CEFOPERAZONE SOD
DESCRIPTION:
MYTICEF (sterile cefoperazone sodium) contain cefoperazone as
cefoperazone sodium. It is a semisynthetic, broad-spectrum cephalosporin
antibiotic. Chemically, cefoperazone sodium is sodium (6R,7R)-7-((R)-2-(4-ethyl-
2,3-dioxo- 1-piperazinecarboxamido)-2-(p- hydroxyphenyl)-acetamido)-3-(((1-
methyl-1H- tetrazol-5-yl)thio)methyl)-8-oxo-5-thia- 1-azabicyclo(4.2.0)oct-2-
ene-2-carboxylate. Its molecular formula is C25H26N9NaO8S2 with a molecular
weight of 667.65.
ACTIONS/CLINICAL PHARMACOLOGY:
High serum and bile levels of MYTICEF are attained after a single dose of the
drug. Table 1 demonstrates the serum concentrations of MYTICEF in normal
volunteers following either a single 15-minute constant rate intravenous
infusion of 1, 2, 3 or 4 grams of the drug, or a single intramuscular injection
of 1 or 2 grams of the drug.
TABLE 1. CEFOPERAZONE SERUM CONCENTRATIONS
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MEAN SERUM CONCENTRATIONS (MCG/ML)
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DOSE/ROUTE 0* 0.5 HR 1 HR 2 HR 4 HR 8 HR 12 HR
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1 g IV 153 114 73 38 16 4 0.5
2 g IV 252 153 114 70 32 8 2
3 g IV 340 210 142 89 41 9 2
4 g IV 506 325 251 161 71 19 6
1 g IM 32** 52 65 57 33 7 1
2 g IM 40** 69 93 97 58 14 4
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* Hours post-administration, with 0 time being the end of the infusion.
** Values obtained 15 minutes post-injection.
The mean serum half-life of MYTICEF is approximately 2.0 hours, independent of
the route of administration.
In Vitro studies with human serum indicate that the degree of MYTICEF reversible
protein binding varies with the serum concentration from 93% at 25 mcg/mL of
MYTICEF to 90% at 250 mcg/mL and 82% at 500 mcg/mL.
MYTICEF achieves therapeutic concentrations in the following body tissues and
fluids:
TISSUE OR FLUID DOSE CONCENTRATION
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Ascitic Fluid 2 g 64 mcg/mL
Cerebrospinal Fluid 50 mg/kg 1.8 mcg/mL to
(in patients with 8.0 mcg/mL
inflamed meninges)
Urine 2 g 3,286 mcg/mL
Sputum 3 g 6.0 mcg/mL
Endometrium 2 g 74 mcg/g
Myometrium 2 g 54 mcg/g
Palatine Tonsil 1 g 8 mcg/g
Sinus Mucous Membrane 1 g 8 mcg/g
Umbilical Cord Blood 1 g 25 mcg/mL
Amniotic Fluid 1 g 4.8 mcg/mL
Lung 1 g 28 mcg/g
Bone 2 g 40 mcg/g
MYTICEF is excreted mainly in the bile. Maximum bile concentrations are
generally obtained between one and three hours following drug administration and
exceed concurrent serum concentrations by up to 100 times. Reported biliary
concentrations of MYTICEF range from 66 mcg/mL at 30 minutes to as high as 6000
mcg/mL at 3 hours after an intravenous bolus injection of 2 grams.
Following a single intramuscular or intravenous dose, the urinary recovery of
MYTICEF over a 12-hour period averages 20-30%. No significant quantity of
metabolites has been found in the urine. Urinary concentrations greater than
2200 mcg/mL have been obtained following a 15-minute infusion of a 2 g dose.
After an IM injection of 2 g, peak urine concentrations of almost 1000 mcg/mL
have been obtained, and therapeutic levels are maintained for 12 hours.
