Dexmedetomidine

For use as a sedative and analgesic in dogs and cats to facilitate clinical examinations, clinical procedures, minor surgical procedures, and minor dental procedures. Dexmedetomidine HCl is also indicated for use as a preanesthetic to general anesthesia in dogs and cats

Dexmedesed®

For use as a sedative and analgesic to facilitate clinical examinations, clinical procedures, minor surgical procedures, and minor dental procedures. It is also indicated for use as a preanesthetic to general anesthesia.<!--EndFragment-->

DexmedVet™

For use as a sedative and analgesic to facilitate clinical examinations, clinical procedures, minor surgical procedures, and minor dental procedures; and as a preanesthetic to general anesthesia.

DEXVETRA™

For use as a sedative and analgesic to facilitate clinical examinations, clinical procedures, minor surgical procedures, and minor dental procedures.

Federal law restricts this drug to use by or on the order of a licensed veterinarian. Do not use DEXDOMITOR in dogs or cats with cardiovascular disease, respiratory disorders, liver or kidney diseases, or in conditions of shock, severe debilitation, or stress due to extreme heat, cold or fatigue.

Dexdomitor®

For use as a preanesthetic to general anesthesia.

Federal law restricts this drug to use by or on the order of a licensed veterinarian. Do not use DEXDOMITOR in dogs or cats with cardiovascular disease, respiratory disorders, liver or kidney diseases, or in conditions of shock, severe debilitation, or stress due to extreme heat, cold or fatigue.

Dexdomitor®

For use as a sedative and analgesic to facilitate clinical examinations, clinical procedures, minor surgical procedures, and minor dental procedures. It is also indicated for use as a preanesthetic to general anesthesia.

Dexmedetomidine Hydrochloride

For use as a sedative and analgesic in dogs to facilitate clinical examinations, clinical procedures, minor surgical procedures, and minor dental procedures.

Federal law restricts this drug to use by or on the order of a licensed veterinarian. Do not use DEXDOMITOR in dogs or cats with cardiovascular disease, respiratory disorders, liver or kidney diseases, or in conditions of shock, severe debilitation, or stress due to extreme heat, cold or fatigue.

Dexdomitor®

For use as a preanesthetic to general anesthesia.

Federal law restricts this drug to use by or on the order of a licensed veterinarian. Do not use DEXDOMITOR in dogs or cats with cardiovascular disease, respiratory disorders, liver or kidney diseases, or in conditions of shock, severe debilitation, or stress due to extreme heat, cold or fatigue.

Dexdomitor®

For the treatment of noise aversion in dogs.

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

SILEO®

Dexmedetomidine Hydrochloride Injection is indicated for use as a sedative and analgesic in dogs and cats to facilitate clinical examinations, clinical procedures, minor surgical procedures, and minor dental procedures. Dexmedetomidine Hydrochloride Injection is also indicated for use as a preanesthetic to general anesthesia in dogs and cats.

Dexmedetomidine Hydrochloride Injection0.5 mg/mL

INDICATIONS: Dexmedesed is indicated for use as a sedative and analgesic in dogs and cats to facilitate clinical examinations, clinical procedures, minor surgical procedures, and minor dental procedures. Dexmedesed is also indicated for use as a preanesthetic to general anesthesia in dogs and cats.

Dexmedesed® (dexmedetomidine hydrochloride) Sterile Injectable Solution-0.5 mg/mL For Intramuscular and Intravenous Use in Dogs For Intramuscular Use in Cats Sedative, Analgesic, Preanesthetic

DexmedVet™ is indicated for use as a sedative and analgesic in dogs and cats to facilitate clinical examinations, clinical procedures, minor surgical procedures, and minor dental procedures. DexmedVet™ is also indicated for use as a preanesthetic to general anesthesia in dogs and cats.

DexmedVet™

SILEO is indicated for the treatment of noise aversion in dogs.

SILEO®

Dexmedetomidine is a potent and selective alpha-2 adrenoceptor agonist that inhibits the release of noradrenaline from noradrenergic neurons. A reduction of heart rate may occur. In a clinical safety study the mean heart rate dropped from 127 bpm to 98 bpm for dogs treated with the dexmedetomidine gel. Oral bioavailability of dexmedetomidine is poor due to extensive first-pass metabolism. No measurable concentrations were found after gastro-intestinal tubing of dexmedetomidine to dogs. When administered via the oral mucosa, enhanced bioavailability is observed as a result of absorption in the oral cavity and the avoidance of first-pass metabolism in the liver. The maximum concentration of dexmedetomidine occurs at about 0.6 hours after both IM and oromucosal administration in dogs. In a pharmacokinetic study in dogs, the oromucosal mean bioavailability of dexmedetomidine was 28%. The apparent volume of distribution of the drug is 0.9 L/kg. In the canine circulation, dexmedetomidine is largely bound to plasma proteins (93%). Dexmedetomidine is eliminated by biotransformation mainly in the liver with a half-life ranging from 0.5 to 0.7 hours after intravenous (IV) administration and 0.5 to 3 hours after oromucosal administration in dogs. Metabolism accounts for more than 98% of the elimination. Known metabolites show no or negligible activity. Metabolites are excreted mainly in the urine with a minor fraction found in the feces.

