Propofol 0.5 %/5 Mg Injection

a) Induction of general anaesthesia

b) Induction of sedation for diagnostic and surgical procedures

c) Short term sedation for surgical and diagnostic procedures in adults provided that there are adequate facilities for monitoring of haemodynamic and oxygenation parameters and if administered by a qualified anaesthetist. PROPOFOL B. BRAUN must not be used for maintenance of general anaesthesia.

Posology

Propofol should be given by medical practitioners trained in anaesthesia. Patients should be constantly monitored and facilities for maintenance of a patent airway, artificial ventilation, oxygen enrichment and other resuscitative facilities should be readily available at all times. Propofol should not be administered by the person conducting the diagnostic or surgical procedure. Supplementary analgesic medicines are required in addition to PROPOFOL B. BRAUN, where analgesia is required. PROPOFOL B. BRAUN has been used in association with spinal and epidural anaesthesia and with commonly used premedication, neuromuscular blocking medicines, inhalation and analgesic medicines; no pharmacological incompatibility has been encountered. Dosage adjustment may be necessary when used together with the above medicines, particularly the narcotics (e.g. morphine, meperidine and fentanyl), combinations of opioids and sedatives (e.g. benzodiazepines, barbiturates, droperidol etc.), supplementary analgesic medicines (e.g. nitrous oxide or opioids) and the potent inhalation medicines (e.g. isoflurane, enflurane and halothane). Where general anaesthesia with PROPOFOL B. BRAUN is used simultaneously with a regional anaesthetic technique, lower doses of PROPOFOL B. BRAUN may be required.

A. ADULTS

Induction of general anaesthesia: PROPOFOL B. BRAUN may be used to induce anaesthesia by slow bolus injection or infusion. In unpremedicated and premedicated patients:

Most adult patients aged less than 55 years are likely to require 1,5 to 2,5 mg/kg (0,3 to 0,5 mL/kg) of PROPOFOL B. BRAUN, (approximately 8 mL every 10 seconds in an average healthy adult) by slow bolus injection or infusion titrated against the response of the patient until clinical signs show onset of anaesthesia. Over the age of 55 years the requirement will generally be less. In patients of ASA Grades 3 and 4, lower rates of administration should be used (approximately 20 mg [4 mL] every 10 seconds). Short term conscious sedation for surgical and diagnostic procedures (see 4.4): To provide sedation for surgical and diagnostic procedures rates of administration should be individualised and titrated to clinical response. Most patients will require 0,5 mg/kg to 1 mg/kg over 1 to 5 minutes to initiate sedation.

B. ELDERLY PATIENTS

In elderly patients the dose requirement for induction of anaesthesia with PROPOFOL B. BRAUN 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. Patients of ASA Grades 3 and 4 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 cardio respiratory depression.

C. CHILDREN

Induction of general anaesthesia: PROPOFOL B. BRAUN is not recommended for use in children less than 3 years of age (see 4.3 and 4.4). It is recommended that PROPOFOL B. BRAUN be given slowly until the clinical signs show the onset of anaesthesia. Adjust dose for age and/or mass. Most patients over 8 years of age are likely to require approximately 2,5 mg/kg (0,50 mL/kg) of PROPOFOL B. BRAUN for induction. Under this age the requirement may be more. Lower dosage is recommended for children of ASA Grades 3 and 4. Short term conscious sedation for surgical and diagnostic procedures: PROPOFOL B. BRAUN is not recommended for conscious sedation in children as safety and efficacy have not been demonstrated.

Method of administration

For intravenous use. General anaesthesia: In accordance with established guidelines for other lipid emulsions a single infusion of PROPOFOL B. BRAUN must not exceed 6 hours. The syringe or giving set and any unused portion of PROPOFOL B. BRAUN or solution containing PROPOFOL B. BRAUN must be discarded at the end of the surgical procedure, or at 6 hours, whichever is the sooner, and replaced as appropriate. If PROPOFOL B. BRAUN is transferred to another container prior to administration, the handling procedures for u201cGeneral anaesthesiau201d (above) should be followed and the product should be discarded and administration lines changed after 6 hours. When PROPOFOL B. BRAUN is used undiluted, it is recommended that equipment such as drop counters, syringe pumps or volumetric infusion pumps should always be used to control infusion rates. PROPOFOL B. BRAUN can be used for infusion undiluted from glass infusion bottles, or plastic syringes.