Repeated administration of MYTICEF at 12-hour intervals does not result in
accumulation of the drug in normal subjects. Peak serum concentrations, areas
under the curve (AUC's), and serum half-lives in patients with severe renal
insufficiency are not significantly different from those in normal volunteers.
In patients with hepatic dysfunction, the serum half-life is prolonged and
urinary excretion is increased. In patients with combined renal and hepatic
insufficiencies, MYTICEF may accumulate in the serum.
MYTICEF has been used in pediatrics, but the safety and effectiveness in
children have not been established. The half-life of MYTICEF in serum is 6-10
hours in low birth-weight neonates.
MICROBIOLOGY
MYTICEF is active In Vitro against a wide range of aerobic and anaerobic, gram-
positive and gram- negative pathogens. The bactericidal action of MYTICEF
results from the inhibition of bacterial cell wall synthesis. MYTICEF has a high
degree of stability in the presence of beta-lactamases produced by most gram-
negative pathogens. MYTICEF is usually active against organisms which are
resistant to other beta-lactam antibiotics because of beta-lactamase production.
MYTICEF is usually active against the following organisms In Vitro and in
clinical infections:
GRAM-POSITIVE AEROBES:
Staphylococcus Aureus, penicillinase and non- penicillinase-producing strains
Staphylococcus Epidermidis
Streptococcus Pneumoniae (formerly Diplococcus Pneumoniae)
Streptococcus Pyogenes (Group A beta-hemolytic streptococci)
Streptococcus Agalactiae (Group B beta-hemolytic streptococci)
Enterococcus (Streptococcus Faecalis, S. Faecium and S. Durans)
GRAM-NEGATIVE AEROBES:
Escherichia Coli
Klebsiella species (including K. Pneumoniae)
Enterobacter species
Citrobacter species
Haemophilus Influenzae
Proteus Mirabilis
Proteus Vulgaris
Morganella Morganii (formerly Proteus Morganii)
Providencia Stuartii
Providencia Rettgeri (formerly Proteus Rettgeri)
Serratia Marcescens
Pseudomonas Aeruginosa
Pseudomonas species
Some strains of Acinetobacter Calcoaceticus
Neisseria Gonorrhoeae
ANAEROBIC ORGANISMS:
Gram-positive cocci (including Peptococcus and Peptostreptococcus)
Clostridium species
Bacteroides Fragilis
Other Bacteroides species
MYTICEF is also active In Vitro against a wide variety of other pathogens
although the clinical significance is unknown. These organisms include:
Salmonella and Shigella species, Serratia Liquefaciens, N. Meningitidis,
Bordetella Pertussis, Yersinia Enterocolitica, Clostridium Difficile,
Fusobacterium species, Eubacterium species and beta-lactamase producing strains
of H. Influenzae and N. Gonorrhoeae.
SUSCEPTIBILITY TESTING:
DIFFUSION TECHNIQUE. For the disk diffusion method of susceptibility testing, a
75 mcg MYTICEF diffusion disk should be used. Organisms should be tested with
the MYTICEF 75 mcg disk since MYTICEF has been shown In Vitro to be active
against organisms which are found to be resistant to other beta-lactam
antibiotics.
Tests should be interpreted by the following criteria:
ZONE DIAMETER INTERPRETATION
Greater than or Susceptible
equal to 21 mm
16-20 mm Moderately Susceptible
Less than or equal Resistant
to 15 mm
Quantitative procedures that require measurement of zone diameters give the most
precise estimate of susceptibility. One such method which has been recommended
for use with the MYTICEF 75 mcg disk is the NCCLS approved standard.
(Performance Standards for Antimicrobic Disk Susceptibility Tests. Second
Information Supplement Vol. 2 No. 2 pp. 49-69. Publisher--National Committee for
Clinical Laboratory Standards, Villanova, Pennsylvania.)
