Atipamezole

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ANTISEDAN (atipamezole hydrochloride) is a synthetic α₂-adrenergic antagonist. The chemical name is 4-(2-ethyl-2,3-dihydro-1H-inden-2-yl)-1H-imidazole hydrochloride. The molecular formula is C₁₄H₁₆N₂•HCl. Each mL of ANTISEDAN contains 5.0 mg atipamezole hydrochloride, 1.0 mg methylparaben (NF), 8.5 mg sodium chloride (USP), and water for injection (USP).

Each mL of ANTISEDAN contains 5.0 mg atipamezole hydrochloride, 1.0 mg methylparaben (NF), 8.5 mg sodium chloride (USP), and water for injection (USP).

Contraindications

Since atipamezole is always used concomitantly with dexmedetomidine or medetomidine, it should not be used in dogs with the following conditions: cardiac disease, respiratory disorders, liver or kidney diseases, dogs in shock, severely debilitated dogs, or dogs stressed due to extreme heat, cold or fatigue.

Administration of atipamezole is contraindicated in dogs with a known hypersensitivity to the drug.

HUMAN WARNINGS: Not for human use. Keep out of reach of children.

Atipamezole hydrochloride can be absorbed and may cause irritation following direct exposure to skin, eyes, or mouth. In case of accidental eye exposure, flush with water for 15 minutes. In case of accidental skin exposure, wash with soap and water. Remove contaminated clothing. If irritation or other adverse reaction occurs (for example, increased heart rate, tremor, muscle cramps), seek medical attention.

In case of accidental oral exposure or injection, seek medical attention. Caution should be used while handling and using filled syringes.

Users with cardiovascular disease (for example, hypertension or ischemic heart disease) should take special precautions to avoid any exposure to this product.

The safety data sheet (SDS) contains more detailed occupational safety information.

To report adverse reactions in users or to obtain a copy of the SDS for this product call 1-888-963-8471.

Note to Physician: This product contains an alpha₂-adrenergic antagonist.

Precautions

1. Handling: ANTISEDAN can produce an abrupt reversal of sedation; therefore, dogs that have recently received ANTISEDAN should be handled with caution. The potential for apprehensive or aggressive behavior should be considered in the handling of dogs emerging from sedation, especially in dogs with a nervous or anxious disposition. Also, avoid in situations that may involve a fall risk.

2. Sedation relapse: While atipamezole does reverse the clinical signs associated with medetomidine or dexmedetomidine sedation, complete physiologic return to pretreatment status may not be immediate or may be temporary, and dogs should be monitored for sedation relapse. Sedation relapse is more likely to occur in dogs that receive an alpha₂-agonist by the IV route, compared to dogs that are sedated using the IM route. Animals should be monitored closely for persistent hypothermia, bradycardia, and depressed respiration, until signs of recovery persist.

3. Analgesia reversal: Atipamezole reverses analgesic effects as well as sedative effects. Additional procedures for the control of pain may be required.

4. Debilitated dogs: The safety of atipamezole has not been evaluated in dogs with compromised health. Geriatric, debilitated, and ill dogs are more likely to experience adverse reactions associated with the administration of alpha₂-antagonists (as well as alpha₂-agonists). Dogs with abnormalities associated with the cardiovascular system are especially at risk.

5. Breeding dogs: ANTISEDAN has not been evaluated in breeding dogs; therefore, the drug is not recommended for use in pregnant or lactating dogs, or in dogs intended for breeding.

6. Minimum age and weight: ANTISEDAN has not been evaluated in dogs less than four months of age or in dogs weighing less than 4.4 lbs (2 kg).

Adverse Reactions

Occasional vomiting may occur. At times, a period of excitement or apprehensiveness may be seen in dogs treated with atipamezole. Other effects of atipamezole include hypersalivation, diarrhea, and tremors.

Clinical Pharmacology

Atipamezole is a potent alpha₂-antagonist which selectively and competitively inhibits alpha₂-adrenergic receptors. The result of atipamezole administration in the dog is the rapid recovery from the sedative and analgesic effects produced by the alpha₂-adrenergic agonists dexmedetomidine or medetomidine. Atipamezole does not reverse the effects of other classes of sedatives, anesthetics, or analgesics.

Atipamezole is rapidly absorbed following intramuscular injection; maximum serum concentration is 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.

Dexmedetomidine or medetomidine activation of peripheral and central alpha₂-adrenergic receptors induces a pattern of pharmacological responses that include sedation, reduction of anxiety, analgesia, and bradycardia.

Blood pressure is initially increased due to peripheral vasoconstriction and thereafter drops to normal or slightly below normal levels.

A transient, decrease in systolic blood pressure occurs immediately after administration of atipamezole to dexmedetomidine- or medetomidine-sedated dogs, followed by a transient increase in arterial pressure within 10 minutes compared to pre-atipamezole levels. This is the opposite of the response to alpha₂-agonist treatment, and is probably due to atipamezole-induced peripheral vasodilation.

Atipamezole administration rapidly abolishes dexmedetomidine- or medetomidine-induced bradycardia, usually within 3 minutes. The magnitude of the effect of atipamezole on heart rate is greater when dexmedetomidine is administered intravenously compared to intramuscularly. Dogs receiving medetomidine or IM dexmedetomidine may not return to pre-sedative heart rates after atipamezole administration and some dogs briefly show heart rate elevations above baseline. Respiratory rate increases following atipamezole injection.