PROPOFOL B. BRAUN can be diluted with 5 % dextrose intravenous infusion only, in PVC infusion bags or glass infusion bottles. Dilutions, which must not exceed 1 in 5 (1 mg propofol per mL) should be prepared aseptically immediately before administration and must be used within 6 hours of preparation. 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 PROPOFOL B. BRAUN. 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 PROPOFOL B. BRAUN in the burette. It is recommended that, when using diluted PROPOFOL B. BRAUN, the volume of 5 % dextrose removed from the infusion bag during the dilution process is totally replaced in volume by PROPOFOL B. BRAUN emulsion. PROPOFOL B. BRAUN may be administered via a Y-piece close to the injection site, into intravenous infusions of dextrose 5 % or sodium chloride 0,9 %. In order to reduce pain on initial injection, that part of the PROPOFOL B. BRAUN used for induction may be mixed with lidocaine (lignocaine) injection in the ratio of 20 parts PROPOFOL B. BRAUN with up to 1 part of 1 % lignocaine injection immediately prior to administration. It is recommended that blood lipid levels be monitored routinely should PROPOFOL B. BRAUN be administered to patients thought to be at particular risk of fat overload. Administration of PROPOFOL B. BRAUN 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 B. BRAUN formulation; 1,0 mL of PROPOFOL B. BRAUN contains 0,1 g of fat. Patients with hypovolaemia should have fluid-volume deficits corrected prior to administration of PROPOFOL B. BRAUN.

• Hypersensitivity to the active substance, propofol or to any of the excipients of PROPOFOL B. BRAUN listed in section 6.1
• PROPOFOL B. BRAUN contains soya-bean oil and should not be used in patients who are hypersensitive to peanuts or soya
• PROPOFOL B. BRAUN is not for use in children under the age of 3 years
• Sedation in intensive care
• Sedation of children of all ages with croup or epiglottitis receiving intensive care (see section 4.4).

Respiration will be depressed and must be monitored to ensure adequate gas exchange. Special care should be exercised when used with other respiratory depressants. A generalised systemic reaction which may be anaphylactic in nature (including angioedema, bronchospasm, erythema and hypotension) may occur following propofol administration u2013 estimated as 1 in 15 000. The abuse of and dependence on propofol, predominantly by health care professionals, have been reported. As with other general anaesthetics, the administration of propofol without airway care may result in fatal respiratory complications. PROPOFOL B. BRAUN must not be used for maintenance of general anaesthesia.

When propofol is administered for conscious sedation, for surgical and diagnostic procedures, patients should be continually monitored for early signs of hypotension, airway obstruction and oxygen desaturation. In case of repeated boli for induction of anaesthesia the maximum fat administration should not exceed 150 mg fat/kg/h which corresponds to 1,5 mL/kg/h of PROPOFOL B. BRAUN. When Propofol is used for sedation during operative procedures, involuntary patient movements may occur. During procedures requiring immobility these movements may be hazardous to the operative site. An adequate period is needed prior to discharge of the patient to ensure full recovery after use of propofol. Very rarely the use of propofol may be associated with the development of a period of post-operative unconsciousness, which may be accompanied by an increase in muscle tone. This may or may not be preceded by a period of wakefulness. Although recovery is spontaneous, appropriate care of an unconscious patient should be administered. Propofol induced impairment is not generally detectable beyond 12 hours. The effects of propofol, the procedure, concomitant medications, the age and the condition of the patient should be considered when advising patients on:

• The advisability of being accompanied on leaving the place of administration
• The timing of recommencement of skilled or hazardous tasks such as driving
• The use of other medicines that may sedate (e.g. benzodiazepines, opiates, alcohol).

Interference with daily activities may continue for up to 24 hours and no legal/contractual decisions should be entered into for 24 hours after receiving anaesthetic/conscious sedation. Alcohol use should also be avoided for the same time period.

