ANNEX I
SUMMARY OF PRODUCT CHARACTERISTICS
1.
ZUPREVO 40 mg/ml solution for injection for pigs
2.
One ml contains:
Active substance:
Tildipirosin 40 mg
For a full list of excipients, see section 6.1.
3.
Solution for injection
Clear yellowish solution
4.
4.1
Pigs
4.2
Treatment of swine respiratory disease (SRD) associated with
Actinobacillus pleuropneumoniae
,
Pasteurella multocida, Bordetella bronchiseptica
and
Haemophilus parasuis
sensitive to tildipirosin.
4.3
Do not use in case of hypersensitivity to macrolide antibiotics or to any of the excipients.
Do not administer intravenously.
4.4
None.
4.5
The safety in piglets less than 4 weeks of age has not been established. Use in young piglets only
according to the benefit/risk assessment by the responsible veterinarian.
Whenever possible, the veterinary medicinal product should only be used based on susceptibility
testing. Official, national and regional antimicrobial policies should be taken into account when the
veterinary medicinal product is used.
Administer strictly intramuscularly.
2
Special precautions to be taken by the person administering the veterinary medicinal product to
animals
Special caution should be taken to avoid accidental self-injection, as toxicology studies in laboratory
animals showed cardiovascular effects after intramuscular administration of tildipirosin. In case of
accidental self-injection, seek medical advice immediately and show the package leaflet or the label to
the physician.
Do not use in automatically powered syringes which have no additional protection system.
Tildipirosin may cause sensitisation by skin contact. If accidental skin exposure occurs, wash the skin
immediately with soap and water. If accidental eye exposure occurs, flush eyes immediately with clean
water.
Wash hands after use.
In target animal safety studies, administration of the maximum recommended injection volume (5 ml)
occasionally caused slight swellings at the injection site that were not painful on palpation. Swellings
persisted for up to 3 days. Pathomorphological injection site reactions resolved completely within 21
days.
During clinical trials, pain on injection and injection site swellings were seen very commonly in
treated pigs. These swellings resolved within 1 to 6 days.
During clinical trials, treatment caused shock symptoms in 2 out of 1048 animals. These symptoms
quickly resolved in one animal, but led to death in the other animal.
4.7 Use during pregnancy and lactation or lay
The safety of the veterinary medicinal product has not been established during pregnancy or lactation.
However, there was no evidence for any selective developmental or reproductive effects in any of the
laboratory studies.
Use only according to the benefit/risk assessment by the responsible veterinarian.
There is cross resistance with other macrolides. Do not administer with antimicrobials with a similar
mode of action such as other macrolides or lincosamides.
4.9
Intramuscular use.
Administer 4 mg tildipirosin/kg body weight (equivalent to 1ml/10 kg body weight) once only.
The injection volume should not exceed 5ml per injection site.
The rubber stopper of the vial may be safely punctured up to 20 times. Otherwise, the use of a
multiple-dose syringe is recommended.
To ensure correct dosage, body weight should be determined as accurately as possible to avoid under-
dosing.
3
It is recommended to treat animals in the early stages of the disease and to evaluate the response to
treatment within 48 hours after injection. If clinical signs of respiratory disease persist or increase, or if
relapse occurs, treatment should be changed using another antibiotic, and continued until clinical signs
have resolved.
In piglets, intramuscular administration of tildipirosin (on three occasions in intervals of 4 days) at 8,
12 and 20 mg/kg body weight (2, 3 and 5 times the recommended clinical dose), resulted in transient
slightly subdued behaviour in one piglet each from the 8 and 12 mg/kg BW group and 2 piglets from
the 20 mg/kg BW group following the first or second injection.
Muscle tremors to the hind legs were observed following the first treatment in one pig each from the
12 and 20 mg/kg BW group. At 20 mg/kg body weight one out of eight animals showed transient
generalized body tremors with inability to stand after the first administration and the animal showed
transient unsteadiness on its feet after the third administration. Another animal developed treatment
related shock after the first administration and was euthanized on welfare grounds. Mortality was
observed at doses of 25 mg/kg body weight and higher.
4.11 Withdrawalperiod
Meat and offal: 9 days
5.
Pharmacotherapeutic group: Macrolide
ATCvet code: QJ01FA96
5.1
Pharmacodynamic properties
Tildipirosin is a 16-membered semi-synthetic macrolide antimicrobial agent. Three amine substituents
at the macrocyclic lactone ring result in a tri-basic character of the molecule.
The product has a long
duration of action; however, the exact clinical effect duration after a single injection is unknown.
Macrolides in general are bacteriostatic antibiotics but for certain pathogens can be bactericidal. They
inhibit essential protein biosynthesis by virtue of their selective binding to bacterial ribosomal RNA
and act by blocking the prolongation of the peptide chain. The effect is generally time-dependent.
