Fresofol MCT/LCT/Fresofol PFS MCT/LCT

Fresofol MCT/LCT/Fresofol PFS MCT/LCT

propofol

Manufacturer:

Fresenius Kabi

Distributor:

Fresenius Kabi
Full Prescribing Info
Contents
Propofol.
Description
Fresofol MCT/LCT: 1 ml emulsion contains 10 mg propofol. Each 50 ml vial contains 500 mg propofol.
Fresofol PFS MCT/LCT: 1 ml emulsion contains 10 mg propofol. Each 50 ml pre-filled syringe contains 500 mg propofol.
Also contains soya-bean oil, triglycerides medium-chain, purified egg phosphatides, glycerol, oleic acid, sodium hydroxide, water for injections.
Pharmaceutical form: Emulsion for injection or infusion.
Action
Pharmacology: Pharmacodynamics: Mechanism of action/Pharmacodynamic effects: Propofol (2,6-diisopropylphenol) is a short-acting general anaesthetic agent with a rapid onset of action. Depending on the rate of injection, the time to induction of anaesthesia is between 30 and 40 seconds. The duration of action after a single bolus administration is short and lasts, depending on the metabolism and elimination, 4 to 6 minutes.
Clinical efficacy and safety: Under the usual maintenance regimen significant accumulation with either repeated injections or infusions of propofol has not been seen. Patients recover consciousness rapidly. Bradycardia and hypotension reported during induction of anaesthesia may be caused by a cerebral vagotonic effect or inhibition of sympathetic activity. However, haemodynamics generally reverts to normal during maintenance of anaesthesia.
Paediatric population: Limited studies on the duration of propofol based anaesthesia in children indicate safety and efficacy is unchanged up to duration of 4 hours. Literature evidence of use in children documents use for prolonged procedures without changes in safety or efficacy.
Pharmacokinetics: Absorption: Propofol is bound to plasma proteins for 98%. Following intravenous administration the pharmacokinetics of propofol can be described by a 3-compartment model.
Distribution/ Biotransformation/Elimination: Propofol is extensively distributed and rapidly cleared from the body (total body clearance: 1.5 - 2 litres/minute). Clearance occurs by metabolic processes, mainly in the liver where it is blood flow dependent, to form inactive conjugates of propofol and its corresponding quinol, which are excreted in urine.
After a single dose of 3 mg/kg intravenously, propofol clearance/kg body weight increased with age as follows: Median clearance was considerably lower in neonates <1 month old (n=25) (20 ml/kg/min) compared to older children (n=36, age range 4 months – 7 years). Additionally, inter-individual variability was considerable in neonates (range 3.7-78 ml/kg/min). Due to this limited trial data that indicates a large variability, no dose recommendations can be given for this age group.
Median propofol clearance in older aged children after a single 3 mg/kg bolus was 37.5 ml/min/kg (4-24 months) (n=8), 38.7 ml/min/kg (11-43 months) (n=6), 48 ml/min/kg (1- 3 years) (n=12), 28.2 ml/min/kg (4-7 years) (n=10) as compared with 23.6 ml/min/kg in adults (n=6).
Indications/Uses
Propofol is a short-acting intravenous general anaesthetic agent for: induction and maintenance of general anaesthesia.
Sedation of artificially ventilated patients in the Intensive Care Unit (ICU).
Sedation for diagnostic and surgical procedures, alone or in combination with local or regional anaesthesia.
Dosage/Direction for Use
Fresofol 1% MCT/LCT/Fresofol PFS MCT/LCT must only be given in hospitals or adequately equipped day therapy units by physicians trained in anaesthesia or in the care of patients in intensive care.
Circulatory and respiratory functions should be constantly monitored (e.g. ECG, pulse oxymetry) and facilities for maintenance of patient airways, artificial ventilation, and other resuscitation facilities should be immediately available at all times.
For sedation during surgical and diagnostic procedures Fresofol 1% MCT/LCT/Fresofol PFS MCT/LCT should not be administered by the same person conducting the surgical or diagnostic procedure.
The dose of Fresofol 1% MCT/LCT/Fresofol PFS MCT/LCT should be individualised based on the response of the patient and premedications used.
Supplementary analgesic agents are generally required in addition to Fresofol 1% MCT/LCT/Fresofol PFS MCT/LCT.
Fresofol PFS MCT/LCT in pre-filled syringe may be administered by a Target Controlled Infusion system for induction and maintenance of general anaesthesia in adults only. Administration of Propofol 1% MCT/LCT in pre-filled syringe by a Target Controlled Infusion system is not recommended for any indication in children. Administration of Fresofol PFS MCT/LCT in pre-filled syringe by a Target Controlled Infusion system is not recommended for intensive care sedation.
General anaesthesia in adults: Induction of anaesthesia: For induction of anaesthesia Fresofol 1% MCT/LCT/Fresofol PFS MCT/LCT should be titrated (approximately 20-40 mg propofol every 10 seconds) against the response of the patient until clinical signs show the onset of anaesthesia.
