CIPROFLOXACIN LACTATE
IT HAS SIMILAR PROPERTIES AS CIPROFLOXACIN HCL, SO SEE BELOW TO CIPROFLOXACIN HCL FOR FULL DETAILS.
DESCRIPTION:
CIPROBID I.V. (ciprofloxacin) is a synthetic broad-spectrum antimicrobial agent
for intravenous (I.V.) administration. Ciprofloxacin, a fluoroquinolone, is 1-
cyclopropyl-6-fluoro- 1,4-dihydro-4-oxo- 7-(1-piperazinyl)-3-quinolinecarboxylic
acid. Its empirical formula is C17H18FN3O3.
Click here to view chemical structure(s).
Ciprofloxacin is a faint to light yellow crystalline powder with a molecular
weight of 331.4. It is soluble in dilute (0.1N) hydrochloric acid and is
practically insoluble in water and ethanol. Ciprofloxacin differs from other
quinolones in that it has a fluorine atom at the 6-position, a piperazine moiety
at the 7-position, and a cyclopropyl ring at the 1-position. CIPROBID I.V.
solutions are available as sterile 1.0% aqueous concentrates, which are intended
for dilution prior to administration, and as 0.2% ready-for-use infusion
solutions in 5% Dextrose Injection. All formulas contain lactic acid as a
solubilizing agent and hydrochloric acid for pH adjustment. The pH range for the
1.0% aqueous concentrates in vials is 3.3 to 3.9. The pH range for the 0.2%
ready-for-use infusion solutions is 3.5 to 4.6.
The plastic container is fabricated from a specially formulated polyvinyl
chloride. Solutions in contact with the plastic container can leach out certain
of its chemical components in very small amounts within the expiration period,
e.g., di(2-ethylhexyl) phthalate (DEHP), up to 5 parts per million. The
suitability of the plastic has been confirmed in tests in animals according to
USP biological tests for plastic containers as well as by tissue culture
toxicity studies.
ACTIONS/CLINICAL PHARMACOLOGY:
Following 60-minute intravenous infusions of 200 mg and 400 mg ciprofloxacin to
normal volunteers, the mean maximum serum concentrations achieved were 2.1 and
4.6 Mu-g/mL, respectively; the concentrations at 12 hours were 0.1 and 0.2 Mu-
g/mL, respectively.
STEADY-STATE CIPROFLOXACIN SERUM CONCENTRATIONS (MU-G/ML) AFTER 60-MINUTE I.V.
INFUSIONS Q 12 H.
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TIME AFTER STARTING THE INFUSION
DOSE 30 MIN 1 HR 3 HR 6 HR 8 HR 12 HR
200 mg 1.7 2.1 0.6 0.3 0.2 0.1
400 mg 3.7 4.6 1.3 0.7 0.5 0.2
The pharmacokinetics of ciprofloxacin are linear over the dose range of 200 to
400 mg administered intravenously. The serum elimination half-life is
approximately 5-6 hours and the total clearance is around 35 L/hr. Comparison of
the pharmacokinetic parameters following the 1st and 5th I.V. dose on a q 12 h
regimen indicates no evidence of drug accumulation.
The absolute bioavailability of oral ciprofloxacin is within a range of 70-80%
with no substantial loss by first pass metabolism. An intravenous infusion of
400 mg ciprofloxacin given over 60 minutes every 12 hours has been shown to
produce an area under the serum concentration time curve (AUC) equivalent to
that produced by a 500-mg oral dose given every 12 hours. An intravenous
infusion of 400 mg ciprofloxacin given over 60 minutes every 8 hours has been
shown to produce an AUC at steady-state equivalent to that produced by a 750-mg
oral dose given every 12 hours. A 400-mg I.V. dose results in a Cmax similar to
that observed with a 750-mg oral dose. An infusion of 200 mg ciprofloxacin given
every 12 hours produces an AUC equivalent to that produced by a 250-mg oral dose
given every 12 hours.
STEADY-STATE PHARMACOKINETIC PARAMETER FOLLOWING MULTIPLE ORAL AND I.V. DOSES
Parameters 500 mg 400 mg 750 mg 400 mg
q12h, P.O. q12h, I.V. q12h, P.O. q8h, I.V.
AUC (Mu-g*hr/mL) 13.7 a 12.7a 31.6b 32.9c
Cmax (Mu-g/mL) 2.97 4.56 3.59 4.07
a AUC0-12h
b AUC 24h=AUC0-12h * 2
c AUC 24h=AUC0-8h * 3
After intravenous administration, approximately 50% to 70% of the dose is
excreted in the urine as unchanged drug. Following a 200-mg I.V. dose,
concentrations in the urine usually exceed 200 Mu-g/mL 0-2 hours after dosing
and are generally greater than 15 Mu-g/mL 8-12 hours after dosing. Following a
400-mg I.V. dose, urine concentrations generally exceed 400 Mu-g/mL 0-2 hours
after dosing and are usually greater than 30 Mu-g/mL 8-12 hours after dosing.
The renal clearance is approximately 22 L/hr. The urinary excretion of
ciprofloxacin is virtually complete by 24 hours after dosing.
The serum concentrations of ciprofloxacin and metronidazole were not altered
when these two drugs were given concomitantly.
Co-administration of probenecid with ciprofloxacin results in about a 50%
reduction in the ciprofloxacin renal clearance and a 50% increase in its
concentration in the systemic circulation. Although bile concentrations of
ciprofloxacin are severalfold higher than serum concentrations after intravenous
dosing, only a small amount of the administered dose (<1%) is recovered from the
bile as unchanged drug. Approximately 15% of an I.V. dose is recovered from the
feces within 5 days after dosing.
After I.V. administration, three metabolites of ciprofloxacin have been
identified in human urine which together accounted for approximately 10% of the
intravenous dose.
In patients with reduced renal function, the half-life of ciprofloxacin is
slightly prolonged and dosage adjustments may be required. (See DOSAGE AND
ADMINISTRATION.)
In preliminary studies in patients with stable chronic liver cirrhosis, no
significant changes in ciprofloxacin pharmacokinetics have been observed.
However, the kinetics of ciprofloxacin in patients with acute hepatic
insufficiency have not been fully elucidated.
Following infusion of 400 mg I.V. ciprofloxacin every eight hours in combination
with 50 mg/kg I.V. piperacillin sodium every 4 hours, mean serum ciprofloxacin
concentrations were 3.02 Mu- g/mL 1/2 hour and 1.18 Mu-g/mL between 6-8 hours
after the end of infusion.
The binding of ciprofloxacin to serum proteins is 20 to 40%.
