Pill Identifier App

Vetoryl 60 mg (Canada)

This page contains information on Vetoryl 60 mg for veterinary use.
The information provided typically includes the following:
  • Vetoryl 60 mg Indications
  • Warnings and cautions for Vetoryl 60 mg
  • Direction and dosage information for Vetoryl 60 mg

Vetoryl 60 mg

This treatment applies to the following species:
Manufacturer: Vétoquinol

Trilostane Capsules for Dogs

For Veterinary Use Only

DIN 02322005

DIN 02322021

DIN 02322048

Indication:

To control hypercortisolism associated with pituitary-dependent and adrenal dependent hyperadrenocorticism in dogs.

Dosage and Administration

The starting dose of VETORYL Capsules is 2.2 - 6.7 mg/kg (1.0 - 3.0 mg/lb) orally once a day based on body weight and capsule size (see Table 1). VETORYL Capsules should be administered with food.

Table 1: Starting Dose

Weight range (kg)

Weight range (lb)

Starting dose (mg) ONCE DAILY

≥ 1.7 to < 4.5

≥ 3.8 to < 10

10

≥ 4.5 to < 10

≥ 10 to < 22

30

≥ 10 to < 20

≥ 22 to < 44

60

≥ 20 to < 40

≥ 44 to < 88

120

≥ 40 to < 60*

≥ 88 to < 132*

180

* Dogs over 60 kg (132 pounds) should be administered the appropriate combination of capsules.

After approximately 10-14 days at this dose, re-examine the dog and conduct a 4-6 hour post-dosing ACTH stimulation test, and take action according to Table 2.

Table 2: Action at ACTH evaluation

Post ACTH serum cortisol

Action
(refer to “Adjusting the dose”)

nmol/L

µg/dL

< 40

< 1.45

Stop treatment until ACTH results show stimulation (return to normal). Re-start at a decreased dose.

40 to 150

1.45 to 5.4

EITHER: If electrolytes are normal, continue on same dose.

OR: If electrolytes are abnormal, stop treatment until electrolytes return to normal. Re-start at decreased dose.

> 150 to 250

> 5.4 to 9.1

EITHER: If clinical signs are well controlled, continue on current dose.

OR: If clinical signs of hyperadrenocorticism are still evident, increase dose.

> 250

> 9.1

Increase initial dose

Adjusting the dose:

Individual dose adjustments and close monitoring are essential. Once daily administration is recommended. Combinations of capsule sizes should be used to increase and decrease the dose. The dose should be slowly increased. The once daily dose should not be increased by more than two times (double) the previous dose. Dogs requiring a decrease in dose following temporary cessation of treatment should be restarted on half the previous dose.

If clinical signs are not controlled for the full day, twice daily dosing may be needed. To switch from a once daily dose to a twice daily dose, increase the total daily dose by 1/3 to 1/2 and divide the total amount into 2 doses given 12 hours apart.

A small percentage of animals may require doses significantly in excess of 10 mg/kg/day. In these situations appropriate additional monitoring for adverse events should be implemented as the safety of doses > 10 mg/kg/day has not been fully evaluated. A small number of dogs do not respond to VETORYL Capsules and alternate therapy should be considered.

Monitoring:

A physical examination, complete blood count, biochemistry with electrolytes and an ACTH stimulation test should be done pre-treatment and then repeated 10-14 days following the start of the treatment. The tests should be repeated 10-14 days after every dose adjustment. If the same dose is continued, a physical examination, biochemistry with electrolytes and an ACTH stimulation should be done at 4 weeks, 12 weeks and then every 3 months after the start of the treatment to monitor the response. It is imperative that the ACTH stimulation test is performed 4-6 hours post-dosing to enable accurate interpretation of results.

Good control is indicated by favourable clinical signs as well as a post-ACTH serum cortisol of 40-250 nmol/L (1.45-9.1 µg/dL). If the ACTH stimulation test is < 40 nmol/L (1.45 µg/dL) and/or an electrolyte imbalance characteristic of hypoadrenocorticism (hyperkalemia and hyponatremia) is found, VETORYL Capsules should be temporarily discontinued until recurrence of clinical signs consistent with hyperadrenocorticism and electrolytes and ACTH test results return to normal (40-250 nmol/L or 1.45-9.1 µg/dL). VETORYL Capsules should be re-introduced at a lower dose.

If owners observe adverse reactions or unusual developments they should be instructed to stop therapy and contact their veterinarian.

Overdose:

Overdose may lead to signs of hypoadrenocorticism (lethargy, anorexia, vomiting, diarrhea, hematemesis, hematochezia, cardiovascular signs, collapse). There is no specific antidote for trilostane. Treatment should be withdrawn and supportive therapy, including corticosteroids, mineralocorticoids and fluid therapy may be indicated depending on clinical signs.

Contraindications

Do not use in animals weighing less than 1.7 kg. Do not divide capsules. Do not use in dogs suffering from primary hepatic disease or renal insufficiency. Do not use in pregnant or nursing bitches or any animals intended for breeding.

The use of VETORYL Capsules is contraindicated in dogs that have demonstrated hypersensitivity to trilostane.

Vetoryl 60 mg Caution

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

Hypoadrenocorticism can develop at any dose of VETORYL Capsules. In some cases, it may take months for adrenal function to return and some dogs never regain adrenal function. During routine monitoring in the 84 day field study, 26.2% of dogs had an ACTH stimulation test result of <40 nmol/L (1.45 µg/dL), but this was not necessarily associated with clinical signs.

A small percentage of dogs may develop corticosteroid withdrawal syndrome1 within 10 days of starting treatment. This phenomenon results from acute withdrawal of circulating glucocorticoids; clinical signs include weakness, lethargy, anorexia, and weight loss. These clinical signs can be differentiated from an early hypoadrenocortical crisis by normal serum electrolyte concentrations and normal ACTH stimulation test results. Corticosteroid withdrawal syndrome should respond to cessation of VETORYL Capsules (duration of discontinuation based on the severity of the clinical signs) and restarting at a lower dose.

Mitotane (o,p’-DDD) treatment will reduce adrenal function. When mitotane therapy is stopped, it is important to wait for both the recurrence of clinical signs consistent with hyperadrenocorticism, and a post-ACTH cortisol level of > 250 nmol/L (9.1 µg/dL) before treatment with VETORYL Capsules is initiated. Close monitoring of adrenal function is advised, as dogs previously treated with mitotane may be more responsive to the effects of VETORYL Capsules.

The use of VETORYL Capsules will not affect the progression of the adrenal or pituitary tumour. By inhibiting cortisol, it may stimulate some pituitary tumours to grow. In dogs with functional adrenal tumours, adrenalectomy should be considered as an option for cases that are good surgical candidates.

Twice daily dosing may not allow time for adrenal recovery and excretion of physiologically necessary glucocorticoid and mineralocorticoid hormones in some dogs. The risk of developing hypoadrenocorticism may be greater; however, in dogs with clinical signs that are not controlled for an entire 24 hour period, twice daily dosing may be required.

Concurrent Medications/Drug Interactions:

Angiotensin Converting Enzyme Inhibitors

The risk of hyperkalemia 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 veterinarian, as there have been a few reports of deaths (including sudden death) in dogs when treated concurrently with trilostane and an ACE inhibitor.

Non-steroidal Anti-inflammatory Drugs (nsaids)

There is no evidence for any direct interaction between non-steroidal anti-inflammatory drugs (NSAIDs) and VETORYL Capsules. However, in view of the elevated cortisol levels in dogs with hyperadrenocorticism, concurrent use with NSAIDs should be closely monitored. In the event of an adverse reaction the NSAID should be discontinued and an alternative method of pain management used.

Warnings

Keep out of reach of children. Not for human use.

Trilostane may decrease testosterone and progesterone synthesis. Women who are pregnant or are intending to become pregnant should avoid handling the capsules.

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 eye or skin, wash immediately with plenty of water. If irritation persists, seek medical advice.

In the event of accidental ingestion, seek medical advice immediately and take the labelled container with you.

Adverse Reactions

The most common adverse reactions reported are poor/reduced appetite, vomiting, lethargy/dullness, diarrhea and weakness. Occasionally, more serious reactions, including severe depression, hemorrhagic diarrhea, collapse, hypoadrenocortical crisis or adrenal necrosis/rupture may occur, and may result in death.

107 dogs were treated in Phase 1 of a 13 centre, open label, 84 day study in the US. Dogs ranged from 6-16 years and weighed 3-54 kg. 91 dogs continued into Phase 2 for a further 91-529 days (mean 348 days). During Phase 1 (up to day 84 of VETORYL treatment), adverse events were observed in 93 dogs (87%); during Phase 2 adverse events were observed in 88 dogs (96%).

In both phases of the US field study, the following adverse reactions (most of which were mild and transient) were seen:

Clinical observations

Phase 1 : Up to 84 days

N=107

Phase 2 : After 84 days

N=91

Number of dogs

% of dogs

Number of dogs

% of dogs

Diarrhea (± blood)

68

63.6

29

31.9

Musculoskeletal signs (including cruciate rupture)

29a

27.1

35

38.5

Lethargy / depression

29

27.1

29

31.9

Inappetence / anorexia

27

25.2

33

36.3

Vomiting

26

24.3

32

35.2

Urinary tract infection / hematuria

18

16.8

18

19.8

Neurological signsb

10

9.3

21

23.1

Hyperadrenocorticism

10

9.3

19c

20.9

Hyperadrenocorticism related skin disorder

10

9.3

16

17.6

Panting

9

8.4

20

22.0

Otitis

9

8.4

15

16.5

Hypoadrenocorticism: consisting of

7

6.5

12

13.2

Hypocortisolemia, electrolytes normal, with clinical signs

1d

0.9

8d

8.8

Adrenal necrosis (1 case unconfirmed)

2e

1.9

NR

-

Atypical: hyperkalemia, hyponatremia, but normocortisolemia

3

2.8

2

2.2

Typical: hypocortisolemia, hyperkalemia, hyponatremia

1d

0.9

2

2.2

Respiratory signs / dysfunction

7

6.5

16

17.6

Mass - various neoplastic & non neoplastic

6

5.6

27

29.7

Polyuria / polydipsia

6

5.6

24

26.4

Pyoderma

6

5.6

11

12.1

Shaking / shivering

6

5.6

6

6.6

Death/euthanasia

5f

4.7

17g

18.7

Inappropriate elimination

5

4.7

15

16.5

Polyphagia

5

4.7

10

11.0

Restless / anxious / pacing

4

3.7

8

8.8

Diabetes mellitus (1 case unconfirmed)

4

3.7

5

5.5

Weight loss

3

2.8

9

9.9

Pancreatitis

1

0.9

3

3.3

Hypertension

1

0.9

1

1.1

Corticosteroid withdrawal syndrome

2d

1.9

NR

-

Soft tissue infection

NR

-

8

8.8

Liver enzymes increased

NR

-

4d

4.4

Azotemia

NR

-

3

3.3

Hemorrhage / anemia

NR

-

2

2.2

Renal disease

NR

-

2

2.2

NR = not reported

a One dog withdrawn from study due to collapse of back legs; one dog withdrawn due to unmasking of degenerative joint disease as cortisol levels reduced.

b Neurological signs consisted of CSN signs, seizure or increase in seizure frequency, facial paralysis, or peripheral nervous system signs.

c One dog withdrawn with hyperadrenocorticism at VETORYL dose of 20 mg/kg/day.

d One dog withdrawn from study.

e Dog adrenal rupture secondary to unconfirmed adrenal necrosis withdrawn from study.

f Due to adrenal necrosis (1 dog); progression of pre-existing congestive heart failure (2 dogs); central nervous system signs (1 dog); cognitive decline (1 dog).

g Due to possible association with VETORYL (2 cases); diseases normally found in geriatric dogs (15 cases).

Less than 1% reported: ocular disease, gastric ulcer, hepatomegaly, immune mediated hemolytic anemia (dog withdrawn from study) and pyrexia.

In Phase 1 of the study (up to Day 84 of treatment) complete blood counts conducted pre- and post-treatment revealed a statistically significant (p<0.05) reduction in red cell parameters (HCT, HGB, and RBC), but the mean values remained within the normal range. Approximately 10% of the dogs had elevated BUN (> 14.3 mmol/L, 40 mg/dL) in the absence of concurrent creatinine elevations, but were, in general, clinically normal at the time of the elevated BUN.

