Frequently asked questions regarding alpha-2 agonist DEXDOMITOR® (dexmedetomidine)

Q: How should I monitor a patient that has received DEXDOMITOR for sedation or as a premedication? A: The monitoring of vital signs is critical for any patient under sedation or anesthesia. It is important to monitor heart rate, blood pressure, palpable pulse quality, and respiratory rate and volume. Because a2 agonists cause peripheral vasoconstriction, the use of pulse oximetry may not adequately reflect the true status of the patient.

Q: What can I expect to see in a patient under DEXDOMITOR sedation? A: The patient may have pale pink or grayish mucous membranes because of peripheral vasoconstriction. The sedation induced by DEXDOMITOR causes a decrease in respiratory rate and a lower body temperature.

Q: What is considered a low heart rate? A: Because of the wide range of dog sizes and corresponding heart rates, normal heart rates should be based on the dog’s body size. A reduction in heart rate following a2 agonist sedation should be expected. Patient status should be evaluated by the simultaneous measurement of many parameters, including pulse quality, respiratory rate and quality, blood pressure, and heart rate.

Q: What is the effect on the respiratory rate? A: DEXDOMITOR does not have a direct effect on respiration. Although the respiratory rate may decrease as a result of sedation, ventilatory volume generally increases, and overall ventilation (gas exchange) remains stable.

Q: I am concerned about hypothermia. A: Hypothermia can occur in a patient following administration of any anesthetic or sedative drug. It is important that body temperature be maintained in all patients undergoing anesthesia or sedation, including those that receive an a2 agonist.

Q: How do I optimize the effects of DEXDOMITOR? A: Several factors can influence the effects of DEXDOMITOR when administered to a patient. A patient that is stressed may have high levels of circulating catecholamines, which can interfere with the activity of DEXDOMITOR. If possible, the patient should be kept calm before injection, and allowed to rest in a quiet, non-stressful environment for at least 15 minutes after injection.

Q: Is there a preferred area of administration for an IM injection of DEXDOMITOR? A: DEXDOMITOR should preferably be given deeply into a muscle, such as the caudal or cranial thigh or epaxial muscle (muscles along the lumbar spine).

Q: What causes the occasional muscle twitching that occurs in DEXDOMITOR-treated patients? A: The muscle twitching observed following DEXDOMITOR administration is not seizure activity and does not require treatment. The exact cause of the twitching is unknown and has been observed following administration of all a2 agonists in a variety of species.

Q: Can DEXDOMITOR be used in sight hounds? A: Yes. There have been no studies showing that sight hounds experience prolonged effects due to dexmedetomidine, and the availability of ANTISEDAN enables predictable recoveries if needed.

Q: Does DEXDOMITOR have an effect on urine production? A: Yes. The increase in urine production is caused by several factors, including transient hyperglycemia and an inhibition of anti-diuretic hormone (ADH). In cats, this effect may be mistaken for urinary incontinence. It is important that patients be allowed to urinate before being sent home.

Important Safety Information Do not use DEXDOMITOR in dogs or cats and ANTISEDAN in dogs 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 should not be administered in the presence of preexisting hypotension, hypoxia, or bradycardia. As with all a2-adrenoceptor agonists, the potential for isolated cases of hypersensitivity, including paradoxical response (excitation), exists with DEXDOMITOR. The use of DEXDOMITOR as a preanesthetic in dogs and cats significantly reduces the amount of induction and maintenance anesthetic requirements. Careful patient monitoring is necessary to avoid anesthetic overdose. Arrhythmias, bradycardia, apnea, emesis, convulsions, hypersalivation may occur with DEXDOMITOR use. Severe dyspnea and respiratory crackles due to acute or delayed pulmonary edema could develop in cats. DEXDOMITOR has not been evaluated for use in breeding, pregnant, or lactating dogs or cats; in dogs younger than 16 weeks of age or in cats younger than 12 weeks of age; in geriatric dogs or cats. Occasional vomiting may occur with ANTISEDAN use. Rarely, a brief state of excitement or apprehensiveness may be seen in ANTISEDAN treated dogs. Other potential side effects of a2-antagonists, such as ANTISEDAN, include hypersalivation, diarrhea, and tremors. For more