After intravenous administration, ciprofloxacin is present in saliva, nasal and
bronchial secretions, sputum, skin blister fluid, lymph, peritoneal fluid, bile,
and prostatic secretions. It has also been detected in the lung, skin, fat,
muscle, cartilage, and bone. Although the drug diffuses into cerebrospinal fluid
(CSF), CSF concentrations are generally less than 10% of peak serum
concentrations. Levels of the drug in the aqueous and vitreous chambers of the
eye are lower than in serum.
MICROBIOLOGY: Ciprofloxacin has IN VITRO activity against a wide range of gram-
negative and gram-positive microorganisms. The bactericidal action of
ciprofloxacin results from interference with the enzyme DNA gyrase which is
needed for the synthesis of bacterial DNA.
Ciprofloxacin has been shown to be active against most strains of the following
microorganisms, both IN VITRO and in clinical infections as described in the
INDICATIONS AND USAGE section of the package insert for CIPROBID I.V.
(ciprofloxacin for intravenous infusion).
AEROBIC GRAM-POSITIVE MICROORGANISMS
ENTEROCOCCUS FAECALIS
(Many strains are only
moderately susceptible.)
STAPHYLOCOCCUS AUREUS
(methicillin susceptible)
STAPHYLOCOCCUS EPIDERMIDIS
STAPHYLOCOCCUS SAPROPHYTICUS
STREPTOCOCCUS PNEUMONIAE
STREPTOCOCCUS PYOGENES
AEROBIC GRAM-NEGATIVE MICROORGANISMS
CITROBACTER DIVERSUS
CITROBACTER FREUNDII
ENTEROBACTER CLOACAE
ESCHERICHIA COLI
HAEMOPHILUS INFLUENZAE
HAEMOPHILUS PARAINFLUENZAE
KLEBSIELLA PNEUMONIAE
MORGANELLA MORGANII
PROTEUS MIRABILIS
PROTEUS VULGARIS
PROVIDENCIA RETTGERI
PROVIDENCIA STUARTII
PSEUDOMONAS AERUGINOSA
SERRATIA MARCESCENS
Ciprofloxacin has been shown to be active against most strains of the following
microorganisms, both IN VITRO and in clinical infections as described in the
INDICATIONS AND USAGE section of the package insert for CIPROBID (ciprofloxacin
hydrochloride) Tablets.
AEROBIC GRAM-POSITIVE MICROORGANISMS
ENTEROCOCCUS FAECALIS
Many strains are only
moderately susceptible.)
STAPHYLOCOCCUS AUREUS
(methicillin susceptible)
STAPHYLOCOCCUS EPIDERMIDIS
STAPHYLOCOCCUS SAPROPHYTICUS
STREPTOCOCCUS PNEUMONIAE
STREPTOCOCCUS PYOGENES
AEROBIC GRAM-NEGATIVE MICROORGANISMS
CAMPYLOBACTER JEJUNI
CITROBACTER DIVERSUS
CITROBACTER FREUNDII
ENTEROBACTER CLOACAE
ESCHERICHIA COLI
HAEMOPHILUS INFLUENZAE
HAEMOPHILUS PARAINFLUENZAE
KLEBSIELLA PNEUMONIAE
MORAXELLA CATARRHALIS
MORGANELLA MORGANII
NEISSERIA GONORRHOEAE
PROTEUS MIRABILIS
PROTEUS VULGARIS
PROVIDENCIA RETTGERI
PROVIDENCIA STUARTII
PSEUDOMONAS AERUGINOSA
SALMONELLA TYPHI
SERRATIA MARCESCENS
SHIGELLA BOYDII
SHIGELLA DYSENTERIAE
SHIGELLA FLEXNERI
SHIGELLA SONNEI
The following IN VITRO data are available, BUT THEIR CLINICAL SIGNIFICANCE IS
UNKNOWN.
Ciprofloxacin exhibits IN VITRO minimum inhibitory concentrations (MICs) of 1
Mu-g/mL or less against most ((>/=) 90%) strains of the following
microorganisms; however, the safety and effectiveness of ciprofloxacin in
treating clinical infections due to these microorganisms have not been
established in adequate and well- controlled clinical trials.
AEROBIC GRAM-POSITIVE MICROORGANISMS
STAPHYLOCOCCUS HAEMOLYTICUS
STAPHYLOCOCCUS HOMINIS
AEROBIC GRAM-NEGATIVE MICROORGANISMS
ACINETOBACTER IWOFFI
AEROMONAS HYDROPHILA
EDWARDSIELLA TARDA
ENTEROBACTER AEROGENES
KLEBSIELLA OXYTOCA
LEGIONELLA PNEUMOPHILA
PASTERUELLA MULTOCIDA
SALMONELLA ENTERITIDIS
VIBRIO CHOLERAE
VIBRIO PARAHAEMOLYTICUS
VIBRIO VULNIFICUS
YERSINIA ENTEROCOLITICA
Most strains of BURKHOLDERIA CEPACIA and some strains of STENOTROPHOMONAS
MALTOPHILIA are resistant to ciprofloxacin as are most anaerobic bacteria,
including BACTEROIDES FRAGILIS and CLOSTRIDIUM DIFFICILE.
Ciprofloxacin is slightly less active when tested at acidic pH. The inoculum
size has little effect when tested IN VITRO. The minimum bactericidal
concentration (MBC) generally does not exceed the minimum inhibitory
concentration (MIC) by more than a factor of 2. Resistance to ciprofloxacin IN
VITRO usually develops slowly (multiple-step mutation).
Ciprofloxacin does not cross-react with other antimicrobial agents such as beta-
lactams or aminoglycosides; therefore, organisms resistant to these drugs may be
susceptible to ciprofloxacin.
IN VITRO studies have shown that additive activity often results when
ciprofloxacin is combined with other antimicrobial agents such as beta-lactams,
aminoglycosides, clindamycin, or metronidazole. Synergy has been reported
particularly with the combination of ciprofloxacin and a beta-lactam; antagonism
is observed only rarely.
SUSCEPTIBILITY TESTS
DILUTION TECHNIQUES: Quantitative methods are used to determine antimicrobial
minimum inhibitory concentrations (MICs). These MICs provide estimates of the
susceptibility of bacteria to antimicrobial compounds. The MICs should be
determined using a standardized procedure. Standardized procedures are based on
a dilution method (REF. 1) (broth or agar) or equivalent with standardized
inoculum concentrations and standardized concentrations of ciprofloxacin powder.
