Convenia Cefovecin Sodium Inj 80Mg/ml 10ml By Zoetis

Each mL of CONVENIA reconstituted lyophile contains cefovecin sodium equivalent to 80.0 mg cefovecin, methylparaben 1.8 mg (preservative), propylparaben 0.2 mg (preservative), sodium citrate dihydrate 5.8 mg and citric acid monohydrate 0.1 mg, sodium hydroxide or hydrochloric acid as required to adjust pH.

INDICATIONS:

Dogs

CONVENIA is indicated for the treatment of skin infections (secondary superficial pyoderma, abscesses, and wounds) in dogs caused by susceptible strains of Staphylococcus intermedius and Streptococcus canis (Group G).

Cats

CONVENIA is indicated for the treatment of skin infections (wounds and abscesses) in cats caused by susceptible strains of Pasteurella multocida.

DOSAGE AND ADMINISTRATION:

Dogs

CONVENIA should be administered as a single subcutaneous injection of 3.6 mg/lb (8 mg/kg) body weight. A second subcutaneous injection of 3.6 mg/lb (8 mg/kg) may be administered if response to therapy is not complete. The decision for a second injection for any individual dog should take into consideration such factors as progress toward clinical resolution, the susceptibility of the causative organisms, and the integrity of the dog’s host-defense mechanisms. Therapeutic drug concentrations after the first injection are maintained for 7 days for S. intermedius infections and for 14 days for S. canis (Group G) infections. Maximum treatment should not exceed 2 injections.

Cats

CONVENIA should be administered as a single, one-time subcutaneous injection at a dose of 3.6 mg/lb (8 mg/kg) body weight. After an injection of CONVENIA, therapeutic concentrations are maintained for approximately 7 days for Pasteurella multocida infections.

General Dosing Information

A sample of the lesion should be obtained for culture and susceptibility testing prior to beginning antimicrobial therapy. Once results become available, continue with appropriate therapy. If acceptable response to treatment is not observed, or if no improvement is seen within 3 to 4 days, then the diagnosis should be re-evaluated and appropriate alternative therapy considered.

CONVENIA may persist in the body for up to 65 days. The effect of remaining concentrations of cefovecin on any subsequent antimicrobial therapies has not been determined. Fluoroquinolone and aminoglycoside antimicrobials have been reported to be compatible with cephalosporin antimicrobial agents.^1,2,3

Table 1: Dose Table for CONVENIA at 8 mg/kg Body Weight

PREPARATION OF SOLUTION FOR INJECTION: To deliver the appropriate dose, aseptically reconstitute CONVENIA with 10 mL sterile water for injection. Shake and allow vial to sit until all material is visually dissolved. The resulting solution contains cefovecin sodium equivalent to 80 mg/mL cefovecin. CONVENIA is light sensitive. The vial should be stored in the original carton and refrigerated when not in use. Use the entire contents of the vial within 56 days of reconstitution.

CONTRAINDICATIONS: CONVENIA is contraindicated in dogs and cats with known allergy to cefovecin or to β-lactam (penicillins and cephalosporins) group antimicrobials. Anaphylaxis has been reported with the use of this product in foreign market experience. If an allergic reaction or anaphylaxis occurs, CONVENIA should not be administered again and appropriate therapy should be instituted. Anaphylaxis may require treatment with epinephrine and other emergency measures, including oxygen, intravenous fluids, intravenous antihistamine, corticosteroids, and airway management, as clinically indicated. Adverse reactions may require prolonged treatment due to the prolonged systemic drug clearance (65 days).

WARNINGS: Not for use in humans. Keep this and all drugs out of reach of children. Consult a physician in case of accidental human exposure. For subcutaneous use in dogs and cats only. Antimicrobial drugs, including penicillins and cephalosporins, can cause allergic reactions in sensitized individuals. To minimize the possibility of allergic reactions.