SILEO®

CLINICAL PHARMACOLOGY: Dexmedetomidine is a potent non-narcotic alpha2 -adrenoceptor agonist which produces sedation and analgesia. These effects are dose dependent in depth and duration. Blood pressure is initially increased due to peripheral vasoconstriction, subsequently dropping to normal or slightly below normal levels. Vasoconstriction may cause mucous membranes to appear pale or mildly cyanotic. This initial vasopressor response is accompanied by a compensatory marked decrease in heart rate mediated by a vagal baroreceptor. The peripheral pulse may feel weak and a transient change in the conductivity of the cardiac muscle may occur, as evidenced by first and second degree atrioventricular blocks. Other arrhythmias may occur. Dexmedetomidine also decreases the respiratory rate and decreases body temperature. The magnitude and duration of the decrease in body temperature is dose dependent. Dexmedetomidine causes depression of gastrointestinal motility due to decrease in smooth muscle activity, increases in blood glucose levels due to inhibition of insulin release, and increases in production of urine. Spontaneous muscle contractions (twitching) can be expected in some dogs sedated with dexmedetomidine. Vomiting in cats has been associated with alpha2 -adrenergic agonist central stimulation of the brain4.

Sedexodine™

Do not use Dexmedetomidine Hydrochloride Injection in dogs or cats with cardiovascular disease, respiratory disorders, liver or kidney diseases, or in conditions of shock, severe debilitation, or stress due to extreme heat, cold or fatigue. As with all alpha2-adrenoceptor agonists, the potential for isolated cases of hypersensitivity, including paradoxical response (excitation), exists.

Dexmedetomidine Hydrochloride Injection0.5 mg/mL

Do not use DexmedVet™ in dogs or cats with cardiovascular disease, respiratory disorders, liver or kidney diseases, or in conditions of shock, severe debilitation, or stress due to extreme heat, cold or fatigue. As with all alpha 2 -adrenoceptor agonists, the potential for isolated cases of hypersensitivity, including paradoxical response (excitation), exists.

DexmedVet™

Do not use SILEO in dogs with severe cardiovascular, respiratory, liver or kidney disease, or in conditions of shock, severe debilitation, or stress due to extreme heat, cold or fatigue. Do not use in dogs with hypersensitivity to dexmedetomidine or to any of the excipients.

SILEO®

Human safety: Not for human use. Keep out of reach of children. Dexmedetomidine hydrochloride can be absorbed following direct exposure to skin, eyes, or mouth, and may cause irritation. 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. Appropriate precautions should be taken while handling and using filled syringes. Accidental topical (including ocular) exposure, oral exposure, or exposure by injection could cause adverse reactions, including sedation, hypotension, and bradycardia. Seek medical attention immediately. Users with cardiovascular disease (for example, hypertension or ischemic heart disease) should take special precautions to avoid any exposure to this product. Caution should be exercised when handling sedated animals. Handling or any other sudden stimuli, including noise, may cause a defense reaction in an animal that appears to be heavily sedated. 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, send request to: info@aspenveterinaryresources.com. Note to physician: This product contains an alpha2 -adrenergic agonist. Animal safety: Dexmedetomidine should not be administered in the presence of preexisting hypotension, hypoxia, or bradycardia. Due to the pronounced cardiovascular effects of dexmedetomidine, only clinically healthy dogs and cats (ASA classes I and II) should be treated. Animals should be frequently monitored for cardiovascular function and body temperature during sedation or anesthesia. Dexmedetomidine sedation is not recommended for cats with respiratory disease. The use of dexmedetomidine as a preanesthetic in dogs and cats significantly reduces the amount of induction and maintenance anesthetic requirements. Careful patient monitoring during anesthetic induction and maintenance is necessary to avoid anesthetic overdose.

Dexased™

Human Safety: Not for human use. Keep out of reach of children. Avoid administering the product if pregnant, as exposure may induce uterine contractions and/or decrease fetal blood pressure. Appropriate precautions should be taken while handling and using filled syringes. Impermeable disposable gloves should be worn when handling the syringe, administering SILEO, or when coming in contact with the dog’s mouth after application. If skin is damaged, dexmedetomidine can be absorbed into the body. In case of skin contact, wash with soap and water. Remove contaminated clothing. SILEO can be absorbed following direct exposure to skin, eyes, or mouth. In case of accidental eye exposure, flush with water for 15 minutes. If wearing contact lenses, eyes should be rinsed first, then remove contact lenses and continue rinsing, then seek medical advice immediately. Accidental exposure may cause sedation and changes in blood pressure. In case of accidental exposure, seek medical attention immediately. Exposure to the product may induce a local or systemic allergic reaction in sensitized individuals. Note to physician: This product contains an alpha-2 adrenoceptor agonist. 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. Animal Safety: SILEO should not be administered in the presence of pre-existing hypotension, hypoxia, or bradycardia. Sensitive dogs may experience a drop in body temperature and heart rate, and may appear sedated. These dogs should be kept warm and not offered food or water until SILEO’s effects have worn off (usually within a few hours). Do not use in dogs sedated from previous dosing.