The antimicrobial activity spectrum of tildipirosin includes:
Actinobacillus pleuropneumoniae
,
Pasteurella multocida
,
Bordetella bronchiseptica
and
Haemophilus
parasuis,
which are the bacterial pathogens most commonly associated with swine respiratory disease
(SRD).
In vitro,
the effect of tildipirosin is bacteriostatic against
Pasteurella multocida
and
B. bronchiseptica
,
and bactericidal for
A. pleuropneumoniae
and
H. parasuis
.
MIC data for the target pathogens (wild type distribution) are presented in the table below.
Species
Range
(µg/ml)
MIC
50
(µg/ml)
MIC
90
(µg/ml)
Actinobacillus pleuropneumoniae
(n=100)
2-16
8
8
Bordetella bronchiseptica (n=87)
0.5-8
2
4
Pasteurella multocida
(n=99)
0.125-2
0.5
1
Haemophilus parasuis
(n=63)
0.032-4
0.5
1
4
Resistance to macrolides generally results from three mechanisms: (1) the alteration of the ribosomal
target site (methylation), often referred to as MLS
B
resistance as it affects macrolides, lincosamides
and group B streptogramins, (2) the utilisation of active efflux mechanism; (3) the production of
inactivating enzymes. Generally, cross-resistance between tildipirosin and other macrolides,
lincosamides or streprogramins is to be expected.
Data were collected on zoonotic bacteria and commensals. MIC values for
Salmonella
were reported
to be in the range of 4-16 µg/ml, and all strains were wild type. For
E. coli
,
Campylobacter
and
Enterococci
, both wild type and non-wild type phenotypes were observed (MIC range 1->64 µg/ml).
5.2
Pharmacokinetic particulars
Tildipirosin administered intramuscularly to pigs at a single dose of 4 mg/kg body weight was rapidly
absorbed reaching average peak plasma concentration of 0.9 µg/ml within 23 minutes (T
max
).
Macrolides are characterised by their extensive partitioning into tissues.
Accumulation at the site of respiratory tract infection is demonstrated by high and sustained
tildipirosin concentrations in lung and bronchial fluid (collected post mortem), which far exceed those
in blood plasma. The mean terminal half life is 4.4 days.
In vitro
binding of tildipirosin to porcine plasma proteins is limited with approximately 30 %.
In pigs, it is postulated that the metabolism of tildipirosin proceeds by reduction and sulphate
conjugation with subsequent hydration (or ring opening), by demethylation, by dihydroxylation and by
S-cysteine and S-glutathione conjugation.
The mean total excretion of the total dose administered within 14 days was about 17% in urine and
57% in faeces.
6.
6.1 List of excipients
Citric acid monohydrate
Propylene glycol
Water for injections
6.2 Incompatibilities
In the absence of compatibility studies, this veterinary medicinal product must not be mixed with other
veterinary medicinal products.
6.3 Shelf life
Shelf life of the veterinary medicinal product as packaged for sale: 2 years
Shelf life after first opening the immediate packaging: 28 days
6.4. Special precautions for storage
Do not store above 25 °C.
6.5 Nature and composition of immediate packaging
Type I amber glass vial with a chlorobutyl rubber stopper and an aluminium cap.
Box containing 1 vial of 20 ml, 50 ml, 100 ml or 250 ml.
Not all pack sizes may be marketed.
6.6
Special precautions for the disposal of unused veterinary medicinal product or waste
materials derived from the use of such products
5
Any unused veterinary medicinal product or waste materials derived from such veterinary medicinal
products should be disposed of in accordance with local requirements.
7.
Intervet International B. V.
Wim de Körverstraat 35
5831 AN Boxmeer
The Netherlands
8.
9.
{DD/MM/YYYY}
10
{MM/YYYY}
Detailed information on this veterinary medicinal product is available on the website of the European
Medicines Agency
http://www.ema.europa.eu/
PROHIBITION OF SALE, SUPPLY AND/OR USE
Not applicable.
6
1.
ZUPREVO 180 mg/ml solution for injection for cattle
2.
One ml contains:
Active substance:
Tildipirosin 180 mg
For a full list of excipients, see section 6.1.
3.
Solution for injection
Clear yellowish solution
4.
4.1
Cattle
4.2
For the treatment and prevention of bovine respiratory disease (BRD) associated with
Mannheimia
haemolytica
,
Pasteurella multocida
and
Histophilus somni
sensitive to tildipirosin.
The presence of the disease in the herd should be confirmed before preventive treatment.
4.3
Do not use in case of hypersensitivity to macrolide antibiotics or to any of the excipients.
4.4
None.
4.5
Whenever possible, the veterinary medicinal product should only be used based on susceptibility
testing.
Official, national and regional antimicrobial policies should be taken into account when the product is
used.
Special precautions to be taken by the person administering the veterinary medicinal product to
animals
Tildipirosin may cause sensitisation by skin contact. If accidental skin exposure occurs, wash the skin
immediately with soap and water. If accidental eye exposure occurs, flush eyes immediately with clean
water.
