Baytril Flavoured Tablets (150 mg) (Canada)

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Baytril Flavoured Tablets (150 mg) Indications
Warnings and cautions for Baytril Flavoured Tablets (150 mg)
Direction and dosage information for Baytril Flavoured Tablets (150 mg)

Baytril Flavoured Tablets (150 mg)

This treatment applies to the following species:

Dogs

Company: Elanco

Enrofloxacin

Flavoured Tablets

FOR VETERINARY USE ONLY

DIN 02239524 - 15 mg

DIN 02239525 - 50 mg

DIN 02239526 - 150 mg

Description

Enrofloxacin is a synthetic chemo-therapeutic agent from the class of the quinolone carboxylic acid derivatives. It has antibacterial activity against a broad spectrum of Gram negative and Gram positive bacteria. (See Table 1). It is rapidly absorbed from the digestive tract, penetrating into all measured body tissues and fluids. (See Table 2). Flavoured tablets are available in three sizes (15, 50, and 150 mg enrofloxacin.

CHEMICAL NOMENCLATURE: 1-cyclopropyl-7-(4-ethyl-1-piperazinyl)-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid.

ACTIONS:

Microbiology: Enrofloxacin, a 4-fluoroquinolone compound, is bactericidal with activity against a broad spectrum of both Gram negative and Gram positive bacteria.

Fluoroquinolones elicit their bactericidal properties through interactions with two intercellular enzymes - DNA gyrase (DNA topoisomerase II) and DNA topoisomerase IV - which are essential for bacterial DNA transcription, synthesis and replication. It is believed that fluoroquinolones actively bind with DNA:ENZYME complexes and thereby inhibit the essential processes catalyzed by the enzymes (DNA supercoiling and chromosomal decatenation)¹. The ultimate outcome of fluoroquinolone intervention is DNA fragmentation and bacterial cell death.^2,3

Enrofloxacin minimum inhibitory concentrations (MICs) were determined for canine and feline bacterial isolates originating from natural infections of the dermal, gastrointestinal, respiratory and urinary systems. Seven hundred and thirty eight (738) isolates were collected from 14 different diagnostic laboratories located throughout the United States. Bacterial identity was confirmed by colony morphology, Gram stain and biochemical testing; for mycoplasmas, identity was confirmed by colony morphology and Dienes stain. The in vitro susceptibilities of all bacterial and mycoplasma isolates were determined by enrofloxacin microbroth dilution methods and the resultant enrofloxacin MIC₅₀ and MIC₉₀ values are presented in Table 1. In vitro susceptibility testing was performed in accordance with guidelines established by the National Committee for Clinical Laboratory Standards (NCCLS; Document M31-P, Volume 14, November 20).

Table 1 - MIC Values for Enrofloxacin Against Canine and Feline Pathogens (Diagnostic laboratory isolates, 1997)

Organism	Isolates	MIC₅₀ (µg/ml)	MIC₉₀ (µg/ml)
Bordetella spp.	25	0.5	0.5
Enterococcus spp.	40	1	2
Escherichia coli	138	0.03	0.06
Klebsiella pneumoniae	32	0.06	0.12
Mycoplasma spp.	76	0.25	0.5
Pasteurella spp.	16	0.015	0.03
Proteus spp.	88	0.12	0.25
Pseudomonas aeruginosa	69	1	8
Salmonella spp.	15	0.06	0.25
Staphylococcus intermedius	119	0.12	0.25
Staphylococcus spp.	120	0.12	0.25

Distribution in the Body: Enrofloxacin penetrates into all canine and feline tissues and body fluids. Concentrations of drug equal to or greater than the MIC for many pathogens (See Tables 1 and 2) are reached in most tissues by two hours after dosing at 2.5 mg/kg and are maintained for 8-12 hours after dosing. Particularly high levels of enrofloxacin are found in urine. A summary of the body fluid/tissue drug levels at 2 to 12 hours after dosing at 2.5 mg/kg is given in Table 2.

