PROVIVE Emulsion for injection Ref.[50449] Active ingredients: Propofol

DOSE

Aseptic technique (refer also to section 4.4)

Strict aseptic technique must always be maintained during the handling of Provive 1%. Provive 1% is for single use in one patient only. Provive 1% can support the growth of micro‐organisms as it is not an antimicrobially‐preserved product. Accordingly, strict aseptic technique must still be adhered to. Do not use if contamination is suspected.

Discard unused portions as directed within the required time limits (see section 4.4/Aseptic technique). There have been reports in which failure to use aseptic technique when handling propofol products was associated with microbial contamination of the product and with fever, infection/sepsis, other life‐threatening illness, and/or death.

ADULTS

Induction of general anaesthesia

Provive 1% may be used to induce anaesthesia by slow bolus injection or infusion. In both un‐ premedicated and premedicated patients, it is recommended that Provive 1% should be titrated (approximately 4mL (40mg) every 10 seconds in an average healthy adult) against the response of the patient until the clinical signs show the onset of anaesthesia. Most adult patients aged less than 55 years are likely to require Provive 1% at 1.5–2.5mg/kg. In elderly patients, requirements will be generally less (see ‘Elderly’, below). In general, slower rates of infusion at induction results in a lower induction dose requirement and greater haemodynamic stability. In patients of ASA grades III and IV, lower rates of administration should be used (approximately 2mL (20mg) every ten seconds).

Recovery from induction doses usually occurs within 5 – 10 minutes.

Maintenance of general anaesthesia

Anaesthesia can be maintained by administering Provive 1% either by continuous infusion or by repeat bolus injections to maintain the depth of anaesthesia required.

• Continuous infusion ‐ The required rate of administration varies considerably between patients, but rates in the region of 4–12mg/kg/hour usually maintain satisfactory anaesthesia.
• Repeat bolus injections ‐ If a technique involving repeat bolus injections is used, increments of 25mg (2.5mL) to 50mg (5mL) may be given according to clinical need.

Sedation during intensive care

When used to provide sedation for ventilated adult patients undergoing intensive care, it is recommended that Provive 1% be given by continuous infusion. The infusion rate should be adjusted according to the depth of sedation required but rates in the region of 0.3–4.0mg/kg/hour should achieve satisfactory sedation. Infusion rates greater than 4.0mg/kg/hour should not be used unless the benefit to the patient outweighs the possible risks.

Monitored conscious sedation for surgical and diagnostic procedures

To provide sedation for surgical and diagnostic procedures in adult patients, rates of administration should be individualised and titrated to clinical response.

Most patients will require 0.5–1mg/kg over 1–5 minutes for onset of sedation.

Maintenance of sedation may be accomplished by titrating Provive 1% infusion to the desired level of sedation; most patients will require 1.5–4.5mg/kg/hour.

In addition to the infusion, bolus administration of 10–20mg may be used if a rapid increase in the depth of sedation is required. In patients in ASA grades III or IV, the rate of administration and dosage may need to be reduced.

ELDERLY

In elderly patients the dose requirement for induction of anaesthesia with Provive 1% is reduced. The reduction should take account of the physical status and age of the patient. The reduced dose should be given at a slower rate and titrated against the response. Induction infusion rates of 300mL/hour (50mg/minute) are associated with less hypotension and apnoea in elderly patients. Where Provive 1% is used for maintenance of anaesthesia or sedation the rate of infusion or target concentration should also be reduced. Patients of ASA grades III and IV will require further reductions in dose and dose rate. Rapid bolus administration (single or repeated) should not be used in the elderly as this may lead to cardiorespiratory depression.

PAEDIATRIC POPULATION

Induction of general anaesthesia

Provive 1% is not recommended for use in infants less than 1 month old.

When used to induce anaesthesia in children, it is recommended that Provive 1% be given slowly until the clinical signs show the onset of anaesthesia. The dose should be adjusted for age and/or weight. Most patients over eight years of age are likely to require approximately 2.5mg/kg Provive 1% for induction of anaesthesia. Under this age the requirement may be more. Lower dosage is recommended for children of ASA grades III or IV.

