INDICATIONS
Oral
Ciprofloxacin is indicated for the treatment of infections
caused by susceptible strains of the designated microorganisms
in the conditions listed below. Please see DOSAGE AND
ADMINISTRATION for specific recommendations.
Acute Sinusitis: Caused by Haemophilus
influenzae, Streptococcus pneumoniae or Moraxella catarrhalis.
Lower Respiratory Tract Infections: Caused
by Escherichia coli, Klebsiella pneumoniae, Enterobacter
cloacae, Proteus mirabilis, Pseudomonas aeruginosa, Haemophilus
influenzae, Haemophilus parainfluenzae, or Streptococcus
pneumoniae. Also, Moraxella catarrhalis for the treatment
of acute exacerbations of chronic bronchitis.
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.
Urinary Tract Infections: Caused by
Escherichia coli, Kiebsiella pneumoniae, Enterobacter
cloacae, Serratia marcescens, Proteus mirabilis, Providencia
rettgeri, Morganella morganii, Citrobacter diversus, Citrobacter
freundii, Pseudomonas aeruginosa, Staphylococcus epidermidis,
Staphylococcus saprophyticus, or Enterococcus faecalis.
Acute Uncomplicated Cystitis in Females:
Caused by Escherichia coli or Staphylococcus saprophyticus.
(See
DOSAGE AND ADMINISTRATION
.)
Chronic Bacterial Prostatitis: Caused
by Escherichia coli or Proteus mirabilis.
Complicated Intra-Abdominal Infection:
(Used in combination with metronidazole) caused by Escherchia
coli, Pseudomonas aeruginosa, Proteus mirabilis, Klebsiella
pneumoniae, or Bacteroides fragilis. (See
DOSAGE AND ADMINISTRATION
.)
Skin and Skin Structure Infections:
Caused by Escherchia coli, Kiebsiella 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.
Infectious Diarrhea: Caused by Escherichia
coli (entarotoxigenic strains), Campylobacter jejuni,
Shigella boydii*, Shigella dysenteriae, Shigella flexneri
or Shigella sonnei* when antibacterial therapy is indicated.
Typhoid Fever (Enteric Fever): Caused
by Salmonella typhi.
NOTE: The efficacy of ciprofloxacin in the eradication
of the chronic typhoid carrier state has not been demonstrated.
Uncomplicated Cervical and Urethral Gonorrhea: Due to
Neisseria gonorrhoeae.
*Although treatment of infections due to this organism
in this organ system demonstrated a clinically significant
outcome, efficacy was studied in fewer than 10 patients.
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 ciprofloxacin may be initiated
before 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.
I.V.
Ciprofloxacin 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 Escherichia
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 ciprofloxacin I.V. may
be initiated before 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.
DOSAGE AND ADMINISTRATION
Oral
The recommended adult dosage for acute sinusitis is 500-mg
every 12 hours.
Lower respiratory tract infections may be treated with
500-mg every 12 hours. For more severe or complicated
infections, a dosage of 750-mg may be given every 12 hours.
Severe/complicated urinary tract infections or urinary
tract infections caused by organisms not highly susceptible
to ciprofloxacin may be treated with 500-mg every 12 hours.
For other mild/moderate urinary infections, the usual
adult dosage is 250-mg every 12 hours.
In acute uncomplicated cystitis in females, the usual
dosage is 100-mg every 12 hours. For acute uncomplicated
cystitis in females, 3 days of treatment is recommended
while 7 to 14 days is suggested for other mild/moderate,
severe or complicated urinary tract infections.
The recommended adult dosage for chronic bacterial prostatitis
is 500-mg every 12 hours.
The recommended adult dosage for oral sequential therapy
of complicated intra-abdominal infections is 500-mg every
12 hours. (To provide appropriate anaerobic activity,
metronidazole should be given according to product labeling.)
Skin and skin structure infections and bone and joint
infections may be treated with 500-mg every 12 hours.
For more severe or complicated infections, a dosage of
750-mg may be given every 12 hours.
The recommended adult dosage for infectious diarrhea
or typhoid lever is 500-mg every 12 hours. For the treatment
of uncomplicated urethral and cervical gonococcal infections,
a single 250-mg dose is recommended.
See PATIENT PACKAGE INSERT.
