Convenia® (cefovecin sodium) in your practice

• Label dose for dogs and cats = 3.6 mg/lb CONVENIA Dosing Chart at 3.6 mg/lb (8 mg/kg or 0.045 mL/lb) subcutaneously (8mg/kg or 0.045 mL/lb) • Reconstituted concentration = 80 mg/mL • Reconstitute with 10 mL of sterile water for injection, USP Weight of Animal Volume of CONVENIA • Use within 56 days after reconstitution 5 lb 0.23 mL • Always refrigerate in original carton to protect from light • Minimum pet age for use is 4 months 10 lb 0.45 mL 15 lb 0.67 mL As with other cephalosporins, CONVENIA will naturally turn amber over time after reconstitution. The color change has 20 lb 0.90 mL no impact on safety or efficacy, provided CONVENIA is kept 40 lb 1.80 mL under proper storage conditions. 60 lb 2.70 mL 80 lb 3.60 mL

100 lb 4.50 mL

Important Safety Information: CONVENIA is not for use in dogs or cats with a history of allergic reactions to penicillins or 0 Days 28 Days 42 Days 56 Days cephalosporins. Similar to other cephalosporins, side effects for both dogs and cats include Examples of color change after the vial has been broached and reconstituted. vomiting, diarrhea, decreased appetite/anorexia and lethargy. The safety of CONVENIA has not been determined in lactating or breeding animals. For more safety information, refer to the Full Prescribing Information.

All trademarks are the property of Zoetis Inc. or its subsidiaries, affiliates and licensees. ©2013 Zoetis Inc. All rights reserved. February 2013. AIF0113010 Cats MICROBIOLOGY: CONVENIA is a cephalosporin antibiotic. Like other β-lactam A total of 291 cats, ranging in age from 2.4 months (1 cat) to 21 years, were included in the antimicrobials, CONVENIA exerts its inhibitory effect by interfering with bacterial field study safety analysis. Adverse reactions reported in cats treated with CONVENIA and cell wall synthesis. This interference is primarily due to its covalent binding to the the active control are summarized in Table 3. penicillin-binding proteins (PBPs) (ie, transpeptidase and carboxypeptidase), which (cefovecin sodium) Table 3: Number of Cats* with Adverse Reactions Reported During the Field Study with are essential for synthesis of the bacterial cell wall. For E. coli, the in vitro activity of CONVENIA. CONVENIA is comparable to other cephalosporins, but due to the high-affinity protein- Antimicrobial for Subcutaneous Injection in Dogs and Cats Only binding, the in vivo free concentration of cefovecin does not reach the MIC90 for CAUTION: Federal (USA) law restricts this drug to use by or on the order of a licensed veterinarian. CONVENIA Active Control E. coli (1.0 μg/mL). CONVENIA is not active against Pseudomonas spp. or enterococci. Adverse Reaction (n=147) (n=144) Dogs DESCRIPTION: Cefovecin sodium is a semi-synthetic broad-spectrum antibacterial agent from the The minimum inhibitory concentration (MIC) values for cefovecin against label-claim pathogens cephalosporin class of chemotherapeutic agents. Cefovecin is the non-proprietary designation for Vomiting 10 14 isolated from skin infections in dogs enrolled in a 2001-2003 field effectiveness study are presented (6R,7R)-7-[[(2Z)-(2-amino-4-thiazolyl)(methoxyimino)acetyl]amino]-8-oxo-3-[(2S)-tetrahydro-2- Diarrhea 7 26 furanyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, monosodium salt. in Table 5. All MICs were determined in accordance with the Clinical and Laboratory Standards Anorexia/Decreased Appetite 6 6 Institute (CLSI) standards. Figure 1: Chemical structure of cefovecin sodium. Lethargy 6 6 Table 5: Activity of CONVENIA against Pathogens Isolated from Dogs Treated with CONVENIA in Field Studies in the US During 2001-2003. Hyper/Acting Strange 1 1 Inappropriate Urination 1 0 Microbiological Number Sample MIC Collection MIC50 MIC90 *Some cats may have experienced more than one adverse reaction or more than one Disease Pathogen Treatment of (Time Relative Range Outcome Isolates μg/mL μg/mL occurrence of the same adverse reaction during the study. to Treatment) μg/mL Four CONVENIA cases had mildly elevated post-study ALT (1 case was elevated pre-study). No clinical abnormalities were noted with these findings. Staphylococcus Success 44 Pre-Treatment 0.12 0.25 ≤ 0.06 - 2 Twenty-four CONVENIA cases had normal pre-study BUN values and elevated post-study intermedius BUN values (37 – 39 mg/dL post-study). There were 6 CONVENIA cases with normal pre- and Skin Failure 4 Pre-Treatment 0.12 - 2 Each mL of CONVENIA reconstituted lyophile contains cefovecin sodium equivalent to 80 mg mildly to moderately elevated post-study creatinine values. Two of these cases also had an Infections cefovecin, methylparaben 1.8 mg (preservative), propylparaben 0.2 mg (preservative), sodium elevated post-study BUN. No clinical abnormalities were noted with these findings. Streptococcus Success 16 Pre-Treatment ≤ 0.06 ≤ 0.06 ≤ 0.06 citrate dihydrate 5.8 mg and citric acid monohydrate 0.1 mg, sodium hydroxide or hydrochloric One CONVENIA-treated cat in a separate field study experienced diarrhea post-treatment canis (Group G) acid as required to adjust pH. lasting 42 days. The diarrhea resolved. Failure 2 Pre-Treatment ≤ 0.06 INDICATIONS: FOREIGN MARKET EXPERIENCE: The following adverse events were reported voluntarily Dogs during post-approval use of the product in dogs and cats in foreign markets: death, tremors/ Cats CONVENIA is indicated for the treatment of skin infections (secondary superficial pyoderma, ataxia, seizures, anaphylaxis, acute pulmonary edema, facial edema, injection site reactions The MIC values for cefovecin against Pasteurella multocida isolated from skin infections abscesses, and wounds) in dogs caused by susceptible strains of Staphylococcus intermedius (alopecia, scabs, necrosis, and erythema), hemolytic anemia, salivation, pruritus, lethargy, (wounds and abscesses) in cats enrolled in a 2001-2003 field effectiveness study are and Streptococcus canis (Group G). vomiting, diarrhea, and inappetance. presented in Table 6. All MICs were determined in accordance with the CLSI standards. Cats For a copy of the Material Safety Data Sheet (MSDS) or to report a suspected adverse Table 6: Activity of CONVENIA against Pathogens Isolated from Cats Treated with CONVENIA CONVENIA is indicated for the treatment of skin infections (wounds and abscesses) in cats reaction call Pfizer Animal Health at 1-800-366-5288. in Field Studies in the US During 2001-2003. caused by susceptible strains of Pasteurella multocida. CLINICAL PHARMACOLOGY: Sample DOSAGE AND ADMINISTRATION: Pharmacokinetics Microbiological Number MIC Collection MIC50 MIC90 Dogs Cefovecin is rapidly and completely absorbed following subcutaneous administration. Non-linear Disease Pathogen Treatment of (Time Relative Range Outcome Isolates μg/mL μg/mL CONVENIA should be administered as a single subcutaneous injection of 3.6 mg/lb (8 mg/kg) body kinetics is exhibited (plasma concentrations do not increase proportionally with dose). Cefovecin to Treatment) μg/mL does not undergo hepatic metabolism and the majority of a dose is excreted unchanged in the weight. A second subcutaneous injection of 3.6 mg/lb (8 mg/kg) may be administered if response Success 57 Pre-Treatment 0.06 0.06 0.06 - 0.12 to therapy is not complete. The decision for a second injection for any individual dog should take urine. Elimination also occurs from excretion of unchanged drug in the bile. Cefovecin is a highly Skin Pasteurella ≤ ≤ ≤ into consideration such factors as progress toward clinical resolution, the susceptibility of the protein-bound molecule in dog plasma (98.5%) and cat plasma (99.8%) and may compete with Infections multocida Failure 1 Pre-Treatment ≤ 0.06 causative organisms, and the integrity of the dog’s host-defense mechanisms. Therapeutic drug other highly protein-bound drugs for plasma protein-binding sites that could result in transient, concentrations after the first injection are maintained for 7 days for S. intermedius infections and higher free drug concentrations of either compound. Pharmacokinetic parameters following EFFECTIVENESS: for 14 days for S. canis (Group G) infections. Maximum treatment should not exceed 2 injections. subcutaneous dosing at 8 mg/kg in the dog and cat are summarized in Table 4. Dogs Cats Table 4: Pharmacokinetic Parameters Reflecting Total Drug Concentrations in Plasma In a double-masked, 1:1 randomized canine field study conducted in the United States, the CONVENIA should be administered as a single, one-time subcutaneous injection at a dose of (mean ± standard deviation or range) Following an 8 mg/kg Intravenous or Subcutaneous effectiveness of CONVENIA was compared to a cephalosporin active control. In this study, 320 3.6 mg/lb (8 mg/kg) body weight. After an injection of CONVENIA, therapeutic concentrations Dose of Cefovecin in Dogs and Cats. dogs with superficial secondary pyoderma, abscesses, or infected wounds were treated with are maintained for approximately 7 days for Pasteurella multocida infections. either a single injection of CONVENIA (n=157) at 3.6 mg/lb (8 mg/kg) body weight or with an oral General Dosing Information MEAN ± SD1 or (Range) active control antibiotic (n=163), administered twice daily for 14 days. In this study, dogs could A sample of the lesion should be obtained for culture and susceptibility testing prior to beginning receive a second course of therapy 14 days after the initial treatment. Of the 320 enrolled dogs, PARAMETER 22 of 157 dogs received 2 treatments of CONVENIA and 35 of 163 dogs received 2 courses of antimicrobial therapy. Once results become available, continue with appropriate therapy. If p acceptable response to treatment is not observed, or if no improvement is seen within 3 to 4 days, Dogs Cats treatment with the active control. In the study, 118 of the 157 enrolled cases were evaluable for effectiveness for CONVENIA, and 117 of the 163 enrolled cases were evaluable for effectiveness of then the diagnosis should be re-evaluated and appropriate alternative therapy considered. h Terminal plasma elimination half-life, T1/2 (h)* 133 ± 16 166 ± 18 the active control antibiotic. CONVENIA was non-inferior to the active control. Table 7 summarizes CONVENIA may persist in the body for up to 65 days. The effect of remaining concentrations AUC (μg·h/mL)*g 10400 ± 1900p 22700 ± 3450 the clinical success rates obtained 28 days after the initiation of the final course of therapy. of cefovecin on any subsequent antimicrobial therapies has not been determined. 0-inf h Fluoroquinolone and aminoglycoside antimicrobials have been reported to be compatible Time of maximum concentration, Tmax (h)* 6.2 (0.5-12.0) 2.0 (0.5-6.0) Table 7: Clinical Success Rates by Treatment Group 28 Days after the Initiation of the with cephalosporin antimicrobial agents.1,2,3 a Final Course of Therapy. Maximum concentration, Cmax (μg/mL)* 121 ± 51 141 ± 12 Table 1: Dose Table for CONVENIA at 8 mg/kg Body Weight. g Vdss (L/kg)** 0.122 ± 0.011 0.090 ± 0.010 Dogs CL (mL/h/kg)**g 0.76 ± 0.13p 0.350 ± 0.40 total Type of Infection Volume of CONVENIA CONVENIA Active Control Weight of Animal (n=118) (n=117) (3.6 mg/lb or 0.045 mL/lb) 1 SD = standard deviation p = a phaseCats effect was observed, only data for the first phase are provided (n=6); all other data Skin (secondaryMICROBIOLOGY: superficial CONVENIA pyoderma, is a cephalosporin antibiotic. Like other β-lactam 5 lb 0.23 mL A total of 291 cats, ranging in age from 2.4 months (1 cat) to 21 years, were included in the antimicrobials, CONVENIA exerts its 109inhibitory (92.4%) effect by interfering108 (92.3%) with bacterial 10 lb 0.45 mL provided are derived from 12 animals abscesses, and infected wounds) * = SC field study safety analysis. Adverse reactions reported in cats treated with CONVENIA and cell wall synthesis. This interference is primarily due to its covalent binding to the 15 lb 0.67 mL ** = IV the active control are summarized in Table 3. CONVENIApenicillin-binding was administered proteins concomitantly (PBPs) with(ie, transpeptidaseother commonly andused carboxypeptidase),veterinary products which a are essential for synthesis of the bacterial cell wall. For E. coli, the in vitro activity of (cefovecin20 lb sodium) 0.90 mL = arithmeticTable mean3: Number of Cats* with Adverse Reactions Reported During the Field Study withsuch as heartworm preventatives, flea control products, sedatives/tranquilizers, anesthetic h = harmonicCONVENIA. mean agents, CONVENIAroutine immunizations, is comparable antihistamines, to other cephalosporins, thyroid hormone but supplementation, due to the high-affinity and non- protein- 40 lb 1.80 mL g binding, the in vivo free concentration of cefovecin does not reach the MIC for Antimicrobial for Subcutaneous Injection in Dogs and Cats Only = geometric mean steroidal anti-inflammatory drugs during the field study. 90 80 lb 3.60 mL E. coli (1.0 μg/mL). CONVENIA is not active against Pseudomonas spp. or enterococci. CAUTION: Federal (USA) law restricts this drug to use by or on the order of a licensed veterinarian.PopulationAdverse Pharmacokinetics Reaction CONVENIA Active Control Cats (n=147) (n=144) In a double-masked,Dogs 1:1 randomized cat field study conducted in the United States, the PREPARATIONDESCRIPTION: OF SOLUTION Cefovecin FOR sodium INJECTION: is a semi-synthetic To deliver broad-spectrum the appropriate antibacterial dose, aseptically agent from Dogs the The minimum inhibitory concentration (MIC) values for cefovecin against label-claim pathogens reconstitutecephalosporin CONVENIA class with of 10 chemotherapeutic mL sterile water foragents. injection. Cefovecin Shake is and the non-proprietaryallow vial to sit untildesignation all Cefovecin for Vomiting plasma concentrations in the dog have been characterized10 by the use of population14 effectiveness of CONVENIA was compared to an active control. In this study, 291 cats with infectedisolated wounds from or abscesses skin infections were in treateddogs enrolled with either in a 2001-2003 a single injection field effectiveness of CONVENIA study (n=147) are presented material(6 isR ,7visuallyR)-7-[[(2 dissolved.Z)-(2-amino-4-thiazolyl)(methoxyimino)acetyl]amino]-8-oxo-3- The resulting solution contains cefovecin sodium equivalent[(2S)-tetrahydro-2- to 80 pharmacokineticDiarrhea (PPK) data. Plasma cefovecin concentration7 data were pooled from26 7 in Table 5. All MICs were determined in accordance with the Clinical and Laboratory Standards mg/mL cefovecin.furanyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic CONVENIA is light sensitive. The vial should be acid, stored monosodium in the original salt. carton and laboratory pharmacokinetic studies, each involving young, normal healthy Beagle dogs. The at 3.6 mg/lb (8 mg/kg) body weight or with an oral active control antibiotic (n=144), administered Anorexia/Decreased Appetite 6 6 once dailyInstitute for 14 (CLSI) days. standards. CONVENIA was non-inferior to the active control. The clinical success refrigeratedFigure when 1: Chemical not in use. structure Use the entire of cefovecin contents sodium of the vial. within 56 days of reconstitution. final dataset contained 591 concentration records from 39 dogs. The simulations from the model provide theLethargy mean population estimate and the 5th and 95th percentile6 of the population estimates6 rates wereTable obtained 5: Activity 28 days of CONVENIA after the initiation against Pathogensof therapy andIsolated are presented from Dogs in Treated Table 8. with CONVENIA CONTRAINDICATIONS: CONVENIA is contraindicated in dogs and cats with known allergy to in Field Studies in the US During 2001-2003. cefovecin or to β-lactam (penicillins and cephalosporins) group antimicrobials. Anaphylaxis of total andHyper/Acting free cefovecin Strange concentrations over time. Figure 2 shows1 the predicted free plasma1 Table 8: Clinical Success Rates by Treatment Group 28 Days after the Initiation of Therapy. has been reported with the use of this product in foreign market experience. If an allergic concentrationsInappropriate following Urination administration of 8 mg/kg body weight1 to dogs. Based upon these0 Sample Cats reaction or anaphylaxis occurs, CONVENIA should not be administered again and appropriateMICROBIOLOGY: predicted concentrations,CONVENIA 95%is ofa thecephalosporin canine population antibiotic. will have activeLike (free)other drug β concentrations-lactam Microbiological Number CollectionCats MIC MIC MIC > the MIC of S. canis (0.06 μg/mL) for approximately 14 days and free concentrations Disease Pathogen Treatment of 50 90 Range A total therapyof 291 cats, should ranging be instituted. in age from Anaphylaxis 2.4 months may (1 requirecat) to 21treatment years, were with includedepinephrine in the and otherantimicrobials, * SomeCONVENIA90 cats mayexerts have its experienced inhibitory moreeffect thanby oneinterfering adverse with reaction bacterial or more than oneType of Infection CONVENIA (Time RelativeActive Control > the MIC for S. intermedius (0.25 μg/mL) for approximately 7 days following a single Outcome Isolates μg/mL μg/mL field studyemergency safety analysis.measures, Adverse including reactions oxygen, reported intravenous in cats treatedfluids, intravenouswith CONVENIA antihistamine, and cell wall synthesis.occurrence90 This ofinterference the same adverse is primarily reaction due during to itsthe covalentstudy. binding to the (n=89) to Treatment) (n=88) μg/mL the active control are summarized in Table 3. penicillin-binding8 mg/kg subcutaneous proteins (PBPs) injection (ie, of cefovecin.transpeptidase (See MICROBIOLOGY and carboxypeptidase),). which corticosteroids, and airway management, as clinically indicated. Adverse reactions may Four CONVENIA cases had mildly elevated post-study ALT (1 case was elevated pre-study). (cefovecin sodium) Table 3:require Number prolonged of Cats* treatment with Adverse due to Reactionsthe prolonged Reported systemic During drug the clearance Field Study (65 days). with are essentialFigure 2:for Population synthesis Predicted of the bacterial Free Concentration cell wall. For of Cefovecin E. coli, the in Plasmain vitro Following activity of a Single Skin (wounds and abscesses)Staphylococcus Success 86 (96.6%)44 Pre-Treatment80 0.12(90.9%)0.25 ≤ 0.06 - 2 CONVENIA is Nocomparable clinical abnormalities to other cephalosporins, were noted with but these due findings.to the high-affinity protein- CONVENIA.WARNINGS: Not for use in humans. Keep this and all drugs out of reach of children. Consult a Subcutaneous Injection of 8 mg/kg Body Weight in Dogs (solid line is population prediction, intermedius binding, the inTwenty-four vivo free CONVENIAthconcentrationth cases of hadcefovecin normal pre-studydoes not BUNreach values the andMIC elevated for post-study Antimicrobial for Subcutaneous Injection in Dogs and Cats Only dotted lines are the 5 and 95 percentiles for the population prediction). 90 CONVENIA was used concomitantly with other commonly used veterinary products such as physician in case of accidental human exposure. For subcutaneous use in dogs and cats only. BUN values (37 – 39 mg/dL post-study). There were 6 CONVENIA cases with normal pre- and Failure 4 Pre-Treatment 0.12 - 2 CAUTION: Federal (USA) law restricts this drug to use by or on the order of a licensed veterinarian. Antimicrobial drugs, including penicillins andCONVENIA cephalosporins, can Activecause Controlallergic reactionsE. incoli (1.0 μg/mL). CONVENIA is not active against Pseudomonas spp. or enterococci. heartwormSkin preventatives, flea control products, sedatives/tranquilizers, anesthetic agents, Adverse ReactionEach mL of CONVENIA reconstituted lyophile contains cefovecin sodium equivalent to 80 mg mildly to moderately elevated post-study creatinine values. Two of these cases also had an Infections DESCRIPTION: Cefovecin sodium is a semi-synthetic broad-spectrum antibacterial agent from the sensitized individuals. To minimize the possibility(n=147) of allergic reactions,(n=144) those handling suchDogs and vaccines during the field study. antimicrobials,cefovecin, including methylparaben cefovecin, 1.8 are mg advised(preservative), to avoid propylparaben direct contact 0.2 of mg the (preservative), product withThe minimumsodium inhibitoryelevated concentration post-study BUN. (MIC) No values clinical for abnormalities cefovecin against were label-claim noted with pathogens these findings. Streptococcus Success 16 Pre-Treatment ≤ 0.06 ≤ 0.06 ≤ 0.06 cephalosporin class of chemotherapeutic agents. Cefovecin is the non-proprietary designation for Vomiting citrate dihydrate 5.8 mg and citric acid monohydrate10 0.1 mg, sodium14 hydroxide or hydrochloric ANIMAL SAFETY: the skin and mucous membranes. isolated from skinOne infections CONVENIA-treated in dogs enrolled cat in in a a2001-2003 separate field field effectiveness study experienced study are presenteddiarrhea post-treatmentDogs canis (Group G) (6R,7R)-7-[[(2Z)-(2-amino-4-thiazolyl)(methoxyimino)acetyl]amino]-8-oxo-3-[(2S)-tetrahydro-2- Diarrhea acid as required to adjust pH. 7 26 lasting 42 days. The diarrhea resolved. furanyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, monosodium salt. PRECAUTIONS: Prescribing antibacterial drugs in the absence of a proven or stronglyin Table 5. All MICs were determined in accordance with the Clinical and Laboratory Standards CONVENIA administered to healthy 4-month-oldFailure dogs at2 doses ofPre-Treatment 12 mg/kg (1.5X), 36 mg/kg (4.5X),≤ 0.06 Anorexia/DecreasedINDICATIONS: Appetite 6 6 Institute (CLSI) standards.FOREIGN MARKET EXPERIENCE: The following adverse events were reported voluntarily Figure 1: Chemical structure of cefovecin sodium. suspected bacterial infection is unlikely to provide benefit to treated animals and may and 60 mg/kg (7.5X) every 7 days by dorsoscapular subcutaneous injections was well-tolerated for LethargyincreaseDogs the risk of the development of drug-resistant6 animal pathogens.6 Table 5: Activityduring of CONVENIA post-approval against use Pathogens of the product Isolated in dogsfrom Dogsand cats Treated in foreign with CONVENIA markets: death, tremors/a total ofCats 5 doses. Vomiting and diarrhea were seen in all treatment groups, with the incidence of CONVENIA is indicated for the treatment of skin infections (secondary superficialin pyoderma,Field Studies ataxia, in the seizures, US During anaphylaxis, 2001-2003. acute pulmonary edema, facial edema, injection site reactionsvomiting The and MIC the incidence values for and cefovecin duration ofagainst diarrhea Pasteurella increasing inmultocida a dose-related isolated manner. from Injectionskin infections Hyper/ActingThe safe Strangeuse of CONVENIA in dogs or cats less than1 4 months of age (see1 Animal Safety) and (alopecia, scabs, necrosis, and erythema), hemolytic anemia, salivation, pruritus, lethargy, in breedingabscesses, or lactating and wounds) animals inhas dogs not caused been determined. by susceptible Safety strains has of not Staphylococcus been established intermedius site irritation(wounds and transient and abscesses) edema occurred in cats with enrolled increasing in frequencya 2001-2003 in a dose-relatedfield effectiveness manner and study are Inappropriateand Urination Streptococcus canis (Group G). 