Most adult patients aged less than 55 years are likely to require 1.5 to 2.5 mg propofol/kg body weight.
In patients over this age and in patients of ASA grades III and IV, especially those with impaired cardiac function, the requirements will generally be less and the total dose of Fresofol 1% MCT/LCT/Fresofol PFS MCT/LCT may be reduced to a minimum of 1 mg propofol/kg bodyweight. Lower rates of administration of Fresofol 1% MCT/LCT/Fresofol PFS MCT/LCT should be used (approximately 2 ml (20 mg propofol every 10 seconds).
Maintenance of anaesthesia: Anaesthesia can be maintained by administering Fresofol 1% MCT/LCT/Fresofol PFS MCT/LCT either by continuous infusion or repeat bolus injections.
For maintenance of anaesthesia generally doses of 4 to 12 mg propofol/kg body weight/h should be given. A reduced maintenance dose of approximately 4 mg propofol/kg body weight/h may be sufficient during less stressful surgical procedures such as minimal invasive surgery.
In elderly patients, patients in unstable general conditions, patients with impaired cardiac function or hypovolaemic patients and patients of ASA grades III and IV, the dosage of Fresofol 1% MCT/LCT/Fresofol PFS MCT/LCT may be reduced further depending on the severity of the patient's condition and on the performed anaesthetic technique.
For maintenance of anaesthesia with Fresofol PFS MCT/LCT in pre-filled syringe 10mg/ml using repeat bolus injections dose increments of 25 to 50 mg propofol (= 2.5-5 ml Fresofol 1% MCT/LCT) should be given according to clinical requirements. Rapid bolus administration (single or repeated) should not be used in the elderly as this may lead to cardiopulmonary depression.
General anaesthesia in children over 1 month of age: Administration of Fresofol 1% MCT/LCT is not advised for general anaesthesia in children younger than 1 month of age.
Induction of anaesthesia: For induction of anaesthesia Fresofol 1% MCT/LCT/Fresofol PFS MCT/LCT should be titrated slowly until the clinical signs show the onset of anaesthesia.
The dose should be adjusted for age and/or body weight. Children over 8 years of age are likely to require approximately 2.5 mg propofol/kg body weight for induction of anaesthesia. Under this age the dose requirement may be higher.
The initial dose should be 3 mg propofol/kg body weight. If necessary, additional doses in steps of 1 mg propofol/kg body weight can be administered.
In younger children, especially between the age of 1 month and 3 years, dose requirements for Fresofol PFS MCT/LCT in pre-filled syringe may be higher (2.5-4 mg/kg bodyweight).
Lower dosages are recommended for young patients at increased risk (ASA grades III and IV).
Administration of propofol by a Target Controlled Infusion (TCI) system is not advised for induction of general anaesthesia in children.
Maintenance of general anaesthesia: Fresofol 1% MCT/LCT: For maintenance of anaesthesia using continuous infusion doses of 9 to 15 mg propofol/kg body weight/h should be given.
Younger children, less than 3 years, may need higher dosage requirements, within the range of recommended dosages, when compared with older paediatric patients.
There is no data on maintenance of anaesthesia with repeated injections of propofol in children.
Dosage should be adjusted individually and particular attention paid to the need for adequate analgesia.
A maximum duration of use of approximately 60 minutes should not be exceeded except where there is a specific indication for longer use e.g. malignant hyperthermia where volatile agents must be avoided.
Administration of propofol by a Target Controlled Infusion (TCI) system is not advised for maintenance of general anaesthesia in children.
Fresofol PFS MCT/LCT: Anaesthesia can be maintained by administering Propofol 1% in pre-filled syringe by infusion or repeated bolus injection to maintain the depth of anaesthesia required. The required rate of administration varies considerably between patients but rates in the region of 9-15 mg/kg/h usually achieve satisfactory anaesthesia. In younger children, especially between the age of 1 month and 3 years, dose requirements may be higher.
For ASA III and IV patients lower doses are recommended (see Precautions).
Sedation in adults (patients over 16 years of age) during intensive care: When used to provide sedation for ventilated patients under intensive care conditions, it is recommended that Fresofol 1% MCT/LCT/Fresofol PFS MCT/LCT should be given by continuous infusion. The dose should be adjusted according to the depth of sedation required. Usually satisfactory sedation is achieved with administration rates in the range of 0.3 to 4.0 mg propofol/kg body weight/h. Rates of infusion greater than 4.0 mg propofol/kg body weight/h are not recommended (see Precautions).
Propofol must not be used for sedation in intensive care of patients of 16 years of age or younger (see Contraindications).
Administration of Fresofol 1% MCT/LCT/Fresofol PFS MCT/LCT by a Target Controlled Infusion (TCI) system is not advised for sedation in the Intensive Care Unit. The duration of administration must not exceed 7 days.
