Atipamezole

For the reversal of the sedative and analgesic effects of dexmedetomidine hydrochloride, and medetomidine hydrochloride in dogs.

Federal law restricts this drug to use by or on the order of a licensed veterinarian.

REVERTIDINE™

Atipamezole Hydrochloride Injection is indicated for the reversal of the sedative and analgesic effects of dexmedetomidine hydrochloride, and medetomidine hydrochloride in dogs.

Atipamezole Hydrochloride Injection Sterile Injectable Solution - 5.0 mg/mL Dexmedetomidine and Medetomidine Reversing Agent For intramuscular use in dogs only

ANTISEDAN is indicated for the reversal of the sedative and analgesic effects of DEXDOMITOR (dexmedetomidine hydrochloride), and DOMITOR (medetomidine hydrochloride) in dogs.

ANTISEDAN® (atipamezole hydrochloride)

INDICATIONS: REVERTIDINE is indicated for the reversal of the sedative and analgesic effects of dexmedetomidine hydrochloride, and medetomidine hydrochloride in dogs.

REVERTIDINE

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.

REVERTIDINE

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.

REVERTIDINE

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 1-888-590-9839 Note to Physician: This product contains an alpha2-adrenergic antagonist.

REVERTIDINE

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

Cropamezole™(atipamezole hydrochloride)Sterile Injectable Solution - 5.0 mg/mL

Federal law restricts this drug to use by or on the order of a licensed veterinarian.

ANTISEDAN® (atipamezole hydrochloride)

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. Contact Information: To report suspected adverse drug events, for technical assistance or to obtain a copy of the SDS, contact Modern Veterinary Therapeutics, LLC at 1-888-590-9839 or modernveterinarytherapeutics.com. For additional information about adverse drug experience reporting for animal drugs, contact FDA at 1-888-FDA-VETS or online at www.fda.gov/reportanimalae.

REVERTIDINE

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. To report suspected adverse drug events, for technical assistance or to obtain a copy of the Safety Data Sheet, contact Covetrus® North America at 855-724-3461 or covetrus.com. For additional information about adverse drug experience reporting for animal drugs, contact FDA at 1-888-FDA-VETS or http://www.fda.gov/reportanimalae.

Atipamezole Hydrochloride Injection Sterile Injectable Solution - 5.0 mg/mL

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.

ANTISEDAN® (atipamezole hydrochloride)

Administer intramuscularly (IM) for reversal of sedation and analgesia regardless of the route used for dexmedetomidine hydrochloride or medetomidine hydrochloride. The atipamezole dose for the reversal of intravenous dexmedetomidine hydrochloride or medetomidine hydrochloride is 3750 mcg/m2. The atipamezole dose for the reversal of IM dexmedetomidine hydrochloride or medetomidine hydrochloride is 5000 mcg/m2.

Intramuscular

CONTRASED™

REVERTIDINE™ is administered intramuscularly (IM) for reversal of sedation and analgesia regardless of the route used for dexmedetomidine or medetomidine. The atipamezole dose for the reversal of IV dexmedetomidine or medetomidine is 3750 mcg/m2. The atipamezole dose for the reversal of IM dexmedetomidine or medetomidine is 5000 mcg/m2.

Intramuscular

Federal law restricts this drug to use by or on the order of a licensed veterinarian.

REVERTIDINE™

The atipamezole dose for the reversal of intravenous (IV) DEXDOMITOR (dexmedetomidine hydrochloride), or DOMITOR (medetomidine hydrochloride) is 3750 mcg/m2. The atipamezole dose for the reversal of intramuscular (IM) DEXDOMITOR (dexmedetomidine hydrochloride), or DOMITOR (medetomidine hydrochloride) is 5000 mcg/m2.

Intramuscular

For intramuscular use only. Not recommended for use in pregnant or lactating animals, or animals intended for breeding. Atipamezole has not been evaluated in breeding animals. Federal law restricts this drug to use by or on the order of a licensed veterinarian.

Antisedan®

Administer 3,750 mcg/m2 intramuscularly for the reversal of intravenous dexmedetomidine hydrochloride or medetomidine hydrochloride and 5,000 mcg/m2 intramuscularly for the reversal of intramuscular dexmedetomidine hydrochloride or medetomidine hydrochloride.

