Brand Name Baytril
Enrofloxacin
Manufacturer Bayer A.G.
No Package Insert Available
Safety Profile Banned by the FDA
BLACK BOX WARNINGS TO BE ADDED
(Read More)
FDA is
notifying the makers of fluoroquinolone antimicrobial
drugs for systemic use of the need to add a boxed warning to
the prescribing information about the increased risk of developing
tendinitis and tendon rupture in patients taking fluoroquinolones
and to develop a Medication Guide for patients.
In view of the potentially fatal consequences of anaphylactic reactions to
Enrofloxacin and other quinolones doctors should take care when prescribing these
drugs.
Peripheral Neuropathy
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.
QUINOLONES MAY HAVE THE POTENTIAL TO PROLONG THE QTc INTERVAL OF THE
ELECTROCARDIOGRAM IN SOME PATIENTS. DUE TO THE LACK OF CLINICAL EXPERIENCE,
QUINOLONES SHOULD BE AVOIDED IN PATIENTS WITH KNOWN PROLONGATION OF THE QTc
INTERVAL, PATIENTS WITH UNCORRECTED HYPOKALEMIA, AND PATIENTS RECEIVING CLASS IA
(E.G. QUINIDINE, PROCAINAMIDE) OR CLASS III (E.G. AMIODARONE, SOTALOL)
ANTIARRHYTHMIC AGENTS.
Ruptures of the shoulder, hand, and Achilles tendons that required surgical
repair or resulted in prolonged disability have been reported in patients
receiving quinolones. Tendon rupture can occur during or after therapy with
quinolones.
Quinolones may cause central nervous system (CNS) events including nervousness,
agitation, insomnia, anxiety, nightmares, or paranoia.
As with other quinolones, disturbances of blood glucose, including symptomatic
hyper- and hypoglycemia, have been reported, usually in diabetic patients
receiving concomitant treatment with an oral hypoglycemic (e. g., glyburide) or
with insulin. In these patients, the monitoring of blood glucose is recommended.
In 2004 new warning labels added to all of the Fluoroquinolones regarding
Peripheral Neuropathy (irreversible nerve damage), Tendon Damage, Heart Problems
(prolonged QT Interval / Torsades de pointes), Pseudomembranous colitis,
Rhabdomyolysis (muscle wasting), Steven Johnson Syndrome, as well as concurrent
usage of NSAIDs contributing to the severity of these reactions.
Although such events have been reported since the mid sixties, the FDA waited
almost forty years to add such warnings to the package inserts. These new
warnings again fail to adequately warn either the patient or the physician.
"Drug companies write the package inserts of all
drugs, carefully including the information they choose and
omitting information they want to avoid. Drug companies underwrite a large
percentage of continuing
education courses for doctors. In doing so, they make sure that the
speakers represent the company view.
Drug companies design studies that are meant to produce favorable results
and then publish the studies in
medical journals. Studies with unfavorable results are not
published. Drug reps typically bring stacks of
studies, all favorable, which impress doctors, who no longer
have the time or motivation to search the
medical literature themselves. Drug reps do not include independent
studies with less favorable
conclusions. Many doctors never see these."
Source:
THE MEDICAL PROFESSION AND THE
CULTURE OF CORRUPTION
Approval Date: June 19, 1997
Freedom of Information Summary
NADA 140-441 and 140-913
I. GENERAL INFORMATION:
NADA 140-441 and 140-913
Sponsor: BAYER Corporation
Agriculture Division
Animal Health
P.O. Box 390
Shawnee, Kansas 66201
Generic Name: enrofloxacin tablets and enrofloxacin injectable
solution
Trade Name: BAYTRIL® Antibacterial Tablets and BAYTRIL® Antibacterial
Injectable Solution
Marketing Status: prescription
Effect of the Supplement: The supplement to NADA 140-441, for dogs and
cats, provides for revisions to 21 CFR 520.812 as indicated below.
Conditions of use - (1) Amount. Administer orally at a rate to provide
5 to 20 mg/kg (2.27 to 9.07 mg/lb) of body weight, either as a single
daily dose or divided into two (2) equal daily doses administered at
twelve (12) hour intervals.