Sedation for diagnostic and surgical procedures in adult patients: To provide sedation during surgical and diagnostic procedures, doses and administration rates should be adjusted according to the clinical response. Most patients will require 0.5-1 mg propofol/kg body weight over 1 to 5 minutes for onset of sedation. Maintenance of sedation may be accomplished by titrating Fresofol 1% MCT/LCT/Fresofol PFS MCT/LCT infusion to the desired level of sedation. Most patients will require 1.5-4.5 mg propofol/kg body weight/h. The infusion may be supplemented by bolus administration of 10-20 mg (1-2 ml Fresofol 1% MCT/LCT/Fresofol PFS MCT/LCT) if a rapid increase of the depth of sedation is required.
In patients older than 55 years and in patients of ASA grades III and IV lower doses of Fresofol 1% MCT/LCT/Fresofol PFS MCT/LCT may be required and the rate of administration may need to be reduced.
Propofol must not be used for sedation for diagnostic and surgical procedures in patients of 16 years of age or younger.
Sedation for diagnostic and surgical procedures in children over 1 month of age: Doses and administration rates should be adjusted according to the required depth of sedation and the clinical response. Most paediatric patients require 1-2 mg/kg bodyweight propofol for onset of sedation. Maintenance of sedation may be accomplished by titrating Fresofol PFS MCT/LCT in pre-filled syringe infusion to the desired level of sedation. Most patients require 1.5-9 mg/kg/h propofol. With Fresofol PFS MCT/LCT in prefilled syringe, the infusion may be supplemented by bolus administration of up to 1 mg/kg bodyweight if a rapid increase of depth of sedation is required.
In ASA III and IV patients lower doses may be required.
Method of administration: For intravenous use.
Fresofol MCT/LCT: Fresofol 1% MCT/LCT can be used for infusion undiluted or diluted with Dextrose 5% intravenous infusion solution or Sodium chloride 0.9% intravenous infusion solution only, in glass infusion bottles.
Containers should be shaken before use.
Use only homogeneous preparations and undamaged containers.
Prior to use, the ampoule neck or rubber membrane should be cleaned using an alcohol spray or a swab dipped in alcohol. After use, tapped containers must be discarded.
Fresofol PFS MCT/LCT: For single use only. Any unused emulsion must be discarded.
Pre-filled syringes should be shaken before use. If two layers can be seen after shaking the emulsion should not be used. Use only homogeneous preparations and undamaged pre-filled syringes.
Propofol 1% (Fresofol PFS MCT/LCT) in pre-filled syringe can be used for infusion undiluted or diluted (see Cautions for Usage). When Propofol 1% (Fresofol PFS MCT/LCT) in pre-filled syringe is infused, it is recommended that equipment such as burettes, drop counter, syringe pumps (including TCI systems) or volumetric infusio pumps should always be used to control infusion rates.
Fresofol 1% MCT/LCT/Fresofol PFS MCT/LCT: Fresofol 1% MCT/LCT/Fresofol PFS MCT/LCT is a lipid containing emulsion without antimicrobial preservatives and may support rapid growth of micro-organisms.
The emulsion must be drawn aseptically into a sterile syringe or giving set immediately after opening the ampoule or breaking the vial seal. Administration must commence without delay.
Asepsis must be maintained for both Fresofol 1% MCT/LCT/Fresofol PFS MCT/LCT and infusion equipment throughout the infusion period.
Co-administration of other medicinal products or fluids added to the Fresofol 1% MCT/LCT/Fresofol PFS MCT/LCT infusion line must occur close to the cannula site using a Y-piece connector or a three-way valve.
Fresofol 1% MCT/LCT must not be mixed with other solutions for infusion or injection. But 5% w/v glucose solution, 0.9% w/v sodium chloride solution or 0.18% w/v sodium chloride and 4% w/v glucose solution may be administered via suitable appendages at the cannula site.
Fresofol 1% MCT/LCT/Fresofol PFS MCT/LCT must not be administered via a microbiological filter.
Fresofol 1% MCT/LCT/Fresofol PFS MCT/LCT and any infusion equipment containing Fresofol 1% MCT/LCT/Fresofol PFS MCT/LCT are for single administration in an individual patient. After use remaining solution of Fresofol 1% MCT/LCT/Fresofol PFS MCT/LCT has to be discarded.
Infusion of undiluted Fresofol 1% MCT/LCT/Fresofol PFS MCT/LCT: When Fresofol 1% MCT/LCT is infused undiluted, it is recommended that equipment such as burettes, drop counter, syringe pumps or volumetric infusion pumps should always be used to control infusion rates.
As usual for fat emulsions, the infusion of Fresofol 1% MCT/LCT/Fresofol PFS MCT/LCT via one infusion system must not exceed 12 hours. After 12 hours, the infusion system and reservoir of Fresofol 1% MCT/LCT must be discarded or replaced if necessary.