The MIC values should be interpreted according to the following criteria:
For testing aerobic microorganisms other than HAEMOPHILUS INFLUENZAE,
HAEMOPHILUS PARAINFLUENZAE, and NEISSERIA GONORRHOEAE():
MIC (MU-G/ML) INTERPRETATION
(=) 1 Susceptible (S)
2 Intermediate (I)
(>/=) 4 Resistant (R)
a These interpretive standards are applicable only to broth microdilution
susceptibility tests with streptococci using cation-adjusted Mueller-Hinton
broth with 2-5% lysed horse blood.
For testing HAEMOPHILUS INFLUENZAE and HAEMOPHILUS PARAINFLUENZAE():
MIC (MU-G/ML) INTERPRETATION
(=) 1 Susceptible (S)
b This interpretive standard is applicable only to broth microdilution
susceptibility tests with HAEMOPHILUS INFLUENZAE and HAEMOPHILUS
PARAINFLUENZAE using HAEMOPHILUS Test Medium REF. 1.
The current absence of data on resistant strains precludes defining any results
other than "Susceptible". Strains yielding MIC results suggestive of a
"nonsusceptible" category should be submitted to a reference laboratory for
further testing.
For testing NEISSERIA GONORRHOEAE():
MIC (MU-G/ML) INTERPRETATION
(=) 0.06 Susceptible (S)
c This interpretive standard is applicable only to agar dilution test with GC
agar base and 1% defined growth supplement.
The current absence of data on resistant strains precludes defining any results
other than "Susceptible". Strains yielding MIC results suggestive of a
"nonsusceptible" category should be submitted to a reference laboratory for
further testing.
A report of "Susceptible" indicates that the pathogen is likely to be inhibited
if the antimicrobial compound in the blood reaches the concentrations usually
achievable. A report of "Intermediate" indicates that the result should be
considered equivocal, and, if the microorganism is not fully susceptible to
alternative, clinically feasible drugs, the test should be repeated. This
category implies possible clinical applicability in body sites where the drug is
physiologically concentrated or in situations where high dosage of drug can be
used. This category also provides a buffer zone which prevents small
uncontrolled technical factors from causing major discrepancies in
interpretation. A report of "Resistant" indicates that the pathogen is not
likely to be inhibited if the antimicrobial compound in the blood reaches the
concentrations usually achievable; other therapy should be selected.
Standardized susceptibility test procedures require the use of laboratory
control microorganisms to control the technical aspects of the laboratory
procedures. Standard ciprofloxacin powder should provide the following MIC
values:
ORGANISM MIC (MU-G/ML)
E. FAECALIS ATCC 29212 0.25 - 2.0
E. COLI ATCC 25922 0.004 - 0.015
H. INFLUENZAE(a) ATCC 49247 0.004 - 0.03
N. GONORRHOEAE(b) ATCC 49226 0.001 - 0.008
P. AERUGINOSA ATCC 27853 0.25 - 1.0
S. AUREUS ATCC 29213 0.12 - 0.5
a This quality control range is applicable to only H. INFLUENZAE ATCC 49247
tested by a broth microdilution procedure using HAEMOPHILUS Test Medium
(HTM) (REF. 1).
b This quality control range is applicable to only N. GONORRHOEAE ATCC 49226
tested by an agar dilution procedure using GC agar base and 1% defined
growth supplement.
DIFFUSION TECHNIQUES:
Quantitative methods that require measurement of zone diameters also provide
reproducible estimates of the susceptibility of bacteria to antimicrobial
compounds. One such standardized procedure (REF. 2) requires the use of
standardized inoculum concentrations. This procedure uses paper disks
impregnated with 5-Mu- g ciprofloxacin to test the susceptibility of
microorganisms to ciprofloxacin.
Reports from the laboratory providing results of the standard single-disk
susceptibility test with a 5-Mu-g ciprofloxacin disk should be interpreted
according to the following criteria:
For testing aerobic microorganisms other than HAEMOPHILUS INFLUENZAE,
HAEMOPHILUS PARAINFLUENZAE, and NEISSERIA GONORRHOEAE():
ZONE DIAMETER (MM) INTERPRETATION
(>/=) 21 Susceptible (S)
16-20 Intermediate (I)
(=) 15 Resistant (R)
a These zone diameter standards are applicable only to tests performed for
streptococci using Mueller-Hinton agar supplemented with 5% sheep blood
incubated in 5% CO2.
For testing HAEMOPHILUS INFLUENZAE and HAEMOPHILUS PARAINFLUENZAE(:)
ZONE DIAMETER (MM) INTERPRETATION
(>/=) 21 Susceptible (S)
b This zone diameter standard is applicable only to tests with HAEMOPHILUS
INFLUENZAE and HAEMOPHILUS PARAINFLUENZAE using HAEMOPHILUS Test Medium
(HTM) (REF. 2).
The current absence of data on resistant strains precludes defining any results
other than "Susceptible". Strains yielding zone diameter results suggestive of a
"nonsusceptible" category should be submitted to a reference laboratory for
further testing.
For testing NEISSERIA GONORRHOEAE():
ZONE DIAMETER (MM) INTERPRETATION
(>/=) 36 Susceptible (S)
c This zone diameter standard is applicable only to disk diffusion tests with
GC agar base and 1% defined growth supplement.
The current absence of data on resistant strains precludes defining any results
other than "Susceptible". Strains yielding zone diameter results suggestive of a
"nonsusceptible" category should be submitted to a reference laboratory for
further testing.
Interpretation should be as stated above for results using dilution techniques.
Interpretation involves correlation of the diameter obtained in the disk test
with the MIC for ciprofloxacin.
As with standardized dilution techniques, diffusion methods require the use of
laboratory control microorganisms that are used to control the technical aspects
of the laboratory procedures. For the diffusion technique, the 5-Mu-g
ciprofloxacin disk should provide the following zone diameters in these
laboratory test quality control strains:
ZONE DIAMETER
ORGANISM (MM)
E. COLI ATCC 25922 30-40
H. INFLUENZAE(a) ATCC 49247 34-42
N. GONORRHOEAE(b) ATCC 49226 48-58
P. AERUGINOSA ATCC 27853 25-33
S. AUREUS ATCC 25923 22-30
a These quality control limits are applicable to only H. INFLUENZAE ATCC 49247
testing using HAEMOPHILUS Test Medium (HTM)2.
b These quality control limits are applicable only to tests conducted with N.
GONORRHOEAE ATCC 49226 performed by disk diffusion using GC agar base and 1%
defined growth supplement.
INDICATIONS AND USAGE:
CIPROBID I.V. is indicated for the treatment of infections caused by susceptible
strains of the designated microorganisms in the conditions listed below when the
intravenous administration offers a route of administration advantageous to the
patient. Please see DOSAGE AND ADMINISTRATION for specific recommendations.
