PACKAGE LEAFLET: INFORMATION FOR THE USER

Ripol 10 mg/ml (1%) emulsion for injection/infusion

Propofol

Read all of this leaflet carefully before you start using this medicine.

-    Keep this leaflet. You may need to read it again.

-    If you have any further questions, ask your doctor or pharmacist.

-    This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.

-    If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

In this leaflet:

1.    What Ripol 10 mg/ml is and what it is used for

2.    Before you use Ripol 10 mg/ml

3.    How to use Ripol 10 mg/ml

4.    Possible side effects

5.    How to store Ripol 10 mg/ml

6.    Further information

1.    WHAT RIPOL 10 MG/ML IS AND WHAT IT IS USED FOR

Ripol 10 mg/ml 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).

Ripol 10 mg/ml will be given to you as an injection by a doctor.

Ripol 10 mg/ml is used to:

-    Induce and maintain general anaesthesia in adults and paediatric patients over 1 month of age

-    Sedate patients over16 years of age receiving artificial respiration in intensive care

-    sedate adults and paediatric patients over 1 month of age during diagnostic and surgical procedures, alone or in combination with local or regional anaesthesia

2.    BEFORE YOU RECEIVE RIPOL 10 MG/ML Do not use Ripol 10 mg/ml

- in patients allergic (hypersensitive) to propofol or any of the other ingredients of Ripol 10 mg/ml.

-    in patients allergic to peanut or soya. This is because Ripol 10 mg/ml contains soya-bean oil.

-    in patients 16 years of age or younger for sedation in intensive care.

Take special care with Ripol 10 mg/ml

-    if you have any other health problems, such as problems with your heart, breathing, kidneys or liver.

-    if your body has lost lots of water (you are hypovolaemic).

-    if you have ever had a fit or convulsion

-    if you have ever been told that you have very high levels of fat in your blood. In these cases your doctor might have to determine your blood fat levels.

-    if you have ever been told that your body has problems using fat. In these cases your doctor might have to determine your blood fat levels.

-    If you have had a head injury together with a high pressure in your head.

-    if you have a condition called hereditary predisposition to acute porphyria.

-    if you are eldery or debilitated, or severely overweight.

The use of Ripol 10 mg/ml is not recommended in newborn infants.

If you are able to go home shortly after receiving propofol you should not go home unaccompanied.

If you are not sure if any of the above apply to you, talk to your doctor or nurse before recieving Ripol 10 mg/ml.

Using other medicines

Please tell your doctor if you are taking or have recently taken any other medicines, including medicines obtained without a prescription. This includes medicines, herbal remedies, health foods or supplements that you have bought yourself.

Take special care when taking/receiving the following medicines:

-    Certain premedications (your anaesthesist knows which medicines can be influenced)

-    Other anaesthetics (including general, local or volatile anaesthetics)

-    Painkillers (analgetics)

-    Strong painkillers (fentanyl or opiods)

-    Parasympatholytic agents (medicines used to treat e. g. painful cramps of organs, asthma or Parkinson's disease)

-    Benzodiazepines (medicines used to treat anxiety)

-    Suxamethonium (muscle relaxant)

-    Neostigmin (medicine used to treat a disease called myasthenia gravis)

-    Ciclosporin (medicine used to prevent transplant rejection)

Using Ripol 10 mg/ml with food and drink

When receiving propofol you should avoid drinking alcohol for at least 8 hours before and after administration of Ripol 10 mg/ml.

Pregnancy and breast-feeding

If you are pregnant you should receive Ripol 10 mg/ml only if absolutely necessary. If you are trying to get pregnant or if you are breast-feeding, talk to your doctor or nurse before receiving this medicine.

You should not breast-feed while receiving propofol and breast milk must be discarded for 24 hours after receiving propofol.

Driving and using machines

After having Ripol 10 mg/ml you may still feel sleepy for some time. Do not drive or use any tools or machines until you are sure the effects have worn off.

If you are able to go home shortly after receiving propofol, do not drive a car.

Ask your doctor when you can start doing these activities again and when you can go back to work.

