ciprofloxacin tablet, film coated Lake Erie Medical DBA Quality Care Products LLC
Ciprofloxacin 500 mgDESCRIPTIONCiprofloxacin Tablets, USP is a synthetic broad spectrum antimicrobial agent for
oral administration. Ciprofloxacin hydrochloride, USP, a fluoroquinolone, is the
monohydrochloride monohydrate salt of
acid. It is a faintly yellowish to light yellow crystalline substance with a
empirical weight of 385.8. Its molecular formula is C17H18FN3O3•HCl•H2O and its chemical structure is
Ciprofloxacin film-coated tablets are available in 250 mg, 500 mg, and 750 mg
(ciprofloxacin equivalent) strengths. Ciprofloxacin tablets are white to
slightly yellowish. The inactive ingredients are colloidal silicon dioxide, corn
starch, hydrogenated vegetable oil, hypromellose, magnesium stearate,
microcrystalline cellulose, polyacrylate dispersion (methylacrylate and
ethylacrylate copolymer), polyethylene glycol, purified water, simethicone
emulsion, sodium starch glycolate, talc, and titanium dioxide.
CLINICAL PHARMACOLOGY AbsorptionCiprofloxacin given as an oral tablet
is rapidly and well absorbed from the gastrointestinal tract after oral
administration. The absolute bioavailability is approximately 70% with no
substantial loss by first pass metabolism. Ciprofloxacin maximum serum
concentrations and area under the curve are shown in the chart for the 250 mg to
1000 mg dose range.
Maximum serum concentrations are attained 1 to 2 hours after oral dosing. Mean
concentrations 12 hours after dosing with 250, 500, or 750 mg are 0.1, 0.2, and
0.4 mcg/mL, respectively. The serum elimination half-life in subjects with
normal renal function is approximately 4 hours. Serum concentrations increase
proportionately with doses up to 1000 mg.
A 500 mg oral dose given every 12 hours has been shown to produce an area under
the serum concentration time curve (AUC) equivalent to that produced by an
intravenous infusion of 400 mg ciprofloxacin given over 60 minutes every 12
hours. A 750 mg oral dose given every 12 hours has been shown to produce an AUC
at steady-state equivalent to that produced by an intravenous infusion of 400 mg
given over 60 minutes every 8 hours. A 750 mg oral dose results in a Cmax similar to that observed with a 400 mg I.V. dose. A 250 mg
oral dose given every 12 hours produces an AUC equivalent to that produced by an
infusion of 200 mg ciprofloxacin given every 12 hours.
DistributionThe binding of ciprofloxacin to
serum proteins is 20 to 40% which is not likely to be high enough to cause
significant protein binding interactions with other drugs.
After oral administration, ciprofloxacin is widely distributed throughout the
body. Tissue concentrations often exceed serum concentrations in both men and
women, particularly in genital tissue including the prostate. Ciprofloxacin is
present in active form in the saliva, nasal and bronchial secretions, mucosa of
the sinuses, sputum, skin blister fluid, lymph, peritoneal fluid, bile, and
prostatic secretions. Ciprofloxacin has also been detected in lung, skin, fat,
muscle, cartilage, and bone. The drug diffuses into the cerebrospinal fluid
(CSF); however, CSF concentrations are generally less than 10% of peak serum
concentrations. Low levels of the drug have been detected in the aqueous and
vitreous humors of the eye.
MetabolismFour metabolites have been identified
in human urine which together account for approximately 15% of an oral dose. The
metabolites have antimicrobial activity, but are less active than unchanged
ciprofloxacin. Ciprofloxacin is an inhibitor of human cytochrome P450 1A2
(CYP1A2) mediated metabolism. Coadministration of ciprofloxacin with other drugs
primarily metabolized by CYP1A2 results in increased plasma concentrations of
these drugs and could lead to clinically significant adverse events of the
coadministered drug (see CONTRAINDICATIONS; WARNINGS;
ExcretionThe serum elimination half-life in
subjects with normal renal function is approximately 4 hours. Approximately 40
to 50% of an orally administered dose is excreted in the urine as unchanged
drug. After a 250 mg oral dose, urine concentrations of ciprofloxacin usually
exceed 200 μg/mL during the first two hours and are approximately 30 μg/mL at 8
to 12 hours after dosing. The urinary excretion of ciprofloxacin is virtually
complete within 24 hours after dosing. The renal clearance of ciprofloxacin,
which is approximately 300 mL/minute, exceeds the normal glomerular filtration
rate of 120 mL/minute. Thus, active tubular secretion would seem to play a
significant role in its elimination. 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 several fold higher than serum
concentrations after oral dosing, only a small amount of the dose administered
is recovered from the bile as unchanged drug. An additional 1 to 2% of the dose
is recovered from the bile in the form of metabolites. Approximately 20 to 35%
of an oral dose is recovered from the feces within 5 days after dosing. This may
arise from either biliary clearance or transintestinal elimination
Drug-drug InteractionsWhen Ciprofloxacin Tablet
is given concomitantly with food, there is a delay in the absorption of the
drug, resulting in peak concentrations that occur closer to 2 hours after dosing
rather than 1 hour. The overall absorption of Ciprofloxacin Tablet, however, is
not substantially affected. Concurrent administration of antacids containing
magnesium hydroxide or aluminum hydroxide may reduce the bioavailability of
ciprofloxacin by as much as 90%. (See PRECAUTIONS.)
