Thiafeline Film-coated Tablets for Cats

Thiafeline Film-coated Tablets for Cats

4. CLINICAL PARTICULARS

4.1 Target species

Cats.

4.2 Indications for use, specifying the target species

For the stabilisation of hyperthyroidism in cats prior to surgical thyroidectomy.
For the long-term treatment of feline hyperthyroidism.

4.3 Contraindications

Do not use in cats suffering from systemic disease such as primary liver disease or
diabetes mellitus.
Do not use in cats showing signs of autoimmune disease.
Do not use in animals with disorders of white blood cells, such as neutropenia and
lymphopenia.
Do not use in animals with platelet disorders and coagulopathies (particularly
thrombocytopenia).
Do not use in pregnant or lactating females. Refer to section 4.7.
Do not use in cases of hypersensitivity to thiamazole or to any of the excipients.

4.4 Special warnings for each target species

None

4.5 Special precautions for use

Special precautions for use in animals

As thiamazole can cause haemoconcentration, cats should always have access to
drinking water.
If more than 10 mg per day is required animals should be monitored particularly
carefully.
Use of the product in cats with renal dysfunction should be subject to careful risk :
benefit assessment by the clinician. Due to the effect thiamazole can have on
reducing the glomerular filtration rate, the effect of therapy on renal function should
be monitored closely as deterioration of an underlying condition may occur.
Haematology must be monitored due to risk of leucopenia or haemolytic anaemia.
Any animal that suddenly appears unwell during therapy, particularly if they are
febrile, should have a blood sample taken for routine haematology and biochemistry.
Neutropenic animals (neutrophil counts <2.5 x 109
/l) should be treated with
prophylactic bactericidal antibacterial drugs and supportive therapy.
Special precautions to be taken by the person administering the veterinary
medicinal product to animals
People with known hypersensitivity to thiamazole should avoid contact with the
veterinary medicinal product.
Do not handle this product if you are allergic to anti-thyroid products. Do not break or
crush tablets. If allergic symptoms develop, such as a skin rash, swelling of the face,
lips or eyes or difficulty in breathing, you should seek medical attention immediately
and show the package leaflet or label to the doctor.
Thiamazole may cause vomiting, epigastric distress, headache, fever, arthralgia,
pruritus and pancytopaenia. Treatment is symptomatic.
In the 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 while handling the tablet or used litter.
Wash hands after use.
Wash hands with soap and water after handling litter used by treated animals.
As thiamazole is a suspected human teratogen, women of child-bearing age and
pregnant should wear gloves when handling litter of treated cats.
Pregnant women should wear gloves when handling this product.

4.6 Adverse reactions (frequency and seriousness)

Adverse reactions have been reported following long term control of hyperthyroidism.
In many cases signs may be mild and transitory and not a reason for withdrawal of
treatment. The more serious effects are mainly reversible when medication is
stopped. Adverse reactions are uncommon. The most common clinical side effects
reported include vomiting, inappetance/anorexia, lethargy, severe pruritus and
excoriations of the head and neck, bleeding diathesis and icterus associated with
hepatopathy, and haematological abnormalities (eosinophilia, lymphocytosis,
neutropenia, lymphopenia, slight leucopenia, agranulocytosis, thrombocytopenia or
haemolytic anaemia). These side effects resolved within 7-45 days after cessation of
thiamazole therapy.

Possible immunological side effects include anaemia, with rare side effects including
thrombocytopenia and serum anti-nuclear antibodies),and, very rarely,
lymphadenopathy can occur. Treatment should be stopped immediately and
alternative therapy considered following a suitable period for recovery.
Following long-term treatment with thiamazole in rodents, an increased risk of
neoplasia in the thyroid gland has been shown to occur, but no evidence is available
in cats.
The frequency of adverse reactions is defined using the following convention:
- very common (more than 1 in 10 animals treated displaying adverse reaction(s))
- common (more than 1 but less than 10 animals in 100 animals treated)
- uncommon (more than 1 but less than 10 animals in 1,000 animals treated)
- rare (more than 1 but less than 10 animals in 10,000 animals treated)
- very rare (less than 1 animal in 10,000 animals treated, including isolated reports).

4.7 Use during pregnancy, lactation or lay

Laboratory studies in rats and mice have shown evidence of teratogenic and
embryotoxic effects of thiamazole. The safety of the product was not assessed in
pregnant or lactating cats. Do not use in pregnant or lactating females.

4.8 Interaction with other medicinal products and other forms of interaction

Concurrent treatment with phenobarbital may reduce the clinical efficacy of
thiamazole.
Thiamazole is known to reduce the hepatic oxidation of benzimidazole wormers and
may lead to increases in their plasma concentrations when given concurrently.
Thiamazole is immunomodulatory, therefore this should be taken into account when
considering vaccination programmes.

