Active ingredients: Propofol
Diprivan 10 mg / ml emulsion for injection for intravenous use
Diprivan 10 mg / ml emulsion for infusion
Diprivan 20 mg / ml emulsion for infusion
Why is Diprivan used? What is it for?
PHARMACOTHERAPEUTIC CATEGORY
General anesthetic - ATC code N01AX10.
HOW DOES THIS MEDICINE WORK?
Propofol is used by the anesthetist for the induction and maintenance of general anesthesia, Diprivan 10 mg / ml in adults and children over one month of age and Diprivan 20 mg / ml in adults and children over 3 years old, during surgery.
It is also used to sedate patients over the age of 16 in intensive care whose breathing is assisted by a machine.
Contraindications When Diprivan should not be used
The product must not be used in case of:
- hypersensitivity (allergy) to propofol or to one of the ingredients of Diprivan, this being known from previous experience. Diprivan contains soybean oil and should not be used in patients with hypersensitivity to peanuts and soybeans.
- pregnant or breastfeeding
- sedation in the intensive care unit in children and adolescents aged 16 years and younger.
Precautions for use What you need to know before taking Diprivan
Diprivan is not recommended for use in neonates.
The use of Diprivan 20 mg / ml is not recommended in children under 3 years of age.
Diprivan should not be used in patients aged 16 years of age or younger for sedation in intensive care as the efficacy and safety of Diprivan for sedation have not been demonstrated (see section When this product should not be used).
Particular caution is required when administering Diprivan to patients with mitochondrial disorders, as these conditions may worsen when patients undergo anesthesia, surgery and intensive care unit care.
The use of Diprivan emulsion for infusion for sedation in intensive care units (ICUs) has been associated with numerous metabolic disorders and organ system failure that can result in death. Concomitances of the following events have been reported: metabolic acidosis, rhabdomyolysis, hyperkalaemia, hepatomegaly, renal failure, hyperlipidaemia, cardiac arrhythmia, Brugada-type ECG (ST-segment elevation and dome-shaped T wave) and rapidly progressing unresponsive heart failure usually to supportive treatment with inotropic drugs. The concomitance of these events has been referred to as propofol infusion syndrome. These events were most observed in patients with severe head damage and children with respiratory tract infections who had received dosages higher than those recommended in adults for sedation in the ICU.
Interactions Which drugs or foods can change the effect of Diprivan
There are several medicines that can interact with propofol. Therefore, always tell your doctor or pharmacist if you are taking any other medicines, even those not prescribed.
Severe lowering of blood pressure following induction of anesthesia with Diprivan has been reported in patients treated with rifampicin.
Warnings It is important to know that:
You should be aware that, for a certain period of time after general anesthesia, the ability to drive and use machines may be affected. This means that until you have fully recovered your reactive faculties after surgery, he shouldn't drive cars.
Propofol infusion via the optimal concentration mode at the site of action may potentially be associated with exacerbation of reductions in blood pressure or breathing pauses, but not beyond the levels associated with manual administration.
Dosage and method of use How to use Diprivan: Dosage
Generally the drug is only available in the hospital. The administration of the drug is subject to certain rules and must only take place under the strict supervision of qualified medical personnel.
The dosage that is most suitable for you is determined by your anesthetist, based on your age, body weight and physical condition. Your doctor will give you the right dose to start and maintain anesthesia or to achieve the desired level of sedation. by carefully evaluating your response and vital signs (pulse, blood pressure, etc.).
Diprivan 10 mg / ml will be given to you by repeated bolus or infusion.
Diprivan 20 mg / ml will only be given to you by infusion. Diprivan 20 mg / ml must not be diluted with other infusion liquids.
Sleep induction occurs in 1-5 minutes after administration. Maintenance of general anesthesia is achieved by:
Diprivan 10 mg / ml by repeated bolus or infusion
Diprivan 20 mg / ml by infusion.
Sedation in intensive care takes place by infusion of propofol; it is recommended not to exceed the dose of 4 mg / kg / h.
In elderly or debilitated patients, in patients with pulmonary, cardiac, renal, hepatic dysfunction or in patients with lower blood volume (hypovolemic) the rate of administration of propofol should be decreased. Elimination of propofol is dependent on the bloodstream, so concomitant administration of drugs that reduce blood flow may also reduce the elimination of propofol. Propofol should be used with particular caution in patients with cardiac dysfunction or severe heart disease and in patients with high intracranial pressure and low blood pressure. Administration of propofol to epileptic patients may increase the risk of convulsions. Particular care should be taken in patients with impaired lipid metabolism and in other conditions where lipid emulsions should be used with caution. After administration of propofol to patients who are thought to be at risk of lipid overload, the treating physician will measure the level of lipids in the blood. If necessary, administration of propofol should be adequate. Diprivan contains 0.0018 mmol of sodium per ml. After 3 days of administering propofol to patients being treated in intensive care units, the treating physician should measure the level of lipids in the blood. Soybean oil can rarely cause allergic reactions. The patient can be discharged after a complete recovery of psychophysical conditions is assured.