A report of "susceptible" indicates that the infecting organism is likely to
respond to MYTICEF therapy and a report of "resistant" indicates that the
infecting organism is not likely to respond to therapy. A "moderately
susceptible" report suggests that the infecting organism will be susceptible to
MYTICEF if a higher than usual dosage is used or if the infection is confined to
tissues and fluids (e.g., urine or bile) in which high antibiotic levels are
attained.
DILUTION TECHNIQUES. Broth or agar dilution methods may be used to determine the
minimal inhibitory concentration (MIC) of MYTICEF. Serial twofold dilutions of
MYTICEF should be prepared in either broth or agar. Broth should be inoculated
to contain 5 X 10 (to the fifth power) organisms/mL and agar "spotted" with 10
(to the fourth power) organisms.
MIC test results should be interpreted in light of serum, tissue, and body fluid
concentrations of MYTICEF. Organisms inhibited by MYTICEF at 16 mcg/mL or less
are considered susceptible, while organisms with MIC's of 17-63 mcg/mL are
moderately susceptible. Organisms inhibited at MYTICEF concentrations of greater
than or equal to 64 mcg/mL are considered resistant, although clinical cures
have been obtained in some patients infected by such organisms.
INDICATIONS AND USAGE:
MYTICEF is indicated for the treatment of the following infections when caused
by susceptible organisms:
RESPIRATORY TRACT INFECTIONS caused by S. Pneumoniae, H. Influenzae, S. Aureus
(penicillinase and non-penicillinase producing strains), S. Pyogenes* (Group A
beta-hemolytic streptococci), P. Aeruginosa, Klebsiella Pneumoniae, E. Coli,
Proteus Mirabilis, and Enterobacter species.
PERITONITIS AND OTHER INTRA-ABDOMINAL INFECTIONS caused by E. Coli, P.
Aeruginosa,* and anaerobic gram-negative bacilli (including Bacteroides
Fragilis).
BACTERIAL SEPTICEMIA caused by S. Pneumoniae, S. Agalactiae*, S. Aureus,
Pseudomonas Aeruginosa*, E. Coli, Klebsiella spp.,* Klebsiella Pneumoniae* ,
Proteus species* (indole-positive and indole- negative), Clostridium spp.* and
anaerobic gram- positive cocci.*
INFECTIONS OF THE SKIN AND SKIN STRUCTURES caused by S. Aureus (penicillinase
and non-penicillinase producing strains), S. Pyogenes*, and P. Aeruginosa.
PELVIC INFLAMMATORY DISEASE, ENDOMETRITIS, AND OTHER INFECTIONS OF THE FEMALE
GENITAL TRACT caused by N. Gonorrhoeae, S. Epidermidis*, S. Agalactiae, E. Coli,
Clostridium spp.,* Bacteroides species (including Bacteroides Fragilis) and
anaerobic gram-positive cocci.
URINARY TRACT INFECTIONS caused by Escherichia Coli and Pseudomonas Aeruginosa.
ENTEROCOCCAL INFECTIONS: Although cefoperazone has been shown to be clinically
effective in the treatment of infections caused by enterococci in cases of
PERITONITIS AND OTHER INTRA-ABDOMINAL INFECTIONS, INFECTIONS OF THE SKIN AND
SKIN STRUCTURES, PELVIC INFLAMMATORY DISEASE, ENDOMETRITIS AND OTHER INFECTIONS
OF THE FEMALE GENITAL TRACT, AND URINARY TRACT INFECTION,* the majority of
clinical isolates of enterococci tested are not susceptible to cefoperazone but
fall just at or in the intermediate zone of susceptibility, and are moderately
resistant to cefoperazone. However, In Vitro susceptibility testing may not
correlate directly with In Vivo results. Despite this, cefoperazone therapy has
resulted in clinical cures of enterococcal infections, chiefly in polymicrobial
infections. Cefoperazone should be used in enterococcal infections with care and
at doses that achieve satisfactory serum levels of cefoperazone.
