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BRIEF SUMMARY: See package insert for full prescribing information NADA 141-267, Approved by FDA. (dexmedetomidine hydrochloride) Sterile Injectable Solution – 0.5 mg/mL (dexmedetomidine hydrochloride) Sterile Injectable Solution – 0.1 mg/mL For intramuscular and intravenous use in dogs and for intramuscular use in cats CAUTION: Federal law restricts this drug to use by or on the order of a licensed veterinarian. INDICATIONS: DEXDOMITOR 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. DEXDOMITOR is also indicated for use as a preanesthetic to general anesthesia in dogs and cats. DOSAGE AND ADMINISTRATION: 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 preanesthetic dose depends on the duration and severity of the procedure, as well the anesthetic regime. Note: in the dog, Dexdomitor is dosed based on body surface area, therefore small dogs will receive a relatively higher mcg/kg dose and larger dogs will receive a relatively lower mcg/kg dose. Cats: Sedation, Analgesia and Preanesthesia: 40 mcg/kg intramus- cularly (IM). When used as a preanesthetic, DEXDOMITOR markedly reduces the amount of induction and maintenance anesthetics required for both dogs and cats. CONTRAINDICATIONS: 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. As with all alpha 2 -adrenoceptor agonists, the potential for isolated cases of hypersensitivity, including paradoxical response (excitation), exists. WARNINGS: 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, fush 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 flled syringes. Accidental topical (including ocular) exposure, oral exposure, or exposure by injection could cause adverse reactions, including seda- tion, 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 material safety data sheet (MSDS) contains more detailed occupa- tional safety information. To report adverse reactions in users or to obtain a copy of the MSDS for this product call 1-800-366-5288. Note to physician: This product contains an alpha 2 -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 signifcantly reduces the amount of induction and maintenance anesthetic requirements. Careful patient monitoring during anesthetic induction and maintenance is necessary to avoid anesthetic overdose. PRECAUTIONS: Apnea may occur with dexmedetomidine use. In the event of apnea, additional oxygen should be supplied. Administration of ANTISEDAN (atipamezole) to dogs is warranted when apnea is accompanied by bradycardia and cyanotic mucous membranes. Adverse reaction reports for dexmedetomidine in cats include rare events of severe dyspnea and respiratory crackles diagnosed as acute pulmonary edema. Dyspnea due to the delayed onset of pulmonary edema could develop in rare instances up to three days after dexmedetomidine administration. Some of these acute and delayed pulmonary edema cases have resulted in death al- though this was not observed in the feline clinical feld studies with dexmedetomidine. In dogs, intramuscular ANTISEDAN (atipamezole) may be routinely used to rapidly reverse the effects of dexmedetomidine. Since analgesic as well as sedative effects will be reversed, pain management may need to be addressed. In cats, ANTISEDAN (atipamezole) has not been evaluated as a routine dexmedetomidine reversal agent. In cats, cases of dyspnea following ANTISEDAN (atipamezole) administration have been reported. Dexmedetomidine has not been evaluated in the presence of other preanesthetics in cats. Although not observed in the feline feld studies, death has been reported in cats receiving dexmedetomidine in conjunction with ketamine and butorphanol. Analgesia resulting from preanesthetic dexmedetomidine may not pro- vide adequate pain control during the postoperative or post-procedural period. Additional pain management should be addressed as needed. Following administration of dexmedetomidine, a decrease in body temperature is likely to occur unless externally maintained. Once established, hypothermia may persist longer than sedation and analgesia. To prevent hypothermia, treated animals should be kept warm and at a constant temperature during the procedure, and until full recovery. Nervous or excited animals with high levels of endogenous cate- cholamines may exhibit a reduced pharmacological response to alpha 2 -adrenoceptor agonists like dexmedetomidine (ineffectiveness). In agitated animals, the onset of sedative/analgesic effects could be slowed, or the depth and duration of effects could be diminished or nonexistent. Therefore, allow