RIPOL 10MG/ML

/ Raz Pharmaceutics

General instructions
Must only be given in hospitals or adequately equipped day therapy units by physicians trained in anaesthesia or in the care of patients in intensive care. Circulatory and respiratory functions should be constantly monitored (e.g. ECG, pulse-oxymeter) and facilities for maintenance of patent airways, artificial ventilation, and other resuscitation facilities should be immediately available at all times. For sedation during surgical or diagnostic procedures propofol should not be given by the same person that carries out the surgical or diagnostic procedure.
Posology
This medical product is given intravenously. The dosage is adjusted individually according to the patient’s response.
General anaesthesia in adults
Induction of anaesthesia: The dose should be titrated (20-40 mg of propofol every 10 seconds) against the patient’s response until the clinical signs show the onset of anaesthesia. Most adult patients younger than 55 years are likely to require 1.5 to 2.5 mg/kg body weight.
In patients over this age and in patients of ASA grades III and IV, especially those with impaired cardiac function, the dosage requirements will be less and the total dose may be reduced to a minimum of 1 mg/kg body weight. In these patients, lower rates of administration should be applied (approximately 2 ml, corresponding to 20 mg every 10 seconds).
Maintenance of anaesthesia: Anaesthesia can be maintained either by continuous infusion or by repeat bolus injections. If a technique involving repeat bolus injections is used, increments of 25 mg (2.5 ml) to 50 mg (5.0 ml) may be given according to clinical requirements. For maintenance of anaesthesia by continuous infusion the dosage requirements usually are in the range of 4-12 mg/kg body weight/h.
In elderly patients, in patients of poor general condition, in patients of ASA grades III and IV and in hypovolaemic patients the dosage may be reduced further depending on the severity of the patient’s condition and on the performed anaesthetic technique.
Rapid bolus administration (single or repeated) should not be used in older people as this may lead to cardiorespiratory depression.
General anaesthesia in children over 1 month of age
Induction of anaesthesititrating as infusiona: Should be slowly titrated against the patient’s response until the clinical signs show the onset of anaesthesia. The dosage should be adjusted according to age and/or body weight.
Most patients over 8 years of age require approximately 2.5 mg/kg body weight of propofol for induction of anaesthesia. In younger children, especially between the age of 1 month and 3 years, dose requirements may be higher (2.5-4 mg/kg body weight).
Maintenance of general anaesthesia: Anaesthesia can be maintained by infusion or repeated bolus injection to maintain the depth of anaesthesia required. The required rate of administration varies considerably between patients but rates in the region of 9-15 mg/kg/h usually achieve satisfactory anaesthesia. In younger children, especially between the age of 1 month and 3 years, dose requirements may be higher.
For ASA III and IV patients lower doses are recommended
Sedation of ventilated patients in the Intensive Care Unit
For sedation during intensive care, it is advised that propofol should be administered by continuous infusion. The infusion rate should be determined by the desired depth of sedation. In most patients sufficient sedation can be obtained with a dosage of 0.3 – 4 mg/kg/h of propofol.
Propofol is not indicated for sedation in intensive care of patients of 16 years of age or younger. Administration of propofol by Target Controlled Infusion (TCI) system is not advised for sedation in the intensive care unit.
Rapid bolus administration (single or repeated) should not be used in older people as this may lead to cardiorespiratory depression.
Sedation for diagnostic and surgical procedures in adults
Doses and administration rates should be adjusted according to the clinical response. Most patients will require 0.5-1 mg/kg body weight over 1 to 5 minutes for onset of sedation. Maintenance of sedation may be accomplished by titrating infusion to the desired level of sedation. Most patients will require 1.5-4.5 mg/kg body weight/h. The infusion may be supplemented by bolus administration of 10-20 mg (1-2 ml) if a rapid increase of the depth of sedation is required.
In patients older than 55 years and in patients of ASA grades III and IV lower doses may be required and the rate of administration may need to be reduced.
Rapid bolus administration (single or repeated) should not be used in older people as this may lead to cardiorespiratory depression.
Sedation for diagnostic and surgical procedures in children over 1 month of age
Doses and administration rates should be adjusted according to the required depth of sedation and the clinical response. Most paediatric patients require 1-2 mg/kg body weight of propofol for onset of sedation. Maintenance of sedation may be accomplished by titrating the infusion to the desired level of sedation. Most patients require 1.5-9 mg/kg/h of propofol. The infusion may be supplemented by bolus administration of up to 1 mg/kg b.w. if a rapid increase of depth of sedation is required.
In ASA III and IV patients lower doses may be required.
Duration of administration
This medical product can be administered for a maximum period of 7 days.
Method of administration
Intravenous use. This medical product is administered intravenously by injection or continuous infusion either undiluted or diluted with 5 % w/v glucose solution or 0.9 % w/v sodium chloride solution as well as in a preservative- free lidocaine injection 1%.
Infusion of undiluted
When administering this medical product by continuous infusion, it is recommended that burettes, drop counters, syringe pumps or volumetric infusion pumps should always be used to control the infusion rates. As established for the parenteral administration of all kinds of fat emulsions, the duration of continuous infusion from one infusion system must not exceed 12 hours. The infusion line and the reservoir of this medical product must be discarded and replaced after 12 hours at the latest. Any portion remaining after the end of infusion or after replacement of the infusion system must be discarded.
Infusion of diluted
For administration of diluted propofol infusion burettes, drop counters, syringe pumps, or volumetric infusion pumps should always be used to control infusion rates and to avoid the risk of accidentally uncontrolled infusion of large volumes of diluted medical product.
The maximum dilution must not exceed 1 part of this medical product with 4 parts of 5 % w/v glucose solution or 0.9 % w/v sodium chloride solution, or 0.18 % w/v sodium chloride and 4 % w/v glucose solution (minimum concentration 2 mg propofol/ml). The mixture should be prepared aseptically immediately prior to administration and must be used within 7 hours of preparation.
In order to reduce pain on initial injection, propofol may be mixed with preservative-free lidocaine injection 1% (mix 20 parts of this medical product with up to 1 part of lidocaine injection 1%).
Before administering the muscle relaxants atracurium or mivacurium after propofol through the same intravenous line, it is recommended that the line be rinsed prior to administration.
Needle Size – It is recommended to use a 21 G-type needle or above
Angle and method of insertion -To prevent Coring (the formation of particles inside the solution), the needle should be inserted at a 45o–60° angle with the opening of the needle tip facing up (i.e., away from the stopper). A small amount of pressure is applied, and the angle is gradually increased as the needle enters the vial. The needle should be at a 90° angle just as the needle bevel passes through the stopper.
See prescribing information for full details.

