Thyroxanil 200 Microgram Tablets for Dogs and Cats

Composition

Each tablet contains:

Active substance:

Levothyroxine sodium 200 µg

(equivalent to levothyroxine 194 μg)

For the full list of excipients, see section 6.1.

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Pharmaceutical form

Tablet.

White to off white, round and convex tablet with a cross-shaped break line on one side and the number 200 on the other side. The tablets can be divided into halves or quarters.

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Pharmacological properties

Pharmacotherapeutic group: Thyroid hormones ATCvet code: QH03AA01

5.1 Pharmacodynamic properties

Levothyroxine is a synthetic homologue of the naturally occurring thyroid hormone, thyroxine (T4). It is converted to the more biologically active triiodothyronine (T3). T3 binds via specific receptors within the plasma membrane, mitochondria and chromatin resulting in changes in DNA transcription and protein synthesis. Onset of action is therefore slow.

Levothyroxine sodium affects the metabolism of carbohydrates, proteins, fats, vitamins, nucleic acids and ions. Levothyroxine sodium stimulates the consumption of oxygen and causes an increased metabolic activity by increasing the number of mitochondria. Protein synthesis is stimulated and the consumption of carbohydrates increases. The fat metabolism is stimulated.

5.2 Pharmacokinetic particulars

After oral intake the gastrointestinal absorption is 10 to 50% in dogs and 10% in cats Cmax is reached in 4-12 hours after administration in dogs and 3-4 hours in cats. After administration of 20 micrograms per kg of active ingredient to 57 hypothyroid dogs, the plasma thyroxine (T4) levels increased in the majority of cases to normal values (20-46 nmol). After absorption into the circulation T4 is deiodinated to T3 in the peripheral tissues. In the dog, over 50% of the T4 produced each day is lost in the faeces. The serum half-life in normal dogs is 10 to 16 hours. In hypothyroid dogs this takes longer. The pharmacokinetics of levothyroxine have not been fully investigated in cats.

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Target species

Dogs and cats.

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Indications

Treatment of primary and secondary hypothyroidism.

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Dosage

Oral use.

The recommended starting dose for dogs and cats is 20 µg levothyroxine sodium per kg body weight per day given as a single daily dose or in two equally divided doses.

Because of variability in absorption and metabolism, the dosage may require alterations before a complete clinical response is observed. The initial dosage and frequency of administration are merely a starting point. Therapy has to be highly individualised and tailored to the requirements of the individual animal especially for cats and small dogs. See also section 4.5 ‘Special precautions for use in animals’ for use in animals <2.5 kg. The dose should be adjusted based on clinical response and plasma thyroxine levels. In the dog and cat, absorption of levothyroxine sodium may be affected by the presence of food. The timing of treatment and its relation to feeding should therefore be kept consistent from day to day. To adequately monitor therapy, trough values (just prior to treatment) and peak values (about four hours after dosing) of plasma T4 can be measured. In adequately dosed animals peak plasma concentration of T4 should be in the high-normal range (approximately 30 to 47 nmol/l) and trough values should be above approximately 19 nmol/l. If T4 levels are outside this range the levothyroxine sodium dose can be adjusted in appropriate increments until the patient is clinically euthyroid and serum T4 is within the reference range. The 200 µg tablets enable adjustment of the levothyroxine dose by 50 µg increments per animal and 600 µg tablets enable adjustment of the levothyroxine dose by 150 µg increments per animal. Plasma T4 levels can be retested two weeks after change of dosage, but clinical improvement is an equally important factor in determining individual dosage and this will take four to eight weeks. When the optimum replacement dose has been attained, clinical and biochemical monitoring may be performed every 6 – 12 months.

The following table is intended as a guide to dispensing the product at approximately the standard starting dose rate of 20 µg levothyroxine sodium per kg bodyweight per day.

= ¼ Tablet = ½ Tablet = ¾ Tablet = 1 Tablet

Tablets can be divided into halves or quarters to ensure accurate dosing. Place the tablet on a flat surface, with its scored side facing up and the convex (rounded) side facing the surface.

Halves: press down with your thumbs on both sides of the tablet.

Quarters: press down with your thumb in the middle of the tablet.

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Contraindications

Do not use in dogs and cats suffering from uncorrected adrenal insufficiency. Do not use in cases of known hypersensitivity to levothyroxine sodium or to any of the excipients.

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Adverse reactions

An exacerbation of skin symptoms, with increased pruritus due to shedding of the old epithelial cells, can occur initially. Pruritus and desquamation have been reported very rarely in spontaneous reports.

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).

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Warnings

Special precautions for use in animals

A sudden increase in demand for oxygen delivery to peripheral tissues, plus the chronotropic effects of levothyroxine sodium, may place undue stress on a poorly functioning heart, causing decompensation and signs of congestive heart failure. Hypothyroid animals with concurrent hypoadrenocorticism have a decreased ability to metabolise levothyroxine sodium and therefore an increased risk of thyrotoxicosis. These animals should be stabilised with glucocorticoid and mineralocorticoid treatment prior to treatment with levothyroxine sodium to avoid precipitating a hypoadrenocortical crisis. After this, thyroid tests should be repeated, then gradual introduction of levothyroxine is recommended (starting with 25% of the normal dose and increasing by 25% increments every fortnight until optimal stabilisation is achieved). Gradual introduction of therapy is also recommended for animals with other concurrent illnesses; particularly in animals with cardiac disease, diabetes mellitus and renal or hepatic dysfunction.

