For intravenous administration

Yüklə 325,95 Kb.

Pdf görüntüsü

səhifə	2/5
tarix	18.04.2017
ölçüsü	325,95 Kb.
	#14567

1 2 3 4 5

Cardiac Anesthesia

DIPRIVAN Injectable Emulsion was evaluated in clinical trials involving patients undergoing

coronary artery bypass graft (CABG).

In post-CABG (coronary artery bypass graft) patients, the maintenance rate of

propofol administration was usually low (median 11 mcg/kg/min) due to the intraoperative

administration of high opioid doses. Patients receiving DIPRIVAN Injectable Emulsion

required 35% less nitroprusside than midazolam patients. During initiation of sedation in

post-CABG patients, a 15% to 20% decrease in blood pressure was seen in the first 60

Reference ID: 3520825

minutes. It was not possible to determine cardiovascular effects in patients with severely

compromised ventricular function.

3

INDICATIONS AND USAGE:

DIPRIVAN Injectable Emulsion is an IV sedative-hypnotic agent that can be used as

described in the table below.

7

Table 3. Indications for DIPRIVAN Injectable Emulsion

Indication Approved

Patient

Population

Initiation and maintenance of Monitored

Anesthesia Care (MAC) sedation

Adults only

Combined sedation and regional anesthesia Adults

only

(see

PRECAUTIONS)

Induction of General Anesthesia

Patients ≥ 3 years of age

Maintenance of General Anesthesia

Patients ≥ 2 months of age

Intensive Care Unit (ICU) sedation of intubated,

mechanically ventilated patients

Adults only

9

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 PRECAUTIONS,_Pediatric_Use'>PRECAUTIONS, Pediatric Use).

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.

Reference ID: 3520825

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

3

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 PRECAUTIONS).

DIPRIVAN Injectable Emulsion is not recommended for use in nursing mothers

because propofol 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).

11

CONTRAINDICATIONS:

DIPRIVAN Injectable Emulsion is contraindicated in patients with a known hypersensitivity

to propofol or any of DIPRIVAN Injectable Emulsion components.

DIPRIVAN Injectable Emulsion is contraindicated in patients with allergies to eggs,

egg products, soybeans or soy products.

WARNINGS:

Use of DIPRIVAN Injectable Emulsion has been associated with both fatal and life

threatening anaphylactic and anaphylactoid reactions.

For general anesthesia or monitored anesthesia care (MAC) sedation, DIPRIVAN

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

Reference ID: 3520825

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), DIPRIVAN 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 DIPRIVAN 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,

lipemia, rhabdomyolysis, hepatomegaly, renal failure, ECG changes* 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 (> 5 mg/kg/h for >

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.

*Coved ST segment elevation (similar to ECG changes of the Brugada syndrome).

Reference ID: 3520825

Abrupt discontinuation of DIPRIVAN 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

DIPRIVAN Injectable Emulsion should be adjusted to maintain a light level of sedation

through the weaning process or evaluation of sedation level (see PRECAUTIONS).

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 not known.

11

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 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. DIPRIVAN Injectable Emulsion vial is never to be accessed more than once or

used on more than one person.

Reference ID: 3520825

1

PRECAUTIONS:

2

General

3

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 (see DOSAGE AND

6

ADMINISTRATION). 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

Reference ID: 3520825

literature indicating that the addition of lidocaine to DIPRIVAN Injectable Emulsion in

quantities greater than 20 mg lidocaine/200 mg DIPRIVAN Injectable Emulsion 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 Injectable Emulsion administration or that it be added to

DIPRIVAN Injectable Emulsion 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 Injectable Emulsion.

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 unknown.

Reference ID: 3520825

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.

11

Intensive Care Unit Sedation

Adult Patients

(See WARNINGS and DOSAGE AND ADMINISTRATION, Handling Procedures.) The

administration of DIPRIVAN Injectable Emulsion should be initiated as a continuous infusion

and changes in the rate of administration made slowly (>5 min) in order to minimize

hypotension and avoid acute overdosage (see DOSAGE AND ADMINISTRATION).

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 desaturation.

Reference ID: 3520825

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 long durations.

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 to 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

Reference ID: 3520825

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 mg/day in adult

patients and 1.5 to 2 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 to 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.

Reference ID: 3520825

1

Neurosurgical Anesthesia

When DIPRIVAN 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 DIPRIVAN Injectable Emulsion. Slower induction, titrated

to clinical responses, will generally result in reduced induction dosage requirements (1 to

2 mg/kg). When increased ICP is suspected, hyperventilation and hypocarbia should

accompany the administration of DIPRIVAN Injectable Emulsion (see DOSAGE AND

11

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 with DIPRIVAN Injectable

Emulsion.

Information for Patients

Patients should be advised that performance of activities requiring mental alertness, such as

operating a motor vehicle, or hazardous machinery or signing legal documents may be

impaired for some time after general anesthesia or sedation.

Reference ID: 3520825

1

Drug Interactions

The induction dose requirements of DIPRIVAN 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 DIPRIVAN 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 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

Reference ID: 3520825

patients, administration of fentanyl concomitantly with DIPRIVAN Injectable Emulsion may

result in serious bradycardia.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Yüklə 325,95 Kb.

Dostları ilə paylaş:

1 2 3 4 5