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CaniQuell (clomipramine hydrochloride)
80 mg (44 - 176 lbs. body weight)
FOR USE IN DOGS ONLY****
** CAUTION:** Federal law restricts this drug for use by or on the order of a licensed veterinarian.
Net contents: 30 tablets
80 mg each

Indications and Usage:

CaniQuell tablets are to be used as part of a comprehensive behavioral management program to treat separation anxiety in dogs greater than 6 months of age. Inappropriate barking or destructive behavior, as well as inappropriate elimination of (urination or defecation) may be alleviated by the use of CaniQuell tablets in conjunction with behavior modification.

Separation anxiety is a complex behavior disorder displayed when the owner (or other attachment figure) leaves the dog. In the absence of the owner or attachment figure, dogs with separation anxiety may exhibit one or more clinical signs. The signs of separation anxiety evaluated in controlled trials were vocalization, destructive behavior, excessive salivation, and inappropriate elimination. Although it may appear that this behavior, which only happens in the dog owner’s absence, is a spiteful action, this behavior is thought to be a result of anxiety experienced by the dog. Therefore, punishment would not be appropriate for the dog with this behavior.

Contraindications:

CaniQuell tablets are contraindicated in dogs with known hypersensitivity to clomipramine or related tricyclic antidepressants.

CaniQuell tablets should not be used in male breeding dogs. Testicular hypoplasia was seen in dogs treated for 1 year at 12.5 times the maximum daily dose.

CaniQuell tablets should not be given in combination, or within 14 days before or after treatment with a monoamine oxidase inhibitor [e.g. selegiline hydrochloride (L-deprenyl), amitraz].

CaniQuell tablets are contraindicated for use in dogs with a history of seizures or concomitantly with drugs which lower the seizure threshold.

Adverse Reactions:

The following adverse reactions have been reported associated with administration of CaniQuell tablets: lethargy/depression, vomiting, diarrhea, elevation in liver enzymes, convulsion(s), increased heart rate, decreased heart rate, increased thirst and confusion. Liver disease has occurred, especially in the presence of pre-existing conditions or with concurrent administration of drugs metabolized by the liver. In overdoses, signs such as vomiting, lethargy or depression, weakness and incoordination, dilated pupils, and vocalization may occur. Consult with your veterinarian if your dog experiences these or any other conditions.

Contact Information: Contact Mizner Bioscience, LLC at 561-570-1875 or miznerbioscience.com. To report suspected adverse drug experiences, contact Mizner Bioscience, LLC at 561-570-1875. For additional information about reporting adverse drug experiences for animal drugs, contact FDA at 1-888-FDA- VETS or http://www.fda.gov/reportanimalae

Keep CaniQuell tablets in a secure location out of reach of dogs, cats, and other animals to prevent accidental ingestion or overdose.

Drug Interactions:

Recommendations on the interaction between clomipramine and other medications are extrapolated from data generated in humans. Plasma levels of tricyclic antidepressants have been reported to be decreased by the concomitant administration of hepatic enzyme inducers (e.g., barbiturates, phenytoin); therefore plasma concentrations of clomipramine may be decreased by the concomitant administration of phenobarbital. Plasma levels of closely related tricyclic antidepressants have been reported to be increased by the concomitant administration of hepatic enzyme inhibitors (e.g., cimetidine, fluoxetine). Tricyclic antidepressants themselves may exhibit hepatic enzyme inhibition and possibly increase plasma levels of barbiturates (phenobarbital). Caution is advised in using clomipramine with anticholinergic or sympathomimetic drugs or with other CNS-active drugs, including general anesthetics and neuroleptics.

Prior to elective surgery with general anesthetics, clomipramine should be discontinued for as long as clinically feasible.

Distributed by: MWI
Boise, ID 83705
www.VetOne.net

Approved by FDA under ANADA # 200-635
Rev. 09/24

Description:

CaniQuell tablets belong to the dibenzazepine class of tricyclic antidepressants. Clomipramine hydrochloride is 3-chloro-5[3-(dimethyl- amino)propyl]-10,11 dihydro-5H dibenz[b,f] azepine monohydrochloride. CaniQuell tablets are oblong, light brown in color and contain clomipramine hydrochloride formulated together with meat components.

