Veraflox (pradofloxacin) tablets (15 mg) (Canada)

Company: Elanco

(pradofloxacin) tablets

15 mg, 60 mg, 120 mg

VETERINARY USE ONLY

DIN 02437392 (15 mg), 02437406 (60 mg), 02437414 (120 mg)

Description

Veraflox (pradofloxacin) tablets 15 mg are brownish single-scored tablets with “P15” on one side.

Veraflox (pradofloxacin) tablets 60 mg are brownish single-scored tablets with “P60” on one side.

Veraflox (pradofloxacin) tablets 120 mg are brownish single-scored tablets with “P120” on one side.

THERAPEUTIC CLASSIFICATION:

Fluoroquinolone antimicrobial

Veraflox (pradofloxacin) tablets (15 mg) Indications:

Veraflox (pradofloxacin) tablets are indicated in dogs for the treatment of:

● Wound infections caused by susceptible strains of the Staphylococcus intermedius group (including S. pseudintermedius),

● Deep pyoderma caused by susceptible strains of the Staphylococcus intermedius group (including S. pseudintermedius).

Dosage and Administration

Dosage:

Dogs: Administer 3.0 mg/kg bodyweight of pradofloxacin once daily. To ensure a correct dosage, bodyweight should be determined as accurately as possible to avoid underdosing.

Due to the available tablet sizes the resulting dose range is 3.0 to 4.5 mg/kg bodyweight according to the following table:

Duration of treatment:

The duration of the treatment depends on the nature and severity of the infection and on the response to treatment.

The choice of Veraflox tablets as the most appropriate treatment should be confirmed by clinical experience and where possible by pathogen culture and drug susceptibility testing. The treatment should be re-considered if no improvement of the clinical conditions is observed within 3 days, or in cases of deep pyoderma 14 days, after starting the treatment.

Contraindications

Do not use in dogs with known hypersensitivity to fluoroquinolones.

Do not use in dogs during the period of growth as developing articular cartilage may be affected. The period of growth depends on the breed. For the majority of breeds, Veraflox tablets must not be used in dogs of less than 12 months of age and in giant breeds less than 18 months.

Do not use in dogs with pre-existing articular cartilage lesions, since lesions may worsen during treatment with fluoroquinolones.

CAUTIONS:

Pyoderma commonly occurs secondary to an underlying disease, thus, it is advisable to determine the underlying cause and to treat the animal accordingly.

Pradofloxacin may increase sensitivity of the skin to sunlight. During treatment, dogs should not be exposed to excessive sunlight.

Excretion via kidneys is an important elimination route for pradofloxacin in dogs. As for other fluoroquinolones, the renal excretion rate of pradofloxacin may be decreased in dogs with impaired kidney function and, therefore, Veraflox tablets should be used with caution in such animals.

Quinolones 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 and may lead to convulsive seizures.

The safety of Veraflox tablets has not been established in dogs that are used for breeding or that are pregnant and/or lactating.

Warnings

To limit the development of antimicrobial resistance:

● Fluoroquinolone drugs such as Veraflox should not be used indiscriminately.

● Veraflox tablets are for oral use in dogs only.

Keep out of reach of children. Individuals with a history of quinolone hypersensitivity should avoid this product. Consult a physician in case of accidental ingestion. In humans, there is a risk of photosensitization within a few hours after exposure to quinolones. If excessive accidental exposure occurs, avoid direct sunlight. Do not eat, drink or smoke while handling this product. Dispose the unused drug in accordance with the Provincial/Municipal guidelines.

Adverse Reactions

Slight and transient digestive tract disorders may occur in very rare cases. This is thought to occur as a result of the action of an oral anti-infective.

Field Studies:

In two European multi-site field studies, a total of 332 dogs (ages 0.4 to 18 years) were evaluated for safety when given either Veraflox tablets at a dose of 3 mg/kg or a positive control article (amoxicillin clavulanic acid) at a dose of 12.5 mg/kg. Treatment duration varied from 7 to 63 days in length. Adverse reactions are summarized in Table 1.

* Some dogs may have experienced more than one adverse reaction or more than one occurrence of the same adverse reaction during the study.

