SUMMARY OF PRODUCT CHARACTERISTICS

1. NAME OF THE VETERINARY MEDICINAL PRODUCT

FORTEKOR Flavour 20 mg Tablets for Dogs

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains:

Active substance:

Benazepril hydrochloride 20 mg

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Tablets.

Beige to light brown, ovaloid, divisible tablets, scored on both sides. The tablets can be divided into halves.

4. CLINICAL PARTICULARS

4.1 Target species

Dogs.

4.2 Indications for use, specifying the target species

Dogs:

Treatment of congestive heart failure.

4.3 Contraindications

Do not use in known cases 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 (section 4.7).

4.4 Special warnings for each target species

None.

4.5 Special precautions for use

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.

The efficacy and safety of the veterinary medicinal product has not been established in dogs below 2.5 kg body weight.

Special precautions to be taken by the person administering the veterinary medicinal product to animals Wash hands after use.

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

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.

4.6 Adverse reactions (frequency and seriousness)

In double-blind clinical trials in dogs with congestive heart failure, the veterinary medicinal 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.

The frequency of adverse reactions is defined using the following convention:

- very common (more than 1 in 10 animals treated displaying adverse reaction(s))

- common (more than 1 but less than 10 animals in 100 animals treated)

- uncommon (more than 1 but less than 10 animals in 1,000 animals treated)

- rare (more than 1 but less than 10 animals in 10,000 animals treated)

- very rare (less than 1 animal in 10,000 animals treated, including isolated reports).

4.7 Use during pregnancy, lactation or lay

Do not use during pregnancy or lactation. The safety of the veterinary medicinal 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.

4.8 Interaction with other medicinal products and other forms of interaction

In dogs with congestive heart failure, the veterinary medicinal 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 veterinary medicinal product in combination with a potassium sparing diuretic because of the risk of hyperkalaemia.

4.9 Amounts to be administered and administration route

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

This product is flavoured and is taken voluntarily by most dogs.

This veterinary medicinal 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)	Fortekor Flavour 20 mg
	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.

4.10 Overdose (symptoms, emergency procedures, antidotes), if necessary

The veterinary medicinal product reduced erythrocyte counts in normal dogs when dosed at 150 mg/kg body weight 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(s)

Not applicable.

5. PHARMACOLOGICAL PROPERTIES

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 veterinary medicinal 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_max 0.5 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_max of 37.6 ng/ml after a dose of 0.5 mg/kg benazepril hydrochloride) are achieved with a T_max of 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 dose of the product is required in cases of renal insufficiency.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Cellulose microcrystalline

Crospovidone

Povidone

Basic butylated methacrylate copolymer

Silicon dioxide anhydrous

Sodium laurilsulphate

Dibutyl sebacate

Silica colloidal anhydrous

Stearic acid

Yeast powder

Artificial powdered beef flavor 6.2 Major incompatibilities

Not applicable.

6.3 Shelf life

Shelf-life of the veterinary medicinal product as packaged for sale: 3 years Shelf-life of tablet halves: 2 days

6.4 Special precautions for storage

This veterinary medicinal product does not require any special storage conditions. Each time an unused half tablet is stored, it should be returned to the open blister space, inserted back into the cardboard box and kept in a safe place out of the sight and reach of children.

6.5 Nature and composition of immediate packaging

14 tablets per aluminium/aluminium blister. Cardboard 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 product should be disposed of in accordance with local requirements.

7. MARKETING AUTHORISATION HOLDER

Elanco Europe Ltd

Form 2, Bartley Way

Bartley Wood Business Park

Hook

RG27 9XA

United Kingdom

8. MARKETING AUTHORISATION NUMBER

Vm 00879/4046

9. DATE OF FIRST AUTHORISATION

28 April 2010

10. DATE OF REVISION OF THE TEXT

September 2020

Approved 09 September 2020