Maintenance of general anaesthesia

Provive 1% is not recommended for use in infants less than 1 month old.

Anaesthesia can be maintained by administering Provive 1% by infusion or repeat bolus injection to maintain the depth of anaesthesia required. The required rate of administration varies considerably between patients but rates in the region of 9 – 15mg/kg/hour usually achieve satisfactory anaesthesia.

Sedation during intensive care

The use of propofol for sedation in children 16 years of age and younger during intensive care is contraindicated.

Monitored conscious sedation for surgical and diagnostic procedures

Provive 1% is not recommended for sedation in children as safety and efficacy have not been demonstrated.

METHOD OF ADMINISTRATION

(see also section 4.4/Pharmaceutical precautions). Intravenous bolus injection or infusion.

Supplementary analgesic agents are generally required in addition to Provive 1%. No pharmacological incompatibility has been noted when Provive 1% has been used in association with spinal and epidural anaesthesia and commonly used pre‐medicants, neuromuscular blocking agents, inhalational agents and analgesics. Lower doses of Provive 1% may be required where general anaesthesia is used as an adduct to regional anaesthetic techniques.

Provive 1% can be infused undiluted from plastic syringes or glass infusion bottles. When Provive 1% is used undiluted to maintain anaesthesia, it is recommended that drop counters, syringe pumps or volumetric infusion pumps be used to control infusion rates.

Provive 1% can be diluted with Glucose 5% Intravenous Infusion and used from glass infusion bottles or PVC infusion bags. Dilutions should be prepared aseptically immediately before administration and must be used within 6 hours of preparation. Such dilutions must not be more dilute than one volume of Provive 1% to four volumes of diluent (propofol 2mg/mL). It is recommended that in order to prepare diluted Provive 1%, the volume of Glucose 5% Intravenous Infusion BP removed from the infusion bag during the dilution process be totally replaced in volume by Provive 1% emulsion. The dilution may be used with a variety of infusion control techniques, but a giving set used alone will not avoid the risk of accidental, uncontrolled infusion of large volumes of diluted Provive 1%. A burette, drop counter or volumetric pump must be included in the infusion line. The risk of uncontrolled infusion must be taken into account when deciding the maximum amount of dilution in the burette.

Provive 1% may be administered via a Y‐piece close to the injection site, into infusions of Glucose 5% Intravenous Infusion BP, Sodium Chloride 0.9% Intravenous Infusion BP, or Glucose 4% with Sodium Chloride 0.18% Intravenous Infusion BP.

Provive 1% may be premixed with alfentanil injection (500mcg/mL alfentanil) in ratios of 20:1 – 50:1v/v. Mixtures should be prepared using aseptic techniques and used within 6 hours.

To reduce pain on initial injection, the part of Provive 1% used for induction may be mixed with Lignocaine Injection.

DILUTION AND CO‐ADMINISTRATION:

Accidental overdosage is likely to cause cardiorespiratory depression. Respiratory depression should be treated by artificial ventilation with oxygen. Cardiovascular depression would require lowering of the patient’s head and, if severe, use of plasma expanders and pressor agents.

For advice on the management of overdose please contact the National Poisons Centre on 0800 POISON (0800 764766).

24 months.

Store below 30°C. Do not freeze. Keep in carton until use to protect contents from light.

Provive 1% is supplied in 20mL, 50mL or 100mL clear glass vials in pack sizes of 5 vials.

Each vial should be shaken before use. Do not use if the emulsion is separated or discoloured.

The emulsion should not be mixed prior to administration with other therapeutic agents or infusion fluids other than Glucose 5% Intravenous Infusion BP. The final concentration of propofol should not be less than 2mg/mL to preserve the emulsion base (see section 4.2/Dilution and co‐administration).

Any portion of the contents remaining after use should be discarded.