Infusion of diluted Fresofol 1% MCT/LCT/Fresofol PFS MCT/LCT: For administering infusion of diluted Fresofol 1% MCT/LCT/Fresofol PFS MCT/LCT, burettes, drop counters or volumetric infusion pumps should always be used to control infusion rates and to avoid the risk of accidentally uncontrolled infusion of large volumes of diluted Fresofol 1% MCT/LCT/Fresofol PFS MCT/LCT. This risk has to be taken into account when the decision for the maximum dilution in the burette is made.
The maximum dilution must not exceed 1 part of Fresofol 1% MCT/LCT with 4 parts of 5% w/v glucose solution or 0.9% w/v sodium chloride solution (minimum concentration 2 mg propofol/ml). The mixture should be prepared aseptically (controlled and validated conditions preserved) immediately prior to administration and must be administered within 6 hours after preparation.
Fresofol 1% MCT/LCT must not be mixed with other solutions for infusion or injection. However co-administration of a 5% w/v glucose solution or 0,9% w/v sodium chloride solution or 0.18% w/v sodium chloride and 4% w/v glucose solution with Fresofol 1% MCT/LCT is permitted via a Y-piece connector close to the injection site.
To reduce pain on the injection site, lidocaine may be injected immediately before the use of Fresofol 1% MCT/LCT/Fresofol PFS MCT/LCT. Alternatively, Fresofol 1% MCT/LCT/Fresofol PFS MCT/LCT may be mixed, immediately for use, with preservative free lidocaine injection (20 parts of Fresofol 1% MCT/LCT/Fresofol PFS MCT/LCT with up to 1 part of 1% lidocaine injection solution) under controlled and validated aseptical conditions. The mixture has to be administered within 6 hours after preparation.
Muscle relaxants like atracurium and mivacurium should only be administered after flush of the same infusion site used for Fresofol 1% MCT/LCT/Fresofol PFS MCT/LCT.
Fresofol PFS MCT/LCT in pre-filled syringe will be injected into a vein by electric pumps, therefore appropriate compatibility should be ensured.
Application of Fresofol PFS MCT/LCT pre-filled syringes: Sterility has to be ensured. The outer surface of the syringe and the plunger rod are not sterile!
1. Take out the syringe from the blister and shake it.
2. Insert the plunger rod by screwing it clock-wise into the syringe.
3. Remove the tip cap from the syringe and connect the infusion line to the syringe. Get rid of the air bubble (a small bubble can remain) and the ready-to-use syringe will be installed in the pump.
Target Controlled Infusion – Administration of Fresofol PFS MCT/LCT in pre-filled syringe by pumps: Administration of Fresofol PFS MCT/LCT in pre-filled syringe by a Target Controlled Infusion system is restricted to induction and maintenance of general anaesthesia in adults. It is not recommended for use in ICU sedation or sedation for surgical and diagnostic procedures, or in children.
Fresofol PFS MCT/LCT in pre-filled syringe may be administered by a Target Controlled Infusion system incorporating appropriate Target Controlled Infusion software. Users must be familiar with the infusion pump users' manual, and with the administration of Propofol 1% (Fresofol PFS MCT/LCT) in pre-filled syringe by Target Controlled Infusion.
The system allows the anaesthetist or intensivist to achieve and control a desired speed of induction and depth of anaesthesia by setting and adjusting target (predicted) plasma and/or effect-side concentrations of propofol. Different modalities of the various pump systems should be considered i.e. the Target Controlled Infusion system might assume that the initial blood propofol concentration in the patient is zero. Therefore, in patients who have received prior propofol, there may be a need to select a lower initial target concentration when commencing Target Controlled Infusion. Similarly, the immediate recommencement of Target Controlled Infusion is not recommended if the pump has been switched off.
Guidance on propofol target concentrations is given below. In view of interpatient variability in propofol pharmacokinetics and pharmacodynamics, in both premedicated and unpremedicated patients the target propofol concentration should be titrated against the response of the patient in order to achieve the depth of anaesthesia required.
Induction and Maintenance of General Anaesthesia during target controlled infusion: In adult patients under 55 years of age anaesthesia can usually be induced with target propofol concentrations in the region of 4-8 microgram/ml. An initial target of 4 microgram/ml is recommended in premedicated patients and in unpremedicated patients an initial target of 6 microgram/ml is advised. Induction time with these targets is generally within the range of 60-120 seconds. Higher targets will allow more rapid induction of anaesthesia but may be associated with more pronounced haemodynamic and respiratory depression.
A lower initial target concentration should be used in patients over the age of about 55 years and in patients of ASA grades 3 and 4. The target concentration can then be increased in steps of 0.5-1.0 microgram/mL at intervals of 1 minute to achieve a gradual induction of anaesthesia.
Supplementary analgesia will generally be required and the extent to which target concentrations for maintenance of anaesthesia can be reduced will be influenced by the amount of concomitant analgesia administered. Target propofol concentrations in the region of 3-6 microgram/mL usually maintain satisfactory anaesthesia.
