ANNEX I
SUMMARY OF PRODUCT CHARACTERISTICS
1.
Yarvitan 5 mg/ml oral solution for dogs
2.
Active substance:
Mitratapide 5 mg/ml
Excipient(s):
Butylated hydroxyanisole (E 320) 2 mg/ml
For a full list of excipients, see section 6.1
3.
Oral solution.
A colourless to slightly yellow solution.
4.
Dogs.
As an aid in the management of overweight and obesity in adult dogs. To be used as part of an overall
weight management programme which also includes appropriate dietary changes. Introducing
appropriate lifestyle changes (e.g. increased exercise), in conjunction with this weight management
programme, may provide additional benefits.
Do not use in dogs with impaired liver function.
Do not use in case of hypersensitivity to the active substance or to any of the excipients.
Do not use in dogs during pregnancy and lactation.
Do not use in dogs less than 18 months of age.
Do not use in dogs in which overweight or obesity is caused by a concomitant systemic disease such
as hypothyroidism or hyperadrenocorticism.
None.
2/20
The use in dogs for breeding purposes has not been evaluated.
If vomiting, significantly reduced appetite or diarrhoea repeatedly occurs, treatment should be
interrupted and the advice of a veterinarian should be sought. Where treatment is interrupted due to
vomiting, it is recommended that when treatment is resumed, the product should be administered after
a meal. In addition, treatment should be interrupted and the advice of a veterinarian should be sought
where the observed body weight loss is severe and rapid.
Special precautions to be taken by the person administering the veterinary medicinal product to
animals
In case of accidental self-administration, seek medical advice immediately and show the package
leaflet or the label to the physician.
If accidental eye contact occurs, flush immediately with copious amounts of water.
A decreased appetite may occur during treatment. This is related to the mode of action of the product
and should not be considered as an adverse reaction unless it becomes very significant.
Vomiting, diarrhoea or softened stools may occur during treatment. In most cases, these effects are
mild and transient. In case an adverse reaction repeatedly occurs or in case the dog stops eating for
two consecutive days, treatment should be interrupted and the advice of a veterinarian should be
sought. In laboratory studies, decreases in serum albumin, globulin, total protein, calcium and alkaline
phosphatase and increases in ALT and AST were detected following administration of the product at
the recommended treatment dose. In addition, hyperkalaemia was occasionally observed. Generally,
the severity of these effects increased with increasing dose. Typically, these findings normalised, or
appeared to be reversing, within two weeks following the end of treatment.
The following adverse reactions were observed during the clinical trials (pooled data*):
Clinical observation
Mitratapide
Placebo
vomiting : occasional (
≤
3x)
20.0%
5.6 %
vomiting : repeated (> 3 x)
10.0 %
2.2 %
diarrhoea / soft stools
10.0%
4.4 %
anorexia / decreased appetite
17.8%
10.0 %
lethargy / weakness
5.2%
2.2 %
* data from 360 dogs over the whole treatment period.
Do not use in dogs during pregnancy and lactation.
No drug interactions were observed in studies where Yarvitan was administered concomitantly with
NSAIDs (carprofen, meloxicam) or ACE inhibitors (enalapril, benazepril). Interactions with other
drug types were not specifically investigated. The absorption of lipid soluble drugs used concomitantly
with mitratapide has not been investigated. Therefore, for dogs receiving treatments in addition to the
product, drug interactions should be monitored closely.
3/20
Administer orally once daily at 0.63 mg mitratapide/kg bodyweight (1 ml of the product per 8 kg)
given for 2 periods of 21 days with 14 days without treatment in between. In order to allow proper
dosing, the dog should be weighed on day 1 and on day 35 (i.e. at the start of each treatment period).
Treatment should be given with food. Use the dosing pipette as provided with the product.
During the first 21 days of treatment, the quantity of food the animal receives may remain unchanged.
Thereafter, feeding should be in accordance with energy requirements for maintenance (to be
calculated by the veterinarian). This can be achieved either with a regular pet food or with a low
calorie (diet) pet food.
