Vetoryl Capsules

Vetoryl® 10 mg Hard Capsules for Dogs

Presentation

1 capsule contains: Active substance: Trilostane 10 mg

Excipients: Titanium dioxide (E171) 0.942 mg

Ferric oxide (yellow) (E172) 0.035 mg

Ferric oxide (black) (E172) 0.532 mg

Maize starch, lactose monohydrate, magnesium stearate.

Capsule shell: Gelatin, titanium dioxide, ferric oxide (yellow), ferric oxide (black).

Grey ink: Titanium dioxide, ferric oxide (black), shellac.

Hard capsule. Ivory body and black cap with the capsule strength printed on the body of the capsule.

Uses

In dogs: For the treatment of pituitary-dependent and adrenal-dependent hyperadrenocorticism (Cushing’s disease and syndrome).

Dosage and administration

Administer orally, once daily, with food. In clinical studies, an average starting dose of 6 mg/kg once daily was effective. The dose should then be titrated according to individual response as determined by monitoring (see below). Practical starting doses are recommended as follows:

Body weight (kg)	Starting dose (mg)	Dosage (mg/kg)
>3 and <10	30	3-10
>10 and <20	60	3-6
>20 and <40	120	3-6
>40	120-240	3-6

In clinical studies, most dogs were eventually stabilised on doses between 2-10 mg/kg/day. Should symptoms not be adequately controlled for an entire 24 hour inter-dose period, consideration should be given to increasing the daily dose by as small an increment as possible and dividing it between morning and evening doses. Do not divide or open capsules.

A small number of animals may require doses significantly in excess of 10 mg per kg body weight per day. In these situations appropriate additional monitoring should be implemented.

The 10 mg capsule should be used in dogs that require particularly small doses of trilostane, and to assist with dosage adjustments.

Monitoring: Samples should be taken for biochemistry (including electrolytes) and an ACTH stimulation test pre-treatment and then at 10 days, 4 weeks, 12 weeks, and thereafter every 3 months, following initial diagnosis and after each dose adjustment. It is imperative that ACTH stimulation tests are performed 4-6 hours post-dosing to enable accurate interpretation of results. Dosing in the morning is preferable as this will allow your veterinary surgeon to perform monitoring tests 4-6 hours following administration of the dose. Regular assessment of the clinical progress of the disease should also be made at each of the above time points.

In the event of a non-stimulatory ACTH stimulation test during monitoring, treatment should be stopped for 7 days and then re-started at a lower dose. Repeat the ACTH stimulation test after a further 14 days. If the result is still non-stimulatory, stop treatment until clinical signs of hyperadrenocorticism recur. Repeat the ACTH stimulation test one month after re-starting treatment.

Contraindications, warnings, etc

Do not use in animals suffering from primary hepatic disease and/or renal insufficiency.

Do not use in dogs weighing less than 3 kg.

Special warnings for each target species: An accurate diagnosis of hyperadrenocorticism is essential.

Where there is no apparent response to treatment, the diagnosis should be re-evaluated. Dose increases may be necessary.

Veterinarians should be aware that dogs with hyperadrenocorticism are at increased risk of pancreatitis. This risk may not diminish following treatment with trilostane.

Special precautions for use in animals: As the majority of cases of hyperadrenocorticism are diagnosed in dogs between the ages of 10-15 years, other pathological processes are frequently present. It is particularly important to screen cases for primary hepatic disease and renal insufficiency as the product is contraindicated in these cases.

Subsequent close monitoring during treatment should be carried out. Particular attention should be paid to liver enzymes, electrolytes, urea and creatinine.

The presence of diabetes mellitus and hyperadrenocorticism together requires specific monitoring.

If a dog has previously been treated with mitotane, its adrenal function will have been reduced. Experience in the field suggests that an interval of at least a month should elapse between cessation of mitotane and the introduction of trilostane. Close monitoring of adrenal function is advised, as dogs may be more susceptible to the effects of trilostane.

The product should be used with extreme caution in dogs with pre-existing anaemia as further reductions in packed-cell volume and haemoglobin may occur. Regular monitoring should be undertaken.

Special precautions to be taken by the person administering the veterinary medicinal product to animals: Trilostane may decrease testosterone synthesis and has anti-progesterone properties. Women who are pregnant or are intending to become pregnant should avoid handling the capsules.

Wash hands with soap and water following accidental exposure and after use.

The content of the capsules may cause skin and eye irritation and sensitisation. Do not divide or open capsules. In the event of accidental breakage of the capsules and contact of the granules with eyes or skin, wash immediately with plenty of water. If irritation persists, seek medical advice.

People with known hypersensitivity to trilostane or any of the excipients should avoid contact with the product.

In the event of accidental ingestion, seek medical advice immediately and show the package leaflet or carton to the physician.

Adverse reactions: Corticosteroid withdrawal syndrome or hypocortisolaemia should be distinguished from hypoadrenocorticism by evaluation of serum electrolytes.

Signs associated with iatrogenic hypoadrenocorticism, including weakness, lethargy, anorexia, vomiting and diarrhoea, may occur, particularly if monitoring is not adequate (see 'Dosage and administration'). Signs are generally reversible within a variable period following withdrawal of treatment. Acute Addisonian crisis (collapse) may also occur (see Overdose). Lethargy, vomiting, diarrhoea and anorexia have been seen in dogs treated with trilostane in the absence of evidence of hypoadrenocorticism.