The serum concentrations of ciprofloxacin and metronidazole were not altered
when these two drugs were given concomitantly.
Concomitant administration with tizanidine is contraindicated (See CONTRAINDICATIONS).
Concomitant administration of ciprofloxacin with theophylline decreases the
clearance of theophylline resulting in elevated serum theophylline levels and
increased risk of a patient developing CNS or other adverse reactions.
Ciprofloxacin also decreases caffeine clearance and inhibits the formation of
paraxanthine after caffeine administration. (See WARNINGS: PRECAUTIONS.)
INDICATIONS AND USAGECiprofloxacin Tablets,
USP are indicated for the treatment of infections caused by susceptible strains
of the designated microorganisms in the conditions and patient populations
listed below. Please see DOSAGE AND
ADMINISTRATION for specific recommendations.Adult PatientsUrinary Tract
Infections caused by Escherichia coli, Klebsiella
pneumoniae, Enterobacter cloacae, Serratia marcescens, Proteus mirabilis,
Providencia rettgeri, Morganella morganii, Citrobacter diversus, Citrobacter
freundii, Pseudomonas aeruginosa, methicillin-susceptible Staphylococcus epidermidis, Staphylococcus saprophyticus,
or Enterococcus faecalis.
Acute Uncomplicated Cystitis in females caused by Escherichia coli or Staphylococcus
Chronic Bacterial Prostatitis
caused by Escherichia coli or Proteus mirabilis.
Respiratory Tract Infections caused by Escherichia
coli, Klebsiella pneumoniae, Enterobacter cloacae, Proteus mirabilis,
Pseudomonas aeruginosa, Haemophilus influenzae, Haemophilus parainfluenzae,
or penicillin-susceptible 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
Acute Sinusitis caused by
Haemophilus influenzae, penicillin-susceptible Streptococcus pneumoniae, or Moraxella
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.
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.
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.Pediatric patients (1 to 17 years of age)Complicated Urinary Tract Infections and Pyelonephritis due to
NOTE: Although effective in
clinical trials, ciprofloxacin is not a drug of first choice in the pediatric
population due to an increased incidence of adverse events compared to controls,
including events related to joints and/or surrounding tissues. (See WARNINGS, PRECAUTIONS, Pediatric
REACTIONS and CLINICAL STUDIES.)
Ciprofloxacin, like other fluoroquinolones, is associated with arthropathy and
histopathological changes in weight-bearing joints of juvenile animals. (See
PHARMACOLOGY.) Adult and Pediatric PatientsInhalational anthrax (post-exposure): To reduce the incidence
or progression of disease following exposure to aerosolized Bacillus anthracis.
concentrations achieved in humans served as a surrogate endpoint reasonably
likely to predict clinical benefit and provided the initial basis for approval
of this indication.5 Supportive clinical information for
ciprofloxacin for anthrax post-exposure prophylaxis was obtained during the
anthrax bioterror attacks of October 2001. (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 Ciprofloxacin
Tablets 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
Ciprofloxacin Tablets and other antibacterial drugs, Ciprofloxacin Tablets
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.CONTRAINDICATIONSCiprofloxacin is
contraindicated in persons with a history of hypersensitivity to ciprofloxacin,
any member of the quinolone class of antimicrobial agents, or any of the product
Fluoroquinolones, including Ciprofloxacin Tablets, are associated
with an increased risk of tendinitis and tendon rupture in all ages. This
adverse reaction most frequently involves the Achilles tendon, and rupture of
the Achilles tendon may require surgical repair. Tendinitis and tendon rupture
in the rotater cuff (the shoulder), the hand, the biceps, the thumb, and other
tendon sites have also been reported. The risk of developing
fluoroquinolone-associated tendinitis and tendon rupture is further increased in
older patients usually over 60 years of age, in patients taking corticosteroid
drugs, and in patients with kidney, heart or lung transplants. Factors, in
addition to age and corticosteroid use, that may independently increase the risk
of tendon rupture include strenuous physical activity, renal failure, and
previous tendon disorders such as rheumatoid arthritis. Tendinitis and tendon
rupture have also occurred in patients taking fluoroquinolones who do not have
the above risk factors. Tendon rupture can occur during or after completion of
therapy; cases occurring up to several months after completion of therapy have
been reported. Ciprofloxacin Tablets should be discontinued if the patient
experiences pain, swelling, inflammation or rupture of a tendon. Patients should
be advised to rest at the first sign of tendinitis or tendon rupture, and to
contact their healthcare provider regarding changing to a non-quinolone
Pregnant WomenTHE SAFETY AND
EFFECTIVENESS OF CIPROFLOXACIN IN PREGNANT AND LACTATING WOMEN HAVE NOT BEEN
ESTABLISHED. (See PRECAUTIONS: Pregnancy,
and Nursing Mothers
subsections.)PediatricsCiprofloxacin should be used in
pediatric patients (less than 18 years of age) only for infections listed in the
USAGE section. An increased incidence of adverse events compared to
controls, including events related to joints and/or surrounding tissues, has
been observed. (See ADVERSE
In pre-clinical studies, oral administration of
ciprofloxacin caused 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.)Cytochrome P450 (CYP450)Ciprofloxacin is an
inhibitor of the hepatic CYP1A2 enzyme pathway. Coadministration of
ciprofloxacin and other drugs primarily metabolized by CYP1A2 (e.g.,
theophylline, methylxanthines, tizanidine) results in increased plasma
concentrations of the coadministered drug and could lead to clinically
significant pharmacodynamic side effects of the coadministered drug.Central Nervous System DisordersConvulsions,
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,
Interactions and ADVERSE
REACTIONS.)TheophyllineSERIOUS AND FATAL
REACTIONS HAVE BEEN REPORTED IN PATIENTS RECEIVING CONCURRENT ADMINISTRATION OF
CIPROFLOXACIN AND THEOPHYLLINE. These reactions have included cardiac
arrest, seizure, status epilepticus, and respiratory failure. Although similar
serious adverse effects 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.Hypersensitivity ReactionsSerious 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. Oxygen,
intravenous steroids, and airway management, including intubation, should be
administered as indicated.