(2) Indications - Enrofloxacin tablets in dogs and cats for the
management of diseases associated with bacteria susceptible to
enrofloxacin. [This statement will replace section (2)(i) and (ii) as
previously approved].
(3) Limitations - Treatment should be continued for at least 2 to 3
days beyond cessation of clinical signs, to a maximum of 30 days for
both dogs and cats.
The supplement to NADA 140-913, for dogs, provides for revisions to 21
CFR 522.812 as indicated below.
(2) Indications - Enrofloxacin injectable solution in dogs for the
management of diseases associated with bacteria susceptible to
enrofloxacin.
II. INDICATIONS FOR USE
Baytril Antibacterial Tablets and Injectable Solution are indicated
for the management of diseases in dogs and cats associated with
bacteria susceptible to enrofloxacin.
III. DOSAGE
A. DOSAGE FORM 5.7 mg, 22.7 mg, and 68 mg enrofloxacin per tablet, and
22.7 mg per mL
B. ROUTE OF ADMINISTRATION Baytril Antibacterial Tablets for oral
administration and Baytril Injectable Solution for intramuscular
administration
C. RECOMMENDED DOSAGES: The dose range of Baytril Antibacterial
Tablets in dogs and cats is 5 to 20 mg/kg (2.27 to 9.07 mg/lb) of body
weight, either as a single dose or divided into two (2) equal daily
doses administered at twelve (12) hour intervals. The dose of Baytril
Injectable Solution for dogs is 2.5 mg/kg (1.13 mg/lb) as a single
injection. The injectable dose should be followed by oral tablet
treatment in 12 hours.
IV. EFFECTIVENESS
A. Clinical efficacy of the recommended minimum dosages have been
established in dogs as indicated and referenced in the Freedom of
Information Summaries for NADA 140-441 dated January 24, 1989, May 4,
1990, and October 29, 1990, and NADA 140-913 dated January 29, 1990.
B. The drugs distribute widely and reach adequate blood and tissue
concentrations in the target animal species. Tissue concentration
values are found in the approved labels, and are presented, or
referenced, in the Freedom of Information Summaries associated with
these approvals.
The wide distribution and activity of these drugs would indicate that
the drugs may be used in several conditions, and is evidenced by the
wide range of recommended conditions, indications, and limitations in
clinical literature as indicated in Table 1.
Table 1. The following literature supports the condition of use. Usage
11 mg/kg BID for 4 days; n = 6 adult dogs
Article/
Journal Reference Walker RD, Stein GE, Hauptman JG, et al.
Pharmacokinetic evaluation of enrofloxacin administered orally to
healthy dogs. Am J Vet Res 1992; 53:2315-2319.
Conclusions/
Explanation -dosage of 11 mg/kg was required to maintain serum
concentrations greater than the MIC90 of Pseudomonas aeruginosa for
the entire dosing interval
- no adverse reactions observed
Usage 100 dogs, 25 cats received 10 mg/kg/day, variable durations
Article/Journal Reference vom Hove W, Lettow E, Opitz M. Experiences
with the anti-infective enrofloxacin (Baytril) in pyodermas in dogs
and cats. Kleintierpraxis 1992; 37:817-822.
Conclusions/Explanation - authors recommend 10 mg/kg/day for bacterial
dermatoses, for at least 3 weeks, to be adapted to individual cases
- dose was well-tolerated and can be safely administered over a period
of several weeks
Usage 5 mg/kg BID, dogs and cats
Article/Journal Reference Aucoin D. Rational antimicrobial therapy in
dermatitis. Proceedings of the 10th ESVD (European Soc. of Vet Derm)
annual congress, Aalborg Denmark, 1993:116-125.
Conclusions/Explanation - recommends increasing to this dose from 5
mg/kg SID if no response is seen in 1 week
- also notes that once or twice daily dosing is possible, depending on
the MIC of the pathogen
Usage 5 - 7.5 mg/kg BID, dogs and cats
Article/Journal Reference Rosychuk R. Management of Otitis Externa.
VetClinNorthAmSmallAnimPract; 1994;24:921-951(1994).
Conclusions/Explanation - this dose recommended for "enhanced effect
[against Pseudomonas infections]"
- "pending culture and sensitivity data, the systemic antibiotic of
choice"
Usage 2.5 - 5 mg/kg BID, dogs
Article/Journal Reference Mason I. Selection and use of antibacterial
agents in canine pyoderma. Practice 1993; 15:29-34.
