choice The Rilexine Palatable Tablets First generation cephalosporin for skin infections Now registered for ONCE daily administration*

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Virbac Dermatology Palatable Tablets The choice First generation cephalosporin for skin infections Now registered for ONCE daily administration* are only available under Veterinary Authorisation. www.virbac.co.nz

Rilexine The first generation, first line treatment for pyoderma Cephalexin is considered the antibiotic of first choice for treating pyoderma. Rilexine are particularly adapted to treat pyoderma due to: Excellent diffusion and persistence in the skin Good oral bioavailability Broad spectrum of activity with a very high efficacy against gram+ve bacteria Good tolerability during long term use Once daily dosing and palatability for ease of administration Good compliance is essential for the successful treatment of pyoderma. The risk of therapeutic failure is relatively high in pyoderma as the minimal duration of antibiotic treatment for pyoderma is about three weeks. This duration is recognised as a factor contributing to a lack of compliance, particularly as treatment should be extended for a week beyond healing as assessed clinically. Compliance is improved when medications are administered once daily rather than 2 or more times a day 1. Pet owner compliance directly impacts the probability of therapeutic success. Once daily dosing and palatable tablets = better compliance Prescribing Rilexine will make administration easier for pet owners, reduce the risk of administration problems and increase compliance Registered for once daily administration (30mg/kg) for the treatment of superficial pyoderma in dogs Highly palatable to improve acceptance of the medication by dogs and cats

Rilexine Dose chart for the treatment of superficial pyoderma in dogs 30mg/kg ONCE DAILY Weight (kg) 75mg 300mg 600mg 2.5kg 1 tablet Further reading: More Rilexine Once a Day Efficacy Studies i. Guaguère E., Maynard L., Salomon C., and Coll. Cephalexin in the treatment of canine pyoderma: comparison of two dose rates. 3rd World Congress of Veterinary Dermatology, Edinburgh Sept. 1996 ii. Guaguère E., Salomon C., Cadot P. and Jasmin P. Comparison of two protocols of administration of cephalexin in the treatment of deep pyoderma in dogs. 4th World Congress of Veterinary Dermatology, San Francisco, Aug. 2000. Published in Veterinary Dermatology 2000, 11, 14-40. 5kg 10kg ½ tablet 1 tablet iii. Maynard L., Guaguère E., and Medaille. Clinical effi cacy of cephalexin administered once or twice daily by oral route in the treatment of superficial pyoderma in dogs. 18th ESVD- ECVD Annual Congress Nice, Sept. 2002 20kg 30kg 40kg 1 tablet 1½ tablets 2 tablets Administration with food can be of benefit if the higher dose is less tolerated in rare cases. In cases of canine deep pyoderma and refractory cases of superficial pyoderma, dose should be doubled (60mg/kg once daily). References 1. Cals JWL., Hopstaken RM., Le Doux PHA., Driessen GA., Nelmans PJ., Dinant GJ. Dose timing and patient compliance with two antibiotic treatment regimes for lower respiratory tract infections in primary care. International Journal of Antimicrobial Agents, 2008. 31 (6) 531-536 2. Toma S, Colombo S, Cornegliani L, Persico P, Galzerano M, Gianino MM, Noli C. (2008) Efficacy and tolerability of once daily cephalexin in canine superficial pyoderma- an open controlled study. Journal of Small Animal Practice 49(8) 384-391 3. Salomon C., Guaguère E. and Maynard L. Comparison of two dose rates of cephalexin in the treatment of superficial pyoderma in dogs. 15th ESVD Congress, Maastricht, Sept. 1998. 4. Lucas R., Sanches C., Flocke M., Pelgrini G., and Reme C. Efficacy of three Cefalexin regimens for the treatment of superficial folliculitis in dogs. 6th World Congress of Veterinary Dermatology, Hong Kong Nov. 2008. 5. Papich M.G. Clinical pharmacology of cephalosporin antibiotics. JAVMA, 1984, 184, 344-347. Rilexine are also registered in dogs and cats for treatment of respiratory, digestive and urinary infections. *Rilexine are registered for once daily administration at 30mg/kg in the treatment of pyoderma in dogs and the treatment of lower urinary tract infections in cats and dogs. In cases of canine deep pyoderma and refractory cases of superficial pyoderma, dose should be doubled (60mg/kg once daily). For all other indications a dose rate of 10-20mg/kg every 12 hours should be administered. 6. Cardoniga R. et al., Penetration of antibiotic into interstitial tissue fluid following parenteral administration of lysin cephalexin. Drug Res. 1979, 29, 1547-1549. 7. Virbac, data on file. 8. Mason I. Antibiotic selection in practice. 17th ESVD Congress, Copenhagen, 2001. 9. Bousquet E., Ganière J.P., Ruvoen N., Larrat M. Postantibiotic effect of cephalexin against isolates of Staphylococcus intermedius obtained from cases of canine pyoderma. Veterinary Dermatology 1999, 10, 253-255. 10. Odenholt-Tornqvist I. et al. Pharmacodynamic effects of subinhibitory concentrations of β-lactam antibiotics in vitro. Antimicrobial agents and chemotherapy, 35, 9, 1834-1839 Virbac New Zealand Ltd 26 30 Maui Street, Pukete, Hamilton, 3200, New Zealand www.virbac.co.nz 0800 847 222 (0800 VIRBAC) Fax: 09 272 7667