Table 2 - Body Fluid/Tissue distribution of Enrofloxacin in Dogs and Cats

Single Oral Dose = 2.5 mg/kg (1.13 mg/lb)

Body Fluids (mcg/mL)	Post-treatment Enrofloxacin Levels
	Canine (n=2)		Feline (n=4)
	2 Hr.	8 Hr.	2 Hr.	12 Hr.
Bile	. . .	. . .	2.13	1.97
Cerebrospinal Fluid	. . .	. . .	0.37	0.10
Urine	43.05	55.35	12.81	26.41
Eye Fluids	0.53	0.66	0.45	0.65
Whole Blood	1.01	0.36	. . .	. . .
Plasma	0.67	0.33	. . .	. . .
Serum	. . .	. . .	0.48	0.18
Tissues (mcg/g) Hematopoietic System
Liver	3.02	1.36	1.84	0.37
Spleen	1.45	0.85	1.33	0.52
Bone Marrow	2.10	1.22	1.68	0.64
Lymph Node	1.32	0.91	0.49	0.21
Urogenital System
Kidney	1.87	0.99	1.43	0.37
Bladder Wall	1.36	0.98	1.16	0.55
Testes	1.36	1.10	1.01	0.28
Prostate	1.36	2.20	1.88	0.55
Ovaries	. . .	. . .	0.78	0.56
Uterine Wall	1.59	0.29	0.81	1.05
Gastrointestinal and Cardiopulmonary Systems
Lung	1.34	0.82	0.91	0.33
Heart	1.88	0.78	0.84	0.32
Stomach	3.24	2.16	3.26	0.27
Small Intestine	2.10	1.11	2.72	0.40
Large Intestine	. . .	. . .	0.94	1.10
Other
Fat	0.52	0.40	0.24	0.11
Skin	0.66	0.48	0.46	0.17
Muscle	1.62	0.77	0.53	0.29
Brain	0.25	0.24	0.22	0.12
Mammary Gland	0.45	0.21	0.36	0.30
Feces	1.65	9.97	0.37	4.18

Pharmacokinetics: In dogs, the absorption and elimination characteristics of the oral formulation are linear (plasma concentrations increase proportionally with dose) when enrofloxacin is administered at up to 11.5 mg/kg, twice daily.⁴ Approximately 80% of the orally administered dose enters the systemic circulation unchanged. The eliminating organs, based on the drug’s body clearance time, can readily remove the drug with no indication that the eliminating mechanisms are saturated. The primary route of excretion is via the urine. The absorption and elimination characteristics beyond this point are unknown. In cats, no oral absorption information is available at other than 2.5 mg/kg, administered orally as a single dose. Saturable absorption and/or elimination processes may occur at greater doses. When saturation of the absorption process occurs, the plasma concentration of the active moiety will be less than predicted, based on the concept of dose proportionality.

Following an oral dose in dogs of 2.5 mg/kg (1.13 mg/lb), enrofloxacin reached 50% of its maximum serum concentration in 15 minutes and peak serum level was reached in one hour. The elimination half-life in dogs is approximately 2 1/2-3 hours at that dose, while in cats it is greater than 4 hours. In a study comparing dogs and cats, the peak concentration and the time to peak concentration were not different.

A graph indicating the mean serum levels following a dose of 2.5 mg/kg (1.13 mg/lb) in dogs (oral and intramuscular) and cats (oral) is shown in Figure 1.

Figure 1 - Serum Concentrations of Enrofloxacin Following a Single Oral or Intramuscular Dose at 2.5 mg/kg in Dogs and a Single Oral Dose at 2.5 mg/kg in Cats.

Breakpoint: Based on in vitro susceptibility, pharmacokinetics and clinical response, the following breakpoints are recommended for canine and feline isolates. These breakpoints have been approved by the National Committee for Clinical Laboratory Standards (NCCLS) and are published in NCCLS document M-31:

Zone Diameter (mm)	MIC µg/mL	Interpretation
≥ 23	≤ 0.5	Susceptible (S)
18 - 22	1 - 2	Flexible Label (F)
≤ 17	≥ 4	Resistant (R)

A report of ‘Susceptible’ indicates that the pathogen is likely to be inhibited by plasma levels generally attained with the lower end of the dose range (2.5 mg/kg BW twice daily or 5.0 mg/kg BW once daily). A report of ‘Flexible Label’ indicates that the pathogen is likely inhibited by plasma levels generally attained with adherence to the principles of FDA-approved Professional Flexible Labeling in dogs. With enrofloxacin, conditions due to ‘F’ bacteria can be treated successfully by administration of an intermediary dose within the lower (>5.0 mg/kg BW once daily) and upper (≤ 20 mg/kg BW once daily) limits of the approved flexible dose range. Determination of the precise dosage is based upon a careful assessment of the interrelationships amongst host (immunocompetency, stress, site of infection, etc.), pathogen (virulence, MIC, emerging resistance, etc.) and chemotherapeutic (dose-dependent vs. time-dependent efficacy, postantibiotic effects, toxicity etc.). A report of ‘Resistant’ indicates that the pathogen is unlikely to be inhibited by plasma levels attained with administration of the highest approved dose (20 mg/kg BW once daily) and alternative antimicrobial therapy should be selected.

