Provive

Package leaflet: Information for the user

Provive
20 mg/ml, emulsion for injection / for infusion
Propofolum
Please read all of this leaflet carefully before this medicine is administered, because
it contains important information for the patient.

• Keep this leaflet, so that you can read it again if necessary.
• If you have any further questions, please consult your doctor, pharmacist or nurse.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm other people, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor, pharmacist or nurse. See: section 4.

Table of contents:

1. What Provive is and what it is used for
2. What you need to know before receiving Provive
3. How to use Provive
4. Possible side effects
5. How to store Provive
6. Contents of the pack and other information

1. What Provive is and what it is used for

Provive is a solution for injection containing the active substance called propofol.
Propofol belongs to a group of medicines known as anaesthetic agents. These medicines are used to induce loss of consciousness (deep sleep) for surgical or other procedures. It may also be used to achieve sedation (a state in which the patient is sleepy but not completely unconscious).
Provive 20 mg/ml is used for:

• Induction and maintenance of general anaesthesia in adults and children aged 3 years and older.
• Sedation of adults and children aged 3 years and older during diagnostic and surgical procedures, either as a single agent or in combination with local or regional anaesthesia.
• Sedation of ventilated patients aged over 16 years requiring intensive care.

2. Important information before using Provive

When not to use Provive

• If the patient is allergic to propofol or any of the other ingredients of this medicine (listed in section 6).
• Provive must not be used to induce sedation in intensive care settings in children aged 16 years and younger (see also "Warnings and precautions").

Warnings and precautions

• Administration of Provive 20 mg/ml is not recommended in neonates.
• Administration of Provive 20 mg/ml is not recommended in children under 3 years of age.
• Provive 20 mg/ml must not be used to induce sedation in intensive care settings in children aged 16 years and younger, as the safety and efficacy of this medicine have not been established in this age group.
• Before starting treatment with Provive, discuss with the doctor if:
  • the patient has ever had a seizure or convulsions,
  • the patient has previously been diagnosed with very high levels of fats in the blood or has disorders in fat metabolism,
  • the patient has any other diseases, such as heart, respiratory, kidney or liver disease,
  • the patient has been feeling unwell for some time,
  • the patient has a disorder of energy metabolism, so-called mitochondrial disease. Provive may worsen the condition of such a patient.
• The person administering Provive will continuously monitor the patient's condition. Provive may be used together with other medicines, such as sleeping tablets or painkillers. In such cases, the patient will be monitored for cardiovascular and respiratory function.
• Prolonged use of Provive in intensive care settings may lead to the need for zinc supplementation (a trace element) in some patients. The person administering Provive will decide when the patient needs supplementation and which preparation to use. In exceptional cases, unconsciousness has occurred in postoperative patients. These patients recovered without complications.
• If any of the following conditions are present in the patient, there is a risk of very rare adverse reactions. These conditions include:
  • reduced blood flow to tissues,
  • severe nerve damage,
  • blood infection (sepsis).

Provive and other medicines
Tell the doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take. This includes medicines available without a prescription.
If the patient is taking any of the following medicines, adverse reactions may occur when used in combination with propofol. This includes, for example, concomitant use of:

• other anaesthetic medicines (administered epidurally or by inhalation),
• medicines used for premedication (the anaesthesiologist will know which medicines are involved),
• muscle relaxants (suxamethonium or benzodiazepines),
• painkillers (e.g. fentanyl),
• medicines affecting the heart (e.g. digoxin),
• rifampicin (an antibiotic).

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to become pregnant, she should consult a doctor or pharmacist before using this medicine.
Provive should not be administered to pregnant women unless absolutely necessary.
For the safety of the infant, breastfeeding must be discontinued during treatment with Provive.

Driving and using machines
The ability to drive and operate machinery may be impaired for some time after the procedure due to the use of this medicine. If the patient returns home on the day of the procedure, they must not drive or operate machinery. If necessary, ask the doctor when it is safe to return to work.

Provive contains soybean oil
Provive contains soybean oil. Do not use if hypersensitivity to peanuts or soybeans has been diagnosed.

Provive contains lecithin from hen's eggs
In individuals with hypersensitivity to this ingredient, their presence may cause problems.

This medicine contains less than 1 mmol of sodium (23 mg) per dose, i.e. the medicine is considered "sodium-free".