URINARY TRACT INFECTIONS caused by ESCHERICHIA COLI (including cases with
secondary bacteremia), KLEBSIELLA PNEUMONIAE subspecies PNEUMONIAE, ENTEROBACTER
CLOACAE, SERRATIA MARCESCENS, PROTEUS MIRABILIS, PROVIDENCIA RETTGERI,
MORGANELLA MORGANII, CITROBACTER DIVERSUS, CITROBACTER FREUNDII, PSEUDOMONAS
AERUGINOSA, STAPHYLOCOCCUS EPIDERMIDIS, STAPHYLOCOCCUS SAPROPHYTICUS, or
ENTEROCOCCUS FAECALIS.
LOWER RESPIRATORY INFECTIONS caused by ESCHERICHIA COLI, KLEBSIELLA PNEUMONIAE
subspecies PNEUMONIAE, ENTEROBACTER CLOACAE, PROTEUS MIRABILIS, PSEUDOMONAS
AERUGINOSA, HAEMOPHILUS INFLUENZAE, HAEMOPHILUS PARAINFLUENZAE, or STREPTOCOCCUS
PNEUMONIAE.
NOTE: Although effective in clinical trials, ciprofloxacin is not a drug of
first choice in the treatment of presumed or confirmed pneumonia secondary to
STREPTOCOCCUS PNEUMONIAE.
NOSOCOMIAL PNEUMONIA caused by HAEMOPHILUS INFLUENZAE or KLEBSIELLA PNEUMONIAE.
SKIN AND SKIN STRUCTURE INFECTIONS caused by ESCHERICHIA COLI, KLEBSIELLA
PNEUMONIAE subspecies PNEUMONIAE, ENTEROBACTER CLOACAE, PROTEUS MIRABILIS,
PROTEUS VULGARIS, PROVIDENCIA STUARTII, MORGANELLA MORGANII, CITROBACTER
FREUNDII, PSEUDOMONAS AERUGINOSA, STAPHYLOCOCCUS AUREUS (methicillin
susceptible), STAPHYLOCOCCUS EPIDERMIDIS, or STREPTOCOCCUS PYOGENES.
BONE AND JOINT INFECTIONS caused by ENTEROBACTER CLOACAE, SERRATIA MARCESCENS,
or PSEUDOMONAS AERUGINOSA.
COMPLICATED INTRA-ABDOMINAL INFECTIONS (used in conjunction with metronidazole)
caused by ESCHERICIA COLI, PSEUDOMONAS AERUGINOSA, PROTEUS MIRABILIS, KLEBSIELLA
PNEUMONIAE, or BACTEROIDES FRAGILIS. (See DOSAGE AND ADMINISTRATION.)
EMPIRICAL THERAPY FOR FEBRILE NEUTROPENIC PATIENTS in combination with
piperacillin sodium. (See DOSAGE AND ADMINISTRATION and CLINICAL STUDIES.)
If anaerobic organisms are suspected of contributing to the infection,
appropriate therapy should be administered.
Appropriate culture and susceptibility tests should be performed before
treatment in order to isolate and identify organisms causing infection and to
determine their susceptibility to ciprofloxacin. Therapy with CIPROBID I.V. may
be initiated before the results of these tests are known; once results become
available, appropriate therapy should be continued.
As with other drugs, some strains of PSEUDOMONAS AERUGINOSA may develop
resistance fairly rapidly during treatment with ciprofloxacin. Culture and
susceptibility testing performed periodically during therapy will provide
information not only on the therapeutic effect of the antimicrobial agent but
also on the possible emergence of bacterial resistance.
CLINICAL STUDIES:
EMPIRICAL THERAPY IN FEBRILE NEUTROPENIC PATIENTS
The safety and efficacy of ciprofloxacin, 400 mg I.V. q 8h, in combination with
piperacillin sodium, 50 mg/kg I.V. q 4h, for the empirical therapy of febrile
neutropenic patients were studied in one large pivotal multicenter, randomized
trial and were compared to those of tobramycin, 2 mg/kg I.V. q 8h, in
combination with piperacillin sodium, 50 mg/kg I.V. q 4h.
The demographics of the evaluable patients were as follows:
TOTAL CIPROFLOXACIN/PIPERACILLIN TOBRAMYCIN/PIPERACILLIN
N = 233 N = 237
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Median Age (years) 47.0 (range 19-84) 50.0 (range 18-81)
Male 114 (48.9%) 117 (49.4%)
Female 119 (51.1%) 120 (50.6%)
Leukemia/Bone
Marrow Transplant 165 (70.8%) 158 (66.7%)
Solid Tumor/Lymphoma 68 (29.2) 79 (33.3%)
Median Duration of
Neutropenia (days) 15.0 (range 1-61) 14.0 (range 1-89)
Clinical response rates observed in this study were as follows:
OUTCOMES CIPROFLOXACIN/PIPERACILLIN TOBRAMYCIN/PIPERACILLIN
N = 233 N = 237
SUCCESS (%) SUCCESS (%)
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Clinical Resolution of
Initial Febrile Episode
with No Modifications of
Empirical Regimen(*) 63 (27.0%) 52 (21.9%)
Clinical Resolution of
Initial Febrile Episode
Including Patients with
Modifications of
Empirical Regimen 187 (80.3%) 185 (78.1%)
Overall Survival 224 (96.1%) 223 (94.1%)
* To be evaluated as a clinical resolution, patients had to have: (1)
resolution of fever; (2) microbiological eradication of infection (if an
infection was microbiologically documented); (3) resolution of signs/symptoms
of infection; and (4) no modification of empirical antibiotic regimen.
CONTRAINDICATIONS:
CIPROBID I.V. (ciprofloxacin) is contraindicated in patients with a history of
hypersensitivity to ciprofloxacin or any member of the quinolone class of
antimicrobial agents.
WARNINGS:
THE SAFETY AND EFFECTIVENESS OF CIPROFLOXACIN IN CHILDREN, ADOLESCENTS (LESS
THAN 18 YEARS OF AGE), PREGNANT WOMEN, AND LACTATING WOMEN HAVE NOT BEEN
ESTABLISHED. (SEE PRECAUTIONS-PEDIATRIC USE, PREGNANCY AND NURSING MOTHERS
SUBSECTIONS.) Ciprofloxacin causes lameness in immature dogs. Histopathological
examination of the weight- bearing joints of these dogs revealed permanent
lesions of the cartilage. Related quinolone-class drugs also produce erosions of
cartilage of weight-bearing joints and other signs of arthropathy in immature
animals of various species. (See ANIMAL PHARMACOLOGY.)
Convulsions, increased intracranial pressure, and toxic psychosis have been
reported in patients receiving quinolones, including ciprofloxacin.
