Rilexine Chewable Tablets (300 mg) (Canada)

Company: Virbac

(cephalexin tablets)

DIN 02442701 300 mg

DIN 02442728 600 mg

Mfr. Std.

VETERINARY USE ONLY

Antimicrobial for oral use in dogs only.

Description

RILEXINE^® Chewable Tablets are a chewable, bisected tablet supplied in 3 strengths.

THERAPEUTIC CLASSIFICATION: RILEXINE^® Chewable Tablets contain cephalexin (as cephalexin monohydrate), a cephalosporin of the beta-lactam class of antibiotics.

Rilexine Chewable Tablets (300 mg) Indications

For the treatment of superficial pyoderma in dogs caused by susceptible strains of Staphylococcus pseudintermedius.

Dosage and Administration

The recommended dose is 22 mg/kg (10 mg/lb) of body weight, given orally twice daily, for 28 days. Appropriate culture and susceptibility tests may be performed before treatment to determine the causative organism and its susceptibility to cephalexin. Therapy with RILEXINE^® Chewable Tablets can be initiated before results of these tests are known; once the results become available, antimicrobial therapy should be adjusted accordingly. If acceptable response to treatment is not observed, then the diagnosis should be reevaluated and appropriate alternative therapy considered.

Contraindications

RILEXINE^® Chewable Tablets are contraindicated in dogs with a known allergy to this cephalexin or the β-lactam (any of the penicillins or cephalosporins) group of antibiotics.

CAUTIONS: Prescribing antibacterial drugs in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to treated animals and may increase the risk of the development of drug-resistant animal pathogens.

The safe use of RILEXINE^® Chewable Tablets in dogs intended for breeding and in pregnant or lactating bitches has not been evaluated.

Cephalexin may cause false positive reactions for glucose in the urine. Occasionally, cephalosporins have been associated with myelotoxicity, thereby creating a toxic neutropenia.

Other haematological reactions observed with cephalosporin therapy include neutropenia, anemia, hypoprothrombinemia, thrombocytopenia, prolonged prothrombin time (PT) and partial thromboplastin time (PTT), platelet dysfunction and transient increases in serum aminotransferases.

Warnings

Keep out of reach of children. Antimicrobials, including penicillins and cephalosporins, can cause allergic reactions in sensitized individuals. Sensitized individuals handling such antimicrobials, including cephalexin, should avoid contact of the product with the skin and mucous membranes.

Adverse Reactions

The most common adverse reactions in dogs include vomiting, diarrhea, anorexia and lethargy. To report suspected adverse reactions call Virbac at 1-800-338-3659.

A total of 211 dogs were included in the field study safety analysis. Adverse reactions reported in dogs treated with RILEXINE^® Chewable Tablets and placebo are summarized in Table 1.

Table 1: Number of Adverse Reactions*

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

No clinically significant differences were observed in the mean values for all laboratory tests including urinalysis between RILEXINE^® Chewable Tablets and placebo-treated dogs. At the end of treatment, group means for neutrophils, WBC and globulin values were significantly higher in the placebo group than in the RILEXINE^® Chewable Tablets group; whereas, group mean values for eosinophils, A/G Ratio values and total protein values were significantly higher in the RILEXINE^® Chewable Tablets group than in the placebo group. For all six of these parameters, the differences were not clinically significant and the mean values for each of the parameters remained within the normal range.

Occasionally, hypersensitivity reactions unrelated to dose can occur with cephalosporins and can manifest as rashes, fever, eosinophilia, lymphadenopathy, haemolytic anemia, arthralgia, or anaphylaxis. For hematological adverse events associated with cephalosporins, see CAUTIONS section.

OTHER INFORMATION:

Clinical Pharmacology - Cephalexin belongs to the cephalosporin family of bactericidal antibiotics. Cephalexin is readily and almost completely absorbed following oral administration (90% absolute bioavailability). Blood concentrations are proportional to dose within the range of at least 15 to 45 mg/kg. Binding to canine plasma proteins is low, ranging from 9 to 13% for cephalexin concentrations of 0.5 to 100 µg/mL.

Food reduces the peak cephalexin concentrations but has negligible effect on the extent of absorption. A summary of the pharmacokinetics (PK) observed in fed and fasted Beagle dogs administered a single 22 mg/kg dose is provided in Table 2.

Table 2: Pharmacokinetics Parameter values (mean ± standard deviation), protein-corrected in fasted and fed dogs following a single administration of 22 mg/kg dose of RILEXINE^® Chewable Tablets (n = 12).

*harmonic mean NA: not applicable

Cephalosporins are associated with time-dependent killing effects. Accordingly, the pharmacodynamic (PD) target is time above MIC (T>MIC). For staphylococcal infections, the goal for time above MIC is 40% of the dosing interval (which translates to 4.8 hrs for a BID dosing schedule). To assess whether or not the PK-PD target is met with a 22 mg/kg BID dosing regimen under fed and fasted conditions, it was assumed that the MIC₉₀ for S. pseudintermedius is 2 µg/mL. Plasma drug concentrations were normalized to exactly a 22 mg/kg dose and corrected for 10% protein binding (protein binding observed in canine plasma). Thus, under both fed and fasted conditions, the PK/PD target for S. pseudintermedius was met in all dogs after the first dose.

