Active ingredients: Bupivacaine
BUPIVACAINE ANGELINI 2.5 mg / ml, solution for injection
BUPIVACAINE ANGELINI 5 mg / ml, solution for injection
BUPIVACAINE ANGELINI 5 mg / ml, hyperbaric solution for injection
BUPIVACAINE ANGELINI 10 mg / ml, hyperbaric solution for injection
Why is Bupivacaine used - Generic Drug? What is it for?
PHARMACOTHERAPEUTIC CATEGORY
Local anesthetics of the amide type.
THERAPEUTIC INDICATIONS
Bupivacaina Angelini can be used in any type of peripheral anesthesia:
- local troncular, loco-regional infiltration
- sympathetic block
- retrograde intravenous block and intra-arterial block - peridural, sacral - spinal subarachnoid.
Bupivacaine Angelini is therefore indicated in all general surgery, orthopedics, ophthalmology, otolaryngology, stomatology, obstetrics and gynecology, dermatology, both used alone and associated with narcosis.
BUPIVACAINA ANGELINI 2,5mg / ml solution for injection
BUPIVACAINA ANGELINI 5mg / ml solution for injection
- Surgical anesthesia in adults and children over 12 years.
- Treatment of acute pain in adults, infants and children over 1 year of age.
BUPIVACAINA ANGELINI 5mg / ml hyperbaric solution for injection
- Spinal anesthesia in adults and children of all ages.
Contraindications When Bupivacaine - Generic Drug should not be used
Hypersensitivity to the active ingredient, to any of the excipients or to other closely related substances from a chemical point of view; in particular towards local anesthetics of the same group (amide type).
The "use of Bupivacaine is" to be avoided in patients for whom pregnancy is known or suspected (see "Pregnancy").
Cases of cardiac arrest have been reported following the use of bupivacaine for epidural anesthesia in parturient women; in most cases, this occurred following the use of the 0.75% solution. Therefore, the use of 0.75% bupivacaine should be avoided in epidural anesthesia in obstetrics. This concentration should be reserved for those surgical procedures in which a high degree of muscle relaxation and a prolonged effect are required. The product is also contraindicated in paracervical block and regional intravenous anesthesia (Bier Block).
General contraindications should be considered in case of intrathecal anesthesia:
- acute active diseases of the central nervous system, such as meningitis, tumors, polio and intracranial haemorrhages - spinal stenosis and active disease of the spine (e.g. spondylitis, tuberculosis, tumor) or recent trauma (e.g. fractures)
- septicemia
- pernicious anemia combined with subacute degeneration of the spinal cord
- pyogenic skin infection at the injection site or surrounding area
- cardiogenic or hypovolemic shock
- coagulation disorders or anticoagulant treatments in progress.
Precautions for use What you need to know before taking Bupivacaine - Generic Drug
The safety and efficacy of some injections of BUPIVACAINE ANGELINI to anesthetize parts of the body during surgery have not been established in children under 12 years and in children under 1 year.
The total posology should be adjusted according to the patient's general condition, age and relevant medical history. Cases of cardiac arrest or death have been reported following the use of bupivacaine for epidural anesthesia or peripheral nerve block. In some cases, resuscitation was difficult or impossible despite the apparently adequate preparation and conduct of the staff. In most cases this has occurred following the use of the 7.5 mg / ml solution.
Intrathecal anesthesia should only be performed by a physician or under the supervision of clinicians with the necessary expertise and experience.
Bupivacaine, like all local anesthetics, when used for local anesthetic procedures that result in high blood concentrations of the drug, can cause acute toxic effects on the central nervous system and cardiovascular system, especially in the case of accidental intravascular administration or injection into highly vascularized areas. Ventricular arrhythmia, ventricular fibrillation, sudden cardiovascular collapse and death have been reported following elevated systemic concentrations of bupivacaine. However, high systemic concentrations are not expected at doses typically used for intrathecal anesthesia.
Regional anesthesia procedures must always be performed in adequately equipped areas and by qualified personnel. It is necessary to have immediate availability of the equipment and drugs necessary for monitoring and emergency resuscitation.
