Now FDA registered for 28 days of use after broaching

Anesthesia can create stress. Manage it with Alfaxan® Multidose(alfaxalone 10 mg/mL injectable anesthetic)

Alfaxan®

MultidoseRegistered for induction and maintenance of anesthesia

NEW

Brief Summary of Prescribing Information

For Animal Use Only NADA#141-342Alfaxan® Multidose (alfaxalone 10 mg/mL)Intravenous injectable anesthetic for use in cats and dogs.

BRIEF SUMMARY OF PRESCRIBING INFORMATIONThis summary does not include all the information needed to use Alfaxan® Multidose safely and effectively. See full package insert for complete information.

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

INDICATIONS:Alfaxan® Multidose is indicated for the induction and maintenance of anesthesia, and for induction of anesthesia followed by maintenance with an inhalant anesthetic, in cats and dogs.

DOSAGE AND ADMINISTRATION (highlights): Please refer to the complete package insert for full prescribing and administration information before use of this product. Administer by intravenous injection only. For induction, administer Alfaxan® Multidose over approximately 60 seconds or until clinical signs show the onset of anesthesia, titrating administration against the response of the patient. Rapid administration of Alfaxan® Multidose may be associated with an increased incidence of cardiorespiratory depression or apnea. Apnea can occur following induction or after the administration of maintenance boluses of Alfaxan® Multidose. The use of preanesthetics may reduce the Alfaxan® Multidose induction dose. The choice and the amount of phenothiazine, alpha2- adrenoreceptor agonist, benzodiazepine or opioid will influence the response of the patient to an induction dose of Alfaxan® Multidose.

When using Alfaxan® Multidose, patients should be continuously monitored, and facilities for the maintenance of a patent airway, artificial ventilation, and oxygen supplementation must be immediately available.

Alfaxan® Multidose contains preservatives. Use within 28 days of first puncture. Any unused Alfaxan® Multidose remaining after 28 days should be discarded.Alfaxan® Multidose should not be mixed with other therapeutic agents prior to administration.

INDUCTION OF GENERAL ANESTHESIA:CATS: Induction dose guidelines range between 2.2 - 9.7 mg/ kg for cats that did not receive a preanesthetic, and between 1.0 - 10.8 mg/kg for cats that received a preanesthetic. The alfaxalone induction dose in the field study was reduced by 10 - 43%, depending on the combination of preanesthetics (dose sparing effect).

DOGS: Induction dose guidelines range between 1.5 - 4.5 mg/kg for dogs that did not receive a preanesthetic, and between 0.2 - 3.5 mg/kg for dogs that received a preanesthetic. The Alfaxalone induction dose in the field study was reduced by 23 - 50% depending on the combination of preanesthetics (dose sparing effect).

Dose sparing of Alfaxan® Multidose will depend on the potency, dose, and time od administration of the various preanesthetics that are used prior to induction. To avoid anesthetic overdose, titrate the administration of Alfaxan® Multidose against the response of the patient. The average Alfaxan® Multidose induction dose rates for healthy cats and dogs given alfaxalone alone, or when alfaxalone is preceded by a preanesthetic, are indicated in species specific tables found in the full package insert. These tables are based on field study results and are for guidance only. The dose and rate for alfaxalone should be based upon patient response.

MAINTENANCE OF GENERAL ANESTHESIA:CATS and DOGS: Following induction of anesthesia with Alfaxan® Multidose and intubation, anesthesia may be maintained using intermittent Alfaxan® Multidose intravenous boluses or an inhalant anesthetic agent. Please review the full package insert for guidance on recommended intermittent doses of Alfaxan® Multidose and the expected duration of effect. Clinical response may vary, and is determined by the dose, rate of administration, and frequency of maintenance injections.

Alfaxan® Multidose maintenance dose sparing is greater in cats and dogs that receive a preanesthetic. Maintenance dose and frequency should be based on the response of the individual

patient.