1 0 vomiting, diarrhea, and inappetance. Sample with repeatpresented injections. in Table Two injection 6. All MICs site reactionswere determined included ain seroma accordance over the with shoulder the CLSI and standards.swelling for IM or IV administration. The long-term effects on injection sites have not been determined. Microbiological Number Collection MIC MIC MIC Disease PathogenFor a copy ofTreatment the Material Safetyof Data Sheet (MSDS) or50 to report90 Range a suspected adverselasting > 30 days. Dogs dosed at 36 mg/kg had a significant (P=0.0088) increase in BUN (all means *Some CONVENIAcats mayCats have is slowly experienced eliminated more from thanthe body, one approximatelyadverse reaction 65 days or more is needed than toone eliminate (Time Relative remainedTable within 6: Activitythe normal of CONVENIArange) compared against to thePathogens controls. Isolated One dog from dosed Cats at 60 Treated mg/kg withexhibited CONVENIA 97% of the administered dose from the body. Animals experiencing an adverse reaction may reaction call OutcomePfizer Animal HealthIsolates at 1-800-366-5288. μg/mL μg/mL occurrence of theCONVENIA same adverse is indicated reaction for duringthe treatment the study. of skin infections (wounds and abscesses) in cats to Treatment) μg/mL a glomerulopathyin Field Studies on histopathology, in the US During and 1 2001-2003. dog in this same group had minimal peliosis hepatis. need to causedbe monitored by susceptible for this duration. strains of Pasteurella multocida. CLINICAL PHARMACOLOGY: Four CONVENIA cases had mildly elevated post-study ALT (1 case was elevated pre-study). At an exaggerated dose of 180 mg/kg (22.5X) in dogs, CONVENIASample caused some injection site No clinicalCONVENIA abnormalitiesDOSAGE has been AND were shown ADMINISTRATION: noted in with an experimentalthese findings. in vitro system to result in an increase in free StaphylococcusPharmacokinetics Success 44 Pre-Treatment 0.12 0.25 ≤ 0.06 - 2 Microbiological Number MIC irritation, vocalization, and edema. Edema resolved withinCollection 8-24 hours. MIC50 MIC90 concentrationsDogs of carprofen, furosemide, doxycycline, and ketoconazole. Concurrent use of these or intermediusCefovecin is rapidly and completely absorbed following subcutaneous administration. Non-linear Disease Pathogen Treatment of (Time Relative Range Twenty-fourother drugsCONVENIA that have cases a high had degree normal of protein-binding pre-study BUN (e.g. values NSAIDs, and propofol, elevated cardiac, post-study anticonvulsant, Cats Outcome Isolates μg/mL μg/mL CONVENIA should be administered as a single subcutaneous injection of 3.6 mg/lb (8 mg/kg) body kinetics is exhibitedFailure (plasma concentrations4 Pre-Treatment do not increase proportionally0.12 with - 2 dose). Cefovecin μg/mL BUN valuesand behavioral (37 – 39 mg/dL medications) post-study). may compete There were with cefovecin-binding 6 CONVENIA cases and withcause normal adverse pre- reactions. and Skin CONVENIA administered to healthy 4-month-old cats at dosesto ofTreatment) 12 mg/kg (1.5X), 36 mg/kg (4.5X), Each mL of CONVENIA reconstituted lyophile contains cefovecin sodium equivalent to 80 mg mildly to moderatelyweight. elevated A second post-study subcutaneous creatinine injection values. of 3.6 Twomg/lb of (8 these mg/kg) cases may bealso administered had an Infectionsif response does not undergo hepatic metabolism and the majority of a dose is excreted unchanged in the urine. Elimination also occurs from excretion of unchanged drug in the bile. Cefovecin is a highlyand 60 mg/kgSkin (7.5X)Pasteurella every 7 days Success by dorsoscapular57 subcutaneousPre-Treatment injections≤ was 0.06 well-tolerated≤ 0.06 ≤ 0.06 - 0.12 cefovecin, methylparaben 1.8 mg (preservative), propylparaben 0.2 mg (preservative), sodium elevatedPositive post-studyto directtherapy BUN. Coombs’ is No not clinical complete. test abnormalities results The decision and werefalse for anoted secondpositive with injection thesereactions findings.for anyfor individual glucose dogin shouldthe take Streptococcus Success 16 Pre-Treatment ≤ 0.06 ≤ 0.06 ≤ 0.06 for a total of 5 doses. Vomiting and diarrhea were observed in cats, with the incidence of vomiting urine haveinto considerationbeen reported such during factors treatment as progress with toward some clinical cephalosporin resolution, theantimicrobials. susceptibility of the protein-bound molecule in dog plasma (98.5%) and cat plasma (99.8%) and may compete with Infections multocida Failure 1 Pre-Treatment ≤ 0.06 citrate dihydrate 5.8 mg and citric acid monohydrate 0.1 mg, sodium hydroxide or hydrochloric One CONVENIA-treated cat in a separate field study experienced diarrhea post-treatment canis (Group G) and the incidence and duration of diarrhea increasing in a dose-related manner. The mean albumin acid as required to adjust pH. Cephalosporincausative antimicrobials organisms, and may the also integrity cause of falsely the dog’s elevated host-defense urine protein mechanisms. determinations. Therapeutic drug other highly protein-bound drugs for plasma protein-binding sites that could result in transient, lasting 42 days. The diarrhea resolved. higher free drugFailure concentrations2 of eitherPre-Treatment compound. Pharmacokinetic≤ 0.06parameters followingvalues for all the CONVENIA-treated cats were significantly lower (P ≤ 0.05) than the control values Some antimicrobials,concentrations includingafter the first cephalosporins, injection are canmaintained cause for lowered 7 days foralbumin S. intermedius values dueinfections to and (all meansEFFECTIVENESS: remained within the normal range) for all time periods. The mean alkaline phosphatase INDICATIONS: FOREIGNinterference MARKETfor 14 EXPERIENCE withdays certain for S. canis testing: The (Group following methods. G) infections. adverse Maximum events were treatment reported should voluntarily not exceed 2 injections.Cats subcutaneous dosing at 8 mg/kg in the dog and cat are summarized in Table 4. during post-approval use of the product in dogs and cats in foreign markets: death, tremors/ values inDogs the 60 mg/kg group were significantly higher (P ≤ 0.0291) than the control values for all time Dogs Occasionally,Cats cephalosporins and NSAIDs have been associated with myelotoxicity, thereby creatingCats CefovecinTable plasma 4: Pharmacokineticconcentrations in theParameters cat have beenReflecting characterized Total Drugby the Concentrations use of PPK data. in Plasmaperiods. In Injection-site a double-masked, irritation 1:1and randomized transient edema canine occurred field withstudy increasing conducted frequency in the inUnited a dose- States, the CONVENIA is indicated for the treatment of skin infections (secondary superficial pyoderma, ataxia, seizures,a toxic neutropeniaCONVENIA anaphylaxis,4. shouldOther acute hematological be pulmonary administered reactions edema, as a single, facialseen withedema, one-time cephalosporins injection subcutaneous site include reactions injection neutropenia, atThe a doseMICPlasma ofvalues (meancefovecin for cefovecin± standard concentration against deviation dataPasteurella or were range) pooled multocida Following from 4isolated laboratoryan 8 mg/kg from pharmacokinetic Intravenousskin infections or studies. Subcutaneous (alopecia, scabs, necrosis, and erythema), hemolytic anemia, salivation, pruritus, lethargy, related mannereffectiveness and with of repeatCONVENIA injections. was Onecompared cat in the to 12a cephalosporin mg/kg group had active a mild control. renal tubular In this and study, 320 abscesses, and wounds) in dogs caused by susceptible strains of Staphylococcus intermedius anemia, 3.6hypoprothrombinemia, mg/lb (8 mg/kg) body thrombocytopenia, weight. After an injectionprolonged of prothrombin CONVENIA, time therapeutic (PT) and concentrations partial(wounds The and final Doseabscesses) dataset of Cefovecin contained in cats in 338Dogsenrolled concentration and inCats. a 2001-2003 records fieldfrom 22effectiveness cats. The simulations study are from the interstitialdogs fibrosis, with superficialand 1 cat in thesecondary 12 mg/kg pyoderma,group had abscesses,mild glomerulosclerosis or infected onwounds histopathology. were treated with and Streptococcus canis (Group G). vomiting, diarrhea, and inappetance. presentedmodel in Tableprovide 6. theAll MICsmean werepopulation determined estimate in as accordance well as the with5th and the 95 CLSIth percentile standards. of the population thromboplastinare maintained time (PTT), for platelet approximately dysfunction 7 anddays transient for Pasteurella increases multocida in serum aminotransferases. infections. At an exaggeratedeither a single dose injection of 180 mg/kg of CONVENIA (22.5X), CONVENIA (n=157) at was 3.6 associated mg/lb (8 mg/kg) with injection body weight site irritation, or with an oral For a copy of the Material Safety Data Sheet (MSDS) or to report a suspected adverse estimates of total and free cefovecin concentrations over time. Figure 3 displays the predicted1 free Cats ADVERSEGeneral REACTIONS: Dosing Information Table 6: Activity of CONVENIA against Pathogens Isolated from Cats TreatedMEAN with CONVENIA± SD or (Range) vocalization,active and control edema. antibiotic Edema resolved(n=163), administeredwithin 8-24 hours. twice On daily day for10, cats14 days. had lowerIn this mean study, white dogs could CONVENIA is indicated for the treatment of skin infections (wounds and abscesses) in cats reaction call Pfizer Animal Health at 1-800-366-5288. in Fieldplasma Studies concentrations in the US During following 2001-2003. administration of 8 mg/kg body weight to cats. Based upon these receive a second course of therapy 14 days after the initial treatment. Of the 320 enrolled dogs, Dogs A sample of the lesion should be obtained for culture and susceptibility testing prior to beginningpredicted PARAMETERconcentrations, 95% of the feline population will have active (free) drug concentrations > the blood cell counts compared to the controls. One cat had a small amount of bilirubinuria on day 10. caused by susceptible strains of Pasteurella multocida. CLINICAL PHARMACOLOGY:antimicrobial therapy. Once results become available, continue with appropriate therapy. If 22 of 157 dogs received 2 treatments of CONVENIA and 35 of 163 dogs received 2 courses of A total of 320 dogs, ranging in age from 8 weeks to 19 years, were included in a field study MIC of Pasteurella multocida (0.06 μg/mL) for approximately 7 days whenDogs administered a singleCats 8p STORAGE INFORMATION: acceptable response to treatment is not observed, or if no improvement is seen within 3 to 4 days,90 Sample treatment with the active control. In the study, 118 of the 157 enrolled cases were evaluable for DOSAGE AND ADMINISTRATION: Pharmacokineticssafety analysis. Adverse reactions reported in dogs treated with CONVENIA and the active mg/kg subcutaneousMicrobiological injection of cefovecin.Number (SeeCollection MICROBIOLOGY MIC). MIC MIC Store the powder and the reconstituted product in the original carton, refrigerated at 2° to 8° C then the diagnosis should be re-evaluated and appropriate alternative therapy considered. 50 90 effectiveness for CONVENIA, and 117 of the 163 enrolled cases were evaluable for effectiveness of Dogs Cefovecincontrol is rapidly are summarizedand completely in Tableabsorbed 2. following subcutaneous administration. Non-linear Disease PathogenTerminalTreatment plasma elimination of half-life,(Time T Relative (h)*h 133 ± 16 Range 166 ± 18 (36° to 46° F). Use the entire contents of the vial within 56 days of reconstitution. PROTECT FROM Figure 3: PopulationOutcome Predicted IsolatesFree Concentration1/2 of Cefovecinμg/mL μg/mL in Plasma Following a the active control antibiotic. CONVENIA was non-inferior to the active control. Table 7 summarizes CONVENIA should be administered as a single subcutaneous injection of 3.6 mg/lb (8 mg/kg) body kinetics is exhibitedCONVENIA (plasma may concentrations persist in the do bodynot increase for up to proportionally 65 days. The with effect dose). of remaining Cefovecin concentrations g to Treatment) μg/mLp LIGHT. Afterthe clinical each use success it is important rates obtained to return 28 days the unusedafter the portion initiation back of the to thefinal refrigerator course of therapy.in the Table 2: Number of Dogs* with Adverse Reactions Reported During the Field Study with Single SubcutaneousAUC0-inf (μg·h/mL)* Injection of 8 mg/kg Body Weight in Cats10400 (solid ± 1900 line is population22700 ± 3450 weight. A second subcutaneous injection of 3.6 mg/lb (8 mg/kg) may be administered if response does not undergoof hepaticcefovecin metabolism on any and subsequent the majority antimicrobial of a dose is excretedtherapies unchanged has not in beenthe determined. th th original carton. As with other cephalosporins, the color of the solution may vary from clear to CONVENIA. prediction, dottedSuccess lines are the 5 57 and 95 percentilesPre-Treatmenth for the≤ 0.06population≤ 0.06 prediction).≤ 0.06 - 0.12 Table 7: Clinical Success Rates by Treatment Group 28 Days after the Initiation of the to therapy is not complete. The decision for a second injection for any individual dog should take urine. EliminationFluoroquinolone also occurs from and excretion aminoglycoside of unchanged antimicrobials drug in the bile.have Cefovecin been reported is a highly to be compatibleSkin Pasteurella Time of maximum concentration, Tmax (h)* 6.2 (0.5-12.0) 2.0 (0.5-6.0) amber at reconstitution and may darken over time. If stored as recommended, solution color does 1,2,3 a Final Course of Therapy. into consideration such factors as progress toward clinical resolution, the susceptibility of the protein-bound moleculewith cephalosporin in dog plasma antimicrobial (98.5%) and agents. cat plasma (99.8%) and may compete with Infections multocidaMaximumFailure concentration,1 C (μg/mL)*Pre-Treatment 121 ± 51 ≤ 0.06 141 ± 12 not adversely affect potency. other highlyAdverse protein-bound Reaction drugs for plasma protein-bindingCONVENIA sites that could result Activein transient, Control max causative organisms, and the integrity of the dog’s host-defense mechanisms. Therapeutic drug Table 1: Dose Table for CONVENIA at 8 mg/kg(n=157) Body Weight. (n=163) Vd (L/kg)**g 0.122 ± 0.011 0.090 ± 0.010HOW SUPPLIED: higher free drug concentrations of either compound. Pharmacokinetic parameters following ss Dogs concentrations after the first injection are maintained for 7 days for S. intermedius infections and EFFECTIVENESS:CL (mL/h/kg)**g 0.76 ± 0.13p 0.350 ± 0.40 CONVENIA is available as a 10 mL multi-use vial containing 800 milligrams of cefovecin as for 14 days for S. canis (Group G) infections. Maximum treatment should not exceed 2 injections. subcutaneousLethargy dosing at 8 mg/kg in the dog and cat are summarized2 in Table 4. 7 total Type of Infection Volume of CONVENIA Dogs a lyophilized cake. CONVENIA Active Control Weight of Animal (n=118) (n=117) Cats Table 4: Anorexia/DecreasedPharmacokinetic Parameters Appetite Reflecting Total Drug5 Concentrations(3.6 mg/lb inor 0.045Plasma8 mL/lb) In a double-masked,1 SD = standard1:1 randomized deviation canine field study conducted in the United States, the (mean ± standard deviation or range) Following an 8 mg/kg Intravenous or Subcutaneous REFERENCES: CONVENIA should be administered as a single, one-time subcutaneous injection at a dose of Vomiting 5 lb 6 0.23 mL 12 effectiveness ofp =CONVENIA a phase effect was comparedwas observed, to a cephalosporinonly data for the active first control. phase areIn thisprovided study, (n=6);320 all other 1Pillaidata SK,Skin Moellering (secondary RC, superficial Eliopoulos pyoderma, GM. Antimicrobial combinations. In: Lorian V, ed. 3.6 mg/lb (8 mg/kg) body weight. After an injection of CONVENIA, therapeutic concentrations Dose of Cefovecin in Dogs and Cats. dogs with superficial secondary pyoderma, abscesses, or infected wounds were treated with 109 (92.4%) 108 (92.3%) Diarrhea 10 lb 6 0.45 mL 7 provided are derived from 12 animals Antibioticsabscesses, in laboratory and infected medicine wounds). 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins, are maintained for approximately 7 days for Pasteurella multocida infections. either a single injection* = SC of CONVENIA (n=157) at 3.6 mg/lb (8 mg/kg) body weight or with an oral Blood in Feces 1 2 2005;365-440. General Dosing Information 15 lb MEAN ± SD10.67 or (Range) mL active control antibiotic** = IV (n=163), administered twice daily for 14 days. In this study, dogs could 2Fish DN,CONVENIA Choi MK, Jungwas administered R. Synergic activity concomitantly of cephalosporins with other plus commonly fluoroquinolones used veterinary against products receive a seconda course of therapy 14 days after the initial treatment. Of the 320 enrolled dogs, A sample of the lesion should be obtained for culture and susceptibility testing prior to beginning PARAMETERDehydration 20 lb 0 0.90 mL 1 = arithmetic mean Pseudomonassuch as aeruginosa heartworm withpreventatives, resistance flea to one control or both products, drugs. sedatives/tranquilizers,J Antimicrob Chemother anesthetic 22 of 157 dogs hreceived 2 treatments of CONVENIA and 35 of 163 dogs received 2 courses of agents, routine immunizations, antihistamines, thyroid hormone supplementation, and non- antimicrobial therapy. Once results become available, continue with appropriate therapy. If Flatulence 40 lb 1 1.80 mL p 0 = harmonic mean 2002;50:1045-1049. Dogs Cats treatment with gthe = geometric active control. mean In the study, 118 of the 157 enrolled cases were evaluable for 3 steroidal anti-inflammatory drugs during the field study. acceptable response to treatment is not observed, or if no improvement is seen within 3 to 4 days, Increased Borborygmi 1 0 Mayer I, Nagy E. Investigation of the synergic effects of aminoglycoside-fluoroquinolone and then the diagnosis should be re-evaluated and appropriate alternative therapy considered. 80 lb 3.60 mL effectiveness for CONVENIA, and 117 of the 163 enrolled cases were evaluable for effectiveness of third-generation cephalosporin combinations against clinical isolates of Pseudomonas spp. J Terminal plasma elimination half-life, T (h)*h 133 ± 16 166 ± 18 Population Pharmacokinetics Cats * 1/2 the active control antibiotic. CONVENIA was non-inferior to the active control. Table 7 summarizes Antimicrob Chemother 1999;43:651-657. CONVENIA may persist in the body for up to 65 days. The effect of remaining concentrations Some dogsPREPARATION mayg have experiencedOF SOLUTION more FOR than INJECTION: one adverse To deliverreactionp the or appropriatemore than one dose , aseptically In a double-masked, 1:1 randomized cat field study conducted in the United States, the AUC (μg·h/mL)* 10400 ± 1900 22700 ± 3450 the clinical successDogs rates obtained 28 days after the initiation of the final course of therapy. 4Birchard SJ, Sherding RG. Saunders manual of small animal practice. 2nd ed. Philadelphia: of cefovecin on any subsequent antimicrobial therapies has not been determined. 