In patients undergoing major block or receiving high doses of the drug, an intravenous catheter must be inserted before administering the local anesthetic. treatment of side effects, systemic toxicity or other complications (see "Side Effects" and "Overdose").
Blockade of the major peripheral nerves may involve the administration of a high volume of local anesthetic in highly vascularized areas, often near large vessels where there is an increased risk of intravascular injection and / or rapid systemic absorption, which can lead to elevated plasma concentrations .
Although regional anesthesia is frequently the anesthetic technique of choice, some patients require special attention to reduce the risk of dangerous side effects:
- elderly or debilitated patients;
- patients with partial or complete heart block as local anesthetics can depress cardiac conduction;
- patients with advanced liver disease or severe renal impairment;
- hypovolaemic patients can develop severe and sudden hypotension during intrathecal anesthesia, regardless of the local anesthetic used. Hypotension usually occurs after intrathecal block in adults;
- patients being treated with class III antiarrhythmic drugs (eg amiodarone) should be closely monitored and ECG monitoring should be considered as cardiac effects can be additive.
Some local anesthetic techniques can be associated with severe adverse reactions, regardless of the local anesthetic used:
- Central nervous block: can cause cardiovascular depression especially in the presence of hypovolemia. Epidural anesthesia should therefore be used with caution in patients with reduced cardiovascular function;
- Retrobulbar injections: they can, in very rare cases, reach the subarachnoid space of the brain causing temporary blindness, cardiovascular collapse, apnea, convulsions, etc. Such reactions must be diagnosed and treated immediately;
- Retro and peribulbar injections of local anesthetics: carry a low risk of persistent muscle dysfunction in the eye. Primary causes include trauma and / or local toxic effects on muscles and / or nerves. The severity of these tissue reactions is related to the extent of the trauma, the concentration of local anesthetic and the duration of tissue exposure to the local anesthetic. As with all local anesthetics, it is therefore necessary to use the lowest doses and concentrations. that can allow to obtain the desired effect. Vasoconstrictors can aggravate tissue reactions and should only be used if indicated. Accidental intra-arterial injections in the cranial and cervical region can cause immediate brain symptoms even at low doses.
- Paracervical block can sometimes cause fetal bradycardia / tachycardia. Careful monitoring of the fetal heart rate is therefore necessary.
A rare but serious adverse reaction following spinal anesthesia is total or high spinal block and subsequent cardiovascular and respiratory depression. Cardiovascular depression is caused by extensive sympathetic block resulting in profound hypotension and bradycardia or even cardiac arrest. Respiratory depression can be caused by blocking the innervation of the respiratory muscles, including the diaphragm. The risk of total or high spinal block is greater in elderly patients. The dose should therefore be reduced in these patients.
The onset of neurological damage is a rare consequence of intrathecal anesthesia and can lead to paraesthesia, anesthesia, motor weakness and paralysis. Occasionally such damage is permanent.
Caution is advised in patients with neurological disorders such as multiple sclerosis, hemiplegia, paraplegia and neuromuscular disorders even if it is believed that intrathecal anesthesia does not adversely affect these disorders. Before starting treatment, it should be considered whether the benefits are greater than the possible risks for the patient.
Epidural anesthesia can cause hypotension and bradycardia. The risk can be reduced by prefilling the circulation with solutions of crystalloids or colloids. Hypotension should be treated immediately with the administration, possibly repeated, of an intravenous sympathomimetic. In children, the dosage should be appropriate for age and weight.
Individual cases of reduced or no efficacy have been reported with the use of Bupivacaine Angelini, especially in the case of spinal anesthesia.
As with other local anesthetics, literature and post-marketing surveillance data report the lack of efficacy following spinal anesthesia in a variable percentage. The most common reasons for this ineffectiveness can be technical problems, inadequate doses or inappropriate patient positioning. In the presence of correct dosages and injection technique, the reason for an inadequate block may be due to maldistribution of the active ingredient, variability in the anatomy of the subarachnoid space, or resistance to the effects of local anesthesia.
When bupivacaine is administered intra-articularly, caution is advised if recent major intra-articular trauma is suspected or when surgery has resulted in "extensive exposure of the joint" as this may accelerate absorption and result in concentrations. higher plasma levels.