Standardized procedures require the use of laboratory quality control organisms for both standardized disk diffusion assays and standardized dilution assays. The 5 µg enrofloxacin disk should give the following zone diameters and enrofloxacin powder should provide the following MIC values for reference strains. The indicated ranges for quality control organisms are NCCLS-approved.

QC Strain	Zone Diameter (mm)	MIC µg/mL
E. coli ATCC 25922	32 - 40	0.008 - 0.03
P. aeruginosa ATCC 27853	15 - 19	1 - 4
S. aureus ATCC 25923	27 - 31	. . .
S. aureus ATCC 25913	. . .	0.03 - 0.12

Baytril Flavoured Tablets (150 mg) Indications

Dogs and Cats: Baytril (enrofloxacin flavoured tablets) are indicated for the treatment of diseases in dogs and cats associated with bacteria susceptible to enrofloxacin.

EFFICACY CONFIRMATION:

Dogs: Clinical efficacy was established in dermal infections (wounds and abscesses) associated with susceptible strains of Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Staphylococcus intermedius; respiratory infections (pneumonia, tonsillitis, rhinitis) associated with susceptible strains of Escherichia coli and Staphylococcus aureus; and urinary cystitis associated with susceptible strains of Escherichia coli, Proteus mirabilis, and Staphylococcus aureus.

Cats: Clinical efficacy was established in dermal infections (wounds and abscesses) associated with susceptible strains of Pasteurella multocida, Staphylococcus aureus, and Staphylococcus epidermidis.

Contraindications

Enrofloxacin is contraindicated in dogs and cats known to be hypersensitive to quinolones.

Dogs: Based on the studies discussed under the section on Animal Toxicology, the use of enrofloxacin is contraindicated in small and medium breeds of dogs during the rapid growth phase (between 2 and 8 months of age). The safe use of enrofloxacin has not been established in large and giant breeds during the rapid growth phase. Large breeds may be in this phase for up to one year of age and the giant breeds for up to 18 months. In clinical field trials utilizing a daily oral dose of 5.0 mg/kg, there were no reports of lameness or joint problems in any breed. However, controlled studies with histological examination of the articular cartilage have not been conducted in the large or giant breeds.

Adverse Reactions

Dogs: Two of the 270 (0.7%) dogs treated with Baytril (enrofloxacin flavoured tablets) at 5.0 mg/kg per day in the clinical field studies exhibited side effects, which were apparently drug related. These two cases of vomition were self-limiting.

Post Approval Experience: The following adverse experiences, although rare, are based on voluntary post-approval adverse drug experience reporting. The categories of reactions are listed in decreasing order of frequency by body system.

Gastrointestinal: Anorexia, diarrhea, vomiting, elevated liver enzymes

Neurologic: ataxia, seizures

Behavioral: Depression, lethargy, nervousness

Cats: No drug-related side effects were reported in 124 cats treated with Baytril (enrofloxacin flavoured tablets) at 5.0 mg/kg per day for 10 days in clinical field studies.

Ocular: Loss of vision, retinal abnormalities (retinal degeneration, retinal atrophy, attenuated retinal vessels, and hyperreflective tapeta have been reported), mydriasis

Gastrointestinal: vomiting, anorexia, elevated liver enzymes, diarrhea

Neurologic: ataxia, seizures

Behavioral: Depression, lethargy, vocalization, aggression

To report suspected adverse drug events or for technical assistance, contact Elanco Canada Limited at 1-800-265-5475.

