CONTRAINDICATIONS
Ciprofloxacin is contraindicated in persons with a history of hypersensitivity to ciprofloxacin or any
member of the quinolone class of antimicrobial agents.
WARNINGS
THE SAFETY AND EFFECTIVENESS OF CIPROFLOXACIN IN PEDIATRIC
PATIENTS, ADOLESCENTS (LESS THAN 18 YEARS OF AGE), PREGNANT
WOMEN, AND LACTATING WOMEN HAVE NOT BEEN ESTABLISHED. (See
PRECAUTIONS, Pediatric Use, Pregnancy, Teratogenic Effects, Pregnancy Category C and
Nursing Mothers) Ciprofloxacin causes lameness in immature dogs. Histopathological examination
of the weight-bearing joints of these dogs revealed permanent lesions of the cartilage. Related
quinolone-class drugs also produce erosions of cartilage of weight-bearing joints and other signs of
arthropathy in immature animals of various species. (See ANIMAL PHARMACOLOGY.)
Convulsions, increased intracranial pressure, and toxic psychosis have been reported in patients
receiving quinolones, including ciprofloxacin. Ciprofloxacin may also cause central nervous system
(CNS) events including: dizziness, confusion, tremors, hallucinations, depression, and, rarely, suicidal
thoughts or acts. These reactions may occur following the first dose. If those 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; PRECAUTIONS, Information for the Patient; DRUG
INTERACTIONS and ADVERSE REACTIONS.)
SERIOUS 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.
Serious and occasionally fatal hypersensitivity (anaphylactic) reactions, some following the first
dose, have been reported in patients receiving quinolone therapy. Some reactions were
accompanied by cardiovascular collapse, loss of consciousness, tingling, pharyngeal or facial edema,
dyspnea, urticaria, and itching. Only a few patients had a history of hypersensitivity reactions.
Serious anaphylactic reactions require immediate emergency treatment with epinephrine. For IV
Only: Besides epinephrine, other resuscitation measures, including oxygen, intravenous fluids,
intravenous antihistamines, corticosteroids, pressor amines, and airway management, as clinically
indicated. For Oral Only: Oxygen, intravenous steroids, and airway management, including
intubatin, should be administered as indicated.
Severe hypersensitivity reactions characterized by rash, fever, eosinophilia, jaundice, and hepatic
necrosis with fatal outcome have also been rarely reported in patients receiving ciprofloxacin along
with other drugs. The possibility that these reactions were related to ciprofloxacin cannot be
excluded. Ciprofloxacin should be discontinued at the first appearance of a skin rash or any other
sign of hypersensitivity.
Pseudomembranous colitis has been reported with nearly all antibacterial agents,
including ciprofloxacin, and may range in severity from mild to life-threatening.
Therefore, it is important to consider this diagnosis in patients who present with diarrhea
subsequent to the administration of antibacterial agents.
Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth
of clostridia. Studies indicate that a toxin produced by Clostridium difficile is one primary cause of
“antibiotic-associated colitis.”
After the diagnosis of pseudomembranous colitis has been established, therapeutic measures should
be initiated. Mild cases of pseudomembranous colitis usually respond to drug discontinuation alone.
In moderate to severe cases, consideration should be given to management with fluids and
electrolytes, protein supplementation, and treatment with an antibacterial drug clinically effective
against C. difficile colitis.
Achilles and other tendon ruptures that required surgical repair or resulted in prolonged disability
have been reported with ciprofloxacin and other quinolones. Ciprofloxacin should be discontinued if
the patient experiences pain, inflammation, or rupture of a tendon.
Oral Only: Ciprofloxacin 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 months.
PRECAUTIONS
General
IV
INTRAVENOUS CIPROFLOXACIN SHOULD BE ADMINISTERED BY SLOW INFUSION
OVER A PERIOD OF 60 MINUTES. Local IV site reactions have been reported with the
intravenous administration of ciprofloxacin. These reactions are more frequent if infusion time is 30
minutes or less or if small veins of the hand are used. (See ADVERSE REACTIONS.)
Oral and IV
Quinolones, including ciprofloxacin, may also cause central nervous system (CNS) events, including
nervousness, agitation, insomnia, anxiety, nightmares or paranoia. (See WARNINGS,
PRECAUTIONS, Information for the Patient and DRUG INTERACTIONS.)