safety information, refer to the full prescribing information. Table 2: PREANESTHESIA DOSE TABLE: Intramuscular sedation, hypotension, and bradycardia. Seek medical Dexmedetomidine has not been evaluated in dogs NADA 141-267, Approved by FDA. (IM) dosing on the basis of body weight. attention immediately. younger than 16 weeks of age, in cats younger than Users with cardiovascular disease (for example, 12 weeks of age, or in geriatric dogs and cats. Preanesthesia in dogs hypertension or ischemic heart disease) should take Dexmedetomidine has not been evaluated for use in Dog Dexmedetomidine Dexmedetomidine special precautions to avoid any exposure to this breeding, pregnant, or lactating dogs or cats. 2 2 Weight 125 mcg/m IM 375 mcg/m IM product. ADVERSE REACTIONS: (dexmedetomidine hydrochloride) lbs kg mcg/kg DEXDOMITOR mcg/kg DEXDOMITOR Caution should be exercised when handling sedated Canine sedation/analgesia field study: In the mL mL animals. Handling or any other sudden stimuli, including field study safety analysis, 106 dogs received Sterile Injectable Solution – 0.5 mg/mL noise, may cause a defense reaction in an animal that dexmedetomidine and 107 received medetomidine. 4-7 2-3 9.4 0.04 28.1 0.12 appears to be heavily sedated. For intramuscular and intravenous use in dogs and for Dogs ranged from 16 weeks to 16 years of age, 7-9 3-4 8.3 0.05 25.0 0.15 The material safety data sheet (MSDS) contains more representing 49 breeds. The following table shows intramuscular use in cats detailed occupational safety information. To report 9-11 4-5 7.7 0.07 23.0 0.20 the number of dogs displaying each clinical observation CAUTION: Federal law restricts this drug to use by or adverse reactions in users or to obtain a copy of the (some dogs experienced more than one adverse on the order of a licensed veterinarian. 11-22 5-10 6.5 0.10 19.6 0.29 MSDS for this product call 1-800-366-5288. reaction). Note to physician: This product contains an alpha - DESCRIPTION: DEXDOMITOR (dexmedetomidine 22-29 10-13 5.6 0.13 16.8 0.38 2 Table 4: Adverse reactions during the canine sedation/ hydrochloride) is a synthetic alpha -adrenoreceptor adrenergic agonist. 2 29-33 13-15 5.2 0.15 15.7 0.44 analgesia field study agonist with sedative and analgesic properties. The PRECAUTIONS: chemical name is (+)-4-[1-(2,3-dimethylphenyl) ethyl]- 33-44 15-20 4.9 0.17 14.6 0.51 For cats, the concurrent use of DEXDOMITOR prior Dexmedetomidine Medetomidine 1H-imidazole monohydrochloride. It is a white, or almost Total n=106 Total n=107 44-55 20-25 4.5 0.20 13.4 0.60 to or with an anesthetic has not been evaluated. white, crystalline, water soluble substance having a Dexmedetomidine in cats has not been evaluated in Ausculted unidentified 19 20 molecular weight of 236.7. The molecular formula is 55-66 25-30 4.2 0.23 12.6 0.69 the presence of other sedatives. arrhythmias C H N •HCl and the structural formula is: 13 16 2 66-73 30-33 4.0 0.25 12.0 0.75 Dexmedetomidine sedation is not recommended for cats with respiratory disease. Adverse reaction reports Severe bradycardia 1 1 73-81 33-37 3.9 0.27 11.6 0.81 for dexmedetomidine include a cat with severe dyspnea requiring treatment CH CH 81-99 37-45 3.7 0.30 11.0 0.90 and respiratory crackles diagnosed as acute pulmonary Apnea requiring 1 0 3 3 edema. The cat’s health history was not known and treatment 99-110 45-50 3.5 0.33 10.5 0.99 the cat recovered with treatment. Slow onset of sedation 1 1 CH Although not observed in the feline field study with N 3 110- 50-55 3.4 0.35 10.1 1.06 (exceeding 30 minutes) 121 dexmedetomidine, rare cases of delayed pulmonary edema, some resulting in death, have been reported Ineffectiveness (dog 3 2 • HCl 121- 55-60 3.3 0.38 9.8 1.13 standing throughout in cats that received medetomidine (another alpha2- N 132 agonist), usually in conjunction with anesthesia. In the study) H 132- 60-65 3.2 0.40 9.5 1.19 these cases, dyspnea due to the delayed onset of Severe hypothermia 2 0 143 pulmonary edema developed up to three days after requiring treatment medetomidine administration. Each mL of DEXDOMITOR contains 0.5 mg 143- 65-70 3.1 0.42 9.3 1.26 Dexmedetomidine should not be administered in the Prolonged recovery 1 4 dexmedetomidine hydrochloride, 1.6 mg methylparaben 154 presence of preexisting hypotension, hypoxia, or (NF), 0.2 mg propylparaben (NF), 9.0 mg sodium The occurrence of ausculted unidentified arrhythmias 154- 70-80 3.0 0.45 9.0 1.35 bradycardia. Due to the pronounced cardiovascular chloride (USP), and water for injection (USP), q.s. (some at multiple time points) decreased following the 176 effects of dexmedetomidine, only clinically healthy administration of atipamezole. INDICATIONS: DEXDOMITOR is indicated for use dogs and cats should be treated. Animals should be >176 >80 2.9 0.47 8.7 1.42 Canine preanesthesia field study: The preanesthesia as a sedative and analgesic in dogs and cats to frequently monitored for cardiovascular function and field study safety analysis included 192 dogs, between facilitate clinical examinations, clinical procedures, The use of dexmedetomidine as a preanesthetic body temperature during sedation or anesthesia. 