Important information about some of the ingredients of Ripol 10 mg/ml

This medicinal product contains soya-bean oil. If you are allergic to peanut or soya, do not use this medicine (see above “Do not use Ripol 10 mg/ml”).

This medicinal product contains less than 1 mmol sodium (23 mg) per 100 ml, i.e. essentially ‘sodium-free’.

3. HOW TO USE RIPOL 10 MG/ML

You will be given Ripol 10 mg/ml by, or under the direct supervision of your anaesthesist or intensive care doctor. It will be given to you as an injection or infusion (drip) into a vein. This is usually in the back of your hand or in your forearm.

-    Your doctor will give you the injection using a needle or through a fine plastic tube called a ‘cannula’.

-    For maintenance of anaesthesia or sedation your medicine may be given as an intravenous infusion (drip) using an electric pump which automatically control the rate at which the infusion is given. This may be done if you are having a long operation or if you are in an Intensive Care Unit.

The dose of Ripol 10 mg/ml will vary depending on other medicines including premedication, your age, body weight and physical condition. The doctor will give you the correct dose to start and to sustain anaesthesia or to achieve the required level of sedation (sleepiness), by carefully watching your responses and vital signs (pulse, blood pressure, breathing etc.).

You may need several different medicines to keep you asleep or sleepy, free from pain, breathing in a healthy way and to keep your blood pressure steady. The doctor will decide which medicines you need and when you need them.

General anaesthesia

Adults

-    For induction of anaesthesia most adult patients aged less than 55 years are likely to require 1.5 to 2.5 mg propofol/kg body weight.

-    For maintenance of anaesthesia generally doses of 4 to 12 mg propofol/kg body weight/hr or repeat bolus injections (using Ripol 10 mg/ml) dose increments of 25 mg to 50 mg are given.

Dose requirements may be lower for elderly patients.

Sedation

Adults and adolescents older than 16 years of age

-    For sedation of adults and adolescents older than 16 years of age during intensive care the dose should be adjusted according to the level of sedation required. Using continous infusion doses of 0.3 to 4.0 mg propofol/kg body weight/hr are typically given. Rates of infusion greater than 4.0 mg propofol/kg body weight/hr are not recommended.

-    For sedation for diagnostic and surgical procedures in adults and adolescents older than 16 years of age generally doses of 0.5 to 1 mg propofol/kg body weight over 1 to 5 minutes are required for onset of sedation. Maintenance of sedation will require 1.5 to 4.5 mg propofol/kg body weight/hr. Additionally, single administration of 10 to 20 mg propofol/kg body weight can be given if a rapid increase of the level of sedation (sleepiness) is required.

General anaesthesia

Paediatric patients older than 1 month of age

-    For induction of anaesthesia most paediatric patients over 8 years are likely to require approximately 2.5 mg propofol/kg body weight.

In patients younger than 8 years the dose might be higher (2.5-4 mg propofol/kg body weight).

-    For maintenance of anaesthesia using continuous infusion doses of 9 to 15 mg propofol/kg body weight/hr usually achieve satisfactory anaesthesia.

In younger children, especially between the age of 1 month and 3 years, may have higher dosage requirements.

Sedation

Paediatric patients older than 1 month of age

-    For sedation of paediatric patients during diagnostic and surgical interventions the dose should be adjusted according to the level of sedation required. Most paediatric patients require doses of 1 - 2 mg propofol/kg body weight for onset of sedation. Maintenance of sedation will require 1.5-9 mg propofol/kg body weight/hr. Additionally, single administration of up to 1 mg propofol/kg body weight can be given if a rapid increase of level of sedation is required.

-    Ripol 10 mg/ml must not be used in paediatric patients of 16 years of age or younger in the indication for sedation in intensive care.

Duration of treatment

When used for sedation, Ripol 10 mg/ml must not be administered for more than 7 days.

If you received more Ripol 10 mg/ml than you should

Your doctor will ensure that you receive the right amount of propofol for you and for the procedure you are undergoing. However, different people need different doses and if you do receive too much for you, your anaesthesist may need to take measures to make sure your heart and breathing are adequately supported. This is why anaesthetic drugs are only administered by doctors trained in anaesthesia or in the care of patients in intensive care.

