VETPRIL 20MG 14 TABLETS – For Canine Heart Failure -Feline Renal

VETPRIL 20mg 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each divisible tablet contains:
Benazepril…………………………………………………………. 4,6mg
(equivalent to 20 mg benazepril hydrochloride)
Excipients:
Titanium dioxide (E171)……………………………………. 1,929mg
Iron oxide yellow (E172) ………………………….. 0,117 mg
Iron oxide red (E172)………………………………… 0,014 mg
Iron oxide black (E172) ………………………….. 0,004 mg
For the full list of excipients, see section 6.1.
3. PHARMACEUTICAL FORM
film-coated tablet
Beige biconvex oblong divisible film-coated tablets
4. CLINICAL DATA
4.1 Target species
Dogs and cats
4.2 Indications for use, specifying the target species
Dogs: Treatment of congestive heart failure in dogs weighing more than 5 kg.
Cats: Reduction of proteinuria associated with chronic kidney disease.
4.3 Contraindications
Do not use in case of hypersensitivity to the active substance or to any of the excipients.
Do not use in cases of hypotension, hypovolemia, hyponatremia or acute renal failure.
Do not use in cases of decreased cardiac output due to aortic or pulmonary stenosis.
Do not use during pregnancy or lactation.
See section 4.7.
4.4 . Special warnings for each target species
Not applicable
4.5 Special precautions for use
Yo. Special precautions for use in animals

During clinical trials (in dogs or cats) no evidence of
renal toxicity of the drug, however, as is routine in cases of
chronic kidney disease, during treatment it is recommended to monitor the
plasma creatinine, urea, and erythrocyte count.
The efficacy and safety of benazepril have not been established in dogs and cats with a
weight less than 2,5 kg.

Wash hands before use.
In case of accidental ingestion, consult a doctor immediately and show him the
label or package insert.
Pregnant women should take special precautions to avoid exposure
accidental oral since it has been observed that in humans the inhibitors of the enzyme
Angiotensin converting cells (ACE) affect the fetus during pregnancy.
4.6 Adverse reactions (frequency and seriousness)
In double-blind clinical trials in dogs with congestive heart failure, benazepril
was well tolerated, with an incidence of adverse reactions lower than that observed in the
placebo-treated dogs.
A small number of dogs may show vomiting, lack of coordination, or signs of
transient fatigue.
In cats and dogs with chronic kidney disease, benazepril might increase the
plasma creatinine concentrations at the start of treatment. A moderate increase of
plasma creatinine concentrations after administration of ACE inhibitors is
compatible with the reduction of glomerular hypertension induced by these agents, and therefore
therefore not necessarily a reason to discontinue treatment in the absence of other signs.
Benazepril may rarely increase food intake in cats.
Rarely, emesis, anorexia, dehydration, lethargy, and diarrhea have occurred in
cats.
It is recommended to monitor plasma creatinine concentrations and blood counts.
erythrocytes during therapy.
4.7 Use during pregnancy, lactation or lay
Do not use during pregnancy or lactation. The safety of benazepril has not been established.
in breeding, pregnant or lactating dogs and cats. Benazepril reduced ovarian/oviductal weights
in cats when administered daily at 10 mg/kg for 52 weeks. They have
observed embryotoxic effects (fetal urinary tract malformation) in trials with
laboratory animals (rats) at doses non-toxic to the mother.
4.8. Interaction with other medicinal products and other forms of interaction
In dogs with congestive heart failure, benazepril has been administered in
combination with veterinary drugs digoxin, diuretics, pimobendan and antiarrhythmics
No demonstrable adverse interactions.
In humans, the combination of ACE inhibitors and anti-inflammatory drugs does not
steroids (NSAIDs) may lead to reduced antihypertensive efficacy or to

renal insufficiency. The combination of benazepril and other antihypertensive agents (eg.
calcium channel blockers, β-blockers or diuretics), anesthetics or sedatives
may lead to increased hypotensive effect. Therefore, the concomitant use of NSAIDs or
Other drugs with a hypotensive effect should be considered with caution. shall
Closely monitor renal function and signs of hypotension (lethargy, weakness,
etc) and treated if necessary.
Interactions with potassium-sparing diuretics such as spironolactone, triamterene, or
amiloride cannot be excluded. It is recommended to monitor plasma potassium levels
when benazepril is used in combination with a potassium-sparing diuretic due to the
risk of hyperkalemia.
4.9 Amounts to be administered and administration route
In dogs:
The dose is 0,23 mg benazepril/kg bw and day, which corresponds to 0,25 mg of benazepril hydrochloride.
benazepril/kg bw and day. It should be administered orally once a day, with meals or
out of them. This dose corresponds to 1 tablet per 20 kg, according to the following table:

If considered clinically necessary and advised by a veterinarian, the
dose (maintaining a single dose).
In cats:
The dose is 0,46 mg benazepril/kg bw and day, which corresponds to 0,50 mg of benazepril hydrochloride.
benazepril/kg bw and day. It should be administered orally once a day, with meals or
out of them. This dose corresponds to 1 tablet per 10 kg, according to the following table:

4.10 Overdose (symptoms, emergency procedures, antidotes), if necessary
Benazepril reduced the erythrocyte count in normal cats at a dose of 10 mg/kg once
once daily for 12 months and in normal dogs at a dose of 150 mg/kg once daily
for 12 months, but this effect was not observed during clinical trials in dogs and
cats at the recommended dose.
Transient and reversible hypotension may occur in cases of accidental overdose.
Treatment consists of intravenous infusion of warm isotonic saline.
4 Waiting time
Not applicable
5. PHARMACOLOGICAL PROPERTIES
Pharmacotherapeutic group: ACE inhibitors, benazepril
ATCvet code: QC09AA07

5.1 Pharmacodynamic properties
Benazepril hydrochloride is a prodrug hydrolyzed in vivo to its active metabolite,
benazeprilat. Benazeprilat is a highly potent selective ACE inhibitor.
thus preventing the conversion of inactive angiotensin I to active angiotensin II and thus
also reducing the synthesis of aldosterone. Therefore, it blocks the effects mediated by the
angiotensin II and aldosterone, including arterial and venous vasoconstriction, retention
of sodium and water by the kidneys and remodeling effects (including cardiac hypertrophy
pathology and degenerative renal changes).
Benazepril causes long-term inhibition of plasma ACE activity in
dogs and cats, producing an inhibition of more than 95% of the maximum effect and an activity
significant (>80% in dogs and >90% in cats) that persists 24 hours after the
administration.
Benazepril reduces blood pressure and heart volume load in dogs with
congestive heart failure.
In cats with experimental kidney disease, benazepril normalized capillary pressure.
elevated glomerular and decreased systemic blood pressure. The reduction of hypertension
glomerulus may slow the progression of kidney disease by inhibiting extra damage to
the kidneys. Placebo-controlled clinical field trials in cats with disease
chronic kidney disease (CKD) have shown that benazepril significantly reduced the levels of
urine protein and urine protein-creatinine (UCP) ratio; this effect is
probably due to the reduction in glomerular hypertension and the beneficial effects
on the glomerular basement membrane.
No effect of benazepril on survival in cats with CKD has been observed, but the
benazepril increased the appetite of cats, particularly in more advanced cases.
5.2. Pharmacokinetic data
Following oral administration, benazepril is rapidly absorbed from the gastrointestinal tract.
A part of absorbed benazepril is hydrolyzed by hepatic enzymes to the active substance,
benazeprilat; the rest is metabolized into hydrolyzed compounds or subsists as
unchanged benazepril. Absolute systemic bioavailability, calculated for oral benazepril
versus intravenous benazepril is approximately 9%. The peak concentration of
benazeprilat is reached in approximately 2 hours, both in fasting and
taking food.
Benazepril and benazeprilat are predominantly bound to plasma proteins. The
Repeated administration leads to a slight accumulation of benazeprilat in the plasma, which
it reaches steady state in less than 4 days.
In dogs, the majority of benazeprilat is rapidly eliminated, and is excreted in the
same proportion through the hepatic and urinary routes.
After administration of a single dose of the veterinary medicinal product (0,23 mg
benazepril/ kg bw), the peak concentration of benazeprilat is reached (Cmax of 40,9
ng/ml) for about 1,5 h (Tmax of 1,5 h), with an AUC of 320,5 ng/ml.h and a lifetime
mean (t1/2) of 12,4 h.

Benazeprilat is excreted 85% via the bile and 15% via the urine in cats.
Benazeprilat voiding does not affect cats with reduced glomerular filtration and therefore
Therefore, no dose adjustment is required.
After administration of a single dose of the veterinary medicinal product in cats (0,46
mg benazepril/ kg bw), the peak concentration of benazeprilat is reached (Cmax of 198,7
ng/ml) for around 1 h (Tmax of 1,03 h), with an AUC of 969,4 ng/ml.h and a lifetime
mean (t1/2) of 13,9 h
6. PHARMACEUTICAL DATA
6.1 List of excipients
Yellow iron oxide (E-172)
Red iron oxide (E-172)
Black iron oxide (E-172)
Titanium dioxide (E-171)
Microcrystalline cellulose
Lactose monohydrate
Povidone
Cornstarch
colloidal anhydrous silica
Magnesium stearate
hypromellose
macro goal 8000
6.2 Incompatibilities
None known.
6.3 Validity period
Shelf-life of the veterinary medicinal product packaged for sale: 18 months
Return any divided tablets to the blister pack and use within one day. The blister should
be put back in the box.
6.4 Special precautions for storage
Do not store at temperatures above 25ºC.
Protect from light. Store in a dry place.
6.5 Nature and composition of immediate packaging:
Blisters made of a transparent PVC/PE/PVDC and aluminum film, with 14
pills.
Boxes with:
– 1 blister (14 tablets)
– 10 blisters (140 tablets)
Not all formats may be marketed.

6.6 Special precautions for disposal of unused veterinary medicinal product
or, where appropriate, the residues derived from its use
Any unused veterinary medicinal product or residues derived from it must be
disposed of in accordance with local regulations.
7. MARKETING AUTHORIZATION HOLDER
Vetpharma Animal Health, SL
Les Cortes, 23
08028 Barcelona
SPAIN
8. MARKETING AUTHORIZATION NUMBER(S)
2666 ESP
9. DATE OF THE FIRST AUTHORIZATION OR RENEWAL OF THE
AUTHORIZATION
November 06th 2012
10. DATE OF REVISION OF THE TEXT
November 06th 2012
PROHIBITION OF SALE, DISPENSATION AND/OR USE
Veterinary use-Medication subject to veterinary prescription
Administration under control or supervision of the veterinarian

See technical sheet

VETPRIL