PropoFlo 28 Sterile Injection 10 mg/mL (Canada)

Company: Zoetis

propofol sterile injection, 10 mg/mL

Intravenous Anesthetic for Dogs

Veterinary Use Only

DIN 02445654

DESCRIPTION:

PropoFlo 28 is a sterile, non-pyrogenic, injectable emulsion for intravenous use in dogs. Each mL contains: Active Ingredient: propofol 10 mg; Preservative: benzyl alcohol 20 mg. Nonmedicinal ingredients: soybean oil 100 mg, glycerol 22.5 mg, purified egg phospholipids 12 mg, oleic acid 0.6 mg, and water for injection q.s. Sodium hydroxide may be added for pH adjustment. PropoFlo 28 sterile injection is isotonic and has a pH of 6.0 to 8.5.

INDICATIONS:

PropoFlo 28 sterile injection is a short-acting intravenous anesthetic agent for use in dogs as follows:

1. As a single injection for induction of general anesthesia for procedures lasting approximately 5 minutes.

2. For induction and maintenance of anesthesia for procedures lasting up to 20 minutes by administering intermittent doses of propofol to effect.

3. For induction of general anesthesia where maintenance is provided by inhalation agents.

Propofol has little or no analgesic effect. Use as a maintenance agent should be restricted to minimally painful surgical procedures, unless the animal has been premedicated with suitable analgesic agents.

DOSAGE AND ADMINISTRATION:

General Directions for Use: Shake the vial thoroughly before opening. Slight creaming, which should disappear after shaking, may be visible upon prolonged standing. Administer by intravenous injection only. Propofol is a white stable emulsion. Do not use if there is evidence of discoloration or phase separation or if particulate matter is present. Maintain strict aseptic technique during handling to avoid contamination. Do not use if contamination is suspected.

Once a vial is opened, the contents begin a 28-day shelf life. The opened vial should be labeled with “Date opened” and “Use by” in the space provided. To avoid microbial overgrowth, the contents must be used within 28 days (4 weeks) of the date opened. The opened vial should be placed in a covered container, held at room temperature and used within the allotted 28-day timeframe. Refrigeration is not recommended. Any unused propofol remaining at the end of 28 days should be discarded. Do not mix PropoFlo 28 sterile injection with other medications in the same syringe.

No specific preanesthetic is either indicated or contraindicated with propofol. The necessity for, choice of, or any necessary reduction of dose for the preanesthetic is left to the discretion of the veterinarian. The dose of propofol is not affected by anticholinergic premedication.

1. Induction

For induction, PropoFlo 28 sterile injection should be titrated against the response of the patient over 60-90 seconds or until clinical signs show the onset of anesthesia. Rapid bolus injection of propofol (≤5 seconds) may be associated with an increased incidence of apnea. The average PropoFlo 28 sterile injection induction dose rates for healthy dogs given propofol alone, or when propofol is preceded by a preanesthetic, are indicated in the table below. This table is based on field study results and is for guidance only. The dose and rate for propofol should be based upon patient response.

PropoFlo 28 Sterile Injection Induction Dose Guidelines

*Doses for preanesthetics may be lower than the label directions for their use as a single medication¹.

The use of preanesthetics markedly reduces propofol requirements. Induction dose sparing was approximately 38% with benzodiazepine/opioid preanesthesia, 47% when dogs were preanesthetized with phenothiazine/opioid, and 58% when dogs were preanesthetized with alpha₂-agonist. As with other sedative hypnotic agents, the amount of opioid and/or alpha₂-agonist premedication will influence the response of the patient to an induction dose of propofol. In the presence of preanesthesia, the dose of propofol may be reduced with increasing age of the animal. The dose of propofol should always be titrated against the response of the patient. During induction, additional low doses of propofol, similar to those used for maintenance with propofol, may be administered to facilitate intubation or the transition to inhalant maintenance anesthesia.

2. Maintenance of General Anesthesia with Intermittent PropoFlo 28 Injections:

Anesthesia can be maintained by administering PropoFlo 28 sterile injection in intermittent IV injections. Maintenance of anesthesia with PropoFlo 28 sterile injection is usually reserved for short procedures up to 20 minutes. The dose frequency and rate should be determined by the clinical response of each patient. The following table is based on field study results and is provided for guidance:

PropoFlo 28 Sterile Injection Maintenance Dose Guidelines

*Doses for preanesthetics may be lower than the label directions for their use as a single medication¹.