Conclusions/Explanation - "in general, doses of antimicrobial agents
are doubled for skin infections..."
Usage 5 mg/kg BID, dogs
Article/Journal Reference Dorfman M, Barsanti J, Budsberg S.
Enrofloxacin concentrations in dogs with normal prostate and dogs with
chronic bacterial prostatitis. Am J Vet Res 1995; 56:386-389.
Conclusions/Explanation - resulted in prostatic fluid and tissue
concentrations exceeding the MIC of most pathogens that cause
bacterial prostatitis
Usage 2.5 - 5.0 mg/kg q12-24h, dogs and cats
Article/Journal Reference McKellar Q. Clinical relevance of the
pharmacologic properties of fluoroquinolones. Supplement to Compendium
on Continuing Education for the Practicing Veterinarian 1996,
18(2):14-21
Conclusions/Explanation - use a 5.0 mg/kg dose.
Usage 10 mg/kg BID, dogs and cats
Article/Journal Reference Ihrke P. Experiences with enrofloxacin in
small animal dermatology. Supplement to Compendium on Continuing
Education for the Practicing Veterinarian 1996, 18(2):35-39.
Conclusions/Explanation - given "occasionally," author notes "dosages
have been effective and without adverse effects..." Also notes a study
where enrofloxacin was administered BID for periods from 2 to 14
weeks, with excellent response in 93.3% of dogs (n=30). Author
concludes: "extended regimen therapy with enrofloxacin has been used
effectively for the management of recurrent deep pyoderma."
Usage 10 mg/kg SID or 5 mg/kg BID, dogs and cats
Article/Journal Reference Carlotti D. (Table of recent studies in:)
New trends in systemic antibiotic therapy of bacterial skin disease in
dogs. Supplement to Compendium on Continuing Education for the
Practicing Veterinarian 1996, 18(2):40-47.
Conclusions/Explanation - given for duration of "3 weeks or more;"
includes other doses given for durations of "1 - 12 weeks and 2 - 6
weeks."
Usage 2.5 - 5 mg/kg, q12h
Article/Journal Reference Hawkins E. Antibiotics for lower respiratory
tract infections. Supplement to Compendium on Continuing Education for
the Practicing Veterinarian 1996, 18(2):59-65.
Conclusions/Explanation - notes "increased dosage may be necessary for
relatively resistant organisms;" she notes that "relatively high
dosages of the drug (11 mg/kg q12h) have been recommended.
Usage 2.5 mg/kg BID, or 5 mg/kg SID
Article/Journal Reference Boothe D. Antimicrobial therapy in the
critically ill patient. Supplement to Compendium on Continuing
Education for the Practicing Veterinarian 1996, 18(2):66-83.
C. Support for a pharmacokinetic based dosage, and the addition of the
dose range to the tablet formulation is presented below.
Investigations into the pharmacodynamic properties of the
fluoroquinolone class of antimicrobials indicate that bacterial
killing is concentration-dependent (as opposed to time-dependent).
Results of the following studies indicated that the most reliable
predictor of successful therapy with flouroquinolones is the
concentration-dependent value described by the ratio of the peak
concentration of the drug divided by the drug's mean inhibitory
concentration for that pathogen (Cmax/MIC).
1. Comparative study with enoxacin and netilmicin in a pharmacodynamic
model to determine importance of ratio of antibiotic peak
concentration to MIC for bactericidal activity and emergence of
resistance. (Blaser J, Stone BB, Groner MC, et al. Antimicrob Agents
Chemother 1987;31:1054-60.)
2. Pharmacokinetic consideration in quinolone therapy. (Nightingale
CH. Pharmacotherapy 1993;13:34S-38S.)
3. Correlation of pharmacokinetic parameters to efficacy of
antibiotics: Relationships between serum concentrations, MIC values,
and bacterial eradication in patients with gram-negative pneumonia. (Schentag
J. Scand J Infect Dis 74 (Suppl):218-234,1991.)
The following in vivo studies confirmed that total daily dose, and not
frequency of administration, was significantly (P < 0.05) associated
with bactericidal activity against E. coli, staphylococcal, and P.
aeruginosa isolates.