ANIMAL TOXICOLOGY:

Dogs: Adult dogs receiving enrofloxacin orally at a daily dosage rate of 52 mg/kg for 13 weeks had only isolated incidences of vomition and inappetence. Adult dogs receiving the tablet formulation for 30 consecutive days at a daily treatment of 25 mg/kg did not exhibit significant clinical signs nor were there effects upon the clinical chemistry, hematological or histological parameters. Daily doses of 125 mg/kg for up to 11 days induced vomition, inappetence, depression, difficult locomotion and death while adult dogs receiving 50 mg/kg/day for 14 days had clinical signs of vomition and inappetence.

Adult dogs dosed intramuscularly for three treatments at 12.5 mg/kg followed by 57 oral treatments at 12.5 mg/kg, all at 12 hour intervals, did not exhibit either significant clinical signs or effects upon the clinical chemistry, hematological or histological parameters.

Oral treatment of 15 to 28 week old growing puppies with daily dosage rates of 25 mg/kg has induced abnormal carriage of the carpal joint and weakness in the hindquarters. Significant improvement of clinical signs is observed following drug withdrawal. Microscopic studies have identified lesions of the articular cartilage following 30 day treatments at either 5, 15 or 25 mg/kg in this age group. Clinical signs of difficult ambulation or associated cartilage lesions have not been observed in 29 to 34 week old puppies following daily treatments of 25 mg/kg for 30 consecutive days nor in 2 week old puppies with the same treatment schedule.

Tests indicated no effect on circulating microfilariae or adult heartworms (Dirofilaria immitis) when dogs were treated at a daily dosage rate of 15 mg/kg for 30 days. No effect on cholinesterase values was observed.

No adverse effects were observed on reproductive parameters when male dogs received 10 consecutive daily treatments of 15 mg/kg/day at 3 intervals (90, 45 and 14 days) prior to breeding or when female dogs received 10 consecutive daily treatments of 15 mg/kg/day at 4 intervals; between 30 and 0 days prior to breeding, early pregnancy (between 10th & 30th days), late pregnancy (between 40th & 60th days), and during lactation (the first 28 days).

Cats: Cats in age ranges of 3 to 4 months and 7 to 10 months received daily treatments of 25 mg/kg for 30 consecutive days with no adverse effects upon the clinical chemistry, hematological or histological parameters. In cats 7-10 months of age treated daily for 30 consecutive days, 2 of 4 receiving 5 mg/kg, 3 of 4 receiving 15 mg/kg, 2 of 4 receiving 25 mg/kg and 1 of 4 nontreated controls experienced occasional vomition. Five to 7 month old cats had no side effects with daily treatments of 15 mg/kg for 30 days, but 2 of 4 animals had articular cartilage lesions when administered 25 mg/kg/day for 30 days.

Doses of 125 mg/kg for 5 consecutive days to adult cats induced vomition, depression, incoordination and death while those receiving 50 mg/kg for 6 days had clinical signs of vomition, inappetence, incoordination and convulsions, but they returned to normal.

Enrofloxacin was administered to thirty-two (8 per group), six to eight month-old cats at doses of 0, 5, 20, and 50 mg/kg once a day for 21 consecutive days. There were no adverse effects observed in cats administered 5 mg/kg body weight of enrofloxacin. The administration of enrofloxacin at 20 mg/kg body weight or greater, resulted in mild to severe retinal degeneration, abnormal electroretinograms, and microscopic changes in the retina.

DRUG INTERACTIONS:

Compounds that contain metal cations (e.g., aluminum, calcium, iron, magnesium) may reduce the absorption of some quinolone-class drugs from the intestinal tract. Concomitant therapy with other drugs that are metabolized in the liver may reduce the clearance rates of the quinolone and the other drug.

Dogs: Enrofloxacin has been administered to dogs at a daily dosage rate of 10 mg/kg concurrently with a wide variety of other health products including anthelmintics (praziquantel, febantel, sodium disophenol), insecticides (fenthion, pyrethrins), heartworm preventatives (diethylcarbamazine) and other antibiotics (ampicillin, gentamicin sulfate, penicillin, dihydrostreptomycin). No incompatibilities with other drugs are known at this time.

Cats: Enrofloxacin was administered at a daily dosage rate of 5 mg/kg concurrently with anthelmintics (praziquantel, febantel), an insecticide (propoxur) and another antibacterial (ampicillin). No incompatibilities with other drugs are known at this time.