Maintenance dose sparing was approximately 48% with benzodiazepine/opioid preanesthesia and 37% when dogs were preanesthetized with phenothiazine/opioid. Repeated maintenance doses of propofol do not result in increased recovery times or dosing intervals, indicating that the anesthetic effects of propofol are not cumulative.

3. Maintenance by Inhalation Agents

Due to the rapid metabolism of propofol, additional low doses of propofol, similar to those used for maintenance with propofol, may be required to complete the transition to inhalant maintenance anesthesia.

CONTRAINDICATIONS:

PropoFlo 28 sterile injection is contraindicated in dogs with a known hypersensitivity to propofol or its components, or whenever general anesthesia or sedation is contraindicated.

CAUTIONS:

● Cardiorespiratory depression, notably apnea, hypotension and oxygen desaturation, may occur following propofol doses used for induction, for maintenance, to complete the transition to inhalant maintenance, or to increase anesthetic depth during inhalant maintenance anesthesia. These effects are usually transient.

● When using PropoFlo 28 sterile injection, 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 may increase the incidence of cardiorespiratory depression (see Dosage and Administration).

● When tachypnea is present in the pre-induction period, it may persist throughout the anesthetic and recovery periods. Tachypnea during propofol maintenance may signal a light plane of anesthesia or a response to painful stimuli.

● Careful monitoring of the patient is necessary when using propofol as a maintenance anesthetic due to the possibility of rapid arousal.

● Preanesthetics may increase the anesthesia or sedative effect of propofol and result in more pronounced changes in systolic, diastolic and mean arterial blood pressures.

● PropoFlo 28 sterile injection in the presence of alpha₂-agonist preanesthesia was evaluated for induction of anesthesia followed by maintenance of anesthesia with inhalation anesthetics, but not when anesthesia was maintained by intermittent doses of PropoFlo 28. The use of an alpha₂-agonist as a preanesthetic reduces the amount of propofol induction anesthetic requirements, and may also have similar effects on propofol maintenance anesthetic requirements. Careful patient monitoring during anesthetic induction and maintenance is necessary to avoid anesthetic overdose. As with all sedative and anesthetic agents, exercise caution when using PropoFlo 28 sterile injection in patients with cardiac, respiratory, renal or hepatic impairment, or in hypovolemic or debilitated dogs. Doses may need to be adjusted downward for premedicated geriatric dogs and severely debilitated dogs.

● Recovery to sternal recumbency may be delayed by about 10 minutes in sighthounds compared to other breeds.

● Effects on fertility, reproductive function and pregnancy have not been evaluated in dogs. Since propofol crosses the placenta, the administration of propofol may lead to neonatal depression.

● PropoFlo 28 sterile injection has not been evaluated in dogs less than 10 weeks of age.

WARNINGS:

Not for human use. Keep out of the reach of children. PropoFlo 28 sterile injection 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. Hypersensitivity reactions to propofol, including anaphylaxis, may occur in some individuals who are also allergic to muscle relaxants². Avoid direct 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.

ADVERSE REACTIONS:

Although all adverse reactions are not reported, the following information is based on voluntary post-approval drug experience reporting. It is generally recognized that this results in significant under-reporting. The adverse events listed here reflect reporting and not necessarily causality. Adverse events are listed by body system, in decreasing order of frequency:

Systemic disorders: lack of efficacy, death, prolonged recovery, cyanosis, pyrexia.

Cardio-vascular disorders: bradycardia, cardiac arrest, arrhythmia, hypotension, tachycardia.

Respiratory tract disorders: apnea, tachypnea, dyspnea.

Neurological disorders: muscle tremor, paddling, seizure, hypertonia, nystagmus, opisthotonus.

Immune system disorders: anaphylactic-type reactions, facial edema, urticaria.