If infiltrations by local anesthesia are practiced in areas without the possibility of collateral circulation (fingers, root of the penis, etc.) it is a precautionary measure to use the anesthetic without vasoconstrictor to avoid ischemic necrosis. use Bupivacaine Angelini 0.50% solution for injection with adrenaline. The product should be used with absolute caution in subjects undergoing treatment with MAOIs or tricyclic antidepressants. Before use, the doctor must ascertain the state of the circulatory conditions of the subjects to be treated. It is advisable to use an adequate dose-test, possibly in combination with adrenaline, in order to promptly avoid an accidental intravenous or intrathecal injection. The anesthetic solution. it must be injected with caution in small doses after about 10 seconds from a preventive aspiration.
Especially when very vascularized areas have to be infiltrated, it is advisable to allow about 2 minutes to elapse before proceeding to the actual loco-regional block.
The patient should be closely monitored by discontinuing administration immediately at the first sign of alarm (e.g., changes in the sensory).
It is necessary to have the immediate availability of equipment, drugs and personnel suitable for emergency treatment, since in rare cases, following the use of local anesthetics, serious reactions, sometimes with a fatal outcome, have been reported, even in the absence of individual hypersensitivity to the anamnesis.
Interactions Which drugs or foods can modify the effect of Bupivacaine - Generic Drug
Tell your doctor or pharmacist if you have recently taken any other medicines, even those without a prescription.
Bupivacaine should be used with caution in patients being treated with other local anesthetics or substances structurally related to amide-type local anesthetics, e.g. certain antiarrhythmics such as lidocaine, mexiletine and tocainide as the systemic toxic effects are additive. Caution is advised in patients treated with class III antiarrhythmics (eg amiodarone) despite the absence of specific drug class interaction studies (see "Precautions for use").
The product should be used with absolute caution in subjects undergoing treatment with MAOIs or tricyclic antidepressants.
Warnings It is important to know that:
Pregnancy and breastfeeding
Ask your doctor or pharmacist for advice before taking any medicine.
Pregnancy
Do not use the drug in known or suspected pregnancy (see "Contraindications").
Feeding time
Like other local anesthetics, bupivacaine can be excreted in breast milk but in such small quantities that there is generally no risk to the newborn.
EFFECTS ON THE ABILITY TO DRIVE VEHICLES AND ON THE USE OF MACHINERY
Local anesthetics, in addition to the direct anesthetic effect, can have a very mild effect on mental function and coordination, even in the absence of obvious central nervous system toxicity, and can temporarily adversely affect locomotion and the degree of alertness.
Dosage and method of use How to use Bupivacaine - Generic Drug: Posology
Use in children and adolescents
Depending on the type of anesthesia required, BUPIVACAINE ANGELINI is slowly infused into the vertebral canal (part of the spine) or other parts of the body by an anesthetist experienced in pediatric anesthetic techniques. Dosages depend on the age and weight of the patient and will be determined by the anesthetist.
BUPIVACAINA ANGELINI 2,5mg / ml solution for injection
BUPIVACAINA ANGELINI 5mg / ml solution for injection
Pediatric patients aged 1 to 12 years
Pediatric regional anesthesia procedures should be performed by qualified physicians with technical experience and familiarity with this type of patient.
The doses shown in the table should be taken as guidelines for use in pediatrics, although variations may occur on an individual basis. In children with a higher body weight, a gradual reduction in dosage is often necessary, which should be based on ideal body weight. .
For the factors that may affect specific blocking techniques and for the individual needs of the patient, the reference texts should be consulted. The lowest dose necessary to obtain adequate anesthesia should be used.
Dosages recommended in children
a) Onset and duration of peripheral nerve block depends on the type of block and the dose administered.
b) Thoracic epidural blocks should be administered in increasing dosages until the desired level of anesthesia is achieved.
In children the dose should be calculated on the basis of weight up to 2 mg / kg.
To prevent accidental intravascular injection, aspirate before and during administration of the main dose. This must be injected slowly in increasing doses, particularly in the lumbar and thoracic epidural route, with constant and close observation of the patient's vital functions.
