CEFOTAXIME SODIUM
DESCRIPTION:
Sterile Claforan(R) (cefotaxime sodium) is a semisynthetic, broad spectrum
cephalosporin antibiotic for parenteral administration. It is the sodium salt of
7-(2-(2-amino-4-thiazolyl) glyoxylamido)-3-(hydroxymethyl)-8-oxo-5-thia- 1-
azabicyclo (4.2.0) oct-2-ene-2-carboxylate 7(squared)(Z)-(o-methyloxime),
acetate (ester). Claforan(R) contains approximately 50.5 mg (2.2 mEq) of sodium
per gram of cefotaxime activity. Solutions of Claforan(R) range from very pale
yellow to light amber depending on the concentration and the diluent used. The
pH of the injectable solutions usually ranges from 5.0 to 7.5.
Claforan(R) is supplied as a dry powder in conventional and ADD-Vantage(R)
System compatible vials, infusion bottles, pharmacy bulk package bottles, and as
a frozen, premixed, iso-osmotic injection in a buffered diluent solution in
plastic containers. Claforan(R), equivalent to 1 gram and 2 grams cefotaxime, is
supplied as frozen, premixed iso-osmotic injections in plastic containers.
Solutions range from very pale yellow to light amber. Dextrose Hydrous, USP has
been added to adjust osmolality (approximately 1.7 g and 700 mg to the 1 g and 2
g cefotaxime dosages, respectively). The injections are buffered with sodium
citrate hydrous, USP. The pH is adjusted with hydrochloric acid and may be
adjusted with sodium hydroxide.
ACTIONS/CLINICAL PHARMACOLOGY:
Following IM administration of a single 500 mg or 1 g dose of Claforan(R) to
normal volunteers, mean peak serum concentrations of 11.7 and 20.5 mcgm/mL
respectively were attained within 30 minutes and declined with an elimination
half- life of approximately 1 hour. There was a dose- dependent increase in
serum levels after the IV administration of 500 mg, 1 g, and 2 g of Claforan(R)
(38.9, 101.7, and 214.4 mcgm/mL respectively) without alteration in the
elimination half-life. There is no evidence of accumulation following repetitive
IV infusion of 1 g doses every 6 hours for 14 days as there are no alterations
of serum or renal clearance. About 60% of the administered dose was recovered
from urine during the first 6 hours following the start of the infusion.
Approximately 20-36% of an intravenously administered dose of 14C-cefotaxime is
excreted by the kidney as unchanged cefotaxime and 15-25% as the desacetyl
derivative, the major metabolite. The desacetyl metabolite has been shown to
contribute to the bactericidal activity. Two other urinary metabolites (M2 and
M3) account for about 20-25%. They lack bactericidal activity.
A single 50 mg/kg dose of Claforan(R) was administered as an intravenous
infusion over a 10- to 15-minute period to 29 newborn infants grouped according
to birth weight and age. The mean half-life of cefotaxime in infants with lower
birth weights (=1500 grams), regardless of age, was longer (4.6 hours) than
the mean half-life (3.4 hours) in infants whose birth weight was greater than
1500 grams. Mean serum clearance was also smaller in the lower birth weight
infants. Although the differences in mean half-life values are statistically
significant for weight, they are not clinically important. Therefore, dosage
should be based solely on age. (See DOSAGE AND ADMINISTRATION section.)
Additionally, no disulfiram-like reactions were reported in a study conducted in
22 healthy volunteers administered Claforan(R) and ethanol.
MICROBIOLOGY
The bactericidal activity of cefotaxime sodium results from inhibition of cell
wall synthesis. Cefotaxime sodium has In Vitro activity against a wide range of
gram-positive and gram-negative organisms. Claforan(R) has a high degree of
stability in the presence of beta-lactamases, both penicillinases and
cephalosporinases, of gram-negative and gram-positive bacteria. Cefotaxime
sodium has been shown to be a potent inhibitor of beta-lactamases produced by
certain gram-negative bacteria. Cefotaxime sodium is usually active against the
following microorganisms both In Vitro and in clinical infections. (See
INDICATIONS AND USAGE).