5 months and 15 years of age, representing 43 breeds minor surgical procedures, and minor dental markedly reduces anesthetic requirements. Injectable Intramuscular ANTISEDAN (atipamezole) may be enrolled for elective procedures conducted under procedures. DEXDOMITOR is also indicated for use induction drug requirements for intubation will be routinely used to rapidly reverse the effects of general anesthesia. The following table shows the as a preanesthetic to general anesthesia in dogs. reduced between 30% and 60%, depending on dexmedetomidine in dogs. Since analgesic as well number of dogs within a treatment group that showed the choice of anesthetic and the dexmedetomidine as sedative effects will be reversed, pain management each clinical sign (some dogs experienced more than DOSAGE AND ADMINISTRATION: may need to be addressed. Dogs: DEXDOMITOR produces sedation and analgesia preanesthetic dose. The concentration of inhalation one adverse reaction). maintenance anesthetic will be reduced between 40% In the event of apnea, accompanied by bradycardia and when administered intramuscularly (IM) at a dose of cyanotic mucous membranes, additional oxygen should Table 5: Adverse reactions during the canine 2 and 60%, depending on the dose of dexmedetomidine. 500 mcg/m , or intravenously (IV) at a dose of 375 be supplied. Aministration of ANTISEDAN (atipamezole) preanesthesia field study 2 The anesthetic dose should always be titrated against mcg/m . Doses for preanesthesia are 125 or 375 mcg/ to dogs exhibiting these signs is warranted. m2 IM. The choice of preanesthetic dose depends on the response of the patient. The choice of anesthetic Treatment Groups is left to the discretion of the veterinarian. Atipamezole has not been evaluated as a routine the duration and severity of the procedure, as well as dexmedetomidine reversal agent in cats. the anesthetic regime. The following two tables may Cats: DEXDOMITOR produces sedation and analgesia Induction Propofol Barbiturate when administered IM at a dose of 40 mcg/kg. The A decrease in body temperature is likely to occur during Anesthetic: be used to determine the correct dexmedetomidine sedation with dexmedetomidine unless externally dosage. Note that the mcg/kg dosage decreases as following table may be used to determine the correct Preanesthetic 0 125 375 0 125 375 dexmedetomidine dosage for cats based on body maintained. Once established, hypothermia may body weight increases. For example, dogs weighing persist longer than sedation and analgesia. To prevent Dose: mcg/ mcg/ mcg/ mcg/ mcg/ mcg/ weight. 2 2 2 2 2 2 2 kg are dosed at 28 mcg/kg dexmedetomidine IV, hypothermia, treated animals should be kept warm m m m m m m n=32 n=32 n=32 n=32 n=32 n=32 compared to dogs weighing 80 kg that are dosed at Table 3: SEDATION/ANALGESIA DOSE TABLE: and at a constant temperature during the procedure, 9 mcg/kg. Due to the small volume of administration, Intramuscular (IM) dosing on the basis of body and until full recovery. accurate dosing is not possible in dogs weighing less weight in cats. Nervous or excited animals with high levels of than 2 kg. Ventricular 0 2 0 4 1 0 endogenous catecholamines may exhibit a reduced premature Sedation/analgesia in cats pharmacological response to alpha -adrenoceptor Table 1: SEDATION/ANALGESIA DOSE TABLE: 2 contractions Intravenous (IV) and intramuscular (IM) dosing on the Cat Dexmedetomidine agonists like dexmedetomidine. In agitated animals, the basis of body weight. Weight 40 mcg/kg IM onset of sedative/analgesic effects could be slowed, or Severe 0 0 1 0 0 1 lbs kg mcg/kg DEXDOMITOR, the depth and duration of effects could be diminished bradycardia Sedation/analgesia in dogs mL or nonexistent. Therefore, allow dogs and cats to rest Tachycardia 0 0 0 1 1 0 Dog Dexmedetomidine Dexmedetomidine quietly for 10 to 15 minutes after injection. Repeat 4-7 2-3 40 0.2 Diarrhea 1 0 0 3 1 1 Weight 375 mcg/m2 IV 500 mcg/m2 IM dosing has not been evaluated. 