Vatinoxan and medetomidine

Indications

Zenalpha is indicated for use as a sedative and analgesic in dogs to facilitate clinical examination, clinical procedures and minor surgical procedures. Zenalpha is not intended for use in cats (see Animal Safety Warnings).

Dosage and Administration

The dose is based on body surface area (BSA). Calculate the dose using 1 mg medetomidine /m 2 BSA or use the dosing table below. Note that the mg/kg dosage decreases as body weight increases. Table 1. IM dose volume based on body weight Dog body weight Dose volume lbs kg mL 4.4 to 7 2 to 3 0.3 7.1 to 9 3.1 to 4 0.4 9.1 to 11 4.1 to 5 0.6 11.1 to 22 5.1 to 10 0.8 22.1 to 29 10.1 to 13 1.0 29.1 to 33 13.1 to 15 1.2 33.1 to 44 15.1 to 20 1.4 44.1 to 55 20.1 to 25 1.6 55.1 to 66 25.1 to 30 1.8 66.1 to 73 30.1 to 33 2.0 73.1 to 81 33.1 to 37 2.2 81.1 to 99 37.1 to 45 2.4 99.1 to 110 45.1 to 50 2.6 110.1 to 121 50.1 to 55 2.8 121.1 to 132 55.1 to 60 3.0 132.1 to 143 60.1 to 65 3.2 143.1 to 154 65.1 to 70 3.4 154.1 to 176 70.1 to 80 3.6 >176 >80 3.8 After administration of Zenalpha, the dog should be allowed to rest quietly until evidence of sedation has occurred (5-15 minutes). The average duration of sedation is 38 minutes. As with all alpha 2 -adrenoceptor agonists, onset of sedation may be delayed or may be inadequate in some dogs. Reversal of Zenalpha: Administration of IM atipamezole hydrochloride at the approved dose to reverse IM medetomidine hydrochloride results in reversal of the sedative and cardiovascular effects of Zenalpha. Reversal of sedation occurs within 5-10 minutes after administration of atipamezole hydrochloride.

Contraindications

Do not use Zenalpha in dogs with cardiac disease, respiratory disorders, shock, severe debilitation, that have hypoglycemia or are at risk of developing hypoglycemia, or are stressed due to extreme heat, cold or fatigue. Zenalpha is contraindicated in dogs with a known sensitivity to medetomidine or vatinoxan.

Warnings

Human User Safety Warnings Not for use in humans. Keep this and all medications out of reach of children and pets. Avoid skin, eye or mucosal contact. Use caution while handling and using filled syringes. Absorption of the active ingredients is possible following exposure via the skin, eye or mucosa. In case of accidental eye exposure, flush eyes with water for 15 minutes, remove contact lenses then continue to flush. In case of accidental skin exposure, wash with soap and water and remove contaminated clothing. If symptoms occur, seek the advice of a physician. In case of accidental oral intake or self-injection, seek medical advice immediately and show the package insert to the physician. DO NOT DRIVE as sedation, loss of consciousness, and changes in blood pressure may occur. Persons with cardiovascular disease (for example, hypertension or ischemic heart disease) should take special precautions to avoid any exposure to this product. Pregnant women should exercise special caution to avoid exposure. Uterine contractions and decreased fetal blood pressure may occur after accidental systemic exposure. Persons with known hypersensitivity to any of the ingredients should avoid contact with Zenalpha. 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. Note to physician: Zenalpha contains medetomidine, an alpha 2 -adrenoceptor agonist, in combination with vatinoxan, a peripherally selective alpha 2 -adrenoceptor antagonist. Symptoms after absorption or accidental self-injection may include dose-dependent sedation, respiratory depression, bradycardia, tachycardia, and hypotension. Animal Safety Warnings Zenalpha should not be administered in the presence of pre-existing hypotension, hypoxia or bradycardia. Due to the pronounced cardiovascular effects of alpha 2 -adrenoceptor agonists, only clinically healthy dogs (American Society of Anesthesiologists [ASA] classes I and II) should be administered Zenalpha. Dogs should be monitored frequently for cardiovascular function and body temperature during sedation. Zenalpha is not intended for use in cats. The use of Zenalpha in cats has been associated with hypotension.

Precautions

Dogs should be monitored frequently during sedation for changes in heart rate, blood pressure, respiratory rate and body temperature. Tachycardia may occur in some dogs after recovery from sedation. In the event of hypoxia or apnea, supplemental oxygen should be administered. Following administration of Zenalpha, a decrease in body temperature may occur and an external heat source may be needed to maintain body temperature. Hypothermia may persist longer than sedation and analgesia. The analgesic effect of Zenalpha will not last longer than the sedative effects. Additional analgesic(s) should be administered as needed (see Effectiveness ). Nervous, excited or agitated dogs with high levels of endogenous catecholamines may exhibit a reduced pharmacological response to Zenalpha (ineffectiveness). The onset of sedative/analgesic effects could be slowed, or the depth and duration of effects could be diminished or nonexistent. Therefore, allow the dog to rest quietly for 10 to 15 minutes after injection. With the alpha 2 -adrenoceptor agonist drug class, including Zenalpha, the potential for isolated cases of hypersensitivity, including paradoxical response (excitation) exists. Repeat dosing with Zenalpha has not been evaluated. Zenalpha has only been evaluated in fasted dogs; therefore, the effects on fed dogs (for example occurrence of vomiting) has not been characterized. The concurrent use of anticholinergic medications and Zenalpha has not been evaluated. Zenalpha may decrease serum glucose in healthy dogs and this effect may persist longer than sedation (see Animal Safety ). The safe use of Zenalpha in dogs with hepatic or renal impairment has not been evaluated. The safe use of Zenalpha has not been evaluated in dogs younger than 4.5 months old. The safe use of Zenalpha has not been evaluated in dogs that are pregnant, lactating, or intended for breeding.