3. How to use Provive

• Provive is administered by an anaesthesiologist or a physician specializing in intensive care medicine.
• Provive is given by intravenous injection into a vein on the back of the hand or on the forearm.
• Sometimes a local anaesthetic (such as lidocaine) may also be administered at the injection site to reduce injection pain.
• The dose administered will depend on the patient's age, body weight, and health status. The physician will use the appropriate dose to induce and maintain anaesthesia or to achieve the required level of sedation. Special attention will be paid to the patient's response and vital signs (pulse, blood pressure, respiratory function, etc.).

If you have any further questions regarding the use of this medicine,
please consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

The following side effects have been reported:

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

• Pain at the injection site during administration of the anaesthetic

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

• Slow heart rate (bradycardia)
• Headache after waking up
• Transient breathing changes (apnoea) during administration of the anaesthetic
• Nausea and vomiting after waking up
• Low blood pressure (hypotension)

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

• Blood clots in a vein or artery (thrombosis)
• Inflammation of the veins

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

• Muscle twitching (movements resembling epilepsy) at the beginning of anaesthesia, during and after waking up, including seizures / epileptic fits (convulsions)

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

• Fluid accumulation in the lungs (pulmonary oedema)
• Pancreatitis, accompanied by severe upper abdominal pain radiating to the back, and nausea and vomiting (pancreatitis)
• Discolouration of urine (usually green)
• Postoperative fever
• Loss of consciousness after surgery
• Hypersensitivity to certain substances (anaphylaxis), which may present as: sudden fluid accumulation in the skin and mucous membranes (e.g. throat or tongue), difficulty breathing and/or itching and rash (angioedema); breathlessness due to muscle or airway spasms (bronchospasm); skin redness (flushing); low blood pressure (hypotension)
• Genital discharge
• Local tissue necrosis (only if Provive is accidentally administered outside the vein)

Frequency not known (cannot be estimated from the available data):

• Blood acidification (metabolic acidosis), excessive potassium levels in the blood (hyperkalaemia; may present as muscle cramps, diarrhoea, nausea or headache), elevated fat levels in the blood (hyperlipidaemia)

• Excessive sense of well-being (euphoria)

• Drug abuse

• Involuntary movements

• Irregular heartbeat (arrhythmia), impaired heart function (heart failure)

• Respiratory depression (depending on the dose of Provive administered)

• Enlarged liver (hepatomegaly)

• Breakdown of muscle tissue, accompanied by muscle cramps, fever and red-brown discoloration of urine (rhabdomyolysis)

• Kidney failure

• Pain at the injection site, swelling at the injection site (only if Provive is accidentally administered outside the vein)

• Changes in ECG (changes indicative of Brugada syndrome)

• Prolonged and painful erection (priapism)

• Hepatitis, acute liver failure [symptoms may include yellowing of the skin and eyes, itching, dark urine, abdominal pain and liver tenderness on palpation (indicated as pain under the front part of the rib cage on the right side of the body), sometimes with loss of appetite]

Reporting of side effects

If any side effects occur, including any not listed in this leaflet, tell your doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:
Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: +48 22 49 21 301, fax: +48 22 49 21 309,
website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorisation holder.
Reporting side effects helps provide more information on the safety of the medicine.

5. How to store Provive

Keep this medicine out of sight and reach of children.
Provive is stored in a hospital setting. Hospital staff are responsible for the proper storage, administration, and disposal of any remaining Provive medicine.
Do not use this medicine after the expiry date stated on the packaging (EXP). The expiry date refers to the last day of the stated month.
Do not store above 25 °C.
Store in the original packaging to protect from light.
Do not store in the refrigerator or freeze.
After first opening, the medicine must be used immediately.
Shake the vial before use.
Do not use the emulsion if, after shaking, two layers are visible.
Only use medicine that has a uniform consistency and comes from undamaged packaging.
For single use only. Any unused emulsion must be discarded.
Medicines must not be disposed of via wastewater or household waste. Ask a pharmacist how to dispose of medicines no longer in use. Such measures will help protect the environment.

6. Contents of the package and other information

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What Provive 20 mg/ml contains
The active substance is propofol.
Each 1 ml of injection emulsion contains 20 mg of propofol.
One 50 ml vial of the medicine contains 1000 mg of propofol.
The other ingredients are: purified soybean oil, glycerol, egg phosphatidylcholine, sodium oleate, sodium hydroxide (for pH adjustment) and water for injections.