Further information on use for Diprivan 10 mg / ml and Diprivan 20 mg / ml
Diprivan can be administered, using a 'Y' device placed near the injection site, simultaneously with intravenous infusions of 5% glucose, 0.9% sodium chloride or 4% glucose with 0.18% sodium chloride.
The pre-filled glass syringe has lower sliding resistance than disposable plastic syringes and works more easily. Therefore, if Diprivan is administered manually using a pre-filled syringe without the aid of a pump, the infusion line between the syringe and the patient should not be left open when unattended. When using pre-filled syringes it is important to ensure compatibility with syringe pumps. In particular, the pumps must be designed in such a way as to prevent the possibility of uncontrolled infusions and must have an occlusion alarm system "with a pressure not exceeding 1000 mmHg". If a programmable pump or equivalent, which offers the possibility of choosing between different types of syringe, the program B "- D" 50/60 ml "PLASTIPAK" must be chosen.
Diprivan 10 mg / ml can be premixed with 500 micrograms / ml solution for injection of alfentanil in the ratio of 20: 1 to 50: 1 v / v. The mixtures must be prepared using sterile technique and must be used within 6 hours of preparation.
TCI (Target Controlled Infusion) - Administration of Diprivan through the "Diprifusor" TCI system
Diprivan can be administered with TCI via the "Diprifusor" TCI system which contains the "Diprifusor" TCI software. This system can only operate by electronically recognizing a site of pre-filled syringes containing Diprivan 10 mg / ml or Diprivan 20 mg / ml.
The "Diprifusor" TCI system is able to automatically adjust the infusion rate to reach the concentration selected by the operator. The user must be familiar with the user manual of the infusion pump, with the administration of Diprivan through the TCI system. and with the correct use of the syringe identification system, all this information can be found in the "Diprifusor" user manual available from AstraZeneca. The "Diprifusor" TCI system can provide two modes of optimal controlled infusion: optimal blood concentration and optimal concentration at the site of action (brain). Previous models provide only the optimal blood concentration mode.
Administration of Diprivan via the "Diprifusor" TCI system is indicated in adults only for the induction and maintenance of general anesthesia. It is not recommended for sedation in the ICU. There are no data on the optimal concentration mode at the site of action for sedation of ventilated ICU patients (see section TCI - Target Controlled Infusion); therefore, such use is not recommended.
Administration of Diprivan via the "Diprifusor" TCI system is not recommended in children in any indication.
To achieve induction and maintenance of anesthesia in adults, Diprivan can be administered by means of a computerized infusion system (TCI).This system allows you to control the induction and depth of anesthesia or sedation through the selection and adjustment of optimal (theoretical) blood or site-of-action concentrations of propofol. The use of the optimal concentration mode at the site of action allows a more rapid induction of sedation or anesthesia than the use of the optimal blood concentration mode. If the "Diprifusor" TCI system has been used for anesthesia, it can be continued in the postoperative period to provide sedation in the ICU, by appropriate selection of the optimal concentration.
Below is a guide to optimal propofol concentrations. In view of the interpersonal variability of the pharmacokinetics and pharmacodynamics of propofol, in both premedicated and non-premedicated patients, the optimal concentrations of propofol should be selected based on the patient's response in order to achieve the required depth of anesthesia.
In adult patients less than 55 years of age, anesthesia can generally be induced with optimal blood concentrations of propofol in the order of 4-8 micrograms / ml or with optimal action-site concentrations of 2.5-4 micrograms / ml. ml. An optimal starting blood concentration of 4 micrograms / ml or an optimal action site concentration of 2.5 micrograms / ml is recommended in premedicated patients and an optimal starting blood concentration of 6 micrograms / ml is recommended in non-premedicated patients. ml or an optimal concentration at the site of action of 4 micrograms / ml. The induction time with optimal blood concentrations is generally 60-120 seconds. Higher optimal blood concentrations allow to obtain a more rapid induction of anesthesia but can lead to a more pronounced respiratory and hemodynamic depression.
When using optimal action site concentrations the use of higher optimal concentrations to achieve faster induction of anesthesia is not necessary and not recommended. Lower starting concentrations should be used in patients over 55 years of age and in ASA grade 3-4 patients (use of the site-to-action mode in ASA grade 4 patients is not recommended). For the site-of-action mode an initial optimal concentration of 0.5-1.0 micrograms / mL should be used. For both optimal concentration modes, the concentrations can then be increased in successive increments of 0.5- 1.0 micrograms / ml at one minute intervals to achieve gradual induction of anesthesia.
