Propofol-lipuro 1% (10 mg / ml) – patient leaflet, side effects, dosage

1. What Propofol is and what it is used for

Propofol belongs to a group of medicines called general anaesthetics. General anaesthetics are used to cause unconsciousness (sleep) so that surgical operations or other procedures can be performed. They can also be used to sedate you (so that you are sleepy but not completely asleep).

Propofol is used to:

• induce and maintain general anaesthesia in adults and children > 1 month
• sedate patients > 16 years of age receiving artificial respiration in intensive care
• sedate adults and children > 1 month during diagnostic and surgical procedures, alone or in combination with local or regional anaesthesia.

2. What you need to know before you use Propofol

Do not use Propofol:

• if you are allergic to propofol, soya, peanut or any of the other ingredients of this medicine (listed in section 6). It must not be used in patients of 16 years of age or younger for sedation during intensive care. Safety and efficacy for these age groups have not been demonstrated.

Warnings and precautions

Talk to your doctor or pharmacist before receiving Propofol.

Special care has to be taken

• if you have serious head injuries,
• if you have a mitochondrial disease,
• if you have a disorder in which your body does not handle fat properly,
• if you have any other health problems which require much caution in the use of fat emulsions,
• if your blood volume is too low (hypovolaemia),
• if you have a low protein concentration in your blood (hypoproteinaemia),
• if you are very weak (debilitated) or have heart, kidney or liver problems,
• if you have high pressure within in the skull,
• if you have problems with your breathing,
• if you have epilepsy,
• if you are undergoing some procedures where spontaneous movements are particularly undesirable. Please tell your doctor if you have one of these diseases or conditions.

If you are receiving other lipids by a drip into your vein at the same time your doctor will pay attention to your total daily fat intake.

Propofol will be administered to you by a physician trained in anaesthesia or intensive care. You will be constantly monitored during anaesthesia and waking-up time.

If you experience signs of the so called ‘propofol infusion syndrome’ (for a detailed list of the symptoms see section 4 ‘Possible side effects’, ‘A doctor must be called immediately if any of the following happens’) your doctor will immediately stop the dosage of propofol.

Please see also section ‘Driving and using machines’ for precautions to be taken after the use of propofol. Children and adolescents

The use of Propofol is not recommended in newborn infants.

This medicine must not be used in patients of 16 years of age or younger for sedation for intensive care (see section ‘Do not use Propofol:’).

Other medicines and Propofol

Tell your doctor or pharmacist if you are taking or have recently taken or might take any other medicines. Propofol has effectively been used with different regional anaesthesia techniques that only numb a part of your body (epidural and spinal anaesthesia).

Additionally, safe use has been demonstrated in combination with

• drugs you receive before surgery
• other medicines like muscle relaxing drugs
• anaesthetic drugs that can be inhaled
• pain killers.

PACKAGE LEAFLET: INFORMATION FOR THE USER

Propofol 1% (10 mg/ml)

emulsion for injection or infusion

Propofol

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.

• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

  However, your physician may give you lower doses of propofol if general anaesthesia or sedation is needed as a supplement to regional anaesthesia techniques. Your doctor will consider that other medicines with an inhibiting effect on the central nervous system may increase the effects of propofol when given together with propofol.

  Special care will also be taken if you receive in parallel an antibiotic containing rifampicin – you may develop profound low blood pressure. Your dose might be reduced by your doctor if you are also treated with valproate (anticonvulsant).

  Propofol with alcohol

  Your doctor will advise you on the consumption of alcohol before and after the use of Propofol 1% (10 mg/ml).

  Pregnancy and breast-feeding

  If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

  Propofol should not be used during pregnancy unless it is definitely needed. It crosses the placenta and may depress the vital functions of the newborn.

  However, propofol may be used during an induced abortion.

  If you are breast-feeding your child, you should stop nursing and discard breast milk for 24 hours after you have received Propofol. Studies in breast-feeding women showed that propofol is excreted in small amounts into the milk.