In clinical trials, treated animals rapidly regained weight following cessation of treatment when diet
was not restricted. In order to avoid this rebound weight gain, it is necessary to continue the feeding
for maintenance regimen after the end of treatment with the product.
Mitratapide therapy should be restricted to one treatment course for an individual dog.
The following clinical signs were observed after 3 or 5 times overdosing in dogs: softened or liquid
faeces, vomiting, salivation, anorexia, severe weight loss, emaciated appearance, dehydration and pale
mucosae.
In case of accidental overdosing, symptomatic therapy should be administered. No specific antidote is
available.
Not applicable.
5.
Pharmacotherapeutic group: Peripherally acting antiobesity products, ATCvet Code: QA08AB90
5.1 Pharmacodynamic properties
Mitratapide is a potent inhibitor of the microsomal triglyceride transfer protein (MTP). Administration
of mitratapide to dogs results in reduced uptake of dietary lipids, dose dependent decreases in serum
cholesterol and triglyceride and an increased presence of triglyceride containing droplets in
enterocytes. It is assumed that these effects are mediated by MTP inhibition at the level of the
enterocyte. This results in blockage of the uptake of dietary lipids. Mitratapide also has a slight
appetite decreasing effect, which is linked to its mode of action. Accumulation of triglycerides inside
the enterocytes may be followed by decreased appetite. Mitratapide has no central effect.
In clinical trials, the following weight loss percentages were obtained:
Percentages of dogs per weight loss category for mitratapide versus placebo:
% of treated dogs*
weight loss category
EU field trial
US field trial
pooled data
placebo
mitratapide
placebo
mitratapide
placebo
mitratapide
≥
10 %
6.8
25.2
9.5
22.5
8.1
23.8
≥
7.5 %
11.4
41.7
11.9
47.3
11.6
44.5
≥
5 %
22.7
63.8
31.0
65.1
26.7
64.4
* : in line with the recommended treatment schedule
4/20
5.2 Pharmacokinetic particulars
Laboratory animals and dogs rapidly absorb orally administered mitratapide. The most important
metabolic transformation is sulphoxidation, which produces three active metabolites. Following oral
administration, the bioavailability of mitratapide (parent compound and metabolites) is in the range
from 55 to 69%, the volume of distribution is approximately 5 l/kg. Mitratapide and its metabolites
bind very extensively (> 99 %) to plasma proteins and distribute to the tissues. After multiple dosing,
the highest concentrations are present in the adrenal glands, liver, jejunum and kidney, but there is no
exposure in the brain, excluding any central effect of the product. Excretion is rapid and mainly via the
faeces.
g/ml attained 3.5 hours after dosing; the
sulphoxide metabolites reach maximum concentration of on average 0.0136
µ
µ
g/ml and 0.0168
µ
g/ml,
g/ml after
17.5 hours. At the end of a three week dosing period, mitratapide attains average steady-state
concentrations of 0.0068
µ
µ
g/ml, the sulphoxide metabolites 0.0089
µ
g/ml and 0.0167
µ
g/ml,
g/ml. The terminal plasma half-life is 6.3 hours for mitratapide,
9.8 hours and 11.7 hours for the sulphoxides, respectively, and 44.7 hours for the sulphone metabolite.
The pharmacokinetic parameters display variable dependency on dose and vary slightly between the
first and the second three week treatment periods of a complete treatment schedule.
µ
6.
6.1 List of excipients
Sucralose
Butylated hydroxyanisole
Macrogol 400
6.2 Incompatibilities
None known.
6.3 Shelf life
Shelf-life of the veterinary medicinal product as packaged for sale: 3 years
Shelf-life after first opening the immediate packaging: 3 months
6.4 Special precautions for storage
Do not refrigerate.This veterinary medicinal product does not require any special storage conditions.
After each dose, the pipette should be washed and dried and the bottle cap screwed back on tightly.
