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 Warnings, Precautions, Pregnancy, Nursing, Abuse - Ciprofloxacin
Cipro Warnings, Precautions, Pregnancy, Nursing, Abuse - Ciprofloxacin
WARNINGS
THE SAFETY AND EFFECTIVENESS OF CIPROFLOXACIN IN PEDIATRIC PATIENTS AND
ADOLESCENTS (LESS THAN 18 YEARS OF AGE), EXCEPT FOR USE IN INHALATIONAL
ANTHRAX (POST-EXPOSURE), PREGNANT WOMEN, AND LACTATING WOMEN HAVE NOT
BEEN ESTABLISHED. (See PRECAUTIONS
: Pediatric Use , Pregnancy
, and Nursing Mothers subsections.) Ciprofloxacin causes lameness
in immature dogs. Histopathological examination of the weight-bearing joints
of these dogs revealed permanent lesions of the cartilage. Related quinolone-class
drugs also produce erosions of cartilage of weight-bearing joints and other
signs of arthropathy in immature animals of various species. (See ANIMAL
PHARMACOLOGY.)
Convulsions, increased intracranial pressure, and toxic psychosis have been
reported in patients receiving quinolones, including ciprofloxacin. Ciprofloxacin
may also cause central nervous system (CNS) events including: dizziness, confusion,
tremors, hallucinations, depression, and rarely, suicidal thoughts or acts.
These reactions may occur following the first dose. If these reactions occur
in patients receiving ciprofloxacin, the drug should be discontinued and appropriate
measures instituted. As with all quinolones, ciprofloxacin should be used with
caution in patients with known or suspected CNS disorders that may predispose
to seizures or lower the seizure threshold (e.g. severe cerebral arteriosclerosis,
epilepsy), or in the presence of other risk factors that may predispose to seizures
or lower the seizure threshold (e.g. certain drug therapy, renal dysfunction).
(See PRECAUTIONS
: General : Information for Patients , Drug Interactions
and ADVERSE REACTIONS.)
SERIOUS AND FATAL REACTIONS HAVE BEEN REPORTED IN PATIENTS RECEIVING CONCURRENT
ADMINISTRATION OF INTRAVENOUS CIPROFLOXACIN AND THEOPHYLLINE. These reactions
have included cardiac arrest, seizure, status epilepticus, and respiratory failure.
Although similar serious adverse events have been reported in patients receiving
theophylline alone, the possibility that these reactions may be potentiated
by ciprofloxacin cannot be eliminated. If concomitant use cannot be avoided,
serum levels of theophylline should be monitored and dosage adjustments made
as appropriate.
Serious and occasionally fatal hypersensitivity (anaphylatic) reactions, some
following the first dose, have been reported in patients receiving quinolone
therapy. Some reactions were accompanied by cardiovascular collapse, loss of
consciousness, tingling, pharyngeal or facial edema, dyspnea, urticaria, and
itching. Only a few patients had a history of hypersensitivity reactions. Serious
anaphylactic reactions require immediate emergency treatment with epinephrine
and other resuscitation measures, including oxygen, intravenous oxygen, intravenous
fluids, intravenous antihistamines, corticosteroids, pressor amines, and airway
management, as clinically indicated.
Severe hypersensitivity reactions characterized by rash, fever, eosinophilia,
jaundice, and hepatic necrosis with fatal outcome have also been reported extremely
rarely in patients receiving ciprofloxacin along with other drugs. The possibility
that these reactions were related to ciprofloxacin cannot be excluded. Ciprofloxacin
should be discontinued at the first appearance of a skin rash or any other sign
of hypersensitivity.
Pseudomembranous colitis has been reported with nearly all antibacterial
agents, including ciprofloxacin, and may range 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.
PRECAUTIONS
General: INTRAVENOUS CIPROFLOXACIN SHOULD BE ADMINISTERED
BY SLOW INFUSION OVER A PERIOD OF 60 MINUTES. Local I.V. site reactions have
been reported with the intravenous administration of ciprofloxacin. These reactions
are more frequent if infusion time is 30 minutes or less or if small veins of
the hand are used. (See ADVERSE REACTIONS.)
