Sedivet 1% Injection, 20 mL Vial

Sedivet 1% Injection

Horse Pain Reliever and Sedative Medication

Sedative & Analgesic For Horses

(romifidine hydrochloride)

Sedivet 1.0% Injection is indicated for use as a sedative and analgesic to facilitate handling, clinical examinations, clinical procedures, and minor surgical procedures in adult horses. Sedivet 1.0% Injection is also indicated as a preanesthetic prior to the induction of general anesthesia in adult horses.

Description: Sedivet 1.0% Injection (romifidine hydrochloride) is an a₂-adrenoceptor agonist with sedative and analgesic properties. The chemical name is 2-bromo-6-fluoro-2-imidazolidinyliden-benzamine-monohydrochloride. It is a crystalline, white, odorless, water soluble substance with a molecular formula of C₉H₉BrFN₃HCl, and a molecular weight of 294.56. Each mL contains 10 mg romifidine hydrochloride, 6.5 mg sodium chloride, 2 mg chlorocresol, and water for injection.

Dosage and Administration: Sedation and Analgesia Dose: Administer slowly as a single IV injection using a dosage range of 40 - 120 g/kg (0.4 - 1.2 mL/100 kg body weight) depending on the depth and duration of sedation that is required. The onset of action occurs in 30 seconds to 5 minutes, and gradually subsides during the next 2 to 4 hours. Degree of sedation and analgesia is dose-and time-dependent; therefore, more profound analgesia will occur with larger doses, as well as closer to the time of injection.

Note: The animal should be allowed to rest quietly for several minutes prior to and following injection.

Note: The duration of analgesia is shorter than the duration of sedation.

Preanesthesia Dose:A single IV injection using a dose of 100 g/kg (1.0 mL/100 kg body weight) was shown to be effective in the preanesthesia dose confirmation study (see Effectiveness). Anesthesia should be induced after maximum sedation is achieved. The administration of a₂-agonists results in anesthetic sparing effects^1,2; therefore, anesthetic doses should be reduced to avoid overdose.

Mild to moderate sedation occurs within 2-4 minutes. Following induction, lateral recumbency occurs within 4 minutes, followed by complete anesthesia within 6-16 minutes. During recovery from anesthesia, sternal recumbency occurs within 12-83 minutes, followed by standing in 17-84 minutes. Recovery time is primarily determined by the choice of induction anesthetic and/or the duration of anesthesia.

Contraindications: Sedivet 1.0% Injection is contraindicated in horses with known hypersensitivity to romifidine.

Intravenous potentiated sulfonamides should not be used in anesthetized or sedated horses as potentially fatal cardiac dysrhythmias may occur.

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

Warnings: Not for human use. Keep this and all drugs out of the reach of children.

Not for horses intended for human consumption.

Although apparently deeply sedated, some horses may still respond to external stimuli with defensive movements (for example, kicking). Sedated horses are frequently ataxic. Routine safety measures should be used to protect practitioners and handlers.

Romifidine hydrochloride can be absorbed and may cause irritation following direct exposure to skin, eyes or mouth. In case of accidental eye exposure, flush with water for 15 minutes. In case of accidental skin exposure, wash with soap and water. Remove contaminated clothing. In case of accidental oral exposure or injection, seek medical attention. If irritation or other adverse reaction occurs (for example, sedation, hypotension, bradycardia), seek medical attention.

As with all injectable drugs causing profound physiological effects, precautions should be taken by practitioners to prevent accidental self-injection when handling and using filled syringes. Users receiving treatment for blood pressure abnormalities should take special precaution to avoid exposure to this product.

Note to Physician: Thisproduct contains an a₂-adrenoceptor agonist andcan be absorbed by oral and dermal routes.

Precautions: The use of Sedivet1.0% Injection with other a₂-agonists is notrecommended since the effects (for example, cardiovascular changes,respiratory depression, ataxia) could be additive.

The adverse effects of Sedivet 1.0% Injection may bepotentiated by the administration of other sedatives, tranquilizers, oropioids.

The use of epinephrine should be avoided sinceepinephrine may potentiate the effects of a₂-agonists.

Anesthetic doses should be reduced in the presenceof Sedivet 1.0% Injection to avoid excessive depression of the centralnervous system.

Sedivet 1.0% Injection has not been evaluated inhorses with compromised cardiovascular function. The effects of bradycardia,increased vascular resistance, decreased cardiac output, and respiratorydepression could be significant in horses with primary myocardial disease,or circulatory shock.

Sedivet 1.0% Injection should not be used in horseswith respiratory disease, hepatic or renal disease, dehydration, or othersystemic conditions of compromised health.

The effects of Sedivet 1.0% Injection have not beenevaluated in horses with colic.

The effects of Sedivet 1.0% Injection have not beenevaluated in pregnant mares, in horses intended for breeding, or in foals.

Adverse Reactions: As with otherdrugs of this class, the administration of Sedivet 1.0% Injection causesbradycardia (possibly profound), first and second degree atrioventricularheart block, and hypotension. The frequency and duration of cardiacarrhythmias have been shown to be dose related.

The following commonly occurring adverse reactionshave been noted using a₂-agonists:hypertension, hypotension, bradycardia, ataxia, piloerection, sweating,muscle tremors, salivation, penile relaxation, urination (about an hourafter treatment), lowering of head (causing passive congestion and swellingof face, lips, upper airways), stridor, decreased gastrointestinal motility,flatulence, and mild colic.