SILEO®

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

DEXDOMITOR®

Canine sedation/analgesia field study: In the field study safety analysis, 106 dogs received dexmedetomidine and 107 received medetomidine. Dogs ranged from 16 weeks to 16 years of age, representing 49 breeds. The following table shows the number of dogs displaying each clinical observation (some dogs experienced more than one adverse reaction). Table 4: Adverse reactions during the canine sedation/analgesia field study Dexmedetomidine Medetomidine Total n= 106 Total n= 107 Ausculted unidentified arrhythmias 19 20 Severe bradycardia requiring treatment 1 1 Apnea requiring treatment 1 0 Slow onset of sedation (exceeding 30 minutes) 1 1 Ineffectiveness (dog standing throughout the study) 3 2 Severe hypothermia requiring treatment 2 0 Prolonged recovery 1 4 The occurrence of ausculted unidentified arrhythmias (some at multiple time points) decreased following the administration of atipamezole. Canine preanesthesia field study: The preanesthesia field study safety analysis included 192 dogs, between 5 months and 15 years of age, representing 43 breeds enrolled for elective procedures conducted under general anesthesia. The following table shows the number of dogs within a treatment group that showed each clinical sign (dogs may have experienced more than one adverse reaction). Table 5: Adverse reactions during the canine preanesthesia field study Treatment Groups Induction Anesthetic: Propofol Barbiturate Preanesthetic Dose: 0 mcg/m2 n=32 125 mcg/m2 n=32 375 mcg/m2 n=32 0 mcg/m2 n=32 125 mcg/m2 n=32 375 mcg/m2 n=32 Emesis 4 7 4 2 3 6 Ventricular premature contractions 0 2 0 4 1 0 Diarrhea 1 0 0 3 1 1 Self trauma 0 2 1 2 1 0 Severe bradycardia 0 0 1 0 0 1 Tachycardia 0 0 0 1 1 0 Urinary incontinence 0 0 0 0 0 1 Other clinical signs observed in dogs treated with dexmedetomidine include decreased respiratory rate and hypothermia. Feline sedation/analgesia field study: The field study safety analysis included 242 cats (122 received dexmedetomidine; 120 received xylazine), 6 months to 17 years of age, and representing 19 breeds. The following table shows the number of cats reported with an adverse reaction (cats may have experienced more than one adverse reaction). Table 6: Adverse reactions during the feline field study Dexmedetomidine n = 122 Xylazine n = 120 Vomiting 70 82 Urinary incontinence 6 11 Hypersalivation 4 5 Involuntary defecation 4 1 Hypothermia 2 1 Diarrhea 2 0 Arrhythmia 1 2 Corneal ulcer 1 0 Cyanosis 1 0 Dyspnea 1 0 The most frequently observed adverse reaction was vomiting in both fasted and fed cats. Other infrequent clinical signs observed in cats treated with dexmedetomidine included fatigue, anorexia, cystitis, and peripheral vascular disorder. One incidence of dyspnea was reported, 43 minutes after dexmedetomidine administration during an oral examination/dental procedure. Prior to dexmedetomidine, the cat was free of clinical signs, but had a history of asthma and respiratory infection. The cat responded successfully to treatment. Feline preanesthesia field study: The field study safety analysis included 184 cats (116 received dexmedetomidine; 68 received saline), 12 weeks to 16 years of age, and representing 11 breeds. The following table shows the number of cats reported with an adverse reaction (cats may have experienced more than one adverse reaction). Table 7: Adverse reactions during the feline preanesthesia field study Induction Anesthetic Ketamine Propofol Preanesthetic Saline n=37 Dexmedetomidine n=64 Saline n=31 Dexmedetomidine n=52 Emesis 2 20 1 12 Pale mucous membranes 11 9 Decreased body temperature 4 Retching 1 1 3 Heart murmur 2 Loose stool 2 Corneal injury 1 Apnea 1 Behavioral change 1 Fluid in endotracheal tube 1 One case of apnea was reported in a cat that received ketamine as the induction agent. This cat required artificial ventilation from the start of the procedure until 30 minutes into recovery when the cat began to breathe on its own. The cat recovered without further problems.

