Each mL (of emulsion) contains Propofol 10 mg.
Excipients/Inactive Ingredients: Soybean Oil, Glycerol, Egg Lecithin and Water for Injections q.s.
Pharmacology: Pharmacodynamics: Propofol (2,6-Diisopropyl phenol) is a short acting general anaesthetic agent with a rapid onset of action of approximately 30 to 40 seconds. Recovery from anaesthesia is usually rapid. The mechanism of action, like all general anaesthetics, is poorly understood.
In general, fall in blood pressure and slight changes in the heart rate are observed when propofol is administered for induction and maintenance of anaesthesia. However, the hemodynamic parameters normally remain relatively stable during maintenance and the incidence of untoward hemodynamic changes is low.
Although ventilatory depression can occur following administration of propofol, any effects are qualitatively similar to those of other intravenous agents and are readily manageable in clinical practice.
Propofol reduces cerebral blood flow, intracranial pressure and cerebral metabolic requirement of oxygen. The reduction in the intracranial pressure is greater in patients with an elevated baseline intracranial pressure. Recovery from anaesthesia is usually rapid and clear headed with a low incidence of headache and post operative nausea and vomiting (PONV).
Pharmacokinetics: The decline in propofol concentrations following a bolus dose or following the termination of an infusion can be described by a three compartment open model. The first phase is characterised by a very rapid distribution (half life 2-4 minutes) followed by rapid elimination (half life 30-60 minutes) and a slower final phase, representative of redistribution of propofol from poorly perfused tissue.
Propofol is extensively distributed and rapidly cleared from the body (total body clearance 1.5 - 2 litres/minute). Clearance occurs by metabolic processes, mainly in the liver, to form inactive conjugates of propofol and its corresponding quinol, which are excreted in urine.
When propofol is used to maintain anaesthesia, the blood concentrations asymptotically approach the steady state value for the given administration rate. The pharmacokinetics are linear over the recommended range of infusion rates of propofol.
PROFOL 1% is a short acting intravenous sedative-hypnotic & general anaesthetic suitable for induction and maintenance of general anaesthesia. It can also be used in ICU (Intensive Care Unit) sedation and MAC (Monitored Anaesthesia Care) sedation.
Dosage of PROFOL 1% must be individualized for each patient, with the dose titrated to achieve the desired clinical effect. Lower doses are usually required for elderly, debilitated or higher risk surgical patient, or those with circulation disorders. The dosage of intravenously administered Propofol should be adjusted according to the type and amount of premedication used.
GENERAL ANAESTHESIA: Induction: Adults up to 55 years of age and/or ASAI OR II patients: Intravenous 2.0 to 2.5 mg per kg of body weight (approximately 40 mg every ten seconds until onset of induction).
Elderly, debilitated, hypovolaemic, and/or ASAIII or IV patients: Intravenous 1.0 to 1.5 mg per kg of body weight (approximately 20 mg every ten seconds until onset of induction).
Maintenance: Adults up to 55 years of age and/or ASAI or II patients: 100 to 200 mcg (0.1 to 0.2 mg) per kg of body weight per minute (6 to 12 mg per kg of body weight per hour).
Elderly, debilitated, hypovolaemic, and/or ASAIII or IV patients: 50 to 100 mcg (0.05 to 0.1 mg) per kg of body weight per minute (3 to 6 mg per kg of body weight per hour).
Intravenous (intermittent): 25 to 50 mg increments, administered as needed. Alternatively some clinicians recommend increments of 500 mcg (0.5 mg) per kg of body weight.
Monitored Anaesthesia Care (MAC) Sedation: Initiation: Adults up to 55 years of age and/or ASA I/or II patients: 100 - 150 mcg/kg/min (6 to 9 mg/kg/hr).
Elderly, ASA III or IV patients: Slow injection similar to adults.
Maintenance: Adults up to 55 years of age and/or ASA I or II patients: 1.5 to 4.5 mg/kg/hr.
Elderly, ASA III or IV patients: Approximately 20% reduction in adult dose.
Intensive Care Unit (ICU) Sedation: Initiation: 5 mcg/kg/min (0.3 mg/kg/hr) for at least 5 min with increments of 5 to 10 mcg/kg/min (0.3 to 0.6 mg/kg/hr) over 5-10 minutes until the desired level of sedation is achieved.
10 mcg/kg/min (0.3 to 0.6 mg/kg/hr) over 5-10 minutes until the desired level of sedation is achieved.
Maintenance: 5 to 50 mcg/kg/min (0.3 to 3 mg/kg/hr) or higher may be required.
CHILDREN: PROFOL 1% is not recommended for use in children less than 3 years of age.
