SUMMARY OF PRODUCT CHARACTERISTICS

VETPRIL 20 mg film-coated tablets for dogs

Each divisible tablet contains:

Active substance:

Benazepril 18.42 mg

(equivalent to Benazepril Hydrochloride 20 mg)

Excipients:

Titanium dioxide (E171) 1.929 mg

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

Film-coated tablets.

Beige oblong biconvexfilm-coated divisible tablets

The tablets can be divided into halves.

4. CLINICAL PARTICULARS:

Dogs

4.2 Indications for use, specifying target species:

In dogs weighing more than 20 kg bw: Treatment of congestive heart failure.

Do not use in case of hypersensitivity to the active substance or to any of the excipients.

Do not use in cases of hypotension, hypovolaemia, hyponatraemia or acute renal failure.

Do not use in cases of cardiac output failure due to aortic or pulmonary stenosis.

Do not use in pregnancy or lactation.

4.4 Special warnings for each target species

None

Special precautions for use in animals

No evidence of renal toxicity of the veterinary medicinal product has been observed in dogs during clinical trials, however, as is routine in cases of chronic kidney disease, it is recommended to monitor plasma creatinine, urea and erythrocyte counts during therapy.

Special precautions to be taken by the person administering the veterinary medicinal product to animals

Pregnant women should take special care to avoid accidental oral exposure, because angiotensin converting enzyme ACE inhibitors have been found to affect the unborn child during pregnancy in humans.

Wash hands after use.

In case of accidental oral ingestion, seek medical advice immediately and show the label or the package leaflet to the physician.

In double-blind clinical trials in dogs with congestive heart failure, the product was well tolerated with an incidence of adverse reactions lower than observed in placebo-treated dogs.

A small number of dogs may exhibit transient vomiting, incoordination or signs of fatigue.

In dogs with chronic kidney disease, the product may increase plasma creatinine concentrations at the start of therapy. A moderate increase in plasma creatinine concentrations following administration of ACE inhibitors is compatible with the reduction in glomerular hypertension induced by these agents, and is therefore not necessarily a reason to stop therapy in the absence of other signs.

Do not use during pregnancy or lactation. The safety of the product has not been established in breeding, pregnant or lactating dogs. Embryotoxic effects (foetal urinary tract malformation) were seen in trials with laboratory animals (rats) at maternally non-toxic doses.

In dogs with congestive heart failure, the product has been given in combination with digoxin, diuretics, pimobendan and anti-arrhythmic veterinary medicinal products without demonstrable adverse interactions.

In humans, the combination of ACE inhibitors and Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) can lead to reduced anti-hypertensive efficacy or impaired renal function. The combination of the product and other anti-hypertensive agents (e.g. calcium channel blockers, β-blockers or diuretics), anaesthetics or sedatives may lead to additive hypotensive effects. Therefore, concurrent use of NSAIDs or other medications with a hypotensive effect should be considered with care. Renal function and signs of hypotension (lethargy, weakness etc) should be monitored closely and treated as necessary.

Interactions with potassium preserving diuretics like spironolactone, triamterene or amiloride cannot be ruled out. It is recommended to monitor plasma potassium levels when using the product in combination with a potassium sparing diuretic because of the risk of hyperkalaemia.

4.9 Amounts to be administered and administration route:

Oral use.

The product should be given orally once daily, with or without food. The duration of treatment is unlimited.

Dogs:

The product should be administered orally at a minimum dose of 0.25 mg (range 0.25-0.5) benazepril hydrochloride/kg body weight once daily, according to the following table:

Weight of dog (kg)	Benazepril hydrochloride 20 mg film-Coated Tablets
	Standard dose	Double dose
>20 - 40	0.5 tablet	1 tablet
>40 – 80	1 tablet	2 tablets

The dose may be doubled, still administered once daily, to a minimum dose of 0.5 mg/kg (range 0.5-1.0), if judged clinically necessary and advised by the veterinary surgeon.

Return any halved tablet to the blister pack and use within 1 day. The blister pack should be inserted back into the cardboard box.

The product reduced erythrocyte counts in normal dogs when dosed at 150 mg/kg once daily for 12 months, but this effect was not observed at the recommended dose during clinical trials in dogs.

