Medofol

Medofol

propofol

Manufacturer:

I.E. Medica

Distributor:

I.E. Medica
Full Prescribing Info
Contents
Propofol.
Description
Each mL contains Propofol USP 10 mg.
Propofol (Medofol injectable emulsion) is a sterile, nonpyrogenic emulsion, containing 10 mg/mL of Propofol suitable for intravenous administration. Propofol is chemically described as 2,6-diisopropylphenol. Propofol is slightly soluble in water and, thus, is formulated in a white, oil-in-water emulsion. The octanol/water partition coefficient for Propofol is 6761:1 at a pH of 6-8.5. The Propofol Injectable Emulsion is isotonic and has a pH of 7-8.5.
Action
Pharmacology: Propofol injectable emulsion is an intravenous sedative-hypnotic agent for use in the induction and maintenance of anesthesia or sedation. Intravenous injection of a therapeutic dose of Propofol induces hypnosis. with minimal excitation, usually within 40 seconds from the start of injection (the time for one arm-brain circulation). As with other rapidly acting intravenous anesthetic agents, the half-time of the blood-brain equilibrium is approximately 1 to 3 minutes, accounting for the rate of induction of anesthesia.
Pharmacodynamics: Pharmacodynamic properties of Propofol are dependent upon the therapeutic blood Propofol concentrations. Steady-state Propofol blood concentrations are generally proportional to Infusion rates. Undesirable effects such as cardio respiratory depression, are likely to occur at higher blood concentrations which result from bolus dosing or rapid increases in infusion rates. An adequate interval (3-5 minutes) must be allowed between dose adjustments in order to assess clinical effects. The hemodynamic effect of Propofol injectable emulsion during induction of anesthesia vary. If spontaneous ventilation is maintained, the major cardiovascular effect is arterial hypotension (sometimes greater than a 30% decrease) with little or no change in heart rate and no appreciable decrease in cardiac output. If ventilation is assisted or controlled (positive pressure ventilation), there is an increase in the incidence and the degree of depression of cardiac output. Addition of an opioid, used as a premedicant, further decreases cardiac output and respiratory drive. If anesthesia is continued by infusion of Propofol injectable emulsion, the stimulation of endotracheal intubation and surgery may return arterial pressure towards normal. However, cardiac output may remain depressed. Comparative clinical studies have shown that hemodynamic effects of Propofol injectable emulsion during induction of anesthesia are generally more pronounced than with other intravenous (IV) Induction agents. Induction of anesthesia with Propofol injectable emulsion is frequently associated with apnea in both adults and pediatric patients. During maintenance of general anesthesia. Propofol injectable emulsion causes a decrease in spontaneous minute ventilation usually associated with an increase in carbon dioxide tension which may be marked depending upon the rate of administration and concurrent use of other medication (e.g., opioid, sedatives, etc.) During monitored anesthesia care (MAC) sedation, attention must be given to the cardiorespiratory effects of Propofol injectable emulsion. Hypotension, oxyhemoglobin, desaturation, apnea, and airway obstruction can occur, especially following a rapid bolus of Propofol injectable emulsion. During initiation of MAC sedation, slow Infusion or slow Injection techniques are preferable over rapid bolus administration. During maintenance of MAC sedation, a variable rate infusion is preferable over intermittent bolus administration in order to minimize undesirable cardio respiratory effects. In the elderly, debilitated, or ASA-PS III or IV patients, rapid (single or repeated) bolus dose administration should not be used for MAC sedation.
Pharmacokinetics: The pharmacokinetics of Propofol are well-described by a three compartment linear model with compartments representing the plasma, rapidly equilibrating tissues, and slowly equilibrating tissues. Following an IV bolus dose, there is rapid equilibrium between the plasma and the brain, accounting for the rapid onset of anesthesia. Plasma levels Initially decline rapidly as a result of both distribution and metabolic clearance. Distribution accounts for about half of this decline following a bolus of Propofol. However, distribution Is not constant over time but decreases as body tissues equilibrate with plasma and become saturated. The rate at which equilibrium occurs is a function of the rate and duration of the infusion. When equilibrium occurs there is no longer a net transfer of Propofol between tissues and plasma. Discontinuation of the recommended doses of Propofol Injectable emulsion after the maintenance of anesthesia for approximately one hour, or for sedation in the ICU for one day. Results in a prompt decrease in blood Propofol concentrations and rapid awakening. Longer Infusions (10 days of ICU sedation) results in accumulation of significant tissue stores of Propofol such that the reduction in circulating Propofol is slowed and the time to awakening is increased. Propofol clearance ranges from 23-50mL/kg/min (1.6 to 3.4 L/min in 70 kg adults). It Is chiefly eliminated by hepatic conjugation to Inactive metabolites which are excreted by the kidney. A glucuronide conjugate accounts for about 50% of the administered dose. Propofol has a steady state volume of distribution (10 day infusion) approaching 60 L/kg in healthy adults. A difference in phamacokinetics due to gender has not been observed. The terminal half-life of Propofol after a 10-day infusion is 1 to 3 days. The clearance of Propofol in the children was similar to adults.
Indications/Uses
Propofol injectable emulsion is an IV sedative-hypnotic agent that can be used as described in Table 1 below:

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Dosage/Direction for Use
Propofol blood concentrations at steady state are generally proportional to infusion rates, especially in individual patients. Undesirable effects such as cardio respiratory depression are likely to occur at higher blood concentrations which result from bolus dosing or rapid increases in the infusion rate. An adequate interval (3 to 5 minutes) must be allowed between dose adjustments to allow for and assess the clinical effects. When administering Propofol injectable emulsion by infusion, syringe or volumetric pumps are recommended to provide controlled infusion rates. Dosages and rates of administration in the following table (see table 2) should be individualized and titrated to clinical response. Safety and dosing requirements to Induction of anesthesia in pediatric patients have only been established for children 3 years of age or older. Safety and dosing requirements for the maintenance of anesthesia have only been established for children 2 months of age and older. (See Table 2).

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Not recommended for use in children.
Administration with Lidocaine: If lidocaine is to be administered to minimize pain an injection of Propofol, it is recommended that it be administered prior to Propofol administration or that it be added to Propofol immediately before administration and in quantities not exceeding 20 mg lidocaine/200 mg Propofol.
Dilution Prior to Administration: Propofol injectable emulsion is provided as ready-to-use formulation. However, should dilution be necessary, it should only be diluted with 5% Dextrose injection, USP, and it should not be diluted a concentration less than 2 mgfmL because it is an emulsion. In diluted form it has been shown to be more stable when in contact with glass than in plastic (95% potency after 2 hours of running infusion in plastic).
Compatibility of Propofol injectable emulsion with the co-administration of blood/serum/plasma has not been established. When administered using a y-type infusion sot, Propofol injectable emulsion has been shown lobe compatible with the following intravenous fluids: 5% Dextrose Injection, Lactated Ringers Injection, Lactated Ringers and 5% Dextrose Injection, 5% Dextrose and 0.45% Sodium Chloride Injection, 5% Dextrose and 0.2% Sodium Chloride Injection.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Do not use if there is evidence of separation of the phases of the emulsion.
Overdosage
If overdosage occurs. Propofol injectable emulsion administration should be discontinued immediately. Overdosage is likely to cause cardio respiratory depression. Respiratory depression should be treated by artificial ventilation with oxygen. Cardiovascular depression may require repositioning of the patient by raising the patients legs, increasing the flow rate of intravenous fluids, and administering pressor agents and/ or anticholinergic agents.
Contraindications
Propofol injectable emulsion is contraindicated in patients with a known hypersensitivity to Propofol injectable emulsion or any of Its components. Propofol injectable emulsion is contraindicated in patients with allergies to eggs, egg products. soybeans and soy products. It is contraindicated to pregnant and lactating women and to patients with history of epilepsy and seizure.
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 cardio respiratory effects are more likely to occur following rapid bolus administration especially in the elderly, debilitated, or ASA-PSIII 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 Infusions 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, lipidemia, rhabdomyolysis, hepatomegaly, cardiac and renal failure. The syndrome is most often associated with prolonged, high-dose infusions (a 5 mg/kg/h for > 48h) but 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 mental 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 Propofol injectable emulsion should be adjusted to maintain a light level of sedation through the weaning process or evaluation of sedation level. 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 portions as directed within the required time limits.
May cause extrapyramidal-like symptoms characterized as Involuntary skeletal muscle movements in susceptible individual.
Special Precautions
Adult and Pediatric Patients: A lower induction dose and a slower maintenance rate of administration should be used in elderly, debilitated, or ASA-PS III or IV patients. Patients should be continuously monitored for early signs of hypotension and/or bradycardia. Apnea requiring ventilatory support often occurs during induction and may persist for more than 60 seconds. Propofol injectable emulsions use requires caution when administered to patients with disorders of lipid metabolism such as primary hyperlipoproteinemia, diabetic hyperlipidemia, and pancreatitis. Very rarely the use of Propofol injectable emulsion may be associated with the development of a period of postoperative unconsciousness which may be accompanied by an increase in muscle tone. This may or may not be preceded by a brief period of wakefulness. When Propofol injectable emulsion is administered to an epileptic patient, there is a risk of seizure during the recovery phase. Attention should be paid to minimize pain on administration of Propofol injectable emulsion. Transient local pain can be minimized if the larger veins of the forearm or antecubital fosse are used. Pain during Intravenous injection may also be reduced by prior injection of IV lidocaine (1 mL of a 1% solution). Pain on injection occurred frequently in pediatric patients (45%) when a small vein of the hand was utilized without lidocaine pretreatment. With lidocaine pretreatment or when antecubital veins were utilized, pain was minimal (Incidence less than 10%) and well tolerated. It is recommended that lidocaine be administered prior to Propofol administration or that it be added to Propofol immediately before administration and in quantities not exceeding 20 mg lidocaine/ 200 mg Propofol.