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

4. POSSIBLE SIDE EFFECTS

Like all medicines, Ripol 10 mg/ml can cause side effects, although not everybody gets them.

affects more than 1 user in 10

affects 1 to 10 users in 100

affects 1 to 10 users in 1,000

affects 1 to 10 users in 10,000

affects less than 1 user in 10,000

frequency cannot be estimated from the available data

Side effects that can happen during anaesthesia

The following side effects can happen during anaesthesia (while the injection is being given to you or when you are sleepy or asleep). Your doctor will be looking out for these. If they happen, your doctor will give you appropriate treatment.

Very common

- A feeling of pain at the site of the injection (while the injection is being given, before you fall asleep)

Common

-    Slow heart beat

-    Mild to moderate low blood pressure

-    Changes in your breathing pattern

-    Hiccups

-    Hot flushes

Uncommon

- Marked low blood pressure

Cough (may also happen when you wake up)

Rare

- Twitching and shaking of your body, or fits (may also happen when you wake up)

Very rare

-    Serious allergic reaction which causes difficulty in breathing or dizziness

-    Build up of fluid in the lungs which can make you very breathless (may also happen when you wake up)

-    Unusual colour of urine (may also happen when you wake up)

Not known

- Spontaneous movements and fits

Side effects that can happen after anaesthesia

The following side effects can happen after anaesthesia (when you are waking up or after you have woken up).

Common

-    Excitations, headache

-    Feeling sick (nausea), being sick (vomiting)

Uncommon

-    Swelling and redness or blood clots at the vein along the injection site

Rare

-    Feeling sexually aroused

-    Dizziness, chills and sensations    of cold

-    Cough

Very rare

-    Being unconscious after the operation (when this has happened, the patients have recovered without problems)

-    Inflamed pancreas (pancreatitis) which causes severe stomach pain (a causal relationship could not be shown)

-    Fever following surgery

-    Changes in ECG (Brugada    type    ECG)

Not known

-    Feeling euphoric

-    Irregular heart beat

-    Increase in liver size

-    Kidney failure

-    Breakdown of muscle cells (rhabdomyolysis), increase in acidity of your blood, high potassium and fat levels in your blood, heart failure with fatal outcome (seen when propofol is used in intensive care at higher doses than recommended)

-    Severe skin and tissue reaction following accidental application beside the vein

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

5. HOW TO STORE RIPOL 10 MG/ML

Keep out of the reach and sight of children.

Do not use Ripol 10 mg/ml after the expiry date which is stated on the label after EXP. The expiry date refers to the last day of that month.

Store below 30°C.

Do not freeze.

Keep the vial/ampoule in the outer carton in order to protect from light.

Shelf life before opening Ampoules/vials: 18 months.

Shelf life after first opening/dilution

The mixture should be prepared aseptically immediately prior to administration and must be administered within 6 hours after preparation.

In accordance with established guidelines for other lipid emulsions, a single infusion of Ripol 10 mg/ml must not exceed 12 hours. At the end of the procedure or at 12 hours, whichever is the sooner, both the container of Ripol 10 mg/ml and the infusion line must be discarded and replaced as appropriate.

Chemical and physical in-use stability of the reconstituted 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.

Do not use Ripol 10 mg/ml if you notice particulate matter.

Medicines should not be disposed of via wastewater or household waste. Your doctor or hospital pharmacist are responsible for the correct storage, use and disposal.

6. FURTHER INFORMATION What RIPOL 10 MG/ML contains

-    The active substance(s) is propofol. 1 milliliter emulsion for injection/infusion contains 10 mg propofol.

-    The other ingredients are soya-bean oil, refined; egg phospholipids, purified; glycerol; sodium hydroxide (for pH-adjustment); water for injections.