Additional analgesia is generally required and the extent of the reduction in optimal concentrations for maintaining anesthesia is related to the amount of analgesic administered concurrently. Optimal blood concentrations of propofol of the order of 3-6 micrograms / ml and optimal action-site concentrations of 2.5-4 micrograms / ml usually induce and maintain satisfactory anesthesia. In the absence of additional analgesia, optimal concentrations above the action-site of 5-6 micrograms / ml may be necessary to facilitate laryngoscopy or to abolish responses to painful stimuli. For both modes of optimal concentration, the expected concentrations upon awakening. of propofol (blood or site of action) are generally in the order of 1.0-2.0 micrograms / ml and depend on the amount of analgesic administered during maintenance. When optimal concentrations are reduced, "Diprifusor" stops transient infusion to allow concentrations to drop and reach a new target faster.
Overdose What to do if you have taken too much Diprivan
There are no known effects to be attributed to Diprivan overdose.
Side Effects What are the side effects of Diprivan
Like all medicines, Diprivan can cause side effects.
Pain at the injection site occurs very commonly after administration of propofol. Clot formation or venous inflammation occurs uncommonly. Particularly when given into a small vein. During the induction, depending on the dose administered and on the concomitant use with other medicines, the following may occur: alterations of the reproductive system and of the breast such as sexual disinhibition, reduction or acceleration of the heartbeat, lowering of blood pressure, respiratory arrest for a few moments, rapid breathing, redness and hiccups. Cases of fluid accumulation in the lungs have been observed. Rarely, in isolated cases, nervous system alterations such as epileptic seizures may occur even hours or days after administration of propofol.
Cough may occur during maintenance therapy with propofol. During the awakening phase, chills, cold sensation, dizziness occur rarely, and there may also be cough, nausea, vomiting and headache. Following prolonged administration, green discoloration of the urine has been reported. Postoperative fever may occur. Diprivan contains soybean oil which can rarely cause allergic reactions, including anaphylaxis. Rare cases of severe hypersensitivity reaction have been reported. Cases of pancreatitis have been observed very rarely after administration of Diprivan; a causal relationship has not been established with certainty. Cases of rhabdomyolysis (muscle damage) with an unknown frequency have been reported after administration of propofol for sedation in intensive care units.
Cases of postoperative unconsciousness and tissue necrosis following accidental administration out of a blood vessel (extravascular) have been reported very rarely.
Cases with unknown frequency of metabolic acidosis, elevated blood potassium levels, hyperlipidaemia, euphoric mood, drug abuse and drug dependence (predominantly by healthcare professionals), involuntary movements, cardiac arrhythmia, heart failure have also been reported. , respiratory depression (dose dependent), hepatomegaly, renal failure, local pain, swelling following accidental administration out of a blood vessel (extravascular), Brugada-type ECG.
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. Undesirable effects can also be reported directly through the national reporting system at "https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse". By reporting side effects you can help provide more information on the safety of this medicine. "
Expiry and Retention
The anesthetist and the hospital pharmacist are responsible for the correct storage, use and distribution of the medicine.
Store at a temperature between + 2 ° C and + 25 ° C. Do not freeze. Do not use after the expiration date.
Keep out of the sight and reach of children.
Composition and pharmaceutical form
COMPOSITION
Diprivan 10 mg / ml
1 ml contains: propofol 10 mg; excipients: sodium edetate, refined soybean oil, purified egg phosphatide, glycerol, sodium hydroxide, water for injections.
Diprivan 20 mg / ml
1 ml contains: propofol 20 mg; excipients: sodium edetate, refined soybean oil, purified egg phosphatide, glycerol, sodium hydroxide, water for injections.
PHARMACEUTICAL FORM AND CONTENT
Diprivan 10 mg / ml emulsion for injection for intravenous use:
- 5 vials of 20 ml
Diprivan 10 mg / ml emulsion for infusion:
- 5 bottles of 20 ml
- Bottle of 50 ml
- Bottle of 100 ml
- 20 ml pre-filled syringe
- 50 ml pre-filled syringe
Diprivan 20 mg / ml emulsion for infusion:
- 10 ml pre-filled syringe
- 50 ml pre-filled syringe
- Bottle of 50 ml.
Not all pack sizes may be marketed.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT
DIPRIVAN 10 MG / ML
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
1 ml contains 10 mg of propofol.
For excipients: see section 6.1.
03.0 PHARMACEUTICAL FORM
Emulsion for injection and intravenous infusion.
White isotonic emulsion, oil in water, for intravenous administration.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
The product is indicated:
• for the induction and maintenance of general anesthesia in adults and children over one month of age.
• for the sedation of patients over 16 years of age who are artificially ventilated in the Intensive Care Units.
04.2 Posology and method of administration
The dose of Diprivan should be individualized by an experienced anesthetist based on the patient's age and / or body weight, sensitivity and concomitant therapy. Propofol is a short-term intravenous anesthetic and has been used in conjunction with spinal anesthesia. and epidural.