Dexmedetomidine Hydrochloride 0.5 mg/mL

In a well-controlled European field study, which included a total of 182 dogs ranging from 2 to 17 years of age and representing both mixed and pure breed dogs (89 treated with dexmedetomidine oromucosal gel and 93 treated with control), no serious adverse reactions were attributed to administration of dexmedetomidine oromucosal gel. Table 2 shows the number of dogs displaying adverse reactions (some dogs experienced more than one adverse reaction). Table 2. Adverse Reactions - Number (%) of dogs Adverse Reaction Control N = 93 Dexmedetomidine 125 mcg/m2 N = 89 Emesis 1 ( 1.1) 4 ( 4.5) Gastroenteritis 0 1 ( 1.1) Periorbital edema 0 1 ( 1.1) Drowsiness 0 1 ( 1.1) Sedation 0 1 ( 1.1) Pale mucous membranes were frequently seen in dogs treated with dexmedetomidine oromucosal gel. In most cases, the effect was transient and no adverse reactions due to mucosal irritation were reported. In a second well-controlled European field study which included a total of 36 dogs ranging from 2 to 17 years of age and representing both mixed and pure breed dogs (12 treated with dexmedetomidine oromucosal gel at 125 mcg/m2, 12 treated with dexmedetomidine oromucosal gel at 250 mcg/m2, and 12 treated with a vehicle control), no serious adverse reactions were attributed to administration of dexmedetomidine oromucosal gel.Table 3 shows the number of dogs displaying adverse reactions (some dogs experienced more than one adverse reaction). Table 3. Adverse Reactions - Number (%) of dogs Adverse Reaction Control N = 12 Dexmedetomidine 125 mcg/m2 N = 12 Dexmedetomidine 250 mcg/m2 N = 12 Sedation 0 2 (16.7) 4 (33.3) Lack of effectiveness 4 (33.3) 0 1 (8.3) Urinary incontinence 0 1 (8.3) 1 (8.3) Emesis 0 2 (16.7) 0 Head tremor 0 0 1 (8.3) Inappropriate urination 0 1 (8.3) 0 Ataxia 0 0 1 (8.3) Mydriasis 0 0 1 (8.3) Anxiety disorder 0 0 1 (8.3) Tachypnea 1 (8.3) 0 0 Lethargy 1 (8.3) 0 0 Tachycardia 1 (8.3) 0 0

SILEO®

For sedative and analgesic administer 375 mcg/m2 by intravenous (IV) injection or 500 mcg/m2 by intramuscular (IM) injection; for preanesthesia administer 125 or 375 mcg/m2 by IM injection

Intramuscular, Intravenous

Dexmedesed®

Administer 500 mcg/m2 intramuscularly (IM) or 375 mcg/m2 of body surface area by intravenous (IV) injection. Note that the mcg/kg dosage decreases as body weight increases.

Intravenous, Intramuscular

Federal law restricts this drug to use by or on the order of a licensed veterinarian. Do not use DEXDOMITOR in dogs or cats with cardiovascular disease, respiratory disorders, liver or kidney diseases, or in conditions of shock, severe debilitation, or stress due to extreme heat, cold or fatigue.

Dexdomitor®

Administer 125 mcg/m2 of body surface area or 375 mcg/m2 of body surface area by intramuscular injection. Note that the mcg/kg dosage decreases as body weight increases.

Intravenous, Intramuscular

Federal law restricts this drug to use by or on the order of a licensed veterinarian. Do not use DEXDOMITOR in dogs or cats with cardiovascular disease, respiratory disorders, liver or kidney diseases, or in conditions of shock, severe debilitation, or stress due to extreme heat, cold or fatigue.

Dexdomitor®

Administer 375 micrograms (mcg) per square meter (/m2) of body surface area by intravenous injection or 500 mcg/m2 of body surface area by intramuscular injection.

Intravenous, Intramuscular

DEXVETRA™

Sedation and Analgesia: 500 mcg/m2 intramuscularly (IM) or 375 mcg/m2 intravenously (IV). Preanesthesia: 125 or 375 mcg/m2 IM.

Intravenous, Intramuscular

Dexmedetomidine Hydrochloride

Administer onto the oral mucosa between the dog’s cheek and gum at the dose of 125 micrograms per square meter.

Oromucosal

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

SILEO®

Administer 125 mcg/m2 of body surface area or 375 mcg/m2 of body surface area by intramuscular injection.

Intravenous, Intramuscular

DEXVETRA™

Sedation, Analgesia and Preanesthesia: 40 mcg/kg intramuscularly (IM)

Intravenous, Intramuscular

Dexmedetomidine Hydrochloride

For sedation, analgesia, or preanesthesia administer 40 mcg/kg IM

Intramuscular, Intravenous

Dexmedesed®

Sedation, Analgesia and Preanesthesia: 40 mcg/kg IM.

Intramuscular, Intravenous

DexmedVet™

40 µg/killogram by intramuscular injection.

Intravenous, Intramuscular

Dexmedetomidine Hydrochloride

40 mcg/kg by intramuscular (IM) injection.

Intravenous, Intramuscular

Federal law restricts this drug to use by or on the order of a licensed veterinarian. Do not use DEXDOMITOR in dogs or cats with cardiovascular disease, respiratory disorders, liver or kidney diseases, or in conditions of shock, severe debilitation, or stress due to extreme heat, cold or fatigue.