Caution should be applied in patients with cardiac, respiratory, renal or hepatic impairment or in hypovolaemic or debilitated patients (see section 4.2). The pharmacokinetics of propofol may be prolonged in people with chronic hepatic cirrhosis or chronic renal impairment. Recovery times may double as a result. The effects of acute hepatic or renal failure on the pharmacokinetics of propofol have not been studied. Propofol clearance is blood flow dependent, therefore, concomitant medication that reduces cardiac output will also reduce propofol clearance. Propofol lacks vagolytic activity and has been associated with reports of bradycardia (occasionally profound) and also asystole. The intravenous administration of an anticholinergic medicine 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 medicines likely to cause bradycardia. When propofol is administered to an epileptic patient, there may be a risk of convulsion. Before anaesthesia of an epileptic patient, it should be checked that the patient has received the antiepileptic treatment. Appropriate care should be applied in patients with disorders of fat metabolism, patients predisposed to fat embolism and in other conditions where lipid emulsions must be used cautiously. Fat metabolism may be disturbed in conditions such as renal insufficiency, uncompensated diabetes mellitus, certain forms of liver insufficiency, metabolic disorders, severe trauma including long-bone and multiple fractures, and sepsis.

Paediatric population

The use of propofol is contraindicated in newborn infants as this patient population has not been fully investigated. Pharmacokinetic data (see section 5.2) indicate that clearance is considerably reduced in neonates and has a very high inter-individual variability. Relative overdose could occur on administering doses recommended for older children and result in severe cardiovascular depression. PROPOFOL B. BRAUN is contraindicated for use in children < 3 years of age due to difficulty in titrating small volumes. 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 B. BRAUN contains 0,1 g of fat.

Additional precautions

Caution should be taken when treating patients with mitochondrial disease. These patients may be susceptible to exacerbations of their disorder when undergoing anaesthesia and surgery. Maintenance of normothermia, provision of carbohydrates and good hydration are recommended for such patients. The early presentations of mitochondrial disease exacerbation and of the u2018propofol infusion syndromeu2019 may be similar. PROPOFOL B. BRAUN contains no antimicrobial preservatives and supports growth of micro-organisms. When PROPOFOL B. BRAUN is to be aspirated, it must be drawn aseptically into a sterile syringe or giving set immediately after opening the ampoule. Administration must commence without delay. Asepsis must be maintained for both PROPOFOL B. BRAUN and infusion equipment throughout the infusion period. Any infusion fluids added to the PROPOFOL B. BRAUN line must be administered close to the cannula site. PROPOFOL B. BRAUN must not be administered via a microbiological filter. If infusion sets with filters are to be used, these must be lipid-permeable.

Special warnings/precautions regarding excipients

PROPOFOL B. BRAUN contains less than 1 mmoL sodium (23 mg) in 20 mL, which is to say essentially u2018sodium freeu2019. PROPOFOL B. BRAUN contains soybean oil, which may cause severe allergic reactions in some cases. PROPOFOL B. BRAUN should not be used in patients with an allergy to peanuts, eggs, or soya protein (see section 4.3).

Propofol has been used in association with spinal and epidural anaesthesia and with commonly used premedicants, neuromuscular blocking medicines, inhalational medicines and analgesic medicines; no pharmacological incompatibility has been encountered. Lower doses of PROPOFOL B. BRAUN may be required where general anaesthesia or sedation is used as an adjunct to regional anaesthetic techniques. The concurrent administration of other CNS depressants such as pre-medication medicines, inhalation medicines, and analgesic medicines may add to the sedative, anaesthetic and cardiorespiratory depressant effects of PROPOFOL B. BRAUN. It is recommended that PROPOFOL B. BRAUN is given after the administration of opioids so that the dose of PROPOFOL B. BRAUN can be carefully titrated against the response. The dosage of PROPOFOL B. BRAUN should be reduced if used with nitrous oxide or halogenated anaesthetics. Although propofol does not potentiate the effects of neuromuscular blockers, bradycardia and asystole have occurred after use of propofol with atracurium or suxamethonium. Neuromuscular blocking medicines atracurium and mivacurium should not be given through the same intravenous line as PROPOFOL B. BRAUN without prior flushing (see section 6.2). 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. Benzodiazepines: Propofol and midazolam have been reported to act synergistically (see section 4.4). Gastrointestinal medicines: The dose of propofol required for induction, is reduced in patients given metoclopramide. General anaesthetics: The use of halothane or isoflurane has been reported to increase serum concentrations of propofol. Synergy has been reported between propofol and etomidate. Local anaesthetics: A reduction in the amount of propofol required to provide adequate hypnosis or sedation has been reported after bupivacaine or lidocaine (lignocaine). However, lidocaine is often added to propofol emulsions to reduce pain at the site of injection. Opioids: Concentrations of propofol were higher in patients pre-treated with fentanyl compared to patients maintained only on nitrous oxide (see section 4.4).

