A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Cipro Indications, Dosage, Storage, Stability - Ciprofloxacin
Cipro Indications, Dosage, Storage, Stability - Ciprofloxacin
INDICATIONS AND USAGE
CIPRO 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.
Urinary Tract Infections caused by Escherichia coli,
Klebsiella 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.
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.
Acute Sinusitis caused by Haemophilus influenzae,
Streptococcus pneumoniae, or Moraxella catarrhalis.
Skin and Skin Structure Infections caused by Escherichia
coli, Klebsiella 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 combination
with metronidazole) caused by Escherichia coli, Pseudomonas aeruginosa,
Proteus mirabilis, Klebsiella pneumoniae, or Bacteroides fragilis.
(See DOSAGE AND ADMINISTRATION.)
Infectious Diarrhea caused by Escherichia coli
(enterotoxigenic 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.
Inhalational anthrax (post-exposure): To reduce the
incidence or progression of disease following exposure to aerosolized Bacillus
anthracis.
Ciprofloxacin serum concentrations achieved in humans serve
as a surrogate endpoint reasonably likely to predict clinical benefit and provide
the basis for this indication.4 (See also, INHALATIONAL
ANTHRAX – ADDITIONAL INFORMATION).
†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 CIPRO 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.
To reduce the development of drug-resistant bacteria and maintain
the effectiveness of CIPRO Tablets and CIPRO Oral Suspension and other antibacterial
drugs, CIPRO Tablets and CIPRO Oral Suspension should be used only to treat
or prevent infections that are proven or strongly suspected to be caused by
susceptible bacteria. When culture and susceptibility information are available,
they should be considered in selecting or modifying antibacterial therapy. In
the absence of such data, local epidemiology and susceptibility patterns may
contribute to the empiric selection of therapy.
DOSAGE AND ADMINISTRATION
CIPRO Tablets and Oral Suspension should be administered orally
as described in the Dosage Guidelines table.
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. The usual duration is 7 to 14 days;
however, for severe and complicated infections more prolonged therapy may be
required. Ciprofloxacin should be administered at least 2 hours before or 6
hours after magnesium/aluminum antacids, or sucralfate, Videx®
(didanosine) chewable/buffered tablets or pediatric powder for oral solution,
or other products containing calcium, iron or zinc.
|
DOSAGE GUIDELINES
|
|
Infection
|
Type or Severity
|
Unit Dose
|
Frequency
|
Usual Durations†
|
|
Urinary Tract
|
Acute Uncomplicated
|
100 mg or 250 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
|
|
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
|
|
Acute Sinusitis
|
Mild/Moderate
|
500 mg
|
q 12 h
|
10 days
|
|
Skin and
|
Mild/Moderate
|
500 mg
|
q 12 h
|
7 to 14 Days
|
|
Skin Structure
|
Severe/Complicated
|
750 mg
|
q 12 h
|
7 to 14 Days
|
|
Bone and Joint
|
Mild/Moderate
|
500 mg
|
q 12 h
|
³ 4 to 6 weeks
|
| |
Severe/Complicated
|
750 mg
|
q 12 h
|
³ 4 to 6 weeks
|
|
Intra-Abdominal*
|
Complicated
|
500 mg
|
q 12 h
|
7 to 14 Days
|
|
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
|
Uncomplicated
|
250 mg
|
single dose
|
single dose
|
|
Gonococcal Infections
|
|
|
|
|
|
Inhalational anthrax (post-exposure)**
|
Adult
|
500 mg
|
q 12 h
|
60 Days
|
| |
Pediatric
|
15 mg/kg per dose, not to exceed 500 mg per dose
|
q 12 h
|
60 Days
|
|
* used in conjunction with metronidazole
|
|
† Generally ciprofloxacin should be continued
for at least 2 days after the signs and symptoms of infection have disappeared,
except for inhalational anthrax (post-exposure).
|
|
** Drug administration should begin as soon as possible
after suspected or confirmed exposure.
|
This indication is based on a surrogate endpoint, ciprofloxacin
serum concentrations achieved in humans, reasonably likely to predict clinical
benefit.4 For a discussion of ciprofloxacin serum concentrations
in various human populations, see INHALATIONAL ANTHRAX – ADDITIONAL
INFORMATION.
Patients whose therapy is started with CIPRO I.V. may be switched
to CIPRO Tablets or Oral Suspension when clinically indicated at the discretion
of the physician (See CLINICAL
PHARMACOLOGY and table below for the equivalent dosing regimens).
Equivalent AUC Dosing Regimens
|
Cipro Oral Dosage
|
Equivalent Cipro I.V. Dosage
|
|
250 mg Tablet q 12 h
|
200 mg I.V. q 12 h
|
|
500 mg Tablet q 12 h
|
400 mg I.V. q 12 h
|
|
750 mg Tablet q 12 h
|
400 mg I.V. q 8 h
|
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
alternative 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.
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)
|
Dose
|
|
> 50
|
See Usual Dosage.
|
|
30 – 50
|
250 – 500 mg q 12 h
|
|
5 – 29
|
250 – 500 mg q 18 h
|
|
Patients on hemodialysis or 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) 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.
