Cardisure Tablets

Target species
Dogs.

Indications for use:
For the treatment of canine congestive heart failure originating from valvular insufficiency (mitral and/or tricuspid regurgitation) or dilated cardiomyopathy.

Contraindications:
Do not use in cases of hypertrophic cardiomyopathies or clinical conditions where an augmentation of cardiac output is not possible for functional or anatomical reasons (e.g. aortic stenosis).

See also Use during pregnancy and lactation.

Special warnings for each target species:
The product should be administered on an empty stomach at least one hour before meals, as absorption is reduced when given with feed.

Special precautions for use in animals:
The product is flavoured. To avoid accidental ingestion the tablets should be stored out of reach of dogs. An in vitro study in rat tissue demonstrated that pimobendan increased glucose-induced insulin release from pancreatic beta-cells in a dose dependent manner. If the product is administered to diabetic dogs, blood glucose levels should be carefully monitored. As pimobendan is metabolised in the liver, particular care should be taken when administering the product to dogs with severe hepatic insufficiency.

Special precautions to be taken by the person administering the veterinary medicinal product to animals

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

Wash hands after use.

Advice to doctors: Accidental ingestion, especially by a child, may lead to the occurrence of tachycardia, orthostatic hypotension, flushing of the face and headaches.

Adverse reactions:
A moderate positive chronotropic effect and vomiting may occur in rare cases. However, these effects are dose-dependent and may be avoided by reducing the dose in these cases. In rare cases transient diarrhoea, anorexia or lethargy have been observed. Although a relationship with pimobendan has not been clearly established, in very rare cases, signs of effects on primary haemostasis (petechiae on mucous membranes, subcutaneous haemorrhages) may be observed during treatment. These signs disappear when the treatment is withdrawn. In rare cases, an increase in mitral valve regurgitation has been observed during chronic pimobendan treatment in dogs with mitral valve disease. Monitoring of cardiac function and morphology is recommended in animals treated with pimobendan.

Use during pregnancy and lactation:
Laboratory studies in rats and rabbits have not produced any evidence of teratogenic or foetotoxic effects. However, these studies have shown evidence of maternotoxic and embryotoxic effects at high doses, and have also shown that pimobendan is excreted into milk. The safety of the product has not been assessed in pregnant or nursing bitches. Use only according to the benefit/risk assessment by the responsible veterinarian.

Interactions:
In pharmacological studies no interaction between the cardiac glycoside ouabain and pimobendan was detected. The pimobendan-induced increase in contractility of the heart is attenuated in the presence of the calcium antagonist verapamil and the beta-antagonist propranolol.

Amounts to be administered and administration route:
The preferable daily dose is 0.5 mg pimobendan/kg body weight.

Do not exceed the recommended dosage.

Determine the body weight accurately before treatment to ensure correct dosage. The tablets should be administered orally at a dose range of 0.2 mg to 0.6 mg pimobendan/kg body weight per day. The dose should be divided into two administrations (0.25 mg/kg body weight each), one half of the dose in the morning and the other half approximately 12 hours later. The maintenance dose should be individually adjusted by the responsible veterinarian according to the severity of the disease.

The product may be combined with a diuretic treatment, e.g. furosemide.

Cardisure flavoured 1.25 mg tablets for dogs: To break a tablet into two halves, place the tablet on an even surface with the scored side up, hold one half of the tablet and press down on the other half.

Cardisure flavoured 2.5 mg/5 mg/10 mg tablets for dogs: To break a double scored tablet into quarters, place the tablet on an even surface with the scored side up and apply pressure on the middle with your thumb.

Each dose should be given approximately one hour before feeding.

Table to show dosing guide: Daily pimobendan dosage: 0.2 - 0.6 mg/kg. The preferable daily dose is 0.5 mg/kg.

No. of tablets per administration (morning and evening)

Body weight (kg)

Daily dosage (mg)

1.25 mg

2.5 mg

5 mg

10 mg

< 5

1.25

-

-

-

5-10

2.5

1

-

-

-

10-20

5

-

1

-

-

21-40

10

-

-

1

-

41-60

20

-

-

-

1

> 60

30

-

-

-

1

Overdose:
In the case of overdose, a positive chronotropic effect and vomiting may occur. In this situation, the dosage should be reduced and appropriate symptomatic treatment should be initiated.

Withdrawal period:
Not applicable.

Pharmacological particulars:
Pharmacotherapeutic group: Cardiac stimulant (phosphodiesterase inhibitor). ATC Vet code: QC01CE90

Pharmacodynamic properties:
Pimobendan, a benzimidazole-pyridazinone derivative, is a non-sympathomimetic, non-glycoside inotropic substance with potent vasodilatative properties.

Pimobendan exerts its stimulatory myocardial effect by a dual mode of action: it increases calcium sensitivity of cardiac myofilaments and inhibits phosphodiesterase (type III). It also exhibits a vasodilatory action through inhibition of phosphodiesterase III activity.

When used in cases of valvular insufficiency in conjunction with furosemide, the product has been shown to improve the quality of life and extend life expectancy in treated dogs. When used in a limited number of cases of dilated cardiomyopathy in conjunction with furosemide, enalapril and digoxin the product has been shown to improve the quality of life and to extend life expectancy in treated dogs.

Pharmacokinetic properties:
Absorption: Following oral administration of this veterinary medicinal product the absolute bio-availability of the active principle is 60-63%. Since this bio-availability is considerably reduced when pimobendan is administered with food or shortly thereafter, it is recommended to treat animals approximately 1 hour before feeding.

Distribution: The volume of distribution is 2.6 l/kg, indicating that pimobendan is distributed readily into the tissues. The mean plasma protein binding is 93%.

Metabolism: The compound is oxidatively demethylated to its major active metabolite (UD-CG 212). Further metabolic pathways are phase II conjugates of UD-CG-212, in essence glucuronides and sulphates.

Elimination: The plasma elimination half-life of pimobendan is 1.1 0.7 hours.

The main active metabolite is eliminated with a plasma elimination half-life of 1.5 0.2 hours. Almost the entire dose is eliminated via faeces.

Pharmaceutical particulars:

Incompatibilities:
None known.

Shelf life:
Shelf life of the veterinary medicinal product as packaged for sale: 30 months.

Shelf life of divided tablets after first opening the blister: 3 days.

Special precautions for storage:
Return any divided tablet to the opened blister and use within 3 days. Do not store above 30C. Keep out of the sight and reach of children

Immediate packaging:
Aluminium PVC/PE/PVDC blister: 10 tablets per blister. 2, 5, 10 or 25 blisters per carton.

Aluminium Aluminium blister:

Cardisure flavoured 1.25 mg/2.5 mg tablets for dogs: 10 tablets per blister. 2, 5, 10 or 25 blisters per carton.

Cardisure flavoured 5 mg/10 mg tablets for dogs: 5 tablets per blister. 4, 10, 20 or 50 blisters per carton.

Not all pack sizes may be marketed.

Disposal:
Any unused veterinary medicinal product or waste materials derived from such veterinary medicinal products should be disposed of in accordance with local requirements.