What Provive 20 mg/ml looks like and contents of the pack
Provive 20 mg/ml is a white oil-in-water emulsion for injection or infusion.
This medicine is supplied in a 50 ml clear glass type II vial, closed with a grey bromobutyl rubber stopper and a plastic cap.

Pack sizes:
50 ml clear glass type II vial with a grey bromobutyl rubber stopper, pack contains 1 vial.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Baxter Holding B.V.
Kobaltweg 49,
3542 CE Utrecht
The Netherlands

Manufacturer/Importer
Tramco Sp. z o.o.
Wolskie, ul. Wolska 14
05-860 Płochocin
Poland
Bieffe Medital S.p.A.
Via Nuova Provinciale
23034 Grosotto (SO)
Italy
Baxter
Boulevard René Branquart 80,
7860 Lessines
Belgium
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Information intended exclusively for healthcare professionals:

Provive may only be administered in hospitals or appropriately equipped medical facilities by physicians specialized in anesthesiology or intensive care medicine.
Continuous monitoring of the patient's cardiovascular and respiratory functions is required, and equipment for maintaining airway patency, artificial ventilation, administration of oxygen with increased concentration, and other resuscitation equipment must be readily available at all times.
Provive 20 mg/ml must not be administered by the person performing the diagnostic or surgical procedure.
The vial should be shaken before use. Do not use the emulsion if two layers are visible after shaking.
Only use the medicinal product if it has a homogeneous consistency and comes from undamaged packaging.
For single use only. Any unused portion of the medicinal product must be discarded.
Before use, clean the rubber stopper with alcohol from a spray bottle or an alcohol-soaked swab. Discard opened vials after use.
Provive 20 mg/ml is a lipid emulsion without preservatives and may support microbial growth.
The emulsion should be withdrawn aseptically into a sterile syringe or infusion set immediately after piercing the vial stopper. Administration should begin immediately. Sterility of Provive 20 mg/ml and the infusion system must be maintained throughout the entire infusion period. Any infusion fluids added to the infusion system through which Provive 20 mg/ml is administered must be given close to the site of the venous cannula insertion. Do not administer Provive 20 mg/ml through infusion systems equipped with microbiological filters.
Provive 20 mg/ml and any infusion sets containing Provive 20 mg/ml are intended for single use in one patient only. In accordance with established guidelines for other lipid emulsions, the duration of a single infusion must not exceed 12 hours. After completion of administration or 12 hours after initiation of infusion—whichever occurs first—the container with Provive 20 mg/ml or the infusion set must be disconnected or, if necessary, replaced with a new one.
For infusions of undiluted Provive 20 mg/ml, devices such as burettes, drip counters, syringe pumps, or volumetric infusion pumps are recommended to control the infusion rate.
Provive is administered undiluted by intravenous continuous infusion. Provive must not be given as intravenous bolus injections for maintenance of anesthesia.
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Provive must not be mixed with other injectable or infusion solutions. However, it is possible to co-administer Provive simultaneously 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 with 40 mg/ml (4%) glucose solution for injection, as well as 10 mg/ml (1%) lidocaine solution for injection without preservatives, using a "Y" connector close to the site of drug administration.
Do not administer Provive through infusion systems equipped with microbiological filters.
Provive and any infusion sets containing Provive are intended for single use in one patient only. Any unused portion of Provive must be discarded.
Infusion of undiluted Provive:
For infusions of undiluted Provive, devices such as burettes, drip counters, syringe pumps, or volumetric infusion pumps are recommended to control the infusion rate.
Provive 20 mg/ml and any infusion sets containing Provive 20 mg/ml are intended for single use in one patient. In accordance with established guidelines for other lipid emulsions, the duration of a single infusion must not exceed 12 hours. After completion of administration or 12 hours after initiation of infusion—whichever occurs first—the container with Provive or the infusion set must be removed or, if necessary, replaced with a new one.
Provive must not be mixed with other injectable or infusion solutions. However, 5% glucose solution, 0.9% sodium chloride solution, or 0.18% sodium chloride and 4% glucose solution may be co-administered using appropriate accessories at the site of venous cannula insertion.
To reduce pain at the site of administration, Provive should be administered into a larger vein, and lidocaine solution for injection may be given prior to induction of anesthesia with Provive.
Neuromuscular blocking agents such as atracurium and mivacurium must not be administered through the same infusion system as Provive without first flushing the system.
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