Kelapril 20 mg, Film-coated Tablets for Dogs

Composition

Each tablet contains:

Active substance:

Benazepril hydrochloride 20 mg

(equivalent to benazepril 18.4 mg)

Excipients:

Reddish-pink, oval divisible film-coated tablets scored on both sides.

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Pharmacological properties

4.1 ATCvet code: QC09AA07

4.2 Pharmacodynamics

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

4.3 Pharmacokinetics

After oral administration of benazepril hydrochloride, peak levels of benazepril are attained rapidly (Tmax 0.58 hour in dogs) and decline quickly as the drug 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 (Cmax of 39.4 ng/ml after a dose of 0.40 mg/kg benazepril hydrochloride) are achieved with a Tmax of 1.43h.

Benazeprilat concentrations decline biphasically: the initial fast phase (t1/2=1.7 hours in dogs) represents elimination of free drug, while the terminal phase (t1/2=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 veterinary medicinal product dose is required in cases of renal insufficiency.

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Target species

Dogs

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Indications

Treatment of congestive heart failure.

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Dosage

Oral use.

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

Dogs:

The 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:

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.

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Contraindications

Do not use in 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 (see section 3.7).

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Adverse reactions

Dogs:

Rare (1 to 10 animals / 10,000 animals treated):

Vomiting;

Fatigue.

Very rare (<1 animal / 10,000 animals treated, including isolated reports):

Elevated creatinine1;

Incoordination.

1 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.

Reporting adverse events is important. It allows continuous safety monitoring of a veterinary medicinal product. Reports should be sent, preferably via a veterinarian, to either the marketing authorisation holder or its local representative or the national competent authority via the national reporting system. See the package leaflet for respective contact details.

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Warnings

Special precautions for safe use in the target species:

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:

People with known hypersensitivity to benazepril hydrochloride should avoid contact with the veterinary medicinal product.

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.

To avoid accidental ingestion, particularly by a child, unused part-tablets should be returned to the open blister space and inserted back into the carton.

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

Wash hands after use.

Special precautions for the protection of the environment:

Not applicable.

3.11 Special restrictions for use and special conditions for use, including restrictions on the use of antimicrobial and antiparasitic veterinary medicinal products in order to limit the risk of development of resistance

Not applicable.

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Use during pregnancy, lactation or lay

Pregnancy and lactation:

Do not use during pregnancy or lactation.

The safety of the veterinary medicinal product has not been established in pregnant or lactating dogs.

Embryotoxic effects (foetal urinary tract malformation) were seen in trials with laboratory animals (rats) at maternally non-toxic doses.

Fertility:

The safety of the veterinary medicinal product has not been established in breeding dogs.

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Interactions

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 veterinary medicinal 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.

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Overdose

The veterinary medicinal 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.

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Special warnings

None.

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Withdrawal period

Not applicable.

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Incompatibilities

Not applicable.

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Immediate packaging

PVC/PVDC – aluminium blister or alu-foil (oPA/PVC) – aluminium blister containing 14 film-coated tablets.

Pack sizes:

Cardboard box with

• 2 blisters (28 tablets);

• 7 blisters (98 tablets).

Not all pack sizes may be marketed.

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Storage

Store below 30°C in the original package.

Store in a dry place.

Each time an unused half tablet is stored, it should be returned to the open blister space inserted back into the cardboard box and used at the next administration.

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Shelf life

Shelf life of the veterinary medicinal product as packaged for sale: 3 years. Shelf life of divided tablets: 2 days.

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Disposal of unused product

Medicines should not be disposed of via wastewater.

Use take-back schemes for the disposal of any unused veterinary medicinal product or waste materials derived thereof in accordance with local requirements and with any national collection systems applicable to the veterinary medicinal product concerned.

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Additional information

Vm 57446/5002

8 DATE OF FIRST AUTHORISATION

12 February 2013

9 DATE OF THE LAST REVISION OF THE SUMMARY OF THE PRODUCT CHARACTERISTICS

January 2025

10 CLASSIFICATION OF VETERINARY MEDICINAL PRODUCT

Veterinary medicinal product subject to prescription.

Find more product information by searching for the ‘Product Information Database’ on www.gov.uk.

Approved 12 February 2025

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Registration holder

VetViva Richter GmbH

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