Rapiva: detailed information

PACKAGE LEAFLET: INFORMATION FOR THE USER

Rapiva 10 mg/ml injectable emulsion or for infusion

Propofol
Generic medicine
Please read this leaflet carefully before this medicine is administered to you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor or pharmacist.
If any of the side effects worsens, or if you notice any side effects not listed in this leaflet, inform your doctor or pharmacist.

Contents of this leaflet:

What Rapiva is and what it is used for
Before you are given Rapiva
How Rapiva will be administered to you
Possible side effects
How to store Rapiva
Further information

1. WHAT RAPIVA IS AND WHAT IT IS USED FOR

Propofol belongs to a group of medicines called general anaesthetics. General anaesthetics are
used to induce loss of consciousness (deep sleep) during surgical operations or other procedures.
They may also be used to sedate you (make you sleepy without fully putting you to sleep).
Rapiva is used for:

Induction and maintenance of general anaesthesia in adults and children over 1 month of age
Sedation of patients over 16 years of age who are on mechanical ventilation in intensive care
Sedation of adults and children over 1 month of age during diagnostic and surgical procedures, either alone or in combination with local or regional anaesthesia

2. BEFORE RAPIVA IS ADMINISTERED TO YOU

Do not use Rapiva:

in patients allergic (hypersensitive) to propofol or to any of the other components of this medicine
in patients allergic (hypersensitive) to soy or peanuts
in patients aged 16 years or younger for sedation in intensive care

Take special care with Rapiva
You must not receive Rapiva, or only with extreme caution and intensive monitoring, if:

you have advanced heart failure
you have any other serious heart disease
you are undergoing electroconvulsive therapy (ECT, a treatment for psychiatric disorders)

The use of Rapiva is not recommended in neonates.
Special caution should be exercised when Rapiva is used for anesthesia in children under 3 years of age. However, currently available data do not suggest significant differences in safety compared to older children.
The safety of propofol for sedation in children and adolescents under 16 years of age during intensive care has not been established.
In general, Rapiva should be administered with caution in elderly or debilitated patients.
Before receiving Rapiva, inform your anesthesiologist or intensive care physician if you have:

heart disease
lung disease
kidney disease
liver disease
seizures (epilepsy)
increased pressure inside the skull (elevated intracranial pressure). In combination with low blood pressure, the amount of blood reaching the brain may be reduced.
altered levels of fats in the blood. If you are receiving total parenteral nutrition (feeding through a vein), your blood fat levels should be monitored.

If you suffer from any of the following conditions, they must be treated before receiving Rapiva:

heart failure
inadequate blood supply to tissues (circulatory failure)
severe respiratory problems (respiratory failure)
dehydration (hypovolemia)
seizures (epilepsy)

Rapiva may increase the risk of:

epileptic seizures
a nerve reflex that slows heart rate (vagotonia, bradycardia)
changes in blood flow to body organs (hemodynamic effects on the cardiovascular system), especially if you are overweight and receive high doses of Rapiva.

Involuntary movements may occur during sedation with Rapiva. Physicians will take into account how this might affect surgical procedures performed under sedation and will take necessary precautions.
Very rarely, after anesthesia, there may be a period of unconsciousness associated with muscle rigidity. This requires medical observation but no further treatment. This will resolve spontaneously.
Injection of Rapiva may be painful. A local anesthetic may be used to reduce pain, but side effects from the local anesthetic may occur.
You will not be allowed to leave the hospital until you are fully conscious.

Taking Rapiva with other medicines
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those not requiring a prescription. This includes herbal medicines, dietary products, or supplements you have purchased.
Special caution is required if you are also taking any of the following medicines:

premedications (your anesthesiologist must be informed)
anesthetics
analgesics (painkillers)
muscle relaxants, e.g., succinylcholine
benzodiazepines (medicines for anxiety), e.g., diazepam
anticholinergic drugs (medicines that inhibit the action of the parasympathetic nervous system, which controls smooth muscle contraction, regulates heart muscle, or stimulates or inhibits glandular secretion)
drugs acting on many internal body functions, such as heart rate, e.g., atropine
potent painkillers, e.g., fentanyl
alcohol
neostigmine (treatment for muscle weakness)
cyclosporine (used to prevent organ rejection)

Taking Rapiva with food and drink
Alcohol and propofol enhance each other's sedative effects. Therefore, you must not drink alcohol immediately before or after receiving Rapiva until you have fully recovered.

