Diprivan Information
Diprivan () Description
Diprivan () (propofol) 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 and has a molecular weight of 178.27. The structural and molecular formulas are:
Propofol is very slightly soluble in water and, thus, is formulated in a white, oil-in-water emulsion. The pKa is 11. The octanol/water partition coefficient for propofol is 6761:1 at a pH of 6-8.5. In addition to the active component, propofol, the formulation also contains soybean oil (100 mg/mL), glycerol (22.5 mg/mL), egg lecithin (12 mg/mL), and disodium edetate (0.005%); with sodium hydroxide to adjust pH. The Diprivan () Injectable Emulsion is isotonic and has a pH of 7-8.5.
Diprivan () Clinical Pharmacology
Diprivan () 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 produces hypnosis rapidly with minimal excitation, usually within 40 seconds from the start of an injection (the time for one arm-brain circulation). As with other rapidly acting intravenous anesthetic agents, the half-time of the blood-brain equilibration is approximately 1 to 3 minutes, and this accounts for the rapid induction of anesthesia.
Diprivan () Indications And Usage
Diprivan () Injectable Emulsion is an IV sedative-hypnotic agent that can be used for both induction and/or maintenance of anesthesia as part of a balanced anesthetic technique for inpatient and outpatient surgery in adult patients and pediatric patients greater than 3 years of age. Diprivan () Injectable Emulsion can also be used for maintenance of anesthesia as part of a balanced anesthetic technique for inpatient and outpatient surgery in adult patients and in pediatric patients greater than 2 months of age. Diprivan () 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 adult patients, Diprivan () Injectable Emulsion, when administered intravenously as directed, can be used to initiate and maintain monitored anesthesia care (MAC) sedation during diagnostic procedures. Diprivan () Injectable Emulsion may also be used for MAC sedation in conjunction with local/regional anesthesia in patients undergoing surgical procedures. (See .)
Safety, effectiveness and dosing guidelines for Diprivan () Injectable Emulsion have not been established for MAC Sedation/light general anesthesia in the pediatric population undergoing diagnostic or nonsurgical procedures and therefore it is not recommended for this use. (See , Pediatric Use).
Diprivan () Injectable Emulsion should only be administered to intubated, mechanically ventilated adult patients in the Intensive Care Unit (ICU) to provide continuous sedation and control of stress responses. In this setting, Diprivan () Injectable Emulsion should be administered only by persons skilled in the medical management of critically ill patients and trained in cardiovascular resuscitation and airway management.
Diprivan () Injectable Emulsion is not indicated for use in Pediatric ICU sedation since the safety of this regimen has not been established. (See , Pediatric Use).
Diprivan () Injectable Emulsion is not recommended for obstetrics, including cesarean section deliveries. Diprivan () Injectable Emulsion crosses the placenta, and as with other general anesthetic agents, the administration of Diprivan () Injectable Emulsion may be associated with neonatal depression. (See .)
Diprivan () Injectable Emulsion is not recommended for use in nursing mothers because Diprivan () 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 .)
Diprivan () Contraindications
Diprivan () Injectable Emulsion is contraindicated in patients with a known hypersensitivity to Diprivan () Injectable Emulsion or its components, or when general anesthesia or sedation are contraindicated.
Diprivan () Warnings
In the elderly, debilitated, or ASA III/IV patients, rapid (single or repeated) bolus administration should not be used during general anesthesia or MAC sedation in order to minimize undesirable cardiorespiratory depression, including hypotension, apnea, airway obstruction, and/or oxygen desaturation.
MAC sedation patients should be continuously monitored by persons not involved in the conduct of the surgical or diagnostic procedure; oxygen supplementation should be immediately available and provided where clinically indicated; and oxygen saturation should be monitored in all patients. 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 initiation (loading) boluses or during supplemental maintenance boluses, especially in the elderly, debilitated, or ASA III/IV patients.
Diprivan () Injectable Emulsion should not be coadministered through the same IV catheter with blood or plasma because compatibility has not been established. 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 is not known.
Diprivan () Precautions
Very rarely the use of Diprivan () 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. Recovery is spontaneous. The clinical criteria for discharge from the recovery/day surgery area established for each institution should be satisfied before discharge of the patient from the care of the anesthesiologist.
When Diprivan () Injectable Emulsion is administered to an epileptic patient, there may be a risk of seizure during the recovery phase.
Attention should be paid to minimize pain on administration of Diprivan () Injectable Emulsion. Transient local pain can be minimized if the larger veins of the forearm or antecubital fossa 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.