0-infoccurrencereconstitute of the same CONVENIA adverse with reaction 10 mL sterileduring water the study. for injection. Shake and allow vial to sit until all Cefovecin plasma concentrations in the dog have been characterized by the use of population effectiveness of CONVENIA was compared to an active control. In this study, 291 cats with Time of maximum concentration, T (h)*h 6.2 (0.5-12.0) 2.0 (0.5-6.0) Table 7: Clinical Success Rates by Treatment Group 28 Days after the Initiation of the PA: WBinfected Saunders wounds Co, 2000;166. or abscesses were treated with either a single injection of CONVENIA (n=147) Fluoroquinolone and aminoglycoside antimicrobials have been reported to be compatible material is visually dissolved.max The resulting solution contains cefovecin sodium equivalent to 80 pharmacokinetic (PPK) data. Plasma cefovecin concentration data were pooled from 7 1,2,3 Mild to moderate elevations a in serum -glutamyl transferase or serum alanineFinal Course of Therapy. with cephalosporin antimicrobial agents. Maximum concentration,mg/mL cefovecin. C (μg/mL)*CONVENIA is light sensitive.121 The ± vial51 should be stored141 ± in12 the original carton and laboratory pharmacokinetic studies, each involving young, normal healthy Beagle dogs. NADA#The at141-285, 3.6 mg/lb Approved (8 mg/kg) by body FDA weight or with an oral active control antibiotic (n=144), administered aminotransferase weremax noted post-treatment in several of the CONVENIA-treated dogs. No once daily for 14 days. CONVENIA was non-inferior to the active control. The clinical success Table 1: Dose Table for CONVENIA at 8 mg/kg Body Weight. Vd (L/kg)**grefrigerated when not in use. Use the entire0.122 contents ± 0.011 of the vial within0.090 ±56 0.010 days of reconstitution. final dataset contained 591 concentration records from 39 dogs. The simulations from the model Distributed by: ss clinical abnormalities were noted with these findings. th Dogsth rates were obtained 28 days after the initiation of therapy and are presented in Table 8. CL (mL/h/kg)**CONTRAINDICATIONS:g CONVENIA is contraindicated0.76 ± 0.13p in dogs 0.350and cats ± 0.40 with known allergy to provide the mean population estimate and the 5 and 95 percentile of the population estimates total Type of Infection Volume of CONVENIA One CONVENIA-treatedcefovecin or to β -lactamdog in a (penicillins separate field and cephalosporins)study experienced group diarrhea antimicrobials. post-treatment Anaphylaxis of total and free cefovecin concentrationsCONVENIA over time. FigureActive 2 shows Control the predicted free plasma Table 8: Clinical Success Rates by Treatment Group 28 Days after the Initiation of Therapy. Weight of Animal lasting 4 weeks. The diarrhea resolved. concentrations following administration(n=118) of 8 mg/kg body weight(n=117) to dogs. Based upon these Div. of Pfizer Inc Revised June 2011 (3.6 mg/lb or 0.045 mL/lb) 1 SD = standardhas deviation been reported with the use of this product in foreign market experience. If an allergic p reaction or anaphylaxis occurs, CONVENIA should not be administered again and appropriate predicted concentrations, 95% of the canine population will have active (free) drug concentrations New York, NY 10017 Cats 11892301 5 lb 0.23 mL = a phaseCats effect was observed, only data for the first phase are provided (n=6); all other data Skin (secondaryMICROBIOLOGY:> thesuperficial MIC CONVENIA of pyoderma,S. canis is(0.06 a μg/mL)109cephalosporin (92.4%) for approximately antibiotic. 14108 days Like(92.3%) andother free β -lactamconcentrations therapy should be instituted. Anaphylaxis may require treatment with epinephrine and other 90 Type of Infection CONVENIA Active Control 10 lb 0.45 mL providedA aretotal derived of 291 fromcats, 12ranging animals in age from 2.4 months (1 cat) to 21 years, were included in abscesses,the antimicrobials, and> infectedthe MIC CONVENIA wounds) for S. intermedius exerts its (0.25inhibitory μg/mL) effectfor approximately by interfering 7 days with following bacterial a single * = SC emergency measures, including oxygen, intravenous fluids, intravenous antihistamine, 90 (n=89) (n=88) field studycorticosteroids, safety analysis. and airwayAdverse management,reactions reported as clinically in cats treatedindicated. with Adverse CONVENIA reactions and maycell wall8 mg/kg synthesis. subcutaneous This interference injection of cefovecin.is primarily (See due MICROBIOLOGY to its covalent). binding to the 15 lb 0.67 mL ** = IV the active control are summarized in Table 3. CONVENIApenicillin-binding was administered proteins concomitantly (PBPs) with(ie, transpeptidaseother commonly andused carboxypeptidase),veterinary products which a require prolonged treatment due to the prolonged systemic drug clearance (65 days). 20 lb 0.90 mL = arithmetic mean such asare heartworm essentialFigure preventatives, 2:for Population synthesis Predictedflea of the control bacterial Free products, Concentration cell wall.sedatives/tranquilizers, For of Cefovecin E. coli, the in Plasmain anestheticvitro Following activity of a Single Skin (wounds and abscesses) 86 (96.6%) 80 (90.9%) (cefovecin sodium) h Table 3: Number of Cats* with Adverse Reactions Reported During the Field Study with = harmonic meanWARNINGS: Not for use in humans. Keep this and all drugs out of reach of children.agents, Consult CONVENIAroutine a Subcutaneous immunizations, is comparable Injection antihistamines, to other of 8 mg/kg cephalosporins, thyroid Body hormone Weight but in supplementation, dueDogs to (solid the linehigh-affinity isand population non- protein- prediction, 40 lb 1.80 mL g CONVENIA. th th = geometric meanphysician in case of accidental human exposure. For subcutaneous use in dogs andsteroidal cats only.binding, anti-inflammatory dotted the linesin vivo are drugs freethe 5 duringconcentration and the95 percentilesfield study.of cefovecin for the population does not prediction). reach the MIC for CONVENIA was used concomitantly with other commonly used veterinary products such as Antimicrobial80 lb for Subcutaneous Injection in Dogs and3.60 Cats mL Only 90 Population PharmacokineticsAntimicrobial drugs, including penicillins and cephalosporins, can cause allergic reactionsCats E. incoli (1.0 μg/mL). CONVENIA is not active against Pseudomonas spp. or enterococci. heartworm preventatives, flea control products, sedatives/tranquilizers, anesthetic agents, CAUTION: Federal (USA) law restricts this drug to use by or on the order of a licensed veterinarian. Adversesensitized Reaction individuals. To minimize the possibilityCONVENIA of allergic reactions,Active those Control handling such and vaccines during the field study. PREPARATION OF SOLUTION FOR INJECTION: To deliver the appropriate dose, aseptically Dogs (n=147) (n=144) In a double-masked,Dogs 1:1 randomized cat field study conducted in the United States, the DESCRIPTION: Cefovecin sodium is a semi-synthetic broad-spectrum antibacterial agent from the antimicrobials, including cefovecin, are advised to avoid direct contact of the producteffectiveness with of CONVENIA was compared to an active control. In this study, 291 cats with ANIMAL SAFETY: reconstitute CONVENIA with 10 mL sterile water for injection. Shake and allow vial to sit until all Cefovecin plasmathe concentrations skin and mucous in themembranes. dog have been characterized by the use of population The minimum inhibitory concentration (MIC) values for cefovecin against label-claim pathogens materialcephalosporin is visually dissolved. class of The chemotherapeutic resulting solution agents. contains Cefovecin cefovecin is the sodium non-proprietary equivalent designation to 80 for Vomiting 10 14 infected wounds or abscesses were treated with either a single injection of CONVENIA (n=147) Dogs (6R,7R)-7-[[(2Z)-(2-amino-4-thiazolyl)(methoxyimino)acetyl]amino]-8-oxo-3-[(2S)-tetrahydro-2-pharmacokinetic (PPK) data. Plasma cefovecin concentration data were pooled from 7 isolated from skin infections in dogs enrolled in a 2001-2003 field effectiveness study are presented mg/mL cefovecin. CONVENIA is light sensitive. The vial should be stored in the original carton and laboratoryDiarrhea pharmacokineticPRECAUTIONS: studies, Prescribing each involving antibacterial young, drugs normal7 in healthy the absence Beagle ofdogs. a26 proven The ator 3.6strongly mg/lbin Table (8 mg/kg) 5. All bodyMICs weightwere determined or with an oralin accordance active control with antibiotic the Clinical (n=144), and Laboratoryadministered Standards CONVENIA administered to healthy 4-month-old dogs at doses of 12 mg/kg (1.5X), 36 mg/kg (4.5X), furanyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, monosodium salt. once daily for 14 days. CONVENIA was non-inferior to the active control. The clinical success and 60 mg/kg (7.5X) every 7 days by dorsoscapular subcutaneous injections was well-tolerated for refrigerated when not in use. Use the entire contents of the vial within 56 days of reconstitution. final datasetAnorexia/Decreased containedsuspected 591 bacterialconcentration Appetite infection records is unlikelyfrom 39 dogs.to provide 6The simulations benefit fromto treated the 6model animals and Institutemay (CLSI) standards. Figure 1: Chemical structure of cefovecin sodium. provide the meanincrease population the riskestimate of the and development the 5th and 95of thdrug-resistant percentile of the animal population pathogens. estimates rates were obtained 28 days after the initiation of therapy and are presented in Table 8. a total of 5 doses. Vomiting and diarrhea were seen in all treatment groups, with the incidence of CONTRAINDICATIONS: CONVENIA is contraindicated in dogs and cats with known allergy to Lethargy 6 6 Table 5: Activity of CONVENIA against Pathogens Isolated from Dogs Treated with CONVENIA vomiting and the incidence and duration of diarrhea increasing in a dose-related manner. Injection cefovecin or to β-lactam (penicillins and cephalosporins) group antimicrobials. Anaphylaxis of total and freeThe cefovecin safe use concentrations of CONVENIA over in dogs time. or Figure cats less 2 shows than 4the months predicted of age free (see plasma Animal TableSafety 8:) in and Clinical Field Studies Success in theRates US by During Treatment 2001-2003. Group 28 Days after the Initiation of Therapy. concentrationsHyper/Acting following Strange administration of 8 mg/kg body weight1 to dogs. Based upon these1 site irritation and transient edema occurred with increasing frequency in a dose-related manner and has been reported with the use of this product in foreign market experience. If an allergic in breeding or lactating animals has not been determined. Safety has not been established with repeat injections. Two injection site reactions included a seroma over the shoulder and swelling predicted concentrations,for IM or IV 95% administration. of the canine Thepopulation long-term will haveeffects active on injection (free) drug sites concentrations have not been determined. Cats reaction or anaphylaxis occurs, CONVENIA should not be administered again and appropriate Inappropriate Urination 1 0 Microbiological Number Sample MIC lasting > 30 days. Dogs dosed at 36 mg/kg had a significant (P=0.0088) increase in BUN (all means therapy should be instituted. Anaphylaxis may require treatment with epinephrine and other > the MIC ofCONVENIA S. canis (0.06 is slowly μg/mL) eliminated for approximately from the body, 14 daysapproximately and free 65concentrations days is needed toType eliminate of Infection Collection MIC MIC 90 Disease Pathogen Treatment CONVENIAof Active Control50 90 Range remained within the normal range) compared to the controls. One dog dosed at 60 mg/kg exhibited emergency measures, including oxygen, intravenous fluids, intravenous antihistamine, > the MIC*Some for 97%cats S. ofintermediusmay the haveadministered experienced (0.25 μ doseg/mL) from morefor theapproximately than body. one Animals adverse 7 days experiencing reaction following or an amore adversesingle than reaction one may (Time Relative 90 Outcome (n=89)Isolates (n=88)μg/mL μg/mL a glomerulopathy on histopathology, and 1 dog in this same group had minimal peliosis hepatis. corticosteroids, and airway management, as clinically indicated. Adverse reactions may 8 mg/kgoccurrence subcutaneousneed of to the injectionbe samemonitored ofadverse cefovecin. for thisreaction duration. (See during MICROBIOLOGY the study.). to Treatment) μg/mL require prolonged treatment due to the prolonged systemic drug clearance (65 days). Figure 2:Four Population CONVENIACONVENIA Predicted cases has beenFreehad mildlyConcentrationshown elevated in an experimental of post-study Cefovecin inALT in vitro Plasma (1 casesystem Following was to elevatedresult a Singlein anpre-study). increase in free At an exaggerated dose of 180 mg/kg (22.5X) in dogs, CONVENIA caused some injection site Skin (wounds and abscesses)Staphylococcus Success 86 (96.6%)44 Pre-Treatment80 0.12(90.9%)0.25 ≤ 0.06 - 2 irritation, vocalization, and edema. Edema resolved within 8-24 hours. WARNINGS: Not for use in humans. Keep this and all drugs out of reach of children. Consult a SubcutaneousNo clinical concentrationsInjection abnormalities of 8 mg/kgof carprofen, were Body noted Weightfurosemide, with inthese Dogs doxycycline, findings. (solid line and is ketoconazole. population prediction, Concurrent use of these or th th physician in case of accidental human exposure. For subcutaneous use in dogs and cats only. dotted linesTwenty-four areother the 5drugsCONVENIA and that 95 have percentiles cases a high had degree for normal the of populationprotein-binding pre-study prediction). BUN (e.g. values NSAIDs, and propofol, elevated cardiac, post-study anticonvulsant,CONVENIA was usedintermedius concomitantly with other commonly used veterinary products such as Cats Antimicrobial drugs, including penicillins and cephalosporins, can cause allergic reactions in BUN valuesand behavioral (37 – 39 mg/dL medications) post-study). may compete There were with cefovecin-binding 6 CONVENIA cases and withcause normal adverse pre- reactions. heartwormand Skin preventatives, flea controlFailure products, sedatives/tranquilizers,4 Pre-Treatment anesthetic agents,0.12 - 2 CONVENIA administered to healthy 4-month-old cats at doses of 12 mg/kg (1.5X), 36 mg/kg (4.5X), sensitized individuals. To minimize the possibility of allergic reactions, those handling such mildly to moderately elevated post-study creatinine values. Two of these cases also hadand an vaccinesInfections during the field study. and 60 mg/kg (7.5X) every 7 days by dorsoscapular subcutaneous injections was well-tolerated Each mL of CONVENIA reconstituted lyophile contains cefovecin sodium equivalent to 80 mg Positive direct Coombs’ test results and false positive reactions for glucose in the for a total of 5 doses. Vomiting and diarrhea were observed in cats, with the incidence of vomiting antimicrobials,cefovecin, including methylparaben cefovecin, 1.8 aremg advised(preservative), to avoid propylparaben direct contact 0.2 of mg the (preservative), product with sodium elevatedurine post-study have BUN.been Noreported clinical duringabnormalities treatment were with noted some with thesecephalosporin findings. antimicrobials.ANIMAL SAFETY: Streptococcus Success 16 Pre-Treatment ≤ 0.06 ≤ 0.06 ≤ 0.06 the skin and mucous membranes. Cephalosporin antimicrobials may also cause falsely elevated urine protein determinations. and the incidence and duration of diarrhea increasing in a dose-related manner. The mean albumin citrate dihydrate 5.8 mg and citric acid monohydrate 0.1 mg, sodium hydroxide or hydrochloric One CONVENIA-treated cat in a separate field study experienced diarrhea post-treatmentDogs values for all the CONVENIA-treated cats were significantly lower (P ≤ 0.05) than the control values Some antimicrobials, including cephalosporins, can cause lowered albumin valuesCONVENIA due to administered canis to(Group healthy G) 4-month-old dogs at doses of 12 mg/kg (1.5X), 36 mg/kg (4.5X), PRECAUTIONS:acid as required Prescribing to adjust antibacterial pH. drugs in the absence of a proven or strongly lasting 42 days. The diarrhea resolved. Failure 2 Pre-Treatment ≤ 0.06 (all means remained within the normal range) for all time periods. The mean alkaline phosphatase suspected bacterial infection is unlikely to provide benefit to treated animals and may interference with certain testing methods. and 60 mg/kg (7.5X) every 7 days by dorsoscapular subcutaneous injections was well-tolerated for INDICATIONS: FOREIGN MARKET EXPERIENCE: The following adverse events were reported voluntarily Cats values in the 60 mg/kg group were significantly higher (P ≤ 0.0291) than the control values for all time increase the risk of the development of drug-resistant animal pathogens. a total of 5 doses.Cefovecin Vomiting plasma and diarrhea concentrations were seen in in the all cattreatment have been groups, characterized with the incidence by the useof of PPK data. Dogs during post-approvalOccasionally, cephalosporins use of the product and NSAIDs in dogs have and been cats associated in foreign withmarkets: myelotoxicity, death, tremors/ thereby creatingCats periods. Injection-site irritation and transient edema occurred with increasing frequency in a dose- a toxic neutropenia4. Other hematological reactions seen with cephalosporins include vomitingneutropenia, and thePlasma incidence cefovecin and duration concentration of diarrhea data increasing were pooled in a dose-related from 4 laboratory manner. pharmacokinetic Injection studies. related manner and with repeat injections. One cat in the 12 mg/kg group had a mild renal tubular and The safeCONVENIA use of CONVENIA is indicated in dogs for theor cats treatment less than of skin 4 months infections of age (secondary (see Animal superficial Safety) and pyoderma, ataxia, seizures, anaphylaxis, acute pulmonary edema, facial edema, injection site reactionssite irritation The andMIC transient values edemafor cefovecin occurred against with increasing Pasteurella frequency multocida in a dose-related isolated from manner skin and infections in breeding or lactating animals has not been determined. Safety has not been established (alopecia,anemia, scabs, hypoprothrombinemia, necrosis, and erythema), thrombocytopenia, hemolytic anemia, prolonged salivation, prothrombin pruritus, time lethargy,(PT) and partial The final dataset contained 338 concentration records from 22 cats. The simulations from the interstitial fibrosis, and 1 cat in the 12 mg/kg group had mild glomerulosclerosis on histopathology. abscesses, and wounds) in dogs caused by susceptible strains of Staphylococcus intermedius with repeat(wounds injections.model and Twoprovide abscesses) injection the meansite in reactions populationcats enrolled included estimate in aa seroma as 2001-2003 well overas the thefield 5 thshoulder and effectiveness 95th andpercentile swelling studyof the populationare for IM orand IV administration.Streptococcus canisThe long-term (Group G) effects. on injection sites have not been determined. vomiting,thromboplastin diarrhea, and time inappetance. (PTT), platelet dysfunction and transient increases in serum aminotransferases.presented in Table 6. All MICs were determined in accordance with the CLSI standards. At an exaggerated dose of 180 mg/kg (22.5X), CONVENIA was associated with injection site irritation, CONVENIA is slowly eliminated from the body, approximately 65 days is needed to eliminate lasting > 30 days.estimates Dogs dosed of total at 36and mg/kg free cefovecinhad a significant concentrations (P=0.0088) over increase time. Figure in BUN 3 displays (all means the predicted free Cats For a copyADVERSE of the REACTIONS: Material Safety Data Sheet (MSDS) or to report a suspected adverseremained Table within 6:plasma Activitythe normal concentrations of CONVENIArange) compared following against to the Pathogensadministration controls. Isolated One of dog8 mg/kg from dosed bodyCats at 60 weightTreated mg/kg to exhibitedwith cats. CONVENIA Based upon these vocalization, and edema. Edema resolved within 8-24 hours. On day 10, cats had lower mean white 97% of the administered dose from the body. Animals experiencing an adverse reaction may blood cell counts compared to the controls. One cat had a small amount of bilirubinuria on day 10. need toCONVENIA be monitored is indicatedfor this duration. for the treatment of skin infections (wounds and abscesses) in cats reactionDogs call Pfizer Animal Health at 1-800-366-5288. a glomerulopathyin Fieldpredicted Studies on histopathology, in concentrations, the US During and 95% 1 2001-2003. dog of thein thisfeline same population group willhad have minimal active peliosis (free) drug hepatis. concentrations > the caused by susceptible strains of Pasteurella multocida. CLINICALA totalPHARMACOLOGY: of 320 dogs, ranging in age from 8 weeks to 19 years, were included in aAt field an exaggerated study MIC 90dose of Pasteurella of 180 mg/kg multocida (22.5X) (0.06 in dogs, μg/mL) CONVENIA for approximately caused 7 some days wheninjection administered site a single 8 STORAGE INFORMATION: CONVENIA has been shown in an experimental in vitro system to result in an increase in free ° ° DOSAGE AND ADMINISTRATION: safety analysis. Adverse reactions reported in dogs treated with CONVENIA andirritation, the active vocalization, mg/kg subcutaneous and edema.Microbiological Edemainjection resolved of cefovecin.Number within (SeeSample 8-24 MICROBIOLOGY hours. ). MIC Store the powder and the reconstituted product in the original carton, refrigerated at 2 to 8 C concentrations of carprofen, furosemide, doxycycline, and ketoconazole. Concurrent use of these or Pharmacokineticscontrol are summarized in Table 2. Collection MIC MIC (36° to 46° F). Use the entire contents of the vial within 56 days of reconstitution. PROTECT FROM other drugsDogs that have a high degree of protein-binding (e.g. NSAIDs, propofol, cardiac, anticonvulsant, Cefovecin is rapidly and completely absorbed following subcutaneous administration. Non-linearCats DiseaseFigurePathogen 3: PopulationTreatment Predicted ofFree Concentration of Cefovecin50 in 90PlasmaRange Following a (Time Relative μg/mL μg/mL LIGHT. After each use it is important to return the unused portion back to the refrigerator in the kinetics Tableis exhibited 2: Number (plasma of concentrationsDogs* with Adverse do not increase Reactions proportionally Reported