dogs and cats to rest quietly for 10 to 15 minutes after injection. Repeat dosing has not been evaluated. Administration of anticholinergic agents in dogs or cats at the same time or after dexmedetomidine could lead to adverse cardiovascular effects. (secondary tachycardia, prolonged hypertension, and cardiac arrhyth- mias 1,2,3 ). However, an anticholinergic drug may be administered to dogs at least 10 minutes before dexmedetomidine for the prevention of the dexmedetomidine-induced reduction in heart rate. Therefore, the routine use of anticholinergics simultaneously with, or after dexmedetomidine in dogs or cats, is not recommended (see ANIMAL SAFETY). Spontaneous muscle contractions (twitching) can be expected in some dogs sedated with dexmedetomidine. Dexmedetomidine has been evaluated only in fasted dogs; therefore, its effects on fed dogs (for example, the occurrence of vomiting) have not been characterized. In cats, there is a high frequency of vomition whether fed or fasted; therefore, fasting is recommended to reduce stomach contents. Dexmedetomidine has not been evaluated in dogs younger than 16 weeks of age, in cats younger than 12 weeks of age, or in geriatric dogs and cats. Dexmedetomidine has not been evaluated for use in breeding, pregnant, or lactating dogs or cats. ADVERSE REACTIONS: Canine sedation/analgesia feld study: In the feld 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 feld study Dexmedetomidine Total n=106 Medetomidine Total n=107 Ausculted unidentifed 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 unidentifed arrhythmias (some at multiple time points) decreased following the administration of atipamezole. Canine preanesthesia feld study: The preanesthesia feld 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 feld study Treatment Groups Induction Anesthetic: Propofol Barbiturate Preanesthetic Dose: 0 mcg/m 2 n=32 125 mcg/m 2 n=32 375 mcg/m 2 n=32 0 mcg/m 2 n=32 125 mcg/m 2 n=32 375 mcg/m 2 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 feld 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 dexmede- tomidine 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 success- fully to treatment. Feline preanesthesia feld study: The feld 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 feld study Induction Anesthetic Ketamine Propofol Preanesthetic Saline n=37 Dexmede- tomidine n=64 Saline n=31 Dexmede- tomidine 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 artifcial 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. POST APPROVAL EXPERIENCE: The following adverse events were obtained from post-approval adverse drug events reported for DEXDOMITOR sterile injectable solution from 2007-2009. Not all adverse reactions are reported. Some adverse reactions occurred when DEXDOMITOR was used alone for sedation; most occurred when DEXDOMITOR was used in the presence of anesthetics and/or other preanesthetics. It is not always possible to reliably estimate the frequency of an adverse event or to establish a causal relationship to the drug, especially when multiple drugs are administered. The following reported adverse events are listed in decreasing order of frequency: Dogs: ineffective for sedation, death, bradycardia, cardiac arrest, apnea, convulsions, vomiting, prolonged sedation, elevated temperature, and delayed sedation. Cats: ineffective for sedation, death, cardiac arrest, vomiting, apnea, prolonged sedation, hypersalivation, hypothermia, bradycardia, cyanotic mucous membranes, sedation too brief, and dyspnea. INFORMATION FOR OWNERS: Owners should notify their veterinarian immediately if their cat experiences diffculty breathing due to the rare possibility of delayed onset of pulmonary edema which has been associated with administration of alpha 2 -adrenergic agonists in cats. ANIMAL SAFETY: Canine safety study: In the multiple dose safety study, dexmedetomidine was administered at 0, 1, 3 or 5 times (X) the recommended IV and IM doses on 3 consecutive days to a total of 36 healthy, young beagles. Two additional groups were given a 3X dose of dexmedetomidine (IV or IM) followed by three 1X doses of the reversal agent, atipamezole (ANTISEDAN), every 30 minutes. This was repeated for a total of 3 days. No deaths occurred during the study. 1X dose group: At the recommended dose, sedation lasted less than 3 hours. During sedation, muscle twitches occurred intermittently, and decreases in temperature, respiratory rate and heart rate were observed in all animals. A slow pupil response to light was seen transiently about