Post-Market Experience:

Although all adverse reactions are not reported, the following adverse reaction information is based on voluntary post-approval drug experience reporting. It is generally recognized that this method of reporting results in significant under-reporting of adverse drug reactions. It should be noted that suspected adverse drug reactions listed reflect reporting and not causality.

In dogs, vomiting, diarrhea, hypersalivation, ataxia and lethargy were very rarely reported.

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

OVERDOSE:

Intermittent vomiting and soft faeces were observed in dogs after repeated oral administration of 2.7 times the maximum recommended dose. In target animal safety studies in dogs pradofloxacin produced no observable adverse reactions when administered orally at 15 mg/kg bodyweight/day (5 times the minimum recommended dose) over a period of 90 days. In laboratory safety studies, overdoses > 26.5 mg/kg pradofloxacin caused bone marrow suppression resulting in varying degrees of leukopenia, anemia and thrombocytopenia.

Clinical Pharmacology

Mode of Action:

The primary mode of action of the fluoroquinolones involves interaction with enzymes essential for major DNA functions such as replication, transcription and recombination. The primary targets for pradofloxacin are the bacterial DNA gyrase and topoisomerase IV enzymes. Reversible association between pradofloxacin and DNA gyrase or DNA topoisomerase IV in the target bacteria results in inhibition of these enzymes and rapid death of the bacterial cell. The rapidity and extent of bacterial killing are directly proportional to the drug concentration.

Pharmacokinetics:

Pradofloxacin is rapidly absorbed following oral administration of Veraflox tablets to fasted dogs, with peak serum concentrations occurring in approximately 2 hours. Pradofloxacin is almost completely absorbed, reaching peak serum concentrations (Cmax) of 1.6 µg/mL. The relative bioavailability of pradofloxacin when administered to fasted dogs is provided in Table 2.

Dose proportional increases in drug concentrations are observed in dogs when Veraflox tablets are administered to fasted dogs in doses ranging from 1 to 9 mg/kg bodyweight. Due to its short elimination half-life, there is minimal pradofloxacin accumulation following multiple daily administrations (accumulation index = 1.1). Approximately 35% of the total drug concentrations are bound to plasma proteins. The volume of distribution (V_d) is >2 L/kg bodyweight.

Pradofloxacin is eliminated from serum with a terminal half-life of approximately 7 hours. Major elimination pathways are glucuronidation as well as renal excretion. Pradofloxacin is cleared from the body at 0.24 L/h/kg. Approximately 40% of the administered product is excreted unchanged via the kidneys.

MICROBIOLOGY:

Veraflox tablets are bactericidal, with activity against Gram-negative, Gram-positive, and anaerobic bacteria. The mechanism of action is dual targeting through inhibition of DNA gyrase and topoisomeriase IV.

The minimum inhibitory concentrations (MICs) for pradofloxacin against Staphylococcus pseudintermedius were determined for isolates obtained from dogs with either wound infections or deep pyoderma enrolled in field studies in Europe in 2001 and 2005 respectively. The MIC values are listed in Table 3.

There were no clinical treatment failures in the Wound Study. In the Deep Pyoderma Study, four (4) isolates from pradofloxacin treatment failure cases had elevated pradofloxacin MICs (Escherichia coli - MIC = 2 µg/mL; Pseudomonas aeruginosa - MIC = 1 µg/mL; Enterococcus faecalis - MIC = 1 µg/mL; Staphylococcus intermedius - MIC = 1 µg/mL).

Effectiveness

Clinical Field Trial for Safety and Efficacy of Veraflox Tablets to treat Deep Pyoderma in Dogs:

A European multicenter (25 sites), controlled, randomised, blinded and blocked clinical field study was conducted to evaluate the efficacy and safety of Veraflox tablets in the treatment of deep pyoderma in dogs.

A total of 135 dogs were randomly allocated to one of the two treatments. Sixty-six (66) dogs were orally treated by the animal owner with Pradofloxacin (treatment group T1) once daily at 3 mg/kg (mean dose = 3.88 ± 1.04 mg/kg) and sixty-nine (69) dogs with the positive control tablets (treatment group T2) twice daily for 14 to 63 consecutive days.