4. Pharmacokinetics of enrofloxacin in clinically normal dogs and mice
and drug pharmacodynamics in neutropenic mice with Escherichia coli
and staphylococcal infections. (Meinen J, McClure J, Rosin E. Am J Vet
Res 1995;56:1219-24.)
5. Pharmacodynamics of a fluoroquinolone antimicrobial agent in a
neutropenic rat model of Pseudomonas sepsis. (Drusano G, Johnson D,
Rosen M, et al. Antimicrob Agents Chemother 1993;37:483-90.)
Results of the following studies indicated that the
area-under-the-inhibitory curve(AUIC), described by the quotient AUC/MIC,
is useful for predicting the therapeutic efficacy of fluoroquinolone
therapy. By simulation models and confirmatory clinical trials, the
authors showed a 24-hour AUIC value 125 was the significant breakpoint
for ensuring antibacterial activity capable of achieving both
microbiological and clinical cures.
6. Pharmacodynamics of intravenous ciprofloxacin in seriously ill
patients. (Forrest A, Nix B, Ballow C, et al. Antimicrob Agents
Chemother 1993;37:1073-81.)
7. Mathematical examination of dual individualization principles: the
relationships between AUC above MIC and area under the inhibitory
curve for cefmenoxime, ciprofloxacin and tobramycin. (Schentag J, Nix
DE, Adelman MH. Pharmacother 1991;25:1050-1057.)
D. Conclusion: The published scientific literature, concerning
fluoroquinolone antimicrobial agents, supports a greater spectrum of
activity in bacteriocidal activity for enrofloxacin with the dose
range and duration as provided by this supplement.
V. ANIMAL SAFETY
Safety of the dose range, for oral formulations, has been established
in cats and dogs and is presented or referenced in the Freedom of
Information Summaries for NADA 140-441. The information indicates that
the tablets are safe within the dose range provided by this
supplemental NADA. In several studies, the oral doses administered
exceeded the recommended upper limit of the dose range for the tablet
formulation. See Tables 2 and 3 which summarize the safety and
toxicology studies filed in NADA 140-441.
Table 2. Baytril Tablets NADA 140-441 Safety trial summary for dogs.
Report # Date Study Title/Author
73146 May 85 Safety Evaluation of BAY Vp 2674; Subchronic (13 week)
Feeding Study in the Dog - Porter
-Tolerated at all doses with no significant adverse effects. Sporadic
emesis, inappetance.
73171 Aug 85 Safety Evaluation for the Use of BAY Vp 2674 Tablets in Young Puppies - Kohlenberg -No adverse effects at 20 mg/kg. Sporadic emesis, inappetance.
73219 Nov 85 Safety Evaluation for the Use of BAY Vp 2674 in D.
immitis Microfilaria Positive Dogs - Kohlenberg
-No effect on microfilaria or adult heartworms.
73229 Dec 85 Safety Evaluation for the Use of BAY Vp 2674 Tablets in
Dogs - Kohlenberg
-Safety margin of at least 5X [of the 2.5 mg/kg BID] dose for 3X [10
day] duration.
-Sporadic emesis, inappetance.
73355 June 86 Safety Evaluation for the Use of BAY Vp 2674 Tablets in
Male Breeding Dogs - Stuke --No adverse effect upon reproductive
parameters.
73828 Dec 88 Safety Evaluation for BAY Vp 2674 in Female Breeding
Dogs - Stuke and Magerkurth ---No adverse effects upon
reproductive parameters
73775 Oct 87 Safety Evaluation of BAY Vp 2674; Repeat of a Subchronic
(13 week) Feeding Study in the Dog [3 month old pups] - Porter
- no death or moribundity; no effect on weight gain, food consumption,
or clinical pathology
parameters
- joint lesions seen in high (2500) and mid-dose (320 ppm) pups
- sporadic emesis, inappetance, loose stool
73788 June 88 Safety Evaluation of BAY Vp 2674: Subchronic (13
week) Feeding Study in Male Dogs [3 month old pups] - Porter
- no death or moribundity
- decreased food consumption, inhibited weight gain in first weeks of
study
- overt toxicity limited to musculo-skeletal system
Table 3. Baytril Tablets NADA 140-441 Safety trial summary for cats.
