Nupovel

Propofol.

White, no precipitation, sterile emulsion for parenteral use.
Each 1 mL contains propofol 10 mg.

Pharmacotherapeutic group: Other general anesthetics. ATC code: N01AX10.
Pharmacology: Pharmacodynamics: Mechanism of Action: Propofol is a short-acting lipophilic intravenous general anesthetic. The drug is unrelated to any of the currently used barbiturate, opioid, benzodiazepine, arylcyclohexylamine, or imidazole intravenous anesthetic agents. Propofol causes global CNS depression, presumably through agonism of GABA_A receptors and perhaps reduced glutamatergic activity through N-methyl-D-aspartate (NMDA) receptor blockade.
Pharmacokinetics: Absorption: Onset of action: Anesthetic: Bolus infusion (Dose dependent): 9-51 seconds (average 30 seconds).
Duration: 3-10 minutes depending on the dose, rate and duration of administration; with prolonged use (10 days ICU sedation) propofol accumulates in tissues and redistributes into plasma when the drug is discontinued, so that the time to awakening (duration of action) is increased; however, if dose is titrated on a daily basis so that the minimum effective dose is utilized, time to awakening may be within 10 to 15 minutes even after prolonged use.
Distribution: Large volume of distribution; highly lipophilic.
V_d: Children 4-12 years: 5-10 L/kg.
Adults: 2-10 L/kg; after a 10-day infusion V_d approaches 60 L/kg; decreased in the elderly.
Protein binding: 97%-99%.
Metabolism: Hepatic to water soluble sulphate and glucuronide conjugates (∼50%).
Half-life elimination: Biphasic: Initial 40 minutes; Terminal: 4-7 hour (after 10 days infusion, may be up to 1-3 days).
Excretion: Urine (∼88% as metabolites, 40% as glucuronide metabolite); feces (<2%).

Nupovel is a short-acting intravenous general anaesthetic for induction and maintenance of general anesthesia in adults and children >1 month.
Sedation for diagnostic and surgical procedures, alone or in combination with local or regional anesthesia in adults and children >1 month.
Sedation of ventilated patients >16 years of age in the intensive care unit.

Nupovel must only be given in hospital 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 always be immediately available. For sedation during surgical or diagnostic procedures Nupovel should not be given by the same person that carries out the surgical or diagnostic procedure.
Supplementary analgesic medical products are generally required in addition to Nupovel.
Nupovel is given intravenously. The dosage is adjusted individually according to the patient's response.
Induction and maintenance of general anaesthesia: Induction of anaesthesia in adults: For induction of anaesthesia Nupovel 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 of propofol/kg body weight (BW).
In older patients 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 of Nupovel may be reduced to 1 mg of propofol/kg BW or less. In these patients lower rates of administration should be applied (approximately 2 mL, corresponding to 20 mg, every 10 seconds).
Maintenance of anaesthesia in adults: Anaesthesia can be maintained by administering Nupovel either by continuous infusion or by repeat bolus injections. If a technique involving repeat bolus injections is used, increments of 25-50 mg of propofol (2.5-5.0 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 BW/h.
In the elderly, 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.
Induction of anaesthesia in children over 1 month of age: For induction of anaesthesia Nupovel should be titrated slowly 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 require approximately 2.5 mg of propofol/kg BW 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 of propofol/kg BW).
Maintenance anaesthesia in children over 1 month of age: Anaesthesia can be maintained by administering Nupovel 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 for diagnostic and surgical procedures in adults: To provide sedative during surgical and diagnostic procedures, doses and administration rates should be adjusted according to the clinical response. Most patients will require 0.5-1 mg of propofol/kg BW over 1 to 5 minutes for onset of sedation. Maintenance of sedation may be accomplished by titrating Nupovel (10 mg/mL) infusion to the desired level of sedation. Most patients will require 1.5-4.5 mg of propofol/kg BW/h. The infusion may be supplemented by bolus administration of 10-20 mg of propofol (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 of propofol 10 mg/mL may be required and the rate of administration may need to be reduced.
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 titration Nupovel (10 mg/mL) as 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 sedative is required.
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 Nupovel be given by continuous infusion. The infusion rate should be determined by the required depth of sedative. In most patients sufficient sedation can be obtained with a dosage of 0.3-4.0 mg of propofol/kg BW/h.
Administration of propofol by Target Controlled Infusion (TCI) system is not advised for sedation in the intensive care unit.
Propofol is not indicated for sedation in intensive care of patients of 16 years of age or younger.
Mode of administration: Nupovel can be used for infusion undiluted or diluted with 5% dextrose (intravenous infusion) only. Dilutions, which must not exceed 1 in 5 (propofol 2 mg/mL), should be prepared aseptically immediately before administration and must be used within 6 hours of preparation.
It is recommended that, when using diluted Nupovel, the volume of 5% dextrose removed from the infusion bag during the dilution process is totally replaced in volume by Nupovel (see "Dilution and Co-administration" Table as follows).
When propofol is used undiluted to maintain anaesthesia, it is recommended that equipment such as syringe pumps or volumetric infusion pumps should always be used to control the infusion rates.
Containers should be shaken before use.
Nupovel may be administered via a Y-piece close to the injection site into infusions of the following: Dextrose 5% intravenous infusion; Sodium chloride 0.9% intravenous infusion; Dextrose 4% and sodium chloride 0.18% intravenous infusion.
In order to reduce pain on initial injection, it may be mixed with preservative-free lidocaine injection 0.5% or 1% as a ratio 1:20 with Nupovel (see Table as follows).