Ciprofloxacin may also cause central nervous system (CNS) events including:
dizziness, confusion, tremors, hallucinations, depression, and, rarely, suicidal
thoughts or acts. These reactions may occur following the first dose. If these
reactions occur in patients receiving ciprofloxacin, the drug should be
discontinued and appropriate measures instituted. As with all quinolones,
ciprofloxacin should be used with caution in patients with known or suspected
CNS disorders that may predispose to seizures or lower the seizure threshold
(e.g. severe cerebral arteriosclerosis, epilepsy), or in the presence of other
risk factors that may predispose to seizures or lower the seizure threshold
(e.g. certain drug therapy, renal dysfunction). (See PRECAUTIONS:
GENERAL,INFORMATION FOR PATIENTS, DRUG INTERACTIONS and ADVERSE REACTIONS.)
SERIOUS AND FATAL REACTIONS HAVE BEEN REPORTED IN PATIENTS RECEIVING CONCURRENT
ADMINISTRATION OF INTRAVENOUS CIPROFLOXACIN AND THEOPHYLLINE. These reactions
have included cardiac arrest, seizure, status epilepticus, and respiratory
failure. Although similar serious adverse events have been reported in patients
receiving theophylline alone, the possibility that these reactions may be
potentiated by ciprofloxacin cannot be eliminated. If concomitant use cannot be
avoided, serum levels of theophylline should be monitored and dosage adjustments
made as appropriate.
Serious and occasionally fatal hypersensitivity (anaphylactic) reactions, some
following the first dose, have been reported in patients receiving quinolone
therapy. Some reactions were accompanied by cardiovascular collapse, loss of
consciousness, tingling, pharyngeal or facial edema, dyspnea, urticaria, and
itching. Only a few patients had a history of hypersensitivity reactions.
Serious anaphylactic reactions require immediate emergency treatment with
epinephrine and other resuscitation measures, including oxygen, intravenous
fluids, intravenous antihistamines, corticosteroids, pressor amines, and airway
management, as clinically indicated.
Severe hypersensitivity reactions characterized by rash, fever, eosinophilia,
jaundice, and hepatic necrosis with fatal outcome have also been reported
extremely rarely in patients receiving ciprofloxacin along with other drugs. The
possibility that these reactions were related to ciprofloxacin cannot be
excluded. Ciprofloxacin should be discontinued at the first appearance of a skin
rash or any other sign of hypersensitivity.
PSEUDOMEMBRANOUS COLITIS HAS BEEN REPORTED WITH NEARLY ALL ANTIBACTERIAL AGENTS,
INCLUDING CIPROFLOXACIN, AND MAY RANGE FROM MILD TO LIFE- THREATENING.
THEREFORE, IT IS IMPORTANT TO CONSIDER THIS DIAGNOSIS IN PATIENTS WHO PRESENT
WITH DIARRHEA SUBSEQUENT TO THE ADMINISTRATION OF ANTIBACTERIAL AGENTS.
Treatment with antibacterial agents alters the normal flora of the colon and may
permit overgrowth of clostridia. Studies indicate that a toxin produced by
CLOSTRIDIUM DIFFICILE is one primary cause of "antibiotic associated colitis".
After the diagnosis of pseudomembranous colitis has been established,
therapeutic measures should be initiated. Mild cases of pseudomembranous colitis
usually respond to 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 C. DIFFICILE colitis.
Achilles and other tendon ruptures that required surgical repair or resulted in
prolonged disability have been reported with ciprofloxacin and other quinolones.
Ciprofloxacin should be discontinued if the patient experiences pain,
inflammation, or rupture of a tendon.
PRECAUTIONS:
GENERAL:
INTRAVENOUS CIPROFLOXACIN SHOULD BE ADMINISTERED BY SLOW INFUSION OVER A PERIOD
OF 60 MINUTES. Local I.V. site reactions have been reported with the intravenous
administration of ciprofloxacin. These reactions are more frequent if infusion
time is 30 minutes or less or if small veins of the hand are used. (See ADVERSE
REACTIONS.)
Quinolones, including ciprofloxacin, may also cause central nervous system (CNS)
events, including nervousness, agitation, insomnia, anxiety, nightmares or
paranoia. (See WARNINGS, INFORMATION FOR PATIENTS and DRUG INTERACTIONS.)
Crystals of ciprofloxacin have been observed rarely in the urine of human
subjects but more frequently in the urine of laboratory animals, which is
usually alkaline. (See ANIMAL PHARMACOLOGY.) Crystalluria related to
ciprofloxacin has been reported only rarely in humans because human urine is
usually acidic. Alkalinity of the urine should be avoided in patients receiving
ciprofloxacin. Patients should be well hydrated to prevent the formation of
highly concentrated urine.
Alteration of the dosage regimen is necessary for patients with impairment of
renal function. (See DOSAGE AND ADMINISTRATION).)
Moderate to severe phototoxicity manifested as an exaggerated sunburn reaction
has been observed in some patients who were exposed to direct sunlight while
receiving some members of the quinolone class of drugs. Excessive sunlight
should be avoided.
As with any potent drug, periodic assessment of organ system functions,
including renal, hepatic, and hematopoietic, is advisable during prolonged
therapy.
INFORMATION FOR PATIENTS:
Patients should be advised that ciprofloxacin may be associated with
hypersensitivity reactions, even following a single dose, and to discontinue the
drug at the first sign of a rash or other allergic reaction.
Ciprofloxacin may cause dizziness and lightheadedness; therefore, patients
should know how they react to this drug before they operate an automobile or
machinery or engage in activities requiring mental alertness or coordination.
Patients should be advised that ciprofloxacin may increase the effect of
theophylline and caffeine. There is a possibility of caffeine accumulation when
products containing caffeine are consumed while taking ciprofloxacin.
Patients should be advised to discontinue treatment; rest and refrain from
exercise; and inform their physician if they experience pain, inflammation, or
rupture of a tendon.
DRUG INTERACTIONS: As with some other quinolones, concurrent administration of
ciprofloxacin with theophylline may lead to elevated serum concentrations of
theophylline and prolongation of its elimination half-life. This may result in
increased risk of theophylline-related reactions. (See WARNINGS.) If concomitant
use cannot be avoided, serum levels of theophylline should be monitored and
dosage adjustments made as appropriate.
Some quinolones, including ciprofloxacin, have also been shown to interfere with
the metabolism of caffeine. This may lead to reduced clearance of caffeine and
prolongation of its serum half- life.
Some quinolones, including ciprofloxacin, have been associated with transient
elevations in serum creatinine in patients receiving cyclosporine concomitantly.