7-9 3-4 40 0.3 Reversible corneal opacity may occur during sedation lbs kg mcg/kg DEXDOMITOR mcg/kg DEXDOMITOR Emesis 4 7 4 2 3 6 mL mL 9-13 4-6 40 0.4 in cats. An eye lubricant should be applied to prevent corneal desiccation that may result from a reduction Urinary 0 0 0 0 0 1 4-7 2-3 28.1 0.12 40.0 0.15 13-15 6-7 40 0.5 in the blink reflex during sedation. incontinence 15-18 7-8 40 0.6 7-9 3-4 25.0 0.15 35.0 0.20 Spontaneous muscle contractions (twitching) Self trauma 0 2 1 2 1 0 18-22 8-10 40 0.7 can be expected in some dogs sedated with 9-11 4-5 23.0 0.20 30.0 0.30 dexmedetomidine. Other clinical signs observed in dogs treated with It is recommended that dogs and cats be fasted for The use of dexmedetomidine as a preanesthetic in dexmedetomidine include decreased respiratory rate 11-22 5-10 19.6 0.29 25.0 0.40 12 hours before treatment with DEXDOMITOR. An dogs significantly reduces the amount of induction and hypothermia. 22-29 10-13 16.8 0.38 23.0 0.50 eye lubricant should be applied to cats to prevent and maintenance anesthetic requirements. Careful Feline sedation/analgesia field study: The field corneal desiccation that may result from a reduction patient monitoring during anesthetic induction study safety analysis included 242 cats (122 received 29-33 13-15 15.7 0.44 21.0 0.60 in the blink reflex during sedation. Following injection and maintenance is necessary to avoid anesthetic dexmedetomidine; 120 received xylazine), 0.5 to 17 33-44 15-20 14.6 0.51 20.0 0.70 of DEXDOMITOR, the animal should be allowed to rest overdose. years of age, and representing 19 breeds. The following quietly for 15 minutes; sedation and analgesia occur Analgesia resulting from preanesthetic table shows the number of cats reported with an 44-55 20-25 13.4 0.60 18.0 0.80 within 5 to 15 minutes, with peak effects at 30 minutes dexmedetomidine in dogs is dose-dependent, and adverse reaction (some cats experienced more than 55-66 25-30 12.6 0.69 17.0 0.90 after dexmedetomidine. may not provide adequate pain control during the one adverse reaction). CONTRAINDICATIONS: Do not use DEXDOMITOR in postoperative or postprocedural period. Additional pain 66-73 30-33 12.0 0.75 16.0 1.00 management should be addressed as needed. Table 6: Adverse reactions during the feline dogs or cats with cardiovascular disease, respiratory field study 73-81 33-37 11.6 0.81 15.0 1.10 disorders, liver or kidney diseases, or in conditions of Administration of anticholinergic agents in dogs at the same time or after dexmedetomidine could lead to shock, severe debilitation, or stress due to extreme Dexmedetomidine Xylazine 81-99 37-45 11.0 0.90 14.5 1.20 adverse cardiovascular effects (secondary tachycardia, heat, cold or fatigue. 1, 2, 3 n=122 n=120 99-110 45-50 10.5 0.99 14.0 1.30 As with all alpha -adrenoceptor agonists, the potential prolonged hypertension, and cardiac arrhythmias ). 2 However, an anticholinergic drug may be administered Vomiting 70 82 110- 50-55 10.1 1.06 13.5 1.40 for isolated cases of hypersensitivity, including paradoxical response (excitation), exists. at least 10 minutes before dexmedetomidine for Urinary incontinence 6 11 121 the prevention of the dexmedetomidine-induced 121- 55-60 9.8 1.13 13.0 1.50 HUMAN WARNINGS: Not for human use. Keep out reduction in heart rate. Therefore, the routine use Hypersalivation 4 5 132 of reach of children. of anticholinergics simultaneously with, or after Involuntary defecation 4 1 Dexmedetomidine hydrochloride can be absorbed dexmedetomidine in dogs, is not recommended (see 132- 60-65 9.5 1.19 12.8 1.60 following direct exposure to skin, eyes, or mouth, 143 ANIMAL SAFETY). Hypothermia 2 1 and may cause irritation. In case of accidental eye The use of anticholinergics in the presence of Diarrhea 2 0 143- 65-70 9.3 1.26 12.5 1.70 exposure, flush with water for 15 minutes. In case of dexmedetomidine has not been evaluated in cats. 154 accidental skin exposure, wash with soap and water. Dexmedetomidine has been evaluated only in fasted Arrhythmia 1 2 Remove contaminated clothing. dogs; therefore, its effects on fed dogs (for example, the 154- 70-80 9.0 1.35 12.3 1.80 Corneal ulcer 1 0 176 Appropriate precautions should be taken while occurrence of vomiting) have not been characterized. handling and using filled syringes. Accidental topical In cats, there is a high frequency of vomition whether Cyanosis 1 0 >176 >80 8.7 1.42 12.0 1.90 (including ocular) exposure, oral exposure, or exposure fed or fasted; therefore, fasting is recommended to by injection could cause adverse reactions, including reduce stomach contents. Dyspnea 1 0 The most frequently observed adverse reaction Recovery times were dose dependent, averaging hours. Muscle twitches, decreases in temperature, arrhythmias characterized by isolated junctional escape was