DIPRIVAN

What it is

DIPRIVAN is a short-acting general anaesthetic agent with a rapid onset of action of approximately 30 seconds. It is a sterile, milky white, isotonic, oil in water emulsion for intravenous infusion or injection containing 10 mg propofol per 1 mL (1% strength) or 20 mg propofol per 1 mL (2% strength). DIPRIVAN produces its sedative and anaesthetic effects principally by positive modulation of the inhibitory function of the neurotransmitter GABA through GABAA receptors.

Approved indications

— Induction of general anaesthesia in adults and children aged one month and older — Maintenance of general anaesthesia in adults and children aged 3 years and older — Maintenance of general anaesthesia in children aged from one month to 3 years for procedures not exceeding 60 minutes, unless alternative anaesthetic agents should be avoided — Sedation of ventilated patients receiving intensive care in patients over 16 years — Monitored conscious sedation for surgical and diagnostic procedures in adults

Dosing overview

For induction of general anaesthesia in unpremedicated and premedicated patients, propofol should be titrated at 20–40 mg every 10 seconds against patient response. Most adult patients less than 55 years require 1.5 to 2.5 mg of propofol per kg body weight. For maintenance by continuous infusion, rates usually in the region of 0.067 to 0.2 mg/kg per minute (4 to 12 mg/kg per hour) maintain satisfactory anaesthesia. If repeat bolus injections are used, increments of 25 to 50 mg may be given according to clinical need. For sedation during intensive care in ventilated adult patients, usually satisfactory sedation is achieved with dosages in the range of 0.3–4.0 mg of propofol per kg body weight per hour. For conscious sedation during surgical and diagnostic procedures, most patients require 0.5–1 mg per kg body weight over 1 to 5 minutes for onset, with maintenance accomplished by titrating infusion to achieve 1.5–4.5 mg per kg body weight per hour.

Key safety warnings

The most commonly observed adverse effects of DIPRIVAN are hypotension and respiratory depression. These effects depend on the propofol dose administered but also on the type of premedication and other concomitant medication. During induction in clinical trials, hypotension and transient apnoea occurred in up to 75% of patients. When DIPRIVAN is used for sedation during intensive care, life-threatening adverse events known as Propofol Infusion Syndrome (PRIS) can occur, including cardiac failure, arrhythmias, metabolic acidosis, rhabdomyolysis, and renal failure. Very rare reports of PRIS in adults treated for more than 48 hours with propofol infusions in excess of 5 mg/kg per hour have been received. The maximum dose of propofol for adult sedation during intensive care should not exceed 4.0 mg/kg per hour. Elevations in serum triglycerides may occur when DIPRIVAN is administered for extended periods of time because it is formulated in an oil-in-water emulsion. Patients at risk of hyperlipidaemia should be monitored for increases in serum triglycerides or serum turbidity, and dosage and infusion rate should be within the ranges recommended. During induction of anaesthesia, hypotension and apnoea commonly occur and may be influenced by the rate of administration and the use of premedicants and other agents, including benzodiazepines. DIPRIVAN lacks vagolytic activity and has been associated with reports of bradycardia (occasionally profound) and asystole. The intravenous administration of an anticholinergic agent before induction or during maintenance of anaesthesia should be considered.

Contraindications

DIPRIVAN is contraindicated in patients with known hypersensitivity to propofol or any of its ingredients (soya oil, medium chain triglycerides, glycerol, egg lecithin, and sodium oleate), and in patients who are allergic to soya or peanut. It is contraindicated for induction and maintenance of general anaesthesia in children younger than 1 month. DIPRIVAN is contraindicated in patients of 16 years of age or younger for sedation during intensive care and for monitored conscious sedation for surgical and diagnostic procedures.

Regulatory history

DIPRIVAN propofol 500 mg/50 mL injection vial and syringe were first listed on the Australian Register of Therapeutic Goods on 13 December 2000, followed by the 1 g/100 mL injection vial on the same date and the 200 mg/20 mL injection vial on 9 February 2001.