Clinical Pharmacology:

Clomipramine hydrochloride reduces the clinical signs of separation anxiety by affecting serotonergic and noradrenergic neuronal transmission in the central nervous system. While clomipramine hydrochloride can cause lethargy in dogs (see Adverse Reactions) its mode of action is not as a sedative. Clomipramine hydrochloride’s capacity to inhibit re-uptake of serotonin in the central nervous system is believed to be the primary mechanism of action. Clomipramine hydrochloride is rapidly absorbed when administered orally. A single-dose crossover study involving 12 dogs evaluated clomipramine hydrochloride bioavailability after IV (2 mg/kg) and oral (4 mg/kg) administration in either a fed or fasted state. The administration of clomipramine hydrochloride in the presence of food resulted in an increase in the rate and extent of drug absorption as shown in the following table (mean ±SD):

	AUC0-inf (nmol hr/L)	Cmax (nmol/L)	Tmax (hr)	Absolute Bioavailability (F)
Fed	1670 ± 575	601 ± 286	1.18 ± 0.32	0.21 ± 0.07
Fasted	1350 ± 447	379 ± 154	1.31 ± 0.32	0.17 ± 0.05

The absolute bioavailability is approximately 25% greater in fed dogs. The apparent terminal plasma half-life ranges from approximately 2 to 9 hours in fed and 3 to 21 hours in fasted dogs. The difference and variability in apparent half-life estimates may be attributable to prolonged drug absorption in the fasted state. The relatively large volume of distribution (3.8 ±0.8 L/kg) suggests that the drug is widely distributed throughout the body. Clomipramine is primarily metabolized in the liver.

Human Warnings:

**Not for use in humans. KEEP OUT OF REACH OF CHILDREN. In case of accidental ingestion seek medical attentionimmediately. In children, accidental ingestion should be regardedas serious. There is no specific antidote for clomipramine.****Overdose in humans causes anticholinergic effects including **effects on the central nervous (e.g.,convulsions) and cardiovascular (e.g.,arrhythmia, tachycardia) systems. Peoplewith known hypersensitivity to clomipramineshould administer the product with caution.

Precautions:

It is important that your dog be closely monitored by your veterinarian while on a treatment plan with CaniQuell tablets and behavior training. You must inform your veterinarian of any current or future medications you are administering to your dog. The use of CaniQuell tablets in conjunction with certain other drugs or when your dog has other illnesses may be contraindicated or increase the risks of adverse reactions.

It is important that you inform your veterinarian of any changes in your dog’s environment including, but not limited to, a new family member, a new pet, a move to a new location, or a change in your existing daily schedule. Some changes may result in an altered
response to therapy.

It is important to inform your veterinarian of any perceived changes in your dog’s behavior, appetite, or overall health while administering any medication. Some dogs display a temporary lethargy with the first few days of CaniQuell tablets treatment. In some cases, signs of separation anxiety, such as vocalization, may temporarily increase at the initiation of treatment. In an overdose situation, seek veterinary attention for your pet as soon as possible.

The safety and efficacy of CaniQuell tablets have not been established in dogs less than 6 months of age or in pregnant or lactating female dogs. CaniQuell tablets should not be used in breeding male dogs (see Contraindications). CaniQuell tablets are not recommended for other behavior problems, such as aggression.

Dosage and Administration:

The recommended daily dose of CaniQuell tablets is 2 to 4 mg/kg/day (0.9 – 1.8 mg/lb/day) (see dosing table below). Your veterinarian will instruct you to give the drug either once a day or divide the daily dose into 2 separate doses depending on your dog’s response to the drug or tolerance to any side effects. CaniQuell tablets may be given with a small amount of food in an attempt to reduce the incidence of vomiting that may be experienced by some dogs. If a dose is missed, the next dose should be administered (without doubling) at the next scheduled dosing time.

Dog Weight (lbs)	CaniQuell per Day	No. Tablets per Day	Tablet Strength
2.75 - 5.5	5 mg	1	5 mg
5.6 - 10.9	10 mg	2	5 mg
11 - 22	20 mg	1	20 mg
22.1 - 44	40 mg	1	40 mg
44.1 - 88	80 mg	1	80 mg
88.1 - 176	160 mg	2	80 mg

Your veterinarian may decrease the dose or discontinue treatment with CaniQuell tablets depending on your dog’s response to treatment. Continued behavior training is recommended, even after cessation of drug therapy.

Storage Conditions:

Store in a dry place at controlled room temperature, between 59° and 77°F (15-25°C). Store unused tablets in the original closed container.

How Supplied:

CaniQuell tablets are available in 5, 20, 40 and 80 mg tablet strengths in color-coded packaging for oral administration to dogs.

KEEP THIS AND ALL DRUGS OUT OF REACH OF CHILDREN.