Short-acting intravenous general anaesthetic for:
* Induction and maintenance of general anaesthesia in adults and children > 1 month.
* Sedation of ventilated patients >16 years of age in the intensive care unit
* Sedation for diagnostic and surgical procedures, alone or in combination with local or regional anaesthesia in adults and children > 1 month.

* Hypersensitivity to the active substance or to any of the excipients
* Should not be used in patients who are hypersensitive to peanuts or soya
* Must not be used in patients of 16 years of age or younger for sedation in intensive care

* Administered for conscious sedation, for surgical and diagnostic procedures, patients should be continually monitored for early signs of hypotension, airway obstruction and oxygen desaturation.
* Involuntary patient movements may occur. During procedures requiring immobility these movements may be hazardous to the operative site.
* Very rarely the use of propofol may be associated with the development of a period of postoperative unconsciousness, which may be accompanied by an increase in muscle tone. This may or may not be preceded by a period of wakefulness. Although recovery is spontaneous, appropriate care of an unconscious patient should be administered.
Advising patients on:
The advisability of being accompanied on leaving the place of administration
The timing of recommencement of skilled or hazardous tasks such as driving
The use of other agents that may sedate (E.g. benzodiazepines, opiates, alcohol.)
* Caution should be applied in patients with cardiac, respiratory, renal or hepatic impairment or in hypovolaemic or debilitated patients.
Propofol clearance is blood flow dependent, therefore, concomitant medication that reduces cardiac output will also reduce propofol clearance.
* Lacks vagolytic activity and has been associated with reports of bradycardia (occasionally profound) and also asystole. The intravenous administration of an anticholinergic agent before induction, or during maintenance of anaesthesia should be considered, especially in situations where vagal tone is likely to predominate, or when propofol is used in conjunction with other agents likely to cause bradycardia.
* Should be instructed to avoid alcohol before and for at least 8 hours after administration.
* During bolus administration for operative procedures, extreme caution should be exercised in patients with acute pulmonary insufficiency or respiratory depression.
Concomitant use of central nervous system depressants e.g., alcohol, general anaesthetics, narcotic analgesics will result in accentuation of their sedative effects. When propofol is combined with centrally depressant drugs administered parenterally, severe respiratory and cardiovascular depression may occur. It is recommended that propofol is administered following the analgesic and the dose should be carefully titrated to the patient’s response.
* During induction of anaesthesia, hypotension and transient apnoea may occur depending on the dose and use of premedicants and other agents.
* Use is not recommended with electroconvulsive treatment.
* Sexual disinhibition may occur during recovery.
Paediatric population
The use of Propofol is not recommended in newborn infants as this patient population has not been fully investigated. Pharmacokinetic data indicate that clearance is considerably reduced in neonates and has a very high inter-individual variability. Relative overdose could occur on administering doses recommended for older children and result in severe cardiovascular depression.
Propofol must not be used in patients of 16 years of age or younger for sedation for intensive care as the safety and efficacy of propofol for sedation in this age group have not been demonstrated.
Advisory statements concerning Intensive Care Unit management
Use of propofol emulsion infusions for ICU sedation has been associated with a constellation of metabolic derangements and organ system failures that may result in death. Reports have been received of combinations of the following: Metabolic acidosis, Rhabdomyolysis, Hyperkalaemia, Hepatomegaly, Renal failure, Hyperlipidaemia, Cardiac arrhythmia, Brugada-type ECG (elevated ST-segment and coved T-wave) and rapidly progressive Cardiac failure usually unresponsive to inotropic supportive treatment. The combination of these events has been referred to as Propofol Infusion Syndrome (PIS).
