Initiation and maintenance of Monitored
Anesthesia Care (MAC) sedation
Combined sedation and regional anesthesia
Induction of General Anesthesia
Mainenance of General Anesthesia
Intensive Care Unit (ICU) sedation of intubated,
mechanically ventilated patients
Adults only (See
Patients ≥ 3 years of age
Safety, effectiveness and dosing guidelines for DIPRIVAN Injectable Emulsion have not
been established for MAC Sedation in the pediatric population; therefore, it is not
recommended for this use. (See
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 the Intensive Care Unit (ICU), DIPRIVAN 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.
DIPRIVAN 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
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 Injectable Emulsion is contraindicated in patients with a known hypersensitivity
to DIPRIVAN Injectable Emulsion or any of its components.
DIPRIVAN Injectable Emulsion is contraindicated in patients with allergies to eggs, egg
products, soybeans or soy products.
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),
DIPRIVAN Injectable Emulsion should be administered only by persons skilled in the
management of critically ill patients and trained in cardiovascular resuscitation and airway
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.
DIPRIVAN Injectable Emulsion should not be coadministered 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
There have been reports in which failure to use aseptic technique when handling
Diprivan 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 (see
DOSAGE AND ADMINISTRATION, Handling Procedures
) 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. DIPRIVAN Injectable Emulsion
use requires caution when administered to patients with disorders of lipid metabolism such as
primary hyperlipoproteinemia, diabetic hyperlipemia, and pancreatitis.
Very rarely the use of DIPRIVAN 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.
Recovery is spontaneous.
When DIPRIVAN 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 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. There have been reports in the
literature indicating that the addition of lidocaine to DIPRIVAN in quantities greater than 20
mg lidocaine/200 mg DIPRIVAN results in instability of the emulsion which is associated
with increases in globule sizes over time and (in rat studies) a reduction in anesthetic
potency. Therefore, it is recommended that lidocaine be administered prior to DIPRIVAN
administration or that it be added to DIPRIVAN immediately before administration and in
quantities not exceeding 20 mg lidocaine/200 mg DIPRIVAN.
Venous sequelae, i.e., phlebitis or thrombosis, have been reported rarely (<1%). In two
clinical studies using dedicated intravenous catheters, no instances of venous sequelae were
observed up to 14 days following induction.
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
Perioperative myoclonia, rarely including convulsions and opisthotonos, has occurred in
association with DIPRIVAN Injectable Emulsion administration.
Clinical features of anaphylaxis, including 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
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.
Adult Patients: (See
continuous infusion and changes in the rate of administration made slowly (>5 min) in order
to minimize hypotension and avoid acute overdosage. (See
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
DIPRIVAN 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
cardiorespiratory depression, including hypotension, apnea, airway obstruction, and oxygen
As with other sedative medications, there is wide interpatient variability in DIPRIVAN
Injectable Emulsion dosage requirements, and these requirements may change with time.
Failure to reduce the infusion rate in patients receiving DIPRIVAN 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 DIPRIVAN Injectable Emulsion infusion for ICU sedation, especially when it is used for
Opioids and paralytic agents should be discontinued and respiratory function optimized prior
to weaning patients from mechanical ventilation. Infusions of DIPRIVAN Injectable
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 DIPRIVAN 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 DIPRIVAN 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.
Since DIPRIVAN Injectable Emulsion is formulated in an oil-in-water emulsion, elevations
in serum triglycerides may occur when DIPRIVAN Injectable Emulsion is administered for
extended periods of time. Patients at risk of hyperlipidemia should be monitored for
increases in serum triglycerides or serum turbidity. Administration of DIPRIVAN Injectable
Emulsion should be adjusted if fat is being inadequately cleared from the body. A reduction
in the quantity of concurrently administered lipids is indicated to compensate for the amount
of lipid infused as part of the DIPRIVAN Injectable Emulsion formulation; 1 mL of
DIPRIVAN Injectable Emulsion contains approximately 0.1 g of fat (1.1 kcal).
EDTA is a strong chelator of trace metals -- including zinc. Although with DIPRIVAN
Injectable Emulsion there are no reports of decreased zinc levels or zinc deficiency-related
adverse events, DIPRIVAN Injectable Emulsion should not be infused for longer than 5 days
without providing a drug holiday to safely replace estimated or measured urine zinc losses.
In clinical trials mean urinary zinc loss was approximately 2.5 to 3.0 mg/day in adult patients
and 1.5 to 2.0 mg/day in pediatric patients.
In patients who are predisposed to zinc deficiency, such as those with burns, diarrhea, and/or
major sepsis, the need for supplemental zinc should be considered during prolonged therapy
with DIPRIVAN Injectable Emulsion.
At high doses (2-3 grams per day), EDTA has been reported, on rare occasions, to be toxic to
the renal tubules. Studies to date in patients with normal or impaired renal function have not
shown any alteration in renal function with DIPRIVAN Injectable Emulsion containing
0.005% disodium edetate. In patients at risk for renal impairment, urinalysis and urine
sediment should be checked before initiation of sedation and then be monitored on alternate
days during sedation.
The long-term administration of DIPRIVAN Injectable Emulsion to patients with renal
failure and/or hepatic insufficiency has not been evaluated.
Neurosurgical Anesthesia: When DIPRIVAN Injectable Emulsion is used in patients with
hypocarbia should accompany the administration of DIPRIVAN Injectable Emulsion. (See
DOSAGE AND ADMINISTRATION.
Cardiac Anesthesia: Slower rates of administration should be utilized in premedicated
patients, geriatric patients, patients with recent fluid shifts, and patients who are
hemodynamically unstable. Fluid deficits should be corrected prior to administration of
DIPRIVAN Injectable Emulsion. In those patients where 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
Information for Patients:
During maintenance of anesthesia or sedation, the rate of DIPRIVAN 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 DIPRIVAN Injectable Emulsion has not
been extensively evaluated. These inhalational agents can also be expected to increase the
anesthetic or sedative and cardiorespiratory effects of DIPRIVAN Injectable Emulsion.
DIPRIVAN 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 premedications or drugs used during
anesthesia or sedation (including a range of muscle relaxants, inhalational agents, analgesic
agents, and local anesthetic agents) have been observed in adults. In pediatric patients,
administration of fentanyl concomitantly with DIPRIVAN Injectable Emulsion may result in