  Driving and using machines

  You should not drive or operate machinery for a while after you have had an injection or infusion of Propofol Your doctor will advise you

  • if you should be accompanied when you are leaving.
  • when you can drive and use machinery again.
  • on the use of other tranquillizing drugs (e.g. tranquillizers, strong pain killers, alcohol).

Propofol contains sodium and soya-bean oil

This medicine contains less than 1 mmol sodium (23 mg) per 100 ml, that is to say essentially ‘sodium-free’. Propofol contains soya oil. If you are allergic to peanut or soya, do not use this medicine.

3. How to use Propofol

Propofol will only be given by persons trained in anaesthesia or by specially trained doctors in a hospital or in an adequately equipped day therapy unit.

Dosage

The dose you are given will vary depending on your age, body weight and physical condition. The doctor will give the correct dose to start and to sustain anaesthesia or to achieve the required level of sedation, by carefully watching your responses and vital signs (pulse, blood pressure, breathing, etc).

The doctor will also observe limits of the time of application, if necessary.

Propofol will only be given for a maximum of 7 days.

Method of administration

You will receive Propofol by intravenous injection or infusion, that is, through a needle or small tube placed in one of your veins. When given as an infusion it may be diluted in advance.

Because Propofol does not contain preservatives, an infusion from one vial of Propofol will not last longer than 12 hours. An infusion from one container of diluted Propofol will not last longer than 6 hours.

Your circulation and breathing will be constantly monitored while you are being given the injection or infusion.

If you received more Propofol than you should

It is unlikely that this occurs because the doses you receive are very carefully controlled.

Yet if you accidentally got an overdose, this could lead to depression of heart function and breathing. In this case your doctor will employ any necessary treatment immediately.

If you have any further questions on the use of this product, ask your doctor or pharmacist.

B|BRAUN

B. Braun Melsungen AG

34209 Melsungen, Germany

Dimension: 335 x 962 mm LLD-Spec.: L11

Production code: 713

GB___0598

0598/12632870/0724 GIF (GA)

Production site: Berlin

V-0100

Table of Adverse Drug Reactions

System Organ Class Frequency Undesirable Effects

Immune system disorders: Very rare

(< 1/10 000)

Anaphylaxis up to anaphylactic shock– may include angioedema, bronchospasm, erythema and hypotension

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

hyperlipidaemia (5)

Psychiatric disorders: Very rare

(< 1/10 000)

Sexual disinhibition

Frequency not known (9) Euphoric mood, drug abuse and drug

dependence (8)

Nervous system disorders: Common

(≥ 1/100, < 1/10)

Headache during recovery phase

Rare

(≥ 1/10 000, < 1/1000)

Epileptiform movements, including convulsions and opisthotonus during induction, maintenance and recovery

Very rare

(< 1/10 000)

Postoperative unconsciousness

Frequency not known (9) Involuntary movements

Cardiac disorders: Common

(≥ 1/100, < 1/10)

Bradycardia (1)

Very rare

(< 1/10 000)

Pulmonary oedema

Frequency not known (9) Cardiac arrhythmia (5), cardiac arrest, cardiac

failure (5), (7)

Vascular disorders: Common

(≥ 1/100, < 1/10)

Hypotension (2)

Respiratory, thoracic and mediastinal

disorders:

Common

(≥ 1/100, < 1/10)

Transient apnoea during induction

Frequency not known (9) Respiratory depression (dose-dependent)

Gastrointestinal disorders: Common

(≥ 1/100, < 1/10)

Nausea and vomiting during recovery phase

Very rare

(< 1/10 000)

Pancreatitis

Hepatobiliary disorders: Frequency not known (9) Hepatomegaly (5), hepatitis (12), acute hepatic

failure (12)

Musculoskeletal and connective

tissue disorders:

Frequency not known (9) Rhabdomyolysis (3), (5)

Reproductive system and breast

disorders:

Frequency not known (9) Priapism

Renal and urinary disorders: Very rare

(< 1/10 000)

Discolouration of urine following prolonged administration

Frequency not known (9) Renal failure (5)

General disorders and administration

site conditions:

Very common

(≥ 1/10)

Local pain on induction (4)

Uncommon

(≥ 1/1000, < 1/100)

Injection site thrombosis and injection site phlebitis

Very rare

(< 1/10 000)

Tissue necrosis (10) following accidental extravascular administration (11)

Frequency not known (9) Local pain, swelling and inflammation following

accidental extravascular administration (11)

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

Injury, poisoning and procedural

complications:

Very rare

(< 1/10 000)

Postoperative fever

⁽¹⁾ Serious bradycardias are rare. There have been isolated reports of progression to asystole.