In two six-month UK field studies with 75 dogs dosed once daily with VETORYL Capsules, the most common adverse reactions seen were lethargy, vomiting, inappetence or anorexia, hyperadrenocorticism-related dermatological signs, diarrhea, polyuria/polydipsia, musculoskeletal signs (lameness, worsening degenerative joint disease) and panting. Other reported events included: change in coat color, vaginal discharge and vulvar swelling in a spayed female, persistent estrus, hypoadrenocorticism, collapse and seizure. One dog died of congestive heart failure, another of pulmonary thromboembolism. Three dogs were euthanized: renal failure (2 dogs), worsening arthritis and deterioration of appetite (1 dog).

In a six-month UK field study with 33 dogs dosed twice daily with VETORYL Capsules, similar adverse reactions were seen as with dogs treated once daily. Two dogs were euthanized due to progression of pituitary-tumour-associated neurological signs (1 dog), and hind limb weakness (1 dog).

86 dogs from UK field studies were included in a follow-up survey (mean duration of follow-up: 82 weeks, range 2-210). 3 dogs were euthanized due to acute onset hemorrhagic diarrhea or hemorrhagic gastroenteritis; it is possible these cases were related to an acute Addisonian crisis, although no diagnostic tests or necropsy were performed. Other adverse reactions were similar to those observed in short-term studies.

Foreign market experience: The following have been reported voluntarily during post-approval use of VETORYL Capsules. The most serious events were death, adrenal necrosis, hypoadrenocorticism (electrolyte alterations, weakness, collapse, anorexia, lethargy, vomiting, diarrhea, and azotemia), and corticosteroid withdrawal syndrome (weakness, lethargy, anorexia, and weight loss). Additional adverse events included: renal failure, diabetes mellitus, pancreatitis, autoimmune hemolytic anemia, vomiting, diarrhea, anorexia, skin reactions (rash, erythematous skin eruptions), hind limb paresis, seizures, neurological signs from growth of adenomas, oral ulceration, and muscle tremors.

Clinical Pharmacology

Trilostane (4α, 5α-epoxy-17β-hydroxy-3-oxoandrostane-2α-carbonitrile) is an orally active synthetic steroid analogue that selectively inhibits 3 â-hydroxysteroid dehydrogenase in the adrenal cortex, thereby inhibiting the conversion of pregnenolone to progesterone. This inhibition blocks production of glucocorticoids and to a lesser extent, mineralocorticoids and sex hormones while steroid precursor levels increase.

Chemical structure

Pharmacokinetic Properties:

Pharmacokinetic data in dogs have demonstrated large inter-individual variability. Trilostane absorption is enhanced by food administration. In healthy dogs, mean maximal plasma concentrations occur 1.7-3.8 hours following administration and return to baseline by about 12 hours. There is no evidence that trilostane or its major metabolite, ketotrilostane, accumulate with time.

Safety and Efficacy Study Information:

Effectiveness

Of the 107 dogs with hyperadrenocorticism that were enrolled in Phase 1 of an 84 day multi-center US field study, 103 dogs were included in the effectiveness assessment. Additionally, 108 dogs could be assessed from the three UK field studies. Results of these studies demonstrated that treatment with VETORYL Capsules resulted in an improvement in clinical signs (decreased thirst, decreased frequency of urination, decreased panting and improvement of appetite and activity). Improvement in post ACTH cortisol levels occurred in most cases within 14 days of starting VETORYL Capsules therapy. By day 84 of Phase 1 of the US field study, 77.3% of dogs were considered treatment successes, with both post ACTH serum cortisol <250 nmol/L (9.1 µg/dL) and clinical improvement.

In Phase 2 of the US field study (continuing after 84 days), mean post ACTH cortisol concentrations for each of the quarterly examination periods were within normal limits and > 75% of dogs were scored as stable or improved on the assessment scoring made at each quarterly examination.

In these three studies, there were a total of 21 dogs diagnosed with hyperadrenocorticism due to either an adrenal tumour or concurrent pituitary and adrenal tumours. Evaluation of these cases failed to demonstrate a difference in clinical, endocrine or biochemical response when compared to cases of pituitary-dependent hyperadrenocorticism.

