硕腾（Zoetis）获 FDA 批准犬用 Convenia RTU（cefovecin）即用型高浓度新剂型，覆盖中大型犬单次注射治疗

R Occasionally, cephalosporins and NSAIDs have been associated with myelotoxicity, thereby creating a
convenia toxic neutropenia4. Other hematological reactions seen with cephalosporins include neutropenia, anemia,
hypoprothrombinemia, thrombocytopenia, prolonged prothrombin time (PT) and partial thromboplastin time (PTT),
(cefovecin sodium) platelet dysfunction and transient increases in serum aminotransferases.
ADVERSE REACTIONS:
Antimicrobial for Subcutaneous Injection in Dogs and Cats Only Dogs
CAUTION: Federal law restricts this drug to use by or on the order of a licensed veterinarian. A total of 320 dogs, ranging in age from 8 weeks to 19 years, were included in a field study safety analysis. Adverse
DESCRIPTIoN: Cefovecin sodium is a semi-synthetic broad-spectrum antibacterial agent from the cephalosporin reactions reported in dogs treated with CONVENIA and the active control are summarized in Table 2.
class of chemotherapeutic agents. Cefovecin is the non-proprietary designation for (6R,7R)-7-[[(2Z)-(2-amino-4-thiazolyl) Table 2: Number of Dogs* with Adverse Reactions Reported During the Field Study with CONVENIA
(methoxyimino)acetyl]amino]-8-oxo-3-[(2S)-tetrahydro-2-furanyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid,
monosodium salt. Adverse Reaction CONVENIA Active Control
Figure 1: Chemical structure of cefovecin sodium. (n=157) (n=163)
S Lethargy 2 7
Anorexia/Decreased Appetite 5 8
N NH S
Vomiting 6 12
OMe N Diarrhea 6 7
Blood in Feces 1 2
NaO Dehydration 0 1
Flatulence 1 0
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 Increased Borborygmi 1 0
monohydrate 0.1 mg, sodium hydroxide or hydrochloric acid as required to adjust pH. *Some dogs may have experienced more than one adverse reaction or more than one occurrence of the same adverse
INDICATIONS: reaction during the study.
Dogs Mild to moderate elevations in serum gamma glutamyl transferase or serum alanine aminotransferase were noted
CONVENIA is indicated for the treatment of skin infections (secondary superficial pyoderma, abscesses, and wounds) post-treatment in several of the CONVENIA-treated dogs. No clinical abnormalities were noted with these findings.
in dogs caused by susceptible strains of Staphylococcus intermedius and Streptococcus canis (Group G). One CONVENIA-treated dog in a separate field study experienced diarrhea post-treatment lasting four weeks.
Cats The diarrhea resolved.
CONVENIA is indicated for the treatment of skin infections (wounds and abscesses) in cats caused by susceptible Cats
strains of Pasteurella multocida. A total of 291 cats, ranging in age from 2.4 months (one 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.
DOSAGE AND ADMINISTRATION:
Dogs Table 3: Number of Cats* with Adverse Reactions Reported During the Field Study with CONVENIA.
CONVENIA should be administered as a single subcutaneous injection of 3.6 mg/lb (8 mg/kg) body weight. A second Adverse Reaction CONVENIA Active Control
(n=147) (n=144)
for a second injection for any individual dog should take into consideration such factors as progress toward clinical Vomiting 10 14
Diarrhea 7 26
for 14 days for S. canis (Group G) infections. Maximum treatment should not exceed 2 injections. Anorexia/Decreased Appetite 6 6
Cats Lethargy 6 6
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 Hyper/Acting Strange 1 1
Pasteurella multocida infections. Inappropriate Urination 1 0
General Dosing Information *Some cats may have experienced more than one adverse reaction or more than one occurrence of the same adverse
A sample of the lesion should be obtained for culture and susceptibility testing prior to beginning antimicrobial therapy. reaction during the study.
