Propofol

Information from Zoetis:

DESCRIPTION: PropoFlo™ 28 is a sterile, nonpyrogenic emulsion containing 10 mg/mL of propofol in a multidose vial for intravenous administration. Each mL contains 10 mg propofol. Propofol is chemically described as 2, 6-diisopropylphenol and has a molecular weight of 178.27. Propofol is very slightly soluble in water and is therefore formulated as a white, oil-in-water emulsion. In addition to the active component, propofol, the formulation also contains soybean oil (100 mg/mL), glycerol (22.5 mg/mL), benzyl alcohol (20 mg/mL), oleic acid (0.6 mg/mL), and egg lecithin (12 mg/mL), with sodium hydroxide to adjust the pH. The PropoFlo™ 28 emulsion is isotonic and has a pH of 6.0-8.5. PropoFlo™ 28 does not meet the propofol injectable emulsion USP specification for free fatty acids.

 INDICATIONS: PropoFlo™ 28 is an intravenous anesthetic injection for use in dogs as follows: For induction of anesthesia. For maintenance of general anesthesia by intermittent bolus injections for short procedures. For induction of general anesthesia where maintenance is provided by inhalant anesthetics. 

DOSAGE AND ADMINISTRATION: Administer by intravenous injection only. Shake the vial thoroughly before opening. Propofol is a white stable emulsion; do not use if there is evidence of separation of the phases. Do not use if there is evidence of excessive creaming or aggregation, if large droplets are visible, or if there are other forms of phase separation indicating that the stability of the product has been compromised. Slight creaming, which should disappear after shaking, may be visible upon prolonged standing. Do not use if particulate matter and discoloration are present. Strict aseptic techniques must always be maintained during handling. Failure to follow aseptic handling procedures may result in microbial contamination causing fever, infection/sepsis, and/or other life threatening illness. 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. The emulsion should not be mixed with other therapeutic agents prior to administration. No specific preanesthetic is either indicated or contraindicated with propofol. The necessity for, choice of, as well as 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.

CONTRAINDICATIONS: PropoFlo™ 28 injection is contraindicated in dogs with a known hypersensitivity to propofol or its components, or when general anesthesia or sedation are contraindicated. 

WARNINGS: Rapid bolus administration (induction or maintenance) or accidental overdosage of propofol may cause undesirable cardiorespiratory depression including hypotension and oxygen desaturation. Respiratory arrest (apnea) could occur. 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. When using propofol, dogs should be continuously monitored and facilities for the maintenance of a patent airway, artificial ventilation, and oxygen supplementation must be immediately available. 

HUMAN WARNINGS: Not for human use. Keep out of the reach of children. Rare cases of self-administration have been reported, including fatalities. PropoFlo™ 28 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 relaxants4 . Avoid inhalation and 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.

PRECAUTIONS: 1. Anesthesia effects: Careful monitoring of the patient is necessary when using propofol as a maintenance anesthetic due to the possibility of rapid arousal. Apnea may occur following maintenance doses of propofol. Following induction, additional propofol may be needed to complete the transition to inhalant maintenance anesthesia due to rapid recovery from propofol. Doses administered during the transition to inhalant anesthesia may result in apnea. Propofol has also been used during inhalant maintenance anesthesia to increase anesthetic depth. Propofol used during inhalant maintenance may result in apnea. 2. Physiological effects: Mild hypotension may occur during propofol anesthesia. 3. Preanesthetics: Preanesthetics may increase the anesthesia or sedative effect of propofol and result in more pronounced changes in systolic, diastolic and mean arterial blood pressures. 4. Alpha2-agonists: PropoFlo™ 28 for maintenance anesthesia was not evaluated in the presence of alpha2-agonist preanesthesia. The use of an alpha2-agonist as a preanesthetic may significantly reduce the amount of propofol induction and maintenance anesthetic requirements. Careful patient monitoring during anesthetic induction and maintenance is necessary to avoid anesthetic overdose. 5. Breeding animals: The use of propofol in pregnant and breeding dogs has not been evaluated. Propofol crosses the placenta and, as with other general anesthetic agents, the administration of propofol may be associated with neonatal depression. 6. Neonates and pups: Propofol has not been evaluated in dogs less than 10 weeks of age. 7. Compromised or debilitated dogs: Doses may need adjustment for geriatric or debilitated patients. The administration of propofol to patients with renal failure and/or hepatic failure has not been evaluated. As with other anesthetic agents, caution should be exercised in dogs with cardiac, respiratory, renal or hepatic impairment, or in hypovolemic or debilitated dogs. Geriatric dogs may require less propofol for induction of anesthesia (see Dosage and Administration). 8. Sighthounds: Propofol induction and maintenance produced satisfactory anesthesia and recoveries in sighthounds. In the clinical study, a total of 27 sighthounds were induced with propofol, 6 of which were maintained on propofol. Induction doses were similar in sighthounds compared to other animals, however, recoveries were delayed. 9. Cardiac arrhythmias: In one study, propofol increased myocardial sensitivity to the development of epinephrine-induced ventricular arrhythmias in a manner similar to other anesthetics5 . In the PropoFlo field study, transient ventricular arrhythmias associated with propofol were observed in 2 of 145 animals induced and maintained on propofol. 10.Concurrent medication: No significant adverse interactions with commonly used drugs have been observed. 11.Perivascular administration: Perivascular administration does not produce local tissue reaction. 12.Aseptic Handling: PropoFlo™ 28 contains benzyl alcohol as a bacteriostatic preservative. Aseptic technique during handling is recommended. Use of vial contents beyond 28 days may result in microbial contamination causing fever, infection/sepsis, and/or other life-threatening illness. Do not use if contamination is suspected. 13.Cats: PropoFlo™ 28 contains benzyl alcohol which may be toxic to cats. 

ADVERSE REACTIONS: The primary side effect of propofol is respiratory depression as evidenced by tachypnea and apnea. Other less frequent adverse reactions include: Respiratory: labored breathing. Cardiovascular: hypotension, hypertension, bradycardia, tachycardia, membrane cyanosis, arrhythmias. Musculoskeletal: fasciculations, tenseness, paddling, movements. Central Nervous System: excitation, opisthotonos, seizures, excessive depression. Gastrointestinal: emesis, retching, salivation.