vomiting in both fasted and fed cats. Other 15-32 minutes to extubation and 71-131 minutes respiratory rates, and heart rates were seen in all dogs. complexes with episodes of junctional escape rhythm infrequent clinical signs observed in cats treated to standing recovery (longer times correspond to No pupil response was noted in six of twelve dogs (IV) were observed during periods of low heart rate or with dexmedetomidine included fatigue, anorexia, higher dexmedetomidine dose). Recovery times also for up to 1.5 hours; decreased transient pupillary light following sinus pauses in all dexmedetomidine dose cystitis, and peripheral vascular disorder. One depended on the induction anesthetic. Recovery reflex was seen for up to 60 minutes in two of twelve groups. In most cases the arrhythmia was no longer incidence of dyspnea was reported, 43 minutes times following barbiturate induction were longer (30 dogs (IM). Vomiting was seen in one of twelve dogs. observed after 1 to 2 hours. Atrioventricular block after dexmedetomidine administration during minutes to extubation and 118 minutes to standing), First and second degree AV blocks were observed in was not observed. Incidences of arrhythmias were an oral examination/dental procedure. Prior to compared to dogs induced with propofol (23 minutes one of twelve dogs. Elevated concentrations of ALT not related to dose; however, more cats were affected dexmedetomidine, the cat was free of clinical signs, to extubation and 84 minutes to standing). were observed in 3 of 12 dogs, without histological by cardiac arrhythmias on the third day of treatment, but had a history of asthma and respiratory infection. Cardiac arrhythmias were monitored by ECG. changes to the liver. compared to the first two days of the study. The The cat responded successfully to treatment. Dexmedetomidine-treated dogs were more frequently Dexmedetomidine demonstrated dose dependent decrease in respiratory rate, but not the duration, was INFORMATION FOR OWNERS: Due to the rare observed with at least one incidence of arrhythmia effects related to its pharmacology when administered dose dependent. The rectal temperature decreased compared to saline controls. The most commonly IV or IM to healthy dogs at doses up to five times the in all dexmedetomidine-treated groups, with the possibility of delayed onset of pulmonary edema st nd which has been associated with administration of observed arrhythmias were bradycardia, 1 and 2 recommended dose. lowest temperatures in the 5X group at 8 hours on all other alpha -adrenergic agonists in cats, animal owners degree AV block, and sinus arrest. Other less frequently Canine safety study with an anticholinergic: In three days. Two cats vomited (40 and 120 mcg/kg). 2 observed arrhythmias included ventricular premature another laboratory safety study, one of three doses of Corneal opacity was noted in all dexmedetomidine- should notify their veterinarian immediately if their cat rd experiences difficulty breathing. complexes, supraventricular premature complexes, 3 an IM anticholinergic drug or saline was administered dose groups, was transient, related to dose and degree AV block, and sinus pause. 10 minutes before, at the same time, or 15 minutes after duration of sedation, and was attributed to lack of CLINICAL PHARMACOLOGY: Dexmedetomidine is a Adverse events included bradycardia, tachycardia, 500 mcg/m2 IM dexmedetomidine. The anticholinergic lubrication with decreased blinking during sedation. potent non-narcotic alpha2-adrenoceptor agonist which VPCs, vomiting, diarrhea, urinary incontinence, and drug was given for the prevention or treatment of Hematology and blood chemistry were unaffected by produces sedation and analgesia. These effects are self trauma (see ADVERSE REACTIONS). dexmedetomidine-induced reduction in heart rate. In treatment. Injection site tolerance was good, with mild dose dependent in depth and duration. Blood pressure The results of the preanesthesia field study demonstrate a crossover design, 18 dogs were used in a total of inflammatory lesions representative of the IM injection is initially increased due to peripheral vasoconstriction, that dexmedetomidine provided anesthetic dose- 72 trials, to evaluate the safety of dexmedetomidine procedure. Gross and histological examination of all subsequently dropping to normal or slightly below sparing, sedation, and analgesia during procedures used with an anticholinergic drug. other tissues did not reveal any abnormalities related normal levels. Vasoconstriction may cause mucous conducted under general anesthesia. Dogs were instrumented for the accumulation of to