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Masivet Tablets for Dogs

Masivet Tablets for Dogs
50mg Tablets » Pot of 30

  • 50mg Tablets » Pot of 30 £54.99
  • 150mg Tablets » Pot of 30 £119.99

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Description

If you live in the United States then it is still possible to buy Kinavet (licensed as Masivet in the UK) from VioVet.

We can accept a prescription from a US veterinary surgeon under a USDA permit obtained by VioVet. We have a template and description of the prescription process on our website here. We would need your vet to date, sign and stamp the prescription, which must also include pet details, product name, strength and dosage. We would recommend that you scan/photograph and then email your completed prescription from your vet to us on [email protected] or upload a file directly via your account on our website.

Orders must be placed by the owner of the dog being treated - we cannot supply veterinary surgeries with Masivet under any circumstances due to FDA / USDA regulations. We also require a specific written order from a licensed veterinarian stating that the animal should receive the unapproved product and provide a justification for the use of the unapproved drug. We also need an explanation as to why Masivet must be prescribed instead of an alternative medication.

We strongly recommend that you look into import regulations affecting you before placing an order. Royal Mail parcels are not routinely checked by customs but any regulations are applied by customs if they inspect a parcel. We will include all relevant documentation as required by our USDA Import Permit for Masivet with every order to smooth the importation process however the FDA may charge a $22.00 Adminsitration Fee for clearance of the documentation. This will be payable, if requested, to the UPS driver on delivery and is a Federal charge not a VioVet or UPS charge. Please be aware that Royal Mail Air Mail is an untracked service. We can offer delivery with UPS, which offers a tracking service and a quicker estimated delivery time, often under one week. The option for shipping with UPS will be available on orders only containing Masivet.

We can only send a maximum of a three month supply per animal per order. You will be contacted if your order exceeds this and your order will be amended to the appropriate quantity.

Orders can be placed on our website and payment can be made by card, PayPal or direct bank transfer (2.5% fee for for PayPal). Unfortunately we are unable to quote in US dollars- your card provider will be able to tell you the conversion rate they are currently using and will automatically take the correct amount for the payment.

If you would like any further information then email us at [email protected] and we'll do our best to help.

Masivet (licensed as Kinavet in the USA) is supplied as a tablet for use against a certain type of cancer affecting dogs. Masivet is regarded as safe enough to be used at home, and is given as a tablet once daily. It acts against mast cell tumours, by inhibiting cell division, therefore preventing further development of the tumours. Not all dogs respond, but the results can be very helpful for others. Close veterinary supervision is recommended at all times and Masivet is prescription only.

What is Masivet?


Masivet contains masitinib, which belongs to a class of medicines having an anticancer action. It is available as round, orange tablets (50 and 150 mg).

What is Masivet used for?

Masivet is used to treat dogs with mast-cell tumours (a type of cancer). It is used for tumourswhich are severe in character (grade 2 or 3) and which cannot be removed with surgery. It isonly used if the presence of a mutated form of the receptor protein c-kit in the tumours hasbeen confirmed before the start of treatment.
The tablets are given by mouth, once a day. The dose depends on the weight of the dog beingtreated.. The duration of treatment depends on the dog’s response to treatment.

How does Masivet work?

The active substance in Masivet, masitinib, is aprotein-tyrosine kinase inhibitor. This meansthat it blocks some specific enzymes known astyrosine kinases. These enzymes can be foundin some receptors on the surface of cells, including the c-kit receptor. Some types of mast-celltumour are linked to a mutation that causes excessive action of c-kit and stimulates the mastcells to divide uncontrollably. By blocking these receptors, Masivet might help to control celldivision, preventing further development of the tumours with this particular mutation.

How has Masivet been studied?

A number of studies with Masivet were carried out either in laboratory dogs or in animalpatients at veterinary practises in Europe and in the USA. The main study compared theeffectiveness of Masivet at the recommended dose of 12.5 mg per kilogramme bodyweightonce a day with placebo (a dummy treatment). The study included dogs of various breeds andboth sexes with mast-cell tumours that had come back after surgery or could not be removedwith surgery. The study population included dogs whose tumours contained mutated ornormal (‘wild-type’) c-kit receptors.


What is the risk associated with Masivet?


The most common side effects with Masivet are gastrointestinal reactions (diarrhoea andvomiting) and hair loss. These reactions are usually mild to moderate and temporary, last forup to four weeks. Dogs under Masivet treatment should be regularly monitored for side effectsby the veterinarian (at least monthly). In case of side effects, the veterinarian might decide tolower the dose of Masivet or to discontinue treatment.
Masivet must not be used in dogs with certain kinds of liver or kidney problems, or anaemia (low red blood cell counts) or neutropenia (low white blood cell counts). It must not be used in dogs less than six months of age or less than 4kg in weight, or bitches that are pregnant or lactating. It should not be used in dogs that may be hypersensitive (allergic) to masitinib orany of the other ingredients. For a full list of all side-effects reported with Masivet, see the Package Leaflet.
Four to six weeks after starting the treatment with Masivet, the veterinarian should check ifthe treatment is likely to be successful.

What are the precautions for the person who gives the medicine or comes into contact with theanimal?