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 mg/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.
HOW SUPPLIED
CIPRO (ciprofloxacin hydrochloride) 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. CIPRO 250 mg, 500 mg, and 750 mg are available in bottles of 50, 100,
and Unit Dose packages of 100. The 100 mg strength is available only as CIPRO
Cystitis pack containing 6 tablets for use only in female patients with acute
uncomplicated cystitis.
| |
Strength
|
NDC Code
|
Tablet Identification
|
|
Bottles of 50:
|
750 mg
|
NDC 0026-8514-50
|
CIPRO 750
|
|
Bottles of 100:
|
250 mg
|
NDC 0026-8512-51
|
CIPRO 250
|
| |
500 mg
|
NDC 0026-8513-51
|
CIPRO 500
|
|
Unit Dose
|
|
|
|
|
Package of 100:
|
250 mg
|
NDC 0026-8512-48
|
CIPRO 250
|
| |
500 mg
|
NDC 0026-8513-48
|
CIPRO 500
|
| |
750 mg
|
NDC 0026-8514-48
|
CIPRO 750
|
|
Cystitis
|
|
|
|
|
Package of 6:
|
100 mg
|
NDC 0026-8511-06
|
CIPRO 100
|
|
Store below 30°C (86°F).
|
CIPRO Oral Suspension is supplied in 5% and 10% strengths.
The drug product is composed of two components (microcapsules containing the
active ingredient and diluent) which must be mixed by the pharmacist. See Instructions
To The Pharmacist For Use/Handling.
| |
Total volume
|
Ciprofloxacin
|
Ciprofloxacin
|
|
|
Strengths
|
after reconstitution
|
Concentration
|
contents per bottle
|
NDC Code
|
|
5%
|
100 mL
|
250 mg/5 mL
|
5,000 mg
|
0026-8551-36
|
|
10%
|
100 mL
|
500 mg/5 mL
|
10,000 mg
|
0026-8553-36
|
Microcapsules and diluent should be stored below 25°C (77°F)
and protected from freezing.
Reconstituted product may be stored below 30°C (86°F) for 14
days. Protect from freezing.
A teaspoon is provided for the patient.
ANIMAL PHARMACOLOGY
Ciprofloxacin and other quinolones have been shown to cause
arthropathy in immature animals of most species tested. (See WARNINGS.)
Damage of weight bearing joints was observed in juvenile dogs and rats. In young
beagles, 100 mg/kg ciprofloxacin, given daily for 4 weeks, caused degenerative
articular changes of the knee joint. At 30 mg/kg, the effect on the joint was
minimal. In a subsequent study in beagles, removal of weight bearing from the
joint reduced the lesions but did not totally prevent them.
Crystalluria, sometimes associated with secondary nephropathy,
occurs in laboratory animals dosed with ciprofloxacin. This is primarily related
to the reduced solubility of ciprofloxacin under alkaline conditions, which
predominate in the urine of test animals; in man, crystalluria is rare since
human urine is typically acidic. In rhesus monkeys, crystalluria without nephropathy
has been noted after single oral doses as low as 5 mg/kg. After 6 months of
intravenous dosing at 10 mg/kg/day, no nephropathological changes were noted;
however, nephropathy was observed after dosing at 20 mg/kg/day for the same
duration.
In dogs, ciprofloxacin at 3 and 10 mg/kg by rapid I.V. injection
(15 sec.) produces pronounced hypotensive effects. These effects are considered
to be related to histamine release, since they are partially antagonized by
pyrilamine, an antihistamine. In rhesus monkeys, rapid I.V. injection also produces
hypotension but the effect in this species is inconsistent and less pronounced.
In mice, concomitant administration of nonsteroidal anti-inflammatory drugs
such as phenylbutazone and indomethacin with quinolones has been reported to
enhance the CNS stimulatory effect of quinolones.
Ocular toxicity seen with some related drugs has not been observed
in ciprofloxacin-treated animals.
CLINICAL STUDIES
Uncomplicated Cystitis
Two double-blind, controlled clinical studies of acute uncomplicated
cystitis in women were performed in the U.S. At the 5-9 day post-therapy follow-up
visit, the clinical resolution rates in the first study, which compared ciprofloxacin
100 mg BID for 3 days to ciprofloxacin 250 mg BID for 7 days, were 87% (82/94)
and 94%, (81/86), respectively. For E. coli, the bacteriological eradication
rates for the first study were 91% (64/70) in the ciprofloxacin 100 mg regimen
and 97% (67/69) in the ciprofloxacin 250 mg regimen. The second study’s bacteriological
eradication rates were 95% (117/123) for the ciprofloxacin 100 mg regimen and
98% (103/105) for the control regimen. Pooled eradication rates for the ciprofloxacin
100 mg treatment arms were 100% (16/16) for S. saprophyticus.