Crystals of ciprofloxacin have been observed rarely in the urine of human subjects but more
frequently in the urine of laboratory animals, which is usually alkaline. (See ANIMAL
PHARMACOLOGY.) Crystalluria related to ciprofloxacin has been reported only rarely in humans
because human urine is usually acidic. Alkalinity of the urine should be avoided in patients receiving
ciprofloxacin. Patients should be well hydrated to prevent the formation of highly concentrated
urine.
Alteration of the dosage regimen is necessary for patients with impairment of renal function. (See
DOSAGE AND ADMINISTRATION.)
Moderate to severe phototoxicity manifested as an exaggerated sunburn reaction has been
observed in some patients who were exposed to direct sunlight while receiving some members of
the quinolone class of drugs. Excessive sunlight should be avoided.
As with any potent drug, periodic assessment of organ system functions, including renal, hepatic,
and hematopoietic, is advisable during prolonged therapy.
Information for the Patient
Oral
Patients Should Be Advised:
That ciprofloxacin may be taken with or without meals. The preferred time of dosing is two
hours after a meal. Patients should also be advised to drink fluids liberally and not take
antacids containing magnesium, aluminum or calcium, products containing iron, or
multivitamins containing zinc. Ciprofloxacin should not be taken concurrently with milk or
yogurt alone, since absorption of ciprofloxacin may be significantly reduced. Dietary calcium
as part of a meal, however, does not significantly affect ciprofloxacin absorption.
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.
To avoid excessive sunlight or artificial ultraviolet light while receiving ciprofloxacin and to
discontinue therapy if phototoxicity occurs.
To discontinue treatment; rest and refrain from exercise; and inform their physician if they
experience pain, inflammation or rupture of a tendon
Ciprofloxacin may cause dizziness and lightheadedness; therefore, patients should know how
they react to this drug before they operate an automobile or machinery or engage in activities
requiring mental alertness or coordination.
That ciprofloxacin may increase the effects of theophylline and caffeine. There is a
possibility of caffeine accumulating when products containing caffeine are consumed while
taking quinolones.
That convulsions have been reported in patients taking quinolones, including ciprofloxacin,
and to notify their physician before taking the drug if there is a history of this condition.
IV
Patients should be advised that ciprofloxacin may be associated with hypersensitivity reactions,
even following a single dose, and to discontinue the drug at the first sign of a skin rash or other
allergic reaction.
Ciprofloxacin may cause dizziness and lightheadedness; therefore, patients should know how they
react to this drug before they operate an automobile or machinery or engage in activities requiring
mental alertness or coordination.
Patients should be advised that ciprofloxacin may increase the effects of theophylline and caffeine.
There is a possibility of caffeine accumulation when products containing caffeine are consumed
while taking ciprofloxacin.
Patients should be advised to discontinue treatment; rest and refrain from exercise; and inform their
physician if they experience pain, inflammation, or rupture of a tendon.
Carcinogenesis, Mutagenesis, and Impairment of Fertility
Oral and IV
Eight in vitro mutagenicity tests have been conducted with ciprofloxacin. Test results are listed
below:
Salmonella/Microsome Test (Negative).
E. coli DNA Repair Assay (Negative).
Mouse Lymphoma Cell Forward Mutation Assay (Positive).
Chinese Hamster V79 Cell HGPRT Test (Negative).
Syrian Hamster Embryo Cell Transformation Assay (Negative).
Saccharomyces cerevisiae Point Mutation Assay (Negative).
Saccharomyces cerevisiae Mitotic Crossover and Gene Conversion Assay (Negative).
Rat Hepatocyte DNA Repair Assay (Positive).
Thus, 2 of the 8 tests were positive, but results of the following 3 in vivo test systems gave negative
results:
Rat Hepatocyte DNA Repair Assay.
Micronucleus Test (Mice).
Dominant Lethal Test (Mice).
Long-term carcinogenicity studies in mice and rats have been completed. After daily oral doses of
750 mg/kg (mice) and 250 mg/kg (rats) were administered for up to 2 years, there was no evidence
that ciprofloxacin had any carcinogenic or tumorigenic effects in these species.