The tablets must be administered whole and should not be divided, broken or ground up. If broken tablets, or the vomit, urine or faeces of a treated dog comes into contact with the skinor eyes, rinse immediately with plenty of water. Children should not have close contact with treated dogs, or their faeces or vomit. If Masivet is taken accidentally, seek medical advice immediately and show the Package Leaflet or the label to the doctor. Do not eat, drink or smoke while treating a dog. For more information, see the Package Leaflet.


Why has Masivet been approved?

The Committee for Medicinal Products for Veterinary Use (CVMP) concluded that thebenefits of Masivet exceed the risks for the treatment of non-resectable mast cell tumours(grade 2 or 3) that have a confirmed mutated c-kit tyrosine kinase receptor and recommended that Masivet be given a marketing authorisation. The benefit-risk balance may be found inmodule 6 of this EPAR.

Other information about Masivet

The European Commission granted a marketing authorisation valid throughout the European Union, for Masivet to AB Science S.A. on 17 November 2008. Information on the prescriptionstatus of this product may be found on the label/outer package. Because this disease is a life threatening condition and the overall number ofdogs affected is expected to be low, the CVMP guidelines on “Minor-Use-Minor-Species (MUMS) data requirements” were applied when assessing the dossier.

This summary was last updated on May 2009.

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Medication Datasheets

150mg Tablets » Pot of 30

SUMMARY OF PRODUCT CHARACTERISTICS

1. NAME OF THE VETERINARY MEDICINAL PRODUCT

MASIVET 50 mg film-coated tablets for dogs
MASIVET 150 mg film-coated tablets for dogs

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each film-coated tablet contains:
Active substance:
Masitinib 50 mg (equivalent to masitinib mesylate 59.6 mg)
Masitinib 150 mg (equivalent to masitinib mesylate 178.9 mg)

Excipients.

For a full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Film-coated tablet
Light-orange, round shape, film-coated tablet embossed with "50" or "150" on one side and the
company logo on the other side.

4. CLINICAL PARTICULARS

4.1 Target species

Dogs.

4.2 Indications for use, specifying the target species

Treatment of non-resectable dog mast cell tumours (Grade 2 or 3) with confirmed mutated c-kit
tyrosine kinase receptor.

4.3 Contraindications

Do not use in pregnant or lactating bitches (see section 4.7).
Do not use in dogs less than 6 months of age or less than 4 kg body weight.
Do not use in dogs suffering from liver impairment, defined as AST or ALT > 3 x Upper Limit of
Normal (ULN). Do not use in dogs suffering from renal function impairment, defined as Urinary
Protein Creatinine (UPC) ratio > 2 or albumin < 1 x Lower Limit of Normal (LLN).
Do not use in dogs with anaemia (haemoglobin < 10 g/dl).
Do not use in dogs with neutropenia defined as absolute neutrophil count < 2,000 /mm3.
Do not use in case of hypersensitivity to the active substance or to any of the excipients.

4.4 Special warnings

For any mast cell tumour treatable by surgery, surgery should be the first choice of treatment.
Masitinib treatment should only be used in dogs with non-resectable mast cell tumours and which
express the mutated c-kit tyrosine kinase receptor. The presence of a mutated tyrosine kinase c-kit
receptor must be confirmed prior to treatment (see also section 5.1).

4.5 Special precautions for use

Special precautions for use in animals

Dogs should be carefully monitored and treatment might need to be adjusted or discontinued, if
necessary.

Monitoring of renal function
Renal function should be adequately monitored every month using dipstick urine testing.
In case of positive semiquantitative dipstick results (protein > 30 mg/dl), urinalysis should be
performed to determine urinary protein creatinine (UPC) ratio, and a blood sample to measure
creatinine, albumin and BUN.
If UPC ratio > 2, or creatinine > 1.5 upper limit of normal (ULN), or albumin < 0.75 lower limit of
normal (LLN) or blood urea nitrogen (BUN) > 1.5 ULN, discontinue treatment.

Monitoring of Protein loss syndrome
Perform every month a dipstick urine test. In case of positive semi-quantitative dipstick results
(protein 30 mg/dl), perform urinalysis to determine urinary protein creatinine (UPC) ratio.
Perform every month a blood measurement of albumin.
In case of UPC ratio > 2 or albumin < 0.75 lower limit of normal (LLN), treatment should be
interrupted until albumin and UPC values have returned to limit value (UPC ratio < 2 and
albumin > 0.75 LLN), treatment can then be continued at the same dose.
If of one of these events (UPC ratio > 2 or albumin < 0.75 LLN) occurs for a second time,
treatment should be permanently discontinued.

Anaemia and/or haemolysis
Dogs should be carefully monitored for signs of (haemolytic) anaemia. In case of clinical signs of
anaemia or haemolysis, haemoglobin, free bilirubin and haptoglobin should be measured and blood
cell counts (including reticulocyte) should be performed.
Treatment should be discontinued in case of:
Haemolytic anaemia, i.e. haemoglobin < 10 g/dl and haemolysis,
i.e. free bilirubin > 1.5 ULN and haptoglobin < 0.1 g/dl,
Anaemia due to lack of regeneration, i.e. haemoglobin< 10 g/dl and
reticulocytes < 80,000/mm3.

