The veterinary medicine Vetoril (trilostan) is produced the pharmacological company Dechra Limited (Great Britain) and day syndrome intended for treatment of a hypophysial and dependent and adrenal-dependent giperadrenokortitsizm (disease and Cushings syndrome) of dogs

On todays by Cushing most widespread hormonal violation at dogs most ten meeting at dogs senior and advanced age . B period disease an organism dog develops raised quantity hormone cortisone which usually developed by an organism an animal at emergence stressful situation . Surplus it hormone negative influences on all internal bodies an animal sharp reduces activity your dog . Excessive development cortisone in 85 % cases investigation tumor ( good-quality or malignant ) adrenal glands or hypophysis .

Smptoma syndrome Cushing

frequent urination,

increased thirst,

muscle weakness,

local alopetion (baldness),

drowsiness.

refore establishment of the diagnosis perhaps after clinical trials and ultrasonography.

Lack of timely treatment not only worsens quality of life of your pet, but also can lead to serious diseases:

• diabetes,
• an infection of kidneys and urinary tract,
• emergence of blood clots in lungs and other illnesses.

Medicine Vetoril in the best way allows to localize today Kushers syndrome and to control his development. By means of this medicine regulating development of a cortisone you will be able to improve quality of life of the pet for many years.

Medicine Vetoril issued in the form of the capsules containing 10, 30, 60 mg of medicine and is accepted orally together with a forage once a day. The dosage of medicine depends on the mass of your dog and approaches according to the instruction medicine (approximately 6 mg/kg of body weight of an animal).

After reception medicine is quickly soaked up in blood and removed with a stake and mochy within day, than and the norm of intake of medicine is caused: once a day.

Medicine has a number of contraindications among which: the ban on prescribing of medicine an animal with a weight a body is less than 3 kg, pregnant with the animal having a renal or liver failure, and also with individual intolerance of separate components.

ATTENTION!!! Before use of medicine the consultation of the veterinarian is necessary. Intake of medicine should be carried out after acquaintance with the instruction for application.

Instruction for veterinary use of Vetoril medicine
(developer organization: Dekhra Limited, Great Britain)

Trade name of medicine: Vetoril® of the capsule (Vetoryl® capsules).

International non-proprietary name: trilostan.
Dosage form:
Capsules Active ingredient: trilostan

Structure:
In one firm gelatin capsule of the medicine Vetoril® of the capsule of 10 mg contains in quality of active ingredients: a trilostana – 10 mg, and as excipients: dioxide of titanium (E171) – 0.942 mg, iron oxide yellow (E172) – 0.035 mg, iron oxide black (E172) – 0.532 mg, corn starch, magnesium stearate and lactoses monohydrate.
In one firm gelatin capsule of the medicine Vetoril® of the capsule of 30 mg or Vetoril® of the capsule of 60 mg contains in quality of active ingredients: a trilostana – 30 or 60 mg respectively, and as excipients: dioxide of titanium (E171) – 1.19 mg, iron oxide yellow (E172) – 0.045 mg, iron oxide black (E172) – 0.672 mg, corn starch, magnesium stearate and lactoses monohydrate.
In one firm gelatin capsule of the medicine Vetoril® of the capsule of 120 mg contains in quality of active ingredients: a trilostana – 120 mg, and as excipients: dioxide of titanium (E171) – 1.885 mg, iron oxide yellow (E172) – 0.071 mg, iron oxide black (E172) – 1.064 mg, corn starch, magnesium stearate and lactoses monohydrate.
Structure of a cover of the capsule: gelatin, dioxide of the titan, iron oxide (yellow), oxide of iron (black).
Structure of a cap of a cover of the capsule: dioxide of the titanium, iron oxide (black), shellac.

application Order:
Vetoril® of the capsule is applied orally with a forage once a day. Clinical trials showed efficiency of an average day dosage — 6 mg/kg of body weight of an animal. The dose has to be picked up concerning reaction to therapy by the corresponding monitoring (see further). The following initial dosages are recommended:

Initial daily dose

Body weight (kg)	Initial dose (mg)
≥ 1.7 - <4.5	10
≥ 4.5 - <10	30
≥ 10 - <20	60
≥ 20 - <40	120
≥ 40 - <60 *	180 (1 x 120 mg and 1 x 60 mg)

* to Dogs, weighing over 60 kg it is necessary to give the corresponding combination of capsules.