Wash hands after use.
7
Special caution should be taken to avoid accidental self-injection, as toxicology studies in laboratory
animals showed cardiovascular effects after intramuscular administration of tildipirosin. In case of
accidental self-injection, seek medical advice immediately and show the package leaflet or the label to
the physician.
Do not use in automatically powered syringes which have no additional protection system.
Pain on injection and injection site swellings are very common in treated animals. Following the
maximum recommended injection site volume of 10 ml, injection site swellings may be associated
with pain on palpation for about one day in individual animals. The swellings are transient and will
usually resolve within 7 to 16 days; in individual animals swellings may persist for 21 days.
Pathomorphological injection site reactions will largely resolve within 35 days.
4.7 Use during pregnancy and lactation
The safety of the veterinary medicinal product has not been established during pregnancy and
lactation. However, there was no evidence for any selective developmental or reproductive effects in
any of the laboratory studies. Use only according to the benefit/risk assessment by the responsible
veterinarian.
There is cross resistance with other macrolides. Do not administer with antimicrobials with a similar
mode of action such as other macrolides or lincosamides.
4.9
Subcutaneous use.
Administer 4 mg tildipirosin/kg body weight (equivalent to 1 ml/45 kg body weight) once only.
For treatment of cattle over 450 kg body weight, divide the dose so that no more than 10 ml are
injected at one site.
The rubber stopper of the vial may be safely punctured up to 20 times. Otherwise, the use of a
multiple-dose syringe is recommended.
To ensure correct dosage, bodyweight should be determined as accurately as possible to avoid
underdosing.
It is recommended to treat animals in the early stages of the disease and to evaluate the response to
treatment within 2 to 3 days after injection. If clinical signs of respiratory disease persist or increase,
treatment should be changed using another antibiotic, and continued until clinical signs have resolved.
In calves, a single subcutaneous injection of 10 times the recommended dose (40 mg/kg body weight)
and repeated subcutaneous administration of tildipirosin (on three occasions in intervals of 7 days) at
4, 12 and 20 mg/kg (1, 3 and 5 times the recommended clinical dose) were well tolerated, apart from
transient clinical signs attributed to injection site discomfort and injection site swellings associated
with pain in some animals.
4.11 Withdrawalperiod
Cattle (Meat and offal): 47 days
8
Not authorised for use in lactating animals producing milk for human consumption.
Do not use in pregnant animals, which are intended to produce milk for human consumption, within 2
months of expected parturition.
5.
Pharmacotherapeutic group: Macrolide
ATCvet code: QJ01FA96
5.1
Pharmacodynamic properties
Tildipirosin is a 16-membered semi-synthetic macrolide antimicrobial agent. Three amine substituents
at the macrocyclic lactone ring result in a tri-basic character of the molecule. The product has a long
duration of action, however, the exact clinical effect duration after a single injection is unknown.
Macrolides in general are bacteriostatic antibiotics but for certain pathogens can be bactericidal. They
inhibit essential protein biosynthesis by virtue of their selective binding to bacterial ribosomal RNA
and act by blocking the prolongation of the peptide chain. The effect is generally time-dependent.
The antimicrobial activity spectrum of tildipirosin includes:
Mannheimia haemolytica
,
Pasteurella multocida
and
Histophilus somni
, the bacterial pathogens most
commonly associated with bovine respiratory disease (BRD).
In vitro
, the effect of tildipirosin is
bactericidal against
M. haemolytica
and
H. somni
, and bacteriostatic against
P. multocida
.
MIC data for the target pathogens (wild type distribution) are presented in the table below.
Species
Range
(µg/ml)
MIC
50
(µg/ml)
MIC
90
(µg/ml)
Mannheimia haemolytica (n=88)
0.125-2
0.5
1
Pasteurella multocida (n=105)
0.125-2
0.5
1
Histophilus somni (n=63)
0.5-8
2
4
Resistance to macrolides generally results from three mechanisms: (1) the alteration of the ribosomal
target site (methylation), often referred to as MLS
B
resistance as it affects macrolides, lincosamides
and group B streptogramins; (2) the utilisation of active efflux mechanism; (3) the production of
inactivating enzymes. Generally, cross-resistance between tildipirosin and other macrolides,
lincosamides or streptogramins is to be expected.
Data were collected on zoonotic bacteria and commensals. MIC values for
Salmonella
were reported
to be in the range of 4-16 µg/ml, and all strains were wild type. For
E. coli
.,
Campylobacter
and
Enterococci
, both wild type and non-wild type phenotypes were observed (MIC range 1->64 µg/ml).
5.2
Pharmacokinetic particulars
Tildipirosin administered subcutaneously to cattle at a single dose of 4 mg/kg body weight resulted in
rapid absorption with average peak plasma concentration of 0.7 µg/ml within 23 minutes (Tmax) and
high absolute bioavailability (78.9%).
Macrolides are characterised by their extensive partitioning into tissues.
Accumulation at the site of respiratory tract infection is demonstrated by high and sustained
tildipirosin concentrations in lung and bronchial fluid, which far exceed those in blood plasma. The
mean terminal half life is approximately 9 days.
In vitro
binding of tildipirosin to bovine plasma and bronchial fluid proteins is limited with
approximately 30 %.
In cattle, it is postulated that metabolism of tildipirosin proceeds by cleavage of the mycaminose sugar
moiety, by reduction and sulphate conjugation with subsequent hydration (or ring opening), by
demethylation, by mono- or dihydroxylation with subsequent dehydration and by S-cysteine and S-
glutathione conjugation.
9
The mean total excretion of the total dose administered within 14 days was about 24% in urine and
40% in faeces.
6.
6.1
List of excipients
Citric acid monohydrate
Propylene glycol
Water for injections
6.2
Incompatibilities
In the absence of compatibility studies, this veterinary medicinal product must not be mixed with other
veterinary medicinal products.
6.3
Shelf life
Shelf life of the veterinary medicinal product as packaged for sale: 2 years
Shelf life after first opening the immediate packaging: 28 days
6.4.
Special precautions for storage
Do not store above 25 °C.
6.5
Nature and composition of immediate packaging
Type I amber glass vial with chlorobutyl rubber stopper and an aluminium cap.
Box containing 1 vial of 20 ml, 50 ml, 100 ml or 250 ml.
Not all pack sizes may be marketed.
6.6
Special precautions for the disposal of unused veterinary medicinal product or waste
materials derived from the use of such products
Any unused veterinary medicinal product or waste materials derived from such veterinary medicinal
products should be disposed of in accordance with local requirements.
7.
Intervet International B. V.
Wim de Körverstraat 35
5831 AN Boxmeer
The Netherlands
8.
9.
{DD/MM/YYYY}
10
10
{MM/YYYY} or <month YYYY>
Detailed information on this veterinary medicinal product is available on the website of the European
Medicines Agency
http://www.ema.europa.eu/
PROHIBITION OF SALE, SUPPLY AND/OR USE
Not applicable.
11
ANNEX II
A.
MANUFACTURING AUTHORISATION HOLDER(S) RESPONSIBLE FOR
BATCH RELEASE
B.
CONDITIONS OR RESTRICTIONS OF THE MARKETING
AUTHORISATION REGARDING SUPPLY OR USE
C.
CONDITIONS OR RESTRICTIONS OF THE MARKETING
AUTHORISATION WITH REGARD TO SAFE AND EFFECTIVE USE
D.
STATEMENT OF THE MRLs
12
A. MANUFACTURING AUTHORISATION HOLDER(S) RESPONSIBLE FOR BATCH
RELEASE
Name and address of the manufacturer(s) responsible for batch release
Intervet International GmbH
Feldstrasse 1 a
85716 Unterschleissheim
Germany
B. CONDITIONS OR RESTRICTIONS OF THE MARKETING AUTHORISATION
REGARDING SUPPLY OR USE
To be supplied only on veterinary prescription.
C. CONDITIONS OR RESTRICTIONS OF THE MARKETING AUTHORISATION WITH
REGARD TO THE SAFE AND EFFECTIVE USE OF THE PRODUCT
Not applicable.
D.
STATEMENT OF THE MRLs
The active substance in Tildipirosin is an allowed substance as described in table 1 of the annex to
Commission Regulation (EU) No 37/2010:
Pharmacologically
active substance
Marker
residue
Animal
species
MRL Target
tissues
Other provisions
Therapeutic
classification
Tildipirosin
Tildipirosin Porcine 1200
μg/kg
800
μg/kg
5000
μg/kg
10000
μg/kg
Muscle
The MRL for muscle
does not apply to the
injection site, where
residue levels should
not exceed 7500
μg/kg.
Provisional MRLs
expire on 1 January
2012.
Macrolide
Skin+fat
Liver
Kidney
Tildipirosin
Tildipirosin Bovine
400
μg/kg
200
μg/kg
2000
μg/kg
3000
μg/kg
Muscle
Not for use in animals
from which milk is
produced for human
consumption.
The MRL for muscle
does not apply to the
injection site, where
residue levels should
not exceed 11500
μg/kg.
Provisional MRLs
expire on 1 January
2012.
Macrolide
Fat
Liver
Kidney
The excipients listed in section 6.1 of the SPC are either allowed substances for which table 1 of the
annex to Commission Regulation (EU) No 37/2010 indicates that no MRLs are required or are
considered as not falling within the scope of Regulation (EC) No 470/2009 when used as in this
veterinary medicinal product.
13
ANNEX III
LABELLING AND PACKAGE LEAFLET
14
A. LABELLING
15
PARTICULARS TO APPEAR ON THE OUTER PACKAGE
Pigs
Carton Box
1.
ZUPREVO 40 mg/ml solution for injection for pigs
Tildipirosin
2.
STATEMENT OF ACTIVE AND OTHER SUBSTANCES
40 mg/ml of tildipirosin
3.
Solution for injection
4.
PACKAGE SIZE
20 ml
50 ml
100 ml
250 ml
5.
Pigs
6.
INDICATION
Treatment of swine respiratory disease (SRD).
7.
METHOD AND ROUTE OF ADMINISTRATION
4 mg tildipirosin/kg body weight
Read the package leaflet before use.
8.
Meat and offal: 9 days
16
9.
SPECIAL WARNINGS
Accidental self-injection may be dangerous. Do not use in automatically powered syringes which have
no additional protection system.
Read the package leaflet before use.
10. EXPIRY DATE
EXP:
Once opened, use within 28 days.
11. SPECIAL STORAGE CONDITIONS
Do not store above 25 °C.
12. SPECIAL PRECAUTIONS FOR THE DISPOSAL OF UNUSED PRODUCTS OR
WASTE MATERIALS, IF ANY
Disposal:
Read the package leaflet.
13. THE WORDS “FOR ANIMAL TREATMENT ONLY” AND CONDITIONS OR
RESTRICTIONS REGARDING SUPPLY AND USE, if applicable
For animal treatment only - to be supplied only on veterinary prescription.
14. THE WORDS “KEEP OUT OF THE REACH AND SIGHT OF CHILDREN”
Keep out of the reach and sight of children.
Intervet International B. V.
Wim de Körverstraat 35
5831 AN Boxmeer
The Netherlands
EU/0/00/000/000-000
17. MANUFACTURER’S BATCH NUMBER
Batch:
17
PARTICULARS TO APPEAR ON THE OUTER PACKAGE
Cattle
Carton Box
1.
ZUPREVO 180 mg/ml solution for injection for cattle
Tildipirosin
2.
STATEMENT OF ACTIVE AND OTHER SUBSTANCES
180 mg/ml of tildipirosin
3.
Solution for injection
4.
PACKAGE SIZE
20 ml
50 ml
100 ml
250 ml
5.
Cattle
6.
Treatment and prevention of bovine respiratory disease (BRD).
7.
METHOD AND ROUTE OF ADMINISTRATION
s.c.
4 mg tildipirosin/kg body weight
Read the package leaflet before use.
8.
Meat and offal: 47 days
Not authorised for use in lactating animals producing milk for human consumption.
Read the package leaflet before use
18
9.
SPECIAL WARNINGS
Accidental self-injection may be dangerous. Do not use in automatically powered syringes which have
no additional protection system.
Read the package leaflet before use.
10. EXPIRY DATE
EXP:
Once opened, use within 28 days.
11. SPECIAL STORAGE CONDITIONS
Do not store above 25 °C.
12. SPECIAL PRECAUTIONS FOR THE DISPOSAL OF UNUSED PRODUCTS OR
WASTE MATERIALS, IF ANY
Disposal:
Read the package leaflet
13. THE WORDS “FOR ANIMAL TREATMENT ONLY” AND CONDITIONS OR
RESTRICTIONS REGARDING SUPPLY AND USE, if applicable
For animal treatment only - to be supplied only on veterinary prescription.
14. THE WORDS “KEEP OUT OF THE REACH AND SIGHT OF CHILDREN”
Keep out of the reach and sight of children.
Intervet International B. V.
Wim de Körverstraat 35
5831 AN Boxmeer
The Netherlands
EU/0/00/000/000-000
17. MANUFACTURER’S BATCH NUMBER
Batch:
19
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS
Pigs
Label (20 ml, 50 ml)
1.
ZUPREVO 40 mg/ml solution for injection for pigs
Tildipirosin
2.
QUANTITY OF THE ACTIVE SUBSTANCE
40 mg/ml of tildipirosin
3.
CONTENTS BY WEIGHT, BY VOLUME OR BY NUMBER OF DOSES
20 ml
50 ml
4.
ROUTE OF ADMINISTRATION
i.m.
5.
Meat and offal: 9 days
6.
BATCH NUMBER
Batch:
7.
EXPIRY DATE
EXP:
Once opened, use by…
8.
THE WORDS “FOR ANIMAL TREATMENT ONLY”
For animal treatment only.
20
PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGE
Pigs
Label (100 ml, 250 ml)
1.
ZUPREVO 40 mg/ml solution for injection for pigs
Tildipirosin
2.
STATEMENT OF ACTIVE AND OTHER SUBSTANCES
40 mg/ml of tildipirosin
3.
Solution for injection
4.
PACKAGE SIZE
100 ml
250 ml
5.
Pigs
6.
INDICATION
Treatment of swine respiratory disease (SRD).
7.
METHOD AND ROUTE OF ADMINISTRATION
i.m.
Read the package leaflet before use.
8.
Meat and offal: 9 days
9.
SPECIAL WARNINGS
Accidental self-injection is dangerous – see package leaflet before use.
21
10. EXPIRY DATE
EXP:
Once opened, use by ….
11. SPECIAL STORAGE CONDITIONS
Do not store above 25 °C.
12. SPECIAL PRECAUTIONS FOR THE DISPOSAL OF UNUSED PRODUCTS OR
WASTE MATERIALS, IF ANY
Disposal:
Read the package leaflet.
13. THE WORDS “FOR ANIMAL TREATMENT ONLY” AND CONDITIONS OR
RESTRICTIONS REGARDING SUPPLY AND USE, if applicable
For animal treatment only - to be supplied only on veterinary prescription.
14. THE WORDS “KEEP OUT OF THE REACH AND SIGHT OF CHILDREN”
Keep out of the reach and sight of children.
Intervet International B. V.
Wim de Körverstraat 35
5831 AN Boxmeer
The Netherlands
EU/0/00/000/000
17. MANUFACTURER’S BATCH NUMBER
Batch:
22
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS
Cattle
Label (20 ml, 50 ml)
1.
ZUPREVO 180 mg/ml solution for injection for cattle
Tildipirosin
2.
QUANTITY OF THE ACTIVE SUBSTANCE(S)
180 mg/ml of tildipirosin
3.
CONTENTS BY WEIGHT, BY VOLUME OR BY NUMBER OF DOSES
20 ml
50 ml
4.
ROUTE OF ADMINISTRATION
S.c.
5.
Meat and offal: 47 days
See package leaflet
6.
BATCH NUMBER
Batch:
7.
EXPIRY DATE
EXP:
Once opened, use by…
8.
THE WORDS “FOR ANIMAL TREATMENT ONLY”
For animal treatment only.
23
PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGE
Cattle
Label (100 ml, 250 ml)
1.
ZUPREVO 180 mg/ml solution for injection for cattle
Tildipirosin
2.
STATEMENT OF ACTIVE AND OTHER SUBSTANCES
180 mg/ml of tildipirosin
3.
Solution for injection
4.
PACKAGE SIZE
100 ml
250 ml
5.
Cattle
6.
Treatment and prevention of bovine respiratory disease (BRD).
7.
METHOD AND ROUTE OF ADMINISTRATION
S.c.
Read the package leaflet before use.
8.
Meat and offal: 47 days
See package leaflet.
9.
SPECIAL WARNINGS
Accidental self-injection is dangerous – see package leaflet before use.
24
10. EXPIRY DATE
EXP:
Once opened, use by…
11. SPECIAL STORAGE CONDITIONS
Do not store above 25 °C.
12. SPECIAL PRECAUTIONS FOR THE DISPOSAL OF UNUSED PRODUCTS OR
WASTE MATERIALS, IF ANY
Disposal:
Read the package leaflet
13. THE WORDS “FOR ANIMAL TREATMENT ONLY” AND CONDITIONS OR
RESTRICTIONS REGARDING SUPPLY AND USE, if applicable
For animal treatment only - to be supplied only on veterinary prescription.
14. THE WORDS “KEEP OUT OF THE REACH AND SIGHT OF CHILDREN”
Keep out of the reach and sight of children.
Intervet International B. V.
Wim de Körverstraat 35
5831 AN Boxmeer
The Netherlands
EU/0/00/000/000
17. MANUFACTURER’S BATCH NUMBER
Batch:
25
B. PACKAGE LEAFLET
26
PACKAGE LEAFLET FOR:
ZUPREVO 40 mg/ml solution for injection for pigs
1.
THE MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH
RELEASE, IF DIFFERENT
Marketing authorisation holder
:
Intervet International B. V.
Wim de Körverstraat 35
5831 AN Boxmeer
The Netherlands
Manufacturer for the batch release
:
Intervet International GmbH
Feldstrasse 1 a
85716 Unterschleissheim
Germany
2.
ZUPREVO 40 mg/ml solution for injection for pigs
Tildipirosin
3.
STATEMENT OF THE ACTIVE SUBSTANCE AND OTHER INGREDIENT(S)
The veterinary medicinal product is a clear yellowish solution for injection containing 40 mg/ml of
tildipirosin
4.
INDICATIONS
Treatment of swine respiratory disease (SRD) associated with
Actinobacillus pleuropneumoniae
,
Pasteurella multocida, Bordetella bronchiseptica
and
Haemophilus parasuis
sensitive to tildipirosin.
5.
Do not use in case of hypersensitivity to macrolide antibiotics, citric acid monohydrate or propylene
glycol.
Do not administer intravenously.
6.
During clinical trials, pain on injection and injection site swellings were seen very commonly in
treated pigs. These swellings resolved within 1 to 6 days.
Following the maximum recommended injection site volume of 5 ml, injection site reactions resolved
completely within 21 days.
During clinical trials, treatment caused shock symptoms in 2 out of 1048 animals. These symptoms
quickly resolved in one animal but led to death in the other animal.
If you notice any serious effects or other effects not mentioned in this package leaflet, please inform
your veterinary surgeon.
27
7.
Pigs
8.
DOSAGE FOR EACH SPECIES, ROUTE AND METHOD OF ADMINISTRATION
Intramuscular use.
Administer 4 mg tildipirosin/kg body weight (equivalent to 1 ml/10 kg body weight) once only.
It is recommended to treat animals in the early stages of the disease and to evaluate the response to
treatment within 48 hours after injection. If clinical signs of respiratory disease persist or increase, or if
relapse occurs, treatment should be changed using another antibiotic, and continued until clinical signs
have resolved.
9.
ADVICE ON CORRECT ADMINISTRATION
The injection volume should not exceed 5 ml per injection site.
The rubber stopper of the vial may be safely punctured up to 20 times. Otherwise, the use of a
multiple-dose syringe is recommended.
To ensure correct dosage, body weight should be determined as accurately as possible to avoid
underdosing.
10. WITHDRAWAL PERIOD
Meat and offal: 9 days
11. SPECIAL STORAGE PRECAUTIONS
Keep out of the reach and sight of children.
Do not store above 25 °C.
Do not use after the expiry date stated on the vial after EXP.
Shelf life after first opening the container: 28 days.
12. SPECIAL WARNING(S)
Precautions for use in animals
The safety in piglets less than 4 weeks of age has not been established. Use in young piglets only
according to the benefit/risk assessment by the responsible veterinarian.
Whenever possible, the veterinary medicinal product should only be used based on susceptibility
testing. Official, national and regional antimicrobial policies should be taken into account when the
veterinary medicinal product is used.
Administer strictly intramuscularly.
The safety of the veterinary medicinal product has not been established during pregnancy or lactation.
However, there was no evidence for any selective developmental or reproductive effects in any of the
laboratory studies. Use only according to the benefit/risk assessment by the responsible veterinarian.
28
In piglets, intramuscular administration of tildipirosin (on three occasions in intervals of 4 days) at 8,
12 and 20 mg/kg bodyweight (2, 3 and 5 times the recommended clinical dose), resulted in transient
slightly subdued behaviour in one piglet each from the 8 and 12 mg/kg BW group and 2 piglets from
the 20 mg/kg bodyweight group following the first or second injection. Muscle tremors to the hind
legs were observed following the first treatment in one pig each from the 12 and 20 mg/kg bodyweight
group.
At 20 mg/kg bodyweight one of eight animals showed transient generalized body tremors with
inability to stand after the first administration and the animal showed transient unsteadiness on its feet
after the third administration. Another animal developed treatment related shock after the first
administration and was euthanised on welfare grounds. Mortality was observed at doses of 25 mg/kg
body weight and higher.
In the absence of compatibility studies, this veterinary medicinal product must not be mixed with other
veterinary medicinal products.
There is cross resistance with other macrolides. Do not administer with antimicrobials with a similar
mode of action such as other macrolides or lincosamides.
Precautions to be taken by the person administering the product
Special caution should be taken to avoid accidental self-injection, as toxicology studies in laboratory
animals showed cardiovascular effects after intramuscular administration of tildipirosin. In case of
accidental self-injection, seek medical advice immediately and show the package leaflet or the label to
the physician.
Do not use in automatically powered syringes which have no additional protection system.
Tildipirosin may cause sensitisation by skin contact. If accidental skin exposure occurs, wash the skin
immediately with soap and water. If accidental eye exposure occurs, flush eyes immediately with clean
water.
Wash hands after use.
13. SPECIAL PRECAUTIONS FOR THE DISPOSAL OF UNUSED PRODUCT OR WASTE
MATERIALS, IF ANY
Ask your veterinary surgeon/pharmacist how to dispose of medicines no longer required. These measures
should help to protect the environment.
14. DATE ON WHICH THE PACKAGE LEAFLET WAS LAST APPROVED
Detailed information on this veterinary medicinal product is available on the website of the European
Medicines Agency http://www.ema.europa.eu/.
15. OTHER INFORMATION
Box containing 1 vial of 20 ml, 50 ml, 100 ml or 250 ml.
Not all pack sizes may be marketed.
29
PACKAGE LEAFLET FOR:
ZUPREVO 180 mg/ml solution for injection for cattle
1.
THE MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH
RELEASE, IF DIFFERENT
Marketing authorisation holder
:
Intervet International B. V.
Wim de Körverstraat 35
5831 AN Boxmeer
The Netherlands
Manufacturer for the batch release
:
Intervet International GmbH
Feldstrasse 1 a
85716 Unterschleissheim
Germany
2.
