For the treatment of urinary tract infections associated with Escherichia coli and/or Proteus spp.

Transcription

1 FAQs about CONVENIA

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3 What is CONVENIA? What is CONVENIA? The active component of CONVENIA is cefovecin, an injectable broad spectrum third generation cephalosporin. It is presented as a lyophilised pellet that, after reconstitution with 10ml of sterile water for injection, contains 80mg/ml cefovecin. What are the indications for CONVENIA? CONVENIA is indicated for use in dogs and cats for the treatment of serious infections that are susceptible to ß-lactam antibiotics. Dogs: For the treatment of the skin and soft tissue infections including pyoderma, wounds and abscesses associated with Staphylococcus intermedius, ß-haemolytic Streptococci, Escherichia coli and/or Pasteurella multocida. For the treatment of urinary tract infections associated with Escherichia coli and/or Proteus spp. Cats: For the treatment of skin and soft tissue abscesses and wounds associated with Pasteurella multocida, Fusobacterium spp., Bacteroides spp., Prevotella oralis, ß-haemolytic Streptococci and/or Staphylococcus intermedius. For the treatment of urinary tract infections associated with Escherichia coli. What is the spectrum of activity of CONVENIA? CONVENIA has an extended spectrum of bactericidal activity against Gram-positive and Gram-negative aerobes and anaerobes, including many penicillinase-producing strains. CONVENIA is not active against Pseudomonas spp., Bordetella spp., Enterococcus spp., or MRSA (methicillin resistant Staphylococcus aureus).

4 What is the dosage and administration method of CONVENIA? A dose of CONVENIA is administered to dogs and cats as a 0.1 ml/kg (8 mg/kg) subcutaneous injection. Animal body weight (kg) Dose volume (ml) How should CONVENIA be stored? Before and after reconstitution, store CONVENIA refrigerated between 2 ºC and 8 ºC. Reconstituted suspension can be stored for 28 days. CONVENIA should be stored in its original box protected from light because of photodegradation, typical of the cephalosporin class. Why does reconstituted CONVENIA change its colour during storage? After mixing, CONVENIA will naturally colour amber over time. This change in colour has no impact on CONVENIA s safety or effi cacy, provided that it is stored according to label directions and used within 28 days of reconstitution. The colour change is a typical characteristic of the cephalosporin class of compounds. Can I use reconstituted CONVENIA after 28 days? Some stability data for CONVENIA is available after 28 days, but the product does begin to degrade and therefore effi cacy can be adversely affected. It is not recommended to use CONVENIA more than 28 days after reconstitution because there is the potential for the drug to fall below specifi cations for potency after 28 days.

5 How is CONVENIA different? CONVENIA is different because its antimicrobial activity persists for up to 14 days after a single injection. What is the advantage of a single injection regimen? A single injection of CONVENIA delivers a course of antibiotics equivalent to 2 weeks of daily, oral antibiotic treatment in a single dose. This helps to maximize compliance by providing an assured course of treatment and removes noncompliance as a contributor to treatment failure. The pet owner is relieved of the burden of giving oral medication at home. What is the mechanism of action of CONVENIA? CONVENIA is bactericidal and works by binding to penicillin binding proteins and interfering with crosslinking of peptidoglycan in bacterial cell walls, causing bacteriolysis and death. What is the pharmacokinetic advantage of CONVENIA? CONVENIA s pharmacokinetics represent an advance in antibiotic therapy. CONVENIA has a uniquely long elimination half-life in dogs and cats: it is highly (>96%) protein bound, has a high affi nity for plasma proteins and a relatively slow rate of excretion by the kidneys. How is it possible for CONVENIA to deliver a course of antibiotic therapy in a single dose? Administration of CONVENIA is the therapeutic equivalent to a continuous infusion of an antibiotic. CONVENIA bound to the plasma protein creates a reservoir, gradually released in small amounts over time as free, active drug. The long duration of CONVENIA in dogs and cats is a natural property of the cefovecin molecule. CONVENIA is not a sustained release formulation or adjuvanted to be long-lasting.

6 What are the pharmacokinetic characteristics of CONVENIA? It is rapidly and completely adsorbed following subcutaneous administration and is extensively distributed to target tissues. It has a very long terminal elimination half-life in both cats and dogs. Mean terminal plasma elimination after subcutaneous injection of 8mg/kg in dogs and cats was hours (SD ± 12.1) and hours (SD ± 18.2) respectively. It is not highly metabolised and is eliminated mainly unchanged via the kidneys. A second minor route of excretion is via the bile. What happens if CONVENIA is left out of the refrigerator, the box, or both? CONVENIA should be stored in the refrigerator in the original box between uses. Limited stability studies have been completed looking at potency of the product in case it is accidentally left out at room temperature in a clinic environment. These studies suggest that a few hours of accidental exposure to room temperature or ambient light should not signifi cantly affect potency.