73768 June 88 Safety Evaluation for Concurrent Treatment of Cats with
BAY Vp 2674 Oral Tablets and Other Commonly Used Feline Health
Products - Kohlenberg
-Compatible with commonly used feline health products
73793 Sept 88 General Safety Evaluation for the Use of BAY Vp 2674
Tablets in Young Cats - Kohlenberg
-No adverse effects
73835 Nov 88 Safety Evaluation for the Use of BAY Vp 2674 Tablets in Young Kittens - Kohlenberg ---No adverse effects
73597 May 86 General Safety in 8 - 10 week old Kittens - Hoffman and
Karbe
-No adverse effects
Conclusions: Enrofloxacin tablets have an adequate margin of safety in
dogs and cats when administered over a dose range of 5 to 20 mg/kg for
a maximum of 30 days.
VI. HUMAN SAFETY
A. Human Food Safety:
Data on human safety, pertaining to consumption of drug residues in
food, were not required for approval of these NADAs. The drug is
labeled for use in dogs and cats, which are non-food animals.
B. User Safety Concerns:
The labeling contains the following warning statement:
Human Warnings:
For use in animals only. Keep out of reach of children.
Avoid contact with eyes. In case of contact, immediately flush eyes
with copious amounts of water for 15 minutes. In case of dermal
contact, wash skin with soap and water. Consult a physician if
irritation persists following ocular or dermal exposures. Individuals
with a history of hypersensitivity to quinolones should avoid this
product. In humans, there is a risk of user photosensitization within
a few hours after excessive exposure to quinolones. If excessive
accidental exposure occurs, avoid direct sunlight. To report adverse
reactions or to obtain a copy of the Material Safety Data Sheet, call
1-800-633-8405.
VI. AGENCY CONCLUSIONS
The data submitted in support of these NADAs satisfy the requirements
of section 512 of the Federal Food, Drug, and Cosmetic Act (FFDCA) and
Part 514 of the implementing regulations (Title 21), and demonstrate
that BAYTRIL® Antibacterial Tablets and BAYTRIL® Antibacterial
Injectable Solution are safe and effective when used according to the
approved conditions of use.
According to the Center's supplemental approval policy 21 CFR
514.106(b)(2)(iii), (iv), (v), & (ix), these are Category II changes
that required a reevaluation of the safety and effectiveness data in
the parent applications.
FDA has carefully considered the potential environmental effects of
this action and has concluded that the action will not have a
significant impact on the human environment and that an environmental
impact statement is not required. FDA's finding of no significant
impact and the evidence supporting that finding, contained in an
environmental assessment, may be seen in the Dockets Management Branch
(HFA-305).
VIII. APPROVED LABELING
A copy of the labeling is attached to this document.
A. Baytril (enrofloxacin) Antimicrobial Tablets No. 20, 500 tablet
bottle, label
B. Baytril (enrofloxacin) Antimicrobial Tablets No. 20, 500 tablet
bottle, package insert
C. Baytril (enrofloxacin) Antimicrobial Tablets No. 60, 250 tablet
bottle, label
D. Baytril (enrofloxacin) Antimicrobial Tablets No. 60, 250 tablet
bottle, package insert
E. Baytril (enrofloxacin) Injectable Solution, 20 mL vial, vial label,
carton label, package insert
Copies of applicable labels may be obtained by writing to the:
Freedom of Information Office
Center for Veterinary Medicine, FDA
7500 Standish Place
Rockville, MD 20855
The following has been associated with fluoroquinolone therapy:
PERIPHERAL NEUROPATHY (as
noted above)
Achilles and other
tendon ruptures that required surgical
repair or resulted in prolonged disability.
Convulsions,
increased intracranial pressure, and
toxic psychosis.
Central nervous system (CNS) events including: dizziness, confusion,
tremors, hallucinations, depression, and, ly,
suicidal thoughts
or acts. These reactions may occur following the first dose.
Severe hypersensitivity reactions characterized by rash, fever,
eosinophilia, jaundice,
and hepatic necrosis with
fatal outcome
Pseudomembranous colitis
and may range in severity from mild to life-threatening.
Lameness in immature dogs with
permanent lesions of the cartilage.