AEROBES, GRAM-POSITIVE: Staphylococcus Aureus, including penicillinase and non-
penicillinase producing strains, Staphylococcus Epidermidis, Enterococcus
species, Streptococcus Pyogenes (Group A beta-hemolytic streptococci),
Streptococcus Agalactiae (Group B streptococci), Streptococcus Pneumoniae
(formerly Diplococcus Pneumoniae).
AEROBES, GRAM-NEGATIVE: Citrobacter species, Enterobacter species, Escherichia
Coli, Haemophilus Influenzae (including ampicillin- resistant H. Influenzae),
Haemophilus Parainfluenzae, Klebsiella species (including K. Pneumoniae),
Neisseria Gonorrhoeae (including penicillinase and non-penicillinase producing
strains), Neisseria Meningitidis, Proteus Mirabilis, Proteus Vulgaris, Proteus
Inconstans Group B, Morganella Morganii, Providencia Rettgeri, Serratia species,
and Acinetobacter species.
NOTE: Many strains of the above organisms that are multiply resistant to other
antibiotics, e.g., penicillins, cephalosporins, and aminoglycosides, are
susceptible to cefotaxime sodium.
Cefotaxime sodium is active against some strains of Pseudomonas Aeruginosa.
ANAEROBES: Bacteroides species, including some strains of B. Fragilis,
Clostridium species (NOTE: Most strains of C. Difficile are resistant.),
Peptococcus species, Peptostreptococcus species, and Fusobacterium species
(including F. Nucleatum).
Cefotaxime sodium is highly stable In Vitro to four of the five major classes of
beta-lactamases described by Richmond et al., including type IIIa (TEM) which is
produced by many gram-negative bacteria. The drug is also stable to beta-
lactamase (penicillinase) produced by staphylococci. In addition, cefotaxime
sodium shows high affinity for penicillin-binding proteins in the cell wall,
including PBP, Ib and III.
Cefotaxime sodium also demonstrates In Vitro activity against the following
microorganisms although clinical significance is unknown: Salmonella species
(including S. Typhi), Providencia species, and Shigella species.
Cefotaxime sodium and aminoglycosides have been shown to be synergistic In Vitro
against some strains of Pseudomonas Aeruginosa.
SUSCEPTIBILITY TESTS
Quantitative methods that require measurement of zone diameters give the most
precise estimate of antibiotic susceptibility. One such procedure (REF. 1) has
been recommended for use with discs to test susceptibility to cefotaxime sodium.
Interpretation involves correlation of the diameters obtained in the disc test
with minimum inhibitory concentration (MIC) values for cefotaxime sodium.
Reports from the laboratory giving results of the standardized single-disc
susceptibility test using a 30 mcgm cefotaxime sodium disc should be interpreted
according to the following criteria:
Susceptible organisms produce zones of 20 mm or greater, indicating that the
tested organism is likely to respond to therapy.
Organisms that produce zones of 15 to 19 mm are expected to be susceptible if
high dosage is used or if the infection is confined to tissues and fluids (e.g.,
urine) in which high antibiotic levels are attained.
Resistant organisms produce zones of 14 mm or less, indicating that other
therapy should be selected.
Organisms should be tested with the cefotaxime sodium disc, since cefotaxime
sodium has been shown by In Vitro tests to be active against certain strains
found resistant when other beta lactam discs are used. The cefotaxime sodium
disc should not be used for testing susceptibility to other cephalosporins.
Organisms having zones of less than 18 mm around the cephalothin disc are not
necessarily of intermediate susceptibility or resistant to cefotaxime sodium.
A bacterial isolate may be considered susceptible if the MIC value for
cefotaxime sodium is not more than 16 mcgm/mL. Organisms are considered
resistant to cefotaxime sodium if the MIC is equal to or greater than 64
mcgm/mL. Organisms having an MIC value of less than 64 mcgm/mL but greater than
16 mcgm/mL are expected to be susceptible if high dosage is used or if the
infection is confined to tissues and fluids (e.g., urine) in which high
antibiotic levels are attained.