INHALATIONAL ANTHRAX – ADDITIONAL INFORMATION
The mean serum concentrations of ciprofloxacin associated with
a statistically significant improvement in survival in the rhesus monkey model
of inhalational anthrax are reached or exceeded in adult and pediatric patients
receiving oral and intravenous regimens. (See DOSAGE
AND ADMINISTRATION.) Ciprofloxacin pharmacokinetics have been evaluated
in various human populations. The mean peak serum concentration achieved at
steady-state in human adults receiving 500 mg orally every 12 hours is 2.97
mg/mL, and 4.56 mg/mL
following 400 mg intravenously every 12 hours. The mean trough serum concentration
at steady-state for both of these regimens is 0.2 mg/mL.
In a study of 10 pediatric patients between 6 and 16 years of age, the mean
peak plasma concentration achieved is 8.3 mg/mL and
trough concentrations range from 0.09 to 0.26 mg/mL,
following two 30-minute intravenous infusions of 10 mg/kg administered 12 hours
apart. After the second intravenous infusion patients switched to 15 mg/kg orally
every 12 hours achieve a mean peak concentration of 3.6 mg/mL
after the initial oral dose. Long-term safety data, including effects on cartilage,
following the administration of ciprofloxacin to pediatric patients are limited.
(For additional information, see PRECAUTIONS,
Pediatric Use.) Ciprofloxacin serum concentrations achieved in humans serve
as a surrogate endpoint reasonably likely to predict clinical benefit and provide
the basis for this indication.4
A placebo-controlled animal study in rhesus monkeys exposed
to an inhaled mean dose of 11 LD50 (~5.5 x 105 spores
(range 5-30 LD50) of B. anthracis was conducted.
The minimal inhibitory concentration (MIC) of ciprofloxacin for the anthrax
strain used in this study was 0.08 mg/mL. In the
animals studied, mean serum concentrations of ciprofloxacin achieved at expected
Tmax (1 hour post-dose) following oral dosing to steady-state ranged
from 0.98 to 1.69 mg/mL. Mean steady-state trough
concentrations at 12 hours post-dose ranged from 0.12 to 0.19 mg/mL5.
Mortality due to anthrax for animals that received a 30-day regimen of oral
ciprofloxacin beginning 24 hours post-exposure was significantly lower (1/9),
compared to the placebo group (9/10) [p= 0.001]. The one ciprofloxacin-treated
animal that died of anthrax did so following the 30-day drug administration
period.6
Instructions To The Pharmacist For Use/Handling Of 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 must be combined
prior to dispensing.
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.
Appropriate Dosing Volumes of the Oral Suspensions:
|
Dose
|
5%
|
10%
|
|
250 mg
|
5 mL
|
2.5
|
mL
|
|
500 mg
|
10 mL
|
5
|
mL
|
|
750 mg
|
15 mL
|
7.5
|
mL
|
CIPRO Oral Suspension should not be administered through feeding
tubes due to its physical characteristics.
Instruct the patient to shake CIPRO Oral Suspension vigorously
each time before use for approximately 15 seconds and not to chew the microcapsules.
References:
1. National Committee for Clinical Laboratory Standards,
Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow
Aerobically-Fifth Edition. Approved Standard NCCLS Document M7-A5, Vol. 20,
No. 2, NCCLS, Wayne, PA, January, 2000. 2. National Committee for Clinical
Laboratory Standards, Performance Standards for Antimicrobial Disk Susceptibility
Tests-Seventh Edition. Approved Standard NCCLS Document M2-A7, Vol. 20, No.
1, NCCLS, Wayne, PA, January, 2000. 3. Report presented at the FDA’s
Anti-Infective Drug and Dermatological Drug Product’s 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. 4. 21 CFR 314.510 (Subpart H –Accelerated Approval of New
Drugs for Life-Threatening Illnesses). 5. Kelly DJ, et al. Serum concentrations
of penicillin, doxycycline, and ciprofloxacin during prolonged therapy in rhesus
monkeys. J Infect Dis 1992; 166:1184-7. 6. Friedlander AM, et al. Postexposure
prophylaxis against experimental inhalational anthrax. J Infect Dis 1993; 167:1239-42.
7. Friedman J, Polifka J. Teratogenic effects of drugs: a resource for
clinicians (TERIS). Baltimore, Maryland: Johns Hopkins University Press, 2000:149-195.
8. Loebstein R, Addis A, Ho E, et al. Pregnancy outcome following gestational
exposure to fluoroquinolones: a multicenter prospective controlled study. Antimicrob
Agents Chemother. 1998;42(6):1336-1339. 9. Schaefer C, Amoura-Elefant
E, Vial T, et al. Pregnancy outcome after prenatal quinolone exposure. Evaluation
of a case registry of the European network of teratology information services
(ENTIS). Eur J Obstet Gynecol Reprod Biol. 1996;69:83-89.
400 Morgan Lane, West Haven, CT 06516, 08753744,
R.2 1/04 Bay o 9867 5202-2-A-U.S.-15 12237 ©2004 Bayer Pharmaceuticals
Corporation Printed in U.S.A., CIPRO (ciprofloxacin*) 5% and 10% Oral Suspension
Made in Italy. CIPRO (ciprofloxacin HCl) Tablets Made in U.S.A. and Germany
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