7 What is the efficacy of CONVENIA? Is CONVENIA as effective as antibiotics with oral dosing regimens? A single injection of CONVENIA is as effective as other oral cephalosporin treatments against feline and canine skin and soft tissue infections (SSTI) and against urinary tract infections (UTI). Field study of SSTI in cats: Treatment outcomes 1 * Clinical success (% ) % 96.2% 98.1% 93.4% 0 14 days after final SC injection 28 days after final SC Injection CONVENIA 8 mg/kg Oral cephalosporin 22mg/kg, once daily * The statistical significance of the results were only measured at 28 days. Similarly, CONVENIA has demonstrated equivalent effi cacy to a multi-day course of amoxycillin/clavulanic acid in feline SSTI s.

8 Field studies of SSTI in dogs: Treatment outcomes 2 * Clinical success (%) % 91.2% 93.2% 94.7% 0 14 days after final SC Injection 28 days after final SC injection CONVENIA 8 mg/kg Oral cephalosporin 22mg/kg, BID UTIs were cured in 91.7% of dogs injected with CONVENIA 3 * 91.7% 65.3% CONVENIA 8 mg/kg Clinical success (%) Oral cephalosporin 22mg/kg, BID For the treatment of canine urinary tract infections, a single dose of CONVENIA demonstrated high effi cacy and safety. 3 * The statistical significance of the results were only measured at 28 days.

9 What clinical trials support CONVENIA? The effi cacy of CONVENIA (cefovecin sodium) suspension for injection has been globally established in 11 separate clinical trials involving over 700 dogs and over 400 cats in Europe, Japan and the USA. Each of these trials was multicenter, randomized, and double-blind. How often can injections be repeated in the case of recurrent infections (e.g. deep pyoderma)? Factors to be considered in the determination of additional doses are the nature and severity of the infection, the susceptibility of the pathogen, and the immune status of the animal. Susceptibility of bacterial pathogens should be determined prior to treatment. In dogs, CONVENIA may be administered on four consecutive occasions at 14 day intervals, equivalent to an 8 week antibiotic course. In cats, CONVENIA may be administered on two consecutive occasions, at 14 day intervals, equivalent to a 4 week antibiotic course.

10 What is the safety profile of CONVENIA? What is the systemic safety of CONVENIA? As with other ß-lactam antibiotics, CONVENIA has an excellent safety profi le. In veterinary patient clinical studies CONVENIA was administered to over 700 dogs and over 400 cats without serious or signifi cant adverse reaction related to CONVENIA administration. What is the safety margin of CONVENIA? In safety studies CONVENIA was administered subcutaneously to healthy 4-month old animals, at 1.5, 4.5, and 7.5 times the recommended dose, once a week (as opposed to once every 2 weeks) for 4 consecutive weeks (total of 5 injections) with no signifi cant adverse reaction attributable to the product. What are the most likely side effects to be seen after the administration of CONVENIA? Over 4 million doses of CONVENIA have been administered in the fi eld to date and this has confi rmed the excellent tolerance profi le of CONVENIA. Side effects are thus rarely to be expected but when seen are typically those most commonly associated with the cephalosporins and include anorexia, lethargy and gastrointestinal signs (diarrhoea, vomiting). Neurological signs (ataxia, muscle tremors and seizures) and injection site reactions have also uncommonly been reported.

11 If an animal develops a suspected hypersensitivity reaction following a dose of CONVENIA, will it persist for an extended period given the drugs extended systemic clearance? This has not been reported in the now large number of cats and dogs to which the product has been administered. Interestingly, when signs of hypersensitivity have been reported, these signs generally resolve following symptomatic treatment within 3 to 5 days. Suspected adverse events should be reported to Pfi zer Animal Health on Does CONVENIA compete with other highly protein bound drugs? In vitro testing has demonstrated that the concentration of some highly bound drugs will increase when they are co-incubated with cefovecin. The clinical signifi cance of these displacement interactions is not, however, known. During CONVENIA safety and effi cacy clinical studies, numerous concurrent treatments (including highly bound drugs such as NSAID S) were administrated to cats and dogs without reports of interactions. It is thus not anticipated that clinicians should need to alter the therapeutic parameters (dose administrated, treatment interval, route of administration) of CONVENIA should it be administrated concurrently with other highly protein bound drugs, although it is recommended that practitioners monitor dogs on concomitant medications for signs of possible drug interactions. Can CONVENIA be used in animals with hypoproteinaemia?? The effi cacy and safety of CONVENIA in hypoteinaemic animals has not been tested. Theoretically, its use in these animals may result in proportionately more free drug with excess, unbound drug expected to be more rapidly excreted by the kidney. It is estimated, however, that for this to occur, the hypoproteinaemia would have to be so severe as to be life threatening.

