propofol

INDICATIONS & USAGE Propofol injectable emulsion is an IV general anesthetic and sedation drug that can be used as described in the table below. TABLE 3. INDICATIONS FOR PROPOFOL INJECTABLE EMULSION Safety, effectiveness and dosing guidelines for propofol injectable emulsion have not been established for MAC Sedation in the pediatric population; therefore, it is not recommended for this use (see PRECAUTIONS , Pediatric Use). Propofol injectable emulsion is not recommended for induction of anesthesia below the age of 3 years or for maintenance of anesthesia below the age of 2 months because its safety and effectiveness have not been established in those populations. In the Intensive Care Unit (ICU), propofol injectable emulsion can be administered to intubated, mechanically ventilated adult patients to provide continuous sedation and control of stress responses only by persons skilled in the medical management of critically ill patients and trained in cardiovascular resuscitation and airway management. Propofol injectable emulsion is not indicated for use in Pediatric ICU sedation since the safety of this regimen has not been established (see PRECAUTIONS , Pediatric Use). Propofol injectable emulsion is not recommended for obstetrics, including Cesarean section deliveries. Propofol injectable emulsion crosses the placenta, and as with other general anesthetic agents, the administration of propofol injectable emulsion may be associated with neonatal depression (see PRECAUTIONS ). Propofol is not recommended for use in nursing mothers because propofol injectable emulsion has been reported to be excreted in human milk, and the effects of oral absorption of small amounts of propofol are not known (see PRECAUTIONS ). INDICATIONS AND USAGE

WARNINGS Use of propofol injectable emulsion has been associated with both fatal and life-threatening anaphylactic and anaphylactoid reactions. For general anesthesia or monitored anesthesia care (MAC) sedation, propofol injectable emulsion should be administered only by persons trained in the administration of general anesthesia and not involved in the conduct of the surgical/diagnostic procedure. Sedated patients should be continuously monitored, and facilities for maintenance of a patent airway, providing artificial ventilation, administering supplemental oxygen, and instituting cardiovascular resuscitation must be immediately available. Patients should be continuously monitored for early signs of hypotension, apnea, airway obstruction, and/or oxygen desaturation. These cardiorespiratory effects are more likely to occur following rapid bolus administration, especially in the elderly, debilitated, or ASA-PS III or IV patients. For sedation of intubated, mechanically ventilated patients in the Intensive Care Unit (ICU), propofol injectable emulsion should be administered only by persons skilled in the management of critically ill patients and trained in cardiovascular resuscitation and airway management. Use of propofol injectable emulsion for both adult and pediatric ICU sedation has been associated with a constellation of metabolic derangements and organ system failures, referred to as Propofol Infusion Syndrome, that have resulted in death. The syndrome is characterized by severe metabolic acidosis, hyperkalemia, lipemia, rhabdomyolysis, hepatomegaly, renal failure, ECG changes1 and/or cardiac failure. The following appear to be major risk factors for the development of these events: decreased oxygen delivery to tissues; serious neurological injury and/or sepsis; high dosages of one or more of the following pharmacological agents: vasoconstrictors, steroids, inotropes and/or prolonged, high-dose infusions of propofol (greater than 5 mg/kg/h for greater than 48h). The syndrome has also been reported following large-dose, short-term infusions during surgical anesthesia. In the setting of prolonged need for sedation, increasing propofol dose requirements to maintain a constant level of sedation, or onset of metabolic acidosis during administration of a propofol infusion, consideration should be given to using alternative means of sedation. Abrupt discontinuation of propofol injectable emulsion prior to weaning or for daily evaluation of sedation levels should be avoided. This may result in rapid awakening with associated anxiety, agitation, and resistance to mechanical ventilation. Infusions of propofol injectable emulsion should be adjusted to maintain a light level of sedation through the weaning process or evaluation of sedation level (see PRECAUTIONS ). Propofol injectable emulsion should not be co-administered through the same IV catheter with blood or plasma because compatibility has not been established. In vitro tests have shown that aggregates of the globular component of the emulsion vehicle have occurred with blood/plasma/serum from humans and animals. The clinical significance of these findings is not known. There have been reports in which failure to use aseptic technique when handling propofol injectable emulsion was associated with microbial contamination of the product and with fever, infection, sepsis, other life-threatening illness, and death. Do not use if contamination is suspected. Discard unused drug product as directed within the required time limits (see DOSAGE AND ADMINISTRATION , Handling Procedures). There have been reports, in the literature and other public sources, of the transmission of bloodborne pathogens (such as Hepatitis B, Hepatitis C and HIV) from unsafe injection practices, and use of propofol vials intended for single use on multiple persons. Propofol injectable emulsion vial is never to be accessed more than once or used on more than one person. 1 Coved ST segment elevation (similar to ECG changes of the Brugada syndrome). Pediatric Neurotoxicity Published animal studies demonstrate that the administration of anesthetic and sedation drugs that block NMDA receptors and/or potentiate GABA activity increase neuronal apoptosis in the developing brain and result in long-term cognitive deficits when used for longer than 3 hours. The clinical significance of these findings is not clear. However, based on the available data, the window of vulnerability to these changes is believed to correlate with exposures in the third trimester of gestation through the first several months of life, but may extend out to approximately three years of age in humans (see PRECAUTIONS , Pregnancy, Pediatric Use; ANIMAL TOXICOLOGY AND OR PHARMACOLOGY ). Some published studies in children suggest that similar deficits may occur after repeated or prolonged exposures to anesthetic agents early in life and may result in adverse cognitive or behavioral effects. These studies have substantial limitations, and it is not clear if the observed effects are due to the anesthetic/sedation drug administration or other factors such as the surgery or underlying illness. Anesthetic and sedation drugs are a necessary part of the care of children needing surgery, other procedures, or tests that cannot be delayed, and no specific medications have been shown to be safer than any other. Decisions regarding the timing of any elective procedures requiring anesthesia should take into consideration the benefits of the procedure weighed against the potential risks.