Hepatic toxicity (ALT or AST elevation), neutropenia
In case of an increase of ALT or AST > 3 ULN, decrease of neutrophil count < 2,000/mm3 or any
other severe adverse events, treatment should be modified as follows:
At the first occurrence, treatment should be interrupted until resolution, and then resumed at the same
dose level;
At the second occurrence of the same event, treatment should be interrupted until resolution; treatment
should then be continued with a reduced dose of 9 mg/kg bodyweight/day;
At the third occurrence of the same event, treatment should be interrupted until resolution; treatment
should then be continued with a dose further reduced to 6 mg/kg/day;
Treatment should be discontinued, if severe adverse reactions are still encountered at the 6 mg/kg/day
dose.

Other precautions
Treatment should be permanently discontinued in case of renal toxicity, immune-mediated haemolytic
anaemia (IMHA) and/or anaemia due to lack of regeneration, and if severe neutropenia, and/or severe
diarrhoea and/or severe vomiting persist after dose reduction.

Dogs should not be used for breeding while under treatment.

Summary of thresholds for laboratory evaluations resulting in contra-indication or
treatment modification (interruption, dose reduction or discontinuation)

Management of Hepatic Toxicity (ALT or AST)
Contra-indication Interruption Dose reduction Discontinuation

3 ULN > 3ULN > 3 ULN > 3ULN
(1st time) (2nd/3rd time) (4th time)
Management of Neutropenia (neutrophil counts)
Contra-indication Interruption Dose reduction Discontinuation
< 2,000/mm3 < 2,000/mm3 < 2,000/mm3 < 2,000/mm3
(1st time) (2nd/3rd time) (4th time)
Management of Protein-Loss Syndrome (Albuminemia and/or UPC)
Contra-indication Interruption Dose reduction Discontinuation
Albumin < 1 LLN Albumin < 0.75 LLN Not applicable Albumin < 0.75 LLN
or UPC > 2 or UPC >2 or UPC > 2
st
(1 time) (2nd time)
Management of Haemolytic and aregenerative Anaemia
(haemoglobin, bilirubin, haptoglobin, reticulocytes)
Contra-indication Interruption Dose reduction Discontinuation
Haemoglobin Not applicable Not applicable Haemoglobin < 10 g/dl
< 10 g/dL and either
free bilirubin > 1.5 ULN and
haptoglobin < 0.1 g/dl
or reticulocytes < 80,000/mm3

Special precautions to be taken by the person administering the veterinary medicinal product to
animals

Repeated dermal contact with masitinib may impair female fertility and foetal development.
The active substance of Masivet can cause skin sensitisation.
Avoid skin contact with faeces, urine, and vomit of treated dogs.
Wear protective gloves while disposing of vomit, urine or faeces of treated dogs.
If broken tablets, vomit, urine or faeces of treated dogs come into contact with the skin, rinse
immediately with plenty of water.

The active substance of Masivet can cause severe eye-irritation and serious damage to the eyes.
Avoid contact with the eyes.
Take care not to touch the eyes before gloves have been removed and disposed of and the
hands have been thoroughly washed.
If the product comes into contact with the eyes, rinse immediately with plenty of water.
People with known hypersensitivity to masitinib should not handle the product.
In case of accidental ingestion, seek medical advice immediately and show the package leaflet or the
label to the physician. Do not eat, drink, or smoke when treating the dog.
Children should not have close contact to treated dogs, treated dog faeces or vomit.

4.6 Adverse reactions (frequency and seriousness)

Very common
Mild to moderate gastrointestinal reactions (diarrhoea and vomiting) with a mean duration of
approximately 21 and 9 days, respectively.
Mild to moderate alopecia with a mean duration of approximately 26 days.

Common
Severe renal toxicity may occur in dogs suffering from renal disorders at the start of treatment
(including high blood creatinine level or proteinuria).
Moderate to severe anaemia (aplastic/haemolytic) with a mean duration of approximately 7 days.
Protein-loss syndrome (mainly due to a decrease in serum albumin).

Mild or moderate neutropenia with a mean duration of approximately 24 days.
Increase in aminotransferase (ALT or AST) with a mean duration of approximately 29 days.
Specific measures to be taken in case of the above reactions are described in section 4.5.

Other commonly observed adverse reactions were in most cases mild or moderate:
Lethargy and asthenia with a mean duration of approximately 8 and 40 days, respectively.
Decrease in appetite or anorexia with a mean duration of 45 days and 18 days, respectively.
Cough (mean duration 23 days).
Lymphadenopathy (mean duration 47 days).
Oedema (mean duration of oedema was 7 days).
Lipoma (mean duration 53 days).

The frequency of adverse reactions is defined using the following convention:
- very common (more than 1 in 10 animals displaying adverse reaction(s) during the course of
one treatment)
- common (more than 1 but less than 10 animals in 100 animals)

4.7 Use during pregnancy, lactation or lay

Do not use in pregnant or lactating bitches. Laboratory studies in rats have shown evidence of
impaired female fertility at dose of 100 mg/kg/day, embryotoxicity and developmental toxicity at dose
above 30 mg/kg/day. Studies in rabbits did however not reveal embryotoxicity or developmental
toxicity.

4.8 Interaction with other medicinal products and other forms of interaction

In vitro tests with human microsomes demonstrate that concomitant treatment with substances which
are metabolised by CYP450 isoforms may result in higher or lower plasma levels of either masitinib or
those substances. No corresponding information is available for dogs. Hence, caution is advised with
the concurrent use of masitinib and other substances.
Concurrent use of other substances with a high degree of protein binding may compete with masitinib
binding and thus cause adverse effects.
The efficacy of Masivet might be reduced in dogs previously treated with chemotherapy and/or
radiotherapy. No information relating to potential cross-resistance with other cytostatic products is
available.