Altered serum levels of phenytoin (increased and decreased) have been reported
in patients receiving concomitant ciprofloxacin.
The concomitant administration of ciprofloxacin with the sulfonylurea glyburide
has, in some patients, resulted in severe hypoglycemia. Fatalities have been
reported.
Quinolones have been reported to enhance the effects of the oral anticoagulant
warfarin or its derivatives. When these products are administered concomitantly,
prothrombin time or other suitable coagulation tests should be closely
monitored.
Probenecid interferes with renal tubular secretion of ciprofloxacin and produces
an increase in the level of ciprofloxacin in the serum. This should be
considered if patients are receiving both drugs concomitantly.
As with other broad-spectrum antimicrobial agents, prolonged use of
ciprofloxacin may result in overgrowth of nonsusceptible organisms. Repeated
evaluation of the patient's condition and microbial susceptibility testing are
essential. If superinfection occurs during therapy, appropriate measures should
be taken.
CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY:
Eight IN VITRO mutagenicity tests have been conducted with ciprofloxacin. Test
results are listed below:
Salmonella/Microsome Test (Negative)
E. COLI DNA Repair Assay (Negative)
Mouse Lymphoma Cell Forward Mutation Assay (Positive)
Chinese Hamster V79 Cell HGPRT Test (Negative)
Syrian Hamster Embryo Cell Transformation Assay (Negative)
SACCHAROMYCES CEREVISIAE Point Mutation Assay (Negative)
SACCHAROMYCES CEREVISIAE Mitotic Crossover and Gene Con version Assay (Negative)
Rat Hepatocyte DNA Repair Assay (Positive)
Thus, two of the eight tests were positive, but results of the following three
IN VIVO test systems gave negative results:
Rat Hepatocyte DNA Repair Assay
Micronucleus Test (Mice)
Dominant Lethal Test (Mice)
Long-term carcinogenicity studies in mice and rats have been completed. After
daily oral doses of 750 mg/kg (mice) and 250 mg/kg (rats) were administered for
up to 2 years, there was no evidence that ciprofloxacin had any carcinogenic or
tumorigenic effects in these species.
Results from photo co-carcinogenicity testing indicate that ciprofloxacin does
not reduce the time to appearance of UV-induced skin tumors as compared to
vehicle control. Hairless (Skh-1) mice were exposed to UVA light for 3.5 hours
five times every two weeks for up to 78 weeks while concurrently being
administered ciprofloxacin. The time to development of the first skin tumors was
50 weeks in mice treated concomitantly with UVA and ciprofloxacin (mouse dose
approximately equal to maximum recommended human dose based upon mg/m(squared)),
as opposed to 34 weeks when animals were treated with both UVA and vehicle. The
times to development of skin tumors ranged from 16-32 weeks in mice treated
concomitantly with UVA and other quinolones.(REF. 3)
In this model, mice treated with ciprofloxacin alone did not develop skin or
systemic tumors. There are no data from similar models using pigmented mice
and/or fully haired mice. The clinical significance of these findings to humans
is unknown.
Fertility studies performed in rats at oral doses of ciprofloxacin up to 100
mg/kg (0.8 times the highest recommended human dose of 1200 mg based upon body
surface area) revealed no evidence of impairment.
PREGNANCY: TERATOGENIC EFFECTS. PREGNANCY CATEGORY C:
Reproduction studies have been performed in rats and mice using oral doses of up
to 100 mg/kg (0.8 and 0.4 times the maximum daily human dose based upon body
surface area, respectively) and I.V. doses of up to 30 mg/kg (0.24 and 0.12
times the maximum daily human dose based upon body surface area, respectively)
and have revealed no evidence of harm to the fetus due to ciprofloxacin. In
rabbits, ciprofloxacin (30 and 100 mg/kg orally) produced gastrointestinal
disturbances resulting in maternal weight loss and an increased incidence of
abortion, but no teratogenicity was observed at either dose. After intravenous
administration of doses up to 20 mg/kg, no maternal toxicity was produced in the
rabbit, and no embryotoxicity or teratogenicity was observed. There are,
however, no adequate and well- controlled studies in pregnant women.
Ciprofloxacin should be used during pregnancy only if the potential benefit
justifies the potential risk to the fetus. (See WARNINGS.)
NURSING MOTHERS:
Ciprofloxacin is excreted in human milk. Because of the potential for serious
adverse reactions in infants nursing from mothers taking ciprofloxacin, a
decision should be made whether to discontinue nursing or to discontinue the
drug, taking into account the importance of the drug to the mother.
PEDIATRIC USE:
Safety and effectiveness in pediatric patients and adolescents less than 18
years of age have not been established. Ciprofloxacin causes arthropathy in
juvenile animals. (See WARNINGS.)
DRUG INTERACTIONS:
DRUG INTERACTIONS: As with some other quinolones, concurrent administration of
ciprofloxacin with theophylline may lead to elevated serum concentrations of
theophylline and prolongation of its elimination half-life. This may result in
increased risk of theophylline-related reactions. (See WARNINGS.) If concomitant
use cannot be avoided, serum levels of theophylline should be monitored and
dosage adjustments made as appropriate.
Some quinolones, including ciprofloxacin, have also been shown to interfere with
the metabolism of caffeine. This may lead to reduced clearance of caffeine and
prolongation of its serum half- life.
Some quinolones, including ciprofloxacin, have been associated with transient
elevations in serum creatinine in patients receiving cyclosporine concomitantly.
Altered serum levels of phenytoin (increased and decreased) have been reported
in patients receiving concomitant ciprofloxacin.
The concomitant administration of ciprofloxacin with the sulfonylurea glyburide
has, in some patients, resulted in severe hypoglycemia. Fatalities have been
reported.
Quinolones have been reported to enhance the effects of the oral anticoagulant
warfarin or its derivatives. When these products are administered concomitantly,
prothrombin time or other suitable coagulation tests should be closely
monitored.
Probenecid interferes with renal tubular secretion of ciprofloxacin and produces
an increase in the level of ciprofloxacin in the serum. This should be
considered if patients are receiving both drugs concomitantly.
As with other broad-spectrum antimicrobial agents, prolonged use of
ciprofloxacin may result in overgrowth of nonsusceptible organisms. Repeated
evaluation of the patient's condition and microbial susceptibility testing are
essential. If superinfection occurs during therapy, appropriate measures should
be taken.
(See also PRECAUTIONS)
ADVERSE REACTIONS:
The most frequently reported events, without regard to drug relationship, among
patients treated with intravenous ciprofloxacin were nausea, diarrhea, central
nervous system disturbance, local I.V. site reactions, abnormalities of liver
associated enzymes (hepatic enzymes), and eosinophilia. Headache, restlessness,
and rash were also noted in greater than 1% of patients treated with the most
common doses of ciprofloxacin.