The predicted propofol concentration on waking is generally in the region of 1.0-2.0 microgram/mL and will be influenced by the amount of analgesia given during maintenance.
Sedation during intensive care (target controlled infusion not advised). Target blood propofol concentration settings in the range of 0.2-2.0 microgram/mL will generally be required. Administration should begin at low target setting which should be titrated against the response of the patient to achieve the depth of sedation desired.
Overdosage
Overdose is likely to cause cardiovascular and respiratory depression. Respiratory depression is treated with artificial ventilation. Cardiovascular depression may require lowering the patient's head and administering plasma volume substitutes and vasopressive agents.
Contraindications
Fresofol 1% MCT/LCT/Fresofol PFS MCT/LCT must not be used: in patients with a known hypersensitivity to propofol, soya, peanut or to any of the excipients excipients: soya-bean oil, refined, triglycerides medium-chain, purified egg phosphatides, glycerol, oleic acid and sodium hydroxide.
In patients of 16 years of age or younger for sedation in intensive care (see Precautions).
Special Precautions
Fresofol 1% MCT/LCT: In patients with cardiac, respiratory, renal or hepatic impairment or in elderly, debilitated, hypovolaemic or epileptic patients or patients with disorders of consciousness Fresofol 1% MCT/LCT should be administered with caution and a reduced administration rate (see Dosage & Administration).
Cardiac, circulatory or pulmonary insufficiency and hypovolaemia should be compensated before administration of Fresofol 1% MCT/LCT.
Before anaesthesia of an epileptic patient, it should be checked that the patient has received the antiepileptic treatment. Although several studies have demonstrated efficacy in treating status epilepticus, administration of propofol in epileptic patients may also increase the risk of seizure.
Fresofol 1% MCT/LCT should not be administered in patients with advanced cardiac failure or other severe myocardial disease except with extreme caution and intensive monitoring. The risk of relative vagotonia may be increased because propofol lacks vagolytic activity, It 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 Fresofol 1% MCT/LCT is used in conjunction with other agents likely to cause a bradycardia.
Use is not recommended with electroconvulsive therapy.
As with other sedative agents, 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.
Special care should be applied in patients with disorders of fat metabolism and in other conditions where lipid emulsions must be used with caution. If patients receive parenteral nutrition it is necessary to take account of the amount of lipid infusion as part of the Fresofol 1% MCT/LCT formulation: 1.0 ml Fresofol 1% MCT/LCT contains 0.1 gram of fat.
Lipids should be monitored in the Intensive Care Unit treatment after 3 days.
Due to a higher dosage in patients with severe overweight the risk of haemodynamic effects on the cardiovascular system should be taken into consideration.
Special care should be recognised in patients with a high intracranial pressure and a low mean arterial pressure as there is a risk of a significant decrease of the intracerebral perfusion pressure.
To reduce pain on the injection site during induction of anaesthesia with Fresofol 1% MCT/LCT, lidocaine can be injected prior to the propofol emulsion.
Dilutions with lidocaine solution must not be used in patients with hereditary acute porphyria.
Propofol is not advised for general anaesthesia in children younger than 1 month of age. The safety of propofol for (background) sedation in children younger than 16 years of age have not been demonstrated.
Although no causal relationship has been established, serious undesirable effects with (background) sedation in patients younger than 16 years of age (including cases with fatal outcome) have been reported during unlicensed use. In particular these effects concerned occurrence of metabolic acidosis, hyperlipidemia, rhabdomyolysis and/ or cardiac failure. These effects were most frequently seen in children with respiratory tract infections who received dosages in excess of those advised in adults for sedation in the intensive care unit. Similarly very rare reports have been received of occurrence of metabolic acidosis, rhabdomyolysis, hyperkalaemia and/or rapidly progressive cardiac failure (in some cases with fatal outcome) in adults who were treated for more than 58 hours with dosages in excess of 5 mg propofol/kg body weight/h. This exceeds the maximum dosage of 4 mg propofol/kg body weight/h currently advised for sedation in the intensive care unit. The patients affected were mainly (but not only) seriously head-injured patients with increased intracranial pressure (ICP). The cardiac failure in such cases was usually unresponsive to inotropic supportive treatment.
Treating physicians are reminded if possible not to exceed the dosage of 4 mg propofol/kg body weight/h.
Prescribers should be alert to these possible undesirable effects and consider decreasing the propofol dosage or switching to an alternative sedative at the first sign of occurrence of symptoms. Patients with raised ICP should be given appropriate treatment to support the cerebral perfusion pressure during these treatment modifications.
Special care should be exercised when propofol is used for anaesthesia in infants and children up to 3 years of age, although currently available data do not suggest significant differences in terms of safety compared with children older than 3 years.
In isolated cases there may be a phase of postoperative unconsciousness that may be accompanied by an increased muscle tone. The occurrence of such an event is not related to whether the patient was awake or not. Although consciousness returns spontaneously, unconscious patients should be kept under close observation.