Dexdomitor®

Dogs: Sedation and Analgesia: 500 mcg/m 2 intramuscularly (IM) or 375 mcg/m 2 intravenously (IV). Preanesthesia: 125 or 375 mcg/m 2 IM. The choice of preanesthetic dose depends on the duration and severity of the procedure, as well as the anesthetic regime. The following two tables may be used to determine the correct dexmedetomidine dosage. Note that the mcg/kg dosage decreases as body weight increases. For example, dogs weighing 2 kg are dosed at 28.1 mcg/kg dexmedetomidine IV, compared to dogs weighing 80 kg that are dosed at 8.7 mcg/kg. Due to the small volume of administration, accurate dosing is not possible in dogs weighing less than 2 kg (4.4 lb). Table 1: CANINE SEDATION/ANALGESIA DOSE TABLE: Intravenous (IV) and Intramuscular (IM) dosing on the basis of body weight Sedexodine 0.5 mg/mL Sedation/analgesia in dogs Dog Weight Dexmedetomidine 375 mcg/m 2 IV Dexmedetomidine 500 mcg/m 2 IM lbs kg mcg/kg mL mcg/kg mL 4.4 to 7 2 to 3 28.1 0.12 40 0.15 7.1 to 9 3.1 to 4 25 0.15 35 0.2 9.1 to 11 4.1 to 5 23 0.2 30 0.3 11.1 to 22 5.1 to 10 19.6 0.29 25 0.4 22.1 to 29 10.1 to 13 16.8 0.38 23 0.5 29.1 to 33 13.1 to 15 15.7 0.44 21 0.6 33.1 to 44 15.1 to 20 14.6 0.51 20 0.7 44.1 to 55 20.1 to 25 13.4 0.6 18 0.8 55.1 to 66 25.1 to 30 12.6 0.69 17 0.9 66.1 to 73 30.1 to 33 12 0.75 16 1 73.1 to 81 33.1 to 37 11.6 0.81 15 1.1 81.1 to 99 37.1 to 45 11 0.9 14.5 1.2 99.1 to 110 45.1 to 50 10.5 0.99 14 1.3 110.1 to 121 50.1 to 55 10.1 1.06 13.5 1.4 121.1 to 132 55.1 to 60 9.8 1.13 13 1.5 132.1 to 143 60.1 to 65 9.5 1.19 12.8 1.6 143.1 to 154 65.1 to 70 9.3 1.26 12.5 1.7 154.1 to 176 70.1 to 80 9 1.35 12.3 1.8 >176 ˃80 8.7 1.42 12 1.9 Table 2: CANINE PREANESTHESIA DOSE TABLE: Intramuscular (IM) dosing on the basis of body weight Sedexodine 0.5 mg/mL Preanesthesia in dogs Dog Weight Dexmedetomidine 125 mcg/m 2 IM Dexmedetomidine 375 mcg/m 2 IM lbs kg mcg/kg mL mcg/kg mL 4.4 to 7 2 to 3 9.4 0.04 28.1 0.12 7.1 to 9 3.1 to 4 8.3 0.05 25 0.15 9.1 to 11 4.1 to 5 7.7 0.07 23 0.2 11.1 to 22 5.1 to 10 6.5 0.1 19.6 0.29 22.1 to 29 10.1 to 13 5.6 0.13 16.8 0.38 29.1 to 33 13.1 to 15 5.2 0.15 15.7 0.44 33.1 to 44 15.1 to 20 4.9 0.17 14.6 0.51 44.1 to 55 20.1 to 25 4.5 0.2 13.4 0.6 55.1 to 66 25.1 to 30 4.2 0.23 12.6 0.69 66.1 to 73 30.1 to 33 4 0.25 12 0.75 73.1 to 81 33.1 to 37 3.9 0.27 11.6 0.81 81.1 to 99 37.1 to 45 3.7 0.3 11 0.9 99.1 to 110 45.1 to 50 3.5 0.33 10.5 0.99 110.1 to 121 50.1 to 55 3.4 0.35 10.1 1.06 121.1 to 132 55.1 to 60 3.3 0.38 9.8 1.13 132.1 to 143 60.1 to 65 3.2 0.4 9.5 1.19 143.1 to 154 65.1 to 70 3.1 0.42 9.3 1.26 154.1 to 176 70.1 to 80 3 0.45 9 1.35 >176 ˃80 2.9 0.47 8.7 1.42 The use of dexmedetomidine as a preanesthetic markedly reduces anesthetic requirements in dogs. Injectable induction drug requirements for intubation will be reduced between 30% and 60%, depending on the choice of anesthetic and the dexmedetomidine preanesthetic dose. The concentration of inhalation maintenance anesthetic will be reduced between 40% and 60%, depending on the dose of dexmedetomidine. The anesthetic dose should always be titrated against the response of the patient. The choice of anesthetic is left to the discretion of the veterinarian. Cats: Sedation, Analgesia and Preanesthesia: 40 mcg/kg intramuscularly (IM). This dose can also be used as a preanesthetic and has been shown to markedly reduce anesthetic requirements in cats. Injectable anesthetic drug requirements for intubation were reduced up to 49%, depending on the choice of induction drug. The concentration of inhalation maintenance anesthetic was reduced between 35% and 44%, depending on the choice of induction drug. The anesthetic dose should always be titrated against the response of the patient. The following table may be used to determine the correct dexmedetomidine dosage for cats based on body weight. Table 3: FELINE DOSE TABLE: Intramuscular (IM) dosing on the basis of body weight in cats Sedexodine 0.5 mg/mL Sedation/analgesia and preanesthesia in cats Cat Weight Dexmedetomidine 40 mcg/kg IM lbs kg mcg/kg mL 2 to 4 1 to 2 40 0.1 4.1 to 7 2.1 to 3 40 0.2 7.1 to 9 3.1 to 4 40 0.3 9.1 to 13 4.1 to 6 40 0.4 13.1 to 15 6.1 to 7 40 0.5 15.1 to 18 7.1 to 8 40 0.6 18.1 to 22 8.1 to 10 40 0.7 It is recommended that dogs and cats be fasted for 12 hours before treatment with Sedexodine. An eye lubricant should be applied to cats to prevent corneal desiccation that may result from a reduction in the blink reflex. Following injection of Dexmedetomidine Hydrochloride Injection, the animal should be allowed to rest quietly for 15 minutes; sedation and analgesia occur within 5 to 15 minutes, with peak effects at 30 minutes after dexmedetomidine.

INTRAMUSCULAR, INTRAVENOUS

Sedexodine™ (dexmedetomidine hydrochloride) Injection0.5 mg/mL Sterile Injectable Solution

Dogs: Sedation and Analgesia: 500 mcg/m2 intramuscularly (IM) or 375 mcg/m2 intravenously (IV). Preanesthesia: 125 or 375 mcg/m2 IM. The choice of preanesthetic dose depends on the duration and severity of the procedure, as well as the anesthetic regime. The following two tables may be used to determine the correct dexmedetomidine dosage. Note that the mcg/kg dosage decreases as body weight increases. For example, dogs weighing 2 kg are dosed at 28.1 mcg/kg dexmedetomidine IV, compared to dogs weighing 80 kg that are dosed at 8.7 mcg/kg. Due to the small volume of administration, accurate dosing is not possible in dogs weighing less than 2 kg (4.4 lb). Table 1: CANINE SEDATION/ANALGESIA DOSE TABLE: Intravenous (IV) and intramuscular (IM) dosing on the basis of body weight Dexmedetomidine Hydrochloride 0.5 mg/mL Sedation/analgesia in dogs Dog Weight Dexmedetomidine 375 mcg/m2 IV Dexmedetomidine 500 mcg/m2 IM lbs Kg mcg/kg mL mcg/kg mL 4.4-7 2-3 28.1 0.12 40 0.15 7.1-9 3.1-4 25 0.15 35 0.2 9.1-11 4.1-5 23 0.2 30 0.3 11.1-22 5.1-10 19.6 0.29 25 0.4 22.1-29 10.1-13 16.8 0.38 23 0.5 29.1-33 13.1-15 15.7 0.44 21 0.6 33.1-44 15.1-20 14.6 0.51 20 0.7 44.1-55 20.1-25 13.4 0.6 18 0.8 55.1-66 25.1-30 12.6 0.69 17 0.9 66.1-73 30.1-33 12 0.75 16 1 73.1-81 33.1-37 11.6 0.81 15 1.1 81.1-99 37.1-45 11 0.9 14.5 1.2 99.1-110 45.1-50 10.5 0.99 14 1.3 110.1-121 50.1-55 10.1 1.06 13.5 1.4 121.1-132 55.1-60 9.8 1.13 13 1.5 132.1-143 60.1-65 9.5 1.19 12.8 1.6 143.1-154 65.1-70 9.3 1.26 12.5 1.7 154.1-176 70.1-80 9 1.35 12.3 1.8 >176 >80 8.7 1.42 12 1.9 Table 2: CANINE PREANESTHESIA DOSE TABLE: Intramuscular (IM) dosing on the basis of body weight Dexmedetomidine Hydrochloride 0.5 mg/mL Preanesthesia in dogs Dog Weight Dexmedetomidine 125 mcg/m2 IM Dexmedetomidine 375 mcg/m2 IM lbs Kg mcg/kg mL mcg/kg mL 4.4-7 2-3 9.4 0.04 28.1 0.12 7.1-9 3.1-4 8.3 0.05 25 0.15 9.1-11 4.1-5 7.7 0.07 23 0.2 11.1-22 5.1-10 6.5 0.1 19.6 0.29 22.1-29 10.1-13 5.6 0.13 16.8 0.38 29.1-33 13.1-15 5.2 0.15 15.7 0.44 33.1-44 15.1-20 4.9 0.17 14.6 0.51 44.1-55 20.1-25 4.5 0.2 13.4 0.6 55.1-66 25.1-30 4.2 0.23 12.6 0.69 66.1-73 30.1-33 4 0.25 12 0.75 73.1-81 33.1-37 3.9 0.27 11.6 0.81 81.1-99 37.1-45 3.7 0.3 11 0.9 99.1-110 45.1-50 3.5 0.33 10.5 0.99 110.1-121 50.1-55 3.4 0.35 10.1 1.06 121.1-132 55.1-60 3.3 0.38 9.8 1.13 132.1-143 60.1-65 3.2 0.4 9.5 1.19 143.1-154 65.1-70 3.1 0.42 9.3 1.26 154.1-176 70.1-80 3 0.45 9 1.35 >176 >80 2.9 0.47 8.7 1.42 The use of dexmedetomidine as a preanesthetic markedly reduces anesthetic requirements in dogs. Injectable induction drug requirements for intubation will be reduced between 30% and 60%, depending on the choice of anesthetic and the dexmedetomidine preanesthetic dose. The concentration of inhalation maintenance anesthetic will be reduced between 40% and 60%, depending on the dose of dexmedetomidine. The anesthetic dose should always be titrated against the response of the patient. The choice of anesthetic is left to the discretion of the veterinarian. Cats: Sedation, Analgesia and Preanesthesia: 40 mcg/kg intramuscularly (IM). This dose can also be used as a preanesthetic and has been shown to markedly reduce anesthetic requirements in cats. Injectable anesthetic drug requirements for intubation were reduced up to 49%, depending on the choice of induction drug. The concentration of inhalation maintenance anesthetic was reduced between 35% and 44%, depending on the choice of induction drug. The anesthetic dose should always be titrated against the response of the patient. The following table may be used to determine the correct dexmedetomidine dosage for cats based on body weight. Table 3: FELINE DOSE TABLE: Intramuscular (IM) dosing on the basis of body weight in cats Dexmedetomidine Hydrochloride 0.5 mg/mL Sedation/analgesia and preanesthesia in cats Cat Weight Dexmedetomidine 40 mcg/kg IM lbs Kg mcg/kg mL 2-4 1-2 40 0.1 4.1-7 2.1-3 40 0.2 7.1-9 3.1-4 40 0.3 9.1-13 4.1-6 40 0.4 13.1-15 6.1-7 40 0.5 15.1-18 7.1-8 40 0.6 18.1-22 8.1-10 40 0.7 It is recommended that dogs and cats be fasted for 12 hours before treatment with Dexmedetomidine Hydrochloride. An eye lubricant should be applied to cats to prevent corneal desiccation that may result from a reduction in the blink reflex. Following injection of Dexmedetomidine Hydrochloride, the animal should be allowed to rest quietly for 15 minutes; sedation and analgesia occur within 5 to 15 minutes, with peak effects at 30 minutes after dexmedetomidine.

