Issued 08/10/2009 – AN 01650/2006
Summary of Product Characteristics
1. NAME OF THE VETERINARY MEDICINAL PRODUCT
Fortekor® 5mg Film-Coated Tablets for Dogs and Cats
2. QUALITATIVE AND QUANTATIVE COMPOSITION
Active substance: One tablet contains 5mg benazepril hydrochloride Excipient(s): For a full list of excipients, see section 6.1
3. Pharmaceutical form Film-coated tablet Light yellow, ovaloid , slightly biconvex tablets with score on both sides, marked “CG” on one side and “LV” on the reverse
4. CLINICAL PARTICULARS 4.1 Target species Dog and cat
4.2 Indications for use, specifying the target species
Treatment of heart failure in dogs Treatment of chronic renal insufficiency in cats
4.3 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 or to any of the excipient(s)
4.4 Special warnings for each target species The efficacy and safety of the product has not been established in cats below 2.5 kg body weight.
4.5 Special precautions for use (i) Special precautions for use in animals 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.
(ii) Special precautions to be taken by the person administering the veterinary medicinal product to animals Wash hands after use
4.6 Adverse reactions (frequency and seriousness) 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. On rare occasions transient signs of hypotension, such as lethargy and ataxia may occur.
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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. Emesis, anorexia, dehydration and lethargy have been reported in rare occasions in this species.
4.7 Use during pregnancy, lactation or lay The safety of Fortekor has not been tested in breeding, pregnant or lactating dogs or cats. Fortekor reduced ovary/oviduct weights in cats when administered daily at 10mg/kg for 52 weeks. ACE inhibitors have been found to be teratogenic in the second and third trimesters in other species.
4.8 Interaction with other medicinal products and other forms of interaction None known in dogs or cats. In dogs with heart failure, Fortekor has been given in combination with digoxin, diuretics and antiarrhythmic drugs without demonstrable adverse interactions. In man, the combination of ACE inhibitors and NSAIDs can lead to reduced antihypertensive 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 sedative 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 benazepril in combination with a potassium sparing diuretic as life- threatening reactions are a possibility.
4.9 Amounts to be administered and administration route 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 benazepril hydrochloride/kg body weight, given according to the following regime. FORTEKOR 5mg Tablets Weight of dog Standard Dose Double (kg) Dose 5 - 10 0.5 tablet 1 tablet 11 - 20 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 10 mg dose is required, veterinary surgeons should consider administering two 5 mg tablets to limit the use of half tablets.
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In cats, Fortekor 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 FORTEKOR (kg) 5mg Tablets 2.5 - 5 0.5 tablet >5 - 10 1 tablet
4.10 Overdose (symptoms, emergency procedures, antidotes), if necessary Fortekor is well tolerated by 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.
4.11 Withdrawal period Not applicable
5. PHARMACOLOGICAL PROPERTIES Pharmacotherapeutic group: ACE inhibitors, plain, ATCvet code: QC09AA07
Fortekor contains benazepril hydrochloride, an orally active inhibitor of angiotensin converting enzyme (ACE).
5.1 Pharmacodynamic properties Benazepril hydrochloride is a pro-drug 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 into 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 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.
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5.2 Pharmacokinetic properties: After oral administration of benazepril hydrochloride, peak levels of benazepril are attained rapidly (tmax 0.5 h 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 0.5mg/kg benazepril hydrochloride) are achieved with a Tmax of 1.25h. In cats, peak benzaprilat concentrations (Cmax of 77.0 ng/ml after a dose of 0.5 mg/kg benazepril 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. Benzaprilat 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 = 19 h 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 0.5mg/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 Fortekor dose is required in either species in cases of renal insufficiency.
Environmental properties Not applicable
6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients Silica, colloidal anhydrous Cellulose, microcrystalline Hydrogenated castor oil Lactose monohydrate Maize starch, pregelatinised Crospovidone Hypromellose iron oxide yellow (E172) Polyethylene glycol 8000 Talc Titanium dioxide (E171)
6.2 Incompatibilities Not applicable
6.3 Shelf-life 3 years.
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6.4 Nature and composition of immediate packaging Do not store above 25°C. Store in a dry place.
Blister pack moulded parts PVC/PE/PVDC 14 tablets packed in cardboard box with an enclosure leaflet.
6.5 Special precautions for the disposal of unused veterinary medicinal product or waste materials derived from the use of such products Any unused product or waste material should be disposed of in accordance with national requirements.
7. MARKETING AUTHORISATION HOLDER
Procured within the EU by Globalmed Ltd, Ground Floor, 134 Church Hill, Essex IG10 1LH, UK.
8. MARKETING AUTHORISATION NUMBER
Vm 24939/4008
9. DATE OF FIRST AUTHORISATION
8 October 2009
10. DATE OF REVISION OF THE TEXT
8 October 2009
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