Inhalant anesthetic maintenance of general anesthesia in cats and dogs: Additional low doses of Alfaxan® Multidose, similar to a maintenance dose, may be required to facilitate the transition to inhalant maintenance anesthesia.

WARNINGS:Animal Safety: When anesthetized using Alfaxan® Multidose, patients should be continuously monitored, and facilities for the maintenance of a patent airway, artificial ventilation, and oxygen supplementation must be immediately available.

Rapid bolus administration or anesthetic overdose may cause cardiorespiratory depression, including hypotension, apnea, hypoxia, or death. Arrhythmias may occur secondary to apnea and hypoxia. In cases of anesthetic overdose, stop Alfaxan® Multidose administration and administer treatment as indicated by the patient’s clinical signs.

Cardiovascular depression should be treated with plasma expanders, pressor agents, anti-arrhythmic agents or other techniques as appropriate for the treatment of the clinical signs.

Human Safety: Not for human use. Keep out of the reach of children.Alfaxan® Multidose should be managed to prevent the risk of diversion, through such measures as restriction of access and the use of drug accountability procedures appropriate to the clinical setting.

Exercise caution to avoid accidental self-injection. Overdose is likely to cause cardiorespiratory depression (such as hypotension, bradycardia and/or apnea). Remove the individual from the source of exposure and seek medical attention. Respiratory depression should be treated by artificial ventilation and oxygen.

Avoid contact of this product with skin, eyes, and clothes. In case of contact, eyes and skin should be liberally flushed with water for 15 minutes. Consult a physician if irritation persists. In the case of accidental human ingestion, seek medical advice immediately and show the package insert or the label to the physician.

The Material Safety Data Sheet (MSDS) contains more detailed occupational safety information.

To report adverse reactions in users or to obtain a copy of the MSDS for this product call 1-844-253-2926.

DRUG ABUSE AND DEPENDENCE:

Controlled Substance: Alfaxan® Multidose contains alfaxalone, a neurosteroid anesthetic and a class IV controlled substance.

Abuse: Alfaxalone is a central nervous system depressant that acts on GABA receptor associated chloride channels, similar to the mechanism of action of Schedule IV sedatives such as benzodiazepines (diazepam and midazolam), barbiturates (phenobarbital and methohexital) and fospropofol. In a drug discrimination behavioral test in rats, the effects of alfaxalone were recognized as similar to those of midazolam. These biochemical and behavioral data suggest that alfaxalone has an abuse potential similar to other Schedule IV sedatives.

Physical dependence: There are no data that assess the ability of alfaxalone to induce physical dependence. However, alfaxalone has a mechanism of action similar to the benzodiazepines and can block the behavioral responses associated with precipitated benzodiazepine withdrawal. Therefore, it is likely that alfaxalone can also produce physical dependence and withdrawal signs similar to that produced by the benzodiazepines.

Psychological dependence: The ability of alfaxalone to produce psychological dependence is unknown because there are no data on the rewarding properties of the drug from animal self-administration studies or from human abuse potential studies.

PRECAUTIONS:Rapid arousal: Careful monitoring of the patient is necessary due to possibility of rapid arousal.Preanesthesia: Benzodiazepines may be used safely prior to Alfaxan® Multidose in the presence of other preanesthetics. However, when a benzodiazepine was used as the sole preanesthetic, excitation occurred in some dogs and cats during Alfaxan® Multidose anesthesia and recovery.Apnea: Apnea may occur following administration of an induction dose, a maintenance dose or a dose administered