12 What is the local tolerability of CONVENIA? Local tolerance is excellent with injection site reactions (swelling, tenderness) rarely reported. In a 30 day laboratory safety study, a single dose of CONVENIA was administered subcutaneously to healthy 7-month old animals at 22.5 times the recommended dose (180 mg/kg) without serious or signifi cant adverse reaction related to CONVENIA administration. Can CONVENIA be used in pregnant and lactating animals? As no studies have been performed in breeding animals with CONVENIA, it should not be used in pregnant or lactating animals. What is the youngest age I can use CONVENIA? The safe use of CONVENIA in animals less than 8 weeks of age has not been established. What breeds of dogs has CONVENIA been used in during clinical trials? In studies conducted to support registration, CONVENIA was administered to 393 dogs representing 63 different pure breeds and 25 different mixed breeds. The most common breeds were: Labrador Retriever, Hound, Golden Retriever, Beagle, Cocker Spaniel, Rottweiler, Pitbull, Poodle, German Shepherd, Dachshund, Lhasa Apso, Shih Tzu, Miniature Schnauzer, Boxer, Yorkshire Terrier, Shetland Sheepdog. What are the Contraindications and Warnings for CONVENIA? CONTRAINDICATIONS: CONVENIA should not be used in: Cases of hypersensitivity to cephalosporin or penicillin antibiotics. Small herbivores (including guinea pigs and rabbits). WARNINGS: Caution should be exercised in patients that have previously shown hypersensitivity reactions to cefovecin, other cephalosporins, penicillins or other drugs. If an allergic reaction occurs, no further cefocevin should be administered and appropriate therapy for ß-lactam hypersensitivity should be instituted. Additionally, because it is highly protein bound, CONVENIA should be used with caution when it is concomitantly used with other protein bound drugs. Such drugs include NSAIDs, anti-convulsant, cardiac and behavioural medications.

13 Why is compliance important? How prevalent is non-compliance with antibiotic regimens in companion animal medicine? Compliance has been extensively studied in human medicine, but has so far received less attention in the veterinary field. However, human behaviour is the key factor in both, situations. Noncompliance data in veterinary medicine vary widely, but consistently indicate that a substantial percentage of pet owners do not comply with treatment instructions. Importantly, studies have confirmed that vets are not able to predict which owners will or will not comply. Percentage of owners assessed as fully compliant % owners % 10% 71% 44% 0 Barter L., et al. 4 Grave K., et al. 5 MEMS Pill count Self report MEMS = Medication Event Monitoring System

14 Has antibiotic noncompliance been demonstrated to have an impact on cure rates? Yes. In a retrospective analysis, cure rates were signifi cantly lower in patients who took less than 80% of their antibiotic therapy compared with those who took more than 80% of medication as prescribed. A review of 6 separate compliance studies shows that treatment success is far greater where patients are compliant rather than noncompliant. Studies by lead author Clinical success (% ) % 59% 95% 50% 82% 57% 100% 68% 88% 68% 89% 70% 0 Anastasio 6 Venuta 7 MASCOT 8 Jordan 9 Green 10 Iiyama 11 Compliant Noncompliant How does CONVENIA help to improve compliance? A single injection of CONVENIA assures that the pet receives its antibiotic treatment as prescribed and eliminates non-compliance as the major cause of treatment failures and/or relapses in antibiotic therapy.

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16 Can I give CONVENIA IM or IV? CONVENIA is only labelled for SC injection. Other than slightly more rapid absorption after IM injection, the pharmacokinetic response after SC and IM injection is comparable. No adverse events were noted when a similar (but not identical) formulation was administrated IV in a pharmacokinetic study. References: 1. Data on file (Study: 1183C ). 2. Data on file (Study: 1163C ). 3. Data on file (Study: 1163C ). 4. Barter L et al. Owner compliance with short term antimicrobial medication in dogs. Aust Vet J 1996;74: Grave K et al. Compliance with short-term oral antibacterial drug treatment in dogs. J Small Anim Pract 1999;40: Anastasio GD et al. Impact of Compliance and Side Effects on the Clinical Outcome of Patients Treated With Oral Erythromycin. Pharmacotherapy 1994;14(2): Venuta A. Azithromycin Compared with Clarithromycin for the Treatment of Streptococcal Pharyngitis in Children. J Med Res 1998;26: MASCOT study group. Clinical efficacy of 3 days versus 5 days of oral amoxicillin for treatment of childhood pneumonia: a multicentre double-blind trial. The Lancet 2002;360: Jordan WC. Doxycycline vs. Tetracycline in the Treatment of Men with Gonorrhea: The Compliance Factor. Sex Transm Dis 1981;8(Suppl. 2): Green JL et al. Recurrence rate of streptococcal pharyngitis related to oral penicillin. J Pediatr 1969;75(2): Iiyama M et al. Juvenile Prescription Treatment Compliance. Pediatrics 2002;43(1). The information contained in this document is consistent with the New Zealand Convenia Approved label. Convenia is a registered trademark of Pfizer Inc. Registered pursuant to the ACVM Act 1997, No A10032 (P.A.R.) Class I. For use only under the authority or prescription of a veterinarian. Active ingredient: cefovecin sodium. Pfizer Animal Health - A division of Pfizer New Zealand Ltd, Level 3, Pfizer House, 14 Normanby Road, Mt Eden, Auckland, New Zealand. Tel: , Fax: