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4.4
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Special warnings (for each
target species)
If for an individual animal,
feed intake is such that the recommended dosage is not realized,
medication should be carried out by parenteral treatment.
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4.5
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Special precautions for use
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4.5i)
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Special precautions for use in
animals
Cross-resistance between tilmicosin and other macrolide
antibiotic has been observed. Use of the
product should be based on susceptibility testing and take into
account official and local antimicrobial policies. Due to likely
variability (time, geographical) in the occurrence of the
resistance of bacteria for tilmicosin, bacteriological sampling and
susceptibility testing are recommended. Inappropriate use of the
product may increase the prevalence of bacteria resistant to
tilmicosin and may decrease the effectiveness of treatment with
tilmicosin related substances.
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4.5ii)
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Special precautions to be taken
by the person administering the veterinary medicinal product to
animals
Accidental ingestion should be
avoided by humans.
People with known
hypersensitivity to macrolide antibiotics should avoid contact with
the veterinary medicinal product.
May cause sensitisation by skin
contact. May cause skin and eye irritation. Avoid direct skin
contact. Wear overalls, safety glasses and impervious gloves when
mixing and handling the product. Wash affected parts if skin
contact occurs. If accidental eye contact occurs, immediately rinse
thoroughly with water. In case of accidental ingestion, or if you
develop symptoms following exposure such as skin rash, seek medical
advice immediately and show the package leaflet or the label to the
physician
Swelling of the face, lips or
eyes or difficulty with breathing are more serious symptoms and
require urgent medical attention.
If the operations involve the
risk of exposure to dust, wear either a disposable filter and half
mask respirator conforming to European Standard EN149 or a
non-disposable respirator to European Standard EN140 fitted with a
filter to EN143. This warning is particularly relevant to on-farm
mixing, where the risk of exposure to dust is likely to be
enhanced.
This warning is particularly
relevant to on-farm mixing, where the risk of exposure to dust is
likely to be enhanced.
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4.6
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Adverse reactions (frequency and
seriousness)
Occasionally, feed intake may decrease (including feed
refusal) in animals receiving medicated feed. This effect is transient
In case of occurrence of allergic
reaction, the treatment should be withdrawn.
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4.7
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Use during pregnancy, lactation
or lay
Laboratory studies in rats have
not produced any evidence of a teratogenic, foetotoxic/embryotoxic
effect of tilmicosin, however, a maternotoxicity was observed at
doses that were close to the therapeutic dosage. The product can be
used in sows whatever the pregnancy stages
The safety of
the veterinary medicinal product has not been established in boars
used for breeding purposes.
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4.8
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Interaction with other medicinal
products and other forms of interaction
Do not use simultaneously with
other macrolides and lincosamides.
Do not use simultaneously with
bacteriostatic antimicrobial agents.
Tilmicosin may lessen the
antibacterial activity of β-lactam antibiotics.
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4.9
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Amount(s) to be administered and
administration route
For oral
administration after incorporation into feed
The product
should be administered to small quantities of feed for immediate
consumption by individual animals. For treatment of groups of pigs,
use an appropriate premix incorporated into medicated feedingstuff
by an authorised feed manufacturer. Pigs to be treated should be separated and treated
individually. The required quantity of the product should be
thoroughly mixed into the daily ration for each individual pig. The
feed containing the oral granules should be provided as the sole
ration for the periods recommended.
Individual
pigs should receive 16 mg tilmicosin per kg bodyweight,
corresponding to 160 mg sproduct/kg
bodyweight, once a day during 15 days. To
avoid underdosing body weight should be determined as accurately as
possible and the amount of
feed that the pig is likely to consume should be estimated. The
correct quantity of the product should be added to the estimated
quantity of daily ration for each pig, in a bucket or similar
receptacle, and thoroughly mixed. The
product should only be added to dry non-pelleted
feed.
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4.10
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Overdose (symptoms, emergency
procedures, antidotes), if necessary
Vomiting and cardio-vascular
collapse are symptoms of overdosing.
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4.11
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Withdrawal period(s)
Meat and offal 21 days.
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5.
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PHARMACOLOGICAL PROPERTIES
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ATC Vet Code:
Pharmacotherapeutic group: Antibacterials for systemic use, macrolides, tilmicosin
ATC vet code: QJ01FA91
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5.1
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Pharmacodynamic properties
Tilmicosin is
a mainly bactericidal semi-synthetic antibiotic of the macrolide
group. It is believed to affect the bacterial protein
synthesis in vitro and in vivo,
without affecting the nucleic acid synthesis. It is mostly
bacteriostatic. It has a bactericidal effect on Pasteurella spp.
Tilmicosin has
a wide spectrum of activity against Gram-positive
organisms and is particularly active against
(Pasteurella, Actinobacillus
pleuropneumoniae) and Mycoplasma organisms of porcine
origin. Tilmicosin
has some activity against certain Gram-negative
micro-organisms.
Cross resistance between
tilmicosin and other macrolide antibiotics has been observed.
Macrolides inhibit protein
synthesis by reversibly binding to the 50S ribosomal subunit.
Bacterial growth is inhibited by induction of the separation of
peptidyl transfer RNA from the ribosome during the elongation
phase.
Ribosomal
methylase, encoded by the erm
gene, can precipitate resistance to macrolides by
alteration of the ribosomal binding site.
The gene that
encodes for an efflux mechanism, mef, also brings about a moderate
degree of resistance.
Resistance is
also brought about by an efflux pump that actively rids the cells
of the macrolide. This efflux pump is chromosomally mediated by
genes referred to as acrAB
genes. Resistance of Pseudomonas species and other
Gramnegative bacteria, enterococci and staphylococci may be
precipitated by chromosomally controlled alteration of permeability
or uptake of the drug.
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5.2
|
Pharmacokinetic properties
Absorption: When administered to pigs
via the oral route at a dose of 400 ppm in the feed
(equivalent to approximately 21.3 mg/kg/day), tilmicosin moves
rapidly out of the serum into areas of low pH. The highest
concentration in the serum (0.23±0.08 µg/ml) was recorded on
day 10 of medication, but concentrations above the limit of
quantification (0.10 µg/ml) were not found in 3 out of 20
animals examined. Lung concentrations increased rapidly between
days 2 and 4, but no significant changes were obtained following
four days of dosing. The maximum concentration in lung tissue
(2.59±1.01 µg/ml) was recorded on day 10 of
medication.
Distribution: Following oral
administration, tilmicosin is distributed throughout the body, but
especially high levels are found in the lung and in lung tissue
macrophages. It is also distributed in the liver and kidney
tissues.
Biotransformation: Several
metabolites are formed, the predominant one being identified as T1.
However the bulk of the tilmicosin is excreted
unchanged.
Elimination: Following oral
administration, tilmicosin is excreted mainly via the bile into the
faeces, but a small proportion is excreted via the
urine.
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6.
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PHARMACEUTICAL PARTICULARS
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6.1
|
List of excipients
Corn cobs
Liquid paraffin
Macrogolglycerol
ricinoleate
Phosphoric acid, concentrated
for pH adjustment
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6.2
|
Incompatibilities
Do not mix into feed containing
bentonite.
In the absence of compatibility
studies, this veterinary medicinal product must not be mixed other
veterinary medicinal products
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6.3
|
Shelf life
Shelf-life of the veterinary
medicinal product as packaged for sale: 3 years.
Shelf life after first opening
the container: 3 months.
Feed to which the oral granules
has been added should be replaced if not consumed within 24
hours.
Store in the original container
in order to protect from moisture.
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6.4
|
Special precautions for
storage
Do not store above 30ºC. Store
in the original container in order to protect from moisture.
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6.5
|
Nature and composition of
immediate packaging
Pack of 0.25 kg or 1 kg in
a polyethylene-lined 3-ply paper bag
Not all pack sizes may be
marketed
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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 material derived from such veterinary medicinal
product should be disposed of in accordance with local
requirements.
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7.
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MARKETING AUTHORISATION
HOLDER
Huvepharma N.V.
Uitbreidingsstraat 80
2600 Antwerpen
Belgium
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8.
|
MARKETING AUTHORISATION
NUMBER
Vm
30282/4015
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9.
|
DATE OF FIRST AUTHORISATION
14 October 2009
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10.
|
DATE OF REVISION OF THE TEXT
July 2014
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PROHIBITION OF SALE, SUPPLY
AND/OR USE
On veterinary prescription.
|
25/07/2014