PROPOFOL BIOQ PHARMA 10 MG / ML (1%) EMULSION FOR INFUSION IN ADMINISTRATION SYSTEM - summary of medicine characteristics

1 NAME OF THE MEDICINAL PRODUCT

Propofol BioQ Pharma 10 mg/ml (1 %) emulsion for infusion in administration sys­tem

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

1 ml emulsion for infusion contains 10 mg propofol. Each pre-filled infusion pump (administration system) contains a 50 ml cartridge corresponding to 500 mg propofol.

Excipient with known effect

1 ml emulsion for infusion contains 100 mg soya-bean oil, refined. Each pre-filled infusion pump (administration system) contains 5 g soya-bean oil, refined.

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Emulsion for infusion

White aqueous isotonic oil-in-water emulsion.

Osmolarity: 285 to 320 mOsm/kg.

pH is in the range of 6.0 – 8.5.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Propofol BioQ Pharma is a short-acting intravenous general anaesthetic for:

– Induction and maintenance of general anaesthesia in adults, adolescents and children > 40 kg.

– Sedation for diagnostic and surgical procedures, alone or in combination with local or regional anaesthesia in adults, adolescents and children > 40 kg.

– Sedation of ventilated patients > 16 years of age in the intensive care unit.

4.2 Posology and method of administration

Propofol BioQ Pharma must only be administered 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 oximetry) and facilities for maintenance patient airways, artificial ventilation, and other resuscitation facilities should be immediately available at all times.

For sedation during surgical and diagnostic procedures Propofol BioQ Pharma should not be administered by the same person conducting the surgical or diagnostic procedure.

Propofol BioQ Pharma has no analgesic properties and therefore supplementary analgesic agents are generally required in addition to Propofol BioQ Pharma.

Posology

The dose of Propofol BioQ Pharma is determined by entering the patient’s weight (minimum value 40 kg) and the infusion rate (in mg/kg body weight/h) into the prefilled infusion pump (administration system, see section 6.6). It should be individually adapted according to the patient’s response.

Propofol BioQ Pharma is not intended for target controlled infusion.

Rapid bolus administration (single or repeated) should not be used in the elderly as this may lead to cardiorespiratory depression.

General anaesthesia in adults, adolescents and children > 40 kg

Induction of anaesthesia

For induction of anaesthesia Propofol BioQ Pharma must be titrated (20 – 40 mg propofol, corresponding to 2 – 4 ml Propofol BioQ Pharma every 10 seconds) against the response of the patient until clinical signs show the onset of anaesthesia by pressing the “Bolus/Prime” button of the pre-filled infusion pump (administration system, see section 6.6).

Usually, an adult patient below 55 years will require 1.5 to 2.5 mg propofol/kg body weight.

In patients over 55 years and in patients of ASA (American Society of Anaesthesiologists) grades III and IV, especially in those with impaired cardiac function, the requirements will generally be less and the total dose of Propofol BioQ

Pharma may be reduced to a minimum of 1 mg propofol/kg body weight. These patients also need lower rates of administration (approximately 2 ml corresponding to 20 mg propofol every 10 seconds).

Maintenance of anaesthesia

Anaesthesia can be maintained by administering Propofol BioQ Pharma by continuous infusion.

When using a continuous infusion for maintenance of anaesthesia, generally doses of 4 to 12 mg/kg body weight/h should be given.

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 Propofol BioQ Pharma may be further reduced depending on the patient’s condition and on the applied anaesthetic method.

Sedation  for diagnostic and surgical interventions in adults, adolescents and children > 40 kg

To provide sedation during surgical and diagnostic interventions, doses and administration rates need to be adapted to the clinical response.

Most patients will require 0.5 to 1.0 mg propofol/kg body weight over 1 to 5 minutes for induction of sedation.

For maintenance of sedation, the Propofol BioQ Pharma infusion should be titrated until the desired level of sedation is achieved. Generally, 1.5 to 4.5 mg/kg body weight/h will be required.

The infusion may be supplemented by bolus injections of 20 mg propofol (2 ml Propofol BioQ Pharma) if a deeper level of sedation is rapidly required.

In patients older than 55 years and in patients of ASA classification III and IV the rate of administration and dosage may need to be reduced.

Sedation of mechanically ventilated adults and adolescents (> 16 years of age) during intensive care

When used to provide sedation for mechanically ventilated patients under intensive care conditions, the administration of Propofol BioQ Pharma as continuous infusion is recommended. The rate of administration has to be adapted to the level of sedation required.

A satisfactory level of sedation can generally be achieved with a dosage of 0.3 –4.0 mg/kg body weight/h (see section 4.4).

It is recommended that blood lipid levels should be monitored if Propofol BioQ Pharma is administered to patients thought to be at particular risk of fat overload. Administration of Propofol BioQ Pharma 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 BioQ Pharma formulation; 1.0 ml of Propofol BioQ Pharma contains approximately 0.1 g of fat.

If the duration of sedation is in excess of 3 days, lipids should be monitored in all patients.

Paediatric population

Propofol BioQ Pharma cannot be used for induction/main­tenance of general anaesthesia and sedation for diagnostic/surgical procedures in children and adolescents with a body weight below 40 kg. However, other propofol formulations are available for use in children > 1 month of age.

Propofol BioQ Pharma is contraindicated in children and adolescents < 16 years of age of age for sedation in intensive care (see section 4.3).

Method of administration

Propofol BioQ Pharma is administered intravenously as a continuous infusion.

The contents of one pre-filled infusion pump (administration system) is intended for single use in one patient.

To reduce pain on the injection site lidocaine may be injected immediately before the use of Propofol BioQ Pharma. For the specific risks of lidocaine see sections 4.4 and 4.8.

See section 6.6 for precautions prior to use and information on the pre-filled infusion pump (administration system).

This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.

Duration of administration

As applies to parenteral administration of all kinds of fat emulsions, the duration of use for one infusion system for a continuous infusion of Propofol BioQ Pharma must not exceed 12 hours.

Propofol can be administered for a maximum of 7 days.

4.3 Contraindications

– Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

– Hypersensitivity to peanut or soya.

– Sedation in the intensive care unit in paediatric patients < 16 years of age (see section 4.4).

4.4 Special warnings and precautions for use

Propofol should be given by health care professionals trained in anaesthesia (or, where appropriate, doctors trained in the care of patients in intensive care).

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 BioQ Pharma should not be administered by the person conducting the diagnostic or surgical procedure.

The abuse of, and dependence on, propofol, predominantly by health care professionals, has been reported. As with other general anaesthetics, the administration of Propofol BioQ Pharma without airway care may result in fatal respiratory complications.

When Propofol BioQ Pharma is administered for conscious sedation, for surgical and for diagnostic procedures, patients should be continually monitored for early signs of hypotension, airway obstruction and oxygen desaturation.

As with other sedative agents, when Propofol BioQ Pharma is used for sedation during surgical procedures, involuntary patient movements may occur. During procedures requiring immobility these movements may be hazardous to the surgical site.

An adequate period is needed prior to discharge of the patient to ensure full recovery after use of Propofol BioQ Pharma. 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 agents that may sedate (e.g. benzodiazepines, opiates,

alcohol)

During induction of anaesthesia, hypotension and transient apnoea may occur depending on the dose and use of premedications and other agents.

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 that reduces cardiac output will also reduce propofol clearance.

Cardiac, circulatory or pulmonary insufficiency and hypovolaemia should be compensated before administration of propofol.

In patients with severe cardiac impairment it is recommended that Propofol BioQ Pharma is given with great caution and under intensive monitoring.

Due to the higher doses to be usually applied in patients with severe overweight, the increased risk of adverse haemodynamic effects should be taken into consideration.

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 the vagal tone is likely to predominate or when Propofol BioQ Pharma is used in conjunction with other agents likely to cause bradycardia.

Elderly

In elderly patients, Propofol BioQ Pharma should be administered with caution and with a reduced administration rate (see section 4.2).

Epilepsy

When Propofol BioQ Pharma 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. 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 propofol is not recommended with electroconvulsive therapy.

Patients with a high intracranial pressure

Special care should be taken in patients with high intracranial pressure and low arterial pressure as there is a risk of significant decrease of the intracerebral perfusion pressure.

Patients with hereditary disorders

Propofol BioQ Pharma must not be used in combination with lidocaine solution in patients with hereditary predisposition to acute porphyria.

Paediatric population

Propofol BioQ Pharma cannot be used for induction/main­tenance of general anaesthesia and sedation for diagnostic/surgical procedures in children and adolescents with a body weight below 40 kg, because this is the minimum weight that can be entered into the pre-filled infusion pump (administration system).

Propofol BioQ Pharma must not be used in patients < 16 years of age for sedation for intensive care as the safety and efficacy of propofol for sedation in this age group have not been demonstrated (see section 4.3).

Advisory statements concerning intensive care unit management

Use of propofol emulsion infusions for ICU sedation has been associated with a constellation of metabolic derangements and organ system failures that may result in death.

Reports have been received of combinations of the following: metabolic acidosis, rhabdomyolysis, hyperkalaemia, hepatomegaly, renal failure, hyperlipidaemia, cardiac arrhythmia, Brugada-type ECG (elevated ST-segment and coved T-wave) and rapidly progressive cardiac failure usually unresponsive to inotropic supportive treatment. Combinations of these events have been referred to as the propofol infusion syndrome. These events were mostly seen in patients with serious head injuries and children with respiratory tract infections who received dosages in excess of those advised in adults for sedation in the intensive care unit.

The following appear to be the major risk factors for the development of these events: decreased oxygen delivery to tissues; serious neurological injury and/or sepsis; high dosages of one or more of the following pharmacological agents – vasoconstrictors, steroids, inotropes and/or propofol (usually following extended dosing at dose rates greater than 4 mg/kg/h for more than 48 hours).

Prescribers should be alert to these events in patients with the above risk factors and immediately discontinue propofol when the above signs develop. All sedative and therapeutic agents used in the intensive care unit (ICU), including propofol, should be titrated to maintain optimal oxygen delivery and haemodynamic parameters. Patients with raised intra-cranial pressure (ICP) should be given appropriate treatment to support the cerebral perfusion pressure during these treatment modifications. Treating physicians are reminded if possible not to exceed the dosage of 4 mg/kg/h.

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 BioQ Pharma is administered to patients thought to be at particular risk of fat overload. Administration of Propofol BioQ Pharma 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 (e.g. parenteral nutrition) concurrently, a reduction in quantity should be made in order to take account of the amount of lipid infused as part of the Propofol BioQ Pharma formulation; 1.0 ml of Propofol BioQ Pharma contains approximately 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 disorders when undergiong anaesthesia, surgery and ICU care. Maintenance or 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.

Propofol BioQ Pharma contains no antimicrobial preservatives and supports growth of micro-organisms.

Propofol BioQ Pharma is for single use in an individual patient. In accordance with established guidelines for other lipid emulsions, a single infusion of Propofol BioQ Pharma must not exceed 12 hours. At the end of the procedure or at 12 hours, whichever is the sooner, both the pre-filled infusion pump (administration system) and the infusion line must be discarded and replaced as appropriate.

Excipients

This medicinal product contains less than 1 mmol sodium (23 mg) per pre-filled infusion pump (administration system), that is to say essentially “sodium-free”.

4.5 Interaction with other medicinal products and other forms of interaction

Propofol BioQ Pharma has been used in association with spinal and epidural anaesthesia and with commonly used premedication, neuromuscular blocking drugs, inhalational agents and analgesic agents; no pharmacological incompatibility has been encountered. Lower doses of Propofol BioQ Pharma may be required where general anaesthesia or sedation is used as an adjunct to regional anaesthetic techniques.

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

Propofol BioQ Pharma can be used in combination with other active substances for anaesthesia (premedication, volatile anaesthetics, analgesics, muscle relaxants, local anaesthetics). Until now no severe interactions with these active substances have been reported. Some of these centrally acting active substances may exhibit a circulatory and respiratory depressive effect, thus leading to increased effects when used together with Propofol BioQ Pharma.

Concomitant use of benzodiazepines, parasympatholytic agents or volatile anaesthetics has been reported to prolong the anaesthesia and to reduce the respiratory rate.

When used in addition to local anaesthesia, the dosage of Propofol BioQ Pharma may need to be reduced.

After additional premedication with opioids there may be a higher incidence and longer duration of apnoea.

Bradycardia and cardiac arrest may occur after treatment with suxamethonium or neostigmine.

It should be taken into consideration that concomitant use of propofol and active substances for premedication, volatile agents or analgesic agents may potentiate anaesthesia and cardiovascular side effects. Concomitant use of central nervous depressants, e.g. alcohol, general anaesthetics, and narcotic analgesics, will result in intensification of their sedative effects.

After administration of fentanyl, the blood level of propofol may be temporarily increased with an increase in the rate of apnoea.

Leucoencephalopathy has been reported with administration of lipid emulsions such as propofol in patients receiving ciclosporin.

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

4.6 Fertility, pregnancy and lactation

Pregnancy

The safety of propofol during pregnancy has not been established. Studies in animals have shown reproductive toxicity (see section 5.3). Propofol BioQ Pharma should not be given to pregnant women except when absolutely necessary. Propofol crosses the placenta and can cause neonatal depression. Propofol BioQ Pharma can, however, be used during an induced abortion.

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.

Breastfeeding

Studies of breastfeeding mothers showed that small quantities of propofol are excreted in human milk. Women should therefore not breastfeed for 24 hours after administration of Propofol BioQ Pharma. Milk produced during this period should be discarded.

4.7 Effects on ability to drive and use machines

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 BioQ Pharma.

After administration of Propofol BioQ Pharma 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 for at least 12 hours before and after administration.

Propofol induced impairment is not generally detectable beyond 12 hours (see section 4.4).

4.8 Undesirable effects

Induction and maintenance of anaesthesia or sedation with propofol is generally smooth with minimal evidence of excitation. 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.

(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/h 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 coadministration 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, see section 4.4.

(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.

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 Yellow Card Scheme, Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9 Overdose

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.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Anaesthetics, general; other general anaesthetics, ATC code: N01AX10

After intravenous injection of propofol, onset of the hypnotic effect occurs rapidly. 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 due to the rapid metabolism and excretion (4 – 6 minutes).

With the recommended dosage schedule a clinically relevant accumulation of propofol after repeated bolus injection or after infusion has not been observed. Patients recover consciousness rapidly.

Bradycardia and hypotension occasionally occur during induction of anaesthesia probably due to a lack of vagolytic activity. The cardio-circulatory situation usually normalises during maintenance of anaesthesia.

5.2 Pharmacokinetic properties

After intravenous administration about 98 % of propofol is bound to plasma protein.

Propofol is extensively distributed (central distribution volume from 0.2 to 0.79 l/kg body weight; steady-state volume is 1.8 – 5.3 l/kg body weight) and rapidly cleared from the body (total body clearance: 1.5–2 l/minute). Clearance occurs by metabolic processes, mainly in the liver where it is blood flow dependent to form inactive conjugates of propofol (glucoronides) and its corresponding metabolite quinol (glucoronides and sulphate compounds), which are excreted in urine (88 % of the administered dose). All metabolites are inactive. Only 0.3 % of the administered dose is excreted unchanged in the urine.

During elimination the decline of blood levels is slower. The elimination half-life during the P-phase is in the range of 30 to 60 minutes. Subsequently a third deep compartment becomes apparent, representing the re-distribution of propofol from weakly perfused tissue.

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.

5.3 Preclinical safety data

Non-clinical data reveal no special hazard for humans based on conventional studies on repeated dose toxicity or genotoxicity.

Carcinogenicity studies have not been conducted.

Reproductive toxicity studies have shown effects related to pharmacodynamic properties of propofol at high doses. Published studies in animals (including primates) at doses resulting in light to moderate anaesthesia demonstrate that the use of anaesthetic agents during the period of rapid brain growth or synaptogenesis results in cell loss in the developing brain that can be associated with prolonged cognitive deficiencies. The clinical significance of these nonclinical findings in not known. Teratogenic effects have not been observed.

In local tolerance studies, intramuscular injection resulted in tissue damage around the injection site.,

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Soya-bean oil, refined

Purified egg phospholipids

Glycerol

Sodium hydroxide (for pH-adjustment)

Water for injections

6.2 Incompatibilities

This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.

The neuromuscular blocking agents, atracurium and mivacurium, should not be given through the same Y-connector as Propofol BioQ Pharma without prior flushing.

6.3 Shelf life

1 year

After first opening

In accordance with established guidelines for other lipid emulsions, a single infusion of Propofol BioQ Pharma must not exceed 12 hours. At the end of the procedure or at 12 hours, whichever is the sooner, both the pre-filled infusion pump (administration system) and the infusion line must be discarded and replaced as appropriate.

Chemical and physical in-use stability of the medicinal product has been demonstrated for 24 hours at 25 °C. From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user.

6.4 Special precautions for storage Do not freeze.

Keep the medicinal product in the outer carton in order to protect from light.

6.5 Nature and contents of container

Each pre-filled infusion pump (administration system, see section 6.6) contains 50 ml emulsion for infusion in a colourless type I glass cartridge with teflon-coated bromobutyl plunger and polypropylene stopper.

Each pack contains one pre-filled infusion pump (administration system).

6.6 Special precautions for disposal and other handling

The simultaneous administration of Propofol BioQ Pharma together with an intravenous infusion solution of glucose 50 mg/ml (5 %) or sodium chloride 9 mg/ml (0.9 %) intravenous infusion solution or a combination solution of glucose 40 mg/ml (4 %) and sodium chloride 1.8 mg/ml (0.18 %) close to the Y-connector near the place of injection, is possible.

For single use only.

Parenteral products should be inspected visually for particulate matter prior to administration. If particulate matter is evident, emulsion should not be used.

The pre-filled infusion pump (administration system) should be shaken before use. If two layers can be seen after shaking, the emulsion should not be used.

Use of the pre-filled infusion pump (administration system)

For detailed instructions on use, warning indicators and error handling, please refer to the enclosed package leaflet.

Elements of the pre-filled infusion pump (administration system)

Activation of the pre-filled infusion pump (administration system)

To activate the pre-filled infusion pump (administration system), the activation tab is pulled from the side of the infusion pump by the attached ring. An alarm will chirp, and the displays will light up.

The tape from the administration line is removed and the tubing uncoiled. The tamper evident cap is removed.

Priming of the system

In order to remove any air trapped in the system, the pre-filled infusion pump (administration system) is turned upside down and the location where the administration line exits the infusion pump is held upwards. To ensure correct priming and orientation of the infusion pump while priming, an overlay with the instructions for priming is attached to the infusion pump. Orient with the arrow on the overlay pointing up and press “Bolus/Prime” then the “Start/Stop” button to prime. Priming can be stopped by pressing the “Start/Stop” button. Luer cap must be removed to prime the line.

If continuous bubbles are observed in the administration line after multiple attempts at priming, the infusion pump may not be used.

Settings and initiation

After connection of the administration line to the patient’s primary IV line, the body weight and the dosage can be set by pressing the “+” or “-“ buttons of the weight and the dosage selector.

The patient weight can be entered in increments of 5 kg (range: 40 – 140 kg) to the value closest to the patient’s weight. The dosage range is 0.3 – 18.0 mg/kg/h. It can be set to the desired value in mg/kg body weight/h. First increase is from 0.3 to 0.5 mg/kg/h. Then increments of 0.5 mg/kg body weight/h (in the range of

0.5 – 5.0 mg/kg body weight/h) and of 1.0 mg/kg body weight/h (in the range of 5.0 –18.0 mg/kg body weight/h) are possible.

Fluid flow is initiated by pressing the “Start/Stop” button. A single green light will indicate that fluid is being delivered. To pause delivery, the “Start/Stop” button may be pressed again. The green light will then switch off indicating that fluid is no longer being delivered.

If paused for 60 minutes, the pre-filled infusion pump (administration system) will permanently deactivate.

A change in weight or dose can be made by pressing the “+” or “-” buttons while delivery is paused.

A change in the dose while fluid is being delivered can be made by pressing the “+” or “-” buttons on the dosage selector to enter the desired setting. The “Start/Stop” button must then be pressed to confirm the rate change, otherwise the settings will revert to the previous settings.

Administration of a bolus

To administer a loading or supplemental bolus dose, press the “Bolus/Prime” button to select a 2 ml or 4 ml bolus dose. A white light next to the bolus volume will illuminate, the pre-filled infusion pump (administration system) will beep, and the green infusion light will flash indicating the bolus must be confirmed. Press the “Start/Stop” button to deliver the bolus. The bolus will deliver over an interval of approximately 10 seconds. To stop a bolus, the “Start/Stop” button can be pressed.

If fluid is already being delivered prior to administration of the bolus, this will be resumed after (stopped) delivery of the bolus.

Deactivation and disposal

After use, the pre-filled infusion pump (administration system) should be permanently deactivated by pressing both “-” buttons simultaneously for 5 seconds. The alarm will sound and all lights and displays will flash, then turn off. The infusion pump will then be non-functional.

The infusion pump including any unused medicinal product and waste material should be disposed in accordance with local requirements.

7 MARKETING AUTHORISATION HOLDER

BioQ Pharma Ltd

Garden Cottage, Hascombe Road

Godalming, Surrey GU8 4AE

United Kingdom

8 MARKETING AUTHORISATION NUMBER(S)

PL 45205/0003

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

08/10/2018