Quinolones, including ciprofloxacin, may also cause central nervous system
(CNS) events, including nervousness, agitation, insomnia, anxiety, nightmares
or paranoia. (See WARNINGS
, Information for Patients , and Drug
Interactions .)
Crystals of ciprofloxacin have been observed rarely in the urine of human subjects
but more frequently in the urine of laboratory animals, which is usually alkaline.
(See ANIMAL PHARMACOLOGY.) Crystalluria related to ciprofloxacin has
been reported only rarely in humans because human urine is usually acidic. Alkalinity
of the urine should be avoided in patients receiving ciprofloxacin. Patients
should be well hydrated to prevent the formation of highly concentrated urine.
Alteration of the dosage regimen is necessary for patients with impairment
of renal function. (See DOSAGE AND ADMINISTRATION .)
Moderate to severe phototoxicity manifested as an exaggerated sunburn reaction
has been observed in some patients who were exposed to direct sunlight while
receiving some members of the quinolone class of drugs. Excessive sunlight should
be avoided.
As with any potent drug, periodic assessment of organ system functions, including
renal, hepatic, and hematopoietic, is advisable during prolonged therapy.
Information For Patients: Patients should be advised that
ciprofloxacin may be associated with hypersensitivity reactions, even following
a single dose, and to discontinue the drug at the first sign of a 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.
Patients should be advised 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.
Drug Interactions: As with some other quinolones, concurrent
administration of ciprofloxacin with theophylline may lead to elevated serum
concentrations of theophylline and prolongation of its elimination half-life.
This may result in increased risk of theophylline-related adverse reactions.
(See WARNINGS
.) If concomitant use cannot be avoided, serum levels of
theophylline should be monitored and dosage adjustments made as appropriate.
Some quinolones, including ciprofloxacin, have also been shown to interfere
with the metabolism of caffeine. This may lead to reduced clearance of caffeine
and prolongation of its serum half-life.
Some quinolones, including ciprofloxacin, have been associated with transient
elevations in serum creatinine in patients receiving cyclosporine concomitantly.
Altered serum levels of phenytoin (increased and decreased) have been reported
in patients receiving concomitant ciprofloxacin.
The concomitant administration of ciprofloxacin with the sulfonylurea has,
in some patients, resulted in severe hypoglycemia. Fatalities have been reported.
Quinolones have been reported to enhance the effects of the oral anticoagulant
warfarin or its derivatives. When these products are administered concomitantly,
prothrombin time or other suitable coagulation tests should be closely monitored.
Probenecid interferes with renal tubular secretion of ciprofloxacin and produces
an increase in the level of ciprofloxacin in the serum. This should be considered
if patients are receiving both drugs concomitantly.
As with other broad-spectrum antimicrobial agents, prolonged use of ciprofloxacin
may result in overgrowth of nonsusceptible organisms. Repeated evaluation of
the patient's condition and microbial susceptibility testing are essential.
If superinfection occurs during therapy, appropriate measures should be taken.
Carcinogenesis, Mutagenesis, Impairment of Fertility: Eight in vitro
mutagenicity tests have been conducted with ciprofloxacin. Test results
are listed below:
Salmonella/Microsome Test (Negative)
E. coli DNA Repair Assay (Negative)
Mouse Lymphoma Cell Forward Mutation Assay (Positive)
Chinese Hamster V 79 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, two of the eight tests were positive, but results of the following three
in vivo test systems gave negative results:
Rat Hepatocyte DNA Repair Assay
Micronucleus Test (Mice)
Dominant Lethal Test (Mice)
Long-term carcinogenicity studies in mice and rats have been completed. After
daily oral doses of 750 mg/kg (mice) and 250 mg/kg (rats) were administered
for up to 2 years, there was no evidence that ciprofloxacin had any carcinogenic
or tumorigenic effects in these species.