Intensive Care Unit Sedation: Adult Patients: The administration of Propofol injectable emulsion should be initiated as continuous infusion and changes in the rate of administration made slowly (>5 min) in order to minimize hypotension and avoid acute over dosage. Patients should be monitored for early signs of significant hypotension and/or cardiovascular depression, which may be profound. These effects are responsive to discontinuation of Propofol injectable emulsion, IV fluid administration, and/or vasopressor therapy. In the elderly, debilitated, or ASA-PS III or IV patients, rapid (single or repeated) bolus administration should not be used during sedation in order to minimize undesirable cardio respiratory depression, including hypotension, apnea. airway obstruction. and oxygen desaturation.
As with other sedative medications, there is wide interpatient variability in Propofol injectable emulsion dosage requirements, and these requirements may change with time. Failure to reduce the infusion rate in patients receiving Propofol injectable emulsion for extended periods may result in excessively high blood concentrations of the drug. Thus, titration to clinical response and daily evaluation of sedation levels are important during use of Propofol injectable emulsion infusion for ICU sedation. especially when It Is used for long durations. Opioids and paralytic agents should be discontinued and respiratory function optimized prior to weaning patients from mechanical ventilation.
Emulsion should be adjusted to maintain a light level of sedation prior to weaning patients from mechanical ventilatory support. Throughout the weaning process. this level of sedation may be maintained in the absence of respiratory depression. Because of the rapid clearance of Propofol injectable emulsion, abrupt discontinuation of a patient's infusion may result in rapid awakening with associated anxiety, agitation, and resistance to mechanical ventilation, making weaning from mechanical ventilation difficult. It is therefore recommended that administration of Propofol injectable emulsion be continued in order to maintain a light level of sedation throughout the weaning process until 10-15 minutes prior to extubation, at which time the infusion can be discontinued. The long-term administration of Propofol injectable emulsion to patients with renal failure and/or hepatic insufficiency has not been evaluated.
Neurosurgical Anesthesia: When Propofol injectable emulsion is used in patients with increased intracranial pressure or Impaired cerebral circulation, significant decreases in mean arterial pressure should be avoided because of the resultant decreases in cerebral perfusion pressure. To avoid significant hypotension and decreases in cerebral perfusion pressure, an infusion or slow bolus of approximately 20 mg every 10 seconds should be utilized instead of rapid, more frequent, and/or larger boluses of Propofol injectable emulsion.
Cardiac Anesthesia: Slower rates of administration should be utilized in premeditated patients, geriatric patients, patients with recent fluid shifts, and patients who are hemodynamically unstable. Fluid deficits should be corrected prior to administration of Propofol injectable emulsion. In those patients whore additional fluid therapy may be contraindicated. other measures. e.g., elevation of lower extremities, or use of pressor agents. may be useful to offset the hypotension which is associated with the induction of anesthesia with Propofol injectable emulsion.
Carcinogenesis, mutagenesis, impairment of fertility: Long term studies in animals have not been performed to evaluate the carcinogenic. Mutagenic impairment of fertility potential of Propofol.
Use in Pregnancy & Lactation: Teratogenic Effects: Pregnancy Category B. There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human responses. this drug should be used during pregnancy only if clearly needed.
Propofol injectable emulsion 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.
Use in Elderly: A lower induction dose and a slower maintenance rate of administration of Propofol injectable emulsion should be used in elderly patients.
Use In Pregnancy & Lactation
Pregnancy: Teratogenic effects: Pregnancy Category B. There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human responses. this drug should be used during pregnancy only if clearly needed.
Labor and Delivery: Propofol injectable emulsion is not recommended for obstetrics, including caesarean 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.
Lactation: Propofol injectable emulsion 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.
Adverse Reactions
Adverse event information is derived from controlled clinical trials and worldwide marketing experience of Propofol. The following estimates of adverse events for Propofol injectable emulsion include data from clinical trials in general anesthesia/MAC sedation. (See Table 3).