It is recommended that the dose of propofol be graded based on the patient's response, up to clinical evidence of initiation of anesthesia.
The contents of one ampoule or one bottle of Diprivan are intended for single use, in one patient only.
For specific instructions regarding the administration of Diprivan via the "Diprifusor" TCI (Target Controlled Infusion) computerized infusion system which contains the "Diprifusor" software see under: "TCI method of administration - Administration of Diprivan via the" Diprifusor "TCI system The use of this system is intended exclusively for the induction and maintenance of anesthesia in adults. The use of the "Diprifusor" TCI system is not recommended for sedation in intensive care or in children.
Induction of general anesthesia
Adults
For adult patients, less than 55 years of age, doses between 1.5 and 2.5 mg / kg are required. In healthy adult patients, an administration rate of 2-4 ml (20 - 40 mg) for ten seconds, approximately, is required.
In high-risk patients, belonging to classes 3 and 4 of the American Society of Anaesthesiologists (ASA) classification, the rate of administration should be 2 ml (20 mg) for 10 seconds.
Children older than 1 month
It is recommended that Diprivan be administered slowly until clinical evidence of onset of anesthesia. The dose should be in proportion to age and / or body weight.
Most children over eight years of age require a dose of approximately 2.5 mg / kg for induction of anesthesia.
For younger children, particularly between 1 month and 3 years, the required dose may be higher (2.5-4 mg / kg). Given the lack of clinical experience, lower doses are recommended for children at increased risk (ASA grade III and IV).
Administration of Diprivan via the "Diprifusor" TCI system is not recommended in children in any indication.
Senior citizens
In patients over 55 years of age, a lower dose is usually required.
Maintenance
Anesthesia should be maintained by administering Diprivan 10 mg / ml to prevent clinical signs of superficial or repeated bolus anesthesia in additional doses ranging from 25 mg (2.5 ml) to 50 mg (5.0 ml) or in continuous infusion:
• in adults: 4 - 12 mg / kg / h.
• in the elderly, defected patients, hypovolaemic patients and patients of ASA grades III and IV: 4 mg / kg / h.
• in children over 1 month of age: the required rate of administration varies considerably between patients, but rates of 9-15 mg / kg / h generally allow satisfactory anesthesia. In younger children, particularly between 1 month and 3 years, the required dose may be higher.
Lower doses are recommended in ASA Grades III and IV patients (see also section 4.4).
Sedation in ventilated patients in the ICU
For sedation of patients in the ICU, Diprivan should be administered by continuous infusion. The rate of infusion depends on the depth of sedation required; generally, infusion rates between 0.3 and 4.0 mg / kg / h allow satisfactory levels of sedation to be achieved (see section 4.4).
Propofol is not indicated for the sedation of patients less than 16 years of age in the ICU (see section 4.3).
It is recommended not to exceed the dose of 4 mg / kg / h.
Administration of Diprivan via the "Diprifusor" TCI system is not recommended during sedation in the ICU.
Administration by infusion
Diprivan 10 mg / ml as it is or diluted in 5% dextrose solution can be administered by intravenous infusion using the various infusion control systems.
When it is used undiluted in the maintenance of anesthesia it is necessary to use syringe pumps or volumetric pumps that allow the control of the infusion rate.
For the diluted emulsion the infusion line must include at least one burette, a dropper or a volumetric pump to avoid the risk of accidental and uncontrollable administration of large volumes of Diprivan 10 mg / ml.
The maximum quantity of diluted solution to be introduced into the burette must be calculated taking into consideration the risk of a possible infusion that cannot be controlled.
Diprivan 10 mg / ml can be administered, via a "Y" device placed near the injection site, at the same time as intravenous infusions of 0.9% sodium chloride or 5% dextrose.
Diprivan 10 mg / ml can be premixed with 5% dextrose intravenous infusion solutions in glass bottles or PVC infusion bags. 1 part of Diprivan 10 mg / ml must be mixed with a maximum of 4 parts of 5% dextrose. In the case of PVC bags it is recommended that the bag be full and that all the volume removed from the bag to prepare the dilution is replaced by an equal volume of Diprivan 10 mg / ml.
The emulsion thus diluted must be prepared taking into account the appropriate rules of asepsis, immediately before administration and must be used within 6 hours of dilution.
Only in cases of induction of anesthesia Diprivan 10 mg / ml can be premixed, immediately before administration and aseptically, with injectable lidocaine hydrochloride (0.5-1%, without preservatives) in the proportion of 20 parts of Diprivan 10 mg / ml and, up to a maximum, of 1 part of injectable lidocaine hydrochloride (0.5-1%, without preservatives).
Diprivan 10 mg / ml can be premixed with 500 mcg / ml solution for injection of alfentanil in the ratio from 20: 1 to 50: 1 v / v. The mixtures must be prepared using sterile technique and must be used within 6 hours of preparation.