OVERDOSAGE:

Accidental overdosage is likely to cause cardiorespiratory depression. Respiratory arrest (apnea) may be observed. Discontinue propofol administration, establish a patent airway, and begin assisted or controlled ventilation with pure oxygen. Cardiovascular depression should be treated with plasma expanders, pressor agents and antiarrhythmic agents, as appropriate for the particular circumstances.

DRUG INTERACTIONS:

Propofol has been used in association with anticholinergics, phenothiazines, alpha₂-agonists, opioids, and benzodiazepines, as well as inhalant anesthetics. No pharmacological incompatibility has been observed. No adverse reactions with commonly used drugs (heartworm preventatives, flea control agents, antibiotics, antiinflammatories) have been observed.

CLINICAL PHARMACOLOGY:

Propofol, a substituted phenol chemically identified as 2,6-diisopropylphenol, is an intravenous, short-acting, sedative hypnotic agent for use in the induction and maintenance of anesthesia. Propofol anesthesia is characterized by rapid onset of effect and a rapid elimination phase. Intravenous injection of propofol in the dog is followed by extensive metabolism of propofol in the liver to inactive conjugates which are excreted in the urine. Elimination from the central compartment occurs rapidly, with an initial elimination phase of less than 10 minutes. Induction of anesthesia will usually be observed within 65-120 seconds after the beginning of propofol administration. The duration of anesthesia following the recommended induction doses averages 5.5-6.5 minutes in preanesthetized and unpreanesthetized animals. The duration of anesthesia following recommended maintenance doses in unpreanesthetized dogs averages 8.5 minutes. In preanesthetized dogs (phenothiazine/opioid or benzodiazepine/opioid), maintenance anesthesia averages 5.0-5.4 minutes after each maintenance dose. Recovery from propofol is rapid: full standing recovery is generally observed within 20 minutes. Hence, PropoFlo 28 sterile injection is particularly well-suited for cases in which a short recovery period is desirable. PropoFlo 28 sterile injection effects are not cumulative following multiple dose administration during maintenance of anesthesia. The use of certain premedicants may result in prolonged recovery. Recovery may be delayed in sighthounds.

ANIMAL SAFETY:

A study in Beagle dogs was conducted to compare the safety of PropoFlo 28 sterile injection at the average induction dose (6.5 mg/kg) and 3x the average induction dose (19.5 mg/kg) with unpreserved PropoFlo sterile injection at 19.5 mg/kg (positive control). A third group treated with saline served as the negative control. There was a dose-related increase in the duration of anesthesia with PropoFlo 28 sterile injection, but no correlation between the duration of anesthesia and the time to recovery. Following recovery from anesthesia, 3 of 4 dogs given the high dose of PropoFlo 28 sterile injection and 4 of 4 dogs given the high dose of unpreserved PropoFlo sterile injection experienced transient difficulty in walking. Electrocardiographic data indicated that PropoFlo 28 sterile injection induced a dose-related sinus tachycardia to a greater degree than the positive control. No clinically significant effects were noted on the morphology of the P-QRS-T complexes in any of the animals. PropoFlo 28 sterile injection also induced dose-related decreases in arterial blood oxygen saturation and in blood pressure. However, the effects at the low dose were minor, and the effects at the high dose were not different than in the positive control. No effects were seen on body weights, cage-side clinical observations, hematology or blood chemistry parameters; and no animal died.

STORAGE:

Store between 15 and 25°C. Protect from freezing. Keep vial in carton or away from light. Once broached use contents within 28 days.

PRESENTATION:

PropoFlo 28 sterile injection is supplied in 20 mL vials containing 10 mg propofol per mL (200 mg propofol per vial).

REFERENCES:

1. Plumb, D.C. ed. Veterinary Drug Handbook, Eighth Edition. Iowa State University Press, Ames, IA (2015).

2. Laxenaire, M.C., E. Mata-Bermejo, D.A. Moneret-Vaurrin and J.L. Gueant. Life-threatening anaphylactoid reactions to propofol (Diprivan^®). Anesthesiology 77:275-280 (1992).

Zoetis is a trademark and PropoFlo is a registered trademarks of Zoetis or its licensors, used under license by Zoetis Canada Inc.

Zoetis Canada Inc., Kirkland QC H9H 4M7

1207-11-2

CPN: 1198528.2