during the transition to inhalant maintenance anesthesia, especially with higher doses and rapid administration. Endotracheal intubation, oxygen supplementation, and intermittent positive pressure ventilation (IPPV) should be administered to treat apnea and associated hypoxemia.Blood Pressure: The myocardial depressive effects of Alfaxan® Multidose combined with the vasodilatory effects of inhalant anesthetics can be additive, resulting in hypotension. Preanesthetics may increase the anesthesia effect of Alfaxan® Multidose and result in more pronounced changes in systolic, diastolic, and mean arterial blood pressures. Transient hypertension may occur, possibly due to elevated sympathetic activity.Body Temperature: A decrease in body temperature occurs during Alfaxan® Multidose anesthesia unless an external heat source is provided. Supplemental heat should be provided to maintain acceptable core body temperature until full recovery.Breeding Animals: Alfaxan® Multidose has not been evaluated in pregnant, lactating, and breeding cats. Alfaxalone crosses the placenta, and as with other general anesthetic agents, the administration of alfaxalone may be associated with neonatal depression.Kittens and Puppies: Alfaxan® Multidose has not been evaluated in cats less than 4 weeks of age or in dogs less than 10 weeks of age.Compromised or Debilitated Cats and Dogs: The administration of Alfaxan® Multidose to debilitated patients or patients with renal disease, hepatic disease, or cardiorespiratory disease has not been evaluated. Doses may need adjustment for geriatric or debilitated patients. Caution should be used in cats or dogs with cardiac, respiratory, renal or hepatic impairment, or in hypovolemic or debilitated cats and dogs, and geriatric animals.Analgesia during anesthesia: Appropriate analgesia should be provided for painful procedures.

ADVERSE REACTIONS:The primary side effects of alfaxalone are respiratory depression (apnea, bradypnea, hypoxia) and cardiovascular derangements (hypertension, hypotension, tachycardia, bradycardia). Other adverse reactions observed in clinical studies include hypothermia, emesis, unacceptable anesthesia quality, lack of effectiveness, vocalization, paddling, and muscle tremors.To report adverse reactions or obtain a copy of the SDS for this product call 1-844-253-2926.For additional information about adverse drug experience reporting for animal drugs, contact FDA at 1-888-FDA-VETS or http://www.fda.gov/AnimalVeterinary/SafetyHealth.

OVERDOSE: Rapid administration, accidental overdose, or relative overdose due to inadequate dose sparing of Alfaxan® Multidose in the presence of preanesthetics may cause cardiopulmonary depression. Respiratory arrest (apnea) may be observed. In cases of respiratory depression, stop drug administration, establish a patent airway, and initiate assisted or controlled ventilation with pure oxygen. Cardiovascular depression should be treated with plasma expanders, pressor agents, antiarrhythmic agents or other techniques as appropriate for the observed abnormality.

HOW SUPPLIED:Alfaxan® Multidose is supplied in 10 mL and 20 mL multiple-dose vials containing 10 mg alfaxalone per mL.Manufactured in Australia by: Jurox Pty Ltd.

Marketed by: Jurox Inc. Kansas City, MO 64111 Phone: 1-844-253-2926

Distributed by: Vedco, Inc. St Joseph, MO 64507

Alfaxan is a registered trademark of Jurox Pty Limited.

US Patent # 7897586 US Patent # 9492552

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Alfaxan Multidose has the same effectiveness, versatility

and wide safety profile as original Alfaxan, but with a

non-irritating preservative that allows the product to

be used for up to 28 days after the vial is broached and

stored at room temperature.

The preservative system in Alfaxan Multidose is

comprised of ethanol (150 mg/mL), chlorocresol

(1.0 mg/mL), and benzethonium chloride (0.2 mg/mL).

Alfaxan Multidose contains alfaxalone, a neuroactive

steroid molecule that does not bind to sex hormone,

glucocorticoid or mineralcorticoid receptors.1,2

• GABA is one of the major inhibitory

neurotransmitters derived from the amino

acid glutamate

• GABA and alfaxalone work in tandem producing

anesthesia by enhancing GABAA receptor-mediated

neurotransmission3

New Alfaxan Multidose Now FDA registered for 28 days

of use after broaching

Alfaxan Multidose - proceed with confidence

What is Alfaxan Multidose?