DEXDOMITOR administration. membranes to appear pale or mildly cyanotic. This Feline sedation/analgesia field study: DEXDOMITOR continuous ECG data. The following arrhythmias were Dexmedetomidine demonstrated dose dependent initial vasopressor response is accompanied by a was evaluated in a masked, controlled, multiple site field recorded during the study (some dogs experienced effects related to its pharmacology when administered compensatory marked decrease in heart rate mediated study, using parallel treatment groups. Effectiveness more than one arrhythmia). IM to healthy cats at doses up to five times the by a vagal baroreceptor. The peripheral pulse may was evaluated in 242 client-owned cats, ranging in age recommended dose. feel weak and a transient change in the conductivity Table 7: Arrhythmias recorded during the canine between 0.5 and 17 years, and in size between 2.3 and laboratory safety study* Feline acute tolerance study: IM DEXDOMITOR of the cardiac muscle may occur, as evidenced by 9.6 kg (5 and 21 lbs). Cats admitted to veterinary clinics was administered once at 10X (400 mcg/kg) the first and second degree atrioventricular blocks. for various procedures requiring restraint, sedation, Type of arrhythmia Number of dogs recommended dose of 40 mcg/kg to 3 female and Other arrhythmias may occur. Dexmedetomidine and/or analgesia were randomized to treatment group (of 18) 3 male 7 month old cats. No mortality was observed. also decreases the respiratory rate and decreases and given dexmedetomidine (122 cats) or xylazine (120 Sedation was observed within 15 minutes of dosing body temperature. The magnitude and duration of cats) once by IM injection. Procedures performed using Second degree AV block 18 and lasted for at least 4 hours with full recovery the decrease in body temperature is dose dependent. dexmedetomidine included dental care, radiography, Third degree AV block 6 noted between 8 and 24 hours after dosing. Transient Dexmedetomidine causes depression of gastrointestinal minor superficial surgery, otitis treatment, blood or urine observations of corneal dehydration and opacity, miosis, motility due to decrease in smooth muscle activity, sample collection, tattooing, microchip placement, Ventricular escape beats 16 pale skin and gingiva, salivation, and watery ocular increases blood glucose levels due to inhibition of and grooming. Ventricular premature contractions 14 discharge were observed in some animals. Vomiting was insulin release, and increases production of urine. Sedation and analgesia occurred within 5 to 15 observed 7 to 11 hours after dosing in all but one animal. Spontaneous muscle contractions (twitching) can be minutes and peak effects were observed 30 minutes Idioventricular rhythm 1 Decreases in heart rate accompanied by prolonged PQ expected in some dogs sedated with dexmedetomidine. after dexmedetomidine. The procedure was easily Supraventricular tachycardia (SVT) 16 and QT intervals were most pronounced 2 to 4 hours Vomiting in cats has been associated with alpha2- performed in 91% of cats beginning 30 minutes after or SVPCs after dosing. No atrioventricular (AV) blocks or escape adrenergic agonist central stimulation of the brain4. dexmedetomidine. Sedative and analgesic effects rhythms were noted. In one cat, incidental and reversible Paroxysmal VT 1 EFFECTIVENESS: waned by three hours after dexmedetomidine. premature junctional complexes were seen at 1 and 2 Canine sedation/analgesia field study: Signs of sedation were deeper for cats receiving Ventricular bigeminy; SVPCs; 1 hours after dosing which were considered secondary to Dexmedetomidine was evaluated in a masked, dexmedetomidine compared to those receiving pulse alternans bradycardia. Slightly lower respiratory rate and reduced xylazine. No clinically relevant differences were rectal temperature were observed 4 to 8 hours after controlled, multi-site field study, using parallel Junctional escape beat 1 treatment groups. Effectiveness was evaluated in 200 observed between dexmedetomidine and xylazine dosing. Observations had returned to normal by 24 (of 213) healthy client-owned dogs, ranging in age with respect to analgesia or physiological variables. *Table does not relate arrhythmias to the presence or hours after dosing. Mild inflammatory lesions observed between 16 weeks and 16 years of age, and in size Heart rate, respiratory rate, and rectal temperature absence of anticholinergic histologically at the injection site were representative between 4.8 lbs and 141 lbs (2.2 kg and 64 kg). Dogs decreased. Bradycardia was observed within 5 to The occurrence of arrhythmias was not related