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* Efficacy of this organism in this organ system was studied in fewer than 10
infections.
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SUSCEPTIBILITY TESTING
Before instituting treatment with MYTICEF, appropriate specimens should be
obtained for isolation of the causative organism and for determination of its
susceptibility to the drug. Treatment may be started before results of
susceptibility testing are available.
COMBINATION THERAPY
Synergy between MYTICEF and aminoglycosides has been demonstrated with many
gram-negative bacilli. However, such enhanced activity of these combinations is
not predictable. If such therapy is considered, In Vitro susceptibility tests
should be performed to determine the activity of the drugs in combination, and
renal function should be monitored carefully. (See PRECAUTIONS, and DOSAGE AND
ADMINISTRATION sections).
CONTRAINDICATIONS:
MYTICEF is contraindicated in patients with known allergy to the cephalosporin-
class of antibiotics.
WARNINGS:
BEFORE THERAPY WITH MYTICEF 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. SERIOUS ACUTE HYPERSENSITIVITY REACTIONS MAY REQUIRE THE
USE OF SUBCUTANEOUS EPINEPHRINE AND OTHER EMERGENCY MEASURES.
PSEUDOMEMBRANOUS COLITIS HAS BEEN REPORTED WITH THE USE OF CEPHALOSPORINS (AND
OTHER BROAD- SPECTRUM ANTIBIOTICS); THEREFORE, IT IS IMPORTANT TO CONSIDER ITS
DIAGNOSIS IN PATIENTS WHO DEVELOP DIARRHEA IN ASSOCIATION WITH ANTIBIOTIC USE.
Treatment with broad-spectrum antibiotics alters normal flora of the colon and
may permit overgrowth of clostridia. Studies indicate a toxin produced by
Clostridium Difficile is one primary cause of antibiotic-associated colitis.
Cholestyramine and colestipol resins have been shown to bind the toxin In Vitro.
Mild cases of colitis may respond to drug discontinuance alone.
Moderate to severe cases should be managed with fluid, electrolyte, and protein
supplementation as indicated.
When the colitis is not relieved by drug discontinuance or when it is severe,
oral vancomycin is the treatment of choice for antibiotic-associated
pseudomembranous colitis produced by C. Difficile. Other causes of colitis
should also be considered.
PRECAUTIONS:
Although transient elevations of the BUN and serum creatinine have been
observed, MYTICEF alone does not appear to cause significant nephrotoxicity.
However, concomitant administration of aminoglycosides and other cephalosporins
has caused nephrotoxicity.
MYTICEF is extensively excreted in bile. The serum half-life of MYTICEF is
increased 2-4 fold in patients with hepatic disease and/or biliary obstruction.
In general, total daily dosage above 4 g should not be necessary in such
patients. If higher dosages are used, serum concentrations should be monitored.
Because renal excretion is not the main route of elimination of MYTICEF (see
ACTIONS/CLINICAL PHARMACOLOGY), patients with renal failure require no
adjustment in dosage when usual doses are administered. When high doses of
MYTICEF are used, concentrations of drug in the serum should be monitored
periodically. If evidence of accumulation exists, dosage should be decreased
accordingly.
The half-life of MYTICEF is reduced slightly during hemodialysis. Thus, dosing
should be scheduled to follow a dialysis period. In patients with both hepatic
dysfunction and significant renal disease, MYTICEF dosage should not exceed 1-2
g daily without close monitoring of serum concentrations.
As with other antibiotics, vitamin K deficiency has occurred rarely in patients
treated with MYTICEF. The mechanism is most probably related to the suppression
of gut flora which normally synthesize this vitamin. Those at risk include
patients with a poor nutritional status, malabsorption states (e.g., cystic
fibrosis), alcoholism, and patients on prolonged hyper- alimentation regimens
(administered either intravenously or via a naso-gastric tube). Prothrombin time
should be monitored in these patients and exogenous vitamin K administered as
indicated.