4.9 Amounts to be administered and administration route

For oral use.

The recommended dose is 12.5 mg/kg (with a dose range of 1114 mg/kg) once daily as presented in
the table below.

In dogs with a bodyweight of less than 15 kg accurate dosing is not always possible. These dogs may
be treated with either 50, 100 or 150 mg, if it is feasible to achieve a target dose of 1114 mg/kg bw.

The tablets must be administered as a whole and should not be divided, broken or ground. If a broken
tablet is rejected by the dog after chewing, it should be disposed of.
Tablets should always be administered in the same manner, with food.

12.5 mg/kg bw Number of tablets per day Dose mg/kg
Dog body-weight in kg 50 mg 150 mg lower weight upper weight

15 18 1 plus 1 13.7 11.1
18 22 2 plus 1 13.9 11.4
22 26 2 13.6 11.5
26 30 1 plus 2 13.5 11.7
30 34 2 plus 2 13.3 11.8
34 38 3 13.2 11.8
38 42 1 plus 3 13.2 11.9
42 46 2 plus 3 13.1 12.0
46 50 4 13.0 12.0
50 54 1 plus 4 13.0 12.0
54 58 2 plus 4 13.0 12.1
58 62 5 12.9 12.1
62 66 1 plus 5 12.9 12.1
66 70 2 plus 5 12.9 12.1
70 74 6 12.9 12.2
74 78 1 plus 6 12.8 12.2
78 2 plus 6 12.8

If the tablet is regurgitated or vomited within 10 minutes following administration, treatment should
be repeated. If the tablet is regurgitated or vomited later than 10 minutes following administration,
treatment should not be repeated.

The treatment should be reviewed after 4 to 6 weeks in order to assess the initial response. Duration of
treatment depends on the response to treatment. Treatment should be maintained in the case of stable
disease, i.e. static, partial or complete tumour response, provided that the product is sufficiently well
tolerated. In case of tumour progression, treatment is unlikely to be successful and the treatment
should be reviewed.

Dose reduction, treatment interruption and treatment discontinuation:

Dogs should be monitored carefully and professional judgement should be used to determine the need
for dose reduction in the event of possible significant adverse reactions (see section 4.5). Doses can be
reduced to 9 mg/kg bodyweight (range 7.510.5 mg/kg) or 6 mg/kg bw (range 4.57.5 mg/kg)
according to the tables below.
During clinical studies, the daily dose was decreased due to adverse events in approximately 16 % of
treated dogs and mainly due to an increase in transaminases.

9 mg per kg bodyweight once daily as presented in the table below.

Number of tablets per day Dose mg/kg
Dog body-weight in 50 mg 150 mg lower weight upper weight
kg

15.0 19.4 1 10.0 7.7
19.4 25.0 1 plus 1 10.3 8.0
25.0 30.6 2 plus 1 10.0 8.2
30.6 36.1 2 9.8 8.3
36.1 41.7 1 plus 2 9.7 8.4
41.7 47.2 2 plus 2 9.6 8.5
47.2 52.8 3 9.5 8.5
52.8 58.3 1 plus 3 9.5 8.6
58.3 63.9 2 plus 3 9.4 8.6
63.9 69.4 4 9.4 8.6
69.4 75.0 1 plus 4 9.4 8.7
75.0 80.6 2 plus 4 9.3 8.7

6 mg per kg bodyweight once daily as presented in the table below.
Number of tablets per day Dose mg/kg
Dog body-weight in 50 mg 150 mg lower weight upper weight
kg

15.0 20.8 2 6.6 4.8
20.8 29.2 1 7.2 5.1
29.2 37.5 1 plus 1 6.9 5.3
37.5 45.8 2 plus 1 6.7 5.5
45.8 54.2 2 6.5 5.5
54.2 62.5 1 plus 2 6.5 5.6
62.5 70.8 2 plus 2 6.4 5.6
70.8 79.2 3 6.4 5.7
79.2 1 plus 3 6.3

4.10 Overdose (symptoms, emergency procedures, antidotes), if necessary

The recommended daily dose of 12.5 mg/kg body weight corresponds to the Maximum Tolerated
Dose (MTD) that was derived from repeat dose toxicity studies in healthy Beagle dogs.

Overdosing signs were observed in toxicity studies conducted in healthy dogs, treated for 39 weeks at
doses of around 2 times the recommended dose (25 mg masitinib), treated for 13 weeks and 4 weeks at
doses of around 3 times the recommended dose (41.7 mg masitinib), and treated for 4 weeks at doses
of around 10 times the recommended dose (125 mg masitinib). The main target organs of toxicity in
dogs are the gastrointestinal tract, the haematopoetic system, the kidney and the liver.

In case of adverse events following overdose, treatment should be discontinued until resolution, and
then resumed at the recommended therapeutic dose level.

4.11 Withdrawal period(s)

Not applicable.

5. PHARMACOLOGICAL PROPERTIES

Pharmacotherapeutic group: protein-tyrosine kinase inhibitor.
ATCvet code: QL01XE90.