During with dose). the CefovecinField CONVENIAStudy with administered Single Subcutaneous to healthyOutcome 4-month-old Injection cats ofIsolates 8at mg/kgdoses ofBody 12 mg/kg Weight (1.5X), in Cats36 mg/kg (solid (4.5X), μg/mLline is population and behavioralCONVENIA medications) should be may administered compete with as cefovecin-binding a single subcutaneous and cause injection adverse of 3.6 reactions. mg/lb (8 mg/kg) body th th to Treatment) original carton. As with other cephalosporins, the color of the solution may vary from clear to does notCONVENIA. undergo hepatic metabolism and the majority of a dose is excreted unchanged inand the 60 mg/kg (7.5X)prediction, every 7dotted days linesby dorsoscapular are the 5 and subcutaneous 95 percentiles injections for the was population well-tolerated prediction). Positiveweight. direct A Coombs’second subcutaneous test results injection and false of 3.6 positive mg/lb (8 reactionsmg/kg) may for be administeredglucose in ifthe response Success 57 Pre-Treatment 0.06 0.06 0.06 - 0.12 amber at reconstitution and may darken over time. If stored as recommended, solution color does to therapy is not complete. The decision for a second injection for any individual dog should take urine. Elimination also occurs from excretion of unchanged drug in the bile. Cefovecin is a highlyfor a totalSkin of 5 doses.Pasteurella Vomiting and diarrhea were observed in cats, with the incidence≤ ≤ of vomiting≤ urine have been reported during treatment with some cephalosporin antimicrobials. CONVENIA Active Control not adversely affect potency. Cephalosporininto consideration antimicrobials such may factors also as cause progress falsely toward elevated clinical urine resolution, protein determinations.the susceptibility of the protein-boundAdverse molecule Reaction in dog plasma (98.5%) and cat plasma (99.8%) and may compete withand the incidenceInfections andmultocida duration of Failurediarrhea increasing1 in a dose-relatedPre-Treatment manner. The mean albumin≤ 0.06 causative organisms, and the integrity of the dog’s host-defense mechanisms. Therapeutic drug other highly protein-bound drugs for plasma protein-binding sites(n=157) that could result in transient,(n=163)values for all the CONVENIA-treated cats were significantly lower (P ≤ 0.05) than the control values HOW SUPPLIED: Some antimicrobials, including cephalosporins, can cause lowered albumin values due to CONVENIA is available as a 10 mL multi-use vial containing 800 milligrams of cefovecin as interferenceconcentrations with certain after testing the first methods. injection are maintained for 7 days for S. intermedius infections and higher freeLethargy drug concentrations of either compound. Pharmacokinetic2 parameters following7(all means EFFECTIVENESS: remained within the normal range) for all time periods. The mean alkaline phosphatase for 14 days for S. canis (Group G) infections. Maximum treatment should not exceed 2 injections.Cats subcutaneous dosing at 8 mg/kg in the dog and cat are summarized in Table 4. values in the 60 mg/kg group were significantly higher (P ≤ 0.0291) than the control values for all time a lyophilized cake. Occasionally, cephalosporins and NSAIDs have been associated with myelotoxicity, thereby creating Cefovecin plasmaAnorexia/Decreased concentrations in the Appetite cat have been characterized by5 the use of PPK data. 8 periods.Dogs Injection-site irritation and transient edema occurred with increasing frequency in a dose- 4 Table 4: Pharmacokinetic Parameters Reflecting Total Drug Concentrations in Plasma REFERENCES: a toxic neutropeniaCats . Other hematological reactions seen with cephalosporins include neutropenia, Plasma cefovecin concentration data were pooled from 4 laboratory pharmacokinetic studies. In a double-masked, 1:1 randomized canine field study conducted in the United States, the 1 (mean ± standardVomiting deviation or range) Following an 8 mg/kg Intravenous6 or Subcutaneous12related manner and with repeat injections. One cat in the 12 mg/kg group had a mild renal tubular and Pillai SK, Moellering RC, Eliopoulos GM. Antimicrobial combinations. In: Lorian V, ed. anemia, CONVENIAhypoprothrombinemia, should be administeredthrombocytopenia, as a single,prolonged one-time prothrombin subcutaneous time (PT) injection and partial at a doseThe of final dataset contained 338 concentration records from 22 cats. The simulations from the interstitialeffectiveness fibrosis, and of 1 CONVENIAcat in the 12 wasmg/kg compared group had to amild cephalosporin glomerulosclerosis active on control. histopathology. In this study, 320 Diarrhea th th 6 7 Antibiotics in laboratory medicine. 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins, thromboplastin3.6 mg/lb time (8 (PTT), mg/kg) platelet body dysfunction weight. After and an transient injection increases of CONVENIA, in serum therapeuticaminotransferases. concentrationsmodel provideDose of the Cefovecin mean population in Dogs estimate and Cats. as well as the 5 and 95 percentile of the population dogs with superficial secondary pyoderma, abscesses, or infected wounds were treated with are maintained for approximately 7 days for Pasteurella multocida infections. estimates of total andBlood free in cefovecin Feces concentrations over time. Figure 3 displays1 the predicted free 2At an exaggeratedeither a single dose injection of 180 mg/kg of CONVENIA (22.5X), CONVENIA (n=157) at was 3.6 associated mg/lb (8 mg/kg) with injection body weight site irritation, or with an oral 2005;365-440. ADVERSE REACTIONS: vocalization, and edema. Edema resolved within 8-24 hours. On day 10, cats had lower mean white 2Fish DN, Choi MK, Jung R. Synergic activity of cephalosporins plus fluoroquinolones against General Dosing Information plasma concentrationsDehydration following administration of 8 mg/kg body weightMEAN to cats.0 ± Based SD1 or upon (Range) these 1 active control antibiotic (n=163), administered twice daily for 14 days. In this study, dogs could Dogs predicted concentrations, 95% of the feline population will have active (free) drug concentrations > the blood cellreceive counts a compared second course to the controls.of therapy One 14 catdays had after a small the amountinitial treatment. of bilirubinuria Of the on 320 day enrolled 10. dogs, Pseudomonas aeruginosa with resistance to one or both drugs. J Antimicrob Chemother A sample of the lesion should be obtained for culture and susceptibility testing prior to beginning PARAMETER 2002;50:1045-1049. A total of 320 dogs, ranging in age from 8 weeks to 19 years, were included in a field study MIC of PasteurellaFlatulence multocida (0.06 μg/mL) for approximately 7 days when administered1 a single 8 0STORAGE22 ofINFORMATION: 157 dogs received 2 treatments of CONVENIA and 35 of 163 dogs received 2 courses of antimicrobial therapy. Once results become available, continue with appropriate therapy. If90 p 3Mayer I, Nagy E. Investigation of the synergic effects of aminoglycoside-fluoroquinolone and safety analysis. Adverse reactions reported in dogs treated with CONVENIA and the active mg/kg subcutaneousIncreased injection Borborygmi of cefovecin. (See ). Dogs1 Cats 0 treatment with the active control. In the study, 118 of the 157 enrolled cases were° evaluable° for acceptable response to treatment is not observed, or if no improvement is seen within 3 to 4 days, MICROBIOLOGY Store the powder and the reconstituted product in the original carton, refrigerated at 2 to 8 C third-generation cephalosporin combinations against clinical isolates of Pseudomonas spp. J control are summarized in Table 2. (36° to 46effectiveness° F). Use the entirefor CONVENIA, contents andof the 117 vial of thewithin 163 56enrolled days of cases reconstitution were evaluable. PROTECT for effectiveness FROM of then the diagnosis should be re-evaluated and appropriate alternative therapy considered. Figure 3: Population* Predicted Free Concentration ofh Cefovecin in Plasma Following a Antimicrob Chemother 1999;43:651-657. TerminalSome plasma dogs elimination may have experiencedhalf-life, T1/2 more(h)* than one 133adverse ± 16 reaction or 166more ± 18thanLIGHT. one Afterthe active each controluse it is antibiotic. important CONVENIA to return the was unused non-inferior portion to backthe active to the control. refrigerator Table 7in summarizes the Table 2:CONVENIA Number of may Dogs* persist with in Adversethe body Reactionsfor up to 65 Reported days. The During effect theof remaining Field Study concentrations with Single Subcutaneous Injection of 8 mg/kg Body Weight in Cats (solid line is population 4Birchard SJ, Sherding RG. Saunders manual of small animal practice. 2nd ed. Philadelphia: AUC occurrence (μg·h/mL)* ofg theth same adverseth reaction during10400 the study. ± 1900p 22700 ± 3450original thecarton. clinical As successwith other rates cephalosporins, obtained 28 days the aftercolor the of initiationthe solution of the may final vary course from clearof therapy. to CONVENIA.of cefovecin on any subsequent antimicrobial therapies has not been determined.prediction, dotted0-inf lines are the 5 and 95 percentiles for the population prediction). PA: WB Saunders Co, 2000;166. Time ofMild maximum to moderate concentration, elevations T (h)*in h serum -glutamyl6.2 (0.5-12.0) transferase2.0 (0.5-6.0)or serumamber alanine atTable reconstitution 7: Clinical and Successmay darken Rates over bytime. Treatment If stored asGroup recommended, 28 Days after solution the color Initiation does of the Fluoroquinolone and aminoglycoside antimicrobials have been reported to be compatible max  not adversely affect potency. NADA# 141-285, Approved by FDA 1,2,3 a Final Course of Therapy. Adversewith Reaction cephalosporin antimicrobial agents. CONVENIA Active Control Maximumaminotransferase concentration, were C noted(μg/mL)* post-treatment in several121 ± 51 of the CONVENIA-treated141 ± 12 dogs. No (n=157) (n=163) clinical abnormalities maxwere noted with these findings. HOW SUPPLIED: Distributed by: Table 1: Dose Table for CONVENIA at 8 mg/kg Body Weight. g Vdss (L/kg)** 0.122 ± 0.011 0.090 ± 0.010CONVENIA is available as a 10 mL multi-use vial containing 800 milligramsDogs of cefovecin as Lethargy 2 7 g p CL One(mL/h/kg)** CONVENIA-treated dog in a separate field 0.76study ± 0.13experienced 0.350diarrhea ± 0.40 post-treatmenta lyophilized cake. total lasting 4 weeks. The diarrhea resolved. Type of Infection CONVENIA Active Control Div. of Pfizer Inc Anorexia/Decreased Weight Appetite of Animal 5 Volume of CONVENIA8 Revised June 2011 (3.6 mg/lb or 0.045 mL/lb) 1 REFERENCES: (n=118) (n=117) New York, NY 10017 11892301 Vomiting 6 12 SD = standard deviation 1 p Pillai SK, Moellering RC, Eliopoulos GM. Antimicrobial combinations. In: Lorian V, ed. Diarrhea 5 lb 6 0.23 mL 7 = a phase effect was observed, only data for the first phase are provided (n=6); all other Antibioticsdata Skin in (secondary laboratory superficialmedicine. 5th pyoderma, ed. Philadelphia, PA: Lippincott Williams & Wilkins, provided are derived from 12 animals abscesses, and infected wounds) 109 (92.4%) 108 (92.3%) Blood in Feces 10 lb 1 0.45 mL 2 2005;365-440. * = SC 2Fish DN, Choi MK, Jung R. Synergic activity of cephalosporins plus fluoroquinolones against Dehydration 15 lb 0 0.67 mL 1 ** = IV CONVENIA was administered concomitantly with other commonly used veterinary products a Pseudomonas aeruginosa with resistance to one or both drugs. J Antimicrob Chemother 20 lb 0.90 mL = arithmetic mean 2002;50:1045-1049.such as heartworm preventatives, flea control products, sedatives/tranquilizers, anesthetic Flatulence 1 0 h agents, routine immunizations, antihistamines, thyroid hormone supplementation, and non- 40 lb 1.80 mL = harmonic mean 3Mayer I, Nagy E. Investigation of the synergic effects of aminoglycoside-fluoroquinolone and Increased Borborygmi 1 0 g = geometric mean steroidal anti-inflammatory drugs during the field study. 80 lb 3.60 mL third-generation cephalosporin combinations against clinical isolates of Pseudomonas spp. J *Some dogs may have experienced more than one adverse reaction or more than one Population Pharmacokinetics AntimicrobCats Chemother 1999;43:651-657. 4 occurrencePREPARATION of the same OF adverse SOLUTION reaction FOR duringINJECTION: the study. To deliver the appropriate dose, aseptically Dogs BirchardIn SJ,a double-masked, Sherding RG. Saunders 1:1 randomized manual ofcat small field animal study practice conducted. 2nd in ed. the Philadelphia: United States, the reconstitute CONVENIA with 10 mL sterile water for injection. Shake and allow vial to sit until all Cefovecin plasma concentrations in the dog have been characterized by the use of populationPA: WB effectiveness Saunders Co, of 2000;166. CONVENIA was compared to an active control. In this study, 291 cats with Mild tomaterial moderate is visually elevations dissolved. in Theserum resulting -glutamyl solution containstransferase cefovecin or serumsodium equivalentalanine to 80 pharmacokinetic (PPK) data. Plasma cefovecin concentration data were pooled fromNADA# 7 infected141-285, wounds Approved or abscessesby FDA were treated with either a single injection of CONVENIA (n=147) aminotransferasemg/mL cefovecin. were noted CONVENIA post-treatment is light sensitive. in several The vial of theshould CONVENIA-treated be stored in the original dogs. cartonNo and laboratory pharmacokinetic studies, each involving young, normal healthy Beagle dogs. The at 3.6 mg/lb (8 mg/kg) body weight or with an oral active control antibiotic (n=144), administered clinical refrigeratedabnormalities when were not noted in use. with Use these the entire findings. contents of the vial within 56 days of reconstitution. final dataset contained 591 concentration records from 39 dogs. The simulations from the model onceDistributed daily for 14 by: days. CONVENIA was non-inferior to the active control. The clinical success rates were obtained 28 days after the initiation of therapy and are presented in Table 8. One CONVENIA-treatedCONTRAINDICATIONS: dog in CONVENIAa separate isfield contraindicated study experienced in dogs anddiarrhea cats withpost-treatment known allergy to provide the mean population estimate and the 5th and 95th percentile of the population estimates lasting 4cefovecin weeks. The or todiarrhea β-lactam resolved. (penicillins and cephalosporins) group antimicrobials. Anaphylaxis of total and free cefovecin concentrations over time. Figure 2 shows the predicted free plasma TableDiv. 8: of Clinical Pfizer Inc Success Rates by Treatment Group 28 Days after Rtheevised Initiation June of2011 Therapy. has been reported with the use of this product in foreign market experience. If an allergic concentrations following administration of 8 mg/kg body weight to dogs. Based upon these New York, NY 10017 11892301 reaction or anaphylaxis occurs, CONVENIA should not be administered again and appropriate predicted concentrations, 95% of the canine population will have active (free) drug concentrations Cats > the MIC of S. canis (0.06 μg/mL) for approximately 14 days and free concentrations therapy should be instituted. Anaphylaxis may require treatment with epinephrine and other 90 Type of Infection CONVENIA Active Control > the MIC for S. intermedius (0.25 μg/mL) for approximately 7 days following a single emergency measures, including oxygen, intravenous fluids, intravenous antihistamine, 90 (n=89) (n=88) corticosteroids, and airway management, as clinically indicated. Adverse reactions may 8 mg/kg subcutaneous injection of cefovecin. (See MICROBIOLOGY). require prolonged treatment due to the prolonged systemic drug clearance (65 days). Figure 2: Population Predicted Free Concentration of Cefovecin in Plasma Following a Single Skin (wounds and abscesses) 86 (96.6%) 80 (90.9%) WARNINGS: Not for use in humans. Keep this and all drugs out of reach of children. Consult a Subcutaneous Injection of 8 mg/kg Body Weight in Dogs (solid line is population prediction, physician in case of accidental human exposure. For subcutaneous use in dogs and cats only. dotted lines are the 5th and 95th percentiles for the population prediction). CONVENIA was used concomitantly with other commonly used veterinary products such as Antimicrobial drugs, including penicillins and cephalosporins, can cause allergic reactions in heartworm preventatives, flea control products, sedatives/tranquilizers, anesthetic agents, sensitized individuals. To minimize the possibility of allergic reactions, those handling such and vaccines during the field study. antimicrobials, including cefovecin, are advised to avoid direct contact of the product with ANIMAL SAFETY: the skin and mucous membranes. Dogs PRECAUTIONS: Prescribing antibacterial drugs in the absence of a proven or strongly CONVENIA administered to healthy 4-month-old dogs at doses of 12 mg/kg (1.5X), 36 mg/kg (4.5X), suspected bacterial infection is unlikely to provide benefit to treated animals and may and 60 mg/kg (7.5X) every 7 days by dorsoscapular subcutaneous injections was well-tolerated for increase the risk of the development of drug-resistant animal pathogens. a total of 5 doses. Vomiting and diarrhea were seen in all treatment groups, with the incidence of The safe use of CONVENIA in dogs or cats less than 4 months of age (see Animal Safety) and vomiting and the incidence and duration of diarrhea increasing in a dose-related manner. Injection in breeding or lactating animals has not been determined. Safety has not been established site irritation and transient edema occurred with increasing frequency in a dose-related manner and for IM or IV administration. The long-term effects on injection sites have not been determined. with repeat injections. Two injection site reactions included a seroma over the shoulder and swelling CONVENIA is slowly eliminated from the body, approximately 65 days is needed to eliminate lasting > 30 days. Dogs dosed at 36 mg/kg had a significant (P=0.0088) increase in BUN (all means 97% of the administered dose from the body. Animals experiencing an adverse reaction may remained within the normal range) compared to the controls. One dog dosed at 60 mg/kg exhibited need to be monitored for this duration. a glomerulopathy on histopathology, and 1 dog in this same group had minimal peliosis hepatis. CONVENIA has been shown in an experimental in vitro system to result in an increase in free At an exaggerated dose of 180 mg/kg (22.5X) in dogs, CONVENIA caused some injection site concentrations of carprofen, furosemide, doxycycline, and ketoconazole. Concurrent use of these or irritation, vocalization, and edema. Edema resolved within 8-24 hours. other drugs that have a high degree of protein-binding (e.g. NSAIDs, propofol, cardiac, anticonvulsant, Cats and behavioral medications) may compete with cefovecin-binding and cause adverse reactions. CONVENIA administered to healthy 4-month-old cats at doses of 12 mg/kg (1.5X), 36 mg/kg (4.5X), Positive direct Coombs’ test results and false positive reactions for glucose in the and 60 mg/kg (7.5X) every 7 days by dorsoscapular subcutaneous injections was well-tolerated urine have been reported during treatment with some cephalosporin antimicrobials. for a total of 5 doses. Vomiting and diarrhea were observed in cats, with the incidence of vomiting Cephalosporin antimicrobials may also cause falsely elevated urine protein determinations. and the incidence and duration of diarrhea increasing in a dose-related manner. The mean albumin Some antimicrobials, including cephalosporins, can cause lowered albumin values due to values for all the CONVENIA-treated cats were significantly lower (P ≤ 0.05) than the control values interference with certain testing methods. (all means remained within the normal range) for all time periods. The mean alkaline phosphatase Cats values in the 60 mg/kg group were significantly higher (P ≤ 0.0291) than the control values for all time Occasionally, cephalosporins and NSAIDs have been associated with myelotoxicity, thereby creating Cefovecin plasma concentrations in the cat have been characterized by the use of PPK data. periods. Injection-site irritation and transient edema occurred with increasing frequency in a dose- a toxic neutropenia4. Other hematological reactions seen with cephalosporins include neutropenia, Plasma cefovecin concentration data were pooled from 4 laboratory pharmacokinetic studies. related manner and with repeat injections. One cat in the 12 mg/kg group had a mild renal tubular and anemia, hypoprothrombinemia, thrombocytopenia, prolonged prothrombin time (PT) and partial The final dataset contained 338 concentration records from 22 cats. The simulations from the interstitial fibrosis, and 1 cat in the 12 mg/kg group had mild glomerulosclerosis on histopathology. thromboplastin time (PTT), platelet dysfunction and transient increases in serum aminotransferases. model provide the mean population estimate as well as the 5th and 95th percentile of the population estimates of total and free cefovecin concentrations over time. Figure 3 displays the predicted free At an exaggerated dose of 180 mg/kg (22.5X), CONVENIA was associated with injection site irritation, ADVERSE REACTIONS: plasma concentrations following administration of 8 mg/kg body weight to cats. Based upon these vocalization, and edema. Edema resolved within 8-24 hours. On day 10, cats had lower mean white Dogs predicted concentrations, 95% of the feline population will have active (free) drug concentrations > the blood cell counts compared to the controls. One cat had a small amount of bilirubinuria on day 10.