Dose has to be picked up by

concerning reaction to therapy by the corresponding monitoring (see further).

If increase in a dose is required, then gradually raise a day dose, using combinations of capsules of the different sizes. Wide range of the sizes of capsules provides optimum dispensing for any dog. It is necessary to accept the smallest dose which will be enough for control of clinical signs.

Eventually if symptoms do not manage to be controlled adequately during the 24-hour period between receptions, then it is necessary to consider a question of increase in a daily dose for 50% and/or to its division into equal morning and evening doses. But you do not divide and do not open the capsule.

doses considerably exceeding 10 mg/kg of weight a day can be required by Some animals. In such cases it is necessary to carry out additional monitoring.

When lower dosages of a trilostan as it can be concerning very small breeds of dog the minimum dosage are required for

will is limited to the size of capsules, and it cannot be lower than 10 mg of a trilostan.

Monitoring:
Before an initiation of treatment, in 10 days, 4 weeks, 12 weeks and further each 3 months after an initiation of treatment and after each increase in a dose it is necessary to perform detailed inspection. The minimum protocol of such survey has to contain the detailed anamnesis, fizikalny inspection, stimulating tests at with AKTG (in 4-6 hours after reception of Vetoril® of the capsule), biochemical blood test (with special attention to electrolytes, kidney and hepatic profiles). For the most exact interpretation it is extremely important to execute the test with AKTG for 4 — 6 hours after reception. Intake of medicine since morning is more preferable as it will allow your doctor to execute monitoring tests for 4 — 6 hours after intake of medicine.

After 10-14 days after the beginning of use of medicine or increase in a dose it is necessary to perform inspection and to execute the stimulating test with AKTG. Act on the basis of results of inspection according to the table:

Post-AKTG cortisol in serum		Action
mkg/dl	nmol/L
<1.45	<40	Stop treatment. To begin anew with reduction of a dose.
From 1.45 to 5.4	From 40 to 150	Continue with the same dosage.
> 5.4 to 9.1	> 150 to 250	Or: To continue with the same dosage if improvement of a clinical picture is observed. Or: To raise a dosage if geperadrenokortitsizm symptoms – are still expressed *
> 9.1	> 250	Increase an initial dose.

* Combinations of capsules with various concentration should be used for slow increase in an initial dose.

According to clinical trials, for the majority of dogs, finally the dose was stabilized at the level of 2-10 mg/kg a day. If symptoms do not pass throughout the 24-hour period between intake of medicine, then it is necessary to consider as far as it is possible, small increase in the general daily dose and/or to divide into morning and evening receptions. But you do not divide and do not open the capsule.

doses considerably exceeding 10 mg/kg of weight a day can be required by Some animals. In such cases it is necessary to carry out additional monitoring.
When are required lower dosages of a trilostan as it can be concerning very small breeds of dog the minimum dosage will is limited to the size of capsules and it cannot be lower than 10 mg of a trilostan.

Contraindication: Contraindication for use of medicine is the individual hypersensibility of an animal to medicine components. It is forbidden to give to dogs weighing less than 3 kilograms, and also at primary liver and renal failure. not to apply
during pregnancy. Data on laboratory animals show teratogenny effect and death of a fruit at early stages of pregnancy.

Scientific data
Vetoril® of the capsule (trilostan) – medicine of group of the adrenal glands suppressing function.

action Mechanism:
Trilostan (4a, 5a-epoxy-17-hydroxy-3-oksoandrosten-2a-karbonitril) is an analog of synthetic steroid which is active at oral application. Trilostan selectively inhibits a 3B-hydroxysteroid hydrogenaza in adrenal gland bark, thus suppressing transformation of a pregnenolon to progesterone. This suppression blocks development of glucocorticoids and to a lesser extent, mineralokortikoid and sex hormones while the level of precursors of steroids increases. Trilostan also counteracts effect of exogenous adrenocorticotropic hormone (AKTG).
It has no direct impact on the central nervous and cardiovascular systems.

