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SPC
1.
NAME OF THE VETERINARY MEDICINAL PRODUCTS
Fortekor® 5
2.
QUALITATIVE AND QUANTITATIVE COMPOSITION
One tablet contains:
Benazepril hydrochloride (CGA 278814A)
5.0mg
Excipients q.s.
192mg
Coating contains the colourant Iron oxide yellow 17268 (E172)
3.
FORTEKOR dose is required in either species in cases of renal
insufficiency.
5.
CLINICAL PARTICULARS
5.1
Target Species:
5.2
Indications for Use:
Treatment of heart failure in dogs
Treatment of chronic renal insufficiency in cats
5.3
Contraindications
None known in cats. Do not use in any dog that has
evidence of cardiac output failure due to aortic stenosis. Do
not use in animals known to be hypersensitive to the active
substance.
5.4
Undesirable effects:
In double-blind clinical trials in dogs with heart failure,
FORTEKOR was well tolerated with an incidence of adverse
effects statistically lower than observed in placebo treated
dogs. A small number of dogs may exhibit transient signs of
fatigue or dizziness.
In cats with chronic renal insufficiency, FORTEKOR may
increase plasma creatinine 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.
FORTEKOR 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.
FORTEKOR may increase food consumption and body
weight in cats.
5.5
Special Precautions for Use:
No evidence of renal toxicity to FORTEKOR has been
observed in dogs or cats during clinical trials. As is routine in
cases of renal insufficiency, it is recommended to monitor
plasma creatinine and urea during therapy. The efficacy and
safety of FORTEKOR has not been established in cats below
2.5kg body weight.
5.6
Use During Pregnancy and Lactation:
The safety of FORTEKOR has not been tested in breeding.
pregnant or lactating dogs or cats. FORTEKOR should
therefore be used only if justified clinically, considering the
risk/benefit ratio. FORTEKOR reduced ovary/oviduct
weights in cats when administered daily at 10 mg/kg for 52
weeks. ACE inhibitors have been found to be teratogenic in
the second and third trimesters in other species.
5.7
Interaction with Other Medicaments:
PHARMACEUTICAL FORM
Film-coated tablets.
4.
PHARMACOLOGICAL PROPERTIES
Summary presentation of the active substance
FORTEKOR contains benzepril hydrochloride, an orally active
inhibitor of angiotensin converting enzyme (ACE)
Pharmacodynamic properties:
Benazepril hydrochloride is a prodrug hydrolysed in vivo to its active
metabolite benazeprilat. Benazeprilat is a highly potent and selective
inhibitor of angiotensin converting enzyme (ACE), thus preventing
the conversion of inactive angiotensin I to active angiotensin II.
Therefore, FORTEKOR blocks effects mediated by angiotensin II,
including vasoconstriction of both arteries and veins, retention of
sodium and water by the kidney and modelling effects (including
pathological cardiac hypertrophy and degenerative renal changes).
FORTEKOR causes long-lasting inhibition of plasma ACE activity in
both cats and dogs, with more than 95% inhibition at peak effect and
significant activity (>80% in dogs and >90% in cats) persisting 24
hours after dosing. FORTEKOR reduces the blood pressure and
volume load on the heart in dogs with heart failure. FORTEKOR
leads to an extension of the life span of dogs with heart failure and
also improves clinical signs, notably reduction in coughing, and
improvement to the quality of life. In cats with experimental renal
insufficiency, FORTEKOR normalized the elevated glomerular
capillary pressure (GCP) and reduced the systemic blood pressure.
Reduction in glomerular hypertension retards the progression of
kidney disease by inhibition of further damage to the kidneys. In a
large clinical trial in cats with chronic kidney insufficiency,
FORTEKOR significantly reduced protein loss in the urine; this effect
is probably mediated via reduced GCP and beneficial effects on the
glomerular basement membrane. FORTEKOR also increased the
appetite, quality of life and the survival time of the cats, particularly in
more advanced cases.