Comorbidities and other risk factors add uncertainty to outcomes

Effectiveness

Quick, anxiety-free unconsciousness4,5,6,7 with

muscle relaxation4,5 allows rapid intubation and

transition to maintenance anesthesia

• Works reliably with all premedicants8

• Rapid onset of anesthesia4,5,9 (usually within

60 seconds)

• The use of premedicants may reduce the

Alfaxan Multidose induction dose

Versatility

• FDA-registered for use in dogs AND cats

• Use for induction AND maintenance of anesthesia

• Use confidently among healthy populations,

special populations (brachycephalic patients,

Sighthounds10, C-sections11 and juvenile dogs and

cats12,13,14), compromised patients (ASA I-V15)

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Helps maintain acceptable cardiovascular

and respiratory parameters

Wide safety margin in case of accidental

overdose:

Dogs and cats recover from doses

equal to 10× and 5× recommended

rates, respectively, with only short-term

ventilation4,5

Repeated over-dosing (dogs and

cats received three doses 5× the

recommended dose, every 48 hours)

caused no observable adverse effects16,17

Alfaxalone does not accumulate18.

Administer repeat boluses to maintain

anesthesia

No pain upon injection IV and non

irritating to tissue19,20

Breathe easier with alfaxalone's wide safety profile

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Rapid recoveries - the final step to a positive outcome

Rapid drug elimination and quick recoveries re-unite the animal and client sooner, so you and your staff can assist other patients.

Alfaxalone is handled by the

patient much like progesterone

Metabolized in the liver

Inactive metabolites excreted

in the bile and urine.

Average time to extubation after

discontinuation of maintenance

anesthesia ≈ 15 minutes

Average time to standing after

extubation ≈ 20 minutes

1) Jurox and Ricera, ”An in vitro study evaluating the binding of alfaxalone…” (Ricerca Study No. AA94464). Records in house 2010; 2) Jurox and Ricera, ”An in vitro study evaluating the binding of alfaxalone…” (Ricerca Study No. AA94047). Records in house 2010; 3) Ibid; 4) Muir, W., et al, “The cardiorespiratory…of alfaxalone in dogs,” Vet Anaesth. and Analg., 2008. 35[6]: 451-462; 5) Muir, W., et al, “The cardiorespiratory…of alfaxalone in cats,” Vet Anaesth. and Analg., 2009. 36[1]: 42-54; 6) Pasloske, K., et al, “A multicenter clinical trial evaluating…Alfaxan administered for dogs…” in Brit. Small Animal Vet. Assn. Cong. 2005; 7) Pasloske, K., et al, “A multicenter clinical trial evaluating…Alfaxan administered for cats…” in Brit. Small Animal Vet. Assn. Cong. 2007; 8) See full prescribing information for guidance on the effects of different premedicant regimes on expected induction and maintenance doses of alfaxalone; 9) Ferre, P. J., et al, ”Plasma pharmacokinetics of alfaxaone…,” CD RTU Vet Anaesth. and Analg., 2006, 33[4], 229-36; 10) Pasloske, K., et al, “Plasma pharmacokinetics of alfaxalone…Greyhound dogs…” Jrnl. of Vet. Pharma. and Thera., 2009. 32: 510-513; 11) Metcalfe, S., et al, “A multi-centre clinical trial evaluating…of Alfaxan administered to bitches…,” 33rd World Small Animal Congress, 2008. WSAVA/FECAVA; 12) O’Hagan, B, et al,” Clinical evaluation of alfaxalone…in dogs less than 12 weeks of age;” Australian Vet. Jrnl., 2012. 90[10], 395-401; 13) O’Hagan, B, et al,” Clinical evaluation of alfaxalone…in cats less than 12 weeks of age;” Australian Vet. Jrnl., 2012. 90[9], 346-350; 14) “Alfaxan…for use in cats and dogs,” US-FDA prescribing information, Rev. February, 2014; 15) Psatha, E., et al, “Clinical efficacy…,” Vet. Anaesth. Analg., 2011.38: 24-36; 16) Schnell, M., et al, “Margin of safety of the anesthetic Alfaxan®, CD RTU…dogs” in ACVIM, 2004; 17) Pasloske, K. and Whittem, T., JX9604.07-H004, "A target animal safety study in cats…,” 2004. On file at Jurox; 18) Whittem, T., et al “The pharmacokinetics and pharmacodynamics of alfaxalone in cats...at clinical and supraclinical doses." J Vet Pharmacol Therap 2008;31(6):571-579. 19) Pasloske K et al. "The bioequivalence...alfaxalone in cyclodextrin plus preservatives...cats", J Vet Pharmacol Therap 2018;41(3):437-446. 20) Goodwin WA and Pasloske K. "A dose ranging study evaluating the pharmacodynamics of RD0327 as an anaesthetic and sedative in rabbits after IM administration. Abstract (O14-1, pg.161), World Congress of Veterinary Anaesthesiology 02SEP15, Kyoto, Japan.