TABLE 16 Dosage Guidelines
|
| Infection |
Type or Severity |
Unit Dose |
Frequency |
Usual Durations* |
| Acute Sinusitis |
Mild/Moderate |
500-mg |
q 12 h |
10 Days |
| Lower Respiratory
Tract |
Mild/Moderate |
500-mg |
q 12 h |
7 to 14 Days |
| |
Severe/Complicated |
750-mg |
q 12 h |
7 to 14 Days |
| Urinary Tract |
Acute Uncomplicated |
100-mg |
q 12 h |
3 Days |
| |
Mild/Moderate |
250-mg |
q 12 h |
7 to 14 Days |
| |
Severe/Complicated |
500-mg |
q 12 h |
7 to 14 Days |
| Chronic Bacterial
Prostatitis |
Mild/Moderate |
500-mg |
q 12 h |
28 Days |
| Intra-Abdominal† |
Complicated |
500-mg |
q 12 h |
7 to 14 Days |
| Skin and Skin Structure |
Mild/Moderate |
500-mg |
q 12 h |
"7 to 14 Days |
| |
Severe/Complicated |
750-mg |
q 12 h |
7 to 14 Days |
| Bone and Joint |
Mild/Moderate |
500-mg |
q 12 h |
³4
to 6 weeks |
| |
Severe/Complicated |
750-mg |
q 12 h |
³4
to 6 weeks |
| Infectious Diarrhea |
Mild/Moderate/Severe |
500-mg |
q 12 h |
5 to 7 Days |
| Typhoid Fever |
Mild/Moderate |
500-mg |
q 12 h |
10 Days |
| Urethral and Cervical
Gonococcal Infections |
Uncomplicated |
250-mg |
single dose |
single dose |
| * Generally
ciprofloxacin should be continued for at least 2
days after the signs and symptoms of infection have
disappeared. |
| † Used
in conjunction with metronidazole. |
One teaspoonful (5 ml) of 5% ciprofloxacin oral suspension
= 250-mg of ciprofloxacin.
One teaspoonful (5 ml) of 10% ciprofloxacin oral suspension
= 500-mg of ciprofloxacin.
See PATIENT PACKAGE INSERT.
TABLE 17
|
| |
Volume (ml) of Oral Suspension |
| Dosage |
5% |
10% |
| 250-mg |
5 ml |
2.5 ml |
| 500-mg |
10 ml |
5 ml |
| 750-mg |
15 ml |
7.5 ml |
Complicated Intra-Abdominal Infections: Sequential therapy
[parenteral to oral¾ 400-mg ciprofloxacin q 12
h (plus IV metronidazole)“ 500-mg ciprofloxacin
HCl tablets q 12 h (plus oral metronidazole)] can be instituted
at the discretion of the physician.
The determination of dosage for any particular patient
must take into consideration the severity and nature of
the infection, the susceptibility of the causative organism,
the integrity of the patient's host-defense mechanisms,
and the status of renal function and hepatic function.
The duration of treatment depends upon the severity of
infection. Generally ciprofloxacin should be continued
for at least 2 days after the signs and symptoms of infection
have disappeared. The usual duration is 7 to 14 days;
however, for severe and complicated infections more prolonged
therapy may be required. Bone and joint infections may
require treatment for 4 to 6 weeks or longer. Chronic
Bacterial Prostatitis should be treated for 28 days. Infectious
diarrhea may be treated for 5-7 days. Typhoid fever should
be treated for 10 days.
Concurrent Use With Antacids or Multivalent Cations:
Concurrent administration of ciprofloxacin with sucrafrate
or divalent and trivalent cations such as iron or antacids
containing magnesium, aluminum or calcium may substantially
interfere with the absorption of ciprofloxacin, resulting
in serum and urine levels considerably lower than desired.
Therefore, concurrent administration of these agents with
ciprofloxacin should be avoided. However, usual dietary
intake of calcium has not been shown to alter the bioavailability
of ciprofloxacin. Single dose bioavailability studies
have shown that antacids may be administered either 2
hours after or 6 hours before ciprofloxacin dosing without
a significant decrease in bioavailability. Histamine H2-receptor
antagonists appear to have no significant effect on the
bioavailability of ciprofloxacin.
Impaired Renal Function: Ciprofloxacin
is eliminated primarily by renal excretion; however, the
drug is also metabolized and partially cleared through
the biliary system of the liver and through the intestine.