INDICATIONS AND USAGE:
TREATMENT
Claforan(R) is indicated for the treatment of patients with serious infections
caused by susceptible strains of the designated microorganisms in the diseases
listed below.
(1) LOWER RESPIRATORY TRACT INFECTIONS, including pneumonia, caused by
Streptococcus Pneumoniae (formerly Diplococcus Pneumoniae), Streptococcus
Pyogenes* (Group A streptococci) and other streptococci (excluding enterococci,
e.g., Streptococcus Faecalis), Staphylococcus Aureus (penicillinase and non-
penicillinase producing), Escherichia Coli, Klebsiella species, Haemophilus
Influenzae (including ampicillin resistant strains), Haemophilus Parainfluenzae,
Proteus Mirabilis, Serratia Marcescens*, Enterobacter species, indole positive
Proteus and Pseudomonas species (including P. Aeruginosa).
(2) GENITOURINARY INFECTIONS. Urinary tract infections caused by Enterococcus
species, Staphylococcus Epidermidis, Staphylococcus Aureus* (penicillinase and
non-penicillinase producing), Citrobacter species, Enterobacter species,
Escherichia Coli, Klebsiella species, Proteus Mirabilis, Proteus Vulgaris*,
Proteus Inconstans group B, Morganella Morganii*, Providencia Rettgeri*,
Serratia Marcescens and Pseudomonas species (including P. Aeruginosa). Also,
uncomplicated gonorrhea (cervical/urethral and rectal) caused by Neisseria
Gonorrhoeae, including penicillinase producing strains.
(3) GYNECOLOGIC INFECTIONS, including pelvic inflammatory disease, endometritis
and pelvic cellulitis caused by Staphylococcus Epidermidis, Streptococcus
species, Enterococcus species, Enterobacter species*, Klebsiella species*,
Escherichia Coli, Proteus Mirabilis, Bacteroides species (including Bacteroides
Fragilis*), Clostridium species, anaerobic cocci (including Peptostreptococcus
species and Peptococcus species) and Fusobacterium species (including F.
Nucleatum*).
Claforan(R), like other cephalosporins, has no activity against Chlamydia
Trachomatis. Therefore, when cephalosporins are used in the treatment of
patients with pelvic inflammatory disease and C. Trachomatis is one of the
suspected pathogens, appropriate anti-chlamydial coverage should be added.
(4) BACTEREMIA/SEPTICEMIA caused by Escherichia Coli, Klebsiella species,
Serratia Marcescens, Staphylococcus Aureus, and Streptococcus species (including
S. Pneumoniae).
(5) SKIN AND SKIN STRUCTURE INFECTIONS caused by Staphylococcus Aureus
(penicillinase and non- penicillinase producing), Staphylococcus Epidermidis,
Streptococcus Pyogenes (Group A streptococci) and other streptococci,
Enterococcus species, Acinetobacter species,* Escherichia Coli, Citrobacter
species (including C. Freundii*), Enterobacter species, Klebsiella species,
Proteus Mirabilis, Proteus Vulgaris,* Morganella Morganii, Providencia
Rettgeri*, Pseudomonas species, Serratia Marcescens, Bacteroides species, and
anaerobic cocci (including Peptostreptococcus* species and Peptococcus species).
(6) INTRA-ABDOMINAL INFECTIONS including peritonitis caused by Streptococcus
species,* Escherichia Coli, Klebsiella species, Bacteroides species, anaerobic
cocci (including Peptostreptococcus* species and Peptococcus* species), Proteus
Mirabilis*, and Clostridium species*.
(7) BONE AND/OR JOINT INFECTIONS caused by Staphylococcus Aureus (penicillinase
and non- penicillinase producing strains), Streptococcus species (including S.
Pyogenes*), Pseudomonas species (including P. Aeruginosa*), and Proteus
Mirabilis.*
(8) CENTRAL NERVOUS SYSTEM INFECTIONS, e.g., meningitis and ventriculitis,
caused by Neisseria Meningitidis, Haemophilus Influenzae, Streptococcus
Pneumoniae, Klebsiella Pneumoniae,* and Escherichia Coli*,
----------
* Efficacy for this organism, in this organ system, has been studied in fewer
than 10 infections.