4.9 Amounts to be administered and administration route

For oral use.
For the stabilisation of feline hyperthyroidism prior to surgical thyroidectomy and for
the long term treatment of feline hyperthyroidism, the recommended starting dose is
5 mg per day.
Wherever possible, the total daily dose should be divided into two and administered
morning and evening. Tablets should not be split.
If, for reasons of compliance, once daily dosing with a 5 mg tablet is preferable, then
this is acceptable although the 2.5 mg tablet given twice daily may be more
efficacious in the short term. The 5 mg tablet is also suitable for cats requiring higher
dose rates.
Haematology, biochemistry and serum total T4 should be assessed before initiating
treatment and after 3 weeks, 6 weeks, 10 weeks, 20 weeks, and thereafter every 3
months. At each of the recommended monitoring intervals, the dose should be
titrated to effect according to the total T4 and to clinical response to treatment. Dose
adjustments should be made in increments of 2.5 mg and the aim should be to
achieve the lowest possible dose rate.
If more than 10 mg per day is required animals should be monitored particularly
carefully.
The dose administered should not exceed 20 mg/day.
For long term treatment of hyperthyroidism the animal should be treated for life.

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

In tolerance studies in young healthy cats, the following dose-related clinical signs
occurred at doses of up to 30 mg/animal/day: anorexia, vomiting, lethargy, pruritus
and haematological and biochemical abnormalities such as neutropenia,
lymphopenia, reduced serum potassium and phosphorus levels, increased
magnesium and creatinine levels and the occurrence of anti-nuclear antibodies. At a
dose of 30 mg/day some cats showed signs of haemolytic anaemia and severe
clinical deterioration. Some of these signs may also occur in hyperthyroid cats treated
at doses of up to 20 mg per day.
Excessive doses in hyperthyroid cats may result in signs of hypothyroidism. This is
however unlikely, as hypothyroidism is usually corrected by negative feedback
mechanisms. Please refer to Section 4.6: Adverse reactions.
If overdosage occurs, stop treatment and give symptomatic and supportive care.

4.11 Withdrawal period(s)

Not applicable.

5. PHARMACOLOGICAL PROPERTIES

Pharmacotherapeutic group:antithyroid preparations, sulphur-containing imidazole
derivates.
ATC Vet Code: QH03BB02.

5.1 Pharmacodynamic properties

Thiamazole acts by blocking the biosynthesis of thyroid hormone in vivo. The primary
action is to inhibit binding of iodide to the enzyme thyroid peroxidase, thereby
preventing the catalysed iodination of thyroglobulin and T3 and T4 synthesis.

5.2 Pharmacokinetic particulars

Absorption
Following oral dosing in healthy cats, thiamazole is rapidly and completely absorbed
with a bioavailability of >75 %. However, there is a considerable variation between
animals.
Peak plasma levels occur approximately 0.5-1 hour after dosing (tmax = 0.69 h). Cmax
is between 1.1 and 2.7 µg/ml (1.78 µg/ml) and half-life is 3.3 h.
Distribution
From man and rats it is known that the drug can cross the placenta and concentrates
in the foetal thyroid gland. There is also a high rate of transfer into breast milk.
The drug residence time in the thyroid gland is assumed to be longer than in the
plasma.
Metabolism and elimination
The metabolism of thiamazole in cats has not been investigated, however, in rats
thiamazole is rapidly metabolised in the thyroid gland. About 64 % of the
administered dose being eliminated in the urine and only 7.8 % excreted in faeces.
This is in contrast with man where the liver is important for the metabolic degradation
of the compound.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Tablet core:
Lactose monohydrate
Povidone
Sodium starch glycolate Type A
Silica, colloidal anhydrous
Magnesium stearate
Coating:
Hypromellose
Cellulose, microcrystalline
Lactose monohydrate
Macrogol
Titanium dioxide (E171)
Carmoisine (E122)

6.2 Major 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 blister in the outer package in order to protect from light.

6.5 Nature and composition of immediate packaging

30 tablets in a cardboard carton containing 1 aluminium/pvc strips each strip with 30
tablets.
60 tablets in a cardboard carton containing 2 aluminium/pvc strips each strip with 30
tablets.
120 tablets in a cardboard carton containing 4 aluminium/pvc strips each strip with 30
tablets.
150 tablets in a cardboard carton containing 5 aluminium/pvc strips each strip with 30
tablets.
300 tablets in a cardboard carton containing 10 aluminium/pvc strips each strip with 30
tablets.
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

Sizes:

2.5mg

5mg