Propofol: Package Insert and Label Information (Page 4 of 6)

Anesthesia in Pediatric Patients

Generally the adverse experience profile from reports of 506 Propofol Injectable Emulsion pediatric patients from 6 days through 16 years of age in the U.S./Canadian anesthesia clinical trials is similar to the profile established with Propofol Injectable Emulsion during anesthesia in adults (see Pediatric percentages [Peds %] below). Although not reported as an adverse event in clinical trials, apnea is frequently observed in pediatric patients.

ICU Sedation in Adults

The following estimates of adverse events include data from clinical trials in ICU sedation (N = 159 adult patients). Probably related incidence rates for ICU sedation were determined by individual case report form review. Probable causality was based upon an apparent dose response relationship and/or positive responses to rechallenge. In many instances the presence of concomitant disease and concomitant therapy made the causal relationship unknown. Therefore, incidence rates for ICU sedation generally represent estimates of the percentage of clinical trial patients which appeared to have a probable causal relationship.

Incidence greater than 1% — Probably Causally Related

Anesthesia/MAC Sedation

ICU Sedation

Cardiovascular:

Bradycardia

Bradycardia

Arrhythmia [Peds: 1.2%]

Tachycardia Nodal [Peds: 1.6%]

Hypotension* [Peds: 17%]

(see also CLINICAL PHARMACOLOGY)

Decreased Cardiac Output

Hypertension [Peds: 8%]

Hypotension 26%

Central Nervous System:

Movement* [Peds: 17%]

Injection Site:

Burning/Stinging or Pain,

17.6% [Peds: 10%]

Metabolic/Nutritional:

Hyperlipemia*

Respiratory:

Apnea

(see also CLINICAL PHARMACOLOGY)

Respiratory Acidosis During

Weaning*

Skin and Appendages:

Rash [Peds: 5%]

Pruritus [Peds: 2%]

Events without an * or % had an incidence of 1% to 3%

*Incidence of events 3% to 10%

Incidence less than 1% — Probably Causally Related

Anesthesia/MAC Sedation

ICU Sedation

Body as a Whole:

Anaphylaxis/Anaphylactoid Reaction

Perinatal Disorder

Tachycardia

Bigeminy

Bradycardia

Premature Ventricular Contractions

Hemorrhage

ECG Abnormal

Arrhythmia Atrial

Fever

Extremities Pain

Anticholinergic Syndrome

Cardiovascular:

Premature Atrial Contractions

Syncope

Central Nervous System:

Hypertonia/Dystonia, Paresthesia

Agitation

Digestive:

Hypersalivation

Nausea

Hemic/Lymphatic:

Leukocytosis

Injection Site:

Phlebitis

Pruritus

Metabolic:

Hypomagnesemia

Musculoskeletal:

Myalgia

Nervous:

Dizziness

Agitation

Chills

Somnolence

Delirium

Respiratory:

Wheezing

Cough

Laryngospasm

Hypoxia

Decreased Lung Function

Skin and Appendages:

Flushing, Pruritus

Special Senses:

Amblyopia

Vision Abnormal

Urogenital:

Cloudy Urine

Green Urine

Incidence less than 1% — Causal Relationship Unknown

Anesthesia/MAC Sedation

ICU Sedation

Body as a Whole:

Asthenia, Awareness, Chest Pain, Extremities Pain, Fever, Increased Drug Effect, Neck Rigidity/Stiffness, Trunk Pain

Fever, Sepsis, Trunk Pain, Whole Body Weakness

Cardiovascular:

Arrhythmia, Atrial Fibrillation, Atrioventricular Heart Block, Bigeminy, Bleeding, Bundle Branch Block, Cardiac Arrest, ECG Abnormal, Edema, Extrasystole, Heart Block, Hypertension, Myocardial Infarction, Myocardial Ischemia, Premature Ventricular Contractions, ST Segment Depression, Supraventricular Tachycardia, Tachycardia, Ventricular Fibrillation

Arrhythmia, Atrial Fibrillation, Bigeminy, Cardiac Arrest, Extrasystole, Right Heart Failure, Ventricular Tachycardia

Central Nervous System:

Abnormal Dreams, Agitation, Amorous Behavior, Anxiety, Bucking/Jerking/Thrashing, Chills/Shivering/Clonic/Myoclonic Movement, Combativeness, Confusion, Delirium, Depression, Dizziness, Emotional Lability, Euphoria, Fatigue, Hallucinations, Headache, Hypotonia, Hysteria, Insomnia, Moaning, Neuropathy, Opisthotonos, Rigidity, Seizures, Somnolence, Tremor, Twitching

Chills/Shivering, Intracranial Hypertension, Seizures, Somnolence, Thinking Abnormal

Digestive:

Cramping, Diarrhea, Dry Mouth, Enlarged Parotid, Nausea, Swallowing, Vomiting

Ileus, Liver Function Abnormal

Hematologic/Lymphatic:

Coagulation Disorder, Leukocytosis

Injection Site:

Hives/Itching, Phlebitis, Redness/Discoloration

Metabolic/Nutritional:

Hyperkalemia, Hyperlipemia

BUN Increased, Creatinine Increased, Dehydration, Hyperglycemia, Metabolic Acidosis, Osmolality Increased

Respiratory:

Bronchospasm, Burning in Throat, Cough, Dyspnea, Hiccough, Hyperventilation, Hypoventilation, Hypoxia, Laryngospasm, Pharyngitis, Sneezing, Tachypnea, Upper Airway Obstruction

Hypoxia

Skin and Appendages:

Conjunctival Hyperemia, Diaphoresis, Urticaria

Rash

Special Senses:

Diplopia, Ear Pain, Eye Pain, Nystagmus, Taste Perversion, Tinnitus

Urogenital:

Oliguria, Urine Retention

Kidney Failure

DRUG ABUSE AND DEPENDENCE

There are reports of the abuse of propofol for recreational and other improper purposes, which have resulted in fatalities and other injuries. Instances of self-administration of Propofol Injectable Emulsion by health care professionals have also been reported, which have resulted in fatalities and other injuries. Inventories of Propofol Injectable Emulsion should be stored and managed to prevent the risk of diversion, including restriction of access and accounting procedures as appropriate to the clinical setting.

OVERDOSAGE

If overdosage occurs, Propofol 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.

DOSAGE AND ADMINISTRATION

Propofol blood concentrations at steady-state are generally proportional to infusion rates, especially in individual patients. Undesirable effects such as cardiorespiratory 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 minutes to 5 minutes) must be allowed between dose adjustments to allow for and assess the clinical effects.

Shake well before use. Do not use if there is evidence of excessive creaming or aggregation, if large droplets are visible, or if there are other forms of phase separation indicating that the stability of the product has been compromised. Slight creaming, which should disappear after shaking, may be visible upon prolonged standing.

When administering Propofol Injectable Emulsion by infusion, syringe or volumetric pumps are recommended to provide controlled infusion rates. When infusing Propofol Injectable Emulsion to patients undergoing magnetic resonance imaging, metered control devices may be utilized if mechanical pumps are impractical.

Changes in vital signs indicating a stress response to surgical stimulation or the emergence from anesthesia may be controlled by the administration of 25 mg (2.5 mL) to 50 mg (5 mL) incremental boluses and/or by increasing the infusion rate of Propofol Injectable Emulsion.

For minor surgical procedures (e.g., body surface) nitrous oxide (60% to 70%) can be combined with a variable rate Propofol Injectable Emulsion infusion to provide satisfactory anesthesia. With more stimulating surgical procedures (e.g., intra-abdominal), or if supplementation with nitrous oxide is not provided, administration rate(s) of Propofol Injectable Emulsion and/or opioids should be increased in order to provide adequate anesthesia.

Infusion rates should always be titrated downward in the absence of clinical signs of light anesthesia until a mild response to surgical stimulation is obtained in order to avoid administration of Propofol Injectable Emulsion at rates higher than are clinically necessary. Generally, rates of 50 mcg/kg/min to 100 mcg/kg/min in adults should be achieved during maintenance in order to optimize recovery times.

Other drugs that cause CNS depression (e.g., sedatives, anesthetics, and opioids) can increase CNS depression induced by propofol. Morphine premedication (0.15 mg/kg) with nitrous oxide 67% in oxygen has been shown to decrease the necessary propofol injection maintenance infusion rate and therapeutic blood concentrations when compared to non-narcotic (lorazepam) premedication.

Induction of General Anesthesia

Adult Patients

Most adult patients under 55 years of age and classified as ASA-PS I or II require 2 mg/kg to 2.5 mg/kg of Propofol Injectable Emulsion for induction when unpremedicated or when premedicated with oral benzodiazepines or intramuscular opioids. For induction, Propofol Injectable Emulsion should be titrated (approximately 40 mg every 10 seconds) against the response of the patient until the clinical signs show the onset of anesthesia. As with other general anesthetics, the amount of intravenous opioid and/or benzodiazepine premedication will influence the response of the patient to an induction dose of Propofol Injectable Emulsion.

Elderly, Debilitated, or ASA-PS III or IV Patients

It is important to be familiar and experienced with the intravenous use of Propofol Injectable Emulsion before treating elderly, debilitated, or ASA-PS III or IV patients. Due to the reduced clearance and higher blood concentrations, most of these patients require approximately 1 mg/kg to 1.5 mg/kg (approximately 20 mg every 10 seconds) of Propofol Injectable Emulsion for induction of anesthesia according to their condition and responses. A rapid bolus should not be used, as this will increase the likelihood of undesirable cardiorespiratory depression including hypotension, apnea, airway obstruction, and/or oxygen desaturation (see DOSAGE AND ADMINISTRATION).