Other serious and sometimes fatal events,
some due to hypersensitivity, and some due to uncertain etiology, have been
reported rarely in patients receiving therapy with quinolones, including
ciprofloxacin. These events may be severe and generally occur following the
administration of multiple doses. Clinical manifestations may include one or
more of the following:
fever, rash, or severe dermatologic reactions (e.g., toxic epidermal
necrolysis, Stevens-Johnson syndrome);
vasculitis; arthralgia; myalgia; serum sickness;
interstitial nephritis; acute renal insufficiency or failure;
hepatitis; jaundice; acute hepatic necrosis or failure;
anemia, including hemolytic and aplastic; thrombocytopenia, including
thrombotic thrombocytopenic purpura; leukopenia; agranulocytosis; pancytopenia;
and/or other hematologic abnormalities.
Clostridium difficile associated
diarrhea (CDAD) has been reported with use of nearly all antibacterial agents,
including Ciprofloxacin Tablets, and may range in severity from mild diarrhea to
fatal colitis. Treatment with antibacterial agents alters the normal flora of
the colon leading to overgrowth of C. difficile .
C. difficile produces toxins A and B which
contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as
these infections can be refractory to antimicrobial therapy and may require
colectomy. CDAD must be considered in all patients who present with diarrhea
following antibiotic use. Careful medical history is necessary since CDAD has
been reported to occur over two months after the administration of antibacterial
If CDAD is suspected or confirmed, ongoing antibiotic use not directed
against C. difficile may need to be discontinued.
Appropriate fluid and electrolyte management, protein supplementation,
antibiotic treatment of C. difficile, and surgical
evaluation should be instituted as clinically indicated.
Peripheral NeuropathyRare cases of sensory or
sensorimotor axonal polyneuropathy affecting small and/or large axons resulting
in paresthesias, hypoesthesias, dysesthesias and weakness have been reported in
patients receiving quinolones, including ciprofloxacin. Ciprofloxacin should be
discontinued if the patient experiences symptoms of neuropathy including pain,
burning, tingling, numbness, and/or weakness, or is found to have deficits in
light touch, pain, temperature, position sense, vibratory sensation, and/or
motor strength in order to prevent the development of an irreversible
condition.SyphilisCiprofloxacin has not been shown to be
effective in the treatment of syphilis. Antimicrobial agents used in high dose
for short periods of time to treat gonorrhea may mask or delay the symptoms of
incubating syphilis. All patients with gonorrhea should have a serologic test
for syphilis at the time of diagnosis. Patients treated with ciprofloxacin
should have a follow-up serologic test for syphilis after three monthsPRECAUTIONS GeneralCrystals 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
Alteration of the dosage regimen is necessary for patients with impairment of
renal function. (See DOSAGE AND
Moderate to severe photosensitivity/phototoxicity reactions, the latter of which
may manifest as exaggerated sunburn reactions (e.g., burning, erythema,
exudation, vesicles, blistering, edema) involving areas exposed to light
(typically the face, “V” area of the neck, extensor surfaces of the forearms,
dorsa of the hands), can be associated with the use of quinolones after sun or
UV light exposure. Therefore, excessive exposure to these sources of light
should be avoided. Drug therapy should be discontinued if phototoxicity occurs
REACTIONS/Post-Marketing Adverse Events).
As with any potent drug, periodic assessment of organ system functions,
including renal, hepatic, and hematopoietic function, is advisable during
Prescribing Ciprofloxacin Tablets in the absence of a proven or strongly
suspected bacterial infection or a prophylactic indication is unlikely to
provide benefit to the patient and increases the risk of the development of
drug-resistant bacteria. ADVERSE REACTIONSAdverse Reactions in Adult PatientsDuring
clinical investigations with oral and parenteral ciprofloxacin, 49,038 patients
received courses of the drug. Most of the adverse events reported were described
as only mild or moderate in severity, abated soon after the drug was
discontinued, and required no treatment. Ciprofloxacin was discontinued because
of an adverse event in 1% of orally treated patients.
The most frequently
reported drug related events, from clinical trials of all formulations, all
dosages, all drug-therapy durations, and for all indications of ciprofloxacin
therapy were nausea (2.5%), diarrhea (1.6%), liver function tests abnormal
(1.3%), vomiting (1%), and rash (1%).