Rilexine Proven efficacy once a day This proven clinical efficacy can be explained by: 1. Excellent diffusion and persistence in the skin Rilexine are concentrated in extra-cellular fluids, where Staphylococci are located and grow in the skin 5. Increased half life at the site of infection: the half-life of Rilexine are 4 times higher in interstitial tissue compared to the plasma half life 6. 2. High skin concentration Higher skin concentrations of Rilexine when given as 30mg/kg dose orally compared to those recorded with the 15 mg/kg dose 7. Increased concentration of Rilexine may be found in the skin of dogs affected by pyoderma, since inflamed tissues have an increased blood flow 8. 3. Post-antibiotic effect Delayed re-growth of bacteria following exposure to an antimicrobial agent, even where the antibiotic concentration falls below the MIC (minimum inhibitory concentration) for a period of time. A post-antibiotic effect of cephalexin was recorded against Staphylococcus intermedius isolated from cases of canine pyoderma. This effect can delay re-growth of Staph.intermedius for over three hours, and increases with the drug concentration 9. 4. Sub-inhibitory effects It has been demonstrated that β-lactam antibiotics in sub-inhibitory concentrations can still inhibit the growth of staphylococci especially if the bacteria have already been exposed to the antibiotics 10. In the animal, antibiotic concentration lower than the MIC may still favour elimination of pathogens by specific and non-specific immunity 10. Not all cephalexins are the same Rilexine presents cephalexin in a formulation that is clinically proven to be efficacious at a dose rate of 30mg/kg Once a Day. No other cephalexin tablet has the same comprehensive range of supporting clinical evidence and studies as Rilexine. Clinical efficacy of a drug depends on the active ingredient, its concentration and the formulation. Formulation is a key element in determining the efficacy of a product at a particular dose rate and frequency. Conclusions drawn from clinical trials are only valid for the particular formulation used in the trial or where bioequivalence has been demonstrated. As such the data presented on the use of Rilexine Once a Day cannot be extrapolated to other cephalexin tablets and their use once daily cannot be justified without clinical evidence.

Rilexine Clinically proven efficacy Trial one Superficial folliculitis Efficacy of three cephalexin regimes for the treatment of superficial folliculitis in dogs 4. Protocol A multi-centric randomised clinical field trial. 51 dogs of various ages and breeds presenting with superficial bacterial folliculitis were included in the study. Animals in the trial were allocated into 3 treatment groups: Rilexine 30 mg/kg SID (15 dogs) Rilexine 30 mg/kg BID (20 dogs) Rilexine 15 mg/kg BID (16 dogs) All animals were examined weekly until remission for a maximum of 5 weeks. Results Staph. intermedius was identified in 66.7% of cases. Clinical cure was achieved in 86.7% of cases in dogs treated with Rilexine 30mg/kg SID after 5 weeks treatment. The time to clinical cure was not significantly different between groups. 86.7 85.0 81.3 Conclusion Rilexine 30mg/kg Once a Day proved to be as effective as 30mg/kg twice daily in the treatment of superficial folliculitis. 30 mg/kg SID 30 mg/kg BID 15 mg/kg BID Dispensing envelopes boost compliance Blistered packs maintain tablet quality and freshness.

Trial two Superficial Pyoderma Comparison of two dose rates of cephalexin in the treatment of superficial pyoderma in dogs 3. Protocol A multi-centric, controlled and randomised clinical trial was performed in 14 veterinary practices. 147 dogs from 3 months to 13 years old, with a clinical diagnosis of superficial pyoderma, were included in the trial. Animals in the trial were allocated into 3 treatment groups: Group C1: Group C2: Group ACA: Rilexine 30 mg/kg SID (48 dogs) Rilexine 15 mg/kg BID (45 dogs) Amoxicillin + Clavulanic acid 12.5 mg/kg BID (54 dogs) All animals were examined weekly for a minimum 28 days and treated until 10 days after a clinical cure was established with a maximum treatment period of 60 days. Results Staphylococci spp were implicated in 67.7% of cases. Clinical cure was achieved in 91.7% of dogs treated with Rilexine Palatable Tablets 30mg/kg SID compared with only 75.9% of dogs treated with ACA. 91.7 93.3 75.9 Conclusion A single daily dose of Rilexine was found to be very effective in the treatment of canine superficial pyoderma. 30 mg/kg SID 15 mg/kg BID Amoxicillin + Clavulanic Acid 12.5 mg/kg BID Trial three Superficial Pyoderma Efficacy and tolerability of once-daily cephalexin in canine superficial pyoderma: an open controlled study 2. Protocol A multi-centric, controlled and randomised open study. 40 dogs from 8 months to 15 years old, with a clinical diagnosis of superficial pyoderma, were included in the trial. Animals in the trial were allocated into 2 treatment groups: Group A: Group B: Rilexine 30-40 mg/kg SID (20 dogs) Rilexine 15-30 mg/kg BID (20 dogs) All animals were examined every two weeks until two weeks after treatment discontinuation. Cephalexin was administered orally until 14 days beyond clinical cure (maximum treatment duration of two months). Results Staphylococcus intermedius was identified in 72.5% of cases. No significant differences were observed when the groups were compared for clinical scores at days 14, 28 or 42. Nor were there any significant differences for time to cure and percentage cured between the two groups. Conclusion This clinical trial shows that once daily Rilexine are as effective as twice daily Rilexine in the treatment of canine superficial pyoderma.