The potential exists, as with all a₂-agonists,for isolated incidences of excitation (paradoxical response).

Rare anaphylactic reactions have been reported,including one or more of the following: urticaria, dyspnea, edema of theupper airways and head, trembling, recumbency, and subsequent death.

Clinical Pharmacology: Romifidine is a potent a₂-adrenoceptor agonistthat produces sedation and analgesia. Sedation is induced by stimulation ofpresynaptic a₂-receptors in the central nervoussystem. Administration of romifidine to conscious or anesthetized horsesresults in a biphasic effect on blood pressure. A transient increase inblood pressure due to peripheral vasoconstriction is followed by acompensatory vagal baroreceptor response resulting in longer lastinghypotension and bradycardia. A transient change in the conductivity of thecardiac muscle may manifest clinically as a partial atrioventricular block.Peripheral vasoconstriction may also lead to a transient reduction ingastrointestinal motility.

Effectiveness: A field study wasconducted to evaluate romifidine as a sedative or a preanesthetic.Clinicians selected an appropriate dose, based on the procedure. Sedativedoses ranged between 30-100 g/kg; preanesthetic doses ranged between 40-100g/kg. The quality of sedation was rated as good or excellent in 18 of23 horses. Of the remaining five horses evaluated for sedation, three wererated as fair and two were rated as poor. When used for preanesthesia,inductions were rated as well-controlled in 16 of 23 horses. Recoveriesfrom anesthesia were evaluated as satisfactory or excellent in 20 of 23horses. Two horses required more than three attempts to stand. One horse waseuthanized without recovery, due to an unfavorable diagnosis unrelated todrug administration.

In a sedation dose confirmation study with acrossover design, twenty horses were used to evaluate romifidine at twodoses: 40 and 120 g/kg. Clinical assessments of depth of sedation,behavioral attitude, stance/posture, head ptosis, ear ptosis, eyelid and lipdrooping were evaluated. Depth and duration of sedation were affected in adose dependent manner. By the response of the horses to thermal noxiousstimuli applied to withers and fetlock, the degree and duration of analgesiawere also shown to be dose dependent. Transient physiological and clinicaleffects included decreased respiratory and heart rates, second degreeatrioventricular block, sweating, increased salivation, stridor, penilerelaxation, and a slight decrease in body temperature. Seventy-five minutesafter receiving the 40 g/kg dose, one older horse with a preexistent gradeIV/VI systolic murmur, experienced ventricular tachycardia that lasted for11.5 minutes. Another horse was diagnosed with pneumonia three days afterreceiving the 120 g/kg dose of romifidine.

In a separate preanesthesia crossover study, theeffectiveness of the 100 g/kg preanesthetic romifidine dose was confirmed.Ten horses were induced with either ketamine or thiopental, followed byisoflurane maintenance anesthesia. The quality of induction, the transitionto inhalant anesthesia, and the quality of anesthesia were scored asexcellent for all horses. All horses except one stood on the first attempt(one stood on the third attempt).

Animal Safety: A toxicity studywas conducted to observe the effects of a single dose of Sedivet 1.0%Injection at 360 g/kg (3X the highest recommended dose) and 600 g/kg (5Xdose), using 3 horses per group. There were no clinically importantalterations of blood gas, acid-base, hematological, or clinical chemistryvalues. The duration of bradycardia and second degree heart block was longerusing the higher dose. Occasional periods of apnea (20 to 40 seconds) werefollowed by several deep successive breaths. Mild respiratory stridor waspresent, and horses periodically exhaled forcefully (snorting) in anapparent effort to clear their upper airways. The duration of sedation wasdose dependent.

Horses exhibited signs of deep sedation, but wouldoccasionally respond to environmental stimuli, only to return to deepsedation shortly thereafter. Mild sweating was observed. Urination commencedat 60-90 minutes and occurred frequently through four hours. One horse,which had been given a small amount of hay before full gastrointestinalmotility had returned, showed mild abdominal discomfort twelve hours afteradministration of 600 g/kg romifidine. Horses in this study were notnecropsied. Toxicity study results for another product in the a₂-agonistclass, showed microscopic foci of myocardial necrosis duringhistopathological examination in one of eight horses that received ten timesthe high end of the recommended dose for that product.

In another safety study, Sedivet 1.0% Injection wasadministered IV at doses of 120 g/kg (1X the highest recommended dose), 360g/kg (3X), and 600 g/kg (5X) for up to 3 consecutive days (9 horses pergroup). Sinus bradycardia (<30 bpm) and second degree heart block were mostpronounced within 30 seconds to 5 minutes, gradually subsiding over two tofour hours. Severe ataxia was observed in the 3X and 5X dose groups.Sweating was noted in all romifidine groups. Horses receiving the 1X doseshowed an initial rise in blood pressure, followed by a return to baselineby 20-30 minutes. In the 3X and 5X groups, increases in blood pressure wereseen at five minutes; returning toward baseline after 1 hour. Respiratoryrates in all groups fell initially, followed by a gradual increase towardbaseline values. Body temperature response varied, increasing slightly inthe 1X and 3X groups, and decreasing slightly in the 5X group.

Storage Information: Store atcontrolled room temperature, 59-86F (15-30C).

How Supplied: Sedivet 1.0%Injection is supplied in 20 mL multi-dose vials containing 10 mg romifidinehydrochloride per mL.