Additional medically important
events that occurred in less than 1% of ciprofloxacin patients are listed
BODY AS A WHOLE: headache, abdominal pain/discomfort, foot pain,
pain, pain in extremities, injection side reaction (ciprofloxacin
SKIN/HYPERSENSITIVITY: allergic reaction, pruritus,
urticaria, photosensitivity/phototoxicity reaction, flushing, fever, chills,
angioedema, edema of the face, neck, lips, conjunctivae or hands, cutaneous
candidiasis, hyperpigmentation, erythema nodosum, sweating
SENSES: blurred vision, disturbed vision (change in color perception,
overbrightness of lights), decreased visual acuity, diplopia, eye pain,
tinnitus, hearing loss, bad taste, chromatopsia
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.
double-blind controlled clinical trials comparing ciprofloxacin tablets (500 mg
BID) to cefuroxime axetil (250 mg - 500 mg BID) and to clarithromycin (500 mg
BID) in patients with respiratory tract infections, ciprofloxacin demonstrated a
CNS adverse event profile comparable to the control drugs.Adverse Reactions in Pediatric Patients
Ciprofloxacin, administered I.V. and/or orally, was compared to a
cephalosporin for treatment of complicated urinary tract infections (cUTI) or
pyelonephritis in pediatric patients 1 to 17 years of age (mean age of 6 ± 4
years). The trial was conducted in the U.S., Canada, Argentina, Peru, Costa
Rica, Mexico, South Africa, and Germany. The duration of therapy was 10 to 21
days (mean duration of treatment was 11 days with a range of 1 to 88 days). The
primary objective of the study was to assess musculoskeletal and neurological
safety within 6 weeks of therapy and through one year of follow-up in the 335
ciprofloxacin- and 349 comparator-treated patients enrolled.
Independent Pediatric Safety Committee (IPSC) reviewed all cases of
musculoskeletal adverse events as well as all patients with an abnormal gait or
abnormal joint exam (baseline or treatment-emergent). These events were
evaluated in a comprehensive fashion and included such conditions as arthralgia,
abnormal gait, abnormal joint exam, joint sprains, leg pain, back pain,
arthrosis, bone pain, pain, myalgia, arm pain, and decreased range of motion in
The affected joints included: knee, elbow, ankle, hip, wrist, and shoulder.
Within 6 weeks of treatment initiation, the rates of these events were 9.3%
(31/335) in the ciprofloxacin-treated group versus 6% (21/349) in
comparator-treated patients. The majority of these events were mild or moderate
in intensity. All musculoskeletal events occurring by 6 weeks resolved (clinical
resolution of signs and symptoms), usually within 30 days of end of treatment.
Radiological evaluations were not routinely used to confirm resolution of the
events. The events occurred more frequently in ciprofloxacin-treated patients
than control patients, regardless of whether they received I.V. or oral therapy.
Ciprofloxacin-treated patients were more likely to report more than one event
and on more than one occasion compared to control patients. These events
occurred in all age groups and the rates were consistently higher in the
ciprofloxacin group compared to the control group. At the end of 1 year, the
rate of these events reported at any time during that period was 13.7% (46/335)
in the ciprofloxacin-treated group versus 9.5% (33/349) comparator-treated
An adolescent female discontinued ciprofloxacin for wrist pain
that developed during treatment. An MRI performed 4 weeks later showed a tear in
the right ulnar fibrocartilage. A diagnosis of overuse syndrome secondary to
sports activity was made, but a contribution from ciprofloxacin cannot be
excluded. The patient recovered by 4 months without surgical intervention
The incidence rates of neurological events within 6 weeks of treatment
initiation were 3% (9/335) in the ciprofloxacin group versus 2% (7/349) in the
comparator group and included dizziness, nervousness, insomnia, and
In this trial, the overall incidence rates of adverse events
regardless of relationship to study drug and within 6 weeks of treatment
initiation were 41% (138/335) in the ciprofloxacin group versus 31% (109/349) in
the comparator group. The most frequent events were gastrointestinal: 15%
(50/335) of ciprofloxacin patients compared to 9% (31/349) of comparator
patients. Serious adverse events were seen in 7.5% (25/335) of
ciprofloxacin-treated patients compared to 5.7% (20/349) of control patients.
Discontinuation of drug due to an adverse event was observed in 3% (10/335) of
ciprofloxacin-treated patients versus 1.4% (5/349) of comparator patients. Other
adverse events that occurred in at least 1% of ciprofloxacin patients were
diarrhea 4.8%, vomiting 4.8%, abdominal pain 3.3%, accidental injury 3%,
rhinitis 3%, dyspepsia 2.7%, nausea 2.7%, fever 2.1%, asthma 1.8% and rash
In addition to the events reported in pediatric patients in
clinical trials, it should be expected that events reported in adults during
clinical trials or post-marketing experience may also occur in pediatric
patients.Post-Marketing Adverse Event ReportThe following
adverse events have been reported from worldwide marketing experience with
quinolones, including ciprofloxacin. Because these events are reported
voluntarily from a population of uncertain size, it is not always possible to
reliably estimate their frequency or establish a causal relationship to drug
exposure. Decisions to include these events in labeling are typically based on
one or more of the following factors: (1) seriousness of the event, (2)
frequency of the reporting, or (3) strength of causal connection to the
events were also reported by persons who received ciprofloxacin for anthrax
post-exposure prophylaxis following the anthrax bioterror attacks of October
2001. (See also INHALATIONAL ANTHRAX –
ADDITIONAL INFORMATION.)Adverse Laboratory Changes
Changes in laboratory parameters listed as adverse events without
regard to drug relationship are listed below:
Elevations of ALT (SGPT) (1.9%), AST (SGOT) (1.7%), alkaline phosphatase (0.8%),
LDH (0.4%), serum bilirubin (0.3%).
