Clomipramine Hydrochloride (2 brand names, 1 dosage form, 1 route)
Available dosage forms: CAPSULE.
Routes of administration: ORAL.
Brand Names
- ANAFRANIL
- CLOMIPRAMINE HYDROCHLORIDE
Indications and Usage
CALMERA 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 (urination or defecation) may be alleviated by the use of CALMERA tablets in conjunction with behavior modification. Separation anxiety is a complex behavior disorder displayed when the owner (or other attachment figure) leaves the dog. The signs of separation anxiety evaluated in controlled trials were vocalization, destructive behavior, excessive salivation, and inappropriate elimination. In the absence of the owner or attachment figure, dogs with separation anxiety may exhibit one or more of these clinical signs. Although the owner (attachment figure) may inadvertently misinterpret this behavior, which only happens in their absence, as spiteful, it is thought to be the result of anxiety experienced by the dog. Punishment is not considered appropriate for a dog with separation anxiety. Proper recognition of clinical signs, including a complete patient history and assessment of the patient’s household environment, is essential to accurately diagnose and treat separation anxiety. The use of CALMERA tablets should not replace appropriate behavioral and environmental management but should be used to facilitate a comprehensive behavior management program.
Dosage and Administration
The recommended daily dose of CALMERA tablets is 2 to 4 mg/kg/day (0.9 -1.8 mg/lb/day) (see dosing table below). It can be administered as a single daily dose or divided twice daily based on patient response and/or tolerance of the side effects. It may be prudent to initiate treatment in divided doses to minimize side effects by permitting tolerance to side effects to develop or allowing the patient time to adapt if tolerance does not develop. To reduce the incidence of vomiting that may be experienced by some dogs, CALMERA tablets may be given with a small amount of food. Dog Weight (lbs) CALMERA 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 The specific methods of behavioral modification used in clinical trials involved desensitization and counterconditioning techniques. Since the manifestation of separation anxiety can vary according to the individual dog, it is advised that a specific behavior modification plan be developed based on a professional assessment of each individual case. Once the desired clinical effect is achieved and the owners have successfully instituted the appropriate behavioral modification, the dose of CALMERA tablets may be reduced to maintain the desired effect or discontinued. Withdrawal side effects were not reported in studies with CALMERA tablets in dogs. However, in clinical practice, it is recommended to taper the individual patient dose while continuing to monitor the dog’s behavior and clinical status through the dose reduction or withdrawal period. Continued behavioral modification is recommended to prevent recurrence of the clinical signs. The effectiveness and clinical safety of CALMERA tablets for long-term use (i.e., for more than 12 weeks) has not been evaluated. Professional judgment should be used in monitoring the patient’s clinical status, response to therapy and tolerance to side eff
Contraindications
CALMERA tablets are contraindicated in dogs with known hypersensitivity to clomipramine or other tricyclic antidepressants. CALMERA 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. CALMERA 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]. CALMERA tablets are contraindicated for use in dogs with a history of seizures or concomitantly with drugs which lower the seizure threshold.
Adverse Reactions
Frequency and category of adverse reactions observed in dogs dosed with CALMERA tablets or placebo were observed in multisite clinical studies as follows. Keep CALMERA tablets in a secure location out of reach of dogs, cats, and other animals to prevent accidental ingestion or overdose. Adverse Reactions Reported in Placebo-Controlled Clinical Field Trials Clomipramine hydrochloride tablets N=180 Placebo N=88 Emesis 36 (20%) 8 (9%) Lethargy 26 (14%) 7 (8%) Diarrhea 17 (9%) 4 (5%) Polydipsia 6 (3%) 0 Decreased Appetite 6 (3%) 3 (3%) Aggression* 3 (2%) 1 (1%) Seizure 2 (1%) 0 Dry Mouth 1 (0.5%) 1 (1%) Tremors 1 (0.5%) 0 Constipation 1 (0.5%) 0 Anisocoria 1 (0.5%) 0 Polyuria 1 (0.5%) 0 Hyperthermia 1 (0.5%) 0 *These dogs displayed growling behavior towards either humans or other dogs. Post-Approval Experience: Although not all adverse reactions are reported, the following adverse reactions are based on voluntary post-approval adverse drug experience reporting: lethargy/depression, anorexia, elevation in liver enzymes, vomiting and diarrhea. Hepatobiliary disease has occurred, especially in the presence of pre-existing conditions or with concurrent administration of drugs metabolized via the hepatic system. Additionally, in an overdose situation, the following signs have been reported: ataxia, convulsion(s), anticholinergic effects (e.g. mydriasis, bradycardia, tachycardia, and arrhythmia) and vocalization. Contact Information: To report adverse drug events contact animalcomplaintreporting@pattersoncompanies.com or 1-561-570-1875. For technical assistance or to obtain a copy of the SDS, contact Aspen Veterinary Resources at info@aspenveterinaryresources.com. For additional information about adverse drug experience reporting for animal drugs, contact FDA at 1-888-FDA-VETS or online at http://www.fda.gov/reportanimalae
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.