to of the IM injection procedure. No treatment related admitted to veterinary clinics for various procedures 15 minutes and heart rates of ≤ 70 beats/minute the presence or absence of the anticholinergic drug. changes were observed in hematology. Mild elevations requiring sedation and/or analgesia received either were seen in 18% of cats. The most commonly Arrhythmias were transient (although frequent over time in some clinical ALT, AST, and CK, were observed 24 dexmedetomidine or medetomidine once, by IV or IM observed arrhythmias assessed with ECG were in some dogs), returning toward baseline levels within hours after dosing, with a trend towards recovery by 48 injection. Procedures included dental care, radiography, atrioventricular dissociation and escape rhythms, 55 minutes after dexmedetomidine. No dogs required hours. Total protein, albumin and globulin levels were minor skin tumor removal, and treatment of otitis. followed by a few incidences of premature complexes treatment related to these arrhythmias, and none of slightly lowered in one cat 48 hours after dosing. Sedation and analgesia occurred within 5 minutes after and one incidence of atrioventricular block. Oxygen these arrhythmias persisted or adversely affected the STORAGE INFORMATION: Store at controlled IV dexmedetomidine, and within 15 minutes after IM saturation, mucous membrane color, capillary refill overall clinical status of any dog in the study. room temperature 15-30°C (59-86°F). Protect from dexmedetomidine, with peak effects approximately time, pulse character, respiratory depth and pattern, Dexmedetomidine without anticholinergic: Without the freezing. at 15 or 30 minutes, respectively. Effects waned by and response of the animal to injection were clinically anticholinergic drug, and in addition to arrhythmias, approximately two hours after IV administration, and by satisfactory. All cats recovered from changes induced dexmedetomidine produced clinically relevant sedation HOW SUPPLIED: DEXDOMITOR is supplied in 10-mL, three hours using the IM route. Dexmedetomidine and by dexmedetomidine. accompanied by a statistically significant reduction in multidose vials containing 0.5 mg of dexmedetomidine medetomidine showed comparable clinical effects. Ninety-seven adverse events were reported after heart rate, respiratory rate, cardiac output, pulmonary hydrochloride per mL. Cardiac rhythms were evaluated by auscultation. dexmedetomidine. The most frequently reported arterial temperature, and mixed venous oxygen tension. REFERENCES: Bradycardia occurred within 5 to 15 minutes after IV adverse reactions included vomiting (70), urinary A statistically significant increase in arterial blood (1) Ko JCH, Fox SMF, Mandsager RE. Effects of dexmedetomidine or medetomidine, and within 15 incontinence (6), hypersalivation (4), involuntary pressure, pulmonary capillary wedge pressure, central preemptive atropine administration on incidence of to 30 minutes after either drug given IM. Sixty-four defecation (4), hypothermia (2), and diarrhea (2) (see venous pressure, and systemic vascular resistance medetomidine-induced bradycardia in dogs. J Am dexmedetomidine-treated dogs and 50 medetomidine- ADVERSE REACTIONS). was noted. No dogs experienced hypotension. Vet Med Assoc 2001; 218:52-58. treated dogs were observed with bradycardia. The results of this field study demonstrate that Dexmedetomidine tended to increase pulmonary (2) Alibhai HIK, Clarke KW, Lee YH, et al. Cardiopulmonary Adverse reactions during the field study included dexmedetomidine produces satisfactory levels of vascular resistance. Dexmedetomidine alone had effects of combinations of medetomidine hydrochloride ausculted unidentified arrhythmias, apnea, hypothermia, sedation and analgesia for clinical examinations and no statistically significant effect on mean pulmonary and atropine sulphate in dogs. Vet Rec 1996; 138:11-13. and ineffectiveness (see ADVERSE REACTIONS). procedures, minor surgical procedures, and minor arterial pressure, arterial pH, arterial carbon dioxide (3) Short, CE. Effects of anticholinergic treatment on the Eleven dogs received concomitant medication during dental procedures. tension, and arterial oxygen tension. cardiac and respiratory systems in dogs sedated with the field study, including amoxicillin, cephalexin, ANIMAL SAFETY: Dexmedetomidine plus anticholinergic: Either of the medetomidine. Vet Rec 1991; 129:310-313. triamcinolone, methyl-prednisolone acetate, neomycin, Canine safety study: In the multiple dose safety two higher anticholinergic doses was effective in the (4) Hikasa Y, Akiba T, Iino Y et al. Central alpha- nystatin, thiostrepton, acepromazine, atropine, and study, dexmedetomidine was administered at 0, 1, prevention or treatment of the dexmedetomidine- adrenoceptor subtypes involved in the emetic pathway atipamezole. 