The efficacy of pradofloxacin was assessed for non-inferiority by comparing the per-protocol population of dogs cured over the study period to the control product. For dogs treated with pradofloxacin (n = 56) the percentage of cured dogs was 85.7% (95% confidence Interval for percentage of cured dogs 75.9 to 93.6%). The percentage of cured dogs treated with the control product (n = 51) was 72.5% (95% confidence interval for percentage of cured dogs 60.4 to 84.1%). Non-inferiority of pradofloxacin to the control product was confirmed (lower 95% confidence limit of 1.29% using a non-inferiority delta of -26%; p = 0.9999).

Clinical Field Trial for Safety and Efficacy of Veraflox Tablets to treat Wound Infections in Dogs:

A European multicenter (17 sites), controlled, randomised, blinded clinical field study was conducted to evaluate the efficacy and safety of Veraflox tablets in the treatment of wound infections in dogs.

A total of 197 dogs were randomly allocated to one of the two treatments. Ninety-eight (98) dogs were orally treated by the animal owner with pradofloxacin (treatment group A) once daily at 3 mg/kg (mean dose = 3.8 ± 1.0 mg/kg) and ninety-nine (99) dogs with the positive control (treatment group B) twice daily for 7 consecutive days. Efficacy was evaluated based on the wound scores determined on day 0, day 7 and day 14. The primary efficacy criterion was the percentage of animals in the per-protocol population cured on day 14.

On study day seven, 52.2% of dogs treated with Veraflox tablets (90%-confidence interval from 41.5% to 62.8%) and 47.1% of dogs treated with control product (90%-confidence interval from 36.9% to 57.6%) were cured. On day 14, all animals (n=67) which were treated with Veraflox tablets were cured (confidence interval from 95.6% to 100%). Animals treated with the control product (n=67) showed a cure rate of 94.0% on day 14 (confidence interval from 86.9% to 97.9%).

Non-inferiority of pradofloxacin to the control product was confirmed on day 14 (lower limit of the 95% confidence limit of 1.4% using a non-inferiority delta of -20%; (p = 0.0001).

ANIMAL SAFETY:

Target Animal Safety:

A controlled laboratory study was conducted to evaluate the safety of Veraflox tablets in dogs. Four groups of eight dogs each (8 to 11 months of age at initial dosing) were treated orally, once daily, at 0, 3, 9 or 15 mg/kg (0, 1, 3 and 5 times the recommended dose) for at least 91 consecutive days. Indices monitored throughout the study included: clinical observations, physical examinations, body weight, food consumption, hematology/coagulation, serum chemistry, urinalysis, ophthalmologic examinations, gross pathology, and microscopic pathology.

Dogs generally remained clinically normal throughout the study (both acclimation and treatment phases). Nonetheless, clinical signs, including emesis, altered fecal consistency, and post-dosing salivation were occasionally observed in all treatment groups. Physical examinations, performed by the clinical veterinarian, were within normal limits for all dogs throughout the entire treatment phase of the study.

Statistical analysis of hematological and coagulation results revealed statistically significant differences in seven of 21 indices for the pairwise control comparisons involving the 1X, 3X, and 5X groups (basophils, monocytes, leukocytes, hematocrit, hemoglobin, mean corpuscular hemoglobin concentration and mean corpuscular volume). None of the statistically significant hematological or coagulation indices were considered to be treatment-induced or biologically relevant.

Statistical analysis of clinical chemistry results revealed statistically significant differences in five of 21 indices for the pairwise control comparisons involving the 1X, 3X, and 5X groups (ALT, amylase, glucose, sodium, phosphorus). All of the statistically significant biochemical differences were considered minimal and none were considered to be treatment induced or biologically relevant. The means for all affected biochemical indices remained within historical reference ranges.

There were no treatment related differences between groups related to body weight, food consumption, urinalysis, ophthalmologic examinations, gross pathology or microscopic pathology.

STORAGE INFORMATION:

Store in the original container. Store up to 25°C. Avoid excessive heat.

How Supplied

Tablets per Carton

15 mg: 70 (10 blisters of 7 tablets)

60 mg: 70 (10 blisters of 7 tablets)

120 mg: 70 (10 blisters of 7 tablets)

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

Veraflox, Elanco and the diagonal bar logo are trademarks of Elanco or its affiliates.

© 2022 Elanco or its affiliates.

19Jun2022

CPN: 1231224.2