PRECAUTIONS:

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

The safe use of CONVENIA in dogs or cats less than 4 months of age (see Animal Safety) and in breeding or lactating animals has not been determined. Safety has not been established for IM or IV administration. 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 97% of the administered dose from the body. Animals experiencing an adverse reaction may need to be monitored for this duration.

CONVENIA has been shown in an experimental in vitro system to result in an increase in free concentrations of carprofen, furosemide, doxycycline and ketoconazole. Concurrent use of these or other drugs that have a high degree of protein-binding (e.g. NSAIDs, propofol, cardiac, anticonvulsant, and behavioral medications) may compete with cefovecin binding and cause adverse reactions.

Positive direct Coombs’ test results and false positive reactions for glucose in the urine have been reported during treatment with some cephalosporin antimicrobials. Cephalosporin antimicrobials may also cause falsely elevated urine protein determinations. Some antimicrobials, including cephalosporins, can cause lowered albumin values due to interference with certain testing methods.

Occasionally, cephalosporins and NSAIDs have been associated with myelotoxicity, thereby creating a toxic neutropenia⁴. Other hematological reactions seen with cephalosporins include neutropenia, anemia, hypoprothrombinemia, thrombocytopenia, prolonged prothrombin time (PT) and partial thromboplastin time (PTT), platelet dysfunction and transient increases in serum aminotransferases.

ADVERSE REACTIONS:

Dogs

A total of 320 dogs, ranging in age from 8 weeks to 19 years, were included in a field study safety analysis. Adverse reactions reported in dogs treated with CONVENIA and the active control are summarized in Table 2.

Table 2: Number of Dogs* with Adverse Reactions Reported During the Field Study with CONVENIA

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

Mild to moderate elevations in serum γ-glutamyl transferase or serum alanine aminotransferase were noted post-treatment in several of the CONVENIA-treated dogs. No clinical abnormalities were noted with these findings.

One CONVENIA-treated dog in a separate field study experienced diarrhea post-treatment lasting 4 weeks. The diarrhea resolved.

Cats

A total of 291 cats, ranging in age from 2.4 months (1 cat) to 21 years, were included in the field study safety analysis. Adverse reactions reported in cats treated with CONVENIA and the active control are summarized in Table 3.

Table 3: Number of Cats* with Adverse Reactions Reported During the Field Study with CONVENIA.

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

Four CONVENIA cases had mildly elevated post-study ALT (1 case was elevated pre-study). No clinical abnormalities were noted with these findings.

Twenty-four CONVENIA cases had normal pre-study BUN values and elevated post-study BUN values (37 - 39 mg/dL post-study). There were 6 CONVENIA cases with normal pre- and mildly to moderately elevated post-study creatinine values. Two of these cases also had an elevated post-study BUN. No clinical abnormalities were noted with these findings.

One CONVENIA-treated cat in a separate field study experienced diarrhea post-treatment lasting 42 days. The diarrhea resolved.

FOREIGN MARKET EXPERIENCE: The following adverse events were reported voluntarily during post-approval use of the product in dogs and cats in foreign markets: death, tremors/ataxia, seizures, anaphylaxis, acute pulmonary edema, facial edema, injection site reactions (alopecia, scabs, necrosis, and erythema), hemolytic anemia, salivation, pruritus, lethargy, vomiting, diarrhea, and inappetance.

For a copy of the Material Safety Data Sheet (MSDS) or to report a suspected adverse reaction call Zoetis Inc. at 1-888-963-8471.

CLINICAL PHARMACOLOGY:

Pharmacokinetics

Cefovecin is rapidly and completely absorbed following subcutaneous administration. Non-linear kinetics is exhibited (plasma concentrations do not increase proportionally with dose). Cefovecin 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 highly protein bound molecule in dog plasma (98.5%) and cat plasma (99.8%) and may compete with other highly protein bound drugs for plasma protein binding sites that could result in transient, higher free drug concentrations of either compound. Pharmacokinetic parameters following subcutaneous dosing at 8 mg/kg in the dog and cat are summarized in Table 4.