Renal – Elevations
of serum creatinine (1.1%), BUN (0.9%), CRYSTALLURIA, CYLINDRURIA, AND
HEMATURIA HAVE BEEN REPORTED.
Other changes occurring in less than 0.1%
of courses were: elevation of serum gammaglutamyl transferase, elevation of
serum amylase, reduction in blood glucose, elevated uric acid, decrease in
hemoglobin, anemia, bleeding diathesis, increase in blood monocytes,
To report SUSPECTED ADVERSE EVENTS, contact West-ward Pharmaceutical Corp. at
1-877-233-2001 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
OVERDOSAGEIn the event of acute overdosage,
reversible renal toxicity has been reported in some cases. The stomach should be
emptied by inducing vomiting or by gastric lavage. The patient should be
carefully observed and given supportive treatment, including monitoring of renal
function and administration of magnesium, aluminum, or calcium containing
antacids which can reduce the absorption of ciprofloxacin. Adequate hydration
must be maintained. Only a small amount of ciprofloxacin (less than 10%) is removed
from the body after hemodialysis or peritoneal dialysis.
Single doses of
ciprofloxacin were relatively non-toxic via the oral route of administration in
mice, rats, and dogs. No deaths occurred within a 14-day post treatment
observation period at the highest oral doses tested; up to 5000 mg/kg in either
rodent species, or up to 2500 mg/kg in the dog. Clinical signs observed included
hypoactivity and cyanosis in both rodent species and severe vomiting in dogs. In
rabbits, significant mortality was seen at doses of ciprofloxacin greater than 2500
mg/kg. Mortality was delayed in these animals, occurring 10 to 14 days after
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 ADMINISTRATIONDOSAGE AND ADMINISTRATION - ADULTSCiprofloxacin
Tablets should be administered orally to adults as described in the Dosage
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
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,
other highly buffered drugs, or other products containing calcium, iron or zincAdults with 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 impairmentWhen only the serum creatinine concentration is known, the following formula may
be used to estimate creatinine
Weight (kg) x (140 - age) Men: Creatinine clearance
(mL/min) = 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. Patients should be carefully monitored.DOSAGE AND ADMINISTRATION -
PEDIATRICSCiprofloxacin Tablets should be administered orally as described
in the Dosage Guidelines table. An increased incidence of adverse events
compared to controls, including events related to joints and/or surrounding
tissues, has been observed. (See ADVERSE REACTIONS
Dosing and initial route of therapy (i.e., I.V. or
oral) for complicated urinary tract infection or pyelonephritis should be
determined by the severity of the infection. In the clinical trial, pediatric
patients with moderate to severe infection were initiated on 6 to 10 mg/kg I.V.
every 8 hours and allowed to switch to oral therapy (10 to 20 mg/kg every 12
hours), at the discretion of the physicianHOW SUPPLIED
Ciprofloxacin Tablets USP,are available
as white, round, film-coated tablets containing 250 mg ciprofloxacin. The 250 mg
tablet is coded with "WW927" on one side.
Ciprofloxacin Tablets, USP area also available as white, capsule shaped,
film-coated tablets containing 500 mg or 750 mg ciprofloxacin. The 500 mg tablet
is coded with "WW928" on one side. The 750 mg tablet is coded with "WW929" on
one side. Ciprofloxacin Tablets, USP 250 mg and 500 mg are available in bottles
of 30's, 100's and 500's.
Ciprofloxacin Tablets, USP 750 mg are available in bottles of 50's and 100's
and Unit Dose Boxes of 100 tablets.
Strength Tablet Identification
Bottles of 30's: 250
mg WW927 500
mg WW928 Bottles of
mg WW929 Bottles of
mg WW927 500
mg WW928 750
mg WW929 Bottles of
mg WW927 500
mg WW928 Unit Dose Boxes of
mg WW927 500
mg WW928 750
Information for PatientsPatients should be
to contact their healthcare provider if they experience pain, swelling, or
inflammation of a tendon, or weakness or inability to use one of their joints;
rest and refrain from exercise; and discontinue Ciprofloxacin Tablets treatment.
The risk of severe tendon disorder with fluoroquinolones is higher in older
patients usually over 60 years of age, in patients taking corticosteroid drugs,
and in patients with kidney, heart or lung transplants.
that antibacterial drugs including Ciprofloxacin Tablets should only be used
to treat bacterial infections. They do not treat viral infections (e.g., the
common cold). When Ciprofloxacin Tablets are prescribed to treat a bacterial
infection, patients should be told that although it is common to feel better
early in the course of therapy, the medication should be taken exactly as
directed. Skipping doses or not completing the full course of therapy may (1)
decrease the effectiveness of the immediate treatment and (2) increase the
likelihood that bacteria will develop resistance and will not be treatable by
Ciprofloxacin Tablets or other antibacterial drugs in the future.