Fair Balance Statement Alfaxan® Multidose (alfaxalone 10 mg/mL)Indications: Alfaxan® Multidose is indicated for the induction and maintenance of anesthesia and for the induction of anesthesia followed by maintenance with an inhalant anesthetic in cats and dogs.Important Alfaxan® Multidose Risk Information: Warnings, precautions and Contraindications: When using Alfaxan® Multidose patients should be continuously monitored, and facilities for the maintenance of a patent airway, artificial ventilation, and oxygen supplementation must be immediately available. Careful monitoring of the patient is necessary due to the possibility of rapid arousal. Alfaxan® Multidose is contraindicated in cats and dogs with a known sensitivity to alfaxalone or its components, or when general anesthesia and/or sedation are contraindicated.Adverse Drug Reactions: the most common side effects of alfaxalone include respiratory and cardiovascular derangements, such as apnea, hypotension and hypertension. Appropriate analgesia should be provided for all painful procedures.Storage and How Supplied: Alfaxan® Multidose should be stored at room temperature (i.e. 68-77°F). Alfaxan® Multidose contains preservatives and is supplied in 10 mL and 20 mL multiple-dose vials. The product can be used for 28 days after broaching the vial and should be stored at room temperature during that period. Any unused Alfaxan® Multidose remaining after 28 days should be discarded.Controlled Substance: Alfaxan® Multidose contains alfaxalone, a neurosteroid anesthetic and a class IV controlled substance. FOI Summary: NADA #141-342US Patents: #7897586 and #9492552See full package for complete information.

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Kansas City, MO 64111

844-253-2926www.jurox.com/us

© 2018 Jurox Pty Ltd Alfaxan is a registered trademark of Jurox Pty Ltd

Alfaxan® Multidose

Premedicant

Average Alfaxan Multidose Induction Dose

(and range) in mg/kg

Dog Cat

No premedicant 2.2 (1.5 – 4.5) 4.0 ( 2.2 – 9.7)

Benzodiazepine + opioid + acepromazine 1.7 (0.9 – 3.5) 2.3 (1.2 – 5.0)

Opioid + acepromazine 1.6 (0.6 – 3.5) 3.2 (1.1 – 10.8)

Alpha 2-agonist 1.1 (0.2 – 2.0) 3.6 (1.1 – 5.0)

(See full prescribing information, including some other combinations of premedicants)

Dose Dog Maintenance of Anesthesia Cat Maintenance of

Anesthesia

Induction 2 mg/kg 5-10 mins 5 mg/kg 15-30 mins

Maintenance 1.5-2.2 mg/kg 6-8 mins 1.4-1.5 mg/kg 3-5 mins

Registered dosing ranges for dogs and cats, with and without premedication

General dosing instructions for dogs and cats