Table 4: Pharmacokinetic Parameters Reflecting Total Drug Concentrations in Plasma (mean ± standard deviation or range) Following an 8 mg/kg Intravenous or Subcutaneous Dose of Cefovecin in Dogs and Cats

¹ SD = standard deviation

^p = a phase effect was observed, only data for the first phase are provided (n=6); all other data provided are derived from 12 animals

* = SC

** = IV

^a = arithmetic mean

^h = harmonic mean

^g = geometric mean

Population Pharmacokinetics

Dogs

Cefovecin plasma concentrations in the dog have been characterized by the use of population pharmacokinetic (PPK) data. Plasma cefovecin concentration data were pooled from seven laboratory pharmacokinetic studies, each involving young, normal healthy Beagle dogs. The final dataset contained 591 concentration records from 39 dogs. The simulations from the model provide the mean population estimate and the 5^th and 95^th percentile of the population estimates of total and free cefovecin concentrations over time. Figure 2 shows the predicted free plasma concentrations following administration of 8 mg/kg body weight to dogs. Based upon these predicted concentrations, 95% of the canine population will have active (free) drug concentrations > the MIC₉₀ of S. canis (0.06 µg/mL) for approximately 14 days and free concentrations > the MIC₉₀ for S. intermedius (0.25 µg/mL) for approximately 7 days following a single 8 mg/kg subcutaneous injection of cefovecin. (See MICROBIOLOGY).

Figure 2: Population Predicted Free Concentration of Cefovecin in Plasma Following a Single Subcutaneous Injection of 8 mg/kg Body Weight in Dogs (solid line is population prediction, dotted lines are the 5^th and 95^th percentiles for the population prediction).

Cats

Cefovecin plasma concentrations in the cat have been characterized by the use of PPK data. Plasma cefovecin concentration data were pooled from 4 laboratory pharmacokinetic studies. The final dataset contained 338 concentration records from 22 cats. The simulations from the model provide the mean population estimate as well as the 5^th and 95^th percentile of the population estimates of total and free cefovecin concentrations over time. Figure 3 displays the predicted free plasma concentrations following administration of 8 mg/kg body weight to cats. Based upon these predicted concentrations, 95% of the feline population will have active (free) drug concentrations > the MIC₉₀ of Pasteurella multocida (0.06 µg/mL) for approximately 7 days when administered a single 8 mg/kg subcutaneous injection of cefovecin. (See MICROBIOLOGY).

Figure 3: Population Predicted Free Concentration of Cefovecin in Plasma Following a Single Subcutaneous Injection of 8 mg/kg Body Weight in Cats (solid line is population prediction, dotted lines are the 5^th and 95^th percentiles for the population prediction).

MICROBIOLOGY: CONVENIA is a cephalosporin antibiotic. Like other β-lactam antimicrobials, CONVENIA exerts its inhibitory effect by interfering with bacterial cell wall synthesis. This interference is primarily due to its covalent binding to the penicillin-binding proteins (PBPs) (i.e., transpeptidase and carboxypeptidase), which are essential for synthesis of the bacterial cell wall. For E. coli, the in vitro activity of CONVENIA is comparable to other cephalosporins, but due to the high-affinity protein-binding, the in vivo free concentration of cefovecin does not reach the MIC₉₀ for E. coli (1.0 µg/mL). CONVENIA is not active against Pseudomonas spp. or enterococci.

Dogs

The minimum inhibitory concentration (MIC) values for cefovecin against label-claim pathogens isolated from skin infections in dogs enrolled in a 2001-2003 field effectiveness study are presented in Table 5. All MICs were determined in accordance with the Clinical and Laboratory Standards Institute (CLSI) standards.

Table 5. Activity of CONVENIA Against Pathogens Isolated from Dogs Treated With CONVENIA in Field Studies in the U.S. During 2001-2003.