that ciprofloxacin may be taken with or without meals and to drink fluids
liberally. As with other quinolones, concurrent administration of ciprofloxacin
with magnesium/aluminum antacids, or sucralfate, Videx®
(didanosine) chewable/buffered tablets or pediatric powder, other highly
buffered drugs, or with other products containing calcium, iron or zinc should
be avoided. Ciprofloxacin may be taken two hours before or six hours after
taking these products. Ciprofloxacin should not be taken with dairy products
(like milk or yogurt) or calcium-fortified juices alone since absorption of
ciprofloxacin may be significantly reduced; however, ciprofloxacin may be taken
with a meal that contains these products.
that ciprofloxacin may be associated with hypersensitivity reactions, even
following a single dose, and to discontinue the drug at the first sign of a skin
rash or other allergic reaction.
that photosensitivity/phototoxicity has been reported in patients receiving
quinolones. Patients should minimize or avoid exposure to natural or artificial
sunlight (tanning beds or UVA/B treatment) while taking quinolones. If patients
need to be outdoors while using quinolones, they should wear loose-fitting
clothes that protect skin from sun exposure and discuss other sun protection
measures with their physician. If a sunburn-like reaction or skin eruption
occurs, patients should contact their physician.
that peripheral neuropathies have been associated with ciprofloxacin use. If
symptoms of peripheral neuropathy including pain, burning, tingling, numbness
and/or weakness develop, they should discontinue treatment and contact their
that 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
that ciprofloxacin increases the effects of tizanidine (Zanaflex®). Patients should not use ciprofloxacin if they are already
that ciprofloxacin may increase the effects of theophylline and caffeine.
There is a possibility of caffeine accumulation when products containing
caffeine are consumed while taking quinolones.
that convulsions have been reported in patients receiving quinolones,
including ciprofloxacin, and to notify their physician before taking this drug
if there is a history of this condition.
that ciprofloxacin has been associated with an increased rate of adverse
events involving joints and surrounding tissue structures (like tendons) in
pediatric patients (less than 18 years of age). Parents should inform their
child’s physician if the child has a history of joint-related problems before
taking this drug. Parents of pediatric patients should also notify their child’s
physician of any joint-related problems that occur during or following
ciprofloxacin therapy. (See WARNINGS, PRECAUTIONS, Pediatric
Use and ADVERSE
that diarrhea is a common problem caused by antibiotics which usually ends
when the antibiotic is discontinued. Sometimes after starting treatment with
antibiotics, patients can develop watery and bloody stools (with or without
stomach cramps and fever) even as late as two or more months after having taken
the last dose of the antibiotic. If this occurs, patients should contact their
physician as soon as possible.
Ciprofloxacin Tablets, are associated with an increased risk of tendinitis and
tendon rupture in all ages. This risk is further increased in older patients
usually over 60 years of age, in patients taking corticosteroid drugs, and in
patients with kidney, heart or lung transplants (See WARNINGS).
CIPROFLOXACIN - ciprofloxacin tablet, film coated West-ward
MEDICATION GUIDECiprofloxacin Tablets, USP
Read the Medication Guide that comes with Ciprofloxacin Tablets before you start
taking it and each time you get a refill. There may be new information. This
Medication Guide does not take the place of talking to your healthcare provider
about your medical condition or your treatment.
What is the most important information I should know about Ciprofloxacin
Tablets?Ciprofloxacin Tablets belong to a class of antibiotics called
fluoroquinolones. Ciprofloxacin Tablets can cause side effects that may be
serious or even cause death. If you get any of the following serious side
effects, get medical help right away. Talk with your healthcare provider about
whether you should continue to take Ciprofloxacin Tablets.
Tendon rupture or swelling of the tendon
Tendons are tough cords of tissue that connect muscles to bones.
Pain, swelling, tears, and inflammation of tendons including the back of the
ankle (Achilles), shoulder, hand, or other tendon sites can happen in people of
all ages who take fluoroquinolone antibiotics, including Ciprofloxacin Tablets.
The risk of getting tendon problems is higher if you:
are over 60 years of age
are taking steroids (corticosteroids)
have had a kidney, heart, or lung transplant. Swelling of the tendon
(tendinitis) and tendon rupture (breakage) have also happened in patients who
take fluoroquinolones who do not have the above risk factors.
Other reasons for tendon ruptures can include:
physical activity or exercise
tendon problems in the past, such as in people with rheumatoid arthritis
Call your healthcare provider right away at the first sign of tendon pain,
swelling or inflammation. Stop taking Ciprofloxacin Tablets until tendinitis or
tendon rupture has been ruled out by your healthcare provider. Avoid exercise
and using the affected area. The most common area of pain and swelling is the
Achilles tendon at the back of your ankle. This can also happen with other
tendons. Talk to your healthcare provider about the risk of tendon rupture with
continued use of Ciprofloxacin Tablets. You may need a different antibiotic that
is not a fluoroquinolone to treat your infection.
Tendon rupture can happen while you are taking or after you have finished
taking Ciprofloxacin Tablets. Tendon ruptures have happened up to several months
after patients have finished taking their fluoroquinolone.
Get medical help right away if you get any of the following signs or
symptoms of a tendon rupture:
What are Ciprofloxacin Tablets?Ciprofloxacin Tablets are a
fluoroquinolone antibiotic medicine used to treat certain infections caused by
certain germs called bacteria.