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Although many strains of enterococci (e.g., S. Faecalis) and Pseudomonas species
are resistant to cefotaxime sodium In Vitro, Claforan(R) has been used
successfully in treating patients with infections caused by susceptible
organisms.
Specimens for bacteriologic culture should be obtained prior to therapy in order
to isolate and identify causative organisms and to determine their
susceptibilities to Claforan(R). Therapy may be instituted before results of
susceptibility studies are known; 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, Claforan(R) may be used concomitantly with an
aminoglycoside. The dosage recommended in the labeling of both antibiotics may
be given and depends on the severity of the infection and the patient's
condition. Renal function should be carefully monitored, especially if higher
dosages of the aminoglycosides are to be administered or if therapy is
prolonged, because of the potential nephrotoxicity and ototoxicity of
aminoglycoside antibiotics. It is possible that nephrotoxicity may be
potentiated if Claforan(R) is used concomitantly with an aminoglycoside.
PREVENTION
The administration of Claforan(R) preoperatively reduces the incidence of
certain infections in patients undergoing surgical procedures (e.g., abdominal
or vaginal hysterectomy, gastrointestinal and genitourinary tract surgery) that
may be classified as contaminated or potentially contaminated.
In patients undergoing cesarean section, intraoperative (after clamping the
umbilical cord) and postoperative use of Claforan(R) may also reduce the
incidence of certain postoperative infections. (See DOSAGE AND ADMINISTRATION
section.)
Effective use for elective surgery depends on the time of administration. To
achieve effective tissue levels, Claforan(R) should be given 1/2 to 1 1/2 hours
before surgery. (See DOSAGE AND ADMINISTRATION section.)
For patients undergoing gastrointestinal surgery, preoperative bowel preparation
by mechanical cleansing as well as with a non-absorbable antibiotic (e.g.,
neomycin) is recommended.
If there are signs of infection, specimens for culture should be obtained for
identification of the causative organism so that appropriate therapy may be
instituted.
CONTRAINDICATIONS:
Claforan(R) is contraindicated in patients who have shown hypersensitivity to
cefotaxime sodium or the cephalosporin group of antibiotics.
WARNINGS:
BEFORE THERAPY WITH CLAFORAN(R) IS INSTITUTED, CAREFUL INQUIRY SHOULD BE MADE TO
DETERMINE WHETHER THE PATIENT HAS HAD PREVIOUS HYPERSENSITIVITY REACTIONS TO
CEFOTAXIME SODIUM, CEPHALOSPORINS, PENICILLINS, OR OTHER DRUGS. THIS PRODUCT
SHOULD BE GIVEN WITH CAUTION TO PATIENTS WITH TYPE I HYPERSENSITIVITY REACTIONS
TO PENICILLIN. ANTIBIOTICS SHOULD BE ADMINISTERED WITH CAUTION TO ANY PATIENT
WHO HAS DEMONSTRATED SOME FORM OF ALLERGY, PARTICULARLY TO DRUGS. IF AN ALLERGIC
REACTION TO CLAFORAN(R) OCCURS, DISCONTINUE TREATMENT WITH THE DRUG. SERIOUS
HYPERSENSITIVITY REACTIONS MAY REQUIRE EPINEPHRINE AND OTHER EMERGENCY MEASURES.
During post-marketing surveillance, a potentially life-threatening arrhythmia
was reported in each of six patients who received a rapid (less than 60 seconds)
bolus injection of cefotaxime through a central venous catheter. Therefore,
cefotaxime should only be administered as instructed in the DOSAGE AND
ADMINISTRATION section.
PSEUDOMEMBRANOUS COLITIS HAS BEEN REPORTED WITH NEARLY ALL ANTIBACTERIAL AGENTS,
INCLUDING CEFOTAXIME, AND MAY RANGE FROM MILD TO LIFE THREATENING. THEREFORE, IT
IS IMPORTANT TO CONSIDER ITS DIAGNOSIS IN PATIENTS WITH DIARRHEA SUBSEQUENT TO
THE ADMINISTRATION OF ANTIBACTERIAL AGENTS.