Local I.V. site reactions have been reported with the intravenous administration
of ciprofloxacin. These reactions are more frequent if the infusion time is 30
minutes or less. These may appear as local skin reactions which resolve rapidly
upon completion of the infusion. Subsequent intravenous administration is not
contraindicated unless the reactions recur or worsen.
Additional events, without regard to drug relationship or route of
administration, that occurred in 1% or less of ciprofloxacin patients are listed
below:
CARDIOVASCULAR: cardiovascular collapse, cardiopulmonary arrest, myocardial
infarction, arrhythmia, tachycardia, palpitation, cerebral thrombosis, syncope,
cardiac murmur, hypertension, hypotension, angina pectoris
CENTRAL NERVOUS SYSTEM: convulsive seizures, paranoia, toxic psychosis,
depression, dysphasia, phobia, depersonalization, manic reaction,
unresponsiveness, ataxia, confusion, hallucinations, dizziness, lightheadedness,
paresthesia, anxiety, tremor, insomnia, nightmares, weakness, drowsiness,
irritability, malaise, lethargy
GASTROINTESTINAL: ileus, jaundice, gastrointestinal bleeding, C. DIFFICILE
associated diarrhea, pseudomembranous colitis, pancreatitis, hepatic necrosis,
intestinal perforation, dyspepsia, epigastric or abdominal pain, vomiting,
constipation, oral ulceration, oral candidiasis, mouth dryness, anorexia,
dysphagia, flatulence
I.V. INFUSION SITE: thrombophlebitis, burning, pain, pruritus, paresthesia,
erythema, swelling
MUSCULOSKELETAL: arthralgia, jaw, arm or back pain, joint stiffness, neck and
chest pain, achiness, flare up of gout
RENAL/UROGENITAL: renal failure, interstitial nephritis, hemorrhagic cystitis,
renal calculi, frequent urination, acidosis, urethral bleeding, polyuria,
urinary retention, gynecomastia, candiduria, vaginitis. Crystalluria,
cylindruria, hematuria, and albuminuria have also been reported.
RESPIRATORY: respiratory arrest, pulmonary embolism, dyspnea, pulmonary edema,
respiratory distress, pleural effusion, hemoptysis, epistaxis, hiccough
SKIN/HYPERSENSITIVITY: anaphylactic reactions, erythema multiforme/Stevens-
Johnson syndrome, exfoliative dermatitis, toxic epidermal necrolysis,
vasculitis, angioedema, edema of the lips, face, neck, conjunctivae, hands or
lower extremities, purpura, fever, chills, flushing, pruritus, urticaria,
cutaneous candidiasis, vesicles, increased perspiration, hyperpigmentation,
erythema nodosum, photosensitivity
Allergic reactions ranging from urticaria to anaphylactic reactions have been
reported. (See WARNINGS.)
SPECIAL SENSES: decreased visual acuity, blurred vision, disturbed vision,
(flashing lights, change in color perception, overbrightness of lights,
diplopia), eye pain, anosmia, hearing loss, tinnitus, nystagmus, a bad taste
Also reported were agranulocytosis, prolongation of prothrombin time, and
possible exacerbation of myasthenia gravis.
Many of these events were described as only mild or moderate in severity, abated
soon after the drug was discontinued, and required no treatment.
In several instances, nausea, vomiting, tremor, irritability, or palpitation
were judged by investigators to be related to elevated serum levels of
theophylline possibly as a result of drug interaction with ciprofloxacin.
randomized, double-blind controlled clinical trials comparing ciprofloxacin
(I.V. and I.V. P.O. sequential) with intravenous beta-lactam control
antibiotics, the CNS adverse event profile of ciprofloxacin was comparable to
that of the control drugs.
POST-MARKETING ADVERSE EVENTS:
Additional adverse events, regardless of relationship to drug, reported from
worldwide marketing experience with quinolones, including ciprofloxacin, are:
BODY AS A WHOLE: change in serum phenytoin
CARDIOVASCULAR: postural hypotension, vasculitis
CENTRAL NERVOUS SYSTEM: agitation, confusion, delirium, dysphasia, myoclonus,
nystagmus, toxic psychosis
GASTROINTESTINAL: constipation, dyspepsia, flatulence, hepatic necrosis,
jaundice, pancreatitis, pseudomembranous colitis (The onset of pseudomembranous
colitis symptoms may occur during or after antimicrobial treatment.)
HEMIC/LYMPHATIC: agranulocytosis, hemolytic anemia, methemoglobinemia,
prolongation of prothrombin time
METABOLIC/NUTRITIONAL: elevation of serum triglycerides, cholesterol, blood
glucose, serum potassium
MUSCULOSKELETAL: myalgia, possible exacerbation of myasthenia gravis,
tendinitis/tendon rupture
RENAL/UROGENITAL: albuminuria, candiduria, renal calculi, vaginal candidiasis
SKIN/HYPERSENSITIVITY: anaphylactic reactions, erythema multiforme/Stevens-
Johnson syndrome, exfoliative dermatitis, toxic epidermal necrolysis
SPECIAL SENSES: anosmia
(See PRECAUTIONS.)
ADVERSE LABORATORY CHANGES:
The most frequently reported changes in laboratory parameters with intravenous
ciprofloxacin therapy, without regard to drug relationship are listed below:
Hepatic-elevations of AST (SGOT), ALT (SGPT), alkaline phosphatase, LDH, and
serum bilirubin;
Hematologic-elevated eosinophil and platelet counts, decreased platelet counts,
hemoglobin and/or hematocrit;
Renal-elevations of serum creatinine, BUN, and uric acid;
Other-elevations of serum creatinine, phosphokinase, serum theophylline (in
patients receiving theophylline concomitantly), blood glucose, and
triglycerides.
Other changes occurring infrequently were: decreased leukocyte count, elevated
atypical lymphocyte count, immature WBCs, elevated serum calcium, elevation of
serum gamma-glutamyl transpeptidase ((gamma) GT), decreased BUN, decreased uric
acid, decreased total serum protein, decreased serum albumin, decreased serum
potassium, elevated serum potassium, elevated serum cholesterol.
Other changes occurring rarely during administration of ciprofloxacin were:
elevation of serum amylase, decrease of blood glucose, pancytopenia,
leukocytosis, elevated sedimentation rate, change in serum phenytoin, decreased
prothrombin time, hemolytic anemia, and bleeding diathesis.