Duration of administration
The duration of administration should not exceed 7 days.
Additional information for use for Diprivan 10 mg / ml
Diprivan can be administered, via a "Y" device placed near the injection site, at the same time as intravenous infusions of 5% glucose, 0.9% sodium chloride or 4% glucose with 0.18% sodium chloride.
The pre-filled glass syringe has lower sliding resistance than disposable plastic syringes and works more easily. Therefore, if Diprivan is administered manually using a pre-filled syringe without the aid of a pump, the infusion line between the syringe and the patient should not be left open when unattended.
When using pre-filled syringes it is important to ensure compatibility with syringe pumps. In particular, the pumps must be designed in such a way as to prevent the possibility of uncontrolled infusions and must have an occlusion alarm system "with a pressure not exceeding 1000 mmHg". If a programmable pump or equivalent, which offers the possibility of choosing between different types of syringe, the program B "- D" 50/60 ml "PLASTIPAK" must be chosen.
TCI (Target Controlled Infusion) - Administration of Diprivan through the "Diprifusor" TCI system.
Administration of Diprivan via the "Diprifusor" TCI system is indicated only for the induction and maintenance of general anesthesia in adults. It is not recommended for sedation in the ICU or in children.
To achieve induction and maintenance of anesthesia in adults, Diprivan can be administered by means of a computerized infusion system (TCI). This system allows anesthetists to achieve and control the rate of induction and depth of anesthesia. desired, through the selection and regulation of optimal (theoretical) blood concentrations of propofol.
Diprivan can only be administered with the TCI via the "Diprifusor" TCI system which contains the "Diprifusor" software.
This system can only operate by electronically recognizing a site of pre-filled syringes containing Diprivan 10 mg / ml or Diprivan 20 mg / ml. The "Diprifusor" TCI system is able to automatically adjust the infusion rate according to the recognized dosage of Diprivan 10 mg / ml or 20 mg / ml. The user must be familiar with the user manual of the infusion pump, with the administration of Diprivan via the TCI system and with the correct use of the syringe identification system. All this information can be found in the training manual of the " Diprifusor "available from AstraZeneca.
Below is a guide to optimal propofol concentrations.
In view of the interpersonal variability of the pharmacokinetics and pharmacodynamics of propofol, in both premedicated and non-premedicated patients, the optimal concentrations of propofol should be selected based on the patient's response in order to achieve the required depth of anesthesia.
In adult patients less than 55 years of age, anesthesia can generally be induced with optimal propofol concentrations of the order of 4-8 mcg / ml. In premedicated patients an initial propofol concentration of 4 mcg / ml is recommended while in non-premedicated patients an initial concentration of 6 mcg / ml is recommended. The induction time with these concentrations is generally 60-120 seconds. Higher concentrations allow for a more rapid induction of anesthesia but can lead to more pronounced respiratory and hemodynamic depression.
Lower starting concentrations should be used in patients over 55 years of age and in ASA grade 3-4 patients. Initial concentrations can then be increased in successive increments of 0.5-1.0 mcg / mL at one minute intervals to achieve gradual induction of anesthesia.
Additional analgesia is generally required and the extent of the reduction in optimal concentrations for maintaining anesthesia is related to the amount of analgesic administered concurrently. Optimal concentrations of propofol of the order of 3-6 mcg / ml usually allow the maintenance of a satisfactory anesthesia.
Upon awakening, the predicted concentrations of propofol are generally in the order of 1.0-2.0 mcg / ml and depend on the amount of analgesic administered during maintenance.
04.3 Contraindications
The use of Diprivan is contraindicated in patients with known hypersensitivity to propofol or to any of the excipients.
Diprivan 1% contains soy oil and should not be used in people who are hypersensitive to peanuts or soy.
Diprivan should not be used in patients aged 16 years or younger for sedation in intensive care.
04.4 Special warnings and appropriate precautions for use
Diprivan should be administered by healthcare professionals who specialize in anesthesia (or, when appropriate, by physicians qualified in the treatment of ICU patients).
Patients should be monitored constantly, and equipment for maintaining a patient's patency, artificial ventilation, oxygen administration, and other resuscitation equipment should be readily available at all times. Diprivan must not be administered by the person performing the diagnostic or surgical procedure.
Abuse of Diprivan, predominantly by healthcare professionals, has been reported. As with other general anesthetic agents, administration of Diprivan without any airway management can lead to fatal respiratory complications.
In case of administration of Diprivan for conscious sedation, for surgical and diagnostic procedures, patients should be constantly monitored in order to detect any early signs of hypotension, airway obstruction and oxygen desaturation.
As with other sedative agents, when Diprivan is used for sedation during surgical procedures, the patient may make involuntary movements. During procedures that require the subject to be immobile, these movements can be dangerous in the operation.