INTRAVENOUS, INTRAMUSCULAR

Dexmedetomidine Hydrochloride 0.5 mg/mL

Dogs: Sedation and Analgesia: 500 mcg/m2 intramuscularly (IM) or 375 mcg/m2 intravenously (IV). Preanesthesia: 125 or 375 mcg/m2 IM. The choice of preanesthetic dose depends on the duration and severity of the procedure, as well as the anesthetic regime. The following two tables may be used to determine the correct dexmedetomidine dosage. Note that the mcg/kg dosage decreases as body weight increases. For example, dogs weighing 2 kg are dosed at 28.1 mcg/kg dexmedetomidine IV, compared to dogs weighing 80 kg that are dosed at 8.7 mcg/kg. Due to the small volume of administration, accurate dosing is not possible in dogs weighing less than 2 kg (4.4 lb). Table 1: CANINE SEDATION/ANALGESIA DOSE TABLE: Intravenous (IV) and intramuscular (IM) dosing on the basis of body weight. DexmedVetTM 0.5 mg/mL Sedation/analgesia in dogs Dog Weight Dexmedetomidine 375 mcg/m2 IV Dexmedetomidine 500 mcg/m2 IM lbs Kg mcg/kg mL mcg/kg mL 4.4-7 2-3 28.1 0.12 40 0.15 7.1-9 3.1-4 25 0.15 35 0.2 9.1-11 4.1-5 23 0.2 30 0.3 11.1-22 5.1-10 19.6 0.29 25 0.4 22.1-29 10.1-13 16.8 0.38 23 0.5 29.1-33 13.1-15 15.7 0.44 21 0.6 33.1-44 15.1-20 14.6 0.51 20 0.7 44.1-55 20.1-25 13.4 0.6 18 0.8 55.1-66 25.1-30 12.6 0.69 17 0.9 66.1-73 30.1-33 12 0.75 16 1 73.1-81 33.1-37 11.6 0.81 15 1.1 81.1-99 37.1-45 11 0.9 14.5 1.2 99.1-110 45.1-50 10.5 0.99 14 1.3 110.1-121 50.1-55 10.1 1.06 13.5 1.4 121.1-132 55.1-60 9.8 1.13 13 1.5 132.1-143 60.1-65 9.5 1.19 12.8 1.6 143.1-154 65.1-70 9.3 1.26 12.5 1.7 154.1-176 70.1-80 9 1.35 12.3 1.8 >176 >80 8.7 1.42 12 1.9 Table 2: CANINE PREANESTHESIA DOSE TABLE: Intramuscular (IM) dosing on the basis of body weight. DexmedVetTM 0.5 mg/mL Preanesthesia in dogs Dog Weight Dexmedetomidine 125 mcg/m2 IM Dexmedetomidine 375 mcg/m2 IM lbs Kg mcg/kg mL mcg/kg mL 4.4-7 2-3 9.4 0.04 28.1 0.12 7.1-9 3.1-4 8.3 0.05 25 0.15 9.1-11 4.1-5 7.7 0.07 23 0.2 11.1-22 5.1-10 6.5 0.1 19.6 0.29 22.1-29 10.1-13 5.6 0.13 16.8 0.38 29.1-33 13.1-15 5.2 0.15 15.7 0.44 33.1-44 15.1-20 4.9 0.17 14.6 0.51 44.1-55 20.1-25 4.5 0.2 13.4 0.6 55.1-66 25.1-30 4.2 0.23 12.6 0.69 66.1-73 30.1-33 4 0.25 12 0.75 73.1-81 33.1-37 3.9 0.27 11.6 0.81 81.1-99 37.1-45 3.7 0.3 11 0.9 99.1-110 45.1-50 3.5 0.33 10.5 0.99 110.1-121 50.1-55 3.4 0.35 10.1 1.06 121.1-132 55.1-60 3.3 0.38 9.8 1.13 132.1-143 60.1-65 3.2 0.4 9.5 1.19 143.1-154 65.1-70 3.1 0.42 9.3 1.26 154.1-176 70.1-80 3 0.45 9 1.35 >176 >80 2.9 0.47 8.7 1.42 The use of dexmedetomidine as a preanesthetic markedly reduces anesthetic requirements in dogs. Injectable induction drug requirements for intubation will be reduced between 30% and 60%, depending on the choice of anesthetic and the dexmedetomidine preanesthetic dose. The concentration of inhalation maintenance anesthetic will be reduced between 40% and 60%, depending on the dose of dexmedetomidine. The anesthetic dose should always be titrated against the response of the patient. The choice of anesthetic is left to the discretion of the veterinarian. Cats: Sedation, Analgesia and Preanesthesia: 40 mcg/kg intramuscularly (IM). This dose can also be used as a preanesthetic and has been shown to markedly reduce anesthetic requirements in cats. Injectable anesthetic drug requirements for intubation were reduced up to 49%, depending on the choice of induction drug. The concentration of inhalation maintenance anesthetic was reduced between 35% and 44%, depending on the choice of induction drug. The anesthetic dose should always be titrated against the response of the patient. The following table may be used to determine the correct dexmedetomidine dosage for cats based on body weight. Table 3: FELINE DOSE TABLE: Intramuscular (IM) dosing on the basis of body weight in cats. DexmedVet 0.5 mg/mL Sedation/analgesia and preanesthesia in cats Cat Weight lbs kg Dexmedetomidine 40 mcg/kg IM mcg/kg mL 2-4 1-2 40 0.1 4.1-7 2.1-3 40 0.2 7.1-9 3.1-4 40 0.3 9.1-13 4.1-6 40 0.4 13.1-15 6.1-7 40 0.5 15.1-18 7.1-8 40 0.6 18.1-22 8.1-10 40 0.7 It is recommended that dogs and cats be fasted for 12 hours before treatment with DexmedVetTM. An eye lubricant should be applied to cats to prevent corneal desiccation that may result from a reduction in the blink reflex. Following injection of DexmedVetTM, the animal should be allowed to rest quietly for 15 minutes; sedation and analgesia occur within 5 to 15 minutes, with peak effects at 30 minutes after dexmedetomidine.

