1.REGIVELL
Obat buatan novell ini dibawa oleh PT ANTAR MITRA SEMBADA selaku distributor resminya.
Regivell consists of Bupivacaine Hydrochloride, Dextrose Monohydrate.
Bupivacaine Hydrochloride - A widely used local anesthetic agent.
Indication: For the production of local or regional anesthesia or analgesia for surgery, for oral surgery procedures, for diagnostic and therapeutic procedures, and for obstetrical procedures.
Regivell (Bupivacaine Hydrochloride) is a widely used local anesthetic agent. Regivell (Bupivacaine Hydrochloride) is often administered by spinal injection prior to total hip arthroplasty. It is also commonly injected into surgical wound sites to reduce pain for up to 20 hours after surgery. In comparison to other local anesthetics it has a long duration of action. It is also the most toxic to the heart when administered in large doses. This problem has led to the use of other long-acting local anaesthetics:ropivacaine and levobupivacaine. Levobupivacaine is a derivative, specifically an enantiomer, of bupivacaine. Systemic absorption of local anesthetics produces effects on the cardiovascular and central nervous systems. At blood concentrations achieved with therapeutic doses, changes in cardiac conduction, excitability, refractoriness, contractility, and peripheral vascular resistance are minimal. However, toxic blood concentrations depress cardiac conduction and excitability, which may lead to atrioventricular block, ventricular arrhythmias and to cardiac arrest, sometimes resulting in fatalities. In addition, myocardial contractility is depressed and peripheral vasodilation occurs, leading to decreased cardiac output and arterial blood pressure. Following systemic absorption, local anesthetics can produce central nervous system stimulation, depression or both.
2.PROPOFOL LIPURO
Obat buatan B Braun ini di distribusikan oleh PT DOS NI ROHA
Name of the Medicinal Product
Propofol-Lipuro 1 %
(10 mg/ml)
emulsion for injection or infusion
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Propofol-Lipuro 1 % (10 mg/ml) contains
per 1 ml per 20 ml ampoule or vial per 50 ml vial per 100 ml vial
Propofol 10 mg 200 mg
500 mg
1000 mg
Excipients with known effect:
1 ml emulsion for injection or infusion contains
Soya-bean oil refined
50 mg
Sodium
0.03 mg
For the full list of excipients, see section 6.1.
3. PHARMACEUTICAL FORM
Emulsion for injection or infusion
White milky oil-in-water emulsion
4. CLINICAL PARTICULARS
4.1 Therapeutic indications
Propofol-Lipuro 1 % (10 mg/ml) is a short-acting intravenous general anaesthetic for
• nduction and maintenance of general anaesthesia in adults and children i > 1 month
• edation of ventilated patients > 16 years of age in the intensive care s unit
• edation for diagnostic and surgical procedures, alone or in combination s
with local or regional anaesthesia in adults and children > 1 month.
4.2 Posology and Method of Administration
General instructions
Propofol-Lipuro 1 % (10 mg/ml) 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-Lipuro 1 % (10 mg/ml) should not be given by the same person that carries out the surgical or diagnostic procedure.
Supplementary analgesic medicinal products are generally required in addition to Propofol-Lipuro 1 % (10 mg/ml).
Posology
Propofol-Lipuro 1 % (10 mg/ml) is given intravenously. The dosage is adjusted individually according to the patient’s response.
• eneral anaesthesia in adults
G
Induction of anaesthesia:
For induction of anaesthesia Propofol-Lipuro 1 % (10 mg/ml) 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 of Propofol-Lipuro 1 % (10 mg/ml) 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 by administering Propofol-Lipuro 1 % (10
mg/ml) 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 Propofol-Lipuro 1 % (10 mg/ml)) to 50 mg (5.0 ml Propofol-Lipuro
1 % (10 mg/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.
• eneral anaesthesia in children over 1 month of age
G
Induction of anaesthesia:
For induction of anaesthesia Propofol-Lipuro 1 % (10 mg/ml) 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 administering Propofol-Lipuro 1 % (10
mg/ml) 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 (see also section 4.4)
• edation of ventilated patients in the Intensive Care Unit
S
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 (see
also section 4.4).
Propofol is not indicated for sedation in intensive care of patients of 16
years of age or younger (see section 4.3).
Administration of propofol by Target Controlled Infusion (TCI) system is
not advised for sedation in the intensive care unit.
• edation for diagnostic and surgical procedures in adults
S
To provide sedation 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/kg body weight over 1
to 5 minutes for onset of sedation. Maintenance of sedation may be accomplished by titrating Propofol-Lipuro 1 % (10 mg/ml) 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 Propofol-Lipuro 1 % (10 mg/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-Lipuro 1 % (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 titrating PropofolLipuro 1 % (10 mg/ml) as in usion to the desired level of sedation. Most
f
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.
Method and duration of administration
• ethod of administration
M
Intravenous use
Propofol-Lipuro 1 % (10 mg/ml) 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 0.18 %
w/v sodium chloride and 4 % w/v glucose solution (see also section 6.6).