Microbiology - Cephalexin like other β-lactam antimicrobials, exerts its inhibitory effect by interfering with bacterial cell wall synthesis. This interference is primarily due to its covalent binding to the penicillin-binding proteins (PBPs) (i.e., transpeptidase and carboxypeptidase), which are essential for synthesis of the bacterial wall. Minimum Inhibitory Concentrations (MICs) for cephalexin against label-claim pathogens isolated from canine pyoderma in a 2008-2009 U.S.A. field trial are presented in Table 3. All MICs were determined in accordance with the Clinical Laboratory Standards Institute (CLSI) standards.

Table 3: Summary of Cephalexin MIC values against S. pseudintermedius isolates from 88 dogs treated with RILEXINE^® Chewable Tablets for bacterial pyoderma in a U.S.A. field study during 2008-2009.

* No post-treatment sampling was conducted due to the absence of lesions

** Of the 27 failures, 10 did not have positive post-treatment cultures

Effectiveness

The clinical effectiveness of RILEXINE^® Chewable Tablets was established in a randomized, multi-location, placebo-controlled field study (see Table 4). In this study, 149 dogs with superficial bacterial pyoderma treated with either RILEXINE^® Chewable Tablets (n=100) at 22 mg/kg (10 mg/lb) body weight or with a negative control (n=49), twice daily for 28 days, were analyzed. RILEXINE^® Chewable Tablets were considered superior to the placebo (70% success rate vs. 14.3% respectively) in the treatment of all bacterial causes of superficial pyoderma. “Of the 100 dogs in the RILEXINE^® Chewable Tablets group, 82 had Staphylococcus pseudintermedius-positive cultures on day 0. Of those 82 dogs that had Staphylococcus pseudintermedius, 57 were treatment successes based on lack of lesions to culture compared to 4/33 dogs in the placebo group.”

Table 4: Primary endpoint: Percentage of Cure* for all bacterial causes of pyoderma (Effectiveness population)

* Absence of lesions at the end of the study

PALATABILITY: The palatability of RILEXINE^® Chewable Tablets were established in two separate multi-location studies. In the first study, 39 client-owned dogs were dosed with RILEXINE^® Chewable Tablets at 22 mg/kg and evaluated for palatability of the product. Palatability testing was performed twice daily prior to feeding for 7 days. Dogs freely consumed (from empty bowl or open hand) 80.8% of their doses. In a second study, 64 client-owned dogs enrolled in the field efficacy study were evaluated in a similar manner and freely consumed 78.4% of their doses.

ANIMAL SAFETY: RILEXINE^® Chewable Tablets was administered orally three times a day to 12-week-old healthy Beagles at 0 mg/kg (placebo), 22 mg/kg (1X), 66 mg/kg (3X), and 110 mg/kg (5X) for 12 weeks and at 22 mg/kg twice a day for 12 weeks. The most common clinical findings included epiphora, salivation, vomiting and diarrhea among all the dose groups. One dog in the 22 mg/kg twice a day, the 22 mg/kg three times a day and the 66 mg/kg three times a day groups had decreased activity. These observations were mild and sporadic.

There were increases in alanine aminotransferase (ALT) in the 110 mg/kg three times a day group and in the 22 mg/kg twice a day group that increased in a dose-dependent pattern. There was an increase in sorbitol dehydrogenase (SDH) in the 110 mg/kg three times a day group compared to the controls. These changes were minimal and the values remained within

expected historical control ranges. There were several decreases in total protein (in the 110 mg/kg three times a day group) and/or globulin (in the 22, 66, and 110 mg/kg three times a day groups) compared to the controls. These changes resulted in occasional increases in albumin/globulin ratios. Although a drug effect cannot be ruled out, these changes were not clinically relevant.

A mild prolongation in prothrombin time (PT) was observed in the 22 mg/kg three times a day group. This was not considered clinically relevant due to the small change that remained within the reference ranges.

One dog in the 110 mg/kg three times a day group had moderate amounts of bilirubinuria at the Week 8 and Week 12 samplings.

No clinical significance was noted.

Cephalexin was not present in any Day 1 samples prior to dosing or in any control animals. After dosing, cephalexin was well absorbed into systemic circulation of the treated dogs. Within gender and dosage level, Week 8 mean trough concentrations were generally higher than the Week 4 and 12 mean trough concentrations (between a 0.9 and 3.6-fold difference).

The mean plasma cephalexin trough concentrations following three times daily administration of the 110 mg/kg dose was 15.1 μg/mL compared to 2.6 µg/mL and 11.8 μg/mL following 22 mg/kg and 66 mg/kg, respectively at week 12 for females. The mean plasma cephalexin trough concentrations following three times daily administration of the 110 mg/kg dose was 9.8 ug/mL compared to 2.7 μg/mL and 10.7 μg/mL following 22 mg/kg and 66 mg/kg, respectively at week 12 for males.

STORAGE INFORMATION: Store at 15°-30°C.

How Supplied

RILEXINE^® Chewable Tablets are supplied as 150 mg, 300 mg and 600 mg tablets, packed in bottles of 100 tablets. Not all bottle sizes may be marketed.

Virbac AH, Inc., P.O. Box 162059, Fort Worth, TX 76161 USA

Imported and distributed by Virbac Canada Inc., 231 Shearson Crescent, Suite 209, Cambridge, ON, N1T 1J5

1-800-338-3659

Revised 31 May 2021

RILEXINE is a registered trademark of Virbac S.A.

© 2021 Virbac Corporation. All Rights Reserved.

CPN: 1177113.0