Pregnancy and breastfeeding
Ask your doctor or pharmacist for advice before taking any medicine.
Rapiva must not be administered to pregnant women unless strictly necessary. If you are breastfeeding, you must stop breastfeeding and discard breast milk for 24 hours after receiving Rapiva. Propofol is excreted in small amounts in breast milk.

Driving and using machines
After receiving Rapiva, you must not drive, operate machinery, or work in hazardous situations.
You must not go home alone and must not drink alcohol until you have fully recovered.

Important information about some excipients in Rapiva:
Rapiva contains soybean oil. If you are allergic to peanuts or soy, do not use this medicine.
This medicine contains less than 1 mmol of sodium (23 mg) in 20 ml, i.e., it is practically “sodium-free”.

3. HOW RAPIVA WILL BE ADMINISTERED TO YOU

Dosage
Rapiva will be administered to you by your anaesthetist or intensive care physician.
The amount of propofol required depends on your age, size, physical condition, and the level of sedation or sleep that needs to be achieved. The doctor will administer the appropriate dose to induce and maintain anaesthesia or to achieve the required level of sedation, carefully monitoring your responses and vital signs (pulse, blood pressure, respiration, etc.). This may also be influenced by other medications you are taking. Most people require 1.5–2.5 mg per kg of body weight to induce drowsiness or sleep, followed by 4 to 12 mg/kg (body weight)/hour. For sedation, propofol doses between 0.3–4.0 mg per kg of body weight/hour are usually sufficient.

Adults
To induce sedation during surgical and diagnostic procedures in adults, a dose of 0.5–1 mg of propofol/kg body weight over 1–5 minutes is usually required to initiate sedation. Maintenance of sedation can be achieved by titrating the Rapiva infusion according to the required level of sedation. In most patients, a dose of 1.5–4.5 mg of propofol/kg body weight/hour is required.

Rapiva is administered by intravenous injection or infusion, usually into the back of the hand or forearm. The anaesthetist may use a needle or a cannula (a thin plastic tube). An electric pump may be used to deliver the injection during long operations and in intensive care settings.

Elderly and debilitated patients may require lower doses.

Children
Children usually require slightly higher doses. The dose should be adjusted according to age and/or body weight.

When used for sedation, Rapiva must not be administered for longer than 7 days.

If you receive more Rapiva than you should
This is unlikely to occur, as the doses you receive are carefully controlled.
If an overdose is accidentally administered, it could lead to depression of cardiac, circulatory, and respiratory function. In such a case, the doctor will immediately initiate all necessary treatments.

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

4. POSSIBLE ADVERSE REACTIONS

Like all medicines, Rapiva can cause adverse reactions, although not everyone experiences them.
These reactions depend on the dose of propofol administered, as well as on the type of premedication and concomitant use of other drugs.

Very common (more than 1 in 10 patients)

Local pain during injection

Common (from 1 to 10 in 100 patients)

Low blood pressure (hypotension)
Weak breathing (respiratory depression)
Spontaneous movements
Slowed heart rate (bradycardia)
Rapid heart rate (tachycardia)
Flushing (hot flushes)
Temporary apnea (respiratory arrest)
Coughing after anesthesia
Hiccups (singultus)
Hyperventilation (increased breathing)
Hypertriglyceridemia (elevated cholesterol or triglycerides in the blood)

Uncommon (from 1 to 10 in 1,000 patients)

Severe low blood pressure (hypotension)
Coughing during anesthesia

Rare (from 1 to 10 in 10,000 patients)

Anaphylaxis (a severe allergic reaction)
Euphoria (feeling of happiness) and sexual excitement during recovery
Headache
Dizziness (spinning sensation)
Chills and sensations of cold during recovery period
Epileptiform movements (similar to epilepsy)
Irregular heartbeat (arrhythmia) during recovery
Coughing during recovery
Discoloration of urine
Postoperative fever
Blood clots (thrombosis) and inflammation of blood vessels (phlebitis)
Skin redness (erythema)
Low blood pressure (hypotension)
Bronchospasm (a condition causing breathing difficulty)
Nausea or vomiting

Very rare (less than 1 in 10,000 patients)