These alternate pathways of drug elimination appear to
compensate for the reduced renal excretion in patients
with renal impairment. Nonetheless, some modification
of dosage is recommended, particularly for patients with
severe renal dysfunction. TABLE 18 provides dosage guidelines
for use in patients with renal impairment; however, monitoring
of serum drug levels provides the most reliable basis
for dosage adjustment.
TABLE 18 Recommended Starting and Maintenance Doses for
Patients With Impaired Renal Function
|
| Creatinine Clearance
(ml/min) |
Dose |
| >50 |
See usual dosage. |
| 30-50 |
250-500 mg q 12 h |
| 5-29 |
250-500 mg q 18 h |
| Patients on hemodialysis
of Peritoneal dialysis |
250-500 mg q 24 h (after
dialysis) |
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) ´ (140-age)] ¸ [72 ´ serum creatinine
(mg/dl)]
Women: 0.85 ´ the value calculated
for men.
The serum creatinine should represent a steady state
of renal function.
In patients with severe infections and severe renal impairment,
a unit dose of 750-mg may be administered at the intervals
noted above; however, patients should be carefully monitored
and the serum ciprofloxacin concentration should be measured
periodically. Peak concentrations (1-2 hours after dosing)
should generally range from 2 to 4 mcg/ml.
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.
I.V.
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 ciprofloxacin I.V. q 12 h
(plus I.V. metronidazole) “ 500 mg ciprofloxacin
HCl Tablets q 12 h (plus oral metronidazole)] can be instituted
at the discretion of the physician. Metronidazole should
be given 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 piperacillin 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.
TABLE 19 Dosage Guidelines Intravenous
|
Infection*
|
Type of Severity |
Unit Dose |
Frequency |
Daily Dose |
| Urinary tract |
Mild/Moderate |
200 mg |
q12h |
400 mg |
| |
Severe/Complicated |
400 mg |
q12h |
800 mg |
| Lower Respiratory
Tract |
Mild/Moderate |
400 mg |
q12h |
800 mg |
| |
Severe/Complicated |
400 mg |
q8h |
1200 mg |
| Nosocomial Pneumonia |
Mild/Moderate/Severe |
400 mg |
q8h |
1200 mg |
| Skin and Skin Structure |
Mild/Moderate |
400 mg |
q12h |
800 mg |
| |
Severe/Complicated |
400 mg |
q 8h |
1200 mg |
| Bone and Joint |
Mild/Moderate |
400 mg |
q12h |
800 mg |
| |
Severe/Complicated |
400 mg |
q 8h |
1200 mg |
| Intra-Abdominal† |
Complicated |
400 mg |
q12h |
800 mg |
| Empirical Therapy
in Febrile Neutropenic Patients |
Severe Ciprofloxacin |
400 mg |
q 8h |
1200 mg |
| |
Piperacillin |
50 mg/kg |
q 4h |
Not to exceed 24 g/day |
* Due
to the designated pathogens. (See
INDICATIONS
AND USAGE.) |
| † Used
in conjunction with metronidazole. (See product
labeling for prescribing information.) |
Ciprofloxacin 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 HCl tablets for oral administration are
available. Parenteral therapy may be changed to oral ciprofloxacin
HCl tablets when the condition warrants, at the discretion
of the physician.
Impaired Renal Function: TABLE 20 provides
dosage guidelines for use in patients with renal impairment;
however, monitoring of serum drug levels provides the
most reliable oasis for dosage adjustment.
TABLE 20 Recommended Starting and Maintenance Doses for
Patients With Impaired Renal Function
|
| Creatinine Clearance
(ml/min) |
Dosage |
| >30 |
See usual dosage |
| 5-20 |
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) ´ (140-age)] ¸ [72 ´ serum
creatinine (mg/dl)]
Women: 0.85 ´ 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
Ciprofloxacin 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 ciprofloxacin I.V. This should be diluted
with a suitable intravenous solution to a final concentration
of 1-2 mg/ml. (See Compatability 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 ciprofloxacin I.V.
Flexible Containers: Ciprofloxacin 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.
5% dextrose injection.
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 ciprofloxacin 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.