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 Four CONVENIA cases had mildly elevated post-study ALT (one case was elevated pre-study). No clinical abnormalities
therapy considered. were noted with these findings.
CONVENIA may persist in the body for up to 65 days. The effect of remaining concentrations of cefovecin on any Twenty-four CONVENIA cases had normal pre-study BUN values and elevated post-study BUN values (37 - 39 mg/dL
subsequent antimicrobial therapies has not been determined. Fluoroquinolone and aminoglycoside antimicrobials post-study). There were 6 CONVENIA cases with normal pre- and mildly to moderately elevated post-study creatinine
have been reported to be compatible with cephalosporin antimicrobial agents.1.23 values. Two of these cases also had an elevated post-study BUN. No clinical abnormalities were noted with these
findings.
Table 1: Dose Table for CONVENIA at 8 mg/kg Body Weight One CONVENIA-treated cat in a separate field study experienced diarrhea post-treatment lasting 42 days. The diarrhea
Volume of CONVENIA resolved.
Weight of Animal (3.6 mg/lb or 0.045 mL/Ib) 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,
5 lb 0.23 mL facial edema, injection site reactions (alopecia, scabs, necrosis, and erythema), hemolytic anemia, salivation, pruritus,
10 lb 0.45 mL lethargy, vomiting, diarrhea, and inappetance.
15 lb 0.67 mL CONTACT INFORMATION:
20 lb 0.90 mL For a copy of the Safety Data Sheet or to report adverse reactions, call Zoetis Inc. at 1-888-963-8471. For additional
40 lb 1.8 mL information about adverse drug experience reporting for animal drugs, contact FDA at 1-888-FDA-VETS or
80 lb 3.6 mL at www.fda.gov/reportanimalae.
CLINICAL PHARMACOLOGY:
PREPARATION OF SOLUTION FOR INJECTION: To deliver the appropriate dose, aseptically reconstitute CONVENIA with Pharmacokinetics
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 Cefovecin is rapidly and completely absorbed following subcutaneous administration. Non-linear kinetics is exhibited
the original carton and refrigerated when not in use. Use the entire contents of the vial within 56 days of reconstitution. (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
CONTRAINDICATIONS: CONVENIA is contraindicated in dogs and cats with known allergy to cefovecin or to β-lactam the bile. Cefovecin is a highly protein bound molecule in dog plasma (98.5%) and cat plasma (99.8%) and may compete
(penicillins and cephalosporins) group antimicrobials. Anaphylaxis has been reported with the use of this product in with other highly protein bound drugs for plasma protein binding sites that could result in transient, higher free drug
foreign market experience. If an allergic reaction or anaphylaxis occurs, CONVENIA should not be administered again concentrations of either compound. Pharmacokinetic parameters following subcutaneous dosing at 8 mg/kg in the dog
and appropriate therapy should be instituted. Anaphylaxis may require treatment with epinephrine and other emergency and cat are summarized in Table 4.
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 Table 4: Pharmacokinetic Parameters Reflecting Total Drug Concentrations in Plasma (mean ± standard deviation or
(65 days). range) Following an 8 mg/kg Intravenous or Subcutaneous Dose of Cefovecin in Dogs and Cats
WARNINGS: Not for use in humans. Keep this and all drugs out of reach of children. Consult a physician in case of MEAN ± SD1 or (Range)
accidental human exposure. For subcutaneous use in dogs and cats only. Antimicrobial drugs, including penicillins and PARAMETER Dogs Cats P
cephalosporins, can cause allergic reactions in sensitized individuals. To minimize the possibility of allergic reactions, Terminal plasma elimination half-life, T1/2 (h)*h 133 ± 16 166 ± 18
those handling such antimicrobials, including cefovecin, are advised to avoid direct contact of the product with the skin
and mucous membranes. AUC0-int (μg.h/mL)*g 10400 ± 1900 P 22700 ± 3450
PRECAUTIONS: Time of maximum concentration, Tmax (h) *h 6.2 (0.5-12.0) 2.0 (0.5-6.0)
Maximum concentration, Cmax (μg/mL) *a 121 ± 51 141 ± 12
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. Vdss (L/kg)**g 0.122 ± 0.011 0.090 ± 0.010
The safe use of CONVENIA in dogs or cats less than 4 months of age (see Animal Safety) and in breeding or lactating CLtal (mL/h/kg)**g 0.76 ± 0.13P 0.350 ± 0.40
animals has not been determined. Safety has not been established for IM or IV administration. The long-term effects 1 SD = standard deviation
on injection sites have not been determined. CONVENIA is slowly eliminated from the body, approximately 65 days is 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
to be monitored for this duration. *= SC
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 a = arithmetic mean
of protein-binding (e.g. NSAIDs, propofol, cardiac, anticonvulsant, and behavioral medications) may compete with h = harmonic mean
cefovecin binding and cause adverse reactions. 9 = geometric mean
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.