A total of 320 dogs, ranging in age from 8 weeks to 19 years, were included in a field study MIC90 of Pasteurella multocida (0.06 μg/mL) for approximately 7 days when administered a single 8 STORAGE INFORMATION: safety analysis. Adverse reactions reported in dogs treated with CONVENIA and the active mg/kg subcutaneous injection of cefovecin. (See MICROBIOLOGY). Store the powder and the reconstituted product in the original carton, refrigerated at 2° to 8° C control are summarized in Table 2. Figure 3: Population Predicted Free Concentration of Cefovecin in Plasma Following a (36° to 46° F). Use the entire contents of the vial within 56 days of reconstitution. PROTECT FROM Table 2: Number of Dogs* with Adverse Reactions Reported During the Field Study with Single Subcutaneous Injection of 8 mg/kg Body Weight in Cats (solid line is population LIGHT. After each use it is important to return the unused portion back to the refrigerator in the CONVENIA. prediction, dotted lines are the 5th and 95th percentiles for the population prediction). original carton. As with other cephalosporins, the color of the solution may vary from clear to amber at reconstitution and may darken over time. If stored as recommended, solution color does not adversely affect potency. Adverse Reaction CONVENIA Active Control (n=157) (n=163) HOW SUPPLIED: Lethargy 2 7 CONVENIA is available as a 10 mL multi-use vial containing 800 milligrams of cefovecin as a lyophilized cake. Anorexia/Decreased Appetite 5 8 REFERENCES: Vomiting 6 12 1Pillai SK, Moellering RC, Eliopoulos GM. Antimicrobial combinations. In: Lorian V, ed. Diarrhea 6 7 Antibiotics in laboratory medicine. 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins, Blood in Feces 1 2 2005;365-440. 2Fish DN, Choi MK, Jung R. Synergic activity of cephalosporins plus fluoroquinolones against Dehydration 0 1 Pseudomonas aeruginosa with resistance to one or both drugs. J Antimicrob Chemother Flatulence 1 0 2002;50:1045-1049. 3 Increased Borborygmi 1 0 Mayer I, Nagy E. Investigation of the synergic effects of aminoglycoside-fluoroquinolone and third-generation cephalosporin combinations against clinical isolates of Pseudomonas spp. J *Some dogs may have experienced more than one adverse reaction or more than one Antimicrob Chemother 1999;43:651-657. occurrence of the same adverse reaction during the study. 4Birchard SJ, Sherding RG. Saunders manual of small animal practice. 2nd ed. Philadelphia: PA: WB Saunders Co, 2000;166. Mild to moderate elevations in serum -glutamyl transferase or serum alanine NADA# 141-285, Approved by FDA aminotransferase were noted post-treatment in several of the CONVENIA-treated dogs. No clinical abnormalities were noted with these findings. Distributed by: One CONVENIA-treated dog in a separate field study experienced diarrhea post-treatment lasting 4 weeks. The diarrhea resolved. Div. of Pfizer Inc Revised June 2011 New York, NY 10017 11892301 Cats MICROBIOLOGY: CONVENIA is a cephalosporin antibiotic. Like other β-lactam A total of 291 cats, ranging in age from 2.4 months (1 cat) to 21 years, were included in the antimicrobials, CONVENIA exerts its inhibitory effect by interfering with bacterial field study safety analysis. Adverse reactions reported in cats treated with CONVENIA and cell wall synthesis.Cats This interference is primarily due to its covalent binding to the MICROBIOLOGY: CONVENIA is a cephalosporin antibiotic. Like other β-lactam the active control are summarized in Table 3. penicillin-bindingA total proteins of 291 cats,(PBPs) ranging (ie, intranspeptidase age from 2.4 monthsand carboxypeptidase), (1 cat) to 21 years, werewhich included in the antimicrobials, CONVENIA exerts its inhibitory effect by interfering with bacterial are essential fieldfor synthesis study safety of the analysis. bacterial Adverse cell wall. reactions For E. reported coli, the in incats vitro treated activity with of CONVENIA and cell wall synthesis. This interference is primarily due to its covalent binding to the (cefovecin sodium) Table 3: Number of Cats* with Adverse Reactions Reported During the Field Study with the active control are summarized in Table 3. penicillin-binding proteins (PBPs) (ie, transpeptidase and carboxypeptidase), which CONVENIA. CONVENIA is comparable to other cephalosporins, but due to the high-affinity protein- (cefovecin sodium) Table 3: Number of Cats* with Adverse Reactions Reported During the Field Study with are essential for synthesis of the bacterial cell wall. For E. coli, the in vitro activity of Antimicrobial for Subcutaneous Injection in Dogs and Cats Only binding, the in vivo free concentration of cefovecin does not reach the MIC90 for E. coli (1.0 μg/mL).CONVENIA. CONVENIA is not active against Pseudomonas spp. or enterococci. CONVENIA is comparable to other cephalosporins, but due to the high-affinity protein- CAUTION: Federal (USA) law restricts this drug to use by or on the order of a licensed veterinarian. Antimicrobial for Subcutaneous InjectionCONVENIA in Dogs and CatsActive Only Control binding, the in vivo free concentration of cefovecin does not reach the MIC for Adverse Reaction (n=147) (n=144) Dogs 90 DESCRIPTION: Cefovecin sodium is a semi-synthetic broad-spectrum antibacterial agent from the CAUTION: Federal (USA) law restricts this drug to use by or on the order of a licensed veterinarian. CONVENIA Active Control E. coli (1.0 μg/mL). CONVENIA is not active against Pseudomonas spp. or enterococci. cephalosporin class of chemotherapeutic agents. Cefovecin is the non-proprietary designation for The minimum inhibitoryAdverse concentration Reaction (MIC) values for cefovecin against label-claim pathogens Vomiting DESCRIPTION: Cefovecin sodium is a semi-synthetic10 broad-spectrum14 antibacterial agentisolated from fromthe skin infections in dogs enrolled in a 2001-2003 field effectiveness(n=147) study are presented(n=144) Dogs (6R,7R)-7-[[(2Z)-(2-amino-4-thiazolyl)(methoxyimino)acetyl]amino]-8-oxo-3-[(2S)-tetrahydro-2- Diarrhea 7 26 in Table 5. All MICs were determined in accordance with the Clinical and Laboratory Standards The minimum inhibitory concentration (MIC) values for cefovecin against label-claim pathogens furanyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, monosodium salt. cephalosporin class of chemotherapeutic agents. Cefovecin is the non-proprietary designation for Vomiting 10 14 isolated from skin infections in dogs enrolled in a 2001-2003 field effectiveness study are presented Anorexia/Decreased(6R,7R)-7-[[(2 AppetiteZ)-(2-amino-4-thiazolyl)(methoxyimino)acetyl]amino]-8-oxo-3-6 6 [(2S)-tetrahydro-2-Institute (CLSI) standards.Diarrhea 7 26 Figure 1: Chemical structure of cefovecin sodium. furanyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, monosodium salt. in Table 5. All MICs were determined in accordance with the Clinical and Laboratory Standards Lethargy 6 6 Table 5: Activity ofAnorexia/Decreased CONVENIA against PathogensAppetite Isolated from Dogs Treated6 with CONVENIA 6 Institute (CLSI) standards. Figure 1: Chemical structure of cefovecin sodium. in Field Studies in the US During 2001-2003. Hyper/Acting Strange 1 1 Lethargy 6 6 Table 5: Activity of CONVENIA against Pathogens Isolated from Dogs Treated with CONVENIA in Field Studies in the US During 2001-2003. Inappropriate Urination 1 0 Hyper/Acting Strange Sample 1 1 Microbiological Number Collection MIC MIC MIC Disease Pathogen Treatment of 50 90 Range *Some cats may have experienced more than one adverse reaction or more than one Inappropriate Urination (Time Relative 1 0 Microbiological Number Sample MIC Outcome Isolates μg/mL μg/mL Collection MIC MIC occurrence of the same adverse reaction during the study. to Treatment) μg/mL 50 90 *Some cats may have experienced more than one adverse reaction or more than one Disease Pathogen Treatment of (Time Relative Range Outcome Isolates μg/mL μg/mL Four CONVENIA cases had mildly elevated post-study ALT (1 case was elevated pre-study). occurrence of the same adverse reaction during the study. to Treatment) μg/mL No clinical abnormalities were noted with these findings. Staphylococcus Success 44 Pre-Treatment 0.12 0.25 ≤ 0.06 - 2 intermediusFour CONVENIA cases had mildly elevated post-study ALT (1 case was elevated pre-study). Twenty-four CONVENIA cases had normal pre-study BUN values and elevated post-study No clinical abnormalities were noted with these findings. Staphylococcus Success 44 Pre-Treatment 0.12 0.25 ≤ 0.06 - 2 BUN values (37 – 39 mg/dL post-study). There were 6 CONVENIA cases with normal pre- and Failure 4 Pre-Treatment 0.12 - 2 Skin Twenty-four CONVENIA cases had normal pre-study BUN values and elevated post-study intermedius Each mL of CONVENIA reconstituted lyophile contains cefovecin sodium equivalent to 80 mg mildly to moderately elevated post-study creatinine values. Two of these cases also had an Infections Failure 4 Pre-Treatment 0.12 - 2 elevated post-study BUN. No clinical abnormalities were noted with these findings. BUN values (37 – 39 mg/dL post-study). There were 6 CONVENIA cases with normal pre- and Skin cefovecin, methylparaben 1.8 mg (preservative), propylparaben 0.2 mg (preservative), sodium Streptococcusmildly to moderately Success elevated16 post-studyPre-Treatment creatinine values.≤ 0.06 Two≤ 0.06 of these≤ 0.06 cases also had an Infections citrate dihydrate 5.8 mg and citric acid monohydrate 0.1 mg, sodium hydroxide or hydrochloric Each mL of CONVENIA reconstituted lyophile contains cefovecin sodium equivalent to 80 mg One CONVENIA-treatedcefovecin, cat methylparaben in a separate 1.8 field mg (preservative), study experienced propylparaben diarrhea 0.2post-treatment mg (preservative), sodium caniselevated (Group post-studyG) BUN. No clinical abnormalities were noted with these findings. Streptococcus Success 16 Pre-Treatment ≤ 0.06 ≤ 0.06 ≤ 0.06 acid as required to adjust pH. lasting 42 days. The diarrhea resolved. citrate dihydrate 5.8 mg and citric acid monohydrate 0.1 mg, sodium hydroxide or hydrochloric One CONVENIA-treatedFailure cat in2 a separatePre-Treatment field study experienced ≤diarrhea 0.06 post-treatment INDICATIONS: canis (Group G) FOREIGN MARKETacid asEXPERIENCE required to: adjustThe following pH. adverse events were reported voluntarily lasting 42 days. The diarrhea resolved. Failure 2 Pre-Treatment ≤ 0.06 during post-approval use of the product in dogs and cats in foreign markets: death, tremors/ Dogs INDICATIONS: Cats FOREIGN MARKET EXPERIENCE: The following adverse events were reported voluntarily CONVENIA is indicated for the treatment of skin infections (secondary superficial pyoderma, ataxia, seizures, anaphylaxis, acute pulmonary edema, facial edema, injection site reactions The MIC values for cefovecin against Pasteurella multocida isolated from skin infections (alopecia, scabs,Dogs necrosis, and erythema), hemolytic anemia, salivation, pruritus, lethargy, during post-approval use of the product in dogs and cats in foreign markets: death, tremors/ Cats abscesses, and wounds) in dogs caused by susceptible strains of Staphylococcus intermedius (wounds and ataxia,abscesses) seizures, in cats anaphylaxis, enrolled acutein a pulmonary2001-2003 edema,field effectiveness facial edema, studyinjection are site reactions and Streptococcus canis (Group G). vomiting, diarrhea,CONVENIA and inappetance. is indicated for the treatment of skin infections (secondary superficialpresented pyoderma, in Table 6. All MICs were determined in accordance with the CLSI standards. The MIC values for cefovecin against Pasteurella multocida isolated from skin infections abscesses, and wounds) in dogs caused by susceptible strains of Staphylococcus intermedius (alopecia, scabs, necrosis, and erythema), hemolytic anemia, salivation, pruritus, lethargy, (wounds and abscesses) in cats enrolled in a 2001-2003 field effectiveness study are Cats For a copy of andthe StreptococcusMaterial Safety canis Data (Group Sheet G) (MSDS). or to report a suspected adverse Table 6: Activityvomiting, of CONVENIA diarrhea, against and inappetance.Pathogens Isolated from Cats Treated with CONVENIA presented in Table 6. All MICs were determined in accordance with the CLSI standards. CONVENIA is indicated for the treatment of skin infections (wounds and abscesses) in cats reaction call Pfizer Animal Health at 1-800-366-5288. in Field Studies in the US During 2001-2003. Cats For a copy of the Material Safety Data Sheet (MSDS) or to report a suspected adverse Table 6: Activity of CONVENIA against Pathogens Isolated from Cats Treated with CONVENIA caused by susceptible strains of Pasteurella multocida. CLINICAL PHARMACOLOGY: reaction call Pfizer Animal Health at 1-800-366-5288. CONVENIA is indicated for the treatment of skin infections (wounds and abscesses) in cats Sample in Field Studies in the US During 2001-2003. DOSAGE AND ADMINISTRATION: Pharmacokineticscaused by susceptible strains of Pasteurella multocida. CLINICAL MicrobiologicalPHARMACOLOGY:Number Collection MIC MIC MIC Disease Pathogen Treatment of 50 90 Range Dogs Cefovecin is rapidlyDOSAGE and completely AND ADMINISTRATION: absorbed following subcutaneous administration. Non-linear (Time Relative Microbiological Number Sample MIC PharmacokineticsOutcome Isolates μg/mL μg/mL Collection MIC MIC CONVENIA should be administered as a single subcutaneous injection of 3.6 mg/lb (8 mg/kg) body kinetics is exhibited (plasma concentrations do not increase proportionally with dose). Cefovecin to Treatment) μg/mL 50 90 Dogs Cefovecin is rapidly and completely absorbed following subcutaneous administration. Non-linear Disease Pathogen Treatment of (Time Relative Range weight. A second subcutaneous injection of 3.6 mg/lb (8 mg/kg) may be administered if response does not undergo hepatic metabolism and the majority of a dose is excreted unchanged in the Outcome Isolates μg/mL μg/mL urine. EliminationCONVENIA also occurs should from be excretion administered of unchanged as a single drug subcutaneous in the bile. Cefovecin injection of is 3.6a highly mg/lb (8 mg/kg)Skin body Pasteurellakinetics is Successexhibited (plasma57 concentrationsPre-Treatment do not increase≤ 0.06 proportionally≤ 0.06 ≤ 0.06 with - 0.12 dose). Cefovecin to Treatment) μg/mL to therapy is not complete. The decision for a second injection for any individual dog should take does not undergo hepatic metabolism and the majority of a dose is excreted unchanged in the into consideration such factors as progress toward clinical resolution, the susceptibility of the protein-bound moleculeweight. A insecond dog plasma subcutaneous (98.5%) andinjection cat plasmaof 3.6 mg/lb (99.8%) (8 mg/kg) and may may compete be administered with ifInfections response multocida Success 57 Pre-Treatment 0.06 0.06 0.06 - 0.12 to therapy is not complete. The decision for a second injection for any individual dog should take urine. EliminationFailure also occurs1 from excretionPre-Treatment of unchanged drug in the≤ bile.0.06 Cefovecin is a highly Skin Pasteurella ≤ ≤ ≤ causative organisms, and the integrity of the dog’s host-defense mechanisms. Therapeutic drug other highly protein-bound drugs for plasma protein-binding sites that could result in transient, Infections multocida higher free druginto concentrations consideration ofsuch either factors compound. as progress Pharmacokinetic toward clinical parameters resolution, followingthe susceptibility of the protein-bound molecule in dog plasma (98.5%) and cat plasma (99.8%) and may compete with Failure 1 Pre-Treatment ≤ 0.06 concentrations after the first injection are maintained for 7 days for S. intermedius infections and EFFECTIVENESS:other highly protein-bound drugs for plasma protein-binding sites that could result in transient, for 14 days for S. canis (Group G) infections. Maximum treatment should not exceed 2 injections. subcutaneous dosingcausative at 8 organisms,mg/kg in the and dog the and integrity cat are ofsummarized the dog’s host-defense in Table 4. mechanisms. Therapeutic drug concentrations after the first injection are maintained for 7 days for S. intermedius infectionsDogs and higher free drug concentrations of either compound. Pharmacokinetic parameters following EFFECTIVENESS: Cats Table 4: Pharmacokineticfor 14 days for S.Parameters canis (Group Reflecting G) infections. Total Maximum Drug Concentrationstreatment should in not Plasma exceed 2In injections. a double-masked,subcutaneous 1:1 randomized dosing at canine8 mg/kg field in the studydog and conducted cat are summarized in the United in Table States, 4. the (mean ± standard deviation or range) Following an 8 mg/kg Intravenous or Subcutaneous Dogs CONVENIA should be administered as a single, one-time subcutaneous injection at a dose of effectiveness ofTable CONVENIA 4: Pharmacokinetic was compared toParameters a cephalosporin Reflecting active control.Total Drug In this Concentrations study, 320 in Plasma 3.6 mg/lb (8 mg/kg) body weight. After an injection of CONVENIA, therapeutic concentrations Dose of CefovecinCats in Dogs and Cats. In a double-masked, 1:1 randomized canine field study conducted in the United States, the CONVENIA should be administered as a single, one-time subcutaneous injection atdogs a dose with of superficial (mean ±secondary standard deviationpyoderma, orabscesses, range) Following or infected an 8wounds mg/kg wereIntravenous treated orwith Subcutaneous are maintained for approximately 7 days for Pasteurella multocida infections. either a single injection of CONVENIA (n=157) at 3.6 mg/lb (8 mg/kg) body weight or with an oral effectiveness of CONVENIA was compared to a cephalosporin active control. In this study, 320 3.6 mg/lb (8 mg/kg) body weight. After an injection of CONVENIA, therapeutic concentrations Dose of Cefovecin in Dogs and Cats. dogs with superficial secondary pyoderma, abscesses, or infected wounds were treated with General Dosing Information are maintained for approximately 7 days for PasteurellaMEAN ± SD multocida1 or (Range) infections. active control antibiotic (n=163), administered twice daily for 14 days. In this study, dogs could receive a second course of therapy 14 days after the initial treatment. Of the 320 enrolled dogs, either a single injection of CONVENIA (n=157) at 3.6 mg/lb (8 mg/kg) body weight or with an oral A sample of the lesion should be obtained for culture and susceptibility testing prior to beginning PARAMETER 1 active control antibiotic (n=163), administered twice daily for 14 days. In this study, dogs could antimicrobial therapy. Once results become available, continue with appropriate therapy. If General Dosing Information 22 of 157 dogs received 2 treatments of CONVENIA and 35 of 163 dogs receivedMEAN 2 ±courses SD or of(Range) A sample of the lesion should be obtained for cultureDogs and susceptibilityCats testingp prior totreatment beginning with the active control. In the study, 118 of the 157 enrolled cases were evaluable for receive a second course of therapy 14 days after the initial treatment. Of the 320 enrolled dogs, acceptable response to treatment is not observed, or if no improvement is seen within 3 to 4 days, PARAMETER 22 of 157 dogs received 2 treatments of CONVENIA and 35 of 163 dogs received 2 courses of antimicrobial therapy. Once results become available, continue with appropriateeffectiveness therapy. If for CONVENIA, and 117 of the 163 enrolled cases were evaluable for effectiveness of p then the diagnosis should be re-evaluated and appropriate alternative therapy considered. h Dogs Cats treatment with the active control. In the study, 118 of the 157 enrolled cases were evaluable for Terminal plasmaacceptable elimination response half-life, to treatment T1/2 (h)* is not observed,133 ± or16 if no improvement166 ± is 18 seen withinthe 3 to active 4 days, control antibiotic. CONVENIA was non-inferior to the active control. Table 7 summarizes CONVENIA may persist in the body for up to 65 days. The effect of remaining concentrations then theg diagnosis should be re-evaluated and appropriatep alternative therapy considered. effectiveness for CONVENIA, and 117 of the 163 enrolled cases were evaluable for effectiveness of AUC (μg·h/mL)* 10400 ± 1900 22700 ± 3450 the clinical successTerminal rates obtained plasma elimination28 days after half-life, the initiation T (h)* of theh final course133 ± of 16 therapy. 166 ± 18 of cefovecin on any subsequent antimicrobial therapies has not been determined. 0-inf 1/2 the active control antibiotic. CONVENIA was non-inferior to the active control. Table 7 summarizes Fluoroquinolone and aminoglycoside antimicrobials have been reported to be compatible Time of maximumCONVENIA concentration, may persist T in (h)* theh body for up6.2 to (0.5-12.0)65 days. The effect2.0 of (0.5-6.0) remaining concentrationsTable 7: Clinical AUC Success (μg·h/mL)* Rates gby Treatment Group 28 Days after10400 the ±Initiation 1900p of the22700 ± 3450 the clinical success rates obtained 28 days after the initiation of the final course of therapy. of cefovecin on anymax subsequent antimicrobial therapies has not been determined. 0-inf with cephalosporin antimicrobial agents.1,2,3 Maximum concentration, C (μg/mL)*a 121 ± 51 141 ± 12 Final Course of Therapy. h Fluoroquinolonemax and aminoglycoside antimicrobials have been reported to be compatible Time of maximum concentration, Tmax (h)* 6.2 (0.5-12.0) 2.0 (0.5-6.0) Table 7: Clinical Success Rates by Treatment Group 28 Days after the Initiation of the Table 1: Dose Table for CONVENIA at 8 mg/kg Body Weight. g 1,2,3 a Final Course of Therapy. Vdss (L/kg)** with cephalosporin antimicrobial agents.0.122 ± 0.011 0.090 ± 0.010 Maximum concentration, C (μg/mL)* Dogs 121 ± 51 141 ± 12 g p max CL (mL/h/kg)** 0.76 ± 0.13 0.350 ± 0.40 g total Table 1: Dose Table for CONVENIA at 8 mg/kg Body Weight. Type of InfectionVd (L/kg)** 0.122 ± 0.011 0.090 ± 0.010 Volume of CONVENIA ss CONVENIA Active Control Dogs Weight of Animal CL (mL/h/kg)**g 0.76 ± 0.13p 0.350 ± 0.40 (3.6 mg/lb or 0.045 mL/lb) 1 total (n=118) (n=117) Type of Infection SD = standard deviation Volume of CONVENIA CONVENIA Active Control p Weight of Animal 5 lb 0.23 mL = a phase effect was observed, only data for the first phase are provided(3.6 (n=6); mg/lb all orother 0.045 data mL/lb) Skin (secondary1 superficial pyoderma, (n=118) (n=117) provided are derived from 12 animals abscesses, and SD infected = standard wounds) deviation 109 (92.4%) 108 (92.3%) 10 lb 0.45 mL 5 lb 0.23 mL p = a phase effect was observed, only data for the first phase are provided (n=6); all other data Skin (secondary superficial pyoderma, * = SC abscesses, and infected wounds) 109 (92.4%) 108 (92.3%) 15 lb 0.67 mL ** = IV 10 lb 0.45 mL CONVENIA wasprovided administered are derived concomitantly from 12 animals with other commonly used veterinary products a * = SC 20 lb 0.90 mL = arithmetic mean 15 lb 0.67 mL such as heartworm preventatives, flea control products, sedatives/tranquilizers, anesthetic CONVENIA was administered concomitantly with other commonly used veterinary products h agents, routine** immunizations, = IV antihistamines, thyroid hormone supplementation, and non- = harmonic mean a such as heartworm preventatives, flea control products, sedatives/tranquilizers, anesthetic 40 lb 1.80 mL g 20 lb 0.90 mL steroidal anti-inflammatory = arithmetic meandrugs during the field study. = geometric mean h agents, routine immunizations, antihistamines, thyroid hormone supplementation, and non- 80 lb 3.60 mL 40 lb 1.80 mL = harmonic mean Population Pharmacokinetics Cats g = geometric mean steroidal anti-inflammatory drugs during the field study. 