Central nervous system (CNS) events, including nervousness, agitation,
insomnia, anxiety,
nightmares or paranoia.
Crystalluria
Moderate to
Pregnancy Warning
Fluoroquinolones caused fetal harm in animal studies, including decreased body weights and malformed bones as well as an increased risk of death. Because of the potential for serious adverse effects to the fetus, these drugs should not be used by pregnant women.
Breast-feeding Warning
Fluoroquinolones are excreted in human milk. Because of the potential for serious adverse effects in nursing infants, you should not take these drugs while nursing.
Additional adverse events reported:
Body as a Whole: Change in
serum phenytoin.
Cardiovascular: Palpitation,
atrial flutter, ventricular ectopy, syncope, hypertension, angina
pectoris, myocardial infarction, cardiopulmonary arrest, cerebral
thromobosis. Cardiovascular collapse, cardiopulmonary arrest,
myocardial infarction, arrhythmia, tachycardia, palpitation, cerebral
thrombosis, syncope, cardiac murmur, hypertension, hypotension, angina
pectoris. Postural hypotension, vasculitis.
Central Nervous System:
Dizziness, lightheadedness, insomnia, nightmares, hallucinations,
manic reaction, irritability, tremor, ataxia, convulsive seizures,
lethargy, drowsiness, weakness, malaise, anorexia, phobia,
depersonalization, depression, paresthesia. Convulsive seizures,
paranoia, toxic psychosis, depression, dysphasia, phobia,
depersonalization, manic reaction, unresponsiveness, ataxia,
confusion, hallucinations, dizziness, lightheadedness, paresthesia,
anxiety, tremor, insomnia, nightmares, weakness, drowsiness,
irritability, malaise, lethargy Agitation, confusion, delirium,
dysphasia, myoclonus, nystagmus, toxic psychosis.
.
Gastrointestinal: Painful oral
mucosa, oral candidiasis, dysphagia, intestinal perforation,
gastrointestinal bleeding. Cholestatic jaundice has been reported.
Ileus, jaundice, gastrointestinal bleeding, C. difficle associated
diarrhea, pseudomembranous colitis, pancreatitis, hepatic necrosis,
intestinal perforation, dyspepsia, epigastric or abdominal pain,
vomiting, constipation, oral ulceration, oral candidiasis, mouth
dryness, anorexia, dysphagia, flatulence Constipation, dyspepsia,
flatulence, hepatic necrosis, jaundice, pancreatitis, pseudomembranous
colitis. (The onset of pseudomembranous colitis symptoms may occur
during or after antimicrobial treatment.)
Hemic/Lymphatic: Agranulocytosis, hemolytic anemia, methemaglobinemia, prolongation of
prothrombin time
Metabolic/Nutritional:
Elevation of serum triglycerides, cholesterol, blood glucose, serum
potassium.
Musculoskeletal: Arthralgia or
back pain, joint stiffness, achiness, neck or chest pain, flare up of
gout. Arthralgia, jaw, arm or back pain, joint stiffness, neck and
chest pain, achiness, flare up of gout Myalgia, possible exacerbation
of myasthenia gravis, tendinitis/tendon rupture.
Renal/Urogenital: Interstitial
nephritis, nephritis, renal failure, polyuria, urinary retention,
urethral bleeding, vaginitis, acidosis. Renal failure, intarstitial
nephritis, hemorrhagic cystitis, renal calcuti, frequent urination,
acidosis, urethral bleeding, polyuria, urinary retention, gynecomastia,
candiduria, vaginitis. Crystalluria, cylindruria, hematuria, and
albuminutia have also been reported.
Albuminuria, candiduria, renal calculi, vaginal candidiasis.