Intramuscular

Atipamezole Hydrochloride Injection

Atipamezole Hydrochloride Injection is administered intramuscularly (IM) for reversal of sedation and analgesia regardless of the route used for dexmedetomidine hydrochloride or medetomidine hydrochloride. The atipamezole dose for the reversal of IV dexmedetomidine hydrochloride or medetomidine hydrochloride is 3750 mcg/m2. The atipamezole dose for the reversal of IM dexmedetomidine hydrochloride or medetomidine hydrochloride is 5000 mcg/m2. The dosage of Atipamezole Hydrochloride Injection is calculated based on body surface area. Use the following tables to determine the correct injection volume or the correct Atipamezole Hydrochloride Injection dosage on the basis of kilograms of body weight. 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: Dose table for Atipamezole Hydrochloride Injection (3750 mcg/m2) when dexmedetomidine or medetomidine is given IV For # lbs For # kg dose = mcg/kg volume = mL Atipamezole Hydrochloride Injection 4-7 2-3 300 0.1 7-9 3-4 250 0.15 9-11 4-5 230 0.2 11-22 5-10 200 0.3 22-33 10-15 170 0.4 33-44 15-20 150 0.5 44-55 20-25 140 0.6 55-66 25-30 130 0.7 66-81 30-37 120 0.8 81-99 37-45 110 0.9 99-110 45-50 105 1.0 110-132 50-60 100 1.1 132-143 60-65 95 1.2 143-165 65-75 93 1.3 165-176 75-80 91 1.4 >176 >80 90 1.5 Table 2: Atipamezole dosing for reversal of IM dexmedetomidine- or medetomidine-induced sedation/analgesia: Dose table for Atipamezole Hydrochloride Injection (5000 mcg/m2) when dexmedetomidine or medetomidine is given IM For # lbs For # kg dose = mcg/kg volume = mL Atipamezole Hydrochloride Injection 4-7 2-3 400 0.15 7-9 3-4 350 0.2 9-11 4-5 300 0.3 11-22 5-10 250 0.4 22-29 10-13 230 0.5 29-33 13-15 210 0.6 33-44 15-20 200 0.7 44-55 20-25 180 0.8 55-66 25-30 170 0.9 66-73 30-33 160 1.0 73-81 33-37 150 1.1 81-99 37-45 145 1.2 99-110 45-50 140 1.3 110-121 50-55 135 1.4 121-132 55-60 130 1.5 132-143 60-65 128 1.6 143-154 65-70 125 1.7 154-176 70-80 123 1.8 >176 >80 120 1.9

INTRAMUSCULAR

Atipamezole Hydrochloride Injection Sterile Injectable Solution - 5.0 mg/mL Dexmedetomidine and Medetomidine Reversing Agent For intramuscular use in dogs only

Inversedine® is administered intramuscularly (IM) for reversal of sedation and analgesia regardless of the route used for dexmedetomidine hydrochloride or medetomidine hydrochloride. The atipamezole dose for the reversal of IV dexmedetomidine hydrochloride or medetomidine hydrochloride is 3750 mcg/m2. The atipamezole dose for the reversal of IM dexmedetomidine hydrochloride or medetomidine hydrochloride is 5000 mcg/m2. The dosage of Inversedine® is calculated based on body surface area. Use the following tables to determine the correct injection volume or the correct Inversedine® dosage on the basis of kilograms of body weight. Note that the mcg/kg dosage decreases as body weight increases. Table 1: Atipamezole dosing for reversal of IV dexmedetomidine hydrochloride- or medetomidine hydrochloride-induced sedation/analgesia: Dose table for Inversedine® (3750 mcg/m2) when dexmedetomidine hydrochloride or medetomidine hydrochloride is given IV For # lb For # kg dose = mcg/kg Volume = mL Inversedine® 4-7 2-3 300 0.1 7-9 3-4 250 0.15 9-11 4-5 230 0.2 11-22 5-10 200 0.3 22-33 10-15 170 0.4 33-44 15-20 150 0.5 44-55 20-25 140 0.6 55-66 25-30 130 0.7 66-81 30-37 120 0.8 81-99 37-45 110 0.9 99-110 45-50 105 1.0 110-132 50-60 100 1.1 132-143 60-65 95 1.2 143-165 65-75 93 1.3 165-176 75-80 91 1.4 >176 >80 90 1.5 Table 2: Atipamezole dosing for reversal of IM dexmedetomidine hydrochloride- or medetomidine hydrochloride- induced sedation/analgesia: Dose table for Inversedine® (5000 mcg/m2) when dexmedetomidine hydrochloride or medetomidine hydrochloride is given IM For # lb For # kg dose = mcg/kg volume = mL Inversedine® 4-7 2-3 400 0.15 7-9 3-4 350 0.2 9-11 4-5 300 0.3 11-22 5-10 250 0.4 22-29 10-13 230 0.5 29-33 13-15 210 0.6 33-44 15-20 200 0.7 44-55 20-25 180 0.8 55-66 25-30 170 0.9 66-73 30-33 160 1.0 73-81 33-37 150 1.1 81-99 37-45 145 1.2 99-110 45-50 140 1.3 110-121 50-55 135 1.4 121-132 55-60 130 1.5 132-143 60-65 128 1.6 143-154 65-70 125 1.7 154-176 70-80 123 1.8 >176 >80 120 1.9