Pediatric Patients

Most patients aged 3 years through 16 years and classified ASA-PS I or II require 2.5 mg/kg to 3.5 mg/kg of Propofol Injectable Emulsion for induction when unpremedicated or when lightly premedicated with oral benzodiazepines or intramuscular opioids. Within this dosage range, younger pediatric patients may require higher induction doses than older pediatric patients. As with other general anesthetics, the amount of intravenous opioid and/or benzodiazepine premedication will influence the response of the patient to an induction dose of Propofol Injectable Emulsion. A lower dosage is recommended for pediatric patients classified as ASA-PS III or IV. Attention should be paid to minimize pain on injection when administering Propofol Injectable Emulsion to pediatric patients. Boluses of Propofol Injectable Emulsion may be administered via small veins if pretreated with lidocaine or via antecubital or larger veins (see PRECAUTIONS, General).

Neurosurgical Patients

Slower induction is recommended using boluses of 20 mg every 10 seconds. Slower boluses or infusions of Propofol Injectable Emulsion for induction of anesthesia, titrated to clinical responses, will generally result in reduced induction dosage requirements (1 mg/kg to 2 mg/kg) (see PRECAUTIONS and DOSAGE AND ADMINISTRATION).

Cardiac Anesthesia

Propofol Injectable Emulsion has been well-studied in patients with coronary artery disease, but experience in patients with hemodynamically significant valvular or congenital heart disease is limited. As with other general anesthetics and sedation drugs, Propofol Injectable Emulsion in healthy patients causes a decrease in blood pressure that is secondary to decreases in preload (ventricular filling volume at the end of the diastole) and afterload (arterial resistance at the beginning of the systole). The magnitude of these changes is proportional to the blood and effect site concentrations achieved. These concentrations depend upon the dose and speed of the induction and maintenance infusion rates.

In addition, lower heart rates are observed during maintenance with Propofol Injectable Emulsion, possibly due to reduction of the sympathetic activity and/or resetting of the baroreceptor reflexes. Therefore, anticholinergic agents should be administered when increases in vagal tone are anticipated.

As with other anesthetic agents, Propofol Injectable Emulsion reduces myocardial oxygen consumption. Further studies are needed to confirm and delineate the extent of these effects on the myocardium and the coronary vascular system.

Morphine premedication (0.15 mg/kg) with nitrous oxide 67% in oxygen has been shown to decrease the necessary Propofol Injectable Emulsion maintenance infusion rates and therapeutic blood concentrations when compared to non-narcotic (lorazepam) premedication. The rate of Propofol Injectable Emulsion administration should be determined based on the patient’s premedication and adjusted according to clinical responses.

A rapid bolus induction should be avoided. A slow rate of approximately 20 mg every 10 seconds until induction onset (0.5 mg/kg to 1.5 mg/kg) should be used. In order to assure adequate anesthesia, when Propofol Injectable Emulsion is used as the primary agent, maintenance infusion rates should not be less than 100 mcg/kg/min and should be supplemented with analgesic levels of continuous opioid administration. When an opioid is used as the primary agent, Propofol Injectable Emulsion maintenance rates should not be less than 50 mcg/kg/min, and care should be taken to ensure amnesia. Higher doses of Propofol Injectable Emulsion will reduce the opioid requirements (see Table 4). When Propofol Injectable Emulsion is used as the primary anesthetic, it should not be administered with the high-dose opioid technique as this may increase the likelihood of hypotension (see PRECAUTIONS, Cardiac Anesthesia).

Table 4. Cardiac Anesthesia Techniques

Primary Agent

Rate

Secondary Agent/Rate

(Following Induction with Primary Agent)

Propofol Injectable Emulsion

OPIOIDa /0.05 mcg/kg/min to 0.075 mcg/kg/min (no bolus)

Preinduction

Anxiolysis

25 mcg/kg/min

Induction

0.5 mcg/kg to 1.5 mg/kg

over 60 sec

Maintenance

(Titrated to Clinical Response)

100 mcg/kg/min to

150 mcg/kg/min

OPIOIDb

Propofol Injectable Emulsion /50 mcg/kg/min to 100 mcg/kg/min (no bolus)

Induction

25 mcg/kg to 50 mcg/kg

Maintenance

0.2 mcg/kg/min to

0.3 mcg/kg/min

a OPIOID is defined in terms of fentanyl equivalents, i.e.,

1 mcg of fentanyl

=

5 mcg of alfentanil (for bolus)

=

10 mcg of alfentanil (for maintenance)

or

=

0.1 mcg of sufentanil

b Care should be taken to ensure amnesia.

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