What Ripol 10 mg/ml looks like and contents of the pack

Ripol 10 mg/ml emulsion for injection/infusion is a white aqueous isotonic oil-in-water emulsion. It is available in 20 ml Type I glass ampoules, or 20, 50 and 100 ml Type I glass vials with bromobutyl rubber stoppers.

Pack sizes:

5 x 20 ml ampoules 5 x 20 ml vials 1 x 50 ml vial 1 x 100 ml vial

Not all pack sizes may be marketed.

Marketing Authorisation Holder

YES Pharmaceutical Development Services GmbH Bahnstr. 42 - 46 61381 Friedrichsdorf Germany

Manufacturer

CORDEN PHARMA S.p.A.

Viale dell’Industria 3 E Reparto via Galilei 17 Caponago, 20040 Italy

This medicinal product is authorised in the Member States of the EEA under the following names:

Germany    Ripol 10 mg/ml Emulsion zur Injektion/Infusion

Italy    Ripol 10 mg/ml Emulsione per Infusione

Netherlands    Ripol 10 mg/ml Emulsie voor injectie / infusie

United Kingdom    Ripol 10 mg/ml Emulsion for injection/infusion

This leaflet was last approved in 05/2012.

The following information is intended for medical or healthcare professionals only: Method of administration

For intravenous use.

Administering Ripol 10 mg/ml through a TCI-system for sedation in intensive care is not recommended.

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.

Containers should be shaken before use. If two layers can be seen after shaking, the emulsion should not be used.

Ripol 10 mg/ml can be used for infusion undiluted or diluted with glucose 50 mg/ml (5%) intravenous infusion solution 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%).

Prior to use, the ampoule neck and rubber stopper should be disinfected using a medicinal alcohol (spray or dipped swab). After use, any remaining contents must be discarded.

Ripol 10 mg/ml does not contain antimicrobial preservatives and is capable of supporting the growth of microorganisms. The emulsion must be drawn aseptically into a sterile syringe or infusion system immediately after opening the ampoule or spiking the vial.

Administration must commence without delay. During infusion sterility of Ripol 10 mg/ml as well as the infusion system must be maintained.

Medicinal products or liquids that are added to a running Ripol 10 mg/ml infusion should be added close to the cannula.

Ripol 10 mg/ml must not be administered via infusion systems that are provided with a microbiological filter.

The contents of one vial of Ripol 10 mg/ml and any infusion equipment are intended for single use in one patient.

Any remainder must be discarded immediately after use.

Infusion of undiluted Ripol 10 mg/ml

When Ripol 10 mg/ml is administered as a continuous infusion, 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 applies to parenteral administration of all kinds of fat emulsions, the duration of use for one infusion system for a continuous infusion of Ripol must not exceed 12 hours. The infusion system and the container must be discarded and replaced after a maximum of 12 hours.

The simultaneous administration of Ripol 10 mg/ml together with an infusion solution of glucose 50 mg/ml (5%), 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.

Any Ripol 10 mg/ml remaining at the end of the infusion period or after changing the system needs to be discarded and destroyed.

Infusion of diluted Ripol 10 mg/ml

When Ripol 10 mg/ml is administered diluted as a continuous infusion it is recommended that equipment such as burettes, drop counter, syringe pumps or volumetric infusion pumps should always be used to control infusion rates and to prevent the accidental administration of large volumes of diluted Ripol 10 mg/ml.

The maximum dilution must not exceed 1 part of Ripol 10 mg/ml and 4 parts of glucose 50 mg/ml (5%) (at least 2 mg propofol/ml) intravenous infusion solution 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%). The mixture should be prepared aseptically immediately prior to administration and must be administered within 6 hours after preparation.

Ripol 10 mg/ml must not be mixed with other solutions for injection or infusion except those mentioned above.

To reduce pain on the injection site lidocaine may be injected immediately before the use of Ripol 10 mg/ml or Ripol 10 mg/ml may be mixed, immediately prior to administration, with preservative-free lidocaine injection.

The infusion system should be rinsed before administration of muscle relaxants like atracurium and mivacurium when using the same infusion system for Ripol 10 mg/ml.

Disposal

Any remaining contents after use should be discarded.

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