Results from photo co-carcinogenicity testing indicate that ciprofloxacin dose
not reduce the time to appearance of UV-induced skin tumors as compared to vehicle
control. Hairless (Skh-1) mice were exposed to UVA light for 3.5 hours five
times every two weeks for up to 78 weeks while concurrently being administered
ciprofloxacin. The time to development of the first skin tumors was 50 weeks
in mice treated concomitantly with UVA and ciprofloxacin (mouse dose approximately
equal to maximum recommended human dose based upon mg/m 2 ), 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
in unknown.
Fertility studies performed in rats at oral doses of ciprofloxacin up to 100
mg/kg (0.8 times the highest recommended human dose of 1200 mg based upon body
surface area) revealed no evidence of impairment.
Pregnancy: Teratogenic Effects. Pregnancy Category C: Reproduction studies
have been performed in rats and mice using oral doses of up to 100 mg/kg (0.8
and 0.4 times the maximum daily human dose based upon body surface area, respectively)
and I.V. doses of up to 30 mg/kg (0.24 and 0.12 times the maximum daily human
dose based upon body surface area, respectively) and have revealed no evidence
of harm to the fetus due to ciprofloxacin. In rabbits, ciprofloxacin (30 and
100 mg/kg orally) produced gastrointestinal disturbances resulting in maternal
weight loss and an increased incidence of abortion, but no teratogenicity was
observed at either dose. After intravenous administration of doses up to 20
mg/kg, no maternal toxicity was produced in the rabbit, and no embryotoxicity
or teratogenicity was observed. There are, however, no adequate and well-controlled
studies in pregnant women. Ciprofloxacin should be used during pregnancy only
if the potential benefit justifies the potential risk to the fetus. (See WARNINGS
.)
Nursing Mothers: Ciprofloxacin is excreted in human milk.
Because of the potential for serious adverse reactions in infants nursing from
mothers taking ciprofloxacin, a decision should be made whether to discontinue
nursing or to discontinue the drug, taking into account the importance of the
drug to the mother.
Pediatric Use: Safety and effectiveness in pediatric patients
and adolescents less than 18 years of age have not been established, except
for use in inhalational anthrax (post-exposure). Ciprofloxacin causes arthropathy
in juvenile animals. (See WARNINGS
.)
For the indication of inhalational anthrax (post-exposure), the risk-benefit
assessment indicates that administration of ciprofloxacin to pediatric patients
is appropriate. For information regarding pediatric dosing in inhalational anthrax
(post-exposure), see DOSAGE AND ADMINISTRATION and INHALATIONAL ANTHRAX ADDITIONAL
INFORMATION.
Short-term safety data from a single trial in pediatric cystic fibrosis patients
are available. In a randomized, double-blind clinical trial for the treatment
of acute pulmonary exacerbations in cystic fibrosis patients (ages 5-17 years),
67 patients received ciprofloxacin I.V. 10 mg/kg/dose q8h for one week followed
by ciprofloxacin tablets 20 mg/kg/dose q12h to complete 10-21 days treatment
and 62 patients received the combination of ceftazidime I.V. 50 mg/kg/dose q8h
and tobramycin I.V. 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-blinded
examiners. Patients were followed 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.
Geriatric Use: In a retrospective analysis of 23 multiple-dose
controlled clinical trials of ciprofloxacin encompassing over 3500 ciprofloxacin
treated patients, 25% of patients were greater than or equal to 65 years of
age and 10% were greater than or equal to 75 years of age. No overall differences
in safety or effectiveness were observed between these subjects and younger
subjects, and other reported clinical experience has not identified differences
in responses between the elderly and younger patients, but greater sensitivity
of some older individuals on any drug therapy cannot be ruled out. Ciprofloxacin
is known to be substantially excreted by the kidney, and the risk of adverse
reactions may be greater in patients with impaired renal function. No alteration
of dosage is necessary for patients greater than 65 years of age with normal
renal function. However, since some older individuals experience reduced renal
function by virtue of their advanced age, care should be taken in dose selection
for elderly patients, and renal function monitoring may be useful in these patients.
(See CLINICAL PHARMACOLOGYand DOSAGE AND ADMINISTRATION .)
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