A disulfiram-like reaction characterized by flushing, sweating, headache, and
tachycardia has been reported when alcohol (beer, wine) was ingested within 72
hours after MYTICEF administration. Patients should be cautioned about the
ingestion of alcoholic beverages following the administration of MYTICEF. A
similar reaction has been reported with other cephalosporins.
Prolonged use of MYTICEF 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.
MYTICEF should be prescribed with caution in individuals with a history of
gastrointestinal disease, particularly colitis.
DRUG LABORATORY TEST INTERACTIONS
A false-positive reaction for glucose in the urine may occur with Benedict's or
Fehling's solution.
CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY
Long term studies in animals have not been performed to evaluate carcinogenic
potential. The maximum duration of MYTICEF animal toxicity studies is six
months. In none of the In Vivo or In Vitro genetic toxicology studies did
MYTICEF show any mutagenic potential at either the chromosomal or subchromosomal
level. MYTICEF produced no impairment of fertility and had no effects on general
reproductive performance or fetal development when administered subcutaneously
at daily doses up to 500 to 1000 mg/kg prior to and during mating, and to
pregnant female rats during gestation. These doses are 10 to 20 times the
estimated usual single clinical dose. MYTICEF had adverse effects on the testes
of prepubertal rats at all doses tested. Subcutaneous administration of 1000
mg/kg per day (approximately 16 times the average adult human dose) resulted in
reduced testicular weight, arrested spermatogenesis, reduced germinal cell
population and vacuolation of Sertoli cell cytoplasm. The severity of lesions
was dose dependent in the 100 to 1000 mg/kg per day range; the low dose caused a
minor decrease in spermatocytes. This effect has not been observed in adult
rats. Histologically the lesions were reversible at all but the highest dosage
levels. However, these studies did not evaluate subsequent development of
reproductive function in the rats. The relationship of these findings to humans
is unknown.
USAGE IN PREGNANCY
PREGNANCY CATEGORY B: Reproduction studies have been performed in mice, rats,
and monkeys at doses up to 10 times the human dose and have revealed no evidence
of impaired fertility or harm to the fetus due to MYTICEF. 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.
USAGE IN NURSING MOTHERS
Only low concentrations of MYTICEF are excreted in human milk. Although MYTICEF
passes poorly into breast milk of nursing mothers, caution should be exercised
when MYTICEF is administered to a nursing woman.
PEDIATRIC USE
Safety and effectiveness in children have not been established. For information
concerning testicular changes in prepubertal rats (see Carcinogenesis,
Mutagenesis, Impairment of Fertility).
DRUG INTERACTIONS:
A disulfiram-like reaction characterized by flushing, sweating, headache, and
tachycardia has been reported when alcohol (beer, wine) was ingested within 72
hours after MYTICEF administration. Patients should be cautioned about the
ingestion of alcoholic beverages following the administration of MYTICEF. A
similar reaction has been reported with other cephalosporins.
(See Also PRECAUTIONS)
ADVERSE REACTIONS:
In clinical studies the following adverse effects were observed and were
considered to be related to MYTICEF therapy or of uncertain etiology:
HYPERSENSITIVITY: As with all cephalosporins, hypersensitivity manifested by
skin reactions (1 patient in 45), drug fever (1 in 260), or a change in Coombs'
test (1 in 60) has been reported. These reactions are more likely to occur in
patients with a history of allergies, particularly to penicillin.
HEMATOLOGY: As with other beta-lactam antibiotics, reversible neutropenia may
occur with prolonged administration. Slight decreases in neutrophil count (1
patient in 50) have been reported. Decreased hemoglobins (1 in 20) or
hematocrits (1 in 20) have been reported, which is consistent with published
literature on other cephalosporins. Transient eosinophilia has occurred in 1
patient in 10.