Results from photo co-carcinogenicity testing indicate that ciprofloxacin does not reduce the time to
appearance of UV-induced skin tumors as compared to vehicle control. Hairless (Skh-1) mice were
exposed to UVA light for 3.5 hours five times every two weeks for up to 78 weeks while
concurrently being administered ciprofloxacin. The time to development of the first skin tumors was
50 weeks in mice treated concomitantly with UVA and ciprofloxacin (mouse dose approximately
equal to maximum recommended human dose based upon mg/m2), as opposed to 34 weeks when
animals were treated with both UVA and vehicle. The times to development of skin tumors ranged
from 16-32 weeks in mice treated concomitantly with UVA and other quinolones.3
In this model, mice treated with ciprofloxacin alone did not develop skin or systemic tumors. There
are no data from similar models using pigmented mice and/or fully haired mice. The clinical
significance of these findings to humans is unknown.
Fertility studies performed in rats at oral doses of ciprofloxacin up to 100 mg/kg (0.8 times the
highest recommended human dose of 1200 mg based upon body surface area) revealed no evidence
of impairment.
Pregnancy, Teratogenic Effects, Pregnancy Category C
Oral and IV
Reproduction studies have been performed in rats and mice using oral doses of up to 100 mg/kg
(0.6 and 0.3 times the maximum daily human dose based upon body surface area, respectively) and
IV doses of up to 30 mg/kg (0.24 and 0.12 times the maximum daily human dose based upon body
surface area, respectively) and have revealed no evidence of harm to the fetus due to ciprofloxacin.
In rabbits, ciprofloxacin (30 and 100 mg/kg orally) produced gastrointestinal disturbances resulting in
maternal weight loss and an increased incidence of abortion, but no teratogenicity was observed at
either dose. After intravenous administration of doses up to 20 mg/kg, no maternal toxicity was
produced in the rabbit, and no embryotoxicity or teratogenicity was observed. There are, however,
no adequate and well-controlled studies in pregnant women. Ciprofloxacin should be used during
pregnancy only if the potential benefit justifies the potential risk to the fetus. (See WARNINGS.)
Nursing Mothers
Oral and IV
Ciprofloxacin is excreted in human milk. Because of the potential for serious adverse reactions in
infants nursing from mothers taking ciprofloxacin, a decision should be made whether to discontinue
nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Pediatric Use
Oral and IV
Safety and effectiveness in pediatric patients and adolescents less than 18 years of age have not
been established. Ciprofloxacin causes arthropathy in juvenile animals. (See WARNINGS.)
Short-term safety data from a single trial in pediatric cystic fibrosis patients are available. In a
radndomized, double-blind clinical trial for the treatment of acute pulmonary exacerbations in cystic
fibrosis patients (ages 5-17 years), 67 patients received ciprofloxacin IV 10 mg/kg/dose q8h for one
week followed by ciprofloxacin HCl tablets 20 mg/kg/dose q12h to complete 10-21 days treatment
and 62 patients received the combination of ceftazidime IV 50 mg/kg/dose q8h and tobramycin IV 3
mg/kg/dose q8h for a total of 10-21 days. Patients less than 5 years of age were not studied. Safety
monitoring in the study included periodic range of motion examinations and gait assessments by
treatment-blihnded examiners. Patients were followe d for an average of 23 days after completing
treatment (range 0-93 days). This study was not designed to determine long term effects and the
safety of repeated exposure to ciprofloxacin.
In the study, injection site reactions were more common in the ciprofloxacin group (24%) than in the
comparison group (8%). Other adverse events were similar in nature and frequency between
treatment arms. Musculoskeletal adverse events were reported in 22% of the patients in the
ciprofloxacin group and 21% in the comparison group. Decreased range of motion was reported in
12% of the subjects in the ciprofloxacin group and 16% in the comparison group. Arthralgia was
reported in 10% of the patients in the ciprofloxacin group and 11% in the comparison group. One of
sixty-seven patients developed arthritis of the knee nine days after a ten day course of treatment
with ciprofloxacin. Clinical symptoms resolved, but an MRI showed knee effusion without other
abnormalities eight months after treatment. However, the relationship of this event to the patient's
course of ciprofloxacin can not be definitively determined, particularly since patients with cystic
fibrosis may develop arthralgias/arthritis as part of their underlying disease process.