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Population Pharmacokinetics EFFECTIVENESS:
Dogs Dogs
Cefovecin plasma concentrations in the dog have been characterized by the use of population pharmacokinetic In a double-masked, 1:1 randomized canine field study conducted in the United States, the effectiveness of CONVENIA
(PPK) data. Plasma cefovecin concentration data were pooled from seven laboratory pharmacokinetic studies, each was compared to a cephalosporin active control. In this study, 320 dogs with superficial secondary pyoderma,
involving young, normal healthy Beagle dogs. The final dataset contained 591 concentration records from 39 dogs. abscesses, or infected wounds were treated with either a single injection of CONVENIA (n = 157) at 3.6 mg/lb (8 mg/kg)
The simulations from the model provide the mean population estimate and the 5th and 95th percentile of the population body weight or with an oral active control antibiotic (n = 163), administered twice daily for 14 days. In this study, dogs
estimates of total and free cefovecin concentrations over time. Figure 2 shows the predicted free plasma concentrations could receive a second course of therapy 14 days after the initial treatment. Of the 320 enrolled dogs, 22 of 157 dogs
following administration of 8 mg/kg body weight to dogs. Based upon these predicted concentrations, 95% of the canine received two treatments of CONVENIA and 35 of 163 dogs received two courses of treatment with the active control.
population will have active (free) drug concentrations > the MICg of S. canis (0.06 μg/mL) for approximately 14 days In the study, 118 of the 157 enrolled cases were evaluable for effectiveness for CONVENIA, and 117 of the 163 enrolled
and free concentrations > the MICg0 for S. intermedius (0.25 μg/mL) for approximately 7 days following a single 8 mg/kg cases were evaluable for effectiveness of the active control antibiotic. CONVENIA was non-inferior to the active control.
subcutaneous injection of cefovecin. (See MICROBIOLOGY.) Table 7 summarizes the clinical success rates obtained 28 days after the initiation of the final course of therapy.
Figure 2: Population Predicted Free Concentration of Cefovecin in Plasma Following a Single Subcutaneous Injection Table 7: Clinical Success Rates by Treatment Group 28 Days after the Initiation of the Final Course of Therapy.
of 8 mg/kg Body Weight in Dogs (solid line is population prediction, dotted lines are the 5th and 95th percentiles for the
population prediction). Dogs
Type of Infection CONVENIA Active Control
100.00 (n=118) (n=117)
Skin (secondary superficial pyoderma, 109 (92.4%) 108 (92.3%)
abscesses, and infected wounds)
10.00 CONVENIA was administered concomitantly with other commonly used veterinary products such as heartworm
preventatives, flea control products, sedatives/tranquilizers, anesthetic agents, routine immunizations, antihistamines,
MIC30 S. intermedius thyroid hormone supplementation, and non-steroidal anti-inflammatory drugs during the field study.