It is necessary to wait an adequate period of time before discharging the patient after using Diprivan, in order to ensure complete recovery of the subject after sedation or general anesthesia. In very rare cases, the administration of Diprivan may be associated with the appearance of a phase of postoperative unconsciousness, which may be accompanied by an increase in muscle tone. This state may or may not be preceded by a wakeful phase. Although awakening is spontaneous, the unconscious patient should be kept under appropriate observation.
Generally, the impairment of cognitive function induced by Diprivan administration is not detectable after 12 hours. The effects of Diprivan, the procedure, concomitant medications, age and condition of the subject should be considered regarding:
• the opportunity to be accompanied when leaving the place of administration
• the timescales envisaged for resuming specialized or dangerous tasks, such as driving vehicles
• the use of other agents that can cause sedation (eg benzodiazepines, opiates, alcoholic beverages).
As with other intravenous anesthetic agents, caution should be exercised in patients with cardiac, respiratory, renal or hepatic insufficiency, or in hypovolaemic or debilitated subjects.
Elimination of Diprivan is dependent on blood flow; consequently, concomitant use of a drug that reduces cardiac output will also decrease the clearance of Diprivan.
Diprivan does not exhibit any vagolytic activity and has been associated with cases of bradycardia (sporadically profound) and also asystole. Intravenous administration of an anticholinergic agent should be considered prior to induction or during maintenance of anesthesia, especially in cases where vagal tone is likely to prevail or when Diprivan is used in combination with other agents likely to cause the appearance of bradycardia.
If Diprivan is administered to an epileptic patient, there may be a risk of developing convulsions.
Particular care should be taken in patients with impaired lipid metabolism and in other conditions where lipid emulsions should be used with caution.
It is recommended that blood lipid levels be monitored when Diprivan is administered to patients at particular risk of lipid overload. Diprivan administration should be adjusted as appropriate if monitoring indicates "insufficient elimination of lipids from the body". If the patient is concomitantly receiving another lipid administered intravenously, its dose should be reduced to account for the amount of lipid infused as part of the Diprivan formulation; 1.0 mL of DIPRIVAN contains approximately 0.1 g of lipids.
The use of Diprivan is not recommended in neonates as this patient population has not been fully studied. Pharmacokinetic data (see section 5.2 of the SmPC) indicate that clearance is significantly reduced in neonates and exhibits very high interindividual variability. . Relative overdose may occur when administered doses recommended for older children, which could lead to severe cardiovascular depression.
Diprivan contains 0.0018 mmol of sodium per mL.
Advice regarding management in the intensive care unit
The safety and efficacy of Diprivan used for (background) sedation in children under the age of 16 have not been demonstrated. Although no cause and effect relationship has been established, serious side effects have been reported in combination with (background) sedation in patients less than 16 years of age (including cases with a fatal outcome), during unauthorized use of Diprivan. In particular, these effects related to the onset of metabolic acidosis, hyperlipidaemia, rhabdomyolysis and / or heart failure. These effects were observed more often in children with respiratory tract infections who received doses higher than the recommended doses in adults for sedation in the intensive care unit.
Concomitances of the following events have been reported: metabolic acidosis, rhabdomyolysis, hyperkalaemia, hepatomegaly, renal failure, hyperlipidaemia, cardiac arrhythmia, Brugada-type ECG (ST-segment elevation and dome-shaped T wave) and rapidly progressing unresponsive heart failure usually to supportive treatment with inotropic drugs (in some cases fatal) in adults. The concomitance of these events has been referred to as propofol infusion syndrome.
The main risk factors for the onset of these events appear to be the following: reduced oxygen supply to the tissues; severe neurological damage and / or sepsis; high doses of one or more of the following pharmacological agents - vasoconstrictors, steroids, inotropes and / o propofol (usually following prolonged administration at a dose greater than 4 mg / kg / hour).
Prescribers should be alert to these events and should consider reducing the dose of Diprivan or switching to an alternative sedative at the first sign of symptom onset. All sedative and therapeutic agents used in the intensive care unit ( UTI), including Diprivan, should be titrated to maintain optimal oxygen supply and hemodynamic parameters. Patients with elevated intracranial pressure (ICP) should receive appropriate treatment to support cerebral perfusion pressure during these therapy modifications. remind the treating physicians not to exceed the dose of 4 mg / kg / hour, if possible.
Other precautions
DIPRIVAN does not contain antimicrobial preservatives and therefore promotes the growth of microorganisms. EDTA is a chelating agent of metal ions, including zinc, and reduces microbial growth rates. The need for zinc supplementation should be considered during prolonged administration of DIPRIVAN, especially in predisposed patients. develop zinc deficiency, including those with burns, diarrhea and / or severe sepsis.
When Diprivan is aspirated, it should be withdrawn under aseptic conditions with a sterile syringe or given immediately after opening the vial or breaking the vial seal. Administration should commence immediately. Asepsis should be maintained for both Diprivan and patients. infusion devices throughout the administration period. Any infusion liquids, added to the Diprivan line, must be administered at the level of the cannula. Diprivan must not be administered via a microbiological filter.