Adverse Reactions

In the field study safety evaluation, 110 dogs received Zenalpha and 113 dogs received dexmedetomidine (control group) for sedation. Dogs ranged in age from 5 months to 14.5 years, weighed 5.1 to 154 lbs, and represented purebreds and breed mixes. Table 2. Adverse reactions during the field study Adverse Reaction Zenalpha (N = 110) n (%) Dexmedetomidine (N = 113) n (%) Diarrhea 4 (3.6) 0 (0) Muscle tremor 2 (1.8) 0 (0) Signs of colitis 2 (1.8) 0 (0) Hypothermia Hypothermia that necessitated use of an external heat source 1 (0.9) 13 (11.5) Vomiting 1 (0.9) 6 (5.3) Involuntary defecation 1 (0.9) 0 (0) Nausea 1 (0.9) 0 (0) Tachycardia, transient 1 (0.9) 0 (0) Prolonged sedation 0 (0) 3 (2.7) Urinary incontinence 0 (0) 2 (1.8) Retching 0 (0) 1 (0.9) Apnea 0 (0) 1 (0.9) Bradycardia 0 (0) 1 (0.9) Hyperthermia 0 (0) 1 (0.9) Field Study Safety Decreased body temperature occurred within 30 minutes after administration for some dogs in both treatment groups and lasted up to 2 hours in the Zenalpha group and 2-6 hours in the control group. There were 57/110 dogs (51.8%) in the Zenalpha group and 77/113 dogs (68.1%) in the control group that had a body temperature ≤99 °F. The respiratory rates decreased in both groups within 5 minutes post dose compared to baseline. The group mean respiratory rate in the Zenalpha group decreased earlier and recovered faster than the control group. Thirty-nine dogs out of 110 (35.4%) in the Zenalpha group and 33/113 dogs (29.2%) in the control group had respiratory rates < 10 breaths per minute (bpm) during the study. The group mean respiratory rate in the Zenalpha group was lowest at 30 minutes post-treatment (14 bpm) and in the control group was lowest at 90 minutes post-treatment (15.5 bpm). Mucous membrane color and capillary refill time were normal for all dogs at all timepoints during the study.

Description

Zenalpha is a combination of medetomidine and vatinoxan hydrochlorides. Medetomidine is a racemic mixture containing the active enantiomer, dexmedetomidine, an alpha 2 -adrenoceptor agonist with sedative and analgesic properties. Vatinoxan is a peripherally selective alpha 2 -adrenoceptor antagonist, which partially counteracts the cardiovascular depressive effects of dexmedetomidine at peripheral alpha 2 -adrenoceptors, while preserving the centrally mediated sedative and analgesic effects of dexmedetomidine. Medetomidine hydrochloride has the chemical name (S,R)-4-[1-(2,3-dimethylphenylethyl)-1H-imidazole hydrochloride. It is a white, crystalline, water soluble substance having a molecular weight of 237 g/mol. The molecular formula is C 13 H 16 N 2 HCl and the structural formula is: Vatinoxan hydrochloride has the chemical name N-(2-((2R,12bS)-2'-oxo-1,3,4,6,7,12b-hexahydrospiro[benzofuro[2,3-a] quinolizine-2,4'-imidazolidine]-3'-yl) ethyl) methane sulfonamide hydrochloride. It is a white to pale yellow, crystalline substance, sparingly soluble in water and having a molecular weight of 455 g/mol. The molecular formula is C 20 H 26 N 4 O 4 S HCl and the structural formula is: Each mL of Zenalpha contains 0.5 mg medetomidine hydrochloride, 10 mg vatinoxan hydrochloride, 32.5 mg mannitol (USP), 4.16 mg citric acid monohydrate (USP), 1.8 mg methylparaben (NF), 0.2 mg propylparaben (NF). Chemical Structure 1 Chemical Structure 2

Storage

Store below 77°F (25°C). In use shelf life: 3 months at 77°F (25°C). Protect from freezing and store in outer carton to protect from light.

FDA adverse event reports

The FDA Center for Veterinary Medicine publishes the adverse event reports it receives through openFDA. The counts below are the reports naming vatinoxan and medetomidine as an active ingredient for each species this label names, as returned on 2026-09-16, coded by the VeDDRA reaction term the reporter chose. Reactions are counted per report, so one report can appear under several terms.

These are counts, not rates. Reporting is voluntary, the number of animals treated is not known, and a widely used product accumulates reports for that reason alone. A report records that an event followed a dose; it does not establish that the product caused it. The counts say nothing about how one product compares with another.