Description:

The active ingredient in FORTEKOR is benazepril hydrochloride which is a second generation non-sulphydryl angiotensin converting enzyme (ACE) inhibitor. Following oral administration, benazepril hydrochloride is absorbed and converted by the liver to its active metabolite, benazeprilat.

Benazeprilat acts by inhibiting angiotensin converting enzyme (ACE). This enzyme is part of the renin-angiotensin cascade system and converts inactive Angiotensin I into biologically-active Angiotensin II, the hormone controlling vasoconstriction and release of aldosterone. Thus, ACE inhibitors prevent constriction of the blood vessels, thereby facilitating blood flow and reducing hypertension.

Indications:

FORTEKOR is indicated for the treatment of heart failure in dogs caused by mitral regurgitation or dilated cardiomyopathy, in combination with standard therapy.

Dosage and Administration:

The minimum recommended dose is 0.25 mg/kg body weight, to be given once daily orally according to the following regime:

FORTEKOR can be given with or without food. The duration of treatment is unlimited. The dose can be doubled, still administered once daily, if judged clinically necessary and advised by the veterinarian.

FORTEKOR may be given in combination with digoxin, diuretics and antiarrhythmic drugs as necessary.

Pharmacology:

Pharmacodynamic Properties: FORTEKOR contains benazepril hydrochloride, a prodrug hydrolysed in vivo to benazeprilat which inhibits angiotensin converting enzyme (ACE), thus preventing the conversion of inactive angiotensin I into active angiotensin II. FORTEKOR reduces all effects mediated by angiotensin II, including vasoconstriction of both arteries and veins and retention of sodium and water by the kidney. FORTEKOR causes long-lasting inhibition of plasma ACE in dogs and cats (per label), with significant inhibition persisting for 24 hours after a single dose. FORTEKOR reduces the pressure and volume load on the heart in dogs with heart failure, and leads to improvements in the quality of life and clinical signs, notably coughing. FORTEKOR also produces a significant reduction in the frequency of mortality as compared to conventional therapy, consistent with an extension in life span. In cats with chronic renal insufficiency, FORTEKOR reduces the protein loss in urine and lowers the systemic and intraglomerular blood pressure.

Pharmacokinetic Properties: Benazepril is rapidly but incompletely absorbed from the gastrointestinal tract following oral administration. Absorbed benazepril is partially hydrolyzed by hepatic enzymes to the active substance, benazeprilat; unchanged benazepril and hydrophilic metabolites account for the remainder. Peak plasma benazeprilat concentrations are attained within about two hours both in fasting and fed situations. Benazepril and benazeprilat are bound to plasma proteins, and in tissues are found mainly in the liver and kidney. The major part of benazeprilat is rapidly eliminated, although there is in addition a slow terminal elimination phase. Benazeprilat is excreted approximately equally via both biliary and urinary routes. Repeated administration of FORTEKOR leads to slight accumulation of benazeprilat in plasma, steady state is attained within four days. Because of its biliary excretion route, there is little risk of bioaccumulation of benazeprilat in dogs with impaired renal function. For this reason, no dose adjustment of FORTEKOR is necessary in cases of renal insufficiency.

Safety:

FORTEKOR is well-tolerated by the target species. In normal dogs overdosage up to 200 fold was asymptomatic. Transient reversible hypotension may occur in cases of accidental overdosage. Therapy should consist of intravenous infusion of warm isotonic saline solution.

FORTEKOR has been given in combination with digoxin, diuretics and/or anti-arrhythmic drugs without demonstrable adverse interactions.

Precautions:

• No evidence of renal toxicity to FORTEKOR has been observed in dogs during clinical trials. Because of the biliary excretion of benazeprilat, there is little risk of bioaccumulation in dogs with impaired renal function. For this reason, no dose adjustment of FORTEKOR is necessary in cases of renal insufficiency. However, as is routine, in cases of renal insufficiency, it is recommended to monitor plasma urea and creatinine levels.
• Signs of hypotension such as tiredness or dizziness may appear in rare cases. Reduce the dose of the diuretic, if necessary.
• The safety of FORTEKOR has not been tested in breeding dogs. FORTEKOR is therefore not recommended for use in pregnant bitches unless justified by the risk/benefit ratio. No data are available in lactating bitches. FORTEKOR should therefore be used only if justified clinically.

Adverse Effects:
In rare cases, fatigue or dizziness may be observed. In double-blind clinical trials, FORTEKOR was well tolerated with an incidence of adverse effects statistically lower than observed in placebo-treated dogs.

Warning:
Keep this and all drugs out of the reach of children.

Presentations:
Light yellow, ovaloid, divisible, film-coated tablets containing 5 mg benazepril. They are scored on both sides and marked "CG" on one side and "LV" on the other.

Reddish orange, ovaloid, divisible, film-coated tablets containing 20 mg benazepril. They are scored on both sides and marked "CG" on one side and "HP" on the other.

Bottles, HDPE, 40 mls., with screw tops, 100 tablets per bottle.

Storage Conditions:
FORTEKOR (Benazepril) tablets should be stored at room temperature, between 15 - 30°C.