80 lb 3.60 mL In a double-masked, 1:1 randomized cat field study conducted in the United States, the PREPARATION OF SOLUTION FOR INJECTION: To deliver the appropriate dose, aseptically Dogs Population Pharmacokinetics Cats reconstitute CONVENIA with 10 mL sterile water for injection. Shake and allow vial to sit until all Cefovecin plasma concentrations in the dog have been characterized by the use of population effectiveness of CONVENIA was compared to an active control. In this study, 291 cats with PREPARATION OF SOLUTION FOR INJECTION: To deliver the appropriate dose, infectedaseptically wounds Dogs or abscesses were treated with either a single injection of CONVENIA (n=147) In a double-masked, 1:1 randomized cat field study conducted in the United States, the material is visually dissolved. The resulting solution contains cefovecin sodium equivalent to 80 pharmacokineticCats reconstitute (PPK) data. CONVENIA Plasma withcefovecin 10 mL sterileconcentration water for injection.data were Shake pooled and allowfrom vial7 to sit untilMICROBIOLOGY: all CONVENIA is a cephalosporin antibiotic. Like other β-lactam effectiveness of CONVENIA was compared to an active control. In this study, 291 cats with mg/mL cefovecin. CONVENIA is light sensitive. The vial should be stored in the original carton and laboratory pharmacokinetic studies, each involving young, normal healthy Beagle dogs. The at 3.6 mg/lb (8 mg/kg)Cefovecin body plasma weight concentrations or with an oral inactive the dogcontrol have antibiotic been characterized (n=144), administered by the use of population A total ofmaterial 291 cats, is visually ranging dissolved. in age from The 2.4resulting months solution (1 cat) contains to 21 years, cefovecin were sodiumincluded equivalent in oncethe daily toantimicrobials, 80 for 14pharmacokinetic days. CONVENIACONVENIA (PPK) was exerts non-inferiordata. itsPlasma inhibitory to thecefovecin active effect control.concentration by Theinterfering clinical data success withwere bacterialpooled from 7 infected wounds or abscesses were treated with either a single injection of CONVENIA (n=147) refrigerated when not in use. Use the entire contents of the vial within 56 days of reconstitution. final datasetfield studycontained safety 591 analysis.concentration Adverse records reactions from 39reported dogs. The in catssimulations treated from with the CONVENIA model and cell wall synthesis. This interference is primarily due to its covalent binding to the at 3.6 mg/lb (8 mg/kg) body weight or with an oral active control antibiotic (n=144), administered mg/mL cefovecin. CONVENIA is lightth sensitive.th The vial should be stored in the originalrates carton were and obtained laboratory 28 days pharmacokinetic after the initiation studies, of therapy each andinvolving are presented young, normal in Table healthy 8. Beagle dogs. The CONTRAINDICATIONS: CONVENIA is contraindicated in dogs and cats with known allergy to providethe the activemeanrefrigerated populationcontrol are when estimate summarized not in and use. the in Use Table 5 the and 3.entire 95 percentile contents ofof the the vial population within 56 estimates days of reconstitution. penicillin-bindingfinal dataset proteins contained (PBPs) 591 concentration (ie, transpeptidase records from and 39 dogs.carboxypeptidase), The simulations fromwhich the model once daily for 14 days. CONVENIA was non-inferior to the active control. The clinical success of total and free cefovecin concentrations over time. Figure 2 shows the predicted free plasma Table 8: Clinical Success Rates by Treatment Group 28 Days after the Initiation of Therapy. rates were obtained 28 days after the initiation of therapy and are presented in Table 8. cefovecin(cefovecin or to β-lactam (penicillins sodium) and cephalosporins) group antimicrobials. Anaphylaxis Table 3:CONTRAINDICATIONS: Number of Cats* with CONVENIA Adverse Reactionsis contraindicated Reported in Duringdogs and the cats Field with Study known with allergy are to essentialprovide for the synthesismean population of the estimatebacterial and cell the wall. 5th and For 95 E.th percentile coli, the ofin thevitro population activity estimatesof has been reported with the use of this product in foreign market experience. If an allergic concentrations following administration of 8 mg/kg body weight to dogs. Based upon these CONVENIA is comparable to other cephalosporins, but due to the high-affinity protein- CONVENIA.cefovecin or to β-lactam (penicillins and cephalosporins) group antimicrobials. Anaphylaxis of total and free cefovecin concentrations over time. Figure 2 shows the predicted free plasma Table 8: Clinical Success Rates by Treatment Group 28 Days after the Initiation of Therapy. reactionAntimicrobial or anaphylaxis for occurs, Subcutaneous CONVENIA Injection should in not Dogs be administeredand Cats Only again and appropriate predicted concentrations, 95% of the canine population will have active (free) drug concentrations binding, the in vivo free concentration of cefovecinCats does not reach the MIC for > the MIC ofhas S. beencanis reported(0.06 μg/mL) with thefor approximatelyuse of this product 14 days in foreign and free market concentrations experience. If an allergic concentrations following administration of 8 mg/kg body weight to dogs. Based90 upon these therapy should be instituted. Anaphylaxis may require treatment with epinephrine and other 90 Type ofE. Infection coli (1.0 μg/mL). CONVENIA is not activeCONVENIA against Pseudomonas Activespp. or Control enterococci. Cats CAUTION: Federal (USA) law restricts this drug to use by or on the order of a licensed veterinarian.> the MIC forreaction S. intermedius or anaphylaxis (0.25 occurs,μg/mL) CONVENIAfor approximately CONVENIAshould not7 days be administered followingActive a again single Control and appropriate predicted concentrations, 95% of the canine population will have active (free) drug concentrations emergency measures, including oxygen, intravenous fluids, intravenous antihistamine, Adverse90 Reaction > the MIC of S. canis (0.06 μg/mL)(n=89) for approximately 14 (n=88)days and free concentrations therapy should be instituted. Anaphylaxis may(n=147) require treatment with(n=144) epinephrine and otherDogs 90 Type of Infection CONVENIA Active Control corticosteroids,DESCRIPTION: and airwayCefovecin management, sodium is a semi-synthetic as clinically indicated.broad-spectrum Adverse antibacterial reactions agent may from 8 themg/kg subcutaneous injection of cefovecin. (See MICROBIOLOGY). > the MIC for S. intermedius (0.25 μg/mL) for approximately 7 days following a single emergency measures, including oxygen, intravenous fluids, intravenous antihistamine,The minimum inhibitory90 concentration (MIC) values for cefovecin against label-claim pathogens (n=89) (n=88) require cephalosporinprolonged treatment class of duechemotherapeutic to the prolonged agents. systemic Cefovecin drug isclearance the non-proprietary (65 days). designationFigure for 2: PopulationVomiting Predicted Free Concentration of Cefovecin10 in Plasma Following a Single14 Skin (wounds 8and mg/kg abscesses) subcutaneous injection of 86cefovecin. (96.6%) (See MICROBIOLOGY80 (90.9%)). (6R,7R)-7-[[(2Z)-(2-amino-4-thiazolyl)(methoxyimino)acetyl]amino]-8-oxo-3-[(2S)-tetrahydro-2- corticosteroids, and airway management, as clinically indicated. Adverse reactions mayisolated from skin infections in dogs enrolled in a 2001-2003 field effectiveness study are presented WARNINGS: Not for use in humans. Keep this and all drugs out of reach of children. Consult a SubcutaneousDiarrhea requireInjection prolonged of 8 mg/kg treatment Body Weight due to in the Dogs prolonged (solid7 line systemic is population drug clearance prediction,26 (65 days). in TableFigure 5. All MICs2: Population were determined Predicted in Free accordance Concentration with the of ClinicalCefovecin and in Laboratory Plasma Following Standards a Single furanyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, monosodium salt. dotted lines are the 5th and 95th percentiles for the population prediction). CONVENIA was used concomitantly with other commonly used veterinary products such as Skin (wounds and abscesses) 86 (96.6%) 80 (90.9%) physician in case of accidental human exposure. For subcutaneous use in dogs and cats only. Anorexia/DecreasedWARNINGS: Not Appetitefor use in humans. Keep this and6 all drugs out of reach of6 children. ConsultInstitute a Subcutaneous (CLSI) standards. Injection of 8 mg/kg Body Weight in Dogs (solid line is population prediction, AntimicrobialFigure drugs,1: Chemical including structure penicillins of cefovecin and cephalosporins, sodium. can cause allergic reactions in heartworm preventatives,dotted lines areflea the control 5th and products, 95th percentiles sedatives/tranquilizers, for the population anesthetic prediction). agents, Lethargyphysician in case of accidental human exposure.6 For subcutaneous use in6 dogs andand cats vaccines only.Table 5: during Activity the of field CONVENIA study. against Pathogens Isolated from Dogs Treated with CONVENIA CONVENIA was used concomitantly with other commonly used veterinary products such as sensitized individuals. To minimize the possibility of allergic reactions, those handling such in Field Studies in the US During 2001-2003. heartworm preventatives, flea control products, sedatives/tranquilizers, anesthetic agents, Hyper/ActingAntimicrobial Strange drugs, including penicillins and cephalosporins,1 can cause1 allergic reactions in antimicrobials, including cefovecin, are advised to avoid direct contact of the product with sensitized individuals. To minimize the possibility of allergic reactions, those handlingANIMAL such SAFETY: and vaccines during the field study. the skin and mucous membranes. Inappropriateantimicrobials, Urination including cefovecin, are advised1 to avoid direct contact0 of the productDogs with Sample CONVENIA administered to healthy 4-month-oldMicrobiological dogs Numberat doses ofCollection 12 mg/kg (1.5X),MIC 36 mg/kgMIC (4.5X),MIC ANIMAL SAFETY: PRECAUTIONS: Prescribing antibacterial drugs in the absence of a proven or strongly the skin and mucous membranes. Disease Pathogen Treatment of 50 90 Range Dogs suspected bacterial infection is unlikely to provide benefit to treated animals and may *Some cats may have experienced more than one adverse reaction or more than andone 60 mg/kg (7.5X) every 7 days by dorsoscapular subcutaneous(Time injections Relative was well-tolerated for PRECAUTIONS: Prescribing antibacterial drugs in the absence of a proven or strongly Outcome Isolates μg/mL μg/mL CONVENIA administered to healthy 4-month-old dogs at doses of 12 mg/kg (1.5X), 36 mg/kg (4.5X), increase the risk of the development of drug-resistant animal pathogens. occurrence of the same adverse reaction during the study. a total of 5 doses. Vomiting and diarrhea were seen in all treatmentto Treatment) groups, with the incidence ofμg/mL suspected bacterial infection is unlikely to provide benefit to treated animalsvomiting and andmay the incidence and duration of diarrhea increasing in a dose-related manner. Injection and 60 mg/kg (7.5X) every 7 days by dorsoscapular subcutaneous injections was well-tolerated for The safe use of CONVENIA in dogs or cats less than 4 months of age (see Animal Safety) and Four CONVENIAincrease thecases risk had of the mildly development elevated post-study of drug-resistant ALT (1 animalcase was pathogens. elevated pre-study). a total of 5 doses. Vomiting and diarrhea were seen in all treatment groups, with the incidence of No clinical abnormalities were noted with these findings. site irritation and transientStaphylococcus edema occurred Success with increasing44 frequencyPre-Treatment in a dose-related0.12 manner0.25 and≤ 0.06 - 2 in breeding or lactating animals has not been determined. Safety has not been established The safe use of CONVENIA in dogs or cats less than 4 months of age (see Animal withSafety repeat) and injections. Two injection site reactions included a seroma over the shoulder and swelling vomiting and the incidence and duration of diarrhea increasing in a dose-related manner. Injection for IM or IV administration. The long-term effects on injection sites have not been determined. Twenty-four CONVENIA cases had normal pre-study BUN values and elevated post-study intermedius site irritation and transient edema occurred with increasing frequency in a dose-related manner and in breeding or lactating animals has not been determined. Safety has not been establishedlasting > 30 days. Dogs dosed at 36 mg/kgFailure had a significant4 (P=0.0088)Pre-Treatment increase in BUN (all means0.12 - 2 CONVENIA is slowly eliminated from the body, approximately 65 days is needed to eliminate BUN valuesfor IM (37 or – IV 39 administration. mg/dL post-study). The long-term There were effects 6 CONVENIA on injection cases sites with have normal not been pre- determined. remainedand Skin within the normal range) compared to the controls. One dog dosed at 60 mg/kg exhibited with repeat injections. Two injection site reactions included a seroma over the shoulder and swelling 97% of theEach administered mL of CONVENIA dose fromreconstituted the body. lyophileAnimals contains experiencing cefovecin an adverse sodium reaction equivalent may to 80 mg mildly toCONVENIA moderately is elevatedslowly eliminated post-study from creatinine the body, values. approximately Two of these 65 days cases is neededalso had toa an glomerulopathyeliminate Infections on histopathology, and 1 dog in this same group had minimal peliosis hepatis. lasting > 30 days. Dogs dosed at 36 mg/kg had a significant (P=0.0088) increase in BUN (all means need tocefovecin, be monitored methylparaben for this duration. 1.8 mg (preservative), propylparaben 0.2 mg (preservative), sodium elevated97% post-study of the administered BUN. No clinical dose abnormalitiesfrom the body. were Animals noted experiencing with these findings.an adverse reaction may Streptococcus Success 16 Pre-Treatment ≤ 0.06 ≤ 0.06 ≤ 0.06 remained within the normal range) compared to the controls. One dog dosed at 60 mg/kg exhibited citrate dihydrate 5.8 mg and citric acid monohydrate 0.1 mg, sodium hydroxide or hydrochloric At an exaggerated dose of 180 mg/kg (22.5X) in dogs, CONVENIA caused some injection site a glomerulopathy on histopathology, and 1 dog in this same group had minimal peliosis hepatis. CONVENIA has been shown in an experimental in vitro system to result in an increase in free One CONVENIA-treatedneed to be monitored cat infor a this separate duration. field study experienced diarrhea post-treatmentirritation, vocalization,canis and (Group edema. G) Edema resolved within 8-24 hours. concentrationsacid as of required carprofen, to adjust furosemide, pH. doxycycline, and ketoconazole. Concurrent use of these or lasting 42 days. The diarrhea resolved. Failure 2 Pre-Treatment ≤ 0.06 At an exaggerated dose of 180 mg/kg (22.5X) in dogs, CONVENIA caused some injection site CONVENIA has been shown in an experimental in vitro system to result in an increaseCats in free other drugsINDICATIONS: that have a high degree of protein-binding (e.g. NSAIDs, propofol, cardiac, anticonvulsant, FOREIGN MARKET EXPERIENCE: The following adverse events were reported voluntarily irritation, vocalization, and edema. Edema resolved within 8-24 hours. and behavioral medications) may compete with cefovecin-binding and cause adverse reactions. concentrations of carprofen, furosemide, doxycycline, and ketoconazole. Concurrent useCONVENIA of these or administered to healthy 4-month-old cats at doses of 12 mg/kg (1.5X), 36 mg/kg (4.5X), Dogs during post-approvalother drugs that use have of a the high product degree ofin protein-bindingdogs and cats (e.g. in foreign NSAIDs, markets: propofol, death, cardiac, tremors/ anticonvulsant,and 60 Catsmg/kg (7.5X) every 7 days by dorsoscapular subcutaneous injections was well-tolerated Cats PositiveCONVENIA direct Coombs’ is indicated test forresults the treatment and false of skinpositive infections reactions (secondary for glucose superficial in the pyoderma, ataxia, seizures,and behavioral anaphylaxis, medications) acute may pulmonary compete with edema, cefovecin-binding facial edema, and injection cause adverse site reactions reactions. The MIC values for cefovecin against Pasteurella multocida isolated from skin infections CONVENIA administered to healthy 4-month-old cats at doses of 12 mg/kg (1.5X), 36 mg/kg (4.5X), for a total of 5 doses. Vomiting and diarrhea were observed in cats, with the incidence of vomiting and 60 mg/kg (7.5X) every 7 days by dorsoscapular subcutaneous injections was well-tolerated urine haveabscesses, been andreported wounds) during in dogs treatment caused bywith susceptible some cephalosporinstrains of Staphylococcus antimicrobials. intermedius (alopecia,Positive scabs, direct necrosis, Coombs’ and erythema), test results hemolytic and false anemia, positive salivation, reactions pruritus, for lethargy,glucoseand thein (woundsincidencethe and durationabscesses) of diarrhea in cats increasing enrolled in ina dose-related a 2001-2003 manner. field Theeffectiveness mean albumin study are Cephalosporinand Streptococcus antimicrobials canis may (Group also G)cause. falsely elevated urine protein determinations. vomiting,urine diarrhea, have andbeen inappetance. reported during treatment with some cephalosporin antimicrobials.presented in Table 6. All MICs were determined in accordance with the CLSI standards. for a total of 5 doses. Vomiting and diarrhea were observed in cats, with the incidence of vomiting Some antimicrobials, including cephalosporins, can cause lowered albumin values due to values for all the CONVENIA-treated cats were significantly lower (P ≤ 0.05) than the control values and the incidence and duration of diarrhea increasing in a dose-related manner. The mean albumin Cats For a copyCephalosporin of the Material antimicrobials Safety Data may Sheetalso cause (MSDS) falsely or toelevated report urinea suspected protein determinations.adverse(all means Table remained 6: Activity within of CONVENIAthe normal range) against for Pathogens all time periods. Isolated The from mean Cats alkaline Treated phosphatase with CONVENIA interference with certain testing methods. Cats values for all the CONVENIA-treated cats were significantly lower (P ≤ 0.05) than the control values CONVENIA is indicated for the treatment of skin infections (wounds and abscesses) in cats reactionSome call Pfizerantimicrobials, Animal Healthincluding at 1-800-366-5288. cephalosporins, can cause lowered albumin valuesvalues due inin the toField 60 mg/kg Studies group in the were US significantly During 2001-2003. higher (P ≤ 0.0291) than the control values for all time (all means remained within the normal range) for all time periods. The mean alkaline phosphatase Occasionally,caused cephalosporins by susceptible and strains NSAIDs of have Pasteurella been associated multocida with. myelotoxicity, thereby creating Cefovecin plasmainterference concentrations with certain in the cattesting have methods. been characterized by the use of PPK data. periods. Injection-site irritation and transient edema occurred with increasing frequency in a dose- 4 CLINICAL PHARMACOLOGY: Cats values in the 60 mg/kg group were significantly higher (P 0.0291) than the control values for all time a toxic neutropenia . Other hematological reactions seen with cephalosporins include neutropenia, Plasma cefovecin concentration data were pooled from 4 laboratory pharmacokinetic studies. related manner and with repeat injections. One cat in the 12 mg/kg group had a mild renal tubular and ≤ DOSAGE AND ADMINISTRATION: Occasionally, cephalosporins and NSAIDs have been associated with myelotoxicity, thereby creating Cefovecin plasmaMicrobiological concentrations Numberin the cat Sample have been characterized by theMIC use of PPK data. periods. Injection-site irritation and transient edema occurred with increasing frequency in a dose- anemia, hypoprothrombinemia, thrombocytopenia, prolonged prothrombin time (PT) and partial The finalPharmacokinetics dataset contained 338 4concentration records from 22 cats. The simulations from the interstitial fibrosis, and 1 cat in the 12 mg/kg group had mild glomerulosclerosisCollection MICon histopathology.MIC a toxic neutropenia . Other hematological reactionsth seenth with cephalosporins include neutropenia, Plasma cefovecin concentration data were pooled from 4 laboratory50 pharmacokinetic90 studies. related manner and with repeat injections. One cat in the 12 mg/kg group had a mild renal tubular and thromboplastinDogs time (PTT), platelet dysfunction and transient increases in serum aminotransferases. model provideCefovecin the ismean rapidly population and completely estimate absorbed as well as following the 5 and subcutaneous 95 percentile administration. of the population Non-linear Disease Pathogen Treatment of (Time Relative Range anemia, hypoprothrombinemia, thrombocytopenia, prolonged prothrombin time (PT) Atand an exaggeratedpartial The dose final of 180dataset mg/kg contained (22.5X), CONVENIA 338 concentration was associated records with from injectionμ g/mL22 cats. siteμg/mL The irritation, simulations from the estimateskinetics of total is and exhibited free cefovecin (plasma concentrations overdo not time. increase Figure proportionally 3 displays the predictedwith dose). free Cefovecin Outcome Isolates μg/mL interstitial fibrosis, and 1 cat in the 12 mg/kg group had mild glomerulosclerosis on histopathology. ADVERSECONVENIA REACTIONS: should be administered as a single subcutaneous injection of 3.6 mg/lb (8 mg/kg) body model provide the mean population estimate asto Treatment)well as the 5th and 95th percentile of the population plasma doesconcentrations notthromboplastin undergo following hepatic time administration metabolism(PTT), platelet and of dysfunction 8 themg/kg majority body and weight oftransient a dose to increasescats. is excreted Based in serumupon unchanged these aminotransferases. invocalization, the and edema. Edema resolved within 8-24 hours. On day 10, cats had lower mean white At an exaggerated dose of 180 mg/kg (22.5X), CONVENIA was associated with injection site irritation, weight. A second subcutaneous injection of 3.6 mg/lb (8 mg/kg) may be administered if response blood cell countsestimates compared of tototal the andSuccess controls. free cefovecin One cat57 had concentrations a smallPre-Treatment amount over of time. bilirubinuria≤ Figure 0.06 3 ≤on displays 0.06 day 10.