Efficiency:
In three field researches took part in the sum of 113 dogs with a giperadrenokortitsizm. Results of these researches showed that use of the medicine Vetoril® of the capsule led to improvement of clinical manifestations (decrease in thirst, decrease in frequency of urination, decrease in short wind, improvement of appetite and activity). Decrease in level of post-AKTG of cortisol was in most cases shown within 14 days after the beginning of use of the medicine Vetoril® of the capsule.
participated 10 dogs with the giperadrenokortitsizm caused by a tumor of an adrenal gland or the accompanying tumors of a hypophysis and adrenal glands In these three researches. Assessment of these cases could not reveal a difference in clinical, endocrine or biochemical reaction in comparison with cases of a hypophysial giperadrenokortitsizm.

Pharmacokinetics: Pharmacokinetic data at dogs showed to
big variability between various individuals. Pharmacokinetic researches on laboratory dogs of breed a beagle established AUC in the range from 52 to 281 mkg/ml/min. when giving medicine with a forage, and from 16 to 175 mkg/ml/min. at intake of medicine on toshchak. In general trilostan it is quickly brought out of plasma and at achievement of the maximum concentration by 1.5 oclock in the range from 0.5 to 2.5 hours returns almost to initial level to the sixth – the twelfth hour after introduction. The main active metabolite of a trilostan, ketotrilostan has similar pharmacokinetics. Besides, there are no proofs that trilostan or its metabolites collect eventually. Bioavailability researches at dogs at oral application showed what trilostan is soaked up better at reception with food.
Removal of a trilostan from an organism was shown on rats. Trilostan and its metabolites were found mainly in excrements of rats that indicates removal with bile as the main way of removal. Researches on monkeys showed what trilostan is brought out of an organism in equal quantities with a stake and urine. Besides, results of researches showed what trilostan is quickly and well soaked up from digestive tract in as rats and monkeys and that it collects in adrenal glands of rats.

Toxicology:
Preclinical studies were conducted on six-month dogs of breed the Beagle divided into groups on 8 dogs in everyone. Groups: 0X (placebo), 1X, 3X, and 5X a multiple maximum initial dose of a trilostan — 6.7 mg/kg twice a day, within 90 days. Three dogs in group 3X (the receiving 20.1 mg/kg twice a day) and five dogs in group 5X (the receiving 33.5 mg/kg twice a day) died between the 23 and 46 day of treatment. They showed the following symptoms: loss of appetite, decrease of the activity, loss of weight, dehydration, soft chair, essential muscular tremor, diarrhea, lying on one side and shaky gait. Blood test revealed the giponatriyemiya, a giperkaliyemiya and an azotemiya corresponding to gipoadrenokortikoidny crisis.
Use of the medicine Vetoril® of the capsule lowered post-AKTG cortisol at all dogs. Dogs in groups 3X and 5X had the lowered activity. A dog from group 5X it is worse than other groups gained weight. Dogs from groups 3X and 5X had the lowered sodium, albumine and the general level of a protein, in comparison with control groups. At dogs of group 5X gematokrit was lower, than in control groups. Dose-dependent growth of amylase was noted. The pathoanatomical research in addition revealed a dose-dependent hypertrophy of bark of an adrenal gland.

Field researches:
In a field research in which 107 dogs – necrosis / apopleksiya adrenal glands (two dogs) participated and a gipoadrenokortitsizm (two dogs) were the heaviest undesirable reactions in a research. One dog suddenly died from necrosis of adrenal glands approximately in one week after an initiation of treatment trilostany. At one dog the adrenal gland apopleksiya, presumably as a result of adrenal gland necrosis, approximately in six weeks after an initiation of treatment trilostany developed. This dog was helped by refusal of a trilostan and the supporting therapy.
At two dogs during treatment developed a gipoadrenokortitsizm. These two dogs had symptoms corresponding to a gipoadrenokortitsizm (drowsiness, anorexia, collapse) and the level of post-AKTG of cortisol — it is less than 0.3 mkg/dl. Both dogs were helped by refusal of a trilostan and the supporting therapy of a gipoadrenokortitsizm (mineralokortikoida glyukokortikoidy) after sharp manifestation. Additional undesirable reactions were observed at 93 dogs. Were the most widespread: diarrhea (31 dogs), drowsiness (30 dogs), absence appetite/anorexia (27 dogs), vomiting (28 dogs), skeletal and muscular symptoms (lameness, progressing of degenerative diseases of joints) (25 dogs), an infection of urinary channels / gematuriya (17 dogs), a shiver/tremor (10 dogs), external otitis (8 dogs), respiratory symptoms (cough, the complicated breath) (7 dogs) and also reactions on skin (seborrhea, an itch) (8 dogs).
Five dogs died or was lulled during the research (one dog in connection with the above secondary necrosis of adrenal glands, two dogs – because of the progressing heart failure with developments of stagnation, one dog – because of the progressing violations of central nervous system and one because of decrease in cognitive abilities which led to allocation violations). In addition to two dogs with necrosis of adrenal glands / apopleksiyey and to two more with a gipoadrenokortitsizm, four more dogs were brought from researches because of possible undesirable reactions, including collapse, drowsiness and a shiver.
showed the Complete analysis of blood which is carried out before treatment significant (p <0.005) decrease in erythrocyte indicators (gematokrit, hemoglobin, quantity of erythrocytes), however values remained within norm. Besides, about 10% of dogs had increased values of urea (BUN) (≥ 40 mg/dl) in the absence of the accompanying increase in creatine. In general, the condition of these dogs was normal.

