Antisedan (Canada)

Each mL of Antisedan contains 5.0 mg atipamezole hydrochloride as the medicinal ingredient, 1.0 mg methylparaben as the preservative, 8.5 mg sodium chloride, and water for injection.

Clinical Pharmacology

Activation of peripheral and central α₂-adrenergic receptors is known to induce a pattern of pharmacological responses including sedation, reduction of anxiety, analgesia, bradycardia, and transient hypertension with a subsequently reduced blood pressure. Atipamezole is a potent α₂-antagonist which selectively and competitively inhibits α₂-adrenergic receptors. The result of atipamezole administration in the dog is the rapid recovery from the sedation and other clinical effects produced by the α₂-adrenergic agonists, dexmedetomidine and medetomidine. Atipamezole is not expected to reverse the effects of other classes of sedatives, anesthetics, or analgesics.

Rapid absorption occurs following intramuscular injection, with a maximum serum concentration reached in approximately 10 minutes. Onset of arousal is usually apparent within 5 to 10 minutes of injection, depending on the depth and duration of dexmedetomidine- or medetomidine-induced sedation. Elimination half-life from serum is less than 3 hours. Atipamezole undergoes extensive hepatic biotransformation, with excretion of metabolites primarily in urine.

A transient, approximately 10%, decrease in systolic blood pressure occurs immediately after administration of atipamezole to dexmedetomidine- or medetomidine-sedated dogs, followed by an increase in pressure within 10 minutes to the pre-atipamezole level. This is the opposite of the response to α₂-agonist therapy, and is probably due to peripheral vasodilatation.

Atipamezole will produce a rapid improvement in dexmedetomidine- or medetomidine-induced bradycardia. An increase in heart rate is usually apparent within approximately 3 minutes of injection, but approximately 40% of dogs are not expected to immediately return to presedative rate. Some dogs may experience brief heart rate elevations above-baseline. Respiratory rate also increases following atipamezole injection.

Antisedan Indications

Antisedan is indicated for the reversal of the clinical effects of the sedative and analgesic agents, Dexdomitor (dexmedetomidine hydrochloride) and Domitor (medetomidine hydrochloride), in dogs.

Warnings

Keep out of reach of children.

CAUTIONS: Antisedan can produce an abrupt reversal of sedation and, presumably, analgesia. The potential for apprehensive or aggressive behavior should be considered in the handling of dogs emerging from sedation, especially those individuals who are likely to be in pain.

Information on use of atipamezole with concurrent drugs is inadequate, therefore caution should be exercised when administering multiple drugs. Animals should be monitored closely, particularly for persistent hypothermia, bradycardia, and depressed respiration, until the animal has recovered completely. Caution should be used in administration of anesthetic agents to elderly or debilitated animals.

While atipamezole does reverse the clinical signs associated with dexmedetomidine or medetomidine sedation, complete physiologic return to pretreatment status may not be immediate and should be monitored.

Antisedan has not been evaluated in breeding animals; therefore, the drug is not recommended for use in pregnant or lactating animals, or in animals intended for breeding.

NOTE TO USERS: Care should be taken to assure that Antisedan is not inadvertently ingested as safety studies have indicated that the drug is absorbed when administered orally. As with all injectable drugs causing profound physiological effects, routine precautions should be employed when handling and using filled syringes, including washing eye and skin areas affected by accidental spillage. In case of accidental human exposure, a physician should be contacted.

Side Effects

Occasional vomiting may occur. Rarely, a brief state of excitement or apprehensiveness may be seen in treated dogs. Other potential side effects of α₂-antagonists include hypersalivation, diarrhea, and tremors.

OVER DOSAGE: Atipamezole was tolerated in healthy dogs receiving doses 10-fold the recommended dose and in dogs receiving repeated doses at 1-, 3-, and 5-fold doses, in the absence of an α₂-antagonist. Signs of overdose were dose-related and consistent with those expected in non-sedated dogs having received a stimulant. Signs seen at elevated doses included excitement, panting, trembling, vomiting, soft or liquid feces or vasodilation (injection) of the sclera. Some localized skeletal muscle injury was seen at the injection site; but no associated clinical signs or complications were observed. Dogs receiving the proper dose in the absence of dexmedetomidine or medetomidine, or 3-fold overdose after dexmedetomidine or medetomidine sedation, exhibited no significant clinical signs.

Dosage and Administration

Antisedan is administered intramuscularly regardless of the route used for Dexdomitor or Domitor. The concentration of Antisedan has been formulated such that the volume of injection is the same (mL for mL) as the recommended dose volume of Dexdomitor or Domitor, and may be given at any time following Dexdomitor or Domitor administration. Although injection volumes are the same, the concentration of Antisedan (5.0 mg/mL) is 10 times that of Dexdomitor (0.5 mg/mL) and 5 times that of Domitor (1.0 mg/mL). Dogs that are sedated but ambulatory may be treated with Antisedan, if warranted.

The dosage of Antisedan is calculated based upon body surface area. Use the following tables to determine the proper injection volume based on bodyweight. Note that the mcg/kg dosage decreases as body weight increases.

Table 1: Atipamezole dosing for reversal of IV dexmedetomidine- or medetomidine-induced sedation/analgesia:

Table 2: Atipamezole dosing for reversal of IM dexmedetomidine- or medetomidine-induced sedation/analgesia:

Storage

Store between 15 and 30°C.

Use within 90 days after first vial puncture.

Puncture a maximum of 100 times, with a needle no larger than 21G.

PRESENTATION: Antisedan is supplied in 10 mL multidose vials.

^® Registered trademark of Orion Corporation; Zoetis Canada Inc., Licensee.

Developed and manufactured by:

Orion Pharma, Orion Corporation, Espoo, Finland

Distributed by:

Zoetis Canada Inc., KIRKLAND QC H9H 4M7

105848-8

6298-11-2

July 2023

CPN: 1198322.6