Owing to limitations in size and divisibility of the tablets, it may not be possible to optimally dose animals weighing less than 2.5 kg. Therefore use of the product in these animals should be based on a careful benefit-risk assessment by the responsible veterinarian.

Special precautions to be taken by the person administering the veterinary medicinal product to animals This product contains a high concentration of levothyroxine sodium and may be harmful when ingested, particularly for children. Pregnant women should handle this veterinary medicinal product with caution. Levothyroxine may cause hypersensitivity (allergy) following ingestion. Avoid skin contact with this product if you know you are sensitized. Wash hands after handling the tablets. In the case of accidental ingestion, seek medical advice immediately and show the package leaflet or the label to the physician.

Any unused tablet portion(s) should be returned to the open blister, stored out of the sight and reach of children and always be used at the next administration.

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Use during pregnancy, lactation or lay

The safety of the veterinary medicinal product has not been established in pregnant or lactating bitches and queens and therefore use of the product in these animals should be based on a benefit-risk assessment by the responsible veterinarian. However, levothyroxine is an endogenous substance and thyroid hormones are essential for the developing foetus, especially during the first period of gestation.

Hypothyroidism during pregnancy may result in major complications such as foetal death and a poor perinatal outcome. Maintenance dose of levothyroxine sodium may need adjustment during pregnancy. Pregnant bitches and queens should therefore be monitored on a regular basis from conception until several weeks after delivery.

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Interactions

A variety of drugs may impair plasma or tissue binding of the thyroid hormones or alter thyroid hormone metabolism (e.g. barbiturates, antacids, anabolic steroids, diazepam, furosemide, mitotane, phenylbutazone, phenytoin, propranolol, large doses of salicylates and sulphonamides). When treating animals that are receiving concurrent medication the properties of these drugs should be taken into consideration.

Oestrogens may increase thyroid requirements.

Ketamine may cause tachycardia and hypertension when used in patients receiving thyroid hormones.

The effect of catecholamines and sympathomimetics is increased by levothyroxine. An increase in the dosage of digitalis may be necessary in a patient that had previously compensated congestive heart failure and that is placed on thyroid hormone supplementation. Following treatment of hypothyroidism in patients with concurrent diabetes, careful monitoring of diabetic control is recommended.

Most patients on chronic high-dose, daily glucocorticoid therapy will have very low or undetectable serum T4 concentrations, as well as subnormal T3 values.

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Overdose

Following administration of overdoses thyrotoxicosis could occur. Thyrotoxicosis as a side effect of mild over-supplementation is uncommon in dogs and cats, owing to the ability of these species to catabolise and excrete thyroid hormones. In case of accidental intake of large amounts of the veterinary medicinal product absorption can be decreased by induction of vomiting and oral administration of both activated charcoal and magnesium sulphate once.

In an acute overdose situation in dogs and cats, the clinical signs are extensions of the hormone’s physiological effects. Acute overdose of levothyroxine may produce vomiting, diarrhoea, hyperactivity, hypertension, lethargy, tachycardia, tachypnoea, dyspnoea, and abnormal pupillary light reflexes.

Following chronic over-supplementation in dogs and cats, clinical signs of hyperthyroidism such as polydipsia, polyuria, panting, weight loss without anorexia, and either or both tachycardia and nervousness may theoretically occur. The presence of these signs should result in evaluation of T4 serum concentrations to confirm the diagnosis, and immediate discontinuance of the supplementation. Once the signs have abated (days to weeks), the thyroid dosage has been reviewed, and the animal has fully recovered, a lower dosage may be instituted, with the animal being monitored closely.

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Special warnings

The diagnosis of hypothyroidism should be confirmed with appropriate tests.

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Withdrawal period

Not applicable.

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Incompatibilities

Not applicable.

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Immediate packaging

Aluminium - PVC blister Cardboard box of 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 blisters. 25 or 30 tablets per blister. Not all pack sizes may be marketed.

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Storage

Do not store above 25°C.

Keep the blisters in the outer carton in order to protect from light.

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Shelf life

Shelf life of the veterinary medicinal product as packaged for sale: 2 years.

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Disposal of unused product

Any unused veterinary medicinal product or waste materials derived from such veterinary medicinal products should be disposed of in accordance with local requirements.

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Additional information

Vm 41821/4031

9 DATE OF FIRST AUTHORISATION

24 June 2016

10 DATE OF REVISION OF THE TEXT

February 2021

Approved: 03/02/21

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Registration holder

Le Vet Beheer B.V.

Wilgenweg 7

3421 TV Oudewater

The Netherlands

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