efficiency Research at long medical examination of dogs in clinic revealed the undesirable reactions similar to undesirable reactions at a short-term research. Most often observed vomiting, diarrhea and the general disorders of a GIT. Also observed: drowsiness, loss appetite/anorexia, warm noise or warm and pulmonary violations, problems with urination, incontinence of urine, infection of urinary channels or diseases of an urinogenital system and neurologic violations. At long medical examination revealed 14 fatal cases, three of which are possibly connected with trilostany. 11 dogs died or were lulled during the research on various reasons which were untied or are connected with application of a trilostan in the unknown way. In two field researches conducted on 75 dogs, the most widespread of undesirable reactions were: vomiting, drowsiness, diarrhea / soft chair and anorexia. Other undesirable reactions included: nocturia, a cornea ulcer, cough, a steady techka, allocations from a vagina and swelling of genitals at the sterilized female, a gipoadrenokortitsizm, violation of balance of electrolytes (the raised potassium at the lowered or normal sodium), faints and paroxysms, a shiver, a muscular tremor, stagnation of a stomach, itch, a set of weight and loss of weight. One dog died from heart failure with developments of stagnation, another – from a pulmonary thrombembolia. Three dogs were lulled during the researches. The renal failure was found in two dogs, at one more – progressing of arthritis and violation of appetite began.

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In a field research at long medical examination of dogs noted the following undesirable reactions: a gipoadrenokortitsizm case (including collapse, a shiver, weakness and vomiting), gipoadrenokortikalny crisis or a renal failure (including an azotemiya, vomiting, dehydration and collapse), chronic faltering allocations from a vagina, hemorrhagic diarrhea, periodic vomiting and distal hypostasis of extremities. Symptoms of a gipoadrenokortitsizm were usually reversible after refusal of medicine, but can become constants. To one dog of Vetoril® of the capsule it was cancelled, however at survey one year later, it still had gipoadrenokortitsizm symptoms. In the report on a research there are messages about fatal cases 5 of which are perhaps connected with intake of medicine. They include dogs who died, or were lulled because of a renal failure, gipoadrenokortikalny crisis, hemorrhagic diarrhea and a hemorrhagic gastroenteritis. Voluntary messages during postregistration application of Vetoril® of the capsule and abroad. The most serious undesirable effects were: death, necrosis of adrenal glands, gipoadrenokortitsizm (change of electrolytes, weakness, collapse, anorexia, drowsiness, vomiting, diarrhea and azotemiya), and syndrome of cancellation of corticosteroids (weakness, drowsiness, anorexia, loss of weight). Additional undesirable reactions included: failure of kidneys, diabetes, pancreatitis, autoimmune hemolytic anemia, vomiting, diarrhea, anorexia, skin reactions (irritation, erythematic skin rash), paresis of back extremities, convulsions, neurologic symptoms because of growth of macroadenomas, ulcers in a mouth and a muscular tremor. The veterinarian has to know that dogs with a giperadrenokortitsizm are exposed to the increased risk of pancreatitis. This risk does not decrease during application of a trilostan. There are no data on influence of medicine on feeding a bough and dogs for reproduction.