ZUPREVO 180 mg/ml solution for injection for cattle
Tildipirosin
3.
STATEMENT OF THE ACTIVE SUBSTANCE AND OTHER INGREDIENT(S)
ZUPREVO is a clear yellowish solution for injection containing 180 mg/ml of tildipirosin
4.
INDICATIONS
For the treatment and prevention of bovine respiratory disease (BRD) associated with
Mannheimia
haemolytica
,
Pasteurella multocida
and
Histophilus somni
sensitive to tildipirosin.
The presence of the disease in the herd should be confirmed before preventive treatment.
5.
Do not use in case of hypersensitivity to macrolide antibiotics, citric acid monohydrate or propylene
glycol.
6.
Pain on injection and injection site swellings are very common in treated animals. Following the
maximum recommended injection site volume of 10 ml, injection site swellings may be associated
with pain on palpation for about one day in individual animals. The swellings are transient and will
usually resolve within 7 to 16 days; in individual animals swellings may persist for 21 days. Injection
site reactions will largely resolve within 35 days.
30
If you notice any serious effects or other effects not mentioned in this package leaflet, please inform
your veterinary surgeon.
7.
Cattle
8.
DOSAGE FOR EACH SPECIES, ROUTE AND METHOD OF ADMINISTRATION
Subcutaneous use.
Administer 4 mg tildipirosin/kg body weight (equivalent to 1 ml/45 kg body weight) once only.
It is recommended to treat animals in the early stages of the disease and to evaluate the response to
treatment within 2 to 3 days after injection. If clinical signs of respiratory disease persist or increase,
treatment should be changed using another antibiotic, and continued until clinical signs have resolved.
9.
ADVICE ON CORRECT ADMINISTRATION
For treatment of cattle over 450 kg body weight, divide the dose so that no more than 10 ml are
injected at one site.
The rubber stopper of the vial may be safely punctured up to 20 times. Otherwise, the use of a
multiple-dose syringe is recommended.
To ensure correct dosage, body weight should be determined as accurately as possible to avoid
underdosing.
10. WITHDRAWAL PERIOD
Meat and offal: 47 days
Not authorised for use in lactating animals producing milk for human consumption.
Do not use in pregnant animals, which are intended to produce milk for human consumption, within 2
months of expected parturition.
11. SPECIAL STORAGE PRECAUTIONS
Keep out of the reach and sight of children.
Do not store above 25 °C.
Do not use after the expiry date which is stated on the vial after EXP.
Shelf life after first opening the container: 28 days.
12. SPECIAL WARNINGS
Precautions for use in animals
Whenever possible, the veterinary medicinal product should only be used based on susceptibility
testing. Official, national and regional antimicrobial policies should be taken into account when the
veterinary medicinal product is used.
The safety of the veterinary medicinal product has not been established during pregnancy and
lactation. However, there was no evidence for any selective developmental or reproductive effects in
any of the laboratory studies. Use only according to the benefit/risk assessment by the responsible
veterinarian.
31
Overdoses of 10 times the recommended dose as well as repeated subcutaneous administration of the
veterinary medicinal product only led to transient clinical signs attributed to injection site discomfort
and injection site swellings associated with pain in some animals.
In the absence of compatibility studies, this veterinary medicinal product must not be mixed with other
veterinary medicinal products.
There is cross resistance with other macrolides. Do not administer with antimicrobials with a similar
mode of action such as other macrolides or lincosamides.
Precautions for the person administering the product
Special caution should be taken to avoid accidental self-injection, as toxicology studies in laboratory
animals showed cardiovascular effects after intramuscular administration of tildipirosin. In case of
accidental self-injection, seek medical advice immediately and show the package leaflet or the label to
the physician.
Do not use in automatically powered syringes which have no additional protection system.
Tildipirosin may cause sensitisation by skin contact. If accidental skin exposure occurs, wash the skin
immediately with soap and water. If accidental eye exposure occurs, flush eyes immediately with clean
water.
Wash hands after use.
13. SPECIAL PRECAUTIONS FOR THE DISPOSAL OF UNUSED PRODUCT OR WASTE
MATERIALS, IF ANY
Ask your veterinary surgeon/pharmacist how to dispose of medicines no longer required. These measures
should help to protect the environment.
14. DATE ON WHICH THE PACKAGE LEAFLET WAS LAST APPROVED
Detailed information on this veterinary medicinal product is available on the website of the European
Medicines Agency
http://www.ema.europa.eu/
.
15. OTHER INFORMATION
Box containing 1 vial of 20 ml, 50 ml, 100 ml or 250 ml.
Not all pack sizes may be marketed.
32
Source: European Medicines Agency
- Please bookmark this page (add it to your favorites).
- If you wish to link to this page, you can do so by referring to the URL address below this line.
https://theodora.com/drugs/eu/zuprevo_veterinary.html
Copyright © 1995-2021 ITA all rights reserved.