Click on icon to see table/diagram/image

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

Hypersensitivity to propofol or any excipient (soya-bean oil, egg phospholipids, disodium edetate, glycerol and sodium hydroxide).
Should not be used in patients who are hypersensitive to peanut or soya.
Must not be used in patients of 16 years of age or younger for sedation for intensive care.
Nupovel is not recommended for induction of anaesthesia in children less than 1 month.

Propofol should be given by those trained in anaesthesia (or, where appropriate, doctors trained in the care of patients in Intensive Care).
Patients should be constantly monitored and facilities for maintenance of a patent airway, artificial ventilation, oxygen enrichment and other resuscitative facilities should be readily available at all times.
Propofol should not be administered by the person conducting the diagnostic or surgical procedure.
The abuse of and dependence on propofol, predominantly by health care professionals, has been reported. As with other general anaesthetics, the administration of propofol without airway care may result in fatal respiratory complications.
When propofol is administered for conscious sedation, for surgical and diagnostic procedures, patients should be continually monitored for early signs of hypotension, airway obstruction and oxygen desaturation.
As with other sedative agents, when propofol is used for sedation during operative procedures, involuntary patient movements may occur. During procedures requiring immobility these movements may be hazardous to the operative site.
An adequate period is needed prior to discharge of the patient to ensure full recovery after use of propofol. Very rarely the use of propofol may be associated with the development of a period of post-operative 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.
Propofol induced impairment is not generally detectable beyond 12 hours. The effects of propofol, the procedure, concomitant medications, the age and the condition of the patient should be considered when 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).
As with other intravenous anaesthetic agents, 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.
Propofol 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.
When propofol is administered to an epileptic patient, there may be a risk of convulsion. Before anaesthesia of an epileptic patient, it should be checked that the patient has received the antiepileptic treatment.
Appropriate care should be applied in patients with disorders of fat metabolism and in other conditions where lipid emulsions must be used cautiously.

Pregnancy: Propofol crosses the placenta and may be associated with neonatal CNS and respiratory depression. Propofol is not recommended for use in obstetrics, including caesarean section deliveries.
Lactation: Propofol is excreted in human milk. Breast-feeding is not recommended.

Side effects that can happen during anesthesia: The following side effects can happen during anesthesia (while the injection is being given to the patient or when the patient is sleepy or asleep). The doctor will be looking out for these. If these happen, the doctor will give the patient appropriate treatment.
Very common (may affect more than 1 in 10 people): A feeling of pain at the site of the injection (while the injection is being given, before the patient falls asleep).
Common (may affect up to 1 in 10 people): Low blood pressure.
Changes in the breathing pattern.
Slow heartbeat.
Rare (may affect up to 1 in 1,000 people): Twitching and shaking of the body, or a fit (may also happen when the patient wakes up).
Unusual colour of urine (may also happen when the patient wakes up).
Very rare (may affect up to 1 in 10,000 people): Allergic reactions.
Stopping of the heartbeat.
Build up of fluid in the lungs which can make the patient very breathless (may also happen when the patient wakes up).
Not known: frequency cannot be estimated from the available data: Shallow breathing.
Priapism.
Side effects that can happen after anesthesia: The following side effects can happen after anesthesia (when the patient is waking up or after the patient has woken up).
Common (may affect up to 1 in 10 people): Feeling sick (nausea).
Being sick (vomiting).
Headache.
Uncommon (may affect up to 1 in 100 people): Swelling and redness along a vein or blood clots.
Very rare (may affect up to 1 in 10,000 people): Feeling sexually aroused.
High temperature (fever).
Redness or soreness where the injection was given.
Being unconscious after the operation. (When this has happened, the patients have recovered without problems).
Tissue damage.
Not known: frequency cannot be estimated from the available data: A feeling of pain at the site of the injection.
Swelling at the site of injection.
Prolonged, often painful erection (priapism).
Other possible side effects: The following side effects have been seen when Propofol is used in intensive care at higher doses than recommended.
Very rare (may affect up to 1 in 10,000 people): Heart failure.
Inflamed pancreas (pancreatitis) which causes severe stomach pain.
Too much acid in the blood. This may make the patient breathe more quickly.
Increased amount of potassium in the blood.
High blood level of a type of fat called lipids.
Abnormal heart beat.
Enlargement of the liver.
Kidney failure.
The following side effects have been seen in children in intensive care when Propofol has been stopped suddenly.
Common (may affect up to 1 in 10 people): 'Withdrawal symptoms'. These include unusual behavior, sweating, shaking and feeling anxious.
Flushing of the skin.
Not known: frequency cannot be estimated from the available data: Euphoric mood.
Involuntary movements.
Drug abuse and dependence on Propofol, mostly by healthcare professionals.
Abnormal ECG.
Breakdown of muscle cells (rhabdomyolysis).

Propofol has been used in association with spinal and epidural anesthesia and with commonly used pre-medicants, neuromuscular blocking drugs, inhalational agents and analgesic agents; no pharmacological incompatibility has been encountered. Lower doses of Nupovel may be required where general anesthesia is used as an adjunct to regional anesthetic techniques.
Profound hypotension has been reported following anesthetic induction 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, anesthetic and cardiorespiratory depressant effects of propofol.
A need for lower propofol doses has been observed in patients taking valproate. When used concomitantly, a dose reduction of propofol may be considered.

Storage condition: Store below 30°C. Do not freeze.

Anaesthetics - Local & General

N01AX10 - propofol ; Belongs to the class of other general anesthetics.

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