Medicinal interactions:
Carefully apply Vetoril® of the capsule along with inhibitors of the enzyme transforming angiotensin as both drugs reduce aldosteron and can have additive action, complicating ability of the patient to keep normal balance of electrolytes, volume of blood and blood supply of kidneys. Not to apply Vetoril® of the capsule along with kaliysberegayushchy diuretic medicines (e.g. spironolakton) as both inhibit aldosteron, increasing giperkaliyemiya probability. Mituotangs application (o, p ’-DDD) reduces function of adrenal glands. Experience of application of Mituotang shows worldwide, after phase-out of Mituotang has to pass not less than a month before beginning to apply the capsule medicine Vetoril®. At the same time it is very important to wait for repeated manifestation of symptoms of a giperadrenokortitsizm, and level of post-AKTG of cortisol> 9.1 mkg/dl (> 250th nmol/L). Fixed observation of function of adrenal glands as the dogs who were earlier undergoing treatment mitotany can be more sensitive to the capsule medicine Vetoril® is recommended.

After selection of an optimum dose of the medicine Vetoril® of the capsule, you perform repeated inspections in 30 days, then through 90 and further each 3 months. The stimulating test with post-AKTG cortisol <1.45 mkg/dl (

If the stimulating test with AKTG <1.45 mkg/dl (

Owners need to tell that they stopped use of medicine and immediately saw the veterinarian in case of undesirable reactions or uncharacteristic development of a clinical picture.
Treatment can begin a giperadrenokortitsizm only in case of confirmation of the diagnosis.
If is not observed the obvious answer to medicine, then the diagnosis it is necessary to reconsider.
Vetoril® of the capsule does not affect a tumor of adrenal glands. In reasonable cases, possible option of treatment it is necessary to consider an adrenalektomiya.

Overdose: in case of overdose the symptomatic treatment of a gipoadrenokortitsizm by means of corticosteroids, mineralokortikoid and intravenous injections can be required.

First application: Any doses of the medicine Vetoril® of the capsule can lead to development of a gipoadrenokortitsizm. In certain cases several months on restoration of functions of adrenal glands can leave, but at some dogs the function of adrenal glands is not restored at all.

In ten days after an initiation of treatment at insignificant percent of dogs the syndrome of cancellation of corticosteroids can develop. This phenomenon arises because of sharp cancellation of the circulating glucocorticoids. Symptoms include: weakness, drowsiness, anorexia and loss of weight. These symptoms should be differentiated from early gipoadrenokortikoidny crisis by measurement of concentration of electrolytes in blood and by results of the stimulating test with AKTG. In this case stop reception of Vetoril® of the capsule for 3-7 days (depending on weight of symptoms) and renewal application with lower dose.

in case of allergic reactions use of the medicine Vetoril® of the capsule is stopped and carry out symptomatic therapy.

Interruption of a course, admission of a dose: Cannot allow interruptions of a course of application. At the admission of one or several doses it is necessary to continue immediately a course in the established dosage and with the same intervals of application.

Side effect: Most widespread undesirable reactions include: small appetite, vomiting, drowsiness/slackness, diarrhea and weakness. Sometimes there are more serious reactions: including a deep depression, hemorrhagic diarrhea, collapse, gipoadrenokortikalny crisis. There can also be necrosis or an apopleksiya of adrenal glands which can lead to death.

Measure of personal prevention: When holding treatment-and-prophylactic actions with use of the medicine Vetoril® of the capsule should follow the general rules of personal hygiene and safety measures provided during the work with medicines.

Upon termination of work it is necessary to wash up carefully hands warm water with soap.
People with hypersensitivity to components of medicine should avoid direct contact with the capsule medicine Vetoril®.
do not pour out contents of capsules and do not try to divide capsules. Do not contact to capsules if you are pregnant or you plan conception soon. Trilostan can have teratogenny effect and early termination of pregnancy.
At accidental swallowing / overdose – it is necessary to see a doctor (at itself it is necessary to have package of medicine) immediately.
forbidden use of empty blisters and boxes from under medicine for the household purposes, they are subject to utilization with household waste.

Storage: Vetoril® of the capsule store at a temperature from 15 °C to 30 °C.
Expiration date: 3 years.

Packing: 10, 30, 60 and 120 mg on 10 capsules in blisters, in boxes on 3 blisters.
Producer: Dechra Limited, Dechra Pharmaceuticals PLC, Great Britain

Species of an animalDogsCategory of veterinary medicineHormonal medicinesArea of application of veterinary medicineDiseases of kidneysMedicinesChemotherapeutic medicinesFormCapsules