5.1 Pharmacodynamic properties

Masitinib is a protein-tyrosine kinase inhibitor which, in vitro, potently and selectively inhibits the
mutated form, in the juxtamembrane (JM) region, of the c-kit receptor. It also inhibits the Platelet
Derived Growth Factor (PDGF) receptor and the Fibroblast Growth Factor Receptor (FGFR3).

In the pivotal clinical field study, dogs of various breeds, ranging in age from two to seventeen years,
were randomly treated with Masivet at a dose of 12.5 mg/kg or with a placebo. In dogs with non-
resectable mast cell tumours, Grade 2 or 3, expressing a mutated tyrosine kinase c-kit receptor,
treatment with Masivet showed a significantly longer Time-to-Tumour Progression (TTP) with a
median of 241 days as compared to 83 days for placebo. Response to treatment with masitinib was
expressed as stable disease; i.e. static, partial or complete response.

Masitinib treatment should only be used in dogs with non-resectable mast cell tumours, which express
the mutated c-kit tyrosine kinase receptor. The presence of a mutated tyrosine kinase c-kit receptor
must be confirmed prior to treatment.

5.2 Pharmacokinetic particulars

Following oral administration in dogs at a dose of 11.2 mg (0.5 mg) per kg of bodyweight, masitinib
is rapidly absorbed and the time to maximal concentration (Tmax) is approximately 2 hours. The
elimination half-life (t) is approximately 36 hours. Masitinib is approximately 93 % bound to
plasma proteins.

Masitinib is metabolised predominantly by N-dealkylation. Excretion takes place in the bile.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Cellulose, microcrystalline
Povidone K30
Pig liver powder
Crospovidone
Magnesium stearate

Tablet coating:
Macrogol 3350
Polyvinyl alcohol
Talc
Titanium dioxide (E171)
Sunset yellow (E110) aluminium lake.

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

Shelf life of the veterinary medicinal product as packaged for sale: 3 years.

6.4. Special precautions for storage

Keep the bottle tightly closed.

6.5 Nature and composition of immediate packaging

White HDPE bottle closed with a thermosealable film and covered by a child-resistant closure cap.
30 ml bottle containing 30 Masivet 50 mg film-coated tablets.
40 ml bottle containing 30 Masivet 50 mg film-coated tablets.
60 ml bottle containing 30 Masivet 150 mg film-coated tablets.

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. MARKETING AUTHORISATION HOLDER

AB Science S.A.
3 avenue George V
75008 Paris
France
Tel.: +33 (0)1 47 20 00 14
Fax: +33 (0)1 47 20 24 11
[email protected]

  1. MARKETING AUTHORISATION NUMBER(S)

EU/2/08/087/001
EU/2/08/087/002
EU/2/08/087/003

  1. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 17/11/2008
Date of last renewal:

10. DATE OF REVISION OF THE TEXT

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.

50mg Tablets » Pot of 30

SUMMARY OF PRODUCT CHARACTERISTICS

1. NAME OF THE VETERINARY MEDICINAL PRODUCT

MASIVET 50 mg film-coated tablets for dogs
MASIVET 150 mg film-coated tablets for dogs

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each film-coated tablet contains:
Active substance:
Masitinib 50 mg (equivalent to masitinib mesylate 59.6 mg)
Masitinib 150 mg (equivalent to masitinib mesylate 178.9 mg)

Excipients.

For a full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Film-coated tablet
Light-orange, round shape, film-coated tablet embossed with "50" or "150" on one side and the
company logo on the other side.

4. CLINICAL PARTICULARS

4.1 Target species

Dogs.

4.2 Indications for use, specifying the target species

Treatment of non-resectable dog mast cell tumours (Grade 2 or 3) with confirmed mutated c-kit
tyrosine kinase receptor.

4.3 Contraindications

Do not use in pregnant or lactating bitches (see section 4.7).
Do not use in dogs less than 6 months of age or less than 4 kg body weight.
Do not use in dogs suffering from liver impairment, defined as AST or ALT > 3 x Upper Limit of
Normal (ULN). Do not use in dogs suffering from renal function impairment, defined as Urinary
Protein Creatinine (UPC) ratio > 2 or albumin < 1 x Lower Limit of Normal (LLN).
Do not use in dogs with anaemia (haemoglobin < 10 g/dl).
Do not use in dogs with neutropenia defined as absolute neutrophil count < 2,000 /mm3.
Do not use in case of hypersensitivity to the active substance or to any of the excipients.

4.4 Special warnings

For any mast cell tumour treatable by surgery, surgery should be the first choice of treatment.
Masitinib treatment should only be used in dogs with non-resectable mast cell tumours and which
express the mutated c-kit tyrosine kinase receptor. The presence of a mutated tyrosine kinase c-kit
receptor must be confirmed prior to treatment (see also section 5.1).

4.5 Special precautions for use

Special precautions for use in animals

Dogs should be carefully monitored and treatment might need to be adjusted or discontinued, if
necessary.

Monitoring of renal function
Renal function should be adequately monitored every month using dipstick urine testing.
In case of positive semiquantitative dipstick results (protein > 30 mg/dl), urinalysis should be
performed to determine urinary protein creatinine (UPC) ratio, and a blood sample to measure
creatinine, albumin and BUN.
If UPC ratio > 2, or creatinine > 1.5 upper limit of normal (ULN), or albumin < 0.75 lower limit of
normal (LLN) or blood urea nitrogen (BUN) > 1.5 ULN, discontinue treatment.