≤ the0.06 predicted - 0.12 free Dogs to therapy is not complete. The decision for a second injection for any individual dog should predictedtake urine. concentrations, EliminationADVERSE 95%also REACTIONS: ofoccurs the feline from population excretion will of haveunchanged active (free) drug drugin the concentrations bile. Cefovecin > the is a highly Skin plasmaPasteurella concentrations following administration of 8 mg/kg body weight to cats. Based upon these vocalization, and edema. Edema resolved within 8-24 hours. On day 10, cats had lower mean white A total of 320 dogs, ranging in age from 8 weeks to 19 years, were included in a field study MIC ofprotein-bound Pasteurella multocida molecule (0.06 in dogμg/mL) plasma for approximately (98.5%) and cat7 days plasma when (99.8%) administered and may a single compete 8 withSTORAGE Infections INFORMATION:multocida into consideration such factors as progress toward clinical resolution, the susceptibility of the90 Dogs predicted concentrations,Failure 95% of the1 feline populationPre-Treatment will have active (free) drug concentrations≤ 0.06 > the blood cell counts compared to the controls. One cat had a small amount of bilirubinuria on day 10. safety analysis. Adverse reactions reported in dogs treated with CONVENIA and the active mg/kg subcutaneous injection of cefovecin. (See MICROBIOLOGY). ° ° causative organisms, and the integrity of the dog’s host-defense mechanisms. Therapeutic drug other highlyA total protein-bound of 320 dogs, drugs ranging for inplasma age fromprotein-binding 8 weeks to sites 19 years, that could were result included in transient, in aStore field the study powder MIC and of thePasteurella reconstituted multocida product (0.06 in μ g/mL)the original for approximately carton, refrigerated 7 days when at 2 administered to 8 C a single 8 STORAGE INFORMATION: control are summarized in Table 2. higher free drug concentrations of either compound. Pharmacokinetic parameters following° ° 90 concentrations after the first injection are maintained for 7 days for S. intermedius infections Figureand 3: Populationsafety analysis.Predicted Adverse Free Concentration reactions reported of Cefovecin in dogs treatedin Plasma with Following CONVENIA a and(36 the to active 46EFFECTIVENESS: F). Usemg/kg the entiresubcutaneous contents injectionof the vial of within cefovecin. 56 days (See of MICROBIOLOGY reconstitution. PROTECT). FROM Store the powder and the reconstituted product in the original carton, refrigerated at 2° to 8° C for 14 days for S. canis (Group G) infections. Maximum treatment should not exceed 2 injections. subcutaneous dosing at 8 mg/kg in the dog and cat are summarized in Table 4. LIGHT. After each use it is important to return the unused portion back to the refrigerator in the ° ° Table 2: Number of Dogs* with Adverse Reactions Reported During the Field Study with Single Subcutaneouscontrol areInjection summarized of 8 mg/kg in Table Body 2. Weight in Cats (solid line is population Dogs Figure 3: Population Predicted Free Concentration of Cefovecin in Plasma Following a (36 to 46 F). Use the entire contents of the vial within 56 days of reconstitution. PROTECT FROM CONVENIA. prediction,Table dotted 4: Pharmacokineticlines are the 5th and Parameters 95th percentiles Reflecting for the populationTotal Drug prediction). Concentrations in Plasmaoriginal carton. As with other cephalosporins, the color of the solution may vary from clear to LIGHT. After each use it is important to return the unused portion back to the refrigerator in the Cats Table 2: Number of Dogs* with Adverse Reactions Reported During the Field amberStudy atwithIn reconstitution a double-masked,Single Subcutaneous and may 1:1 darken randomized Injection over time. canine of If stored8 fieldmg/kg as study recommended,Body conducted Weight insolution in Cats the color(solidUnited does lineStates, is population the (mean ± standard deviation or range) Following an 8 mg/kg Intravenous or Subcutaneous th th original carton. As with other cephalosporins, the color of the solution may vary from clear to CONVENIA should be administered as a single, one-time subcutaneous injection at a dose of CONVENIA. not adverselyeffectiveness affectprediction, potency. of CONVENIA dotted lines was are compared the 5 and to a95 cephalosporin percentiles activefor the control. population In this prediction). study, 320 Adverse3.6 mg/lbReaction (8 mg/kg) body weight. After an injectionCONVENIA of CONVENIA, therapeuticActive Control concentrations Dose of Cefovecin in Dogs and Cats. dogs with superficial secondary pyoderma, abscesses, or infected wounds were treated with amber at reconstitution and may darken over time. If stored as recommended, solution color does are maintained for approximately 7 days for Pasteurella(n=157) multocida infections.(n=163) HOW SUPPLIED:either a single injection of CONVENIA (n=157) at 3.6 mg/lb (8 mg/kg) body weight or with an oral not adversely affect potency. Adverse Reaction CONVENIA Active Control LethargyGeneral Dosing Information 2 7 MEAN(n=157) ± SD1 or (Range)(n=163)CONVENIAactive is controlavailable antibiotic as a 10 (n=163), mL multi-use administered vial containing twice daily 800 for milligrams 14 days. In of this cefovecin study, dogs as could HOW SUPPLIED: A sample of the lesion should be obtained for culture and susceptibility testing prior to beginning a lyophilizedreceive cake. a second course of therapy 14 days after the initial treatment. Of the 320 enrolled dogs, CONVENIA is available as a 10 mL multi-use vial containing 800 milligrams of cefovecin as Anorexia/Decreased Appetite 5 8 PARAMETERLethargy 2 7 22 of 157 dogs received 2 treatments of CONVENIA and 35 of 163 dogs received 2 courses of antimicrobial therapy. Once results become available, continue with appropriate therapy. If p REFERENCES: a lyophilized cake. Vomitingacceptable response to treatment is not observed, or6 if no improvement is seen12 within 3 to 4 days, Anorexia/Decreased Appetite Dogs5 Cats 8 1Pillai SK,treatment Moellering with the RC, active Eliopoulos control. GM.In the Antimicrobial study, 118 of thecombinations. 157 enrolled casesIn: Lorian were V,evaluable ed. for effectiveness for CONVENIA, and 117 of the 163 enrolled cases were evaluable for effectiveness of REFERENCES: Diarrheathen the diagnosis should be re-evaluated and appropriate6 alternative therapy7 considered. Vomiting h 6 12Antibiotics in laboratory medicine. 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins, 1 Terminal plasma elimination half-life, T (h)* 133 ± 16 166 ± 18 the active control antibiotic. CONVENIA was non-inferior to the active control. Table 7 summarizes Pillai SK, Moellering RC, Eliopoulos GM. Antimicrobial combinations. In: Lorian V, ed. Blood in Feces 1 2 1/2 2005;365-440. Antibiotics in laboratory medicine. 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins, CONVENIA may persist in the body for up to 65 days. The effect of remaining concentrations AUC (μg·h/mL)*Diarrhea g 10400 ± 19006 p 22700 ± 34507 2Fish DN,the Choi clinical MK, success Jung R. ratesSynergic obtained activity 28 days of cephalosporins after the initiation plus of fluoroquinolones the final course of againsttherapy. of cefovecin on any subsequent antimicrobial therapies has not been determined. 0-inf 2005;365-440. Dehydration 0 1 Blood in Feces h 1 2Pseudomonas aeruginosa with resistance to one or both drugs. J Antimicrob Chemother 2 Fluoroquinolone and aminoglycoside antimicrobials have been reported to be compatible Time of maximum concentration, Tmax (h)* 6.2 (0.5-12.0) 2.0 (0.5-6.0) Table 7: Clinical Success Rates by Treatment Group 28 Days after the Initiation of the Fish DN, Choi MK, Jung R. Synergic activity of cephalosporins plus fluoroquinolones against Flatulence 1,2,3 1 0 Dehydration a 0 12002;50:1045-1049.Final Course of Therapy. with cephalosporin antimicrobial agents. Maximum concentration, C (μg/mL)* 121 ± 51 141 ± 12 3 Pseudomonas aeruginosa with resistance to one or both drugs. J Antimicrob Chemother Increased Borborygmi 1 0 max Mayer I, Nagy E. Investigation of the synergic effects of aminoglycoside-fluoroquinolone and 2002;50:1045-1049. Table 1: Dose Table for CONVENIA at 8 mg/kg Body Weight. Vd (L/kg)**Flatulenceg 0.122 ± 0.0111 0.090 ± 0.0100third-generation cephalosporin combinations against clinical isolates of Pseudomonas spp. J ss Dogs 3Mayer I, Nagy E. Investigation of the synergic effects of aminoglycoside-fluoroquinolone and * CL (mL/h/kg)**Increasedg Borborygmi 0.76 ± 0.131 p 0.350 ± 0.400Antimicrob Chemother 1999;43:651-657. Some dogs may have experienced more than one adverse reaction or more than one total Type of Infection third-generation cephalosporin combinations against clinical isolates of Pseudomonas spp. J Volume of CONVENIA 4Birchard SJ, Sherding RG. Saunders manual of small animalCONVENIA practice . 2nd ed. Philadelphia:Active Control occurrence of the same Weight adverse of Animal reaction during the study. * Antimicrob Chemother 1999;43:651-657. (3.6 mg/lb or 0.045 mL/lb) 1 Some dogs may have experienced more than one adverse reaction or more thanPA: one WB Saunders Co, 2000;166. (n=118) (n=117) SD = standardoccurrence deviation of the same adverse reaction during the study. 4Birchard SJ, Sherding RG. Saunders manual of small animal practice. 2nd ed. Philadelphia: Mild to moderate elevations5 lb in serum -glutamyl transferase0.23 mL or serum alanine p = a phase effect was observed, only data for the first phase are provided (n=6); all other NADA#data 141-285,Skin (secondary Approved superficial by FDA pyoderma, PA: WB Saunders Co, 2000;166. aminotransferase were noted post-treatment in several of the CONVENIA-treated dogs. No provided are derived from 12 animals abscesses, and infected wounds) 109 (92.4%) 108 (92.3%) 10 lb 0.45 mL Mild to moderate elevations in serum -glutamyl transferase or serum alanineDistributed by: NADA# 141-285, Approved by FDA clinical abnormalities were noted with these findings. * = SC aminotransferase were noted post-treatment in several of the CONVENIA-treated dogs. No One CONVENIA-treated15 doglb in a separate field study experienced0.67 diarrheamL post-treatment ** = IV clinical abnormalities were noted with these findings. CONVENIA was administered concomitantly with other commonly used veterinary products Distributed by: a lasting 4 weeks. The diarrhea20 lb resolved. 0.90 mL = arithmetic mean suchD asiv. ofheartworm Pfizer Inc preventatives, flea control products, sedatives/tranquilizers,Revised June 2011 anesthetic h One CONVENIA-treated dog in a separate field study experienced diarrhea post-treatmentagents, routine immunizations, antihistamines, thyroid hormone supplementation, and non- 40 lb 1.80 mL = harmonic mean New York, NY 10017 11892301 Cats MICROBIOLOGY:g = geometriclasting CONVENIA mean 4 weeks. Theis diarrheaa cephalosporin resolved. antibiotic. Like other β-lactam steroidal anti-inflammatory drugs during the field study. Div. of Pfizer Inc Revised June 2011 A total of 291 cats, ranging80 lb in age from 2.4 months (1 cat) to 21 years,3.60 mL were included in the antimicrobials, CONVENIA exerts its inhibitory effect by interfering with bacterial New York, NY 10017 11892301 Population Pharmacokinetics Cats field study safety analysis. Adverse reactions reported in cats treated with CONVENIA and cell wall synthesis. This interference is primarily due to its covalent binding to the In a double-masked, 1:1 randomized cat field study conducted in the United States, the the activePREPARATION control are summarizedOF SOLUTION in Table FOR 3.INJECTION: To deliver the appropriate dose, asepticallypenicillin-binding Dogs proteins (PBPs) (ie, transpeptidase and carboxypeptidase), which reconstitute CONVENIA with 10 mL sterile water for injection. Shake and allow vial to sit until all effectiveness of CONVENIA was compared to an active control. In this study, 291 cats with (cefovecin sodium) Table 3: Number of Cats* with Adverse Reactions Reported During the Field Study with are essentialCefovecin for plasmasynthesis concentrations of the bacterial in the celldog wall.have beenFor E. characterized coli, the in byvitro the activity use of populationof material is visually dissolved. The resulting solution contains cefovecin sodium equivalent to 80 pharmacokinetic (PPK) data. Plasma cefovecin concentration data were pooled from 7 infected wounds or abscesses were treated with either a single injection of CONVENIA (n=147) CONVENIA. CONVENIA is comparable to other cephalosporins, but due to the high-affinity protein- at 3.6 mg/lb (8 mg/kg) body weight or with an oral active control antibiotic (n=144), administered mg/mL cefovecin. CONVENIA is light sensitive. The vial should be stored in the original cartonbinding, and laboratory the in vivopharmacokinetic free concentration studies, eachof cefovecin involving young,does not normal reach healthy the BeagleMIC fordogs. The Antimicrobial for Subcutaneous Injection in Dogs and Cats Only 90 once daily for 14 days. CONVENIA was non-inferior to the active control. The clinical success refrigerated when not in use. Use the entire contents of the vial within 56 days of reconstitution.E. coli (1.0final μg/mL). dataset CONVENIA contained is591 not concentration active against records Pseudomonas from 39 dogs. spp. orThe enterococci. simulations from the model CAUTION: Federal (USA) law restricts this drug to use by or on the order of a licensed veterinarian. CONVENIA Active Control th th rates were obtained 28 days after the initiation of therapy and are presented in Table 8. AdverseCONTRAINDICATIONS: Reaction CONVENIA is contraindicated in dogs and cats with known allergy to provide the mean population estimate and the 5 and 95 percentile of the population estimates (n=147) (n=144) Dogs Table 8: Clinical Success Rates by Treatment Group 28 Days after the Initiation of Therapy. DESCRIPTION: Cefovecin sodium is a semi-synthetic broad-spectrum antibacterial agent from the cefovecin or to β-lactam (penicillins and cephalosporins) group antimicrobials. AnaphylaxisThe minimumof total inhibitory and free concentrationcefovecin concentrations (MIC) values over for cefovecintime. Figure against 2 shows label-claim the predicted pathogens free plasma cephalosporin class of chemotherapeutic agents. Cefovecin is the non-proprietary designation for Vomitinghas been reported with the use of this product10 in foreign market experience.14 If an allergicisolated concentrationsfrom skin infections following in dogs administration enrolled in a 2001-2003 of 8 mg/kg field body effectiveness weight to studydogs. are Based presented upon these (6R,7R)-7-[[(2Z)-(2-amino-4-thiazolyl)(methoxyimino)acetyl]amino]-8-oxo-3-[(2S)-tetrahydro-2- Diarrheareaction or anaphylaxis occurs, CONVENIA should7 not be administered again26 and appropriatein Table predicted 5. All MICs concentrations, were determined 95% in of theaccordance canine population with the willClinical have and active Laboratory (free) drug Standards concentrations Cats furanyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, monosodium salt. > the MIC of S. canis (0.06 μg/mL) for approximately 14 days and free concentrations therapy should be instituted. Anaphylaxis may require treatment with epinephrine and other 90 Type of Infection CONVENIA Active Control Anorexia/Decreased Appetite 6 6 Institute> (CLSI) the standards.MIC for S. intermedius (0.25 μg/mL) for approximately 7 days following a single Figure 1: Chemical structure of cefovecin sodium. emergency measures, including oxygen, intravenous fluids, intravenous antihistamine, 90 (n=89) (n=88) Lethargycorticosteroids, and airway management, as clinically6 indicated. Adverse6 reactions Tablemay 5:8 Activity mg/kg subcutaneous of CONVENIA injectionagainst Pathogens of cefovecin. Isolated (See MICROBIOLOGYfrom Dogs Treated). with CONVENIA in Field Studies in the US During 2001-2003. Hyper/Actingrequire prolonged Strange treatment due to the prolonged1 systemic drug clearance1 (65 days). Figure 2: Population Predicted Free Concentration of Cefovecin in Plasma Following a Single Skin (wounds and abscesses) 86 (96.6%) 80 (90.9%) InappropriateWARNINGS: Urination Not for use in humans. Keep this and1 all drugs out of reach of0 children. Consult a Subcutaneous Injection of 8 mg/kg Body WeightSample in Dogs (solid line is population prediction, physician in case of accidental human exposure. For subcutaneous use in dogs and cats only. dotted lines are the 5Microbiologicalth and 95th percentilesNumber for the population prediction). MIC CONVENIA was used concomitantly with other commonly used veterinary products such as Collection MIC50 MIC90 *Some Antimicrobialcats may have drugs, experienced including penicillinsmore than and one cephalosporins, adverse reaction can orcause more allergic than reactionsone Disease in Pathogen Treatment of (Time Relative Range heartworm preventatives, flea control products, sedatives/tranquilizers, anesthetic agents, Outcome Isolates μg/mL μg/mL occurrencesensitized of the individuals.same adverse To reactionminimize during the possibility the study. of allergic reactions, those handling such to Treatment) μg/mL and vaccines during the field study. Four CONVENIAantimicrobials, cases includinghad mildly cefovecin, elevated post-studyare advised ALT to (1avoid case direct was contactelevated of pre-study). the product with ANIMAL SAFETY: No clinicalthe abnormalitiesskin and mucous were membranes. noted with these findings. Staphylococcus Success 44 Pre-Treatment 0.12 0.25 ≤ 0.06 - 2 Dogs PRECAUTIONS: Prescribing antibacterial drugs in the absence of a proven or strongly intermedius CONVENIA administered to healthy 4-month-old dogs at doses of 12 mg/kg (1.5X), 36 mg/kg (4.5X), Twenty-four CONVENIA cases had normal pre-study BUN values and elevated post-study and 60 mg/kg (7.5X) every 7 days by dorsoscapular subcutaneous injections was well-tolerated for BUN valuessuspected (37 – 39 bacterial mg/dL post-study). infection isThere unlikely were to 6 CONVENIAprovide benefit cases towith treated normal animals pre- and and Skinmay Failure 4 Pre-Treatment 0.12 - 2 increase the risk of the development of drug-resistant animal pathogens. a total of 5 doses. Vomiting and diarrhea were seen in all treatment groups, with the incidence of Each mL of CONVENIA reconstituted lyophile contains cefovecin sodium equivalent to 80 mg mildly to moderately elevated post-study creatinine values. Two of these cases also had an Infections vomiting and the incidence and duration of diarrhea increasing in a dose-related manner. Injection cefovecin, methylparaben 1.8 mg (preservative), propylparaben 0.2 mg (preservative), sodium elevatedThe post-study safe use BUN. of CONVENIA No clinical in dogsabnormalities or cats less were than noted 4 months with these of age findings. (see Animal Safety) and Streptococcus Success 16 Pre-Treatment ≤ 0.06 ≤ 0.06 ≤ 0.06 in breeding or lactating animals has not been determined. Safety has not been established site irritation and transient edema occurred with increasing frequency in a dose-related manner and citrate dihydrate 5.8 mg and citric acid monohydrate 0.1 mg, sodium hydroxide or hydrochloric One CONVENIA-treated cat in a separate field study experienced diarrhea post-treatment canis (Group G) with repeat injections. Two injection site reactions included a seroma over the shoulder and swelling acid as required to adjust pH. lasting 42for days. IM or The IV administration. diarrhea resolved. The long-term effects on injection sites have not been determined. CONVENIA is slowly eliminated from the body, approximately 65 days is needed to eliminate Failure 2 Pre-Treatment ≤ 0.06 lasting > 30 days. Dogs dosed at 36 mg/kg had a significant (P=0.0088) increase in BUN (all means INDICATIONS: FOREIGN97% MARKET of the administered EXPERIENCE dose: The from following the body. adverse Animals events experiencing were reported an adverse voluntarily reaction may remained within the normal range) compared to the controls. One dog dosed at 60 mg/kg exhibited Dogs during post-approvalneed to be monitored use of the for product this duration. in dogs and cats in foreign markets: death, tremors/ Cats a glomerulopathy on histopathology, and 1 dog in this same group had minimal peliosis hepatis. ataxia, seizures, anaphylaxis, acute pulmonary edema, facial edema, injection site reactions CONVENIA is indicated for the treatment of skin infections (secondary superficial pyoderma, CONVENIA has been shown in an experimental in vitro system to result in an increase in Thefree MIC values for cefovecin against Pasteurella multocida isolated from skin infections At an exaggerated dose of 180 mg/kg (22.5X) in dogs, CONVENIA caused some injection site abscesses, and wounds) in dogs caused by susceptible strains of Staphylococcus intermedius (alopecia, scabs, necrosis, and erythema), hemolytic anemia, salivation, pruritus, lethargy, (wounds and abscesses) in cats enrolled in a 2001-2003 field effectiveness study are irritation, vocalization, and edema. Edema resolved within 8-24 hours. vomiting,concentrations diarrhea, and of inappetance. carprofen, furosemide, doxycycline, and ketoconazole. Concurrent use of these or and Streptococcus canis (Group G). other drugs that have a high degree of protein-binding (e.g. NSAIDs, propofol, cardiac, anticonvulsant,presented in Table 6. All MICs were determined in accordance with the CLSI standards. Cats Cats For a copyand behavioralof the Material medications) Safety may Data compete Sheet with (MSDS) cefovecin-binding or to report and a cause suspected adverse adverse reactions. Table 6: Activity of CONVENIA against Pathogens Isolated from Cats Treated with CONVENIA CONVENIA administered to healthy 4-month-old cats at doses of 12 mg/kg (1.5X), 36 mg/kg (4.5X), reaction call Pfizer Animal Health at 1-800-366-5288. CONVENIA is indicated for the treatment of skin infections (wounds and abscesses) in cats Positive direct Coombs’ test results and false positive reactions for glucose in inthe