Clomicalm 5 (Canada)

Manufacturer: Novartis

(clomipramine Hydrochloride)

DIN: 02239207 (5 mg), 02239206 (20 mg), 02239205 (80 mg)

CLOMICALM^® is a twice daily oral treatment for dogs which has been shown to be effective when administered in combination with behavioural modification techniques for the treatment of anxieties and stereotypies (obsessive compulsive disorder).

Introduction

Novartis Animal Health Canada Inc. encourages you to take time to read this package insert which describes the use of CLOMICALM^® (Clomipramine hydrochloride) to treat certain behavioural concerns in dogs. CLOMICALM^® is only available through veterinarians.

Description

The active ingredient in CLOMICALM^® is clomipramine hydrochloride. The active ingredient in vivo is clomipramine and its major metabolite, desmethylclomipramine. Both clomipramine and desmethylclomipramine contribute to the broad-spectrum of action of CLOMICALM^® by blocking the neuronal re-uptake of both noradrenaline and serotonin (5-HT). CLOMICALM^® therefore possesses the properties of both a tricyclic antidepressant and a serotonin re-uptake inhibitor.

Clomicalm 5 Indications

Treatment of anxieties and for the treatment of stereotypies (obsessive compulsive disorders) such as lick dermatitis.

Dosage

CLOMICALM^® is administered twice daily at a dose of 1-2 mg/kg to give a total daily dose of 2-4 mg/kg according to the following table:

Body weight	Dosage per administration
	CLOMICALM 5	CLOMICALM 20	CLOMICALM 80
1.25 - 2.5 kg >2.5 - 5 kg	0.5 tablet 1 tablet
>5 - 10 kg >10 - 20 kg		0.5 tablet 1 tablet
>20 - 40 kg >40 - 80 kg			0.5 tablet 1 tablet

Administration

CLOMICALM^® is given orally with or without food. In clinical trials, CLOMICALM^® has been shown to be effective when administered for 2-3 months in combination with behavioural modification techniques for the treatment of anxieties (generalized anxiety and anxiety when separated from the owner). CLOMICALM^® has been shown to be also effective in the treatment of stereotypies (obsessive-compulsive disorder) such as lick dermatitis when administered for a minimum of 1 month.

Pharmacodynamic Properties

CLOMICALM^® contains clomipramine hydrochloride. The active ingredient in vivo is clomipramine and its major metabolite, desmethylclomipramine. Both clomipramine and desmethylclomipramine contribute to the effects of CLOMICALM^®: clomipramine is a potent and selective 5-HT re-uptake inhibitor while desmethylclomipramine is a potent and selective noradrenaline re-uptake inhibitor. The principle mechanism of action of CLOMICALM^® is potentiation of the effects of noradrenaline and 5-HT in the brain by inhibiting their neuronal re-uptake. In addition, CLOMICALM^® has anticholinergic effects by antagonism of cholinergic muscarinic receptors.

Pharmacokinetic Properties

Clomipramine is well absorbed (>80%) from the gastrointestinal tract in dogs when administered orally. When administered to fasted dogs, peak plasma levels of clomipramine and desmethylclomipramine are rapidly reached (1-1.5 hours). The pharmacokinetics of clomipramine and desmethylclomipramine are not significantly affected by co-administration of CLOMICALM^® with food.

Clomipramine is extensively bound to plasma proteins (>97%). Clomipramine and its metabolites are rapidly distributed in the body with high concentrations being achieved in organs and tissues (including the lungs, heart and brain) and low concentrations remaining in the blood.

The major route of biotransformation of clomipramine is demethylation to desmethylclomipramine. Additional polar metabolites also exist.

The elimination t _1/2 of clomipramine is 6.4 hours and that of desmethylclomipramine is 3.8 hours. The principle route of excretion is via the bile (>80%) with the remainder via the kidneys.

Side Effects

CLOMICALM^® may cause mild and intermittent vomiting in some dogs, this may be improved by co-administration with a small quantity of food.

Overdose

Oral administration of clomipramine at 40 mg/kg caused no significant signs of toxicity in dogs. Administration of toxicological doses of clomipramine (735 mg/kg) to dogs caused non-specific signs of CNS inhibition and convulsions. There is no specific antidote. In the event of overdose, treatment should be supportive.

Safety

This product is well tolerated by the target species.

Use During Pregnancy And Lactation

The safety of CLOMICALM^® has not been established in male and female reproductive dogs. CLOMICALM^® is recommended for use in breeding dogs only if the benefit/risk ratio is considered justified by the veterinarian.

Interaction With Other Medicaments

The need for specific precautions has not been established in dogs. In clinical trials, there were no adverse effects when CLOMICALM^® was used with a variety of antibiotics, vaccines, anti-parasitic drugs, and CNS active drugs. CLOMICALM^® may potentiate the effects of CNS depressant drugs such as barbiturates. It is recommended not to administer CLOMICALM^® in combination with, or within 2 weeks of cessation of therapy with, monoamine oxidase inhibitors.

Precautions

Tolerability studies and clinical trials have demonstrated no need for special precautions with the use of CLOMICALM^® in dogs. From its known mechanism of action, it is recommended to use CLOMICALM^® with care in dogs with cardiac arrhythmias, epilepsy or narrow angle glaucoma.

Warning

Keep out of reach of children. If accidentally swallowed, call a physician.

Presentation

CLOMICALM is available in divisable, flavored tablets of 3 dosage strengths:

Dosage Strength	Content of clomipramine hydrochloride per tablet
CLOMICALM 5	5 mg
CLOMICALM 20	20 mg
CLOMICALM 80	80 mg

Bottles, HDPE, 40 mL, with screw caps, 30 tablets/bottle.

Storage Conditions

Store at room temperature in a dry place. Store unused product in the original container.

^®Registered Trademark of Novartis Animal Health Canada Inc.

Nac No.

12310030