Treatment with antibacterial agents alters the normal flora of the colon and may
permit overgrowth of Clostridia. Studies indicate that a toxin produced by
Clostridium Difficile is one primary cause of antibiotic-associated colitis.
After the diagnosis of pseudomembranous colitis has been established,
appropriate therapeutic measures should be initiated. Mild cases of colitis may
respond to drug discontinuance 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 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:
Claforan(R) should be prescribed with caution in individuals with a history of
gastrointestinal disease, particularly colitis.
Because high and prolonged serum antibiotic concentrations can occur from usual
doses in patients with transient or persistent reduction of urinary output
because of renal insufficiency, the total daily dosage should be reduced when
Claforan(R) is administered to such patients. Continued dosage should be
determined by degree of renal impairment, severity of infection, and
susceptibility of the causative organism.
Although there is no clinical evidence supporting the necessity of changing the
dosage of cefotaxime sodium in patients with even profound renal dysfunction, it
is suggested that, until further data are obtained, the dose of cefotaxime
sodium be halved in patients with estimated creatinine clearances of less than
20 mL/min/1.73 M(squared).
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: Weight (kg) X (140 - age)
72 X serum creatinine
Females: 0.85 X above value
As with other antibiotics, prolonged use of Claforan(R) may result in overgrowth
of nonsusceptible organisms. Repeated evaluation of the patient's condition is
essential. If superinfection occurs during therapy, appropriate measures should
be taken.
As with other beta-lactam antibiotics, granulocytopenia and, more rarely,
agranulocytosis may develop during treatment with Claforan(R), particularly if
given over long periods. For courses of treatment lasting longer than 10 days,
blood counts should therefore be monitored.
Claforan(R), like other parenteral anti-infective drugs, may be locally
irritating to tissues. In most cases, perivascular extravasation of Claforan(R)
responds to changing of the infusion site. In rare instances, extensive
perivascular extravasation of Claforan(R) may result in tissue damage and
require surgical treatment. To minimize the potential for tissue inflammation,
infusion sites should be monitored regularly and changed when appropriate.
DRUG INTERACTIONS: Increased nephrotoxicity has been reported following
concomitant administration of cephalosporins and aminoglycoside antibiotics.
CARCINOGENESIS, MUTAGENESIS: Long-term studies in animals have not been
performed to evaluate carcinogenic potential. Mutagenic tests included a
micronucleus and an Ames test. Both tests were negative for mutagenic effects.
PREGNANCY (CATEGORY B): Reproduction studies have been performed in mice and
rats at doses up to 30 times the usual human dose and have revealed no evidence
of impaired fertility or harm to the fetus because of cefotaxime sodium.
However, there are no well-controlled studies in pregnant women. Because animal
reproductive studies are not always predictive of human response, this drug
should be used during pregnancy only if clearly needed.
NONTERATOGENIC EFFECTS: Use of the drug in women of childbearing potential
requires that the anticipated benefit be weighed against the possible risks.
In perinatal and postnatal studies with rats, the pups in the group given 1200
mg/kg of Claforan(R) were significantly lighter in weight at birth and remained
smaller than pups in the control group during the 21 days of nursing.
NURSING MOTHERS: Claforan(R) is excreted in human milk in low concentrations.
Caution should be exercised when Claforan(R) is administered to a nursing woman.
PEDIATRIC USE: See Precautions above regarding perivascular extravasation. The
potential for toxic effects in pediatric patients from chemicals that may leach
from the plastic in single dose Galaxy(R) containers (premixed Claforan(R)
Injection) has not been determined.
DRUG INTERACTIONS:
Increased nephrotoxicity has been reported following concomitant administration
of cephalosporins and aminoglycoside antibiotics.
(See Also PRECAUTIONS)
ADVERSE REACTIONS:
Claforan(R) is generally well tolerated. The most common adverse reactions have
been local reactions following IM or IV injection. Other adverse reactions have
been encountered infrequently.