3 or 5 times (X) the recommended IV and IM doses induced reduction in heart rate. Anticholinergic in cats. Eur J Pharmacol 1992; 229:241-251. The results of this field study demonstrate that on 3 consecutive days to a total of 36 healthy, young (higher doses) given after dexmedetomidine caused dexmedetomidine produces satisfactory levels of beagles. Two additional groups were given a 3X dose marked increases in the occurrence of various cardiac arrhythmias, especially second degree AV block. When U.S. Patent No. 4,910,214 sedation and analgesia for clinical examinations and of dexmedetomidine (IV or IM) followed by three 1X DEXDOMITOR® is a trademark of Orion Corporation. procedures, minor surgical procedures, and minor doses of the reversal agent, atipamezole (ANTISEDAN), the higher doses of anticholinergic drug were given at dental procedures. every 30 minutes. This was repeated for a total of 3 the same time or 15 minutes after dexmedetomidine, Canine preanesthesia field study: The use of days. No deaths occurred during the study. large increases in heart rate (p<0.01) and blood dexmedetomidine as a preanesthetic was evaluated 1X dose group: At the recommended dose, sedation pressure (p<0.05) were seen. Increases were dose in a controlled, multi-site field study, using parallel lasted less than 3 hours. During sedation, muscle related; the highest anticholinergic dose elicited more treatment groups. Effectiveness was evaluated in 192 twitches occurred intermittently, and decreases in frequent arrhythmias and larger increases in heart rate healthy, client-owned dogs, between 5 months and temperature, respiratory rate and heart rate were and blood pressure. 15 years of age, weighing 4 to 196 lbs (2 kg to 89 observed in all animals. A slow pupil response to light In conclusion, moderate doses of anticholinergic drug Mfd by: kg). Dogs received IM dexmedetomidine or saline was seen transiently about 15 minutes after dosing in given prior to dexmedetomidine performed best for the Orion Pharma as a preanesthetic to general anesthesia. All dogs one of twelve dogs. Second degree atrioventricular (AV) prevention of dexmedetomidine-induced reduction of Orion Corporation were induced by an injectable anesthetic; half of the blocks were observed in one of twelve dogs. heart rate in dogs. The routine use of anticholinergics Espoo, Finland dogs were maintained with an inhalation anesthetic. 3X dose group: At 3 times the recommended dose, given simultaneously with, or after dexmedetomidine, Procedures included castration, ovariohysterectomy, the duration of sedation was between two and eight is not recommended. Feline safety study: In a multiple dose safety study, skin surgery, radiography, physical examination, dental hours. During sedation, muscle twitches occurred, and Distributed by: procedures, ear cleaning, anal sac treatment, and temperature, respiratory rate, and heart rate decreased DEXDOMITOR was administered intramuscularly grooming. in all dogs. The pupillary light reflex was transiently (IM) at 1X, 3X, and 5X (40, 120, and 200 mcg/kg) the Compared to saline controls, dexmedetomidine IM decreased for up to 90 minutes in four of twelve dogs. recommended dose of 40 mcg/kg on 3 consecutive reduced induction drug requirements by 30-36% Vomiting was seen in two of twelve dogs. One dog days to healthy cats 6 to 8 months old. A control group Div. of Pfizer Inc (at 125 mcg/m2) and by 38-61% (at 375 mcg/m2). experienced first and second degree AV blocks; second received the product vehicle as a placebo (0X). No NY, NY 10017 Inhalation anesthetic requirements were 40-60% degree AV block was observed in three of twelve dogs. mortality was observed. The depth and duration of less for dexmedetomidine-preanesthetized dogs. Elevated concentrations of alanine aminotransferase sedation was dose dependent, lasting approximately The number of dogs with clinical signs of pain was (ALT) were observed in one dog, without histological 2 hours in the 1X group, 2 to 4 hours in the 3X group, less for at least 30 minutes after the procedure in dogs changes to the liver. and greater than 8 hours in the 5X group. The lowest 2 recorded individual heart rate was 60 beats/minute treated with 375 mcg/m dexmedetomidine, compared 5X dose group: At 5 times the recommended dose, November 2007 to saline controls. the duration of sedation was between four and eight and occurred in the 5X dose group (2 cats). Cardiac