Children less than 18 years of age have a
higher chance of getting bone, joint, or tendon (musculoskeletal) problems such
as pain or swelling while taking Ciprofloxacin Tablets. Ciprofloxacin Tablets
should not be used as the first choice of antibiotic medicine in children under
18 years of age. Ciprofloxacin Tablets should not be used in children under 18
years old, except to treat specific serious infections, such as complicated
urinary tract infections and to prevent anthrax disease after breathing the
anthrax bacteria germ (inhalational exposure).
Sometimes infections are
caused by viruses rather than by bacteria. Examples include viral infections in
the sinuses and lungs, such as the common cold or flu. Antibiotics, including
Ciprofloxacin Tablets, do not kill viruses.
Call your healthcare provider if you think your condition is not
getting better while you are taking Ciprofloxacin Tablets.
Who should not take Ciprofloxacin Tablets?
Do not take Ciprofloxacin Tablets if you:
have ever had a severe allergic reaction to an antibiotic known as a
fluoroquinolone, or are allergic to any of the ingredients in Ciprofloxacin
Tablets. Ask your healthcare provider if you are not sure. See the list of
ingredients in Ciprofloxacin Tablets at the end of this Medication Guide.
also take a medicine called tizanidine (Zanaflex®).
Serious side effects from tizanidine are likely to happen.
What should I tell my healthcare provider before taking Ciprofloxacin
Tell your healthcare provider about all your medical
conditions, including if you:
have tendon problems
have central nervous system problems (such as epilepsy)
have nerve problems
have or anyone in your family has an irregular heartbeat, especially a
condition called “QT prolongation”
have a history of seizures
have kidney problems. You may need a lower dose of Ciprofloxacin Tablets if
your kidneys do not work well.
have rheumatoid arthritis (RA) or other history of joint problems
have trouble swallowing pills
are pregnant or planning to become pregnant. It is not known if
ciprofloxacin tablets will harm your unborn child.
are breast-feeding or planning to breast-feed. Ciprofloxacin passes into
breast milk. You and your healthcare provider should decide whether you will
take Ciprofloxacin Tablets or breast-feed.
Tell your healthcare provider about all the medicines you
take, including prescription and non-prescription medicines, vitamins and
herbal and dietary supplements. Ciprofloxacin Tablets and other medicines can
affect each other causing side effects. Especially tell your healthcare provider
if you take:
an NSAID (Non-Steroidal Anti-Inflammatory Drug). Many common medicines for
pain relief are NSAIDs. Taking an NSAID while you take Ciprofloxacin Tablets or
other fluoroquinolones may increase your risk of central nervous system effects
and seizures. See “What are the possible side
effects of Ciprofloxacin Tablets?”
Certain medicines may keep Ciprofloxacin Tablets from working correctly.
Take Ciprofloxacin Tablets either 2 hours before or 6 hours after taking these
an antacid, multivitamin, or other product that has magnesium, calcium,
aluminum, iron, or zinc
didanosine (Videx®, Videx®
Ask your healthcare provider if you are not sure if any of your medicines are
Know the medicines you take. Keep a list of your medicines and show it to
your healthcare provider and pharmacist when you get a new medicine.
How should I take Ciprofloxacin Tablets?
Take Ciprofloxacin Tablets exactly as prescribed by your healthcare
Take Ciprofloxacin Tablets in the morning and evening at about the same time
each day. Swallow the tablet whole. Do not split, crush or chew the tablet. Tell
your healthcare provider if you can not swallow the tablet whole.
Ciprofloxacin Tablets can be taken with or without food.
Ciprofloxacin Tablets should not be taken with dairy products (like milk or
yogurt) or calcium-fortified juices alone, but may be taken with a meal that
contains these products.
Drink plenty of fluids while taking Ciprofloxacin Tablets.
Do not skip any doses, or stop taking Ciprofloxacin Tablets even if you
begin to feel better, until you finish your prescribed treatment, unless:
help make sure that all of the bacteria are killed and lower the chance that the
bacteria will become resistant to Ciprofloxacin Tablets. If this happens,
ciprofloxacin tablets and other antibiotic medicines may not work in the future.
If you miss a dose of Ciprofloxacin Tablets, take it as soon as you
remember. Do not take two doses at the same time, and do not take more than two
doses in one day.
If you take too much, call your healthcare provider or get medical help
If you have been prescribed Ciprofloxacin
Tablets after being exposed to anthrax:
Ciprofloxacin Tablets have been approved to lessen the chance of getting
anthrax disease or worsening of the disease after you are exposed to the anthrax
Take Ciprofloxacin Tablets exactly as prescribed by your healthcare
provider. Do not stop taking Ciprofloxacin Tablets without talking with your
healthcare provider. If you stop taking ciprofloxacin tablets too soon, it may
not keep you from getting the anthrax disease.
Side effects may happen while you are taking Ciprofloxacin Tablets. When
taking your Ciprofloxacin Tablets to prevent anthrax infection, you and your
healthcare provider should talk about whether the risks of stopping
Ciprofloxacin Tablets too soon are more important than the risks of side effects
with Ciprofloxacin Tablets.
If you are pregnant, or plan to become pregnant while taking Ciprofloxacin
Tablets, you and your healthcare provider should decide whether the benefits of
taking Ciprofloxacin Tablets for anthrax are more important than the risks.
What should I avoid while taking Ciprofloxacin Tablets?
Ciprofloxacin Tablets can make you feel dizzy and lightheaded. Do not drive,
operate machinery, or do other activities that require mental alertness or
coordination until you know how Ciprofloxacin Tablets affect you.