1.00 Cats
Cefovecin Concentrations (mcg/mL) In a double-masked, 1:1 randomized cat field study conducted in the United States, the effectiveness of CONVENIA
was compared to an active control. In this study, 291 cats with infected wounds or abscesses were treated with
either a single injection of CONVENIA (n = 147) at 3.6 mg/lb (8 mg/kg) body weight or with an oral active control antibiotic
0.10 (n = 144), administered 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.
Table 8: Clinical Success Rates by Treatment Group 28 Days after the Initiation of Therapy.
0.01 MICg0 S. canis Cats
0 2 4 6 8 10 12 14
Time After Dose (days) Type of Infection CONVENIA Active Control
(n=89) (n=88)
Cats
Cefovecin plasma concentrations in the cat have been characterized by the use of PPK data. Plasma cefovecin Skin (wounds and abscesses) 86 (96.6%) 80 (90.9%)
concentration data were pooled from four 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 CONVENIA was used concomitantly with other commonly used veterinary products such as heartworm preventatives,
5th and 95th percentile of the population estimates of total and free cefovecin concentrations over time. Figure 3 displays flea control products, sedatives/tranquilizers, anesthetic agents, and vaccines during the field study.
the predicted free plasma concentrations following administration of 8 mg/kg body weight to cats. Based upon these ANIMAL SAFETY:
predicted concentrations, 95% of the feline population will have active (free) drug concentrations > the MIĆg of
Pasteurella multocida (0.06 μg/mL) for approximately 7 days when administered a single 8 mg/kg subcutaneous injection Dogs
of cefovecin. (See MICROBIOLOGY.) CONVENIA administered to healthy four month old dogs at doses of 12 mg/kg (1.5 X),
36 mg/kg (4.5 X), and 60 mg/kg (7.5 X) every seven days by dorsoscapular subcutaneous injections was well-tolerated
Figure 3: Population Predicted Free Concentration of Cefovecin in Plasma Following a Single Subcutaneous Injection for a total of 5 doses. Vomiting and diarrhea were seen in all treatment groups, with the incidence of vomiting and the
of 8 mg/kg Body Weight in Cats (solid line is population prediction, dotted lines are the 5th and 95th percentiles for the incidence and duration of diarrhea increasing in a dose-related manner. Injection site irritation and transient edema
population prediction). occurred with increasing frequency in a dose-related manner and with repeat injections. Two injection site reactions
1000.00 included a seroma over the shoulder and swelling lasting > 30 days. Dogs dosed at 36 mg/kg had a significant (p = 0.0088)
100.00
edema. Edema resolved within 8-24 hours.
Cats
10.00 CONVENIA administered to healthy four month old cats at doses of 12 mg/kg (1.5 X), 36 mg/kg (4.5 X), and 60 mg/kg
(7.5 X) every seven days by dorsoscapular subcutaneous injections was well tolerated for a total of 5 doses. Vomiting
Cefovecin Concentrations (mcg/mL) and diarrhea were observed in cats, with the incidence of vomiting, and the incidence and duration of diarrhea
1.00 increasing in a dose-related manner. The mean albumin values for all the CONVENIA-treated cats were significantly
lower (p ≤ 0.05) than the control values (all means remained within the normal range) for all time periods. The mean
alkaline phosphatase values in the 60 mg/kg group were significantly higher (p ≤ 0.0291) than the control values for all
0.10 time periods. Injection-site irritation and transient edema occurred with increasing frequency in a dose-related manner
MIC90 and with repeat injections. One cat in the 12 mg/kg group had a mild renal tubular and interstitial fibrosis, and one cat in
the 12 mg/kg group had mild glomerulosclerosis on histopathology.
At an exaggerated dose of 180 mg/kg (22.5X), CONVENIA was associated with injection site irritation, vocalization and
0 2 4 6 8 10 12 14 edema. Edema resolved within 8-24 hours. On Day 10, cats had lower mean white blood cell counts compared to the
Time After Dose (days) controls. One cat had a small amount of bilirubinuria on Day 10.