OVERDOSAGE:
In the event of acute overdosage, the patient should be carefully observed and
given supportive treatment. Adequate hydration must be maintained. Only a small
amount of ciprofloxacin (<10%) is removed from the body after hemodialysis or
peritoneal dialysis.
In mice, rats, rabbits and dogs, significant toxicity including tonic/clonic
convulsions was observed at intravenous doses of ciprofloxacin between 125 and
300 mg/kg.
DOSAGE AND ADMINISTRATION:
The recommended adult dosage for urinary tract infections of mild to moderate
severity is 200 mg I.V. every 12 hours. For severe or complicated urinary tract
infections, the recommended dosage is 400 mg I.V. every 12 hours.
The recommended adult dosage for lower respiratory tract infections, skin and
skin structure infections, and bone and joint infections of mild to moderate
severity is 400 mg I.V. every 12 hours.
For severe/complicated infections of the lower respiratory tract, skin and skin
structure, and bone and joint, the recommended adult dosage is 400 mg I.V. every
8 hours.
The recommended adult dosage for mild, moderate, and severe nosocomial pneumonia
is 400 mg I.V. every 8 hours.
COMPLICATED INTRA-ABDOMINAL INFECTIONS: Sequential therapy (parenteral to oral-
400 mg CIPROBID I.V. q 12 h (plus I.V. metronidazole) -> 500 mg CIPROBID Tablets
q 12 h (plus oral metronidazole)) can be instituted at the discretion of the
physician. Metronidazole should be give according to product labeling to provide
appropriate anaerobic coverage.
The recommended adult dosage for empirical therapy of febrile neutropenic
patients is 400 mg I.V. every 8 hours in combination with pipericillin sodium 50
mg/kg I.V. q 4 hours, not to exceed 24 g/day (300 mg/kg/day), for 7-14 days.
The determination of dosage for any particular patient must take into
consideration the severity and nature of the infection, the susceptibility of
the causative microorganism, the integrity of the patient's host-defense
mechanisms and the status of renal and hepatic function.
DOSAGE GUIDELINES
----------------------------------------------
INTRAVENOUS
INFECTION**/* TYPE OR SEVERITY UNIT DOSE FREQUENCY DAILY DOSE
Urinary tract Mild/Moderate 200 mg q12h 400 mg
Severe/Complicated 400 mg q12h 800 mg
Lower Mild/Moderate 400 mg q12h 800 mg
Respiratory Tract Severe/Complicated 400 mg q8h 1200 mg
Nosocomial
Pneumonia Mild/Moderate/Severe 400 mg q8h 1200 mg
Skin and Mild/Moderate 400 mg q12h 800 mg
Skin Structure Severe/Complicated 400 mg q8h 1200 mg
Bone and Joint Mild/Moderate 400 mg q12h 800 mg
Severe/Complicated 400 mg q8h 1200 mg
Intra-Abdominal* Complicated 400 mg q12h 800 mg
Empirical Therapy Severe
in Febrile Ciprofloxacin 400 mg q8h 1200 mg
Neutropenic +
Patients Piperacillin 50 mg/kg q4h Not to exceed
24 g/day
-------------------------------------------------------------------------------------------------------------------------------------------------------------------------
* used in conjunction with metronidazole. (See product labeling for
prescribing information.)
**/* DUE TO THE DESIGNATED PATHOGENS (See INDICATIONS AND USAGE.)
CIPROBID I.V. SHOULD BE ADMINISTERED BY INTRAVENOUS INFUSION OVER A PERIOD OF 60
MINUTES.
Parenteral drug products should be inspected visually for particulate matter and
discoloration prior to administration.
Ciprofloxacin hydrochloride (CIPROBID Tablets) for oral administration are
available. Parenteral therapy may be changed to oral CIPROBID Tablets when the
condition warrants, at the discretion of the physician. For complete dosage and
administration information, see CIPROBID Tablets package insert.
IMPAIRED RENAL FUNCTION: The following table provides dosage guidelines for use
in patients with renal impairment; however, monitoring of serum drug levels
provides the most reliable basis for dosage adjustment.
RECOMMENDED STARTING AND MAINTENANCE DOSES FOR PATIENTS WITH
IMPAIRED RENAL FUNCTION
------------------------------------------------------------------------------------------------------------------------------------------------
CREATININE CLEARANCE
(ML/MIN) DOSAGE
> 30 See usual dosage.
5-29 200-400 mg q 18-24 hr
When only the serum creatinine concentration is known, the following formula may
be used to estimate creatinine clearance:
Men: Creatinine clearance (mL/min) = WEIGHT (KG) x (140 - AGE)
-------------------------
72 x serum creatinine (mg/dL)
Women: 0.85 x the value calculated for men.
The serum creatinine should represent a steady state of renal function.
For patients with changing renal function or for patients with renal impairment
and hepatic insufficiency, measurement of serum concentrations of ciprofloxacin
will provide additional guidance for adjusting dosage.
INTRAVENOUS ADMINISTRATION
CIPROBID I.V. should be administered by intravenous infusion over a period of 60
minutes. Slow infusion of a dilute solution into a large vein will minimize
patient discomfort and reduce the risk of venous irritation.
VIALS (INJECTION CONCENTRATE):
THIS PREPARATION MUST BE DILUTED BEFORE USE. The intravenous dose should be
prepared by aseptically withdrawing the concentrate from the vial of CIPROBID
I.V. This should be diluted with a suitable intravenous solution to a final
concentration of 1-2 mg/mL. (See COMPATIBILITY AND STABILITY.) The resulting
solution should be infused over a period of 60 minutes by direct infusion or
through a Y-type intravenous infusion set which may already be in place.
If this method or the "piggyback" method of administration is used, it is
advisable to discontinue temporarily the administration of any other solutions
during the infusion of CIPROBID I.V.
FLEXIBLE CONTAINERS:
CIPROBID I.V. is also available as a 0.2% premixed solution in 5% dextrose in
flexible containers of 100 mL or 200 mL. The solutions in flexible containers
may be infused as described above.
COMPATIBILITY AND STABILITY
Ciprofloxacin injection 1% (10 mg/mL), when diluted with the following
intravenous solutions to concentrations of 0.5 to 2.0 mg/mL, is stable for up to
14 days at refrigerated or room temperature storage.
0.9% Sodium Chloride Injection, USP
5% Dextrose Injection, USP
Sterile Water for Injection
10% Dextrose for Injection
5% Dextrose and 0.225% Sodium Chloride for Injection
5% Dextrose and 0.45% Sodium Chloride for Injection
Lactated Ringer's for Injection
If CIPROBID I.V. is to be given concomitantly with another drug, each drug
should be given separately in accordance with the recommended dosage and route
of administration for each drug.
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