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Drug Abuse and Dependence: Rare cases of self-administration of Propofol Injectable emulsion by health care professionals have been reported, including some fatalities. Propofol injectable emulsion should be managed to prevent the risk of diversion, including restriction of access and accounting procedures as appropriate to the clinical setting.
Drug Interactions
The induction dose requirements of Propofol injectable emulsion may be reduced in patients with intramuscular or intravenous premedication, particularly with narcotics (e.g., morphine, meperidine and fentanyl, etc.) and combinations of opioids and sedatives (e.g. benzodiazepines, barbiturates, chloral hydrate, droperidol etc). These agents may increase the anesthetic or sedative effects of Propofol injectable emulsion and may also result in more pronounced decreases in systolic, diastolic, and mean arterial pressures and cardiac output.
During maintenance of anesthesia or sedation, the rate of Propofol injectable emulsion administration should be adjusted according to the desired level of anesthesia or sedation and may be reduced in the presence of supplemental analgesic agents (e.g., nitrous oxide or opioids). The concurrent administration of potent inhalational agents (e.g. isoflurane, enflurane, and halothane) during maintenance with Propofol injectable emulsion has not been extensively evaluated. These inhalational agents can also be expected to increase the anesthetic or sedative and cardiorespiratory effects of Propofol injectable emulsion.
Propofol injectable emulsion does not cause a clinically significant change in onset, intensity or duration of action of the commonly used neuromuscular blocking agents (e.g., succinylcholine and nondepolarizing muscle relaxants). No significant adverse interactions with commonly used premedication or drugs used during anesthesia or sedation (including a range of muscle relaxants, observed in adults. In pediatric patients, administration of fentanyl concomitantly with prenatal injectable emulsion may result in serious bradycardia.
Storage
Store at temperatures not exceeding 30°C.
Diluted Solution: Stored at temperatures 2°C-8°C.
Shelf-Life: 24 months.
Diluted Solution: Not more than 12 hours.
ATC Classification
N01AX10 - propofol ; Belongs to the class of other general anesthetics.
Presentation/Packing
Emulsion for inj (vial) 10 mg/mL x 10 mL x 1's, 20 mL x 1's.
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