HEPATIC: Of 1285 patients treated with cefoperazone in clinical trials, one
patient with a history of liver disease developed significantly elevated liver
function enzymes during MYTICEF therapy. Clinical signs and symptoms of
nonspecific hepatitis accompanied these increases. After MYTICEF therapy was
discontinued, the patient's enzymes returned to pre-treatment levels and the
symptomatology resolved. As with other antibiotics that achieve high bile
levels, mild transient elevations of liver function enzymes have been observed
in 5-10% of the patients receiving MYTICEF therapy. The relevance of these
findings, which were not accompanied by overt signs or symptoms of hepatic
dysfunction, has not been established.
GASTROINTESTINAL: Diarrhea or loose stools has been reported in 1 in 30
patients. Most of these experiences have been mild or moderate in severity and
self-limiting in nature. In all cases, these symptoms responded to symptomatic
therapy or ceased when cefoperazone therapy was stopped. Nausea and vomiting
have been reported rarely.
Symptoms of pseudomembranous colitis can appear during or for several weeks
subsequent to antibiotic therapy (see WARNINGS).
RENAL FUNCTION TESTS: Transient elevations of the BUN (1 in 16) and serum
creatinine (1 in 48) have been noted.
LOCAL REACTIONS: MYTICEF is well tolerated following intramuscular
administration. Occasionally, transient pain (1 in 140) may follow
administration by this route. When MYTICEF is administered by intravenous
infusion some patients may develop phlebitis (1 in 120) at the infusion site.
DOSAGE AND ADMINISTRATION:
The usual adult daily dose of MYTICEF is 2 to 4 grams per day administered in
divided doses every 12 hours.
In severe infections or infections caused by less sensitive organisms, the total
daily dose and/or frequency may be increased. Patients have been successfully
treated with a total daily dosage of 6-12 grams divided into 2, 3 or 4
administrations ranging from 1.5 to 4 grams per dose.
In a pharmacokinetic study, a total daily dose of 16 grams was administered to
severely immunocompromised patients by constant infusion without complications.
Steady state serum concentrations were approximately 150mcg/mL in these
patients.
When treating infections caused by Streptococcus Pyogenes, therapy should be
continued for at least 10 days.
Solutions of MYTICEF and aminoglycoside should not be directly mixed, since
there is a physical incompatibility between them. If combination therapy with
MYTICEF and an aminoglycoside is contemplated (see INDICATIONS) this can be
accomplished by sequential intermittent intravenous infusion provided that
separate secondary intravenous tubing is used, and that the primary intravenous
tubing is adequately irrigated with an approved diluent between doses. It is
also suggested that MYTICEF be administered prior to the aminoglycoside. In
Vitro testing of the effectiveness of drug combination(s) is recommended.
RECONSTITUTION
The following solutions may be used for the initial reconstitution of MYTICEF
(sterile cefoperazone sodium):
TABLE 1. SOLUTIONS FOR INITIAL RECONSTITUTION.
5% Dextrose Injection (USP)
5% Dextrose and 0.9% Sodium Chloride Injection (USP)
5% Dextrose and 0.2% Sodium Chloride Injection (USP)
10% Dextrose Injection (USP)
Bacteriostatic Water for Injection (Benzyl Alcohol or Parabens) (USP)* */*
0.9% Sodium Chloride Injection (USP)
Normosol(R) M and 5% Dextrose Injection
Normosol(R) R
Sterile Water for Injection*
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* Not to be used as a vehicle for intravenous infusion
*/* Preparations containing Benzyl Alcohol should not be used in neonates.
GENERAL RECONSTITUTION PROCEDURES
MYTICEF (sterile cefoperazone sodium) for intravenous or intramuscular use may
be initially reconstituted with any compatible solution mentioned above in Table
1. Solutions should be allowed to stand after reconstitution to allow any
foaming to dissipate to permit visual inspection for complete solubilization.