Animal Safety

In an initial 12 week laboratory study in Beagles, three treatment groups (3 animals/sex/group) received doses of 1X, 2X and 5X the recommended average starting dose of VETORYL Capsules of 6 mg/kg once daily. A control group received empty gelatine capsules only. A decrease was recorded in food consumption values of the 5X group females only from day 11 through to study termination. Serum concentrations of sodium and chloride decreased between days 7 and 28 in all treated dogs and red blood cell counts decreased in treated male dogs. These were considered to be pharmacological effects.

In a subsequent study, VETORYL Capsules were administered to 8 healthy 6 month old Beagles per group at 0X (empty capsules), 1X, 3X and 5X the maximum starting dose of 6.7 mg/kg twice daily for 90 days. Three animals in the 3X group (receiving 20.1 mg/kg twice daily) and five animals in the 5X (receiving 33.5 mg/kg twice daily) died between Days 23 and 46. They showed one or more of the following clinical signs: decreased appetite, decreased activity, weight loss, dehydration, soft stool, slight muscle tremors, diarrhea, lateral recumbency, and staggering gait. Bloodwork showed hyponatremia, hyperkalemia, and azotemia, consistent with hypoadrenocortical crisis. Post-mortem findings included epithelial necrosis or cystic dilation of duodenal mucosal crypts, gastric mucosal or thymic hemorrhage, atrial thrombosis, pyelitis and cystitis, and inflammation of the lungs.

ACTH stimulated cortisol release was reduced in all dogs treated with VETORYL Capsules. The dogs in the 3X and 5X groups had decreased activity. The 5X dogs had less weight gain than the other groups. The 3X and 5X dogs had lower sodium, albumin, total protein, and cholesterol compared to the control dogs. The 5X dogs had lower mean corpuscular volume than the controls. There was a dose dependent increase in amylase. Post-mortem findings included dose dependent adrenal hypertrophy in all treated dogs, including dogs in the 1X group.

Information for dog owners:

Be aware that the following side effects may indicate that your dog is having a problem with VETORYL Capsules:

- Stops eating or looses interest in food

- Vomiting

- Change in bowel movement (such as diarrhea or loose stools)

- Depression, lethargy or decreased activity.

As VETORYL Capsules control the hyperadrenocoticism, there should be a decrease in food and water consumption to normal levels.

Serious adverse reactions associated with this drug can occur without warning and, in rare situations, result in death. Discontinue VETORYL Capsules and contact your veterinarian IMMEDIATELY if you think your dog has a medical problem or side effect from VETORYL Capsules.

It is extremely important for your dog to visit your veterinarian regularly for checkups when taking VETORYL Capsules.

Storage

Store between 15°C and 30°C.

Presentation:

Vetoryl 10 mg Capsules, code 992125

Vetoryl 30 mg Capsules, code 990862

Vetoryl 60 mg Capsules, code 990867

Each carton contains a total of 30 capsules (3 blister packs, each containing 10 capsules).

Manufacturer: Dechra Ltd., Dechra House, Jamage Industrial Estate, Talke Pits, Stoke-on-Trent, ST7 1XW, UK

Distributed by: Vétoquinol N.-A. Inc., 2000 ch. Georges, Lavaltrie, QC, J5T 3S5, Canada

VETORYL is a registered trademark of Dechra, Ltd.

1 Greco D S, Behrend E N (1995) Corticosteroid withdrawal syndrome. In Kirk’s Current Veterinary Therapy XII; Bonagura J. (ed): W B Saunders, Philadelphia PA: pp 413-5.

F623

NAC No.: 12343020

VÉTOQUINOL N.-A. INC.
Commercial Division

2000, CHEMIN GEORGES, LAVALTRIE, QC, J5T 3S5
Telephone:   450-586-2252
Order Desk:   800-363-1700
Fax:   450-586-4649
Website:   www.vetoquinol.ca
Email:   info@vetoquinol.ca
Every effort has been made to ensure the accuracy of the Vetoryl 60 mg information published above. However, it remains the responsibility of the readers to familiarize themselves with the product information contained on the Canadian product label or package insert.

Copyright © 2014 North American Compendiums. Updated: 2014-05-28

(web5)