Containers should be shaken before use.
Before use, the neck of the ampoule or the surface of the rubber stopper
of the vial should be cleaned with medicinal alcohol (spray or swabs).
After use, tapped containers must be discarded.
Propofol-Lipuro 1 % (10 mg/ml) contains no antimicrobial preservatives
and supports growth of microorganisms. Therefore, Propofol-Lipuro 1 %
(10 mg/ml) is to be drawn up aseptically into a sterile syringe or an infusion set immediately after opening the ampoule or breaking the vial seal.
Administration must commence without delay. Asepsis must be maintained for both Propofol-Lipuro 1 % (10 mg/ml) and the infusion equipment throughout the infusion period.
Any medicinal products or fluids added to a running Propofol-Lipuro
1 % (10 mg/ml) infusion must be administered close to the cannula site.
Propofol-Lipuro 1 % (10 mg/ml) must not be administered via infusion
sets with microbiological filters.
The contents of one ampoule or one vial of Propofol-Lipuro 1 %
(10 mg/ml) and any syringe containing Propofol-Lipuro 1 % (10 mg/ml)
are for single use in one patient.
Infusion of undiluted Propofol-Lipuro 1 % (10 mg/ml)
When administering Propofol-Lipuro 1 % (10 mg/ml) 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 of Propofol-Lipuro 1 %
(10 mg/ml) from one infusion system must not exceed 12 hours. The
infusion line and the reservoir of Propofol-Lipuro 1 % (10 mg/ml) must
be discarded and replaced after 12 hours at the latest. Any portion of
Propofol-Lipuro 1 % (10 mg/ml) remaining after the end of infusion or
after replacement of the infusion system must be discarded.
Infusion of diluted Propofol-Lipuro 1 % (10 mg/ml)
For administering infusion of diluted Propofol-Lipuro 1 % (10 mg/ml),
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 PropofolLipuro 1 % (10 mg/ml).
The maximum dilution must not exceed 1 part of Propofol-Lipuro 1 %
(10 mg/ml) 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 6 hours of preparation.
In order to reduce pain on initial injection, Propofol-Lipuro 1 % (10 mg/
ml) may be mixed with preservative-free lidocaine injection 1 % (mix 20
parts of Propofol-Lipuro 1 % (10 mg/ml) with up to 1 part of lidocaine
injection 1 %).
Before giving the muscle relaxants atracurium or mivacurium subsequent to Propofol-Lipuro 1 % (10 mg/ml) through the same intravenous
line, it is recommended that the line be rinsed prior to administration.
Propofol may also be used by Target Controlled Infusion. Due to the different algorithms available on the market for dosage recommendations
please refer to the instructions for use leaflet of the device manufacturer.
• uration of administration
D
Propofol-Lipuro 1 % (10 mg/ml) can be administered for a maximum period of 7 days.
4.3 Contraindications
Propofol-Lipuro 1 % (10 mg/ml) is contraindicated in patients with a known hypersensitivity to propofol or to any of the excipients. Propofol-Lipuro 1 % (10 mg/ml) contains soya-bean oil and should not be
used in patients who are hypersensitive to peanut or soya. Propofol-Lipuro 1 % (10 mg/ml) must not be used in patients of 16 years of age or younger for sedation for intensive care.
4.4 Special Warnings and Precautions for Use
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 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:
• he advisability of being accompanied on leaving the place of adminisT tration
T • he timing of recommencement of skilled or hazardous tasks such as driving
• he use of other agents that may sedate (e.g. benzodiazepines, opiates, T 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 ia administered to an epileptic patient, there may be a
risk of convulsion. 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; 1.0 ml of Propofol-Lipuro 1 % (10 mg/ml) contains 0.1 g of fat. The use of propofol is not recommended in newborn infants as this patient population has not been fully investigated. Pharmacokinetic data (see section 5.2) 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. Advisory statements concerning Intensive Care Unit management The safety and efficacy of propofol for (background) sedation in children younger than 16 years of age have not been demonstrated. Although no causal relationship has been established, serious undesirable effects with (back-ground) sedation in patients younger than 16 years of age (including cases with fatal outcome) have been reported during unlicensed use. In particular these effects concerned occurrence of metabolic acidosis, hyperlipidemia, rhabdomyolysis and/or cardiac failure. These effects were most frequently seen in children with respiratory tract infections who received dosages in excess of those advised in adults for sedation in the intensive care unit. 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 (in some cases
with fatal outcome) in adults Combinations of these events have been referred to as the Propofol infusion syndrome. The following appear to be the major risk factors for the development of these events: decreased oxygen delivery to tissues; serious neurological injury and/or sepsis; high dosages of one or more of the following pharmacological agents - vasoconstrictors, steroids, inotropes and/or propofol (usually following extended dosing at dose rates greater than 4 mg/kg/h).
Prescribers should be alert to these events and consider decreasing the propofol dosage or switching to an alternative sedative at the first sign of occurrence of symptoms. All sedative and therapeutic agents used
in the intensive care unit (ICU), including propofol, should be titrated