Monitoring of Protein loss syndrome
Perform every month a dipstick urine test. In case of positive semi-quantitative dipstick results
(protein 30 mg/dl), perform urinalysis to determine urinary protein creatinine (UPC) ratio.
Perform every month a blood measurement of albumin.
In case of UPC ratio > 2 or albumin < 0.75 lower limit of normal (LLN), treatment should be
interrupted until albumin and UPC values have returned to limit value (UPC ratio < 2 and
albumin > 0.75 LLN), treatment can then be continued at the same dose.
If of one of these events (UPC ratio > 2 or albumin < 0.75 LLN) occurs for a second time,
treatment should be permanently discontinued.

Anaemia and/or haemolysis
Dogs should be carefully monitored for signs of (haemolytic) anaemia. In case of clinical signs of
anaemia or haemolysis, haemoglobin, free bilirubin and haptoglobin should be measured and blood
cell counts (including reticulocyte) should be performed.
Treatment should be discontinued in case of:
Haemolytic anaemia, i.e. haemoglobin < 10 g/dl and haemolysis,
i.e. free bilirubin > 1.5 ULN and haptoglobin < 0.1 g/dl,
Anaemia due to lack of regeneration, i.e. haemoglobin< 10 g/dl and
reticulocytes < 80,000/mm3.

Hepatic toxicity (ALT or AST elevation), neutropenia
In case of an increase of ALT or AST > 3 ULN, decrease of neutrophil count < 2,000/mm3 or any
other severe adverse events, treatment should be modified as follows:
At the first occurrence, treatment should be interrupted until resolution, and then resumed at the same
dose level;
At the second occurrence of the same event, treatment should be interrupted until resolution; treatment
should then be continued with a reduced dose of 9 mg/kg bodyweight/day;
At the third occurrence of the same event, treatment should be interrupted until resolution; treatment
should then be continued with a dose further reduced to 6 mg/kg/day;
Treatment should be discontinued, if severe adverse reactions are still encountered at the 6 mg/kg/day
dose.

Other precautions
Treatment should be permanently discontinued in case of renal toxicity, immune-mediated haemolytic
anaemia (IMHA) and/or anaemia due to lack of regeneration, and if severe neutropenia, and/or severe
diarrhoea and/or severe vomiting persist after dose reduction.

Dogs should not be used for breeding while under treatment.

Summary of thresholds for laboratory evaluations resulting in contra-indication or
treatment modification (interruption, dose reduction or discontinuation)

Management of Hepatic Toxicity (ALT or AST)
Contra-indication Interruption Dose reduction Discontinuation

3 ULN > 3ULN > 3 ULN > 3ULN
(1st time) (2nd/3rd time) (4th time)
Management of Neutropenia (neutrophil counts)
Contra-indication Interruption Dose reduction Discontinuation
< 2,000/mm3 < 2,000/mm3 < 2,000/mm3 < 2,000/mm3
(1st time) (2nd/3rd time) (4th time)
Management of Protein-Loss Syndrome (Albuminemia and/or UPC)
Contra-indication Interruption Dose reduction Discontinuation
Albumin < 1 LLN Albumin < 0.75 LLN Not applicable Albumin < 0.75 LLN
or UPC > 2 or UPC >2 or UPC > 2
st
(1 time) (2nd time)
Management of Haemolytic and aregenerative Anaemia
(haemoglobin, bilirubin, haptoglobin, reticulocytes)
Contra-indication Interruption Dose reduction Discontinuation
Haemoglobin Not applicable Not applicable Haemoglobin < 10 g/dl
< 10 g/dL and either
free bilirubin > 1.5 ULN and
haptoglobin < 0.1 g/dl
or reticulocytes < 80,000/mm3

Special precautions to be taken by the person administering the veterinary medicinal product to
animals

Repeated dermal contact with masitinib may impair female fertility and foetal development.
The active substance of Masivet can cause skin sensitisation.
Avoid skin contact with faeces, urine, and vomit of treated dogs.
Wear protective gloves while disposing of vomit, urine or faeces of treated dogs.
If broken tablets, vomit, urine or faeces of treated dogs come into contact with the skin, rinse
immediately with plenty of water.

The active substance of Masivet can cause severe eye-irritation and serious damage to the eyes.
Avoid contact with the eyes.
Take care not to touch the eyes before gloves have been removed and disposed of and the
hands have been thoroughly washed.
If the product comes into contact with the eyes, rinse immediately with plenty of water.
People with known hypersensitivity to masitinib should not handle the product.
In case of accidental ingestion, seek medical advice immediately and show the package leaflet or the
label to the physician. Do not eat, drink, or smoke when treating the dog.
Children should not have close contact to treated dogs, treated dog faeces or vomit.

4.6 Adverse reactions (frequency and seriousness)

Very common
Mild to moderate gastrointestinal reactions (diarrhoea and vomiting) with a mean duration of
approximately 21 and 9 days, respectively.
Mild to moderate alopecia with a mean duration of approximately 26 days.

Common
Severe renal toxicity may occur in dogs suffering from renal disorders at the start of treatment
(including high blood creatinine level or proteinuria).
Moderate to severe anaemia (aplastic/haemolytic) with a mean duration of approximately 7 days.
Protein-loss syndrome (mainly due to a decrease in serum albumin).

