Propofol

What it is used for

DIPRIVAN is an intravenous general anesthetic and sedation drug indicated for:

• Induction of General Anesthesia for Patients Greater than or Equal to 3 Years of Age
• Maintenance of General Anesthesia for Patients Greater than or Equal to 2 Months of Age
• Initiation and Maintenance of Monitored Anesthesia Care (MAC) Sedation in Adult Patients
• Sedation for Adult Patients in Combination with Regional Anesthesia
• Intensive Care Unit (ICU) Sedation of Intubated, Mechanically Ventilated Adult Patients

Limitations of Use

DIPRIVAN 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.

Safety, effectiveness and dosing guidelines for DIPRIVAN have not been established for MAC sedation in the pediatric population; therefore, it is not recommended for this use.

DIPRIVAN is not indicated for use in Pediatric ICU sedation since the safety of this regimen has not been established.

Side effects, and when to stop

The following serious or otherwise important adverse reactions are discussed elsewhere in the labeling:

• Hypersensitivity reaction
• Hypotension and/or bradycardia
• Propofol Infusion Syndrome

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.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Anesthesia and MAC Sedation in Adults

The following estimates of adverse events for DIPRIVAN include data from clinical trials in general anesthesia/MAC sedation (N=2889 adult patients). The adverse events listed below as probably causally related are those events in which the actual incidence rate in patients treated with DIPRIVAN was greater than the comparator incidence rate in these trials. Therefore, incidence rates for anesthesia and MAC sedation in adults generally represent estimates of the percentage of clinical trial patients which appeared to have probable causal relationship.

The adverse experience profile from reports of 150 patients in the MAC sedation clinical trials is similar to the profile established with DIPRIVAN during anesthesia (see Table 3 below). During MAC sedation clinical trials, significant respiratory events included cough, upper airway obstruction, apnea, hypoventilation, and dyspnea.

Anesthesia in Pediatric Patients

Generally, the adverse experience profile from reports of 506 DIPRIVAN pediatric patients from 6 days through 16 years of age in the US/Canadian anesthesia clinical trials is similar to the profile established with DIPRIVAN during anesthesia in adults. 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.

Postmarketing Experience

During the post-marketing period, there have been rare reports of local pain, swelling, blisters, and/or tissue necrosis following accidental extravasation of DIPRIVAN.

Venous sequelae, i.e., phlebitis or thrombosis, have been reported rarely (<1%).

Who should not take it

DIPRIVAN is contraindicated in patients with a known hypersensitivity to propofol or any of DIPRIVAN components.

DIPRIVAN is contraindicated in patients with a history of anaphylaxis to eggs, egg products, soybeans or soy products.

Other medicines and interactions

Opioids and Sedatives

The induction dose requirements of DIPRIVAN may be reduced in patients with intramuscular or intravenous premedication, particularly with opioids (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 and may also result in more pronounced decreases in systolic, diastolic, and mean arterial pressures and cardiac output.

In pediatric patients, administration of fentanyl concomitantly with DIPRIVAN may result in serious bradycardia.

Analgesic Agents

During maintenance of anesthesia or sedation, the rate of DIPRIVAN 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, sevoflurane, desflurane, enflurane, and halothane) during maintenance with DIPRIVAN are routinely used. These inhalational agents can also be expected to increase the anesthetic or sedative and cardiorespiratory effects of DIPRIVAN.

Valproate

The concomitant use of valproate and propofol may lead to increased blood levels of propofol. Reduce the dose of propofol when co-administering with valproate. Monitor patients closely for signs of increased sedation or cardiorespiratory depression.

Common Neuromuscular Blocking Agents

DIPRIVAN 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).

Common Drugs Used as Premedication or Drugs Used During Anesthesia or Sedation

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.