Delayed epileptiform seizures (seizures resembling epilepsy after recovery)
Fluid in the lungs (pulmonary edema)
Inflammation of the pancreas (pancreatitis)
Severe tissue reactions after accidental injection into tissues
Rhabdomyolysis (breakdown of muscle fibers)
Metabolic acidosis (acidic blood)
High potassium levels in the blood (hyperkalemia)
Cardiac dysfunction (heart problems)
Postoperative unconsciousness

When Rapiva is administered in combination with lidocaine (a local anesthetic used to reduce injection site pain), the following adverse reactions may occur rarely:

Dizziness
Vomiting
Drowsiness
Seizures
Slowed heart rate (bradycardia)
Irregular heartbeat (cardiac arrhythmia)
Shock

Reporting of adverse reactions
If you experience any adverse reaction, including those not listed in this leaflet,
contact your doctor or pharmacist. You may also report adverse reactions
directly through the national reporting system at
http://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting
adverse reactions, you can help provide more information on the safety of this
medicine.
If any of the adverse reactions worsen, or if you notice any adverse reaction
not listed in this leaflet, inform your doctor or pharmacist.

5. HOW TO STORE RAPIVA

Keep out of the reach and sight of children.
Do not use Rapiva after the expiry date stated on the vial and carton following “EXP”.
The expiry date refers to the last day of the month.
Do not store above 25°C.
Do not freeze.
After opening, the product must be used immediately.
Dilutions with glucose 50 mg/ml (5%) solution for injection, sodium chloride 9 mg/ml (0.9%) solution for
injection, or sodium chloride 1.8 mg/ml (0.18%) and glucose 40 mg/ml (4%) solution for injection and
lidocaine 10 mg/ml (1%) solution for injection without preservatives. The mixture must be prepared
aseptically (under controlled and validated conditions) immediately before administration and must be
administered within 12 hours after preparation.
Shake the container before use.
If two layers are visible after shaking, the emulsion must not be used.
Use only homogeneous preparations and intact containers.
For single use only. Any unused emulsions must be discarded.
The anaesthetist and hospital pharmacist are responsible for the proper storage, use, and disposal of propofol.

6. OTHER INFORMATION

What Rapiva contains
The active substance is propofol.
Each ml of injectable or infusion emulsion contains 10 mg of propofol.
Each 20 ml vial contains 200 mg of propofol.
Each 50 ml vial contains 500 mg of propofol.
Each 100 ml vial contains 1000 mg of propofol.
The other excipients are: Refined soybean oil, medium-chain triglycerides, glycerol, egg lecithin, sodium oleate, sodium hydroxide (to adjust pH), water for injectable preparations.

Description of the appearance of Rapiva and contents of the pack
White oil-in-water injectable or infusion emulsion.
This medicinal product is supplied as:
Injectable or infusion emulsion in colourless glass vials (Type II) with grey bromobutyl rubber closures.
Pack sizes:
Colourless glass vials (Type II) of 20 ml with grey bromobutyl rubber closures, packs of 1, 5 and 10 units.
Colourless glass vials (Type II) of 50 ml with grey bromobutyl rubber closures, packs of 1 and 10 units.
Colourless glass vials (Type II) of 100 ml with grey bromobutyl rubber closures, packs of 1 and 10 units.
It is possible that not all pack sizes are marketed.

Marketing Authorisation Holder and Manufacturer
Baxter Holding BV,
Kobaldweg 49,
3542CE Utrecht,
The Netherlands

Manufacturer
Peckforton Pharmaceuticals Limited
Golden Gate Lodge Crewe Hall, Weston Road, Crewe
CW1 6UL, United Kingdom.
UAB Norameda
Vilnius, Lithuania.
SIDEFARMA - Sociedade Industrial de Expansão Farmacêutica, S.A.,
Guiné 26, 2685, Portugal.
SIA “UNIFARMA”
Vangažu iela 23,
Rīga, Latvia

