Download KELAPRIL 2.5 mg / 5 mg / 20 mg

KELAPRIL 2.5 mg / 5 mg / 20 mg
ORAL TABLETS FOR DOGS AND CATS
One tablet contains 2.5 mg, 5 mg or 20 mg benazepril hydrochloride
easy
Film-coated tablets for
administration
well
Treats cardiac (dogs) as
ency
as renal (cats) insuffici
Very well tolerated
KELAPRIL 2.5 mg / 5 mg / 20 mg
film coated tablets for dogs and cats
Inhibitors of the angiotensin converting enzyme (ACE) are of great benefit for the management of
congestive heart failure in dogs, improving symptoms and tolerance to exercise as well as extending the life
span of the animal. In cats with chronic renal insufficiency they decrease proteinuria and systemic arterial
pressure, and delay the progression of the disease.
The Renin-Angiotensin-System
Congestive heart failure in dogs
The precursor molecule Angiotensinogen is produced in
the liver and cleaved to make Angiotensin I by rennin, an
enzyme released by the juxtaglomerular cells. This
Angiotensin I is in turn converted into Angiotensin II
catalysed by the Angiotensin Converting Enzyme or ACE,
located in the pulmonary and renal endothelium.
In congestive heart failure the heart is unable to provide
adequate circulation to meet the body’s needs. Chronic
valvular disease in small dog breeds, and dilated
cardiomyopathy are the most common causes.
Benazepril blocks the conversion of Angiotensin I into
Angiotensin II, and inhibits in this way its rapid response,
slow response, as well as morphologic reactions.
Due to increased pressure in the veins, fluid leaks into
the lungs (pulmonary edema) and the peritoneal cavity
(ascites).
Early signs are non-specific, but when failure progresses
rapid breathing, coughing, abdominal swelling and a
marked loss of weight become apparent. At a later stage
laboured breathing, cyanosis and syncope occur.
Clinical efficacy
162 dogs with congestive heart failure 1 were treated with
0.25 – 0.5 mg benazepril per kg bw. Benazepril significantly
extended the life span of the dogs from 158 in the placebo
group, to 428 days in the treated group.
ACE inhibition
Benazepril acts by inhibition of the Angiotensin Converting
Enzyme, resulting in less conversion of Angiotensin I into
Angiotensin II.
Benazepril will therefore lead to vasodilatation and a
decrease in fluid retention.
As a consequence the blood flows more freely through
the widened vessels, thereby reducing the amount of
work the heart has to do.
Pharmacokinetics
After oral administration benazepril is rapidly absorbed
from the gastrointestinal tract and consequently hydrolyzed
in the liver to form the active moiety benazeprilat.
Following the administration of KELAPRIL maximal serum
concentrations are reached after 1.43 hr (Tmax) in dogs
and 1.91 hr in cats.
After a period of one year, 49 % of the benazepril treated
dogs survived, compared to only 20 % in the placebo group.
Results also indicate that the outcome is significantly
better when benazepril therapy starts early in the
progress of the disease.
Benazepril delayed the time to evolve from moderate (class
II) to advanced (class III) cardiac insufficiency by a factor of
2 compared to placebo: 394 days instead of 209 days.
At 28 days after the start of treatment significantly more
dogs showed improved exercise tolerance (57 %) and
global condition (61 %) as compared to placebo treated
animals (34 % and 33 % resp.).
Tolerance in dogs
The percentage of dogs showing undesirable events was
not significantly different between the benazepril group
and the placebo group.
Chronic renal insufficiency in cats
Chronic renal failure is characterized by gradual and
irreversible decrease of glomerular filtration rate, result of
a gradual loss of renal functional mass2.
In compensation the remaining nephrons suffer functional
and structural changes in order to maintain filtration rate
constant. These functional adaptations refer to hyperfiltration, which is produced by an increase in glomerular
capillaries blood flow and pressure. This increased
glomerular pressure is in the long run deleterious for the
kidney. It leads to proteinuria and consecutive local
inflammation causing progressive renal injury.
Benazepril may lower glomerular pressure by decreasing
systemic blood pressure and vasoconstriction of the
efferent arterioles.
In cats the Urine Protein / Creatinine (UPC) ratio of ≥ 0.5
is indicative of persistent renal proteinuria.
In animals with naturally occurring Chronic Renal Faillure
and an UPC > 1.0, significantly longer survival times
were evident: 402 days in benazepril group vs. 149 days
in placebo group.
Beneficial effect on appetite was observed in cats with
more pronounced proteinuria (UPC >1.0).