Venous sequelae (phlebitis or thrombosis) have been reported rarely (
Intra-arterial injection in animals did not induce local tissue effects. Accidental intra-arterial injection has been reported in patients, and, other than pain, there were no major sequelae.
Intentional injection into subcutaneous or perivascular tissues of animals caused minimal tissue reaction. During the post-marketing period, there have been rare reports of local pain, swelling, blisters, and/or tissue necrosis following accidental extravasation of Diprivan () Injectable Emulsion.
Perioperative myoclonia, rarely including convulsions and opisthotonos, has occurred in temporal relationship in cases in which Diprivan () Injectable Emulsion has been administered.
Clinical features of anaphylaxis, which may include angioedema, bronchospasm, erythema, and hypotension, occur rarely following Diprivan () Injectable Emulsion administration.
There have been rare reports of pulmonary edema in temporal relationship to the administration of Diprivan () Injectable Emulsion, although a causal relationship is unknown.
Very rarely, cases of unexplained postoperative pancreatitis (requiring hospital admission) have been reported after anesthesia in which Diprivan () Injectable Emulsion was one of the induction agents used. Due to a variety of confounding factors in these cases, including concomitant medications, a causal relationship to Diprivan () Injectable Emulsion is unclear.
Diprivan () Injectable Emulsion has no vagolytic activity. Reports of bradycardia, asystole, and rarely, cardiac arrest have been associated with Diprivan () Injectable Emulsion. Pediatric patients are susceptible to this effect, particularly when fentanyl is given concomitantly. The intravenous administration of anticholinergic agents (e.g., atropine or glycopyrrolate) should be considered to modify potential increases in vagal tone due to concomitant agents (e.g., succinylcholine) or surgical stimuli.
Diprivan () Adverse Reactions
Adverse event information is derived from controlled clinical trials and worldwide marketing experience. In the description below, rates of the more common events represent US/Canadian clinical study results. Less frequent events are also derived from publications and marketing experience in over 8 million patients; there are insufficient data to support an accurate estimate of their incidence rates. These studies were conducted using a variety of premedicants, varying lengths of surgical/diagnostic procedures, and various other anesthetic/sedative agents. Most adverse events were mild and transient.
Diprivan () Drug Abuse And Dependence
Rare cases of self-administration of Diprivan () Injectable Emulsion by health care professionals have been reported, including some fatalities. Diprivan () Injectable Emulsion should be managed to prevent the risk of diversion, including restriction of access and accounting procedures as appropriate to the clinical setting.
Diprivan () Overdosage
If overdosage occurs, Diprivan () Injectable Emulsion administration should be discontinued immediately. Overdosage is likely to cause cardiorespiratory depression. Respiratory depression should be treated by artificial ventilation with oxygen. Cardiovascular depression may require repositioning of the patient by raising the patient's legs, increasing the flow rate of intravenous fluids, and administering pressor agents and/or anticholinergic agents.
Diprivan () Dosage And Administration
Dosage and rate of administration should be individualized and titrated to the desired effect, according to clinically relevant factors, including preinduction and concomitant medications, age, ASA physical classification, and level of debilitation of the patient.
Diprivan () Summary Of Dosage Guidelines
Dosages and rates of administration in the following table should be individualized and titrated to clinical response. Safety and dosing requirements for 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.
For complete dosage information, see - Individualization of Dosage.
- 5% Dextrose Injection, USP
- Lactated Ringers Injection, USP
- Lactated Ringers and 5% Dextrose Injection
- 5% Dextrose and 0.45% Sodium Chloride Injection, USP
- 5% Dextrose and 0.2% Sodium Chloride Injection, USP
Diprivan () How Supplied
Diprivan () Injectable Emulsion is available in ready to use 20 mL infusion vials, 50 mL infusion vials, and 100 mL infusion vials containing 10mg/mL of propofol.
20 mL infusion vials (NDC 0310-0300-22)
50 mL infusion vials (NDC 0310-0300-50)
100 mL infusion vials (NDC 0310-0300-11)
Propofol undergoes oxidative degradation, in the presence of oxygen, and is therefore packaged under nitrogen to eliminate this degradation path.
Store between 4-22°C (40-72°F). Do not freeze. Shake well before use.
All trademarks are the property of the AstraZeneca group of companies
© AstraZeneca 2001, 2004, 2005
Manufactured for:
AstraZeneca Pharmaceuticals, LP
Wilmington, DE 19850
By: AstraZeneca S.p.A.,
Caponago, Italy
Made in Italy
Rev 08/05 SIC 30193-00