Diprivan and any syringe containing Diprivan are to be used for a single dose in a single patient. In accordance with established guidelines for other lipid emulsions, a single infusion of Diprivan should not exceed 12 hours. At the end of the procedure or at 12 hours, whichever comes first, both the bag containing Diprivan and the infusion line should be discarded and replaced as appropriate.
04.5 Interactions with other medicinal products and other forms of interaction
Diprivan has been used in combination with spinal and epidural anesthesia and with drugs commonly used for premedication neuromuscular blocking drugs, inhaled agents and analgesics; no pharmacological incompatibility has been found. Lower doses of Diprivan may need to be used when general anesthesia or sedation are used in addition to regional anesthetic techniques.
04.6 Pregnancy and lactation
The safety of Diprivan during pregnancy has not been established. Diprivan should not be administered to pregnant women unless clearly necessary. Diprivan passes through the placenta and can cause neonatal depression. However, Diprivan can be used during an induced abortion.
Studies in lactating women have shown that small amounts of Diprivan are excreted in breast milk. Therefore, women should not breastfeed for 24 hours after Diprivan administration. Milk produced during this time should not be used.
04.7 Effects on ability to drive and use machines
Patients should be advised that performance in specialized activities, for example driving vehicles and operating machines, may be impaired for some time after using Diprivan.
In general, the impairment induced by Diprivan administration is not detectable after 12 hours (see section 4.4).
04.8 Undesirable effects
Induction and maintenance of anesthesia or sedation with Diprivan generally occur uniformly with minimal evidence of arousal. The most commonly reported adverse drug reactions are pharmacologically predictable side effects of an anesthetic / sedative agent such as hypotension.
The nature, severity and incidence of adverse events observed in patients who received Diprivan may be related to the condition of the recipients and the operative or therapeutic procedures implemented.
Table of adverse drug reactions
Severe cases of bradycardia are rare. Isolated cases of progression to asystole have been reported.
Occasionally, hypotension may require the use of intravenous fluids and a reduction in the rate of administration of Diprivan.
Very rare cases of rhabdomyolysis have been reported when Diprivan was administered at doses above 4 mg / kg / hour for sedation in the ICU.
It can be minimized by using the major veins of the forearm or antecubital fossa. With the use of Diprivan 1%, local pain can also be minimized by concomitant administration of lidocaine.
Concomitance of these events, described as "propofol infusion syndrome", can be observed in seriously ill patients who often have multiple risk factors for the occurrence of such events (see section 4.4).
Brugada type ECG - ST segment elevation and T wave with dome morphology detected on the ECG.
Rapidly progressing (in some cases fatal) heart failure in adults. In these cases, heart failure generally did not respond to supportive treatment with inotropic drugs.
Substance abuse, predominantly by health professionals.
Frequency not known, as it cannot be estimated from the available data from clinical studies.
04.9 Overdose
Accidental overdose is likely to cause cardiorespiratory depression, which must be treated by artificial ventilation with oxygen.Cardiovascular depression may require the patient's head to be lowered and, if severe, the use of plasma expanders and hypertensive agents.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: other general anesthetics.
The ATC code is N01AX10. Propofol is a short-acting intravenous anesthetic for induction and maintenance of general anesthesia and for sedation of intensive care patients. Propofol has rapid onset of action and duration of anesthesia. depending on the dose and the co-medication, it ranges from 10 minutes to 1 hour.
Awakening from anesthesia is usually quick and clear. Eye opening is possible within 10 minutes. The mechanism of action of propofol has not yet been elucidated. No specific receptor sites have been identified. It is generally known that anesthetics cause a non-specific effect at the lipid level of the membranes.
A limited number of studies on the duration of propofol-generated anesthesia in children indicate that safety and efficacy remain unchanged for up to 4 hours. The literature relating to use in children documents use in prolonged procedures with no changes in safety or efficacy.
05.2 "Pharmacokinetic properties
Propofol is 97% bound to plasma proteins. An elimination half-life of between 277 and 403 minutes was found after intravenous infusion. After bolus administration, propofol kinetics can be described by a three-compartment type model: a very rapid distribution phase (t½ = 1.8 - 4.1 minutes), a beta elimination phase (t½ = 30 -60 minutes) and a gamma elimination phase (t½ = 200-300 minutes). In the gamma elimination phase, the decrease in blood levels occurs slowly due to the slow redistribution from deep compartments, probably adipose tissues. This phase does not affect the awakening time in clinical practice.
Propofol is mainly metabolised through a conjugation process in the liver with a clearance of approximately 2 l / min but there is also an extra hepatic metabolism. Inactive metabolites are eliminated by the kidneys (approximately 88%).
At the usual maintenance doses there is no significant drug accumulation after surgery of at least 5 hours.