Tolerance in cats
Benazepril is safe in cats with chronic renal failure,
because the active moiety, benazeprilat, is principally
(85 %) eliminated via biliary excretion, and therefore
does not accumulate in the body of animals with renal
diseases.
Posology
KELAPRIL should be given orally once daily, with or
without food. The duration of treatment is unlimited.
Dogs
A minimum dose of 0.25 mg (range 0.25-0.5) benazepril
HCl per kg body weight once daily.
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.
KELAPRIL 2.5 mg
Weight of
Double
Standard
dog (kg)
dose
dose
2.5 - 5
0.5 tablet
> 5 - 10
1 tablet
> 10 - 20
–
1 tablet
KELAPRIL 5 mg
Standard
dose
–
Standard
dose
Double
dose
–
2 tablets 0.5 tablet
1 tablet
KELAPRIL 20 mg
Double
dose
–
–
–
1 tablet
–
–
2 tablets
–
–
> 20 - 40
–
–
–
–
0.5 tablet
1 tablet
> 40 - 80
–
–
–
–
1 tablet
2 tablets
Cats
KELAPRIL 2.5 mg and 5 mg should be administered
orally at a minimum dose of 0.5 mg (range 0.5-1.0)
benazepril HCl per kg body weight once daily according
to the following table:
Weight of cat (kg)
KELAPRIL 2.5 mg
KELAPRIL 5 mg
2.5 - 5
1 tablet
0.5 tablet
> 5 - 10
2 tablets
1 tablet
References
1.The BENCH STUDY GROUP
The effect of benazepril on survival times and clinical signs in dogs
with congestive heart failure: Results of a multicenter, prospective,
rando-mized, double-blinded, placebo-controlled, long-term clinical
trial. Journal of Veterinary Cardiology, Vol. 1, No. 1, May 1999.
2. KING J.N., GUNN-MOORE D.A., TASKER S., GLEADHILL A.,
STREHLAU G., BENRIC STUDY GROUP.
Tolerability and efficacy of Benazepril in cats with chronic kidney
di-sease. J. Vet. Intern. Med. 20:1054-1064 – 2006.
PRIL
Advantages of KELA
d cats
§ efficacious in dogs an
as well
§ treats cardiac (dogs)
ncy
as renal (cats) insufficie
§ very well tolerated
FOR ANIMAL TREATMENT ONLY
RESTRICTED VETERINARY MEDICINE
KELAPRIL 2.5 mg, film-coated tablets for dogs and cats
KELAPRIL 5 mg, film-coated tablets for dogs and cats
KELAPRIL 20 mg, film-coated tablets for dogs
Benazepril hydrochloride
ACTIVE INGREDIENT AND QUANTITIES:
KELAPRIL 2.5 mg: Each tablet contains 2.5 mg Benazepril hydrochloride.
KELAPRIL 5 mg: Each tablet contains 5 mg Benazepril hydrochloride.
KELAPRIL 20 mg: Each tablet contains 20 mg Benazepril hydrochloride.
USE CLAIMS:
KELAPRIL 2.5 mg / KELAPRIL 5 mg: For the treatment of heart failure due
to mitral regurgitation and dilated cardiomyopathy in dogs, hypertrophic
cardiomyopathy in cats, and chronic renal insufficiency in dogs and cats.
KELAPRIL 20 mg: For the treatment of heart failure due to mitral regurgitation and dilated cardiomyopathy and chronic renal insufficiency in dogs.
DIRECTIONS FOR USE:
For oral use only. KELAPRIL should be given once daily, with or without
food. The duration of treatment is unlimited.
DOGS:
In dogs, the recommended oral dose is 0.25-0.5mg benazepril
hydrochloride/kg body weight, given according to the following regime:
KELAPRIL 2.5 mg
Weight of Standard
dog (kg)
dose
Double
dose
2.5 - < 5
0.5 tablet
1 tablet
5 - 10
1 tablet
KELAPRIL 5 mg
Standard
dose
2 tablets 0.5 tablet
11 - 20
1 tablet
Double
dose
KELAPRIL 20 mg
Standard
dose
Double
dose
1 tablet
2 tablets
21 - 40
0.5 tablet
1 tablet
41 - 80
1 tablet
2 tablets
The dose may be doubled, still administered once daily, if judged
clinically necessary and advised by the veterinary surgeon.
CATS:
In cats, KELAPRIL should be administered orally at a dose of 0.5-1.0 mg
benazepril hydrochloride/kg body weight once daily according to the
following table:
Weight of cat (kg)
KELAPRIL 2.5 mg
KELAPRIL 5 mg
2.5 - 5
1 tablet
0.5 tablet
> 5 - 10
2 tablets
1 tablet
REGISTRANT/NEW ZEALAND AGENT:
Registered to KELA N.V., St. Lenaartseweg 48, 2320 Hoogstraten,
BELGIUM, [email protected], + 32 3 340 04 11, manufactured in Belgium.