Vigorous and prolonged agitation may be necessary to solubilize MYTICEF in
higher concentrations (above 333 mg cefoperazone/mL). The maximum solubility of
MYTICEF (sterile cefoperazone sodium) is approximately 475 mg cefoperazone/mL of
compatible diluent.
PREPARATION FOR INTRAVENOUS USE
GENERAL. MYTICEF (sterile cefoperazone sodium) concentrations between 2 mg/mL
and 50 mg/mL are recommended for intravenous administration.
PREPARATION OF VIALS. Vials of MYTICEF (sterile cefoperazone sodium) may be
initially reconstituted with a minimum of 2.8 mL per gram of cefoperazone of any
compatible reconstituting solution appropriate for intravenous administration
listed above in Table 1. For ease of reconstitution the use of 5 mL of
compatible solution per gram of MYTICEF is recommended. The entire quantity of
the resulting solution should then be withdrawn for further dilution and
administration using any of the following vehicles for intravenous infusion:
TABLE 2. VEHICLES FOR INTRAVENOUS INFUSION
5% Dextrose Injection (USP)
5% Dextrose and Lactated Ringer's Injection
5% Dextrose and 0.9% Sodium Chloride Injection (USP)
5% Dextrose and 0.2% Sodium Chloride Injection (USP)
10% Dextrose Injection (USP)
Lactated Ringer's Injection (USP)
0.9% Sodium Chloride Injection (USP)
Normosol(R) M and 5% Dextrose Injection
Normosol(R) R
PREPARATION OF PIGGY BACK UNITS. MYTICEF (sterile cefoperazone sodium) in Piggy
Back Units for intravenous use may be prepared by adding between 20 mL and 40 mL
of any appropriate diluent listed in Table 2 per gram of cefoperazone. If 5%
Dextrose and Lactated Ringer's Injection or Lactated Ringer's Injection (USP) is
the chosen vehicle for administration the MYTICEF (sterile cefoperazone sodium)
should initially be reconstituted using 2.8-5 m per gram of any compatible
reconstituting solution listed in Table 1 prior to the final dilution.
The resulting intravenous solution should be administered in one of the
following manners:
INTERMITTENT INFUSION: Solutions of MYTICEF should be administered over a 15-30
minute time period.
CONTINUOUS INFUSION: MYTICEF can be used for continuous infusion after dilution
to a final concentration of between 2 and 25 mg cefoperazone per mL.
PREPARATION FOR INTRAMUSCULAR INJECTION
Any suitable solution listed above may be used to prepare MYTICEF (sterile
cefoperazone sodium) for intramuscular injection. When concentrations of 250
mg/mL or more are to be administered, a lidocaine solution should be used. These
solutions should be prepared using a combination of Sterile Water for Injection
and 2% Lidocaine Hydrochloride Injection (USP) that approximates a 0.5%
Lidocaine Hydrochloride Solution. A two-step dilution process as follows is
recommended: First, add the required amount of Sterile Water for Injection and
agitate until MYTICEF powder is completely dissolved. Second, add the required
amount of 2% lidocaine and mix.
FINAL STEP 1 STEP 2
CEFOPERAZONE VOLUME OF VOLUME OF WITHDRAWABLE
CONCENTRATION STERILE WATER 2% LIDOCAINE VOLUME* */*
1 g vial 333 mg/mL 2.0 mL 0.6 mL 3 mL
250 mg/mL 2.8 mL 1.0 mL 4 mL
2 g vial 333 mg/mL 3.8 mL 1.2 mL 6 mL
250 mg/mL 5.4 mL 1.8 mL 8 mL
When a diluent other than Lidocaine HCl Injection (USP) is used reconstitute
as follows:
CEFOPERAZONE VOLUME OF WITHDRAWABLE
CONCENTRATION DILUENT TO BE ADDED VOLUME*
1 g vial 333 mg/mL 2.6 mL 3 mL
250 mg/mL 3.8 mL 4 mL
2 g vial 333 mg/mL 5.0 mL 6 mL
250 mg/mL 7.2 mL 8 mL
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* There is sufficient excess present to allow for withdrawal of the stated
volume.
