Propofol

It should be taken into consideration that concomitant use of propofol and medicinal products for premedication, inhalation agents or analgesic agents may potentiate anaesthesia and cardiovascular side effects. Concomitant use of central nervous system depressants (e.g. alcohol, general anaesthetics, narcotic analgesics) will result in intensification of their sedative effects. When propofol is combined with centrally depressant drugs administered parenterally, severe respiratory and cardiovascular depression may occur.

Co-administration with dexmedetomidine is likely to lead to an enhancement of effects. Propofol dose required for sedation may have to be reduced in the presence of dexmedetomidine.

A need for lower propofol doses has been observed in patients taking midazolam. The co-administration of propofol with midazolam is likely to result in enhanced sedation and respiratory depression. When used concomitantly, a dose reduction of propofol should be considered.

Profound hypotension has been reported following anaesthetic induction with propofol in patients treated with rifampicin.

A need for lower propofol doses has been observed in patients taking valproate. When used concomitantly, a dose reduction of propofol may be considered.

Use of propofol is not recommended with electroconvulsive therapy.

Caution should be taken when treating patients with mitochondrial disease. These patients may be susceptible to exacerbations of their disorder when undergoing anaesthesia, surgery and ICU care. Maintenance of normothermia, provision of carbohydrates and good hydration are recommended for such patients. The early presentations of mitochondrial disease exacerbation and of the 'propofol infusion syndrome' may be similar.

Appropriate care should be applied in patients with disorders of fat metabolism and in other conditions where lipid emulsions must be used cautiously.

It is recommended that blood lipid levels should be monitored if propofol is administered to patients thought to be at particular risk of fat overload. Administration of propofol should be adjusted appropriately if the monitoring indicates that fat is being inadequately cleared from the body. If the patient is receiving other intravenous lipid concurrently, a reduction in quantity should be made in order to take account of the amount of lipid infused as part of the propofol formulation; 1.0 mL of propofol contains approximately 0.1 g of fat.

As with other intravenous anaesthetic agents, caution should be applied in patients with cardiac, respiratory, renal or hepatic impairment or in hypovolaemic or debilitated patients.

Propofol 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 propofol is used in conjunction with other agents likely to cause bradycardia.

When propofol is administered to an epileptic patient, there may be a risk of convulsion.

The safety of propofol during pregnancy has not been established. Studies in animals have shown reproductive toxicity. Propofol should not be given to pregnant women except when absolutely necessary. Propofol crosses the placenta and can cause neonatal depression. Propofol can, however, be used during an induced abortion. High doses (more than 2.5 mg/kg for induction or 6 mg/kg/h for maintenance of anaesthesia) should be avoided.

Studies of breast-feeding mothers showed that small quantities of propofol are excreted in human milk. Women should therefore not breast-feed for 24 hours after administration of propofol. Milk produced during this period should be discarded.

Patients should be advised that performance of skilled tasks, such as driving and operating machinery, may be impaired for some time after general anaesthesia.

Propofol induced impairment is not generally detectable beyond 12 hours.

General

Induction and maintenance of anaesthesia or sedation is generally smooth with minimal evidence of excitation, although spontaneous movements may be seen in some patients. The most commonly reported ADRs are pharmacologically predictable side effects of an anaesthetic/sedative agent, such as hypotension. The nature, severity and incidence of adverse events observed in patients receiving propofol may be related to the condition of the recipients and the operative or therapeutic procedures being undertaken.

The following definitions of frequencies are used: Very common (≥1/10), common (≥1/100 to <1/10), uncommon ((≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000) and not known (cannot be estimated from the available data).

Table of Adverse Drug Reactions:

¹ Serious bradycardias are rare. There have been isolated reports of progression to asystole.
² Occasionally, hypotension may require use of intravenous fluids and reduction of the administration rate of propofol.
³ Very rare reports of rhabdomyolysis have been received where propofol has been given at doses greater than 4 mg/kg/hr for ICU sedation.
⁴ May be minimised by using the larger veins of the forearm and antecubital fossa. With propofol 1% local pain can also be minimised by the co-administration of lidocaine.
⁵ Combinations of these events, reported as "Propofol Infusion Syndrome", may be seen in seriously ill patients who often have multiple risk factors for the development of the events.
⁶ Brugada-type ECG - elevated ST-segment and coved T-wave in ECG.
⁷ Rapidly progressive cardiac failure (in some cases with fatal outcome) in adults. The cardiac failure in such cases was usually unresponsive to inotropic supportive treatment.
⁸ Abuse of and drug dependence on propofol, predominantly by health care professionals.
⁹ Not known as it cannot be estimated from the available clinical trial data.
¹⁰ Necrosis has been reported where tissue viability has been impaired.
¹¹ After both long- and short-term treatment and in patients without underlying risk factors.

Local

The local pain which may occur during the induction phase can be minimised by the use of the larger veins in the forearm and antecubital fossa. With propofol 1% local pain can also be minimised by the co‑administration of lidocaine. Thrombosis and phlebitis are rare. Accidental clinical extravasation and animal studies showed minimal tissue reaction. Intra‑arterial injection in animals did not induce local tissue effects.