HOW SUPPLIED
Oral
Cipro Tablets: Cipro tablets are available
as round, slightly yellowish film-coated tablets containing
100-mg or 250-mg ciprofloxacin. The 100-mg tablet is coded
with the word “CIPRO” on one side and “100”
on the reverse side. The 250-mg tablet is coded with the
word “CIPRO” on one side and “250”
on the reverse side. Cipro is also available as capsule
shaped, slightly yellowish film-coated tablets containing
500-mg or 750-mg ciprofloxacin. The 500-mg tablet is coded
with the word “CIPRO” on one side and “500”
on the reverse side. The 750-mg tablet is coded with the
word “CIPRO” on one side and “750”
on the reverse side.
Storage: Store below 30°C (86°F).
Cipro Oral Suspension: Cipro oral suspension
is supplied in 5% (5 g ciprofloxacin in 100 ml) and 10%
(10 g ciprofloxacin in 100 ml) strengths. The drug product
is composed of two components (microcapsules and diluent)
which are mixed prior to dispensing. (See PATIENT PACKAGE
INSERT.)
TABLE 21
|
| Total volume after reconstitution |
Ciprofloxacin contents
after reconstitution |
Ciprofloxacin contents
per bottle |
| 100 ml |
250 mg/5 ml |
5000 mg |
| 100 ml |
500 mg/5 ml |
10,000 mg |
Storage: Microcapsules and diluent should
be stored below 25°C (77°F) and protected from
freezing.
Storage: Reconstituted product may be
stored below 30°C (86°F). Protect from freezing.
A teaspoon is provided for the patient.
I.V.
Cipro I.V. is available as a clear, colorless to slightly
yellowish solution. Cipro I.V. is available in 200 mg
and 400 mg strengths. The concentrate is supplied in vials
while the premixed solution is supplied in flexible containers.
Storage
Vials: Store between 5°-30°C
(41°-86°F).
Flexible Container: Store between 5°-25°C
(47°-77°F).
Protect from light, avoid excessive heat, protect from
freezing.
Ciprofloxacin is also available as Cipro tablets 100,
250, 500, and 750 mg.
PRODUCT LISTING
| Solution
- Intravenous - 10 mg/ml |
| 20 ml x 10 |
Cipro I.V., Bayer
|
00026-8562-20
|
| 40 ml x 10 |
Cipro I.V., Bayer
|
00026-8564-64
|
| 120 ml x 6 |
Cipro I.V., Bayer
|
00026-8566-65
|
| Solution
- Intravenous - 200 mg/100 ml |
| 100 ml x 24 |
Cipro I.V., Bayer
|
00026-8552-36
|
| Solution
- Intravenous - 400 mg/200 ml |
| 200 ml x 24 |
Cipro I.V., Bayer
|
00026-8554-63
|
| Solution
- Ophthalmic - 0.3% |
| 2 ml |
Ciloxan, Alcon
|
00065-0656-25
|
| 5 ml |
Ciloxan, Alcon
|
00065-0656-05
|
| Tablet
- Oral - 100 mg |
| 6's |
Cipro, Bayer
|
00026-8511-06
|
| Tablet
- Oral - 250 mg |
| 100's |
Cipro, Bayer
|
00026-8512-51
|
| Tablet
- Oral - 500 mg |
| 100's |
Cipro, Bayer
|
00026-8513-51
|
| Tablet
- Oral - 750 mg |
| 50's |
Cipro, Bayer
|
00026-8514-50
|
REFERENCES
1. National Committee for Clinical Laboratory Standards,
Methods for Dilution Antimicrobial Susceptibility Tests
for Bacteria That Grow Aerobically-Fourth Edition. Approved
Standard NCCLS M7 , Vol. 17, No. 2, NCCLS, Wayne, PA,
January, 1997.
2. National Committee for Clinical Laboratory Standards,
Performance Standards for Antimicrobial Disk Susceptibility
Tests-Sixth Edition. Approved Standard NCCLS Document
M2-A6, Vol. 17, No. 1, NCCLS, Wayne, PA, January, 1997.
3. Report presented at the FDA's Anti-Infective Drug
and Dermalogical Drug Products Advisory Committee meeting,
March 31, 1993, Silver Spring, MD, Report available from
FDA, CDER, Advisors and Consultants Staff, HFD-21, 1901
Chapman Avenue, Room 200, Rockville, MD 20852, USA.
| |