Propofol is widely distributed and rapidly eliminated from the body (total body clearance: 1.5 - 2 liters / minute). Clearance occurs through metabolic processes, mainly in the liver, dependent on blood flow, with the formation of inactive conjugates of propofol and its corresponding quinol, which are excreted in the urine.
After intravenous administration of a single dose of 3 mg / kg, the clearance / kg body weight of propofol increased with age as follows: the median clearance was considerably lower in infants less than one month of age ( n = 25) (20 mL / kg / min) compared to that of older children (n = 36, age range 4 months - 7 years). Furthermore, inter-individual variability was considerable in neonates (range 3.7 - 78 ml / kg / min). The limited data relating to this study, which indicate a considerable variability, do not allow the identification of recommended doses for this age group.
Following a single 3 mg / kg bolus dose, the median clearance of propofol in older children was 37.5 ml / kg / min (4 - 24 months) (n = 8), 38 , 7 ml / Kg / min (11 - 43 months) (n = 6), 48 ml / Kg / min (1 - 3 years) (n = 12), 28.2 ml / Kg / min (4 - 7 years) (n = 10) compared to 23.6 ml / kg / min in adults (n = 6).
05.3 Preclinical safety data
Preclinical data based on conventional studies of repeated dose toxicity or genotoxicity did not reveal any particular risk for humans.
Carcinogenicity studies have not been conducted. For reproductive toxicity, see section 4.6. Paravenous, subcutaneous and intramuscular injections resulted in mild or moderate intolerances limited to the injection site.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Sodium edetate
Refined soybean oil
Purified egg phosphatide
Glycerol
Sodium hydroxide
Water for injections.
06.2 Incompatibility
The muscle relaxant agents, atracurium and mivacurium should not be administered through the same infusion line as Diprivan without first flushing it thoroughly.
Diprivan 10 mg / ml can be pre-mixed with 5% glucose solutions in PVC bags or glass infusion bottles, lidocaine for injection, alfentanil for injection in plastic syringes (see section 4.2).
06.3 Period of validity
Diprivan 10 mg / ml
3 years:
- 5 ampoules of 20 ml
- 5 bottles of 20 ml
- Bottle of 50 ml
- Bottle of 100 ml
2 years:
- 20 ml pre-filled syringe
- 50 ml pre-filled syringe
Shelf life after dilution: use within 6 hours of dilution.
06.4 Special precautions for storage
Store at a temperature between + 2 ° and + 25 ° C. Do not freeze.
06.5 Nature of the immediate packaging and contents of the package
Vials, bottles and syringes made of neutral, clear, colorless glass, type I.
The rubber parts of the bottles and syringes are latex-free.
Diprivan 10 mg / ml emulsion for injection for intravenous use:
- 5 ampoules of 20 ml containing propofol 10 mg / ml
Diprivan 10 mg / ml emulsion for infusion:
- 5 bottles of 20 ml containing propofol 10 mg / ml
- 50 ml bottle containing 10 mg / ml propofol
- 100 ml bottle containing 10 mg / ml propofol
- 20 ml pre-filled syringe containing 10 mg / ml propofol and connecting needle
- 50 ml pre-filled syringe containing 10 mg / ml propofol and connecting needle.
06.6 Instructions for use and handling
Protect your fingers when opening the vials.
To eliminate the risk of bacterial contamination, strict aseptic techniques must be used in handling the propofol emulsion.
Shake well before use.
Any leftover content, after the first use, must be eliminated.
Filters with porosity less than 10 microns should not be used when administering Diprivan.
07.0 MARKETING AUTHORIZATION HOLDER
AstraZeneca S.p.A.
Volta Palace
Via F. Sforza - Basiglio (MI).
08.0 MARKETING AUTHORIZATION NUMBER
Diprivan 10 mg / ml emulsion for injection for intravenous use
5 vials of 20 ml - A.I.C. 026114013
Diprivan 10 mg / ml emulsion for infusion
5 bottles of 20 ml - A.I.C. 026114090
Bottle of 50 ml - A.I.C. 026114025
100 ml bottle - A.I.C. 026114037
20 ml pre-filled syringe - A.I.C. 026114049
50 ml pre-filled syringe - A.I.C. 026114052.
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Diprivan 10 mg / ml emulsion for injection for intravenous use
5 vials of 20 ml - AIC: June 1988 / Renewal: June 2005
Diprivan 10 mg / ml emulsion for infusion
5 bottles of 20 ml - AIC: January 2004 / Renewal: June 2005
50 ml bottle - AIC: June 1988 / Renewal: June 2005
100 ml bottle - AIC: April 1992 / Renewal: June 2005
20 ml pre-filled syringe - AIC: March 1997 / Renewal: June 2005
50 ml pre-filled syringe - AIC: March 1997 / Renewal: June 2005
10.0 DATE OF REVISION OF THE TEXT
May 2012
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