PROVIVE

What it is

PROVIVE is a sterile, milky white, isotonic, oil-in-water emulsion for intravenous infusion or injection. Each millilitre contains 10 mg of propofol. The formulation contains soya oil, medium chain triglycerides, glycerol, egg lecithin, sodium hydroxide, oleic acid and water for injections. Propofol is a short-acting general anaesthetic agent with a rapid onset of action of approximately 30 seconds.

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 adults. — Monitored conscious sedation for surgical and diagnostic procedures in adults.

Dosing overview

**Induction of General Anaesthesia (Adults)** PROVIVE should be titrated (20 to 40 mg of propofol every 10 seconds) against the response of the patient until the clinical signs show the onset of anaesthesia. Most adult patients less than 55 years are likely to require 1.5 to 2.5 mg of propofol per kilogram of body weight. Recovery from induction doses usually occurs within 5 to 10 minutes. **Maintenance of General Anaesthesia (Adults)** For continuous infusion, rates in the region of 0.067 to 0.2 mg/kg body weight per minute (4 to 12 mg/kg body weight per hour) usually maintain satisfactory anaesthesia. If repeat bolus injections are used, increments of 25 to 50 mg of propofol may be given according to clinical need. **Sedation During Intensive Care (Adults)** Satisfactory sedation is usually achieved with dosages in the range of 0.3 to 4.0 mg of propofol per kilogram of body weight per hour, and infusion rates greater than 4.0 mg/kg/h are not recommended. **Monitored Conscious Sedation (Adults)** Most patients will require 0.5 to 1 mg of propofol per kilogram of body weight over 1 to 5 minutes for onset of sedation. Maintenance of sedation may be accomplished by titrating PROVIVE infusion to the desired level of sedation—most patients will require 1.5 to 4.5 mg of propofol per kilogram of body weight per hour. **Elderly Patients** In elderly patients the dose requirement for induction of anaesthesia is reduced, taking account of the physical status and age of the patient, and the reduced dose should be given at a slower rate and titrated against the response.

Key safety warnings

The most commonly observed adverse effects of propofol are hypotension and respiratory depression. During induction of anaesthesia, hypotension and apnoea commonly occur and may be influenced by the rate of administration, the use of premedicants and other agents, including benzodiazepines. Administration of propofol without airway care may result in fatal respiratory complications. PROVIVE lacks vagolytic activity and has been associated with reports of bradycardia (occasionally profound) and also asystole. The intravenous administration of an anticholinergic agent before induction, or during maintenance of anaesthesia should be considered, especially in situations where vagal tone is likely to predominate or when PROVIVE is used in conjunction with other agents likely to cause a bradycardia. When propofol 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 rapidly progressive cardiac failure (in some cases with a fatal outcome). Very rare reports of occurrence of PRIS in adults treated for more than 48 hours with propofol infusions in excess of 5 mg/kg/hour have been reported. Major risk factors for the development of these events include decreased oxygen delivery to tissues; serious neurological injury and/or sepsis; and high dosages of vasoconstrictors, steroids, inotropes and/or propofol. Because PROVIVE is formulated in an oil-in-water emulsion, elevations in serum triglycerides may occur when administered for extended periods of time. Lipids should be monitored in ICU treatment after 3 days. Propofol is contraindicated for sedation in children as safety and efficacy have not been demonstrated. Although no causal relationship has been established, serious adverse events (including fatalities) have been observed from spontaneous reports of unregistered use. These events were seen more frequently in children with respiratory tract infections (including croup) given doses in excess of those recommended for adults. PROVIVE contains no antimicrobial preservatives and supports growth of microorganisms. Therefore, PROVIVE is to be drawn up aseptically into a sterile syringe or an infusion set immediately after opening the ampoule or breaking the vial seal. Administration must commence without delay.

Contraindications

PROVIVE is contraindicated in patients with a known hypersensitivity to propofol or to any of the other ingredients contained in PROVIVE, namely soya oil, medium chain triglycerides, glycerol, egg lecithin, sodium hydroxide and oleic acid. It is contraindicated in patients who are allergic to soya or peanut, in children younger than 1 month for induction and maintenance of anaesthesia, and 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

PROVIVE 1% propofol was first registered on the ARTG on 6 May 2005 in three strengths: 200 mg/20 mL, 500 mg/50 mL, and 1000 mg/100 mL emulsions for injection as vials. The MCT/LCT variant of PROVIVE was added to the ARTG on 5 March 2010, also in three strengths: 200 mg/20 mL, 500 mg/50 mL, and 1000 mg/100 mL emulsions for injection as vials.