Transient reversible hypotension may occur in cases of accidental overdose. Therapy should consist of intravenous infusion of warm isotonic saline.

4.11 Withdrawal period:

Not applicable

Pharmacotherapeutic group: ACE inhibitors, plain.

ATCvet code: QC09AA07

5.1 Pharmacodynamic properties

Benazepril hydrochloride is a prodrug hydrolysed in vivo to its active metabolite, benazeprilat.

Benazeprilat is a highly potent and selective inhibitor of ACE, thus preventing the conversion of inactive angiotensin I to active angiotensin II and thereby also reducing synthesis of aldosterone. Therefore, it blocks effects mediated by angiotensin II and aldosterone, including vasoconstriction of both arteries and veins, retention of sodium and water by the kidney and remodelling effects (including pathological cardiac hypertrophy and degenerative renal changes).

The product causes long-lasting inhibition of plasma ACE activity, with more than 95% inhibition at peak effect and significant activity (>80% in dogs) persisting 24 hours after dosing.

The product reduces the blood pressure and volume load on the heart in dogs with congestive heart failure.

5.2. Pharmacokinetic particulars

After oral administration of benazepril hydrochloride, peak levels of benazepril are attained rapidly (T_max0.5 hour in dogs) and decline quickly as the active substance is partially metabolised by liver enzymes to benazeprilat. The systemic bioavailability is incomplete (~13% in dogs) due to incomplete absorption (38% in dogs) and first pass metabolism.

In dogs, peak benazeprilat concentrations (C_maxof 37.6 ng/ml after a dose of 0.5 mg/kg benazepril hydrochloride) are achieved with a T_maxof 1.25 hours.

Benazeprilat concentrations decline biphasically: the initial fast phase (t_1/2=1.7 hours in dogs) represents elimination of free drug, while the terminal phase (t_1/2=19 hours in dogs) reflects the release of benazeprilat that was bound to ACE, mainly in the tissues. Benazepril and benazeprilat are extensively bound to plasma proteins (85-90%), and in tissues are found mainly in the liver and kidney.

There is no significant difference in the pharmacokinetics of benazeprilat when benazepril hydrochloride is administered to fed or fasted dogs. Repeated administration of the veterinary medicinal product leads to slight bioaccumulation of benazeprilat (R=1.47 in dogs with 0.5 mg/kg), steady state being achieved within a few days (4 days in dogs).

Benazeprilat is excreted 54% via the biliary and 46% via the urinary route in dogs. The clearance of benazeprilat is not affected in dogs with impaired renal function and therefore no adjustment of the product dose is required in either species in cases of renal insufficiency.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Iron oxide yellow (E-172)

Iron oxide red (E-172)

Iron oxide black (E-172

Titanium dioxide (E-171)

Cellulose microcrystalline

Lactose monohydrate

Povidone

Maize starch

Silica colloidal anhydrous

Magnesium stearate

Hypromellose

Macrogol 8000

6.2 Incompatibilities

Not applicable

6.3 Shelf-life

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

Shelf-life of halved tablets: 24 hours

6.4 Special precautions for storage:

Do not store above 25°C.

Keep the blister in the outer carton in order to protect from light and moisture.

Any unused divided tablet portion should be returned into the blister, kept within the outer carton.

6.5 Nature and composition of immediate packaging:

Blister made of clear film of PVC/PE/PVDC and aluminium film containing 14 tablets.

Box with:

- 1 blister (14 tablets)

- 2 blisters (28 tablets)

- 4 blisters (56 tablets)

- 10 blisters (140 tablets)

Not all pack sizes may be marketed.

6.6 Special precautions for the disposal of unused veterinary medicinal product or waste materials derived from the use of such products

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

7. MARKETING AUTHORISATION HOLDER

Vetpharma Animal Health, S.L

Les Corts, 23

08028 Barcelona

Spain

8. MARKETING AUTHORISATION NUMBER

Vm 32509/4020

9. DATE OF THE FIRST AUTHORISATION

21 December 2015

10. DATE OF REVISION OF THE TEXT

December 2015

PROHIBITION OF SALE, SUPPLY AND/OR USE

To be supplied only on veterinary prescription.

Administration by a veterinary surgeon or under their direct responsibility.

Approved: 21 December 2015