Mild or moderate neutropenia with a mean duration of approximately 24 days.
Increase in aminotransferase (ALT or AST) with a mean duration of approximately 29 days.
Specific measures to be taken in case of the above reactions are described in section 4.5.

Other commonly observed adverse reactions were in most cases mild or moderate:
Lethargy and asthenia with a mean duration of approximately 8 and 40 days, respectively.
Decrease in appetite or anorexia with a mean duration of 45 days and 18 days, respectively.
Cough (mean duration 23 days).
Lymphadenopathy (mean duration 47 days).
Oedema (mean duration of oedema was 7 days).
Lipoma (mean duration 53 days).

The frequency of adverse reactions is defined using the following convention:
- very common (more than 1 in 10 animals displaying adverse reaction(s) during the course of
one treatment)
- common (more than 1 but less than 10 animals in 100 animals)

4.7 Use during pregnancy, lactation or lay

Do not use in pregnant or lactating bitches. Laboratory studies in rats have shown evidence of
impaired female fertility at dose of 100 mg/kg/day, embryotoxicity and developmental toxicity at dose
above 30 mg/kg/day. Studies in rabbits did however not reveal embryotoxicity or developmental
toxicity.

4.8 Interaction with other medicinal products and other forms of interaction

In vitro tests with human microsomes demonstrate that concomitant treatment with substances which
are metabolised by CYP450 isoforms may result in higher or lower plasma levels of either masitinib or
those substances. No corresponding information is available for dogs. Hence, caution is advised with
the concurrent use of masitinib and other substances.
Concurrent use of other substances with a high degree of protein binding may compete with masitinib
binding and thus cause adverse effects.
The efficacy of Masivet might be reduced in dogs previously treated with chemotherapy and/or
radiotherapy. No information relating to potential cross-resistance with other cytostatic products is
available.

4.9 Amounts to be administered and administration route

For oral use.

The recommended dose is 12.5 mg/kg (with a dose range of 1114 mg/kg) once daily as presented in
the table below.

In dogs with a bodyweight of less than 15 kg accurate dosing is not always possible. These dogs may
be treated with either 50, 100 or 150 mg, if it is feasible to achieve a target dose of 1114 mg/kg bw.

The tablets must be administered as a whole and should not be divided, broken or ground. If a broken
tablet is rejected by the dog after chewing, it should be disposed of.
Tablets should always be administered in the same manner, with food.

12.5 mg/kg bw Number of tablets per day Dose mg/kg
Dog body-weight in kg 50 mg 150 mg lower weight upper weight

15 18 1 plus 1 13.7 11.1
18 22 2 plus 1 13.9 11.4
22 26 2 13.6 11.5
26 30 1 plus 2 13.5 11.7
30 34 2 plus 2 13.3 11.8
34 38 3 13.2 11.8
38 42 1 plus 3 13.2 11.9
42 46 2 plus 3 13.1 12.0
46 50 4 13.0 12.0
50 54 1 plus 4 13.0 12.0
54 58 2 plus 4 13.0 12.1
58 62 5 12.9 12.1
62 66 1 plus 5 12.9 12.1
66 70 2 plus 5 12.9 12.1
70 74 6 12.9 12.2
74 78 1 plus 6 12.8 12.2
78 2 plus 6 12.8

If the tablet is regurgitated or vomited within 10 minutes following administration, treatment should
be repeated. If the tablet is regurgitated or vomited later than 10 minutes following administration,
treatment should not be repeated.

The treatment should be reviewed after 4 to 6 weeks in order to assess the initial response. Duration of
treatment depends on the response to treatment. Treatment should be maintained in the case of stable
disease, i.e. static, partial or complete tumour response, provided that the product is sufficiently well
tolerated. In case of tumour progression, treatment is unlikely to be successful and the treatment
should be reviewed.

Dose reduction, treatment interruption and treatment discontinuation:

Dogs should be monitored carefully and professional judgement should be used to determine the need
for dose reduction in the event of possible significant adverse reactions (see section 4.5). Doses can be
reduced to 9 mg/kg bodyweight (range 7.510.5 mg/kg) or 6 mg/kg bw (range 4.57.5 mg/kg)
according to the tables below.
During clinical studies, the daily dose was decreased due to adverse events in approximately 16 % of
treated dogs and mainly due to an increase in transaminases.

9 mg per kg bodyweight once daily as presented in the table below.

Number of tablets per day Dose mg/kg
Dog body-weight in 50 mg 150 mg lower weight upper weight
kg

15.0 19.4 1 10.0 7.7
19.4 25.0 1 plus 1 10.3 8.0
25.0 30.6 2 plus 1 10.0 8.2
30.6 36.1 2 9.8 8.3
36.1 41.7 1 plus 2 9.7 8.4
41.7 47.2 2 plus 2 9.6 8.5
47.2 52.8 3 9.5 8.5
52.8 58.3 1 plus 3 9.5 8.6
58.3 63.9 2 plus 3 9.4 8.6
63.9 69.4 4 9.4 8.6
69.4 75.0 1 plus 4 9.4 8.7
75.0 80.6 2 plus 4 9.3 8.7

6 mg per kg bodyweight once daily as presented in the table below.
Number of tablets per day Dose mg/kg
Dog body-weight in 50 mg 150 mg lower weight upper weight
kg

15.0 20.8 2 6.6 4.8
20.8 29.2 1 7.2 5.1
29.2 37.5 1 plus 1 6.9 5.3
37.5 45.8 2 plus 1 6.7 5.5
45.8 54.2 2 6.5 5.5
54.2 62.5 1 plus 2 6.5 5.6
62.5 70.8 2 plus 2 6.4 5.6
70.8 79.2 3 6.4 5.7
79.2 1 plus 3 6.3

4.10 Overdose (symptoms, emergency procedures, antidotes), if necessary

The recommended daily dose of 12.5 mg/kg body weight corresponds to the Maximum Tolerated
Dose (MTD) that was derived from repeat dose toxicity studies in healthy Beagle dogs.

