villanova, Pa: NCCLS; 1991.
2. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum
creatinine. Nephron. 1976;16:31-41.
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