Baytril Flavoured Tablets (150 mg) Caution

Quinolone-class drugs should be used with caution in animals with known or suspected Central Nervous System (CNS) disorders. In such animals, quinolones have, in rare instances, been associated with CNS stimulation which may lead to convulsive seizures.

Quinolone-class drugs have been associated with cartilage erosions in weight-bearing joints and other forms of arthropathy in immature animals of various species.

In rare instances, use of this product in cats has been associated with retinal toxicity. Safety in breeding or pregnant cats has not been established.

Warnings:

To limit the development of antimicrobial resistance: - fluoroquinolone drugs such as Baytril tablets should not be used indiscriminately - Baytril tablets should not be used in food producing animals.

Keep out of reach of children.

Baytril Flavoured Tablets (150 mg) Dosage And Administration

Dogs: The dose range of Baytril (enrofloxacin flavoured tablets) in dogs is 5 to 20 mg/kg (2.27-9.07 mg/lb) of body weight, either as a single dose or divided into two (2) equal daily doses administered at twelve (12) hour intervals. Selection of a dose within this range should be based on clinical experience, the severity of disease, and susceptibility of the pathogen.

Animals which receive doses in the upper-end of the dose range should be carefully monitored for clinical signs that may include inappetence, depression, and vomition.

Cats: The dose of Baytril (enrofloxacin flavoured tablets) in cats is 5 mg/kg (2.27 mg/lb) of body weight, either as a single dose or divided into two (2) equal daily doses administered at twelve (12) hour intervals. In rare instances, use of this product in cats has been associated with retinal toxicity. Based on post approval experience, cats should be carefully monitored for clinical signs of mydriasis and/or changes in the retina.

Dogs & Cats: The duration of treatment should be selected based on clinical evidence. Generally, administration of Baytril flavoured tablets should continue for at least 2-3 days beyond cessation of clinical signs. For severe and/or complicated infections, more prolonged therapy, up to 30 days, may be required. If no improvement is seen within five days, the diagnosis should be reevaluated and a different course of therapy considered.

The lower limit of the dose range in dogs and the daily dose for cats was based on efficacy studies in dogs and cats where enrofloxacin was administered at 2.5 mg/kg twice daily. Target animal safety and toxicology were used to establish the upper limit of the dose range for dogs and treatment duration for dogs and cats.

Palatability:

In a palatability study in dogs, 58% of flavoured Baytril 50 mg tablets were voluntarily consumed, compared with 23% of unflavoured tablets. If necessary, the tablets may be offered to dogs in food or hand-administered (pilled). In cats, flavoured Baytril tablets should be pilled.

Storage

Do not store above 40°C.

How Supplied

Baytril Tablets Tablet Size	Tablets/Carton
15 mg	1 strips of 10 tablets
15 mg	10 strips of 10 tablets
50 mg	1 strips of 10 tablets
50 mg	10 strips of 10 tablets
150 mg	1 strips of 10 tablets
150 mg	10 strips of 10 tablets

References

¹ Hooper DC and Wolfson JS. Mechanisms of quinolone action and bacterial killing, in Quinolone Antimicrobial Agents. Washington DC, American Society for Microbiology, 2nd ed., 1993, 53-75.

² Gootz TD and Brightly KE. Fluoroquinolone antibacterials: sar. mechanism of action, resistance and clinical aspects. Medicinal Research Reviews 1996; 16(5): 433-486.

³ Drlica K and Zhoa X. DNA gyrase, topoisomerase IV and the 4-quinolones. Microbiology and Molecular Biology Reviews 1997; 61(3): 377-392.

⁴ Walker RD et al, Pharmacokinetic evaluation of enrofloxacin administered orally to healthy dogs. American Journal of Veterinary Research 1992; 53(12): 2315-2319.

Elanco Canada Limited, 1919 Minnesota Court, Suite 401, Mississauga, Ontario L5N 0C9

Baytril, is sold by Elanco or its affiliates and is not a product of Bayer. The Product Name Baytril, is owned by Bayer and used under license.

10Jun2022

CPN: 1231201.1

ELANCO CANADA LIMITED
1919 MINNESOTA COURT, SUITE 401, MISSISSAUGA, ON, L5N 0C9

Customer Service:		800-265-5475
Fax:		519-821-7831
Website:		www.elanco.ca
Email:		elancocanadacustomerservice@elancoah.com

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