6.5 Nature and composition of immediate packaging
55, 120 or 210 ml amber glass bottle (type III) with a child resistant polypropylene closure and dosing
pipette. The dosing pipette has a gradation in body weight:
•
up to 36 kg for the 55 ml bottle
•
up to 36 kg for the 120 ml bottle
•
up to 48 kg for the 210 ml bottle
Not all pack sizes may be marketed.
5/20
In fed dogs, a single dose of 0.63 mg mitratapide/kg bodyweight results in maximum concentrations of
the parent substance in plasma of on average 0.012
respectively after 6.5 hours and 8.5 hours; the sulphone metabolite reaches 0.0092
respectively, the sulphone 0.0471
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.
Janssen Pharmaceutica N.V.
Turnhoutseweg 30
B-2340 Beerse
Belgium
8.
EU/2/06/063/001-3
9.
14/11/2006
PROHIBITION OF SALE, SUPPLY AND/OR USE
Not applicable.
Detailed information on this veterinary medicinal product is available on the website of the European
Medicines Agency (EMEA)
http://www.emea.europa.eu/
6/20
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
7/20
A. MANUFACTURING AUTHORISATION HOLDER(S) RESPONSIBLE FOR BATCH
RELEASE
Name and address of the manufacturer(s) responsible for batch release
Janssen Pharmaceutica N.V.
Turnhoutseweg 30
B-2340 Beerse
Belgium
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
Not applicable.
8/20
ANNEX III
LABELLING AND PACKAGE LEAFLET
9/20
A. LABELLING
10/20
PARTICULARS TO APPEAR ON THE OUTER PACKAGE
CARTON
1.
Yarvitan 5 mg/ml oral solution for dogs
2.
STATEMENT OF ACTIVE AND OTHER SUBSTANCES
Mitratapide 5 mg/ml
3.
Oral solution.
4.
PACKAGE SIZE
55 ml:
≤
10 kg BW
120 ml:
≤
22 kg BW
210 ml:
≤
40 kg BW
5.
Dogs
6.
As an aid in the management of overweight and obesity in adult dogs.
7.
METHOD AND ROUTE(S) OF ADMINISTRATION
Oral use.
8.
9.
SPECIAL WARNING(S), IF NECESSARY
Read the package leaflet before use.
11/20
10. EXPIRY DATE
EXP:
Once opened, use within 3 months.
11. SPECIAL STORAGE CONDITIONS
Do not refrigerate.
12. SPECIAL PRECAUTIONS FOR THE DISPOSAL OF UNUSED PRODUCTS OR
WASTE MATERIALS, IF ANY
Any unused veterinary medicinal product or waste materials derived from such veterinary medicinal
product should be disposed of in accordance with local requirements.
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.
Janssen Pharmaceutica N.V.
B-2340 Beerse, Belgium
EU/0/00/000/001
55 ml
EU/0/00/000/002
120 ml
EU/0/00/000/003
210 ml
17. MANUFACTURER’S BATCH NUMBER
Lot
12/20
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS
LABEL AMBER GLASS BOTTLE 55 ML
1.
Yarvitan 5 mg/ml oral solution for dogs
2.
QUANTITY OF THE ACTIVE SUBSTANCE(S)
Mitratapide 5 mg/ml
3.
CONTENTS BY WEIGHT, BY VOLUME OR BY NUMBER OF DOSES
55 ml
4.
ROUTE(S) OF ADMINISTRATION
Oral use.
5.
6.
BATCH NUMBER
Lot:
7.
EXPIRY DATE
EXP {month/year}
Once opened, use within 3 months.
8.
THE WORDS “FOR ANIMAL TREATMENT ONLY”
For animal treatment only.
13/20
PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGE
LABEL AMBER GLASS BOTTLE 120 and 210 ml
1.
Yarvitan 5 mg/ml oral solution for dogs
2.