Field Studies in the US During 2001-2003. and 60 mg/kg (7.5X) every 7 days by dorsoscapular subcutaneous injections was well-tolerated caused by susceptible strains of Pasteurella multocida. CLINICAL PHARMACOLOGY: for a total of 5 doses. Vomiting and diarrhea were observed in cats, with the incidence of vomiting urine have been reported during treatment with some cephalosporin antimicrobials. Sample DOSAGE AND ADMINISTRATION: Cephalosporin antimicrobials may also cause falsely elevated urine protein determinations. Microbiological Number MIC and the incidence and duration of diarrhea increasing in a dose-related manner. The mean albumin Pharmacokinetics Collection MIC MIC values for all the CONVENIA-treated cats were significantly lower (P ≤ 0.05) than the control values Disease Pathogen Treatment of 50 90 Range Dogs CefovecinSome is rapidly antimicrobials, and completely including absorbed cephalosporins, following subcutaneous can cause administration.lowered albumin Non-linear values due to (Time Relative (all means remained within the normal range) for all time periods. The mean alkaline phosphatase interference with certain testing methods. Outcome Isolates μg/mL μg/mL CONVENIA should be administered as a single subcutaneous injection of 3.6 mg/lb (8 mg/kg) body kinetics is exhibited (plasma concentrations do not increase proportionally with dose). Cefovecin Cats to Treatment) μg/mL values in the 60 mg/kg group were significantly higher (P ≤ 0.0291) than the control values for all time does not undergo hepatic metabolism and the majority of a dose is excreted unchanged in the Cefovecin plasma concentrations in the cat have been characterized by the use of PPK data. weight. A second subcutaneous injection of 3.6 mg/lb (8 mg/kg) may be administered if response Occasionally, cephalosporins and NSAIDs have been associated with myelotoxicity, thereby creating Success 57 Pre-Treatment ≤ 0.06 ≤ 0.06 ≤ 0.06 - 0.12 periods. Injection-site irritation and transient edema occurred with increasing frequency in a dose- to therapy is not complete. The decision for a second injection for any individual dog should take urine. Eliminationa toxic neutropenia also occurs4. Other from hematologicalexcretion of unchanged reactions seen drug with in the cephalosporins bile. Cefovecin include is a highly neutropenia, Skin PlasmaPasteurella cefovecin concentration data were pooled from 4 laboratory pharmacokinetic studies. related manner and with repeat injections. One cat in the 12 mg/kg group had a mild renal tubular and into consideration such factors as progress toward clinical resolution, the susceptibility of the protein-boundanemia, molecule hypoprothrombinemia, in dog plasma thrombocytopenia,(98.5%) and cat plasma prolonged (99.8%) prothrombin and may competetime (PT) withand partialInfections The multocidafinal datasetFailure contained 338 1concentrationPre-Treatment records from 22 cats. The simulations≤ 0.06 from the interstitial fibrosis, and 1 cat in the 12 mg/kg group had mild glomerulosclerosis on histopathology. causative organisms, and the integrity of the dog’s host-defense mechanisms. Therapeutic drug other highlythromboplastin protein-bound time (PTT),drugs platelet for plasma dysfunction protein-binding and transient sites increases that could in serumresult aminotransferases.in transient, model provide the mean population estimate as well as the 5th and 95th percentile of the population higher free drug concentrations of either compound. Pharmacokinetic parameters following estimates of total and free cefovecin concentrations over time. Figure 3 displays the predicted free At an exaggerated dose of 180 mg/kg (22.5X), CONVENIA was associated with injection site irritation, concentrations after the first injection are maintained for 7 days for S. intermedius infections and ADVERSE REACTIONS: EFFECTIVENESS: for 14 days for S. canis (Group G) infections. Maximum treatment should not exceed 2 injections. subcutaneous dosing at 8 mg/kg in the dog and cat are summarized in Table 4. plasma concentrations following administration of 8 mg/kg body weight to cats. Based upon these vocalization, and edema. Edema resolved within 8-24 hours. On day 10, cats had lower mean white Dogs Dogs predicted concentrations, 95% of the feline population will have active (free) drug concentrations > the blood cell counts compared to the controls. One cat had a small amount of bilirubinuria on day 10. Cats Table 4: Pharmacokinetic Parameters Reflecting Total Drug Concentrations in Plasma A total of 320 dogs, ranging in age from 8 weeks to 19 years, were included in a field studyIn a double-masked,MIC of Pasteurella 1:1 randomized multocida (0.06canine μg/mL) field for studyapproximately conducted 7 days in the when United administered States, the a single 8 STORAGE INFORMATION: CONVENIA should be administered as a single, one-time subcutaneous injection at a dose of (mean ± standard deviation or range) Following an 8 mg/kg Intravenous or Subcutaneous 90 safety analysis. Adverse reactions reported in dogs treated with CONVENIA and the activeeffectiveness mg/kg ofsubcutaneous CONVENIA wasinjection compared of cefovecin. to a cephalosporin (See active control.). In this study, 320 ° ° 3.6 mg/lb (8 mg/kg) body weight. After an injection of CONVENIA, therapeutic concentrations Dose of Cefovecin in Dogs and Cats. MICROBIOLOGY Store the powder and the reconstituted product in the original carton, refrigerated at 2 to 8 C control are summarized in Table 2. dogs with superficial secondary pyoderma, abscesses, or infected wounds were treated with ° ° are maintained for approximately 7 days for Pasteurella multocida infections. Figure 3: Population Predicted Free Concentration of Cefovecin in Plasma Following a (36 to 46 F). Use the entire contents of the vial within 56 days of reconstitution. PROTECT FROM either a single injection of CONVENIA (n=157) at 3.6 mg/lb (8 mg/kg) body weight or with an oral LIGHT. After each use it is important to return the unused portion back to the refrigerator in the Table 2: Number of Dogs* with Adverse Reactions Reported During1 the Field Study withactive controlSingle antibioticSubcutaneous (n=163), Injection administered of 8 twicemg/kg daily Body for Weight14 days. in In Cats this study,(solid dogsline iscould population General Dosing Information CONVENIA. MEAN ± SD or (Range) prediction, dotted lines are the 5th and 95th percentiles for the population prediction). original carton. As with other cephalosporins, the color of the solution may vary from clear to A sample of the lesion should be obtained for culture and susceptibility testing prior to beginning receive a second course of therapy 14 days after the initial treatment. Of the 320 enrolled dogs, amber at reconstitution and may darken over time. If stored as recommended, solution color does PARAMETER 22 of 157 dogs received 2 treatments of CONVENIA and 35 of 163 dogs received 2 courses of antimicrobial therapy. Once results become available, continue with appropriate therapy. If p not adversely affect potency. acceptable response to treatment is not observed, or if no improvement is seen within 3 to 4 days, Adverse Reaction CONVENIADogs CatsActive Control treatment with the active control. In the study, 118 of the 157 enrolled cases were evaluable for then the diagnosis should be re-evaluated and appropriate alternative therapy considered. (n=157) (n=163) effectiveness for CONVENIA, and 117 of the 163 enrolled cases were evaluable for effectiveness of HOW SUPPLIED: Terminal plasma elimination half-life, T (h)*h 133 ± 16 166 ± 18 CONVENIA is available as a 10 mL multi-use vial containing 800 milligrams of cefovecin as Lethargy 1/2 2 7 the active control antibiotic. CONVENIA was non-inferior to the active control. Table 7 summarizes CONVENIA may persist in the body for up to 65 days. The effect of remaining concentrations AUC (μg·h/mL)*g 10400 ± 1900p 22700 ± 3450 the clinical success rates obtained 28 days after the initiation of the final course of therapy. a lyophilized cake. of cefovecin on any subsequent antimicrobial therapies has not been determined. 0-inf Anorexia/Decreased Appetite 5 8 Fluoroquinolone and aminoglycoside antimicrobials have been reported to be compatible Time of maximum concentration, T (h)*h 6.2 (0.5-12.0) 2.0 (0.5-6.0) Table 7: Clinical Success Rates by Treatment Group 28 Days after the Initiation of the REFERENCES: Vomiting max 6 12 1Pillai SK, Moellering RC, Eliopoulos GM. Antimicrobial combinations. In: Lorian V, ed. with cephalosporin antimicrobial agents.1,2,3 Maximum concentration, C (μg/mL)*a 121 ± 51 141 ± 12 Final Course of Therapy. Diarrhea max 6 7 Antibiotics in laboratory medicine. 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins, Table 1: Dose Table for CONVENIA at 8 mg/kg Body Weight. Vd (L/kg)**g 0.122 ± 0.011 0.090 ± 0.010 2005;365-440. ss Blood in Feces 1 2 Dogs CL (mL/h/kg)**g 0.76 ± 0.13p 0.350 ± 0.40 2Fish DN, Choi MK, Jung R. Synergic activity of cephalosporins plus fluoroquinolones against total Type of Infection Volume of CONVENIA Dehydration 0 1 CONVENIA Active Control Pseudomonas aeruginosa with resistance to one or both drugs. J Antimicrob Chemother Weight of Animal (n=118) (n=117) (3.6 mg/lb or 0.045 mL/lb) 1 SD = standardFlatulence deviation 1 0 2002;50:1045-1049. 3 5 lb 0.23 mL p = a phaseIncreased effect was Borborygmi observed, only data for the first phase are1 provided (n=6); all other0 data Skin (secondary superficial pyoderma, Mayer I, Nagy E. Investigation of the synergic effects of aminoglycoside-fluoroquinolone and 109 (92.4%) 108 (92.3%) third-generation cephalosporin combinations against clinical isolates of Pseudomonas spp. J 10 lb 0.45 mL provided are derived from 12 animals abscesses, and infected wounds) * = SC *Some dogs may have experienced more than one adverse reaction or more than one Antimicrob Chemother 1999;43:651-657. 15 lb 0.67 mL ** = IV occurrence of the same adverse reaction during the study. CONVENIA was administered concomitantly with other commonly used veterinary products 4Birchard SJ, Sherding RG. Saunders manual of small animal practice. 2nd ed. Philadelphia: 20 lb 0.90 mL a = arithmetic mean such as heartworm preventatives, flea control products, sedatives/tranquilizers, anesthetic PA: WB Saunders Co, 2000;166. h Mild to moderate elevations in serum -glutamyl transferase or serum alanineagents, routine immunizations, antihistamines, thyroid hormone supplementation, and non- 40 lb 1.80 mL = harmonic mean NADA# 141-285, Approved by FDA g = geometricaminotransferase mean were noted post-treatment in several of the CONVENIA-treated dogs.steroidal No anti-inflammatory drugs during the field study. 80 lb 3.60 mL clinical abnormalities were noted with these findings. Distributed by: Population Pharmacokinetics Cats PREPARATION OF SOLUTION FOR INJECTION: To deliver the appropriate dose, aseptically One CONVENIA-treated dog in a separate field study experienced diarrhea post-treatmentIn a double-masked, 1:1 randomized cat field study conducted in the United States, the Dogs lasting 4 weeks. The diarrhea resolved. Div. of Pfizer Inc reconstitute CONVENIA with 10 mL sterile water for injection. Shake and allow vial to sit until all Cefovecin plasma concentrations in the dog have been characterized by the use of population effectiveness of CONVENIA was compared to an active control. In this study, 291 cats with Revised June 2011 material is visually dissolved. The resulting solution contains cefovecin sodium equivalent to 80 pharmacokinetic (PPK) data. Plasma cefovecin concentration data were pooled from 7 infected wounds or abscesses were treated with either a single injection of CONVENIA (n=147) New York, NY 10017 11892301 mg/mL cefovecin. CONVENIA is light sensitive. The vial should be stored in the original carton and laboratory pharmacokinetic studies, each involving young, normal healthy Beagle dogs. The at 3.6 mg/lb (8 mg/kg) body weight or with an oral active control antibiotic (n=144), administered refrigerated when not in use. Use the entire contents of the vial within 56 days of reconstitution. final dataset contained 591 concentration records from 39 dogs. The simulations from the model once daily for 14 days. CONVENIA was non-inferior to the active control. The clinical success rates were obtained 28 days after the initiation of therapy and are presented in Table 8. CONTRAINDICATIONS: CONVENIA is contraindicated in dogs and cats with known allergy to provide the mean population estimate and the 5th and 95th percentile of the population estimates cefovecin or to β-lactam (penicillins and cephalosporins) group antimicrobials. Anaphylaxis of total and free cefovecin concentrations over time. Figure 2 shows the predicted free plasma Table 8: Clinical Success Rates by Treatment Group 28 Days after the Initiation of Therapy. has been reported with the use of this product in foreign market experience. If an allergic concentrations following administration of 8 mg/kg body weight to dogs. Based upon these reaction or anaphylaxis occurs, CONVENIA should not be administered again and appropriate predicted concentrations, 95% of the canine population will have active (free) drug concentrations Cats > the MIC of S. canis (0.06 μg/mL) for approximately 14 days and free concentrations therapy should be instituted. Anaphylaxis may require treatment with epinephrine and other 90 Type of Infection CONVENIA Active Control > the MIC for S. intermedius (0.25 μg/mL) for approximately 7 days following a single emergency measures, including oxygen, intravenous fluids, intravenous antihistamine, 90 (n=89) (n=88) corticosteroids, and airway management, as clinically indicated. Adverse reactions may 8 mg/kg subcutaneous injection of cefovecin. (See MICROBIOLOGY). require prolonged treatment due to the prolonged systemic drug clearance (65 days). Figure 2: Population Predicted Free Concentration of Cefovecin in Plasma Following a Single Skin (wounds and abscesses) 86 (96.6%) 80 (90.9%) WARNINGS: Not for use in humans. Keep this and all drugs out of reach of children. Consult a Subcutaneous Injection of 8 mg/kg Body Weight in Dogs (solid line is population prediction, physician in case of accidental human exposure. For subcutaneous use in dogs and cats only. dotted lines are the 5th and 95th percentiles for the population prediction). CONVENIA was used concomitantly with other commonly used veterinary products such as Antimicrobial drugs, including penicillins and cephalosporins, can cause allergic reactions in heartworm preventatives, flea control products, sedatives/tranquilizers, anesthetic agents, sensitized individuals. To minimize the possibility of allergic reactions, those handling such and vaccines during the field study. antimicrobials, including cefovecin, are advised to avoid direct contact of the product with ANIMAL SAFETY: the skin and mucous membranes. Dogs PRECAUTIONS: Prescribing antibacterial drugs in the absence of a proven or strongly CONVENIA administered to healthy 4-month-old dogs at doses of 12 mg/kg (1.5X), 36 mg/kg (4.5X), suspected bacterial infection is unlikely to provide benefit to treated animals and may and 60 mg/kg (7.5X) every 7 days by dorsoscapular subcutaneous injections was well-tolerated for increase the risk of the development of drug-resistant animal pathogens. a total of 5 doses. Vomiting and diarrhea were seen in all treatment groups, with the incidence of The safe use of CONVENIA in dogs or cats less than 4 months of age (see Animal Safety) and vomiting and the incidence and duration of diarrhea increasing in a dose-related manner. Injection in breeding or lactating animals has not been determined. Safety has not been established site irritation and transient edema occurred with increasing frequency in a dose-related manner and for IM or IV administration. The long-term effects on injection sites have not been determined. with repeat injections. Two injection site reactions included a seroma over the shoulder and swelling CONVENIA is slowly eliminated from the body, approximately 65 days is needed to eliminate lasting > 30 days. Dogs dosed at 36 mg/kg had a significant (P=0.0088) increase in BUN (all means 97% of the administered dose from the body. Animals experiencing an adverse reaction may remained within the normal range) compared to the controls. One dog dosed at 60 mg/kg exhibited need to be monitored for this duration. a glomerulopathy on histopathology, and 1 dog in this same group had minimal peliosis hepatis. CONVENIA has been shown in an experimental in vitro system to result in an increase in free At an exaggerated dose of 180 mg/kg (22.5X) in dogs, CONVENIA caused some injection site concentrations of carprofen, furosemide, doxycycline, and ketoconazole. Concurrent use of these or irritation, vocalization, and edema. Edema resolved within 8-24 hours. other drugs that have a high degree of protein-binding (e.g. NSAIDs, propofol, cardiac, anticonvulsant, Cats and behavioral medications) may compete with cefovecin-binding and cause adverse reactions. CONVENIA administered to healthy 4-month-old cats at doses of 12 mg/kg (1.5X), 36 mg/kg (4.5X), Positive direct Coombs’ test results and false positive reactions for glucose in the and 60 mg/kg (7.5X) every 7 days by dorsoscapular subcutaneous injections was well-tolerated urine have been reported during treatment with some cephalosporin antimicrobials. for a total of 5 doses. Vomiting and diarrhea were observed in cats, with the incidence of vomiting Cephalosporin antimicrobials may also cause falsely elevated urine protein determinations. and the incidence and duration of diarrhea increasing in a dose-related manner. The mean albumin Some antimicrobials, including cephalosporins, can cause lowered albumin values due to values for all the CONVENIA-treated cats were significantly lower (P ≤ 0.05) than the control values interference with certain testing methods. (all means remained within the normal range) for all time periods. The mean alkaline phosphatase Cats values in the 60 mg/kg group were significantly higher (P ≤ 0.0291) than the control values for all time Occasionally, cephalosporins and NSAIDs have been associated with myelotoxicity, thereby creating Cefovecin plasma concentrations in the cat have been characterized by the use of PPK data. periods. Injection-site irritation and transient edema occurred with increasing frequency in a dose- a toxic neutropenia4. Other hematological reactions seen with cephalosporins include neutropenia, Plasma cefovecin concentration data were pooled from 4 laboratory pharmacokinetic studies. related manner and with repeat injections. One cat in the 12 mg/kg group had a mild renal tubular and anemia, hypoprothrombinemia, thrombocytopenia, prolonged prothrombin time (PT) and partial The final dataset contained 338 concentration records from 22 cats. The simulations from the interstitial fibrosis, and 1 cat in the 12 mg/kg group had mild glomerulosclerosis on histopathology. thromboplastin time (PTT), platelet dysfunction and transient increases in serum aminotransferases. model provide the mean population estimate as well as the 5th and 95th percentile of the population estimates of total and free cefovecin concentrations over time. Figure 3 displays the predicted free At an exaggerated dose of 180 mg/kg (22.5X), CONVENIA was associated with injection site irritation, ADVERSE REACTIONS: plasma concentrations following administration of 8 mg/kg body weight to cats. Based upon these vocalization, and edema. Edema resolved within 8-24 hours. On day 10, cats had lower mean white Dogs predicted concentrations, 95% of the feline population will have active (free) drug concentrations > the blood cell counts compared to the controls. One cat had a small amount of bilirubinuria on day 10.

A total of 320 dogs, ranging in age from 8 weeks to 19 years, were included in a field study MIC90 of Pasteurella multocida (0.06 μg/mL) for approximately 7 days when administered a single 8 STORAGE INFORMATION: safety analysis. Adverse reactions reported in dogs treated with CONVENIA and the active mg/kg subcutaneous injection of cefovecin. (See MICROBIOLOGY). Store the powder and the reconstituted product in the original carton, refrigerated at 2° to 8° C control are summarized in Table 2. Figure 3: Population Predicted Free Concentration of Cefovecin in Plasma Following a (36° to 46° F). Use the entire contents of the vial within 56 days of reconstitution. PROTECT FROM Table 2: Number of Dogs* with Adverse Reactions Reported During the Field Study with Single Subcutaneous Injection of 8 mg/kg Body Weight in Cats (solid line is population LIGHT. After each use it is important to return the unused portion back to the refrigerator in the CONVENIA. prediction, dotted lines are the 5th and 95th percentiles for the population prediction). original carton. As with other cephalosporins, the color of the solution may vary from clear to amber at reconstitution and may darken over time. If stored as recommended, solution color does not adversely affect potency. Adverse Reaction CONVENIA Active Control (n=157) (n=163) HOW SUPPLIED: Lethargy 2 7 CONVENIA is available as a 10 mL multi-use vial containing 800 milligrams of cefovecin as a lyophilized cake. Anorexia/Decreased Appetite 5 8 REFERENCES: Vomiting 6 12 1Pillai SK, Moellering RC, Eliopoulos GM. Antimicrobial combinations. In: Lorian V, ed. Diarrhea 6 7 Antibiotics in laboratory medicine. 5th ed. Philadelphia, PA: Lippincott Williams & Wilkins, Blood in Feces 1 2 2005;365-440. 2Fish DN, Choi MK, Jung R. Synergic activity of cephalosporins plus fluoroquinolones against Dehydration 0 1 Pseudomonas aeruginosa with resistance to one or both drugs. J Antimicrob Chemother Flatulence 1 0 2002;50:1045-1049. 3 Increased Borborygmi 1 0 Mayer I, Nagy E. Investigation of the synergic effects of aminoglycoside-fluoroquinolone and third-generation cephalosporin combinations against clinical isolates of Pseudomonas spp. J *Some dogs may have experienced more than one adverse reaction or more than one Antimicrob Chemother 1999;43:651-657. occurrence of the same adverse reaction during the study. 4Birchard SJ, Sherding RG. Saunders manual of small animal practice. 2nd ed. Philadelphia: PA: WB Saunders Co, 2000;166. Mild to moderate elevations in serum -glutamyl transferase or serum alanine NADA# 141-285, Approved by FDA aminotransferase were noted post-treatment in several of the CONVENIA-treated dogs. No clinical abnormalities were noted with these findings. Distributed by: One CONVENIA-treated dog in a separate field study experienced diarrhea post-treatment lasting 4 weeks. The diarrhea resolved. Div. of Pfizer Inc Revised June 2011 New York, NY 10017 11892301