These events were mostly seen in patients with serious head injuries and children with respiratory tract infections who received dosages in excess of those advised in adults for sedation in the intensive care unit.
* Appropriate care should be applied in patients with disorders of fat metabolism and in other conditions where lipid emulsions must be used cautiously. It is recommended that blood lipid levels should be monitored if propofol is administered to patients thought to be at particular risk of fat overload. Administration of propofol should be adjusted appropriately if the monitoring indicates that fat is being inadequately cleared from the body. If the patient is receiving other intravenous lipid concurrently, a reduction in quantity should be made in order to take account of the amount of lipid infused as part of the propofol formulation.
Additional Precautions
* Caution should be taken when treating patients with mitochondrial disease. These patients may be susceptible to exacerbations of their disorder when undergoing anaesthesia, surgery and ICU care.
Maintenance of normothermia, provision of carbohydrates and good hydration are recommended for such patients. The early presentations of mitochondrial disease exacerbation and of the ‘propofol infusion syndrome’ may be similar.
* Any infusion fluids added to the line must be administered close to the cannula site. This medical product must not be administered via a microbiological filter.
See prescribing information for full details.

Very common: Local pain on induction
Common: Headache during recovery phase, Bradycardia, Hypotension, Transient apnoea during induction, Nausea and vomiting during recovery phase.
See prescribing information for full details.

Association with spinal and epidural anaesthesia and with commonly used premedicants, neuromuscular blocking drugs, inhalational agents and analgesic agents; no pharmacological incompatibility has been encountered. Lower doses of propofol may be required where general anaesthesia is used as an adjunct to regional anaesthetic techniques.
Profound hypotension has been reported following anaesthetic with propofol in patients treated with rifampicin.
The concurrent administration of other CNS depressants such as pre-medication drugs, inhalation agents, analgesic agents may add to the sedative, anaesthetic and cardiorespiratory depressant effects
A need for lower propofol doses has been observed in patients taking valproate. When used concomitantly, a dose reduction of propofol may be considered.
A need for lower propofol doses has been observed in patients taking midazolam. The
coadministration of propofol with midazolam is likely to result in enhanced sedation and respiratory depression. When used concomitantly, a dose reduction of propofol should to be considered.
Co-administration with dexmedetomidine is likely to lead to an enhancement of effects. Propofol dose required for sedation may have to be reduced in the presence of dexmedetomidine.

Pregnancy: The safety during pregnancy has not been established. Should not be given to pregnant women except when absolutely necessary. However, can be used during an induced abortion.
Lactation: Studies of breast-feeding mothers showed that small quantities are excreted in human milk. Women should therefore not breast-feed for 24 hours after administration. Milk produced during this period should be discarded.

Accidental overdose is likely to cause cardiorespiratory depression.
Respiratory depression should be treated by artificial ventilation with oxygen. Cardiovascular depression would require lowering the patient’s head and, if severe, use of plasma expanders and pressor agents.

Moderate influence on the ability to drive and use machines. Patients should be advised that performance at skilled tasks, such as driving and operating machinery, may be impaired for some time after general anaesthesia. induced impairment is not generally detectable beyond 12 hours