STATEMENT OF ACTIVE AND OTHER SUBSTANCES
Mitratapide 5 mg/ml
3.
Oral solution
4.
PACKAGE SIZE
120 ml
210 ml
5.
Dogs
6.
7.
METHOD AND ROUTE(S) OF ADMINISTRATION
Oral use.
8.
9.
SPECIAL WARNING(S), IF NECESSARY
Read the package leaflet before use.
14/20
10. EXPIRY DATE
EXP:
Once opened, use within 3 months.
11. SPECIAL STORAGE CONDITIONS
Do not refrigerate
12. SPECIAL PRECAUTIONS FOR THE DISPOSAL OF UNUSED PRODUCTS OR
WASTE MATERIALS, IF ANY
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”
Janssen Pharmaceutica N.V.
B-2340 Beerse, Belgium
EU/0/00/000/002
120 ml
EU/0/00/000/003
210 ml
17. MANUFACTURER’S BATCH NUMBER
Lot:
15/20
B. PACKAGE LEAFLET
16/20
PACKAGE LEAFLET
Yarvitan 5 mg/ml oral solution for dogs
Read all of this leaflet carefully before you start administering the medicine to your dog:
•
Keep this leaflet. You may need to read it again
•
If you have further questions, please ask your veterinary surgeon or your pharmacist
•
This medicine has been prescribed for your dog only and you should not pass it on to others.
1.
THE MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH
RELEASE, IF DIFFERENT
Janssen Pharmaceutica N.V.
Turnhoutseweg 30
B-2340 Beerse
Belgium
2.
Yarvitan 5 mg/ml oral solution for dogs
Mitratapide
3.
STATEMENT OF THE ACTIVE SUBSTANCE(S) AND OTHER INGREDIENT(S)
Mitratapide 5 mg/ml
Butylated hydroxyanisole (E 320)
Yarvitan is a colourless to slightly yellow solution.
4.
Yarvitan is indicated as an aid in the management of overweight and obesity in adult dogs. The
treatment is part of an overall weight management programme which also includes a nutrition
programme. Introducing appropriate lifestyle changes (e.g. increased exercise), in conjunction with
this weight management programme, may provide additional benefits.
5.
Do not administer Yarvitan:
•
if your dog has impaired liver function.
•
if your dog is hypersensitive (allergic) to mitratapide or to any of the other ingredients.
•
if your dog is pregnant or during lactation.
•
in dogs less than 18 months of age.
•
if overweight or obesity in your dog is caused by a concomitant systemic disease such as
hypothyroidism (this is due to a malfunction of the thyroid gland) or hyperadrenocorticism.(this
is due to a malfunction of the adrenal gland).
17/20
6.
Tell your veterinary surgeon if you notice any of the following:
•
significant loss of appetite. Loss of appetite may occur during treatment. This is related to the
mode of action of the product and should not be considered as a side effect, unless it becomes
very significant (this is when your dog stops eating for two consecutive days).
•
vomiting
•
diarrhoea
•
softened stools
In most of the cases, these side effects are mild and do not last very long. In case a side effect
repeatedly occurs or in case the dog stops eating for two consecutive days, stop the administration of
Yarvitan to your dog and seek the advice of your veterinary surgeon as soon as possible. In laboratory
studies, decreases in serum albumin, globulin, total protein, calcium and alkaline phosphatase and
increases in ALT and AST were detected following administration of the product at the recommended
treatment dose. In addition, hyperkalaemia was occasionally observed. Generally, the severity of these
effects increased with increasing dose. Typically, these findings normalised, or appeared to be
reversing, within two weeks following the end of treatment.
If you notice any serious effects or other effects not mentioned in this leaflet, please inform your
veterinary surgeon.
7.
Dogs.
8.
DOSAGE FOR EACH SPECIES, ROUTE(S) AND METHOD OF ADMINISTRATION
Always administer Yarvitan exactly as your veterinary surgeon has instructed you. You should check
with your veterinary surgeon if you are unsure. The usual dose is once daily 0.63 mg mitratapide/kg
bodyweight (1 ml of the product per 8 kg). The dosing pipettes provided with the product show
graduations corresponding to the correct body weight of the dog.