Respiratory: Dyspnea,
epistaxis, laryngeal or pulmonary edema, hiccough, hemophysis,
bronchospasm, pulmonary embolism. Respiratory arrest, pulmonary
embolism, dyspnea, pulmonary edema, respiratory distress, pleural
effusion, hemoptysis, epistaxis, hiccough
Skin/Hypersensitivity:
Pruritus, urticaria, photosensitivity, flushing, fever, chills,
angioedema, edema of the face, neck, lips, conjunctivae or hands,
cutaneous candidiasis, hyperpigmentation, erytherna nodosum. Allergic
reactions ranging from urticaria to anaphylactic reactions have been
reported. Anaphylactic reactions, erythema multiforme/Stevens-Johnson
syndrome, exfoliative dermatitis, toxic epidermal necrolysis,
vasculitis, angioedema, edema of the lips, face, neck, conjunctivae,
hands or lower extremities, purpura, fever, chills, flushing, pruritus,
urtigaria, cutaneous candidiasis, vesicles, increased perspiration,
hyperpigmentation, erythema nodosum, photosensitivity. Allergic
reactions ranging from urticaria to anaphylactic reactions have been
reported. Anaphylactic reactions, erythema multiforme/Stevens-Johnson
syndrome, exfoliative dermatitis, toxic epidermal necrolysis.
Special Senses: Blurred
vision, disturbed vision (change in color perception, overbrightness
of lights), decreased visual acuity, diplopia, eye pain, tinnitus,
hearing loss, bad taste. Decreased visual acuity, blurred vision,
disturbed vision (flashing lights, change in color perception,
overbrightness of lights, diplopia), eye pain, anosmia, hearing loss,
tinnitus, nystagmus, a bad taste. Also reported were agranulocytosis,
prolongation of prothrombin time, and possible exacerbation of
myasthenia gravis. anosmia, taste loss.
Adverse Laboratory Changes
Oral
Changes in Laboratory Parameters Listed as Adverse Events:
Hepatic: Elevations of ALT
(SGPT), AST (SGOT), alkaline phosphatase , LDH , serum bilirubin.
Hematologic: Eosinophilia, leukopenia, decreased blood platelets,
elevated blood platelets, pancytopenia.
Renal: Elevations of serum
creatinine, BUN, CRYSTALLURIA, CYLINDRURIA, AND HEMATURIA HAVE BEEN
REPORTED.
Other Changes: 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, leukocytosis.
I.V.
The most frequently reported changes in laboratory parameters with
intravenous fluoroquinolone therapy:
Hepatic: Elevations of AST
(SGOT), ALT (SGPT), alkaline phosphatase, LDH, and serum bilirubin.
Hematologic: Elevated eosinophil and platelet counts, decreased
platelet counts, hemoglobin and/or hematocrit.
Renal: Elevations of serum creatinine, BUN, and uric acid.
Other: Elevations of serum creatinine, phosphokinase, serum theophylline (in patients receiving theophylline concomitantly), blood glucose, and triglycerides.
Other changes occurring infrequently were: decreased leukocyte
count, elevated atypical lymphocyte count, immature WBCs, elevated
serum calcium, elevation of serum gamma-glutamyl transpeptidose
(GI), decreased BUN, decreased uric acid, decreased total serum
protein, decreased serum albumin, decreased serum potassium, elevated
serum potassium, elevated serum cholesterol.
Other changes occurring ly during administration of fluoroquinolone were: elevation of serum amylase, decrease of blood
glucose, pancytopenia, leukocytosis, elevated sedimentation rate,
change in serum phenytoin, decreased prothrombin time, hemolytic
anemia, and bleeding diathesis.
ANIMAL PHARMACOLOGY
Oral and I.V.
“Fluoroquinolone and other quinolones have been shown to cause
arthropathy in immature animals of most species tested. …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… In a subsequent
study in beagles, removal of weight bearing from the joint reduced the
lesions but did not totally prevent them.”
Source:
www.rxlist.com
“Crystalluria, sometimes associated with secondary nephropathy, occurs
in laboratory animals dosed with fluoroquinolone….In rhesus monkeys, crystalluria without nephropathy has been noted after single oral
doses as low as 5 mg/kg…In dogs, ciprofloxacin at 3 and 10 mg/kg by
rapid IV injection (15 sec.) produces pronounced hypotensive
effects…In rhesus monkeys, rapid IV injection also produces
hypotension but the effect in this species is inconsistent and less
pronounced.”
Source:
www.rxlist.com
“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."
Source:
www.rxlist.com
"Ocular toxicity seen with some related drugs has not been observed
in ciprofloxacin-treated animals.”
Source:
www.rxlist.com
All brand names are trademarks of their respected manufacturers.
The information being provided above is to be considered a quick
reference guide. For complete information please view the
complete package insert at
www.rxlist.com