There have been occasional isolated reports of adrenal necrosis in treated dogs which may result in hypoadrenocorticism.

Subclinical renal dysfunction may be unmasked by treatment with the product.

Treatment may unmask arthritis due to a reduction in endogenous corticosteroid levels.

A small number of reports have been received of sudden death during treatment.

Other mild, rare, adverse effects include ataxia, hypersalivation, bloating, muscle tremors and skin changes.

Use during pregnancy and lactation: Do not use in pregnant or nursing bitches or in any animals intended for breeding.

Interactions: The possibility of interactions with other medicinal products has not been specifically studied. Given that hyperadrenocorticism tends to occur in older dogs, many will be receiving concurrent medication. In clinical studies, no interactions were observed.

The risk of hyperkalaemia developing should be considered if trilostane is used in conjunction with potassium-sparing diuretics or ACE inhibitors. The concurrent use of such drugs should be subject to a risk/benefit analysis by the veterinary surgeon, as there have been a few reports of deaths (including sudden death) in dogs when treated concurrently with trilostane and an ACE inhibitor.

Overdose: Overdose may lead to signs of hypoadrenocorticism (lethargy, anorexia, vomiting, diarrhoea, cardiovascular signs, collapse). There were no mortalities following chronic administration at 3 x the maximum recommended dose to healthy dogs, however mortalities may be expected if higher doses are administered to dogs with hyperadrenocorticism.

There is no specific antidote for trilostane. Treatment should be withdrawn and supportive therapy, including corticosteroids, correction of electrolyte imbalances and fluid therapy may be indicated depending on the clinical signs.

In cases of acute overdosage, induction of emesis followed by administration of activated charcoal may be beneficial.

Any iatrogenic adrenocortical insufficiency is usually quickly reversed following cessation of treatment. However in a small percentage of dogs, effects may be prolonged. Following a one week withdrawal of trilostane treatment, treatment should be reinstated at a reduced dose rate.

Pharmaceutical precautions

Do not store above 25°C. Keep the blister pack in the outer carton. Do not use after the expiry date stated on the blister.

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

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

Legal category

POM-V

Packaging quantities

Three PVC-PVdc/aluminium foil blister strips each containing 10 capsules.

Further information

For animal treatment only. To be supplied only on veterinary prescription. Keep out of the reach and sight of children.

Manufacturers: Dales Pharmaceuticals, Snaygill Industrial Estate, Keighley Road, Skipton, North Yorkshire, BD23 2RW.

Penn Pharmaceutical Services, 23/24 Tafarnaubach Industrial Estate, Tredegar, South Wales, NP22 3AA.

Date of last review: January 2013

Marketing authorisation holder (if different from distributor)

Dechra Limited, Dechra House, Jamage Industrial Estate, Talke Pits, Stoke-on-Trent, Staffordshire, ST7 1XW.

Marketing authorisation number

Vm 10434/4068.

GTIN (Global Trade Item No)

Vetoryl 10 mg Hard Capsules for Dogs

05055031418947

Vetoryl® 30 mg Hard Capsules for Dogs

Presentation

Each capsule contains: Active substance: Trilostane 30 mg

Excipients: Titanium dioxide (E171) 1.19 mg

Yellow iron oxide (E172) 0.045 mg

Black iron oxide (E172) 0.672 mg

Also contains maize starch, lactose monohydrate, magnesium stearate, gelatin.

Hard capsules. Ivory body and black cap with the capsule strength printed on the body of the capsule.

Uses

For the treatment of pituitary-dependent and adrenal-dependent hyperadrenocorticism (Cushing's disease and syndrome) in dogs.

Dosage and administration

Administer orally, once daily, with food. In clinical studies, an average starting dose of 6 mg/kg once daily was effective. The dose should then be titrated according to individual response as determined by monitoring (see below). Practical starting doses are recommended as follows:

Body weight (kg)	Starting dose (mg)	Dosage (mg/kg)
>3 and <10	30	3-10
>10 and <20	60	3-6
>20 and <40	120	3-6
>40	120-240	3-6

In clinical studies, most dogs were eventually stabilised on doses between 2-10 mg/kg/day.

Should symptoms not be adequately controlled for an entire 24 hour inter-dose period, consideration should be given to increasing the daily dose by as small an increment as possible and dividing it between morning and evening doses. Do not divide or open capsules.

A small number of animals may require doses significantly in excess of 10 mg per kg body weight per day. In these situations appropriate additional monitoring should be implemented.

Due to the limitation in capsule size, it may not be possible to provide optimal control for smaller dogs requiring lower doses of trilostane.

Monitoring: Samples should be taken for biochemistry (including electrolytes) and an ACTH stimulation test pre-treatment and then at 10 days, 4 weeks, 12 weeks, and thereafter every 3 months, following initial diagnosis and after each dose adjustment. It is imperative that ACTH stimulation tests are performed 4-6 hours post-dosing to enable accurate interpretation of results. Regular assessment of the clinical progress of the disease should also be made at each of the above time points.