Administer the product orally during 2 periods of 21 days with an interval of 14 days without
treatment in between.
Day 1-21
Day 22-35
Day 36-56
treatment
no treatment
treatment
normal feeding
nutrition programme
nutrition programme
9.
ADVICE ON CORRECT ADMINISTRATION
In order to allow proper dosing, the dog should be weighed on day 1 and day 35 (this is at the start of
each treatment period).
Use the dosing pipette as provided with the product. Fill the syringe by pulling the plunger until it
reaches the mark on the dosing pipette corresponding to the correct body weight of the dog.
Treatment should be given with food. Therefore, administer the product with the syringe onto a
portion of the food. Once the dog has eaten the complete portion, give the remaining amount of food
to the dog.
After each dose, the syringe should be removed from the bottle. The pipette should be washed and
dried and the cap should be screwed back on tightly.
18/20
During the first 21 days of treatment, the quantity of food the animal receives may remain unchanged.
Thereafter, your dog should follow a nutrition programme. Your veterinary surgeon will advise you on
the type of food your dog will need. This can be achieved either with a regular pet food or with a low
calorie (diet) pet food.
In order to avoid rebound weight gain, it is necessary to continue the feeding for maintenance regimen
after the end of treatment with the product.
Mitratapide therapy should be restricted to one treatment course for an individual dog.
10. WITHDRAWAL PERIOD
Not applicable.
11. SPECIAL STORAGE PRECAUTIONS
Keep out of the reach and sight of children.
Do not refrigerate.
This veterinary medicinal product does not require any special storage conditions.
Do not use after the expiry date stated on the label and carton (EXP.).
Shelf-life after first opening the container: 3 months.
12. SPECIAL WARNING(S)
The safety of the veterinary medicinal product has not been established during pregnancy and
lactation. The use in dogs for breeding purposes has not been evaluated.
Please inform your veterinary surgeon if your dog is taking or has recently taken any other medicines,
even those not prescribed. No drug interactions were observed in studies where Yarvitan was
administered concomitantly with NSAIDs (carprofen, meloxicam) or ACE inhibitors (enalapril,
benazepril). The absorption of lipid soluble drugs used concomitantly with mitratapide has not been
investigated. Your veterinary surgeon should monitor closely the intake of any other medicines in
addition to the product.
In case vomiting, diarrhoea, softening stools repeatedly occurs or in case the dog stops eating for two
consecutive days, stop the administration of Yarvitan to your dog and seek the advice of your
veterinary surgeon as soon as possible. Where treatment is interrupted due to vomiting, it is
recommended that when treatment is resumed, the product should be administered after a meal. In
addition, treatment should be interrupted and the advice of a veterinarian should be sought where the
observed body weight loss is severe and rapid.
In case of accidental overdosing, symptomatic therapy should be administered. No specific antidote is
available.
Special precautions to be taken by the person administering the veterinary medicinal product to
animals
In case of accidental self-administration, seek medical advice immediately and show the package
leaflet or the label to the physician.
If accidental eye contact occurs, flush immediately with copious amounts of water.
19/20
13. SPECIAL PRECAUTIONS FOR THE DISPOSAL OF UNUSED PRODUCT OR WASTE
MATERIALS, IF ANY
Medicines should not be disposed of via wastewater or household waste.
Ask your veterinary surgeon 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
07/2007
Detailed information on this product is available on the website of the European Medicines Agency
(EMEA)
http://www.emea.europa.eu/
15. OTHER INFORMATION
Pack sizes – amber glass bottles containing : 55ml:
≤
10 kg bodyweight, 120ml:
≤
22 kg bodyweight,
40 kg bodyweight.
Not all pack sizes may be marketed.
≤
20/20
210ml:
Source: European Medicines Agency
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