INTRAMUSCULAR, INTRAVENOUS

DexmedVet™

Always provide the Client Information Sheet with SILEO and instruct the client how to properly operate the SILEO dosing syringe (see Client Information Sheet for Owner/Handler Use and Safety). SILEO is administered onto the oral mucosa between the dog’s cheek and gum at the dose of 125 mcg/m2. The gel is absorbed through the oral mucosa and therefore it should NOT be swallowed. If the gel is swallowed, the product may not be effective. If the gel is swallowed, do not repeat the dose for at least two hours. The following table provides the acceptable dosage for each weight range. Each dot (●) represents 0.25 mL of SILEO. Each ml contains the equivalent to 0.1mg dexmedetomidine hydrochloride. Table 1. Dosage by body weight Bodyweight (lb) Number of dots 4.4-12.1 1 ● 12.2-26.5 2 ●● 26.6-44.0 3 ●●● 44.1-63.9 4 ●●●● 64.0-86.0 5 ●●●●● 86.1-110.2 6 ●●●●●● 110.3-137.8 7 ●●●●●●● 137.9-166.4 8 ●●●●●●●● 166.5-196.2 9 ●●●●●●●●● 196.3-220.5 10 ●●●●●●●●●● If the dose is more than 6 dots, divide the dose between both sides of the mouth. The first dose of SILEO should be administered approximately 30-60 minutes before the fear and/or anxiety-eliciting noise stimulus, immediately after the dog shows first signs of anxiety or fear related to noise, or when the owner detects a typical noise stimulus (e.g. sound of fireworks) eliciting anxiety or fear in the dog. Typical signs of anxiety and fear associated with noise aversion are panting, trembling, pacing, seeking people, trying to hide, trying to escape, freezing behavior, refusing to eat food or treats, inappropriate urination or defecation, and salivation. Administering SILEO without use of the SILEO syringe will result in incorrect dosing, which may result in lack of efficacy or overdose. Dosing should be performed by an adult. Impermeable disposable gloves should be worn when administering SILEO and when handling the SILEO syringe. If noise lasts longer than 2-3 hours and the dog’s signs of fear and/or anxiety reappear, another dose may need to be given. To avoid overdosing, there should always be at least two hours’ pause between dosages. No more than 5 doses can be given during one noise event. A partially used syringe can be used again within 2 weeks after initial opening, if there is enough gel for a complete dose for the dog. To minimize the risk of incorrect dosing, a partially used syringe that does not have enough gel for a complete dose should not be used. Any unused product or waste material should be disposed of according

ORAL

SILEO®