Pregnancy

The safety of PROPOFOL B. BRAUN during pregnancy has not been established. Studies in animals have shown reproductive toxicity. PROPOFOL B. BRAUN should not be given to pregnant women. Propofol crosses the placenta and has been associated with neonatal depression. PROPOFOL B. BRAUN can, however, be used during termination of pregnancy in the first trimester.

Breastfeeding

Studies of breast-feeding mothers showed that small quantities of propofol are excreted in human milk. Safety to the neonate has not been established. Women should therefore not breastfeed for 24 hours after administration of PROPOFOL B. BRAUN. Milk produced during this period should be discarded.

Fertility

No data available.

Patients should be advised that performance at skilled tasks, such as driving and operating machinery, may be impaired for some time after use of PROPOFOL B. BRAUN. After administration of PROPOFOL B. BRAUN, the patient should be kept under observation for an appropriate period of time. The patient should not be allowed to go home unaccompanied and should be instructed to avoid consumption of alcohol.

Induction of anaesthesia or sedation with propofol is generally smooth with minimal evidence of excitation. The most commonly reported adverse reactions are pharmacologically predictable side effects of an anaesthetic/sedative medicine, such as hypotension and apnoea. These effects depend on the propofol dose administered but also on the type of premedication and other concomitant medication. 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.

Table of Adverse Drug Reactions

Undesirable effects are listed according to their frequencies as follows:

System Organ Class Frequency Undesirable Effects

Immune system disorders: Less Frequent Anaphylaxis u2013 may include angioedema, bronchospasm, erythema and hypotension

Metabolism and nutritional disorders: Frequency not known (9) Metabolic acidosis (5), hyperkalaemia (5), hyperlipidaemia (5)

Psychiatric disorders: Frequency not known (9) Euphoric mood, drug abuse and drug dependence (8) Less frequent Sexual disinhibition

Nervous system disorders: Frequent Headache during recovery phase Less Frequent Epileptiform movements, including convulsions and opisthotonus during induction, maintenance and recovery, syncope, postoperative unconsciousness Frequency not known (9) Involuntary movements

Cardiac disorders: Frequent Bradycardia (1) Less Frequent Pulmonary oedema tachycardia, premature ventricular contractions, premature atrial contractions, abnormal ECG, ST segment depression Frequency not known (9) Cardiac dysrhythmia (5), cardiac failure (5), (7)

Vascular disorders: Frequent Hypotension (2), flushing

Respiratory, thoracic and mediastinal disorders: Frequent Transient apnoea during induction Frequency not known (9) Respiratory depression (dose-dependent)

Gastrointestinal disorders: Frequent Nausea and vomiting during recovery phase, hiccups Less frequent Pancreatitis

Hepatobiliary disorders Frequency not known (9) Hepatomegaly (5)

Musculoskeletal and connective tissue disorders: Frequency not known (9) Rhabdomyolysis (3),

Renal and urinary disorders Less frequent Discolouration of urine following prolonged administration Frequency not known (9) Renal failure (5)

General disorders and administration site conditions: Frequent Local pain on induction (4) Less frequent Injection site thrombosis and injection site phlebitis, tissue necrosis (10) following accidental extravascular administration (11) Frequency not known (9) Local pain and swelling, following accidental extravascular administration (11)

Investigations Frequency not known (9) Brugada type ECG (5), (6)

Injury, poisoning and procedural complications: Less frequent Postoperative fever (1) Serious bradycardias are less frequent. 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) 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 B. BRAUN local pain can also be minimised by the co-administration of lidocaine (lignocaine). (5) Combinations of these events, reported as u201cPropofol infusion syndromeu201d, 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) Treatment is symptomatic and may include immobilisation and, if possible, elevation of affected limb, cooling, close observation, consultation of surgeon if necessary.

Reporting of side effects

Reporting suspected adverse reactions after authorization of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Health care providers are asked to report any suspected adverse reactions to SAHPRA via u201c6.04 Adverse Drug Reaction Reporting Formu201d, found online under SAHPRAs publications: https://primaryreporting.who-umc.org/ZA. By reporting side effects, you can help provide more information on the safety of PROPOFOL B. BRAUN.

Symptoms

Accidental overdosage is likely to cause cardiorespiratory depression.

Treatment

Respiratory depression should be treated by artificial ventilation with oxygen. Cardiovascular depression may require lowering of the patientu2019s head and, if severe, administering plasma expanders and pressor medicines.