Peritonsillar infiltration should be performed in children over 2 years of age, using 2.5 mg / ml bupivacaine at a dose of 7.5-12.5 mg per tonsil.
Ilioinguinal-ileoipogastric blocks should be performed in children aged at least 1 year or older, using bupivacaine 2.5 mg / ml at a dose of 0.1-0.5 ml / kg equivalent to 0.25-1.25 mg / kg. Children 5 years of age or older should be treated with bupivacaine 5 mg / ml at a dose of 1.25-2 mg / kg.
For penile blockade use bupivacaine 5mg / ml with a total dose of 0.2-0.5ml / kg equivalent to 1-2.5mg / kg.
The safety and efficacy of BUPIVACAINE ANGELINI in children below 1 year of age have not been established. Only a limited amount of data is available.
The safety and efficacy of intermittent epidural bolus injections or continuous infusion have not been established. Only a limited amount of data is available.
BUPIVACAINA ANGELINI 5mg / ml hyperbaric solution for injection
Newborns, infants and children up to 40 kg.
BUPIVACAINE ANGELINI 5mg / ml hyperbaric solution for injection can be used in children.
One of the differences between young children and adults is a relatively high CSF volume in neonates and infants which requires a relatively higher dose / kg to proceed at the same level of block compared to adults.
Pediatric regional anesthesia procedures should be performed by qualified physicians with technical experience and familiarity with this type of patient.
The doses shown in the table should be taken as guidelines for use in pediatrics, although variations may occur on an individual basis. For the factors that may affect specific blocking techniques and for the individual needs of the patient, the texts should be consulted. The lowest dose necessary to achieve adequate anesthesia should be used.
Dosages recommended in newborns, infants and children
Adults
Bupivacaine is usually used in minimum dosages, varying according to the indications, from 2-3 mg to 100-150 mg as indicated for guidance in the table:
(a): posology s "means for each intercostal space.
(b): starting with 10 ml then 3-5-8 ml every 4-6 hours, depending on the segments to be anesthetized and the age of the patient.
Warning: the vials, as they do not contain preservatives, are to be used for one administration only. Any inventories will be discarded.
The maximum dosage for an adult and for a single administration should not exceed 150 mg, corresponding to 30 ml of the 0.50% solution and 60 ml of the 0.25% solution; more generally, the safety dose, both for adults and for children, which it is advisable not to exceed, is 2 mg / kg for a single administration.
In prolonged analgesic therapy, doses ranging from 0.25 to 1 mg / kg of body weight are usually used; the administration can be repeated 2-3 times in 24 hours.
N.B. When carrying out prolonged blocks for subsequent bolus administration, the risk of reaching toxic plasma concentrations or inducing neuronal damage locally must be considered.
The dose to be administered should be calculated based on the experience of the physician and knowledge of the patient's clinical status. It is necessary to use the lowest doses that can allow adequate anesthesia to be obtained. Individual variations may occur in relation to the start-up times and duration. For the factors that may affect specific blocking techniques and for the individual needs of the patient, the reference texts should be consulted. The degree of diffusion of anesthesia can be difficult to predict but is influenced by the volume of drug administered especially as regards isobaric solutions.
To prevent accidental intravascular injection, aspiration should be performed before and during administration of the main dose, which should be injected slowly or in increasing doses. During the procedure, carefully monitor the patient's vital functions and maintain verbal contact. In case epidural anesthesia is required, it is recommended to precede a test dose of 3-5 ml of bupivacaine with epinephrine.
An "accidental intravascular injection can be recognized by a temporary increase in heart rate; an" accidental intrathecal injection is recognized by signs of spinal block. At the first sign of toxicity, discontinue administration immediately (see "Adverse Effects - Acute Systemic Toxicity and Treatment of Acute Systemic Toxicity").
The specific gravity of Bupivacaine at 0.25% or 0.50% is 1.006 at 20 ° C and 0.997 at 37 ° C; Bupivacaine at 1% hyperbaric solution has a specific gravity of 1.045 at 20 ° C and of 1.035 at 37 ° C.
Any overdose of anesthetic should be avoided and never given two maximum doses of the latter without an interval of at least 