*/* Final lidocaine concentration will approximate that obtained if a 0.5%
Lidocaine Hydrochloride Solution is used as diluent.
STORAGE AND STABILITY: MYTICEF (sterile cefoperazone sodium) is to be stored at
or below 25 deg C (77 deg F) and protected from light prior to reconstitution.
After reconstitution, protection from light is not necessary.
The following parenteral diluents and approximate concentrations of MYTICEF
provide stable solutions under the following conditions for the indicated time
periods. (After the indicated time periods, unused portions of solutions should
be discarded.)
ROOM TEMPERATURE (15 DEG-25 DEG C/59 DEG-77 DEG F) APPROXIMATE
24 HOURS CONCENTRATIONS
Bacteriostatic Water for Injection
(Benzyl Alcohol or Parabens) (USP)...............................300 mg/mL
5% Dextrose Injection (USP).................................2 mg to 50 mg/mL
5% Dextrose and Lactated Ringer's Injection.................2 mg to 50 mg/mL
5% Dextrose and 0.9% Sodium Chloride Injection (USP)........2 mg to 50 mg/mL
5% Dextrose and 0.2% Sodium Chloride Injection (USP)........2 mg to 50 mg/mL
10% Dextrose Injection (USP)................................2 mg to 50 mg/mL
Lactated Ringer's Injection (USP)....................................2 mg/mL
0.5% Lidocaine Hydrochloride Injection (USP).......................300 mg/mL
0.9% Sodium Chloride Injection (USP).......................2 mg to 300 mg/mL
Normosol(R) M and 5% Dextrose Injection.....................2 mg to 50 mg/mL
Normosol(R) R...............................................2 mg to 50 mg/mL
Sterile Water for Injection........................................300 mg/mL
Reconstituted MYTICEF solutions may be stored in glass or plastic syringes,
or in glass or flexible plastic parenteral solution containers.
REFRIGERATOR TEMPERATURE (2 DEG-8 DEG C/36 DEG-46 DEG F) APPROXIMATE
5 DAYS CONCENTRATIONS
Bacteriostatic Water for Injection
(Benzyl Alcohol or Parabens) (USP)...............................300 mg/mL
5% Dextrose Injection (USP).................................2 mg to 50 mg/mL
5% Dextrose and 0.9% Sodium Chloride Injection (USP)........2 mg to 50 mg/mL
5% Dextrose and 0.2% Sodium Chloride Injection (USP)........2 mg to 50 mg/mL
Lactated Ringer's Injection (USP)....................................2 mg/mL
0.5% Lidocaine Hydrochloride Injection (USP).......................300 mg/mL
0.9% Sodium Chloride Injection (USP).......................2 mg to 300 mg/mL
Normosol(R) M and 5% Dextrose Injection.....................2 mg to 50 mg/mL
Normosol(R) R...............................................2 mg to 50 mg/mL
Sterile Water for Injection........................................300 mg/mL
Reconstituted MYTICEF solutions may be stored in glass or plastic syringes,
or in glass or flexible plastic parenteral solution containers.
FREEZER TEMPERATURE (-20 DEG TO -10 DEG C/-4 DEG TO 14 DEG F) APPROXIMATE
3 WEEKS CONCENTRATIONS
5% Dextrose Injection (USP).........................................50 mg/mL
5% Dextrose and 0.9% Sodium Chloride Injection (USP).................2 mg/mL
5% Dextrose and 0.2% Sodium Chloride Injection (USP).................2 mg/mL
5 WEEKS
0.9% Sodium Chloride Injection (USP)...............................300 mg/mL
Sterile Water for Injection........................................300 mg/mL
Reconstituted MYTICEF solutions may be stored in plastic syringes, or in
flexible plastic parenteral solution containers.
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