Induction of general anaesthesia: When used to induce anaesthesia in children above 3 years of age, it is recommended that PROFOL 1% be given slowly until the clinical signs show the onset of anaesthesia. The dose should be adjusted for age and/or weight. Most patients over 8 years of age are likely to require approximately 2.5 to 3.5 mg per kg of body weight PROFOL 1% for induction of anaesthesia. Under this age the requirement may be more. Lower dosage is recommended for children of ASA grades III and IV.
Maintenance of general anaesthesia: Anaesthesia can be maintained by administering PROFOL 1% by infusion or repeat bolus injection to maintain the depth of anaesthesia required. The required rate of administration varies considerably between patients but rates in the region of 7.5 to 18 mg/kg/hr usually achieve satisfactory anaesthesia.
Administration: PROFOL 1% can be used for infusion undiluted form syringes or glass containers. When PROFOL 1% 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 infusion rates.
PROFOL 1% may also be used diluted with 5% Dextrose Intravenous Injection only and the final concentration should not be less than 2 mg per ml to preserve the emulsion base. Dilutions should be prepared aseptically immediately before administration. The mixture is stable up to 6 hours.
The dilution may be used with a variety of infusion control techniques but a giving set used alone will not avoid the risk of accidental, uncontrolled infusion of large volumes of diluted PROFOL 1%. A suitable controlled infusion device such as volumetric pump must be included in the infusion line.
PROFOL 1% may be administered via a Y-piece close to the injection site, into infusions of 5% Dextrose Injection, 0.45%, Sodium chloride & 5% Dextrose injection and 0.2% Sodium Chloride & 5% Dextrose Injection.
Pain associated with PROFOL 1% can be reduced by concomitant use of local anaesthetic agents most commonly lignocaine. For effective use lignocaine 1%, 2 mL or 2%, 1 mL needs to be given immediately before administration of PROFOL 1% or mixing it with PROFOL 1% just prior to use of propofol. Propofol has no analgesic properties and therefore supplementary analgesic agents are generally required in addition to propofol. PROFOL 1% has been used in association with spinal and epidural anaesthesia and with commonly used premedicants, neuromuscular blocking drugs, inhalational agents and analgesic agents; no pharmacological incompatibility has been reported. Lower doses of PROFOL 1% may be required where general anaesthesia is used as an adjunct to regional anaesthesia techniques.
Accidental overdosage is likely to cause cardiorespiratory depression. Respiratory depression should be treated by artificial ventilation with oxygen. Cardiovascular depression may require raising the patients legs, increasing the flow rates of I.V. fluids and the use of pressor agents and/or anticholinergic agents.
There is no absolute contraindication to the use of PROFOL 1% but it is contraindicated in patients with a known hypersensitivity to Propofol injection or its components, or when general anaesthesia or sedation is contraindicated.
PROFOL 1% should be given by those trained in anaesthesia or, where appropriate; doctors trained in the care of patients in the intensive care. The facilities for maintenance of a patient airway, ventilation, oxygen enrichment and other resuscitative facilities should be readily available at all times. PROFOL 1% should not be administered by the person conducting the diagnostic or surgical procedure.
When PROFOL 1% is administered patients should be continually monitored for early signs of hypotension, airway obstruction and oxygen desaturation.
An adequate period is needed prior to discharge of the patients to ensure full recovery after general anaesthesia. As with other intravenous anaesthetic agents, caution should be applied in patients with cardiac, respiratory, renal or hepatic impairment or hypovolaemic or debilitated patients. Propofol lacks vagolytic activity and has been associated with reports of bradycardia, occasionally profound, and also asystole. The intravenous administration of anticholinergic agent before induction or during maintenance of anaesthesia should be considered, especially in situations where vagal tone is likely to predominate or when PROFOL 1% is used in conjunction with other agents likely to cause bradycardia.
When PROFOL 1% is administered to an epileptic patients there may be a risk of convulsion during the recovery phase.
Appropriate care should be applied in patients with disorders of fat metabolism and in other conditions where lipid emulsion must be used cautiously.
It is recommended that blood lipid levels should be monitored if PROFOL 1% is administered to patients thought to be at particular risk of fat overload. Administration of PROFOL 1% 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 PROFOL 1% formulation; 1.0 ml of PROFOL 1% contains approximately 0.1 g of fat.
Additional Precautions: PROFOL 1% contains no antimicrobial preservatives and supports growth of micro-organisms.
When PROFOL 1% is to be aspirated, it must be drawn aseptically into a sterile syringe or giving set immediately after breaking the vial seal. Administration must commence without delay. Asepsis must be maintained for both PROFOL 1% and infusion equipment throughout the infusion period. Any infusion fluids added to the PROFOL 1% must be administered close to the cannula site. PROFOL 1% must not be administered via a microbiological filter. PROFOL 1% is for single use in an individual patient. For use in long term maintenance of anaesthesia it is recommended that the infusion line and reservoir of PROFOL 1% must be discarded and replaced at regular intervals.