Avoid sunlamps, tanning beds, and try to limit your time in the sun.
Ciprofloxacin Tablets can make your skin sensitive to the sun (photosensitivity)
and the light from sunlamps and tanning beds. You could get severe sunburn,
blisters or swelling of your skin. If you get any of these symptoms while taking
Ciprofloxacin Tablets, call your healthcare provider right away. You should use
a sunscreen and wear a hat and clothes that cover your skin if you have to be in
What are the possible side effects of Ciprofloxacin Tablets?
Other serious side effects of Ciprofloxacin Tablets include:
Central Nervous System Effects
Seizures have been reported in people who take fluoroquinolone antibiotics
including Ciprofloxacin Tablets. Tell your healthcare provider if you have a
history of seizures. Ask your healthcare provider whether taking Ciprofloxacin
Tablets will change your risk of having a seizure.
Central Nervous System (CNS) side effects may happen as soon as after taking
the first dose of Ciprofloxacin Tablets. Talk to your healthcare provider right
away if you get any of these side effects, or other changes in mood or behavior:
hear voices, see things, or sense things that are not there (hallucinations)
feel anxious or nervous
feel more suspicious (paranoia)
suicidal thoughts or acts
Serious allergic reactions Allergic reactions can
happen in people taking fluoroquinolones, including Ciprofloxacin Tablets, even
after only one dose. Stop taking Ciprofloxacin Tablets and get emergency medical
help right away if you get any of the following symptoms of a severe allergic
trouble breathing or swallowing
swelling of the lips, tongue, face
throat tightness, hoarseness
yellowing of the skin or eyes. Stop taking Ciprofloxacin Tablets and tell
your healthcare provider right away if you get yellowing of your skin or white
part of your eyes, or if you have dark urine. These can be signs of a serious
reaction to Ciprofloxacin Tablets (a liver problem).
Skin rash may happen in people taking ciprofloxacin tablets even after only
one dose. Stop taking ciprofloxacin tablets at the first sign of a skin rash and
call your healthcare provider. Skin rash may be a sign of a more serious
reaction to ciprofloxacin tablets.
Serious heart rhythm changes (QT prolongation and
torsades de pointes)
Tell your healthcare provider right away if you have a change in your heart
beat (a fast or irregular heartbeat), or if you faint. Ciprofloxacin Tablets may
cause a rare heart problem known as prolongation of the QT interval. This
condition can cause an abnormal heartbeat and can be very dangerous. The chances
of this event are higher in people:
who are elderly
with a family history of prolonged QT interval
with low blood potassium (hypokalemia)
who take certain medicines to control heart rhythm (antiarrhythmics)
Intestine infection (Pseudomembranous colitis)
Pseudomembranous colitis can happen with most antibiotics, including
Ciprofloxacin Tablets. Call your healthcare provider right away if you get
watery diarrhea, diarrhea that does not go away, or bloody stools. You may have
stomach cramps and a fever. Pseudomembranous colitis can happen 2 or more months
after you have finished your antibiotic.
Changes in sensation and possible nerve damage
Damage to the nerves in arms, hands, legs, or feet can happen in people who
take fluoroquinolones, including Ciprofloxacin Tablets. Talk with your
healthcare provider right away if you get any of the following symptoms of
peripheral neuropathy in your arms, hands, legs, or feet:
Ciprofloxacin Tablets may need to be stopped to prevent permanent nerve
Low blood sugar (hypoglycemia)
People who take Ciprofloxacin Tablets and other fluoroquinolone medicines
with the oral anti-diabetes medicine glyburide (Micronase, Glynase, Diabeta,
Glucovance)can get low blood sugar (hypoglycemia) which can sometimes be severe.
Tell your healthcare provider if you get low blood sugar with Ciprofloxacin
Tablets. Your antibiotic medicine may need to be changed.
Increased chance of problems with joints and tissues around joints in
children under 18 years old. Tell your child’s healthcare provider if your child
has any joint problems during or after treatment with Ciprofloxacin Tablets.
The most common side effects of Ciprofloxacin Tablets include:
vaginal yeast infection
changes in liver function tests
pain or discomfort in the abdomen
These are not all the possible side effects of Ciprofloxacin Tablets. Tell
your healthcare provider about any side effect that bothers you, or that does
not go away.
Call your doctor for medical advice about side effects. You may report side
effects to FDA at 1-800-FDA-1088.
How should I store Ciprofloxacin Tablets?Store
at 20-25°C (68-77°F) [See USP Controlled Room Temperature]. Keep Ciprofloxacin Tablets and all medicines out of the reach of
children.General Information about Ciprofloxacin Tablets
Medicines are sometimes prescribed for purposes other than those
listed in a Medication Guide. Do not use Ciprofloxacin Tablets for a condition
for which it is not prescribed. Do not give Ciprofloxacin Tablets to other
people, even if they have the same symptoms that you have. They may harm them.
This Medication Guide summarizes the most important information about
Ciprofloxacin Tablets. If you would like more information about Ciprofloxacin
Tablets, talk with your healthcare provider. You can ask your healthcare
provider or pharmacist for information about Ciprofloxacin Tablets that is
written for healthcare professionals. For more information call 1-866-850-2876.
What are the ingredients in Ciprofloxacin Tablets?