THE MOST FREQUENT ADVERSE REACTIONS (GREATER THAN 1%) ARE:
Local (4.3%)--Injection site inflammation with IV administration. Pain,
induration, and tenderness after IM injection.
Hypersensitivity (2.4%)--Rash, pruritus, fever, and eosinophilia and less
frequently urticaria and anaphylaxis.
Gastrointestinal (1.4%)--Colitis, diarrhea, nausea, and vomiting.
Symptoms of pseudomembranous colitis can appear during or after antibiotic
treatment.
Nausea and vomiting have been reported rarely.
LESS FREQUENT ADVERSE REACTIONS (LESS THAN 1%) ARE:
Cardiovascular System--Potentially life- threatening arrhythmias following rapid
(less than 60 seconds) bolus administration via central venous catheter have
been observed.
Hematologic System--Neutropenia, transient leukopenia, eosinophilia,
thrombocytopenia and agranulocytosis have been reported. Some individuals have
developed positive direct Coombs Tests during treatment with Claforan(R)
(cefotaxime sodium injection) and other cephalosporin antibiotics. Rare cases of
hemolytic anemia have been reported.
Genitourinary System--Moniliasis, vaginitis.
Central Nervous System--Headache.
Liver--Transient elevations in SGOT, SGPT, serum LDH, and serum alkaline
phosphatase levels have been reported.
Kidney--As with some other cephalosporins, interstitial nephritis and transient
elevations of BUN and creatinine have been occasionally observed with
Claforan(R).
DOSAGE AND ADMINISTRATION:
ADULTS
Dosage and route of administration should be determined by susceptibility of the
causative organisms, severity of the infection, and the condition of the patient
(see table for dosage guidelines). Claforan(R) may be administered IM or IV
after reconstitution. Premixed Claforan(R) Injection is intended for IV
administration after thawing. The maximum daily dosage should not exceed 12
grams.
GUIDELINES FOR DOSAGE OF CLAFORAN(R)
DAILY DOSE
TYPE OF INFECTION (GRAMS) FREQUENCY AND ROUTE
Gonococcal urethritis/cervicitis
in males and females 0.5 0.5 gram IM (single dose)
Rectal gonorrhea in females 0.5 0.5 gram IM (single dose)
Rectal gonorrhea in males 1 1 gram IM (single dose)
Uncomplicated infections 2 1 gram every 12 hours
IM or IV
Moderate to severe infections 3-6 1-2 grams every 8 hours
IM or IV
Infections commonly needing
antibiotics in higher dosage
(e.g., septicemia) 6-8 2 grams every 6-8 hours IV
Life-threatening infections up to 12 2 grams every 4 hours IV
If C. Trachomatis is a suspected pathogen, appropriate anti-chlamydial coverage
should be added, because cefotaxime sodium has no activity against this
organism.
To prevent postoperative infection in contaminated or potentially contaminated
surgery, the recommended dose is a single 1 gram IM or IV administered 30 to 90
minutes prior to start of surgery.
CESAREAN SECTION PATIENTS
The first dose of 1 gram is administered intravenously as soon as the umbilical
cord is clamped. The second and third doses should be given as 1 gram
intravenously or intramuscularly at 6 and 12 hours after the first dose.
NEONATES, INFANTS, AND CHILDREN
The following dosage schedule is recommended:
Neonates (birth to 1 month):
0-1 week of age 50 mg/kg per dose every
12 hours IV
1-4 weeks of age 50 mg/kg per dose every
8 hours IV
It is not necessary to differentiate between premature and normal-gestational
age infants.
Infants and Children (1 month to 12 years): For body weights less than 50 kg,
the recommended daily dose is 50 to 180 mg/kg IM or IV body weight divided into
four to six equal doses. The higher dosages should be used for more severe or
serious infections, including meningitis. For body weights 50 kg or more, the
usual adult dosage should be used; the maximum daily dosage should not exceed 12
grams.
IMPAIRED RENAL FUNCTION--see PRECAUTIONS section.