INTRAMUSCULAR

VETONE® Inversedine®(atipamezole hydrochloride)5.0 mg/mLSterile Injectable SolutionDexmedetomidine and Medetomidine Reversing Agent

ANTISEDAN is administered intramuscularly (IM) for reversal of sedation and analgesia regardless of the route used for DEXDOMITOR or DOMITOR. The atipamezole dose for the reversal of IV DEXDOMITOR or DOMITOR is 3750 mcg/m2. The atipamezole dose for the reversal of IM DEXDOMITOR or DOMITOR is 5000 mcg/m2. The dosage of ANTISEDAN is calculated based on body surface area. Use the following tables to determine the correct injection volume or the correct ANTISEDAN dosage on the basis of kilograms of body weight. 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: Dose table for ANTISEDAN (3750 mcg/m2) when dexmedetomidine or medetomidine is given IV For # lbs For # kg dose = mcg/kg volume = mL ANTISEDAN 4-7 2-3 300 0.1 7-9 3-4 250 0.15 9-11 4-5 230 0.2 11-22 5-10 200 0.3 22-33 10-15 170 0.4 33-44 15-20 150 0.5 44-55 20-25 140 0.6 55-66 25-30 130 0.7 66-81 30-37 120 0.8 81-99 37-45 110 0.9 99-110 45-50 105 1.0 110-132 50-60 100 1.1 132-143 60-65 95 1.2 143-165 65-75 93 1.3 165-176 75-80 91 1.4 >176 >80 90 1.5 Table 2: Atipamezole dosing for reversal of IM dexmedetomidine- or medetomidine-induced sedation/analgesia: Dose table for ANTISEDAN (5000 mcg/m2) when dexmedetomidine or medetomidine is given IM For # lbs For # kg dose = mcg/kg volume = mL ANTISEDAN 4-7 2-3 400 0.15 7-9 3-4 350 0.2 9-11 4-5 300 0.3 11-22 5-10 250 0.4 22-29 10-13 230 0.5 29-33 13-15 210 0.6 33-44 15-20 200 0.7 44-55 20-25 180 0.8 55-66 25-30 170 0.9 66-73 30-33 160 1.0 73-81 33-37 150 1.1 81-99 37-45 145 1.2 99-110 45-50 140 1.3 110-121 50-55 135 1.4 121-132 55-60 130 1.5 132-143 60-65 128 1.6 143-154 65-70 125 1.7 154-176 70-80 123 1.8 >176 >80 120 1.9

INTRAMUSCULAR

ANTISEDAN® (atipamezole hydrochloride)

DOSAGE AND ADMINISTRATION : REVERTIDINE is administered intramuscularly (IM) for reversal of sedation and analgesia regardless of the route used for dexmedetomidine or medetomidine. The atipamezole dose for the reversal of IV dexmedetomidine or medetomidine is 3750 mcg/m2 . The atipamezole dose for the reversal of IM dexmedetomidine or medetomidine is 5000 mcg/m2. The dosage of REVERTIDINE is calculated based on body surface area. Use the following tables to determine the correct injection volume or the correct REVERTIDINE dosage on the basis of kilograms of body weight. Note that the mcg/kg dosage decreases as body weight increases.

INTRAMUSCULAR

REVERTIDINE