Effects on the Ability to Drive and Operate Machinery: Patients should be advised that performance of skilled tasks, such as driving and operating machinery, may be impaired for some time after general anaesthesia.
Use in Pregnancy: PROFOL 1% should not be used in pregnancy. Propofol has been used, however during termination of pregnancy in the first trimester.
Obsterics: Propofol crosses the placenta and may be associated with neonatal depression, it should not be used for obstetric anaesthesia.
Use in Lactation: Safety to the neonate following the use of PROFOL 1% in mothers who are breast feeding has not been established.
Pregnancy: PROFOL 1% should not be used in pregnancy. Propofol has been used, however during termination of pregnancy in the first trimester.
Obsterics: Propofol crosses the placenta and may be associated with neonatal depression, it should not be used for obstetric anaesthesia.
Lactation: Safety to the neonate following the use of PROFOL 1% in mothers who are breast feeding has not been established.
Induction of anaesthesia is generally smooth with minimal evidence of excitation. During induction of anaesthesia, hypotension and transient apnoea may occur depending on the dose and use of premedicants and other agents. Burning in throat, wheezing, cough, hiccough have been reported. During the recovery phase, nausea, vomiting and headache occur in only a small proportion of patients. Convulsions, including Myoclonus and opisthotonos, have been reported rarely and usually after termination of product. Rarely, clinical features of anaphylaxis, which may include angioedema, bronchospasm, erythema & hypotension, occur following PROFOL 1% administration. Pulmonary oedema has been observed. There have been reports of post-operative fever. Rarely, discoloration of urine has been reported following prolonged administration of PROFOL 1%.
The local pain which may occur during the induction phase can be minimised by the use of the larger veins of the forearm and antecubital fossa. With PROFOL 1% local pain can also be minimised by the coadministration of lignocaine (see Administration under Dosage & Administration). Thrombosis and phlebitis are rare. Accidental clinical extravasation and animal studies with Propofol showed minimal tissue reaction. Intra-arterial injection in animals did not induce local tissue effects.
The induction dose requirements of PROFOL 1% may be reduced in patients with premedication with narcotics (eg, morphine, meperidine and fentanyl, etc.) and combinations of opioids and sedatives (eg, benzodiazepines, barbiturates, chloral hydrate, droperidol, etc). These agents may increase the anaesthetic or sedative effects of PROFOL 1% and may also result in more pronounced decreases in systolic, diastolic, and mean arterial pressures and cardiac output. During maintenance of anaesthesia or sedation the rate of PROFOL 1% administration should be adjusted according to the desired level of sedation and may be reduced in the presence of supplemental analgesic agents (eg, nitrous oxide or opioids). The concurrent administration of inhalational agents (eg, isoflurane, enflurane, and halothane) during maintenance is expected to increase the anaesthetic or sedative and cardiorespiratory effects of PROFOL 1%. PROFOL 1% does not cause a clinically significant change in onset, intensity or duration of action of the commonly used neuromuscular blocking agents (eg, succinyl choline and nondepolarizing muscle relaxants). No significant adverse reactions with commonly used premedication or drugs used during anaesthesia or sedation (including a range of muscle relaxants, inhalational agents, analgesics, and local anaesthetics) have been observed.
Instructions for Use and Handling: Containers should be shaken before use. Any portion of the contents remaining after use should be discarded.
Asepsis for PROFOL 1% and infusion equipment must be maintained (see Additional Precautions under Precautions).
Incompatibilities: PROFOL 1% should not be mixed prior to administration with injections or infusion fluids other than with 5% Dextrose in glass infusion bottles or Lignocaine Injection. PROFOL 1% should not be coadministered through the same I.V. catheter with blood or plasma; although the clinical significance is not known. In vitro studies have shown that the globular component of the emulsion vehicle has formed aggregates when in contact with human plasma.
Stability: PROFOL 1% injection contains no antimicrobial preservatives, and the vehicle is capable of supporting the rapid growth of micro-organisms; particulate or bacterial contamination may be difficult to detect because PROFOL 1% is opaque, therefore, strict aseptic technique must be maintained. PROFOL 1% should be drawn into sterile syringes or connected to a volumetric infusion device immediately after the container is opened, and administered promptly. Unused portions of the injection as well as reservoirs, I.V. lines, or solutions containing PROFOL 1% must be discarded at the end of the procedure or within 6 hours, whichever occurs sooner. PROFOL 1% should not be used if there is evidence of separation of the emulsion phases.
Store below 25°C. Do not freeze.
N01AX10 - propofol ; Belongs to the class of other general anesthetics.
Emulsion inj 1% (white, oil in water, isotonic emulsion for intravenous injection) x 20 mL, 50 mL.