Pharmacokinetic properties:
After oral administration of benazepril hydrochloride, peak levels of
benazepril are attained rapidly (Tmax 0.5h in dogs, and within 2h in
cats) and decline quickly (t1/2 =1.4h in cats) as the drug is partially
metabolised by liver enzymes to benazeprilat. In dogs, unchanged
benazepril and hydrophilic metabolites account for the remainder. In
dogs, peak benazeprilat concentrations (Cmax of 26.7 ng/ml after a
dose of 0.5 mg/kg benazepril hydrochloride) are achieved with a Tmax
of 1.25h. In cats, peak benazeprilat concentrations (Cmax of 77.0
ng/ml after a dose of 0.5 mg/kg benazeprii hydrochloride) are
achieved with a Tmax of 2h. The systemic bioavailability is incomplete
(~13% in dogs) due to incomplete absorption (38% in dogs and
<30% in cats) and first pass metabolism.
Benazeprilat concentrations decline biphasically: the initial fast
phase (t1/2 =1.7h in dogs and t1/2 =2.4h in cats) represents elimination
of free drug, while the terminal phase (t1/2 =19h in dogs and t1/2 =29h
in cats) reflects the release of benazeprilat that was bound to ACE
mainly in the tissues. Benazepril and benazeprilat are extensively
bound to plasma proteins, 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 FORTEKOR leads to slight
bioaccumulation of benazeprilat (R=1.47 in dogs and R=1.36 in cats
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 and 85% via the biliary and 15% via the urinary route in
cats. The clearance of benazeprilat is not affected in dogs or cats
with impaired renal function and therefore no adjustment of
Dog and Cat
None known in dogs or cats. In dogs with heart failure,
FORTEKOR has been given in combination with digoxin,
diuretics and anti-arrythmic drugs without demonstrable
adverse interactions. In man, the combination of ACE
inhibitors and NSAIDs can lead to reduced anti-hypertensive
efficacy or impaired renal function. The combination of
FORTEKOR 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, triamteren or amilorid 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 a possibility.
5.8
Posology and Method of Administration:
For oral use only. In both dogs and cats, FORTEKOR should
be given orally once daily, with or without food. The duration
of treatment is unlimited.
In dogs, the recommended oral dose is 0.25 - 0.5mg/kg body weight,
given according to the following regime:
Weight of
dog (kg)
5 -10
11-20
Standard
Dose
0.5 tablet
1 tablet
Double
Dose
1 tablet
2 tablets
The dose may be doubled, still administered once daily, if judged
clinically necessary and advised by the veterinary surgeon. When the
10mg dose is required, veterinary surgeons should consider
administering two 5mg tablets to limit the use of half tablets.
In cats, FORTEKOR should be administered orally at a dose of 0.5 –
1.0mg benazepril hydrochloride/kg body weight once daily according
to the following table:
Weight of cat
(kg)
2.5 - 5
>5 - 10
5.9
Standard Dose
0.5 tablet
1 tablet
Overdose
FORTEKOR is well tolerated by the target species. In
normal dogs overdosage up to 200 fold was asymptomatic.
In 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.
5.10 Special Warnings for each Target Species:
None
5.11 Withdrawal Periods:
Not applicable
5.12 Special Precautions to be taken by the Person Administering
the Product:
Wash hands after use.
6.
PHARMACEUTICAL PARTICULARS
6.1
Incompatibilities (major):
Not applicable
6.2
Shelf-Life:
3 years.
6.3
Special Precautions for Use:
Store in a dry place. Do not store above 25oC. Store in the
original container. 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
reach of children.
6.4
Nature and Contents of Container:
Blister pack moulded parts PVC/PE/PVDC: 2 x 14 tablets
packed in cardboard box with an enclosure leaflet. (14
tablets per blister)
6.5
Special Precautions for the Disposal of Unused Product or
Waste Materials:
Any unused product or waste should be disposed of in
accordance with national requirements.
7.
FINAL INFORMATION
7.1
Name or Corporate Name and Permanent Address or
Registered Place of Business of the Holder of the Authorisation
to place the Product on the Market: Procured within the E.U.
and re-packaged by:
Munro Wholesale Medical Supplies Ltd.,
10 Stroud Road, East Kilbride, G75 0YA
7.2
Manufacturer:
Novartis Santé Animale S.A., Huningue, France
7.3
Marketing Authorisation No.:
Fortekor 5 Vm 03243/4000
7.4
Trade Marks
Fortekor® is a Registered Trade Mark
7.5
Legal category
Prescription Only Medicine
POM
7.6
Date of approval of SPC: 23 June 2004
7.7
Date of first authorisation: 23 June 2004