Fresofol 1% MCT/LCT contains soybean oil, which might cause severe allergic reaction in rare cases.
Full recovery from general anaesthesia should be confirmed prior to discharge.
Fresofol PFS MCT/LCT: As with other sedative agents, 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.
In isolated cases there may be a phase of postoperative unconsciousness that may be accompanied by an increased muscular tone. The appearance of this period is not dependent whether the patient came out of an anaesthetic or not. Although consciousness is spontaneously regained the unconscious patient should be kept under intensive observation. Full recovery from general anaesthesia should be confirmed prior to discharge.
Paediatric population: The use of Fresofol PFS MCT/LCT in pre-filled syringe is not recommended for newborn infants as this patient population has not been fully investigated. Pharmacokinetic data indicate that clearance is considerably reduced in neonates with a very high interindividual variability. Relative overdose could occur administering doses recommended for older children resulting in severe cardiovascular depression.
Fresofol PFS MCT/LCT in pre-filled syringe is not recommended for general anaesthesia in children younger than 1 month of age. In any case, special care should be exercised when propofol is used for anaesthesia in infants and children up to 3 years of age, although currently available data do not suggest significant differences in terms of safety compared with children older than 3 years.
Administration of Fresofol PFS MCT/LCT in pre-filled syringe by a Target Controlled Infusion system is not recommended for any indication in children.
The safety of propofol for (background) sedation in the intensive care unit in children and adolescents younger than 16 years of age has not been demonstrated. Although no causal relationship has been established, serious undesirable effects with (background) sedation in patients younger than 16 years of age (including cases with fatal outcome) have been reported during unlicensed use. In particular, these effects concerned occurrence of metabolic acidosis, hyperlipidemia, rhabdomyolysis, renal failure and/or cardiac failure. These effects were most frequently seen in children with respiratory tract infections who received dosages in excess of those advised in adults for sedation in the ICU.
Special patient groups: Cardiac, circulatory or pulmonary insufficiency and hypovolaemia. 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 clearance is blood flow dependent, therefore, concomitant medication which reduces cardiac output will also reduce propofol clearance.
Cardiac, circulatory or pulmonary insufficiency and hypovolaemia should be compensated before administration of Fresofol PFS MCT/LCT in pre-filled syringe.
Fresofol PFS MCT/LCT in pre-filled syringe should not be administered in patients with advanced cardiac failure or other severe myocardial disease except with extreme caution and intensive monitoring.
The risk of relative vagotonia may be increased because propofol lacks vagolytic activity. It 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 with Fresofol PFS MCT/LCT in pre-filled syringe should be considered, especially in situations where vagal tone is likely to predominate or when Fresofol PFS MCT/LCT in prefilled syringe is used in conjunction with other agents likely to cause a bradycardia.
Epilepsy: Before anaesthesia of an epileptic patient, it should be checked that the patient has received the antiepileptic treatment. Although several studies have demonstrated efficacy in treating status epilepticus, administration of propofol in epileptic patients may also increase the risk of seizure.
Use of Fresofol PFS MCT/LCT in pre-filled syringe is not recommended with electroconvulsive therapy.
Patients with disorders of fat metabolism: Special care should be applied in patients with disorders of fat metabolism and in other conditions where lipid emulsions must be used with caution. If patients receive parenteral nutrition it is necessary to take account of the amount of lipid infusion as part of the Propofol 1% MCT/LCT in pre-filled syringe formulation: 1.0 mL Fresofol PFS MCT/LCT in pre-filled syringe contains 0.1 gram of fat.
Lipids should be monitored in the Intensive Care Unit treatment every 2 days.
Due to a higher dosage in patients with severe overweight the risk of haemodynamic effects on the cardiovascular system should be taken into consideration.
Patients with a high intracranial pressure: Special care should be recognised in patients with a high intracranial pressure and a low mean arterial pressure as there is a risk of a significant decrease of the intracerebral perfusion pressure.
Similarly very rare reports have been received of occurrence of metabolic acidosis, rhabdomyolysis, hyperkalaemia, arrhythmias and/or rapidly progressive cardiac failure (in some cases with fatal outcome) in adults who were treated for more than 48 hours with dosages in excess of 5 mg propofol/kg bodyweight/h. This exceeds the maximum dosage of 4 mg propofol/ kg bodyweight/h currently advised for sedation in the intensive care unit. The patients affected were mainly (but not only) seriously head-injured patients with increased intracranial pressure (ICP). The cardiac failure in such cases was usually unresponsive to inotropic supportive treatment.
Treating physicians are reminded if possible not to exceed the dosage of 4 mg propofol/kg bodyweight/h. Prescribers should be alert to these possible undesirable effects and consider decreasing the propofol dosage or switching to an alternative sedative at the first sign of occurrence of respective symptoms. Patients with raised ICP should be given appropriate treatment to support the cerebral perfusion pressure during these treatment modifications.