MICROBIOLOGY: CONVENIA is a cephalosporin antibiotic. Like other β-lactam antimicrobials, CONVENIA exerts its STORAGE INFORMATION:
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 Store the powder and the reconstituted product in the original carton, refrigerated at 2° to 8° C (36° to 46° F). Use the
the bacterial cell wall. For E. coli, the in vitro activity of CONVENIA is comparable to other cephalosporins, but due to the entire contents of the vial within 56 days of reconstitution. PROTECT FROM LIGHT. After each use it is important to
high-affinity protein-binding, the in vivo free concentration of cefovecin does not reach the MICg for E. coli (1.0 μg/mL). return the unused portion back to the refrigerator in the original carton. As with other cephalosporins, the color of the
CONVENIA is not active against Pseudomonas spp. or enterococci. solution may vary from clear to amber at reconstitution and may darken over time. If stored as recommended, solution
Dogs color does not adversely affect potency.
The minimum inhibitory concentration (MIC) values for cefovecin against label-claim pathogens isolated from skin HOW SUPPLIED:
infections in dogs enrolled in a 2001-2003 field effectiveness study are presented in Table 5. All MICs were determined CONVENIA is available as a 10 mL multi-use vial containing 800 milligrams of cefovecin as a lyophilized cake.
in accordance with the Clinical and Laboratory Standards Institute (CLSl) standards.
REFERENCES:
Table 5. Activity of CONVENIA Against Pathogens Isolated from Dogs Treated With CONVENIA in Field Studies in the Pillai SK, Moellering RC, and Eliopoulos GM. 2005. Antimicrobial combinations, pp 365-440. In V. Lorian (ed.)
U.S. During 2001-2003. Antibiotics in Laboratory Medicine, 5th ed., Lippincott, Williams, and Wilkins, Philadelphia, PA.
²Fish DN, Choi MK, and Jung R: Synergic activity of cephalosporins plus fluoroquinolones against Pseudomonas
Microbiological Number Sample MIC aeruginosa with resistance to one or both drugs. Journal of Antimicrobial Chemotherapy (2002) 50, 1045–1049.
Disease Pathogen Treatment of Collection MIC50 MICg0 Range 3Mayer I and Nagy E: Investigation of the synergic effects of aminoglycoside-fluoroquinolone and third-generation
Outcome Isolates (Time Relative μg/mL μg/mL pg/mL cephalosporin combinations against clinical isolates of Pseudomonas spp. Journal of Antimicrobial Chemotherapy (1999)
to Treatment) 43, 651–657.
Staphylococcus Success 44 Pre-Treatment 0.12 0.25 ≤ 0.06 - 2 4Birchard SJ and Sherding RG. Saunders Manual of Small Animal Practice, 2nd edition. W.B. Saunders Co. 2000: p. 166.
Skin intermedius Failure 4 Pre-Treatment 0.12 - 2
infections Streptococcus Success 16 Pre-Treatment ≤ 0.06 ≤ 0.06 ≤ 0.06 Approved by FDA under NADA # 141-285
canis (Group G) Failure 2 Pre-Treatment ≤ 0.06
zoetis
Cats
The MIC values for cefovecin against Pasteurella multocida isolated from skin infections (wounds and abscesses) in Distributed by:
cats enrolled in a 2001-2003 field effectiveness study are presented in Table 6. All MICs were determined in accordance Zoetis Inc.
with the CLSI standards. Kalamazoo, MI 49007
Table 6. Activity of CONVENIA Against Pathogens Isolated from Cats Treated With CONVENIA in Field Studies in the Revised: July 2022
U.S. During 2001-2003. 40039675A&P
Microbiological Number Sample MIC
Disease Pathogen Treatment of Collection MIC50 MICg0 Range
Outcome Isolates (Time Relative μg/mL pg/mL pg/mL
to Treatment)
Skin Pasteurella Success 57 Pre-Treatment ≤ 0.06 ≤ 0.06 ≤ 0.06 -0.12
infections multocida Failure 1 Pre-Treatment ≤ 0.06