This medicine is authorised in the European Community member states under the following names:

| European Country | Trade Name | |----------------------|----------------| | Germany (RMS) | Propofol Claris 1% (10 mg/ml) MCT Emulsion zur Injektion/Infusion | | Austria | Propofol Claris 1% (10 mg/ml) MCT Emulsion zur Injektion/Infusion | | Czech Republic | Propofol Norameda 10 mg/ml Emulsion for Injection/Infusion | | Denmark | Profast (Propofol, 10 mg/ml Emulsion for injection/Infusion) | | Estonia | Spiva (Propofol, 10 mg/ml Emulsion for Injection/Infusion) | | Greece | Spiva (Propofol, 10 mg/ml Emulsion for Injection/Infusion) | | Finland | Rapiva (Propofol, 10 mg/ml Emulsion for Injection/Infusion) | | France | Spiva (Propofol, 10 mg/ml Emulsion for Injection/Infusion) | | Hungary | Spiva (Propofol, 10 mg/ml Emulsion for Injection/Infusion) | | Ireland | Propofol, 10 mg/ml Emulsion for Injection/Infusion | | Italy | Rapiva (Propofol, 10 mg/ml Emulsion for Injection/Infusion) | | Latvia | Rapiva 10 mg/ml emulsion for injection/infusion (Rapiva 10 mg/ml emulsija injekcijām/infūzijām) | | Lithuania | Spiva (Propofol Norameda 10 mg/ml injekcinė/infuzinė emulsija) | | Luxembourg | Spiva (Propofol, 10 mg/ml Emulsion for Injection/Infusion) | | Netherlands | Rapiva (Propofol, 10 mg/ml Emulsion for Injection/Infusion) | | Norway | Spifol (Propofol, 10 mg/ml Emulsion for Injection/Infusion) | | Poland | Propofol Norameda | | Portugal | Rapiva (Propofol, 10 mg/ml Emulsion for Injection/Infusion) | | Romania | Profast 10 mg/ml emulsie injectabila/perfuzabila | | Sweden | Spiva (Propofol, 10 mg/ml Emulsion for Injection/Infusion) | | Slovenia | Rapiva 10 mg/ml emulzija za injiciranje/infundiranje | | Slovakia | Profast 10 mg/ml Emulsion for Injection/Infusion | | United Kingdom | Propofol 10 mg/ml Emulsion for injection/infusion |

This patient information leaflet was last approved on

The following information is intended exclusively for physicians or healthcare professionals:
Rapiva must be administered only by specialists in anaesthesia or intensive care, and only in hospitals or day-care units adequately equipped. Circulatory and respiratory functions must be continuously monitored (e.g., ECG, pulse oximeter), and equipment for maintaining airway patency, artificial ventilation, and other resuscitation measures must always be immediately available.
For sedation during surgical procedures or diagnostic examinations, Rapiva must not be administered by the same person performing the surgical or diagnostic procedure.
During continuous infusion administration of Rapiva, the use of burettes, drip chambers, syringe pumps or volumetric pumps is recommended to control the infusion rate.
Shake the container before use. If two layers are visible after shaking, the emulsion must not be used.
Use only homogeneous preparations and intact containers.
For single use only. Any unused emulsion must be discarded.
Before use, clean the surface of the vial's rubber stopper with alcohol (spray or swab).
After use, re-capped containers must be discarded.
Rapiva is a lipid-containing emulsion without antimicrobial preservatives and, therefore, rapid microbial growth may occur.
The emulsion must be aseptically withdrawn into a sterile syringe or infusion set immediately after breaking the seal. Administration should be started immediately.
Aseptic conditions must be maintained for both Rapiva and the infusion system throughout the entire duration of the infusion.
Co-administration of other drugs or fluids added to the Rapiva infusion line must be performed close to the cannula insertion site using a Y-connector or a three-way valve.
Rapiva may be used for infusion either undiluted or diluted.
Rapiva must only be mixed with the following products: glucose 50 mg/ml (5%) injectable solution, sodium chloride 9 mg/ml (0.9%) injectable solution, sodium chloride 1.8 mg/ml (0.18%) and glucose 40 mg/ml (4%) injectable solution, and lidocaine 10 mg/ml (1%) preservative-free injectable solution.
The final concentration of propofol must not be lower than 2 mg/ml.
However, co-administration of Rapiva together with glucose 50 mg/ml (5%) injectable solution, sodium chloride 9 mg/ml (0.9%) injectable solution, or sodium chloride 1.8 mg/ml (0.18%) and glucose 40 mg/ml (4%) injectable solution via a Y-connector near the injection site is possible.
Rapiva must not be administered using infusion sets equipped with microbiological filters.
Rapiva and any infusion set containing Rapiva are intended for single use in one specific patient. After use, any unused residue must be discarded.