⁽²⁾ Occasionally, hypotension may require use of intravenous fluids and reduction of the administration rate of propofol. ⁽³⁾ Very rare reports of rhabdomyolysis have been received where propofol has been given at doses greater than 4 mg/kg/hr for ICU sedation.

⁽⁴⁾ May be minimised by using the larger veins of the forearm and antecubital fossa. With Propofol local pain can also be minimised by the co-administration of lidocaine.

⁽⁵⁾ Combinations of these events, reported as “Propofol infusion syndrome”, may be seen in seriously ill patients who often have multiple risk factors for the development of the events, 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.

⁽¹¹⁾ Treatment is symptomatic and may include immobilisation and, if possible, elevation of affected limb, cooling, close

observation, consultation of surgeon if necessary.

⁽¹²⁾ After both long- and short-term treatment and in patients without underlying risk factors.

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 at:

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

4.9 Overdose

Symptoms

Accidental overdose is likely to cause cardiorespiratory depression.

Treatment

Respiratory depression should be treated by artificial ventilation with oxygen. Cardiovascular depression may 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: other general anaesthetics, ATC-code: N01AX10.

Mechanism of action, pharmacodynamic effect

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.

4. Possible side effects

Like all medicines, Propofol 1% (10 mg/ml) this medicine can cause side effects, although not everybody gets them.

A doctor must be called immediately if any of the following happens

Common (may affect up to 1 in 10 people):

• Low blood pressure that might occasionally need infusion of fluids and reduction of the speed of administration of propofol.
• Too low heartbeat that might be serious in rare cases.

Rare (may affect up to 1 in 1,000 people):

• Convulsions like in epilepsy

Very rare (may affect up to 1 in 10,000 people):

• Allergic reactions up to allergic shock including swelling of the face, tongue or throat, wheezing breath, skin redness and low blood pressure
• There have been cases of unconsciousness occurring after operations. You will therefore be carefully observed during the waking-up time.
• Water in the lungs (lung oedema) after administration of propofol
• Inflammation of the pancreas

Not known (frequency cannot be estimated from the available data):

• There have been reports of isolated cases of severe adverse reactions presenting as a combination of the following symptoms: breakdown of muscle tissue, accumulation of acidic (sour) substances in the blood, abnormally high blood potassium level, high blood fat levels, abnormalities in the electrocardiogram (Brugada-type ECG), liver enlargement, irregular heart-beat, kidney failure and heart failure. This has been called the “propofol infusion syndrome”. Some of the affected patients eventually died. These effects have only been seen in patients in intensive care, mostly in patients with serious head injuries and in children with respiratory tract infections who received doses higher than 4 mg of propofol per kg body weight per hour. See also section 2, ‘Warnings and precautions’.
• Hepatitis (inflammation of the liver), acute liver failure (symptoms can include yellowing skin and eyes, itching, dark coloured urine, stomach pain and liver tenderness (indicated by pain under the front of the rib cage on your right-hand side), sometimes with loss of appetite).

Other side effects are:

Very common (may affect more than 1 in 10 people):

• Pain at the injection site occurring during the first injection. The pain may be reduced by injecting propofol into larger veins of the forearm. Injection of lidocaine (a local anaesthetic) and propofol at the same time also helps to reduce the pain at the injection site.

Common (may affect up to 1 in 10 people):

• Short interruption of breathing
• Headache during the time of recovery
• Sickness or vomiting during the time of recovery

Uncommon (may affect up to 1 in 100 people):

• Blood clots in veins or inflammation of veins at the injection site

Very rare (may affect up to 1 in 10,000 people):

• Loss of sexual control during the time of recovery
• Abnormal colour of urine after longer lasting administration of propofol
• Cases of fever after an operation
• Tissue damage after the medicine was accidentally injected outside of a vein

Not known (frequency cannot be estimated from the available data):

• Involuntary movements
• Abnormally good mood
• Drug abuse and drug dependence
• Failure of the heart
• Cardiac arrest
• Shallow breathing
• Prolonged and painful erection of the penis
• Pain and/or swelling at the injection site after the medicine was accidentally injected outside of a vein
• Breakdown of muscle tissue has been reported very rarely in cases where propofol has been given at greater doses than recommended for sedation in intensive care units

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly (see details below). By reporting side effects you can help provide more information on the safety of this medicine.

United Kingdom (GB and NI):

Yellow Card Scheme

Website: www.mhra.gov.uk/yellowcard

5. How to store Propofol

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the label and the carton. The expiry date refers to the last day of that month.

Do not store above 25 °C. Do not freeze.

Propofol must be used immediately after opening the vial or ampoule.

Dilutions of Propofol must be used immediately after preparation.

Do not use Propofol if two separate layers can be seen after shaking the product or if it is not milky-white.

6. Contents of the pack and other information

What Propofol contains

• The active substance is propofol

  Each millilitre of Propofol 1% (10 mg/ml) contains 10 mg of propofol.

  1 ampoule with 10 ml contains 100 mg propofol.

  1 ampoule or vial with 20 ml contains 200 mg propofol.

  1 vial with 50 ml contains 500 mg propofol.

  1 vial with 100 ml contains 1000 mg propofol.

• The other ingredients are:

  Soya-bean oil refined,

  Medium-chain triglycerides,

  Egg phospholipids for injection,

  Glycerol,

  Sodium oleate,

  Water for injections

What Propofol looks like and contents of the pack

It is an emulsion for injection or infusion.

It is a milky-white oil-in-water emulsion.

It comes in:

• glass ampoules of 10 millilitres, available in packs of 10 ampoules
• glass ampoules of 20 millilitres, available in packs of 5 ampoules
• glass vials of 20 millilitres, available in packs of 10 vials
• glass vials of 50 or 100 millilitres, available in packs of one or 10 vials.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

B. Braun Melsungen AG

Carl-Braun-Straße 1 Postal address:

34212 Melsungen, Germany 34209 Melsungen, Germany

Phone: +49/5661/71-0

Fax: +49/5661/71-4567

This medicine is authorised in the Member States of the European Economic Area and in the United Kingdom (GB and NI) under the following names:

Propofol-Lipuro 1% (10 mg/ml): Cyprus, Czech Republic, Greece, Slovak Republic

Propofol-Lipuro 10 mg/ml: Estonia, Finland, Germany, Lithuania, Luxembourg, Norway, Sweden Propofol B. Braun: Italy

Propofol-Lipuro 1%: Portugal

Propofol-Lipuro, 10mg/ml: Poland

Propofol “B. Braun” 10 mg/ml: Denmark

Propofol-Lipuro 10 mg/ml,

emulsie voor injectie of infusie: The Netherlands

Propofol-Lipuro 10 mg/ml

emulsija injekcijām vai infūzijām: Latvia

Propofol-Lipuro 10 mg/ml Emulsion

zur Injektion oder Infusion: Austria

Propofol-Lipuro 10 mg/ml

emulzija za injiciranje ali infundiranje: Slovenia

Propofol-Lipuro 1% (10 mg/ml)

emulsion for injection or infusion: Ireland, Malta

PROPOFOL LIPURO 1 % (10 mg/ml),

émulsion injectable ou pour perfusion: France

Propofol 1% (10 mg/ml)

emulsion for injection or infusion: United Kingdom (GB and NI)

PROPOFOL LIPURO 10 mg/ml

emulsión inyectable y para perfusión: Spain

This leaflet was last revised in 07/2024.

The following information is intended for healthcare professionals only:

The containers are for single use in one patient only.

The containers should be shaken before use.

Before use, the neck of the ampoule or the surface of the rubber stopper of the vial should be cleaned with medicinal alcohol (spray or swabs).

The infusion line and the reservoir of Propofol must be discarded and replaced after 12 hours at the latest. Any unused emulsion must be thrown away at the end of administration. Any unused product or waste material should be disposed of in accordance with local requirements.

For complete information on this medicinal product please refer to the summary of product characteristics. ----✁----------✁----------✁----------✁----------✁----------✁----------✁----------✁--------✁----------✁----------✁----------✁----------✁----------✁----------✁----------✁----------✁

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.

5.2 Pharmacokinetic properties

Absorption

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

Distribution

After intravenous bolus administration the initial blood level of propofol declines rapidly due to rapid distribution into different compartments (a-phase). The distribution half-life has been calculated as 2-4 minutes.

During elimination the decline of blood levels is slower. The elimination half-life during the b-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.

The central volume of distribution is in the range of 0.2-0.79 l/kg body weight, the steady-state volume of distribution in the range of 1.8-5.3 l/kg body weight.

Biotransformation

Propofol is mainly metabolised in the liver to form glucuronides of propofol and glucuronides and sulphate conjugates of its corresponding quinol. All metabolites are inactive.

Elimination

Propofol is rapidly cleared from the body (total clearance approx. 2 l/min). Clearance occurs by metabolism, mainly in the liver, where it is blood flow dependent. Clearance is higher in paediatric patients compared with adults. About 88% of an administered dose is excreted in the form of metabolites in urine. Only 0.3% is excreted unchanged in urine.

Paediatric population

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).

5.3 Preclinical safety data

Preclinical data reveal no specific hazard for humans based on conventional studies on repeated dose toxicity or genotoxicity. Carcinogenicity studies have not been conducted.

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 is 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,

medium-chain triglycerides,

glycerol,

egg phospholipids for injection,

sodium oleate,

water for injections.

6.2 Incompatibilities

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

6.3 Shelf life

2 years.

After first opening:

To be used immediately.

After dilution according to directions:

Administration of dilutions must commence immediately after preparation.

6.4 Special precautions for storage

Do not store above 25 °C.

Do not freeze.

6.5 Nature and contents of container

Colourless Type I glass ampoules containing 10 or 20 ml of emulsion.

Colourless Type II glass vials sealed with bromobutyl rubber stoppers and aluminium caps containing 20 ml, 50 ml or 100 ml of emulsion.

Pack sizes:

glass ampoules: 10 x 10 ml, 5 x 20 ml

glass vials: 10 x 20 ml, 1 x 50 ml, 10 x 50 ml, 1 x 100 ml, 10 x 100 ml

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

Any unused product or waste material should be disposed of in accordance with local requirements. Containers should be shaken before use.

For single use only. Any portion of contents remaining after first use must be discarded, see section 4.2. If two layers can be seen after shaking, the medicinal product should not be used.

Propofol should only be mixed with the following products: glucose 50 mg/ml (5% w/v) solution for infusion, sodium chloride 9 mg/ml (0.9% w/v) solution for infusion, or sodium chloride 1.8 mg/ml (0.18% w/v) and glucose 40 mg/ml (4% w/v) solution, and preservative-free lidocaine 10 mg/ml (1%) solution for injection (see section 4.2 “Method and duration of administration” “Infusion of diluted Propofol”)

Co-administration of Propofol together with glucose 50 mg/ml (5% w/v) solution for infusion or sodium chloride 9 mg/ml (0.9% w/v) solution for infusion, or sodium chloride 1.8 mg/ml (0.18%) and glucose 40 mg/ml (4% w/v) solution via a Y-connector close to the injection site is possible.

7 MARKETING AUTHORISATION HOLDER

B. Braun Melsungen AG

Carl-Braun-Strasse 1

34212 Melsungen

Germany

P.O. Box 1110/1120

D-34209 Melsungen, Germany

Telephone: +49-5661-71-0

Telefax: +49-5661-71-2950

8 MARKETING AUTHORISATION NUMBER(S)

PL 03551/0055

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

26/05/2000 / 05/05/2009

10 DATE OF REVISION OF THE TEXT

07.2024