Pain on the injection site: To reduce pain on the injection site during induction of anaesthesia with Fresofol PFS MCT/LCT in pre-filled syringe, lidocaine can be injected prior to the propofol emulsion.
Intravenous lidocaine must not be used in patients with hereditary acute porphyria.
This medicinal product contains less than 1 mmol (23 mg) sodium per 100 mL, i.e. essentially ‘sodium- free’.
Effects on ability to drive and use machines: Fresofol 1% MCT/LCT/Fresofol PFS MCT/LCT has major influence on the ability to drive and use machines. After administration of Fresofol 1% MCT/LCT/Fresofol PFS MCT/LCT, the patient should be kept under observation for an appropriate period of time. The patient should be instructed not to drive, operate machinery, or work in potentially hazardous situations. The patient should not be allowed to go home unaccompanied, and should be instructed to avoid consumption of alcohol.
Use In Pregnancy & Lactation
Pregnancy: The safety of propofol during pregnancy has not been established. Therefore, propofol should not be used in pregnant women unless clearly necessary. Propofol crosses the placenta and may be associated with neonatal depression. High doses (more than 2.5 mg propofol/kg body weight for induction or 6 mg propofol/kg body weight/h for maintenance of anaesthesia) should be avoided.
Lactation: Studies in breast-feeding women showed that propofol is excreted in small amounts into the milk. Therefore, mothers should stop breast-feeding and discard breast milk for 24 hours after administration of propofol.
Adverse Reactions
Commonly observed side effects of propofol are hypotension and respiratory depression. These effects depend on the propofol dose administered but also on the type of premedication and other concomitant medication.
In this section undesirable effects are defined as follows: 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); Not known (cannot be estimated from the available data).
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Immune system disorders: Rare: Clinical features of anaphylaxis, which may include Quincke's oedema, bronchospasm, erythema and hypotension.
Very rare: Allergic reactions caused by soya-bean oil.
Metabolism and nutrition disorders: Common: Hypertriglyceridemia.
Psychiatric disorders: Rare: Euphoria and sexual disinhibition during the recovery period.
Nervous system disorders: Common: During induction of anaesthesia spontaneous movements and myocloni, minimal excitation.
Rare: Headache, vertigo, shivering and sensations of cold during the recovery period.
Epileptiform movements including convulsions and opisthotonus.
Very rare: Delayed epileptiform attacks, the delay period ranging from a few hours to several days. Risk of convulsions in epileptic patients after administration of propofol. Cases of postoperative unconsciousness (see Precautions).
Cardiac disorders/Vascular disorders: Common: During induction of anaesthesia, hypotension, bradycardia, tachycardia, hot flushes.
Uncommon: Marked hypotension. This may require a lowering of the administration rate of Fresofol 1% MCT/LCT and/or fluid replacement therapy, if necessary vasoconstrictive medicinal products. Account should be taken of the possibility of a severe drop in blood pressure in patients with impaired coronary or cerebral perfusion or those with hypovolaemia.
Bradycardia during general anaesthesia with progressive severity (asystole). The intravenous administration of an anticholinergic medicinal product prior to induction or during maintenance of anaesthesia should be considered (see Precautions).
Rare: Arrhythmia during the recovery period. Thrombosis and phlebitis.
Vascular disorders: Rare: Thrombosis and phlebitis.
Respiratorv, thoracic and mediastinal disorders: Common: During induction of anaesthesia hyperventilation, transient apnoea, coughing, singultus.
Uncommon: Coughing during maintenance of anaesthesia.
Rare: Coughing during the recovery period.
Very rare: Pulmonary oedema.
Gastrointestinal disorders: Rare: Nausea or vomiting during the recovery period.
Very rare: Pancreatitis has been reported after administration of propofol. A causal relationship, however, could not be established.
Skin and subcutaneous tissue disorders: Very rare: Severe tissue responses after accidental paravenous application.
Renal and urinary disorders: Rare: Cases of discoloration of urine following prolonged administration of propofol.
General disorders and administration site conditions: Very common: Local pain occurring during the initial injection. Prophylaxis or treatment see as follows.
The local pain which may occur during the initial injection of Fresofol 1% MCT/LCT/Fresofol PFS MCT/LCT can be minimised by the co-administration of lidocaine (see Dosage & Administration) and by injection or infusion into the larger veins of the forearm and antecubital fossa. Upon co-administration of lidocaine the following undesirable effects may occur rarely (≥1:10,000 to <1:1,000): giddiness, vomiting, drowsiness, convulsions, bradycardia, cardiac arrhythmia and shock.
Rare: Cases of post-operative fever.
Very rare: There have been reports of isolated cases of severe undesirable effects presenting as a complex of symptoms including: rhabdomyolysis, metabolic acidosis, hyperkalaemia, and cardiac failure, sometimes with fatal outcome. Most of these effects have been observed in patients in intensive care with doses exceeding 4 mg/kg body weight/h. For more detail, see Precautions.
Reporting of Suspected Adverse Reactions: Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system.
Drug Interactions
Fresofol 1% MCT/LCT/Fresofol PFS MCT/LCT can be used in combination with other medicinal products for anaesthesia (premedications, volatile anaesthetics, analgesics, muscle relaxants, local anaesthetics). Severe interactions with these medicinal products have been reported. Some of these centrally acting medicinal products may exhibit a circulatory and respiratory depressive effect, thus leading to increased effects when used together with Fresofol 1% MCT/LCT/Fresofol PFS MCT/LCT.
Lower doses may be required when general anaesthesia is carried out in conjunction with regional anaesthesia.
Concomitant use of benzodiazepines, parasympatholytic agents or inhalational anaesthetics has been reported to prolong the anaesthesia and to reduce the respiratory rate.
After additional premedication with opioids, the sedative effects of propofol may be intensified and prolonged, and there may be a higher incidence and longer duration of apnoea. 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 Fresofol 1% MCT/LCT/Fresofol PFS MCT/LCT is combined with centrally depressant agents administered parenterally, severe respiratory and cardiovascular depression may occur.
After administration of fentanyl, the blood level of propofol may be temporarily increased with an increase in the rate of apnoea.
Bradycardia and cardiac arrest may occur after treatment with suxamethonium or neostigmin. Leucoencephalopathy has been reported with administration of lipid emulsions such as propofol in patients receiving cyclosporine.
Caution For Usage
Incompatibilities: Fresofol 1% MCT/LCT should not be mixed prior to administration with injection or infusion solutions other than 5% w/v glucose solution or 0.9% w/v sodium chloride solution or 1% lidocaine injection solution (see Dosage & Administration). Final propofol concentration must not be below 2 mg/ml.
Fresofol PFS MCT/LCT in pre-filled syringe must not be mixed with other medicinal products except those mentioned in Pharmaceutical Precautions.
Pharmaceutical precautions: Do not use Fresofol 1% MCT/LCT/Fresofol PFS MCT/LCT after the expiry date which is stated on the syringe and the outer packaging after EXP. The expiry date refers to the last day of that month.
Fresofol 1% MCT/LCT: Prior to use, the ampoule neck or rubber membrane should be cleaned using an alcohol spray or a swab dipped in alcohol. After use, tapped containers must be discarded.
Administration of the emulsion must commence without delay after opening the ampoule or breaking the vial seal.
The infusion of undiluted Fresofol 1% MCT/LCT via one infusion system must not exceed 12 hours.
Dilutions with 5% w/v glucose solution or 0.9% w/v sodium chloride solution or an admixture 1% lidocaine injection solution (at least 2 mg propofol per ml should be prepared aseptically (controlled and validated conditions preserved) immediately before administration and must be administered within 6 hours after preparation.
For single use. Any unused emulsion must be discarded.
If two layers can be seen after shaking the emulsion should not be used.
Use only homogeneous preparations and undamaged containers.
Fresofol PFS MCT/LCT: After first opening the product must be used immediately.
Administration systems with undiluted Fresofol PFS MCT/LCT in pre-filled syringe should be replaced 12 hours after opening of the syringe. Fresofol PFS MCT/LCT in pre-filled syringe should not be mixed prior to administration with injection or infusion solutions other than glucose 50 mg/mL (5%) solution for injection or sodium chloride 9 mg/mL (0.9%) solution for injection or preservative free lidocaine 10 mg/mL (1%) solution for injection. The maximum dilution must not exceed 1 part of Fresofol PFS MCT/LCT in pre-filled syringe with 4 parts of glucose 50 mg/mL (5%) solution for injection or sodium chloride 9 mg/mL (0.9%) solution for injection (minimum concentration 2 mg propofol/ml). The mixture should be prepared aseptically (controlled and validated conditions preserved) immediately prior to administration and must be administered within 6 hours after preparation (see Dosage & Administration).
Final propofol concentration must not be below 2 mg/mL.
Co-administration of a glucose 50 mg/mL (5%) solution for injection or sodium chloride 9 mg/ml solution for injection or sodium chloride 1.8 mg/ mL (0.18%) solution for injection and glucose 40 mg/mL (4%) solution for injection with Fresofol PFS MCT/LCT in prefilled syringe is permitted via a Y-piece connector close to the injection site.
Storage
Do not store above 25°C. Do not freeze.
ATC Classification
N01AX10 - propofol ; Belongs to the class of other general anesthetics.
Presentation/Packing
Fresofol MCT/LCT: Emulsion for IV infusion (vial) 10 mg/mL (1% w/v) x 50 mL x 1's.
Fresofol PFS MCT/LCT: Emulsion for IV infusion (pre-filled syringe) 10 mg/mL (1% w/v) (white, homogenous oil in water emulsion) x 50 mL x 1's
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