Infusion of undiluted Rapiva solutions:
During continuous infusion of undiluted Rapiva solution, the use of burettes, drip chambers, syringe pumps or volumetric pumps is recommended to control the infusion rate.
As established for parenteral administration of any type of fat emulsion, the duration of continuous infusion of Rapiva via one specific infusion system must not exceed 12 hours. The infusion tubing and Rapiva container must be discarded or replaced within a maximum of 12 hours.

Infusion of diluted Rapiva solutions:
During continuous infusion of diluted Rapiva solution, the use of burettes, drip chambers, syringe pumps or volumetric pumps is recommended to control the infusion rate and to avoid the risk of accidental uncontrolled infusion of large volumes of diluted Rapiva. This risk must be considered when deciding on the maximum dilution in the burette.
Maximum dilution must not exceed 1 part of Rapiva with 4 parts of glucose 50 mg/ml (5%) injectable solution, sodium chloride 9 mg/ml (0.9%) injectable solution, or sodium chloride 1.8 mg/ml (0.18%) and glucose 40 mg/ml (4%) injectable solution (minimum propofol concentration 2 mg/ml).
The mixture must be prepared aseptically (under controlled and validated conditions) immediately before administration and must be administered within 12 hours of preparation.
This medicinal product must not be mixed with other products except those mentioned above.

To reduce injection site pain, lidocaine may be injected immediately before Rapiva, or Rapiva may be mixed immediately before use with a preservative-free lidocaine injectable solution (20 parts of Rapiva with a maximum of 1 part of lidocaine 10 mg/ml (1%) injectable solution), under controlled and validated aseptic conditions. The mixture must be administered within 12 hours of preparation.

The muscle relaxants atracurium or mivacurium must not be administered through the same intravenous administration system as Rapiva without first flushing the system.

Rapiva 20 mg/ml emulsion for injection/infusion
Propofol
Generic medicine

Please read this leaflet carefully before this medicine is administered to you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor or pharmacist.
If any side effect worsens, or if you notice any side effect not listed in this leaflet, inform your doctor or pharmacist.

Contents of this leaflet:

What Rapiva is and what it is used for
Before you are given Rapiva
How Rapiva will be given to you
Possible side effects
How to store Rapiva
Other information

1. WHAT RAPIVA IS AND WHAT IT IS USED FOR

Induction and maintenance of general anaesthesia in adults and children over 3 years of age
Sedation of patients over 16 years of age receiving mechanical ventilation in intensive care
Sedation of adults and children over 3 years of age during diagnostic and surgical procedures, either alone or in combination with local or regional anaesthesia

2. BEFORE RAPIVA IS ADMINISTERED TO YOU

Do not use Rapiva:

in patients allergic (hypersensitive) to propofol or to any of the other components of this medicine
in patients allergic (hypersensitive) to soy or peanuts
in patients aged 16 years or younger for intensive care sedation

Exercise particular caution with Rapiva
You must not receive Rapiva, or only receive it with extreme caution and intensive monitoring, if:

you have advanced heart failure
you have any other serious heart disease
you are undergoing electroconvulsive therapy (ECT, a treatment for psychiatric conditions)

The use of Rapiva 20 mg/ml is not recommended in children under 3 years of age.
Particular caution should be exercised when Rapiva is used for anesthesia in children under 3 years of age. However, currently available data do not suggest significant differences in safety compared to older children.
The safety of propofol for sedation in children and adolescents under 16 years of age during intensive care treatment has not been established.
In general, Rapiva must be administered with caution in elderly or debilitated patients.
Before receiving Rapiva, inform your anesthesiologist or intensive care physician if you have:

heart disease
lung disease
kidney disease
liver disease
seizures (epilepsy)
increased pressure inside the skull (increased intracranial pressure). In combination with low blood pressure, the amount of blood reaching the brain may be reduced.
altered fat (lipid) levels in the blood. If you are receiving total parenteral nutrition (feeding through a vein), your blood fat levels should be monitored.

If you suffer from any of the following conditions, they must be treated before you receive Rapiva:

heart failure
inadequate blood supply to tissues (circulatory failure)
severe respiratory problems (respiratory failure)
dehydration (hypovolemia)
seizures (epilepsy)

Rapiva may increase the risk of:

epileptic seizures
a nerve reflex that slows heart rate (vagotonia, bradycardia)
changes in blood flow to body organs (haemodynamic effects on the cardiovascular system), especially if you are overweight and receive high doses of Rapiva.