Overdosing signs were observed in toxicity studies conducted in healthy dogs, treated for 39 weeks at
doses of around 2 times the recommended dose (25 mg masitinib), treated for 13 weeks and 4 weeks at
doses of around 3 times the recommended dose (41.7 mg masitinib), and treated for 4 weeks at doses
of around 10 times the recommended dose (125 mg masitinib). The main target organs of toxicity in
dogs are the gastrointestinal tract, the haematopoetic system, the kidney and the liver.

In case of adverse events following overdose, treatment should be discontinued until resolution, and
then resumed at the recommended therapeutic dose level.

4.11 Withdrawal period(s)

Not applicable.

5. PHARMACOLOGICAL PROPERTIES

Pharmacotherapeutic group: protein-tyrosine kinase inhibitor.
ATCvet code: QL01XE90.

5.1 Pharmacodynamic properties

Masitinib is a protein-tyrosine kinase inhibitor which, in vitro, potently and selectively inhibits the
mutated form, in the juxtamembrane (JM) region, of the c-kit receptor. It also inhibits the Platelet
Derived Growth Factor (PDGF) receptor and the Fibroblast Growth Factor Receptor (FGFR3).

In the pivotal clinical field study, dogs of various breeds, ranging in age from two to seventeen years,
were randomly treated with Masivet at a dose of 12.5 mg/kg or with a placebo. In dogs with non-
resectable mast cell tumours, Grade 2 or 3, expressing a mutated tyrosine kinase c-kit receptor,
treatment with Masivet showed a significantly longer Time-to-Tumour Progression (TTP) with a
median of 241 days as compared to 83 days for placebo. Response to treatment with masitinib was
expressed as stable disease; i.e. static, partial or complete response.

Masitinib treatment should only be used in dogs with non-resectable mast cell tumours, which express
the mutated c-kit tyrosine kinase receptor. The presence of a mutated tyrosine kinase c-kit receptor
must be confirmed prior to treatment.

5.2 Pharmacokinetic particulars

Following oral administration in dogs at a dose of 11.2 mg (0.5 mg) per kg of bodyweight, masitinib
is rapidly absorbed and the time to maximal concentration (Tmax) is approximately 2 hours. The
elimination half-life (t) is approximately 36 hours. Masitinib is approximately 93 % bound to
plasma proteins.

Masitinib is metabolised predominantly by N-dealkylation. Excretion takes place in the bile.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Cellulose, microcrystalline
Povidone K30
Pig liver powder
Crospovidone
Magnesium stearate

Tablet coating:
Macrogol 3350
Polyvinyl alcohol
Talc
Titanium dioxide (E171)
Sunset yellow (E110) aluminium lake.

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

Shelf life of the veterinary medicinal product as packaged for sale: 3 years.

6.4. Special precautions for storage

Keep the bottle tightly closed.

6.5 Nature and composition of immediate packaging

White HDPE bottle closed with a thermosealable film and covered by a child-resistant closure cap.
30 ml bottle containing 30 Masivet 50 mg film-coated tablets.
40 ml bottle containing 30 Masivet 50 mg film-coated tablets.
60 ml bottle containing 30 Masivet 150 mg film-coated tablets.

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. MARKETING AUTHORISATION HOLDER

AB Science S.A.
3 avenue George V
75008 Paris
France
Tel.: +33 (0)1 47 20 00 14
Fax: +33 (0)1 47 20 24 11
[email protected]

  1. MARKETING AUTHORISATION NUMBER(S)

EU/2/08/087/001
EU/2/08/087/002
EU/2/08/087/003

  1. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 17/11/2008
Date of last renewal:

10. DATE OF REVISION OF THE TEXT

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.

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Reviews (94)

Q & A

Below are some recent questions we've received regarding Masivet Tablets for Dogs, including answers from our team.

1 June 2018 at 12:06am

MASIVET

DR RENNIE SHOOP

CAN YOU TREAT AN 8.3# DOG WITH MASIVET

  • Veterinary Advisor

Masivet must not be used in dogs less than six months of age or less than 4kg in weight. The dose rate is 12.5mg/kg once daily.

15 April 2016 at 8:55pm

Masitinib

Cheryl Woodring

  • VioVet customer since 2016
  • From: Washington, United States

Is this a generic drug for masitinib? I sent in a prescription and just want to make sure I'm paying for the correct one. I need the 150 mg not the 50 mg.

  • Non-Executive Director

The only brand name mastinib is sold under in the UK is Masivet. This is the original brand and not a generic. Other brand names can be chosen by the manufacturer when marketing it in other countries, but the product is the same. If your vet has prescribed mastinib, then Masivet is correct for you.