New Zealand agent: Phoenix Pharm Distributors Ltd,
[email protected], + 9 476 7391.
EXPIRY DATE:
Tablet halves should be used within 2 days.
Shelf-life of the veterinary medicinal product as packaged for sale: 24 months.
NET CONTENTS:
28 tablets – 98 tablets.
STORAGE INSTRUCTIONS:
KELAPRIL 2.5 mg: Store below 25°C in original blister.
KELAPRIL 5 mg: Store below 30°C in original blister.
KELAPRIL 20 mg: Store below 30°C in original blister.
Keep out of the reach and sight of children.
Store in a dry place.
Each time an unused half tablet is stored, it should be returned to the
open blister space and inserted back into the cardboard box.
ADVERSE EFFECTS, CAUTIONS AND CONTRAINDICATIONS:
Adverse effects:
On rare occasions transient signs of hypotension, such as lethargy and
ataxia may occur.
In cats with chronic renal insufficiency, KELAPRIL may increase plasma
creatinin concentrations at the start of therapy. This effect is related to
the therapeutic effect of the product in reducing blood pressure, and
therefore is not necessarily a reason to stop therapy in the absence of
other signs. As is routine in cases of chronic renal insufficiency, it is
recommended to monitor plasma creatinine during therapy.
Benazepril reduced erythrocyte counts in normal cats at high doses, but
this effect was not observed at the recommended dose during clinical
trials in cats with chronic renal insufficiency. As is routine in cases of
chronic renal insufficiency, it is recommended to monitor erythrocyte
counts during therapy.
KELAPRIL may increase food consumption and body weight in cats.
Emesis, anorexia, dehydration and lethargy have been reported in rare
occasions in this species. If you notice any serious effects or other effects
not mentioned in this leaflet, please inform your veterinary surgeon.
Special warnings for each target species:
The efficacy and safety of the product has not been established in dogs
and cats below 2.5 kg body weight.
Special precautions for use in animals:
No evidence of renal toxicity to the product has been observed in dogs
or cats during clinical trials. As is routine in cases of renal insufficiency,
it is recommended to monitor plasma creatinin and urea during therapy.
User warnings:
Wash hand after use.
Pregnant women should take special care to avoid accidental oral
exposure.
People sensitive to benazepril hydrochloride or some of the excipients
should not handle this product.
In case of accidental ingestion, seek medical advice immediately and
show this label to the doctor.
Use during pregnancy and lactation:
The safety of KELAPRIL has not been tested in breeding, pregnant or
lactating dogs or cats. The product should therefore be used only if
justified clinically, considering the risk/benefit ratio.
ACE inhibitors have been found to be teratogenic in the second and
third trimesters in other species.
Interaction with other medicinal products and other forms of interaction:
None known in dogs or cats.
In dogs with heart failure, benazepril has been given in combination
with digoxin, diuretics and anti-arrhythmic drugs without demonstrable
adverse interactions.
The combination of KELAPRIL and other anti-hypertensive agents,
anaesthetics or sedatives may lead to additive hypotensive effects.
Therefore, concurrent use of 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 when 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 benazepril in combination
with a potassium sparing diuretic as life threatening reactions are possible.
Overdose (symptoms, emergency procedures, antidotes):
KELAPRIL is well tolerated in the target species. In normal dogs,
overdosage up to 200-fold was asymptomatic. In normal cats, a 10-fold
overdosage daily for one year was asymptomatic. Transient reversible
hypotension may occur in cases of accidental overdosage. Therapy
should consist of intravenous infusion of warm isotonic saline.
Special precautions for the disposal of unused product or waste materials:
Any unused product or waste material should be disposed of in
accordance with local requirements.
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, 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 pregnant or lactating dogs or cats because the safety of
benazepril hydrochloride has not been established during pregnancy or
lactation in these species.
KELAPRIL 2.5 mg: ACVM Registration No. A10942
KELAPRIL 5 mg: ACVM Registration No. A10943
KELAPRIL 20 mg: ACVM Registration No. A10944
See www.foodsafety.govt.nz for registration conditions.
PHOENIX PHARM DISTRIBUTORS LTD § PO Box 31-363, Milford, Auckland
Telephone: 09 476 7391 § Facsimile: 09 479 5555
E-mail: [email protected] § Website: www.phoenixpharm.co.nz