Involuntary movements may occur during sedation with Rapiva. Your doctors will take into account how this might affect surgical procedures performed under sedation and will adopt necessary precautions.
Very rarely, after anesthesia, there may be a period of unconsciousness associated with muscle rigidity. This requires medical observation but no further treatment. This will resolve spontaneously.
Injection of Rapiva may be painful. A local anesthetic may be used to reduce pain, but side effects from the local anesthetic may occur.
You will not be allowed to leave the hospital until you are fully conscious.

Taking Rapiva with other medicines
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those not requiring a prescription. This includes medicines, herbal products, dietary products, or supplements you have purchased.
Particular attention is required if you are also taking any of the following medicines:

premedications (your anesthesiologist must be informed)
anesthetics
analgesics (painkillers)
muscle relaxants, e.g., succinylcholine
benzodiazepines (medicines for anxiety), e.g., diazepam
anticholinergic drugs (medicines that inhibit the action of the parasympathetic nervous system, which controls smooth muscle contraction, regulates heart muscle, and stimulates or inhibits glandular secretion)
drugs acting on many internal body functions such as heart rate, e.g., atropine
strong painkillers, e.g., fentanyl
alcohol
neostigmine (treatment for muscle weakness)
cyclosporine (used to prevent organ rejection)

Driving and using machines
After receiving Rapiva, you must not drive, operate machinery, or work in hazardous situations. You must not go home alone and you must not drink alcohol until you have fully recovered.

Important information about some excipients in Rapiva:
Rapiva contains soybean oil. If you are allergic to peanuts or soy, do not use this medicine.
This medicine contains less than 1 mmol of sodium (23 mg) per 20 ml, i.e., it is practically “sodium-free”.

3. HOW RAPIVA WILL BE ADMINISTERED TO YOU

Dosage
Rapiva will be administered to you by your anaesthetist or intensive care doctor.
The amount of propofol needed depends on your age, size, physical condition, and the level of sedation or
sleep required. The doctor will administer the correct dose to induce and maintain anaesthesia or to achieve the necessary level of sedation, carefully monitoring your responses and vital signs (pulse, blood pressure, respiration, etc.). This may also be influenced by other medications you are taking. Most people require 1.5–2.5 mg per kg of body weight to induce drowsiness or sleep, followed by 4 to 12 mg/kg (body weight)/hour. For sedation, propofol doses between 0.3–4.0 mg per kg of body weight/hour are usually sufficient.

Adults
To induce sedation during surgical and diagnostic procedures in adults, a dose of 0.5–1 mg propofol/kg body weight over 1–5 minutes is usually required to initiate sedation. Maintenance of sedation can be achieved by titrating the Rapiva infusion according to the required level of sedation. In most patients, a rate of 1.5–4.5 mg propofol/kg body weight/hour is required.
The infusion may be supplemented with bolus doses of 10–20 mg (0.5–1 ml of Rapiva) if a rapid increase in sedation depth is needed.

Rapiva is administered by intravenous injection or infusion, usually into the back of the hand or forearm. The anaesthetist may use a needle or a cannula (a thin plastic tube). An electric pump may be used to deliver the infusion during long procedures and in intensive care settings.
Elderly and debilitated patients may require lower doses.

Children
Children usually require slightly higher doses. The dose should be adjusted according to age and/or body weight.

When used for sedation, Rapiva must not be administered for longer than 7 days.

If you have further questions about the use of this product, please consult your doctor or pharmacist.

4. POSSIBLE ADVERSE REACTIONS

Very common (more than 1 in 10 patients)

local pain during injection

Common (from 1 to 10 in 100 patients)

low blood pressure (hypotension)
weak breathing (respiratory depression)
spontaneous movements
slowed heart rate (bradycardia)
rapid heart rate (tachycardia)
hot flushes
temporary apnea (respiratory arrest)
coughing after anesthesia
hiccups (singultus)
hyperventilation (increased breathing)
hypertriglyceridemia (elevated cholesterol or triglycerides in the blood)

Uncommon (from 1 to 10 in 1,000 patients)

severe low blood pressure (hypotension)
coughing during anesthesia

Rare (from 1 to 10 in 10,000 patients)

anaphylaxis (a severe allergic reaction)
euphoria (feeling of happiness) and sexual excitement during recovery
headache
dizziness
chills and cold sensations during the recovery period
epileptiform movements (similar to epilepsy)
irregular heartbeat (arrhythmia) during recovery
coughing during recovery
discoloration of urine
postoperative fever
blood clots (thrombosis) and inflammation of blood vessels (phlebitis)
skin redness (erythema)
low blood pressure (hypotension)
bronchospasm (a condition causing breathing difficulty)
nausea or vomiting