NOTE: As with antibiotic therapy in general, administration of Claforan(R)
should be continued for a minimum of 48 to 72 hours after the patient
defervesces or after evidence of bacterial eradication has been obtained; a
minimum of 10 days of treatment is recommended for infections caused by Group A
beta-hemolytic streptococci 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 of several weeks and doses smaller than those indicated above
should not be used.
PREPARATION OF CLAFORAN(R) STERILE
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Claforan(R) for IM or IV administration should be reconstituted as follows:
APPROXIMATE
DILUENT WITHDRAWABLE CONCENTRATION
STRENGTH (ML) VOLUME (ML) (MG/ML)
------------------------------------------------------------------------------------------------------------------------------------------------------
500 mg vial* (IM) 2 2.2 230
1 g vial* (IM) 3 3.4 300
2 g vial* (IM) 5 6.0 330
500 mg vial* (IV) 10 10.2 50
1 g vial* (IV) 10 10.4 95
2 g vial* (IV) 10 11.0 180
1 g infusion 50-100 50-100 20-10
2 g infusion 50-100 50-100 40-20
10 g bottle 47 52.0 200
10 g bottle 97 102.0 100
*In conventional vials
Shake to dissolve; inspect for particulate matter and discoloration prior to
use. Solutions of Claforan(R) range from very pale yellow to light amber,
depending on concentration, diluent used, and length and condition of storage.
FOR INTRAMUSCULAR USE: Reconstitute VIALS with Sterile Water for Injection or
Bacteriostatic Water for Injection as described above.
FOR INTRAVENOUS USE: Reconstitute VIALS with at least 10 mL of Sterile Water for
Injection. Reconstitute INFUSION BOTTLES with 50 or 100 mL of 0.9% Sodium
Chloride Injection or 5% Dextrose Injection. For other diluents, see
COMPATIBILITY AND STABILITY section.
PHARMACY BULK PACKAGE: Reconstitute with 47 mL of diluent for an approximate
concentration of 200 mg/mL or 97 mL of diluent for an approximate concentration
of 100 mg/mL. Stock solutions may be further diluted for IV infusion with
diluents as listed in COMPATIBILITY AND STABILITY section.
NOTE: Solutions of Claforan(R) must not be admixed with aminoglycoside
solutions. If Claforan(R) and aminoglycosides are to be administered to the same
patient, they must be administered separately and not as mixed injection.
A SOLUTION OF 1 G CLAFORAN(R) IN 14 ML OF STERILE WATER FOR INJECTION IS
ISOTONIC.
IM ADMINISTRATION: As with all IM preparations, Claforan(R) should be injected
well within the body of a relatively large muscle such as the upper outer
quadrant of the buttock (i.e., gluteus maximus); aspiration is necessary to
avoid inadvertent injection into a blood vessel. Individual IM doses of 2 grams
may be given if the dose is divided and is administered in different
intramuscular sites.
IV ADMINISTRATION: The IV route is preferable for patients with bacteremia,
bacterial septicemia, peritonitis, meningitis, or other severe or life-
threatening infections, or for patients who may be poor risks because of lowered
resistance resulting from such debilitating conditions as malnutrition, trauma,
surgery, diabetes, heart failure, or malignancy, particularly if shock is
present or impending.
For intermittent IV administration, a solution containing 1 gram or 2 grams in
10 mL of Sterile Water for Injection can be injected over a period of three to
five minutes. Cefotaxime should not be administered over a period of less than
three minutes. (See WARNINGS.) With an infusion system, it may also be given
over a longer period of time through the tubing system by which the patient may
be receiving other IV solutions. However, during infusion of the solution
containing Claforan(R), it is advisable to discontinue temporarily the
administration of other solutions at the same site.
For the administration of higher doses by continuous IV infusion, a solution of
Claforan(R) may be added to IV bottles containing the solutions discussed below.
DIRECTIONS FOR USE OF CLAFORAN(R) (CEFOTAXIME SODIUM INJECTION) IN GALAXY
CONTAINER (PL 2040 PLASTIC)
Claforan(R) Injection in Galaxy containers (PL 2040 plastic) is for continuous
or intermittent infusion using sterile equipment.
STORAGE
Store in a freezer capable of maintaining a temperature of -20 deg C/-4 deg F.
THAWING OF PLASTIC CONTAINER
Thaw frozen container at room temperature or under refrigeration (at or below 5
deg C). (DO NOT FORCE THAW BY IMMERSION IN WATER BATHS OR BY MICROWAVE
IRRADIATION.)
Check for minute leaks by squeezing container firmly. If leaks are detected,
discard solution as sterility may be impaired.
DO NOT ADD SUPPLEMENTARY MEDICATION.
The container should be visually inspected. 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. Agitate after solution has
reached room temperature. If after visual inspection the solution remains cloudy
or if an insoluble precipitate is noted or if any seals or outlet ports are not
intact, the container should be discarded.
The thawed solution is stable for 10 days under refrigeration (at or below 5 deg
C) or 24 hours at or below 22 deg C. Do not refreeze thawed antibiotics.
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 INTRAVENOUS 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.
PREPARATION OF CLAFORAN(R) STERILE IN ADD- VANTAGE(R) SYSTEM
Claforan(R) Sterile 1 g or 2 g may be reconstituted in 50 mL or 100 mL of 5%
Dextrose or 0.9% Sodium Chloride in the ADD-Vantage(R) diluent container. Refer
to enclosed, separate INSTRUCTIONS FOR ADD-VANTAGE(R) SYSTEM.
COMPATIBILITY AND STABILITY
Solutions of Claforan(R) Sterile reconstituted as described above (PREPARATION
OF CLAFORAN(R) STERILE) remain chemically stable (potency remains above 90%) as
follows when stored in original containers and disposable plastic syringes:
STRENGTH RECONSTITUTED STABILITY AT OR STABILITY UNDER
CONCENTRATION MG/ML BELOW 22 DEG C REFRIGERATION
AT OR BELOW 5 DEG C
ORIGINAL PLASTIC
CONTAINERS SYRINGES
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500 mg vial IM 200 12 hours 7 days 5 days
1g vial IM 300 12 hours 7 days 5 days
2g vial IM 330 12 hours 7 days 5 days
500 mg vial IV 50 24 hours 7 days 5 days
1g vial IV 95 24 hours 7 days 5 days
2g vial IV 180 12 hours 7 days 5 days
1g infusion bottle 10-20 24 hours 10 days
2g infusion bottle 20-40 24 hours 10 days
Reconstituted solutions stored in original containers and plastic syringes
remain stable for 13 weeks frozen.
For the 10g bottle withdraw reconstituted contents immediately. However, if it
is not possible, aliquoting operations must be completed within four hours of
reconstitution. Discard the reconstituted stock solution 4 hours after initial
entry.
Reconstituted solutions may be further diluted up to 1000 mL with the following
solutions and maintain satisfactory potency for 24 hours at or below 22 deg C,
and at least 5 days under refrigeration (at or below 5 deg C): 0.9% Sodium
Chloride Injection; 5 or 10% Dextrose Injection; 5% Dextrose and 0.9% Sodium
Chloride Injection; 5% Dextrose and 0.45% Sodium Chloride Injection; 5% Dextrose
and 0.2% Sodium Chloride Injection; Lactated Ringer's Solution; Sodium Lactate
Injection (M/6); 10% Invert Sugar Injection, 8.5% TRAVASOL(R) (Amino Acid)
Injection without Electrolytes.
Solutions of Claforan(R) Sterile reconstituted in 0.9% Sodium Chloride Injection
or 5% Dextrose Injection in Viaflex(R) plastic containers maintain satisfactory
potency for 24 hours at or below 22 deg C, 5 days under refrigeration (at or
below 5 deg C) and 13 weeks frozen. Solutions of Claforan(R) Sterile
reconstituted in 0.9% Sodium Chloride Injection or 5% Dextrose Injection in the
ADD-Vantage(R) flexible containers maintain satisfactory potency for 24 hours at
or below 22 deg C. DO NOT FREEZE.
NOTE: Claforan(R) solutions exhibit maximum stability in the pH 5-7 range.
Solutions of Claforan(R) should not be prepared with diluents having a pH above
7.5, such as Sodium Bicarbonate Injection.
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