Very rare (less than 1 in 10,000 patients)

delayed epileptiform seizures (epilepsy-like symptoms after recovery)
fluid in the lungs (pulmonary edema)
inflammation of the pancreas (pancreatitis)
severe tissue reactions following accidental injection into tissues
rhabdomyolysis (breakdown of muscle fibers)
metabolic acidosis (acidic blood)
high potassium levels in the blood (hyperkalemia)
cardiac dysfunction (heart problems)
postoperative unconsciousness

When Rapiva is administered in combination with lidocaine (a local anesthetic used to reduce injection site pain), the following adverse reactions may occur rarely:

dizziness
vomiting
somnolence (drowsiness)
seizures
slowed heart rate (bradycardia)
irregular heartbeat (cardiac arrhythmia)
shock

Reporting of adverse reactions
If you experience any adverse reaction, including those not listed in this leaflet,
please inform your doctor or pharmacist. You may also report adverse reactions
directly through the national reporting system at the website
http://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting
adverse reactions, you can help provide more information on the safety of this
medicine.
If any of the adverse reactions worsen, or if you notice any adverse reaction not
listed in this leaflet, please inform your doctor or pharmacist.

5. HOW TO STORE RAPIVA

Keep out of the reach and sight of children.
Do not use Rapiva after the expiry date stated on the vial and carton after “EXP”.
The expiry date refers to the last day of the month.
Do not store above 25°C.
Do not freeze.
After opening, the product must be used immediately.
Shake the container before use.
If two layers are visible after shaking, the emulsion must not be used.
Use only homogeneous preparations and intact containers.
For single use only. Any unused emulsion must be discarded.
The anaesthetist and hospital pharmacist are responsible for the correct storage, use, and disposal of propofol.

6. OTHER INFORMATION

What Rapiva contains
The active substance is propofol.
Each ml of injectable or infusion emulsion contains 20 mg of propofol.
Each 50 ml vial contains 1000 mg of propofol.
The other excipients are: refined soybean oil, medium-chain triglycerides, glycerol, egg lecithin, sodium oleate, sodium hydroxide (to adjust pH), water for injections.

Description of the appearance of Rapiva and contents of the pack
Injectable or infusion oil-in-water emulsion, white.
This medicine is supplied as:
Injectable or infusion emulsion in colourless glass vials (Type II) with grey bromobutyl rubber closures.
Pack sizes:
Colourless glass vials (Type II) of 50 ml with grey bromobutyl rubber closures, packs of 1 and 10 units.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Baxter Holding BV,
Kobaldweg 49,
3542CE Utrecht,
The Netherlands

Manufacturer
Peckforton Pharmaceuticals Limited
Golden Gate Lodge Crewe Hall, Weston Road, Crewe
CW1 6UL, United Kingdom.
UAB Norameda
Vilnius, Lithuania.
SIDEFARMA - Sociedade Industrial de Expansão Farmacêutica, S.A.,
Guiné 26, 2685, Portugal.

This medicine is authorised in the Member States of the European Community under the following names:

| Country | Invented Names | |--------|----------------| | Germany | Propofol Claris 2% (20 mg/ml) Emulsion zur Injektion/Infusion | | Austria | Propofol Claris 2% (20 mg/ml) MCT Emulsion zur Injektion/Infusion | | Czech Republic | Propofol Norameda 20 mg/ml Emulsion for Injection/Infusion | | Denmark | Profast (Propofol, 20 mg/ml Emulsion for injection/Infusion) | | Estonia | Spiva (Propofol, 20 mg/ml Emulsion for Injection/Infusion) | | Finland | Rapiva (Propofol, 20 mg/ml Emulsion for Injection/Infusion) | | France | Spiva (Propofol, 20 mg/ml Emulsion for Injection/Infusion) | | Hungary | Spiva (Propofol, 20 mg/ml Emulsion for Injection/Infusion) | | Ireland | Propofol, 20 mg/ml Emulsion for Injection/Infusion | | Italy | Rapiva (Propofol, 20 mg/ml Emulsion for Injection/Infusion) | | Latvia | Rapiva 20 mg/ml emulsion for injection/infusion (Rapiva 20 mg/ml emulsija injekcijām/infūzijām) | | Lithuania | Spiva (Propofol Norameda 20 mg/ml injekcinė/infuzinė emulsija) | | Luxembourg | Spiva (Propofol, 20 mg/ml Emulsion for Injection/Infusion) | | The Netherlands | Rapiva (Propofol, 20 mg/ml Emulsion for Injection/Infusion) | | Norway | Spifol (Propofol, 20 mg/ml Emulsion for Injection/Infusion) | | Poland | Propofol Norameda | | Portugal | Spiva (Propofol, 20 mg/ml Emulsion for Injection/Infusion) | | Romania | Profast 20 mg/ml emulsie injectabila/perfuzabila | | Sweden | Spiva (Propofol, 20 mg/ml Emulsion for Injection/Infusion) | | Slovenia | Rapiva 20 mg/ml emulzija za injiciranje/infundiranje | | United Kingdom | Propofol 20 mg/ml Emulsion for injection/infusion |

This patient information leaflet was last approved on

The following information is intended exclusively for physicians or healthcare professionals:
Rapiva must be administered only by specialists trained in anaesthesia or in the care of intensive care patients, and only in hospitals or day-care units adequately equipped for this purpose. Circulatory and respiratory functions must be continuously monitored (e.g. with ECG, pulse oximeter), and equipment for maintaining airway patency, artificial ventilation, and other resuscitation measures must always be immediately available.
For sedation during surgical procedures or diagnostic examinations, Rapiva must not be administered by the same person performing the surgical or diagnostic procedure.
During continuous infusion administration of Rapiva, burettes, drip sets, syringe pumps or volumetric pumps are recommended to control the infusion rate.
Shake the container before use. If two layers are visible after shaking, the emulsion must not be used.
Use only homogeneous preparations and intact containers.
For single use only. Any unused emulsion must be discarded.
Before use, clean the surface of the rubber closure of the vial with alcohol (spray or swab).
After use, re-closed containers must be discarded.
Rapiva is a lipid-containing emulsion without antimicrobial preservatives, and therefore rapid microbial growth may occur.
The emulsion must be withdrawn under aseptic conditions into a sterile syringe or infusion set immediately after breaking the seal. Administration should follow immediately.
Aseptic conditions must be maintained for both Rapiva and the infusion system throughout the entire duration of the infusion.
Co-administration of other drugs or fluids added to the Rapiva infusion line should be performed close to the cannula insertion site using a Y-connector or three-way stopcock.
Rapiva 20 mg/ml is administered intravenously undiluted as a continuous infusion.
Rapiva 20 mg/ml must not be administered by repeated bolus injection for maintenance of anaesthesia.
Rapiva 20 mg/ml must not be mixed with other injectable or infusion solutions.
However, co-administration of Rapiva with 50 mg/ml (5%) glucose solution for injection, 9 mg/ml (0.9%) sodium chloride solution for injection, or 1.8 mg/ml (0.18%) sodium chloride and 40 mg/ml (4%) glucose solution for injection, and preservative-free 10 mg/ml (1%) lidocaine solution for injection is possible via a Y-connector near the injection site.
Rapiva must not be administered using infusion sets equipped with microbiological filters.
Rapiva and any infusion sets containing Rapiva are intended for single use in one specific patient. After use, any unused residue must be discarded.

Infusion of undiluted Rapiva solutions:
During continuous infusion of undiluted Rapiva solution, the use of burettes, drip sets, syringe pumps or volumetric pumps is recommended to control the infusion rate.
As established for parenteral administration of any fat emulsion, the duration of continuous infusion of Rapiva via one specific infusion system must not exceed 12 hours. The infusion tubing and the Rapiva container must be discarded or replaced within 12 hours at the latest.
Rapiva must not be mixed with other injectable or infusion solutions. However, 5% w/v glucose, 0.9% w/v sodium chloride, or 0.18% w/v sodium chloride and 4% w/v glucose solutions may be administered via appropriate side ports near the cannula insertion site.
To reduce pain at the injection site, Rapiva should be administered into a larger vein or a solution of injectable lidocaine may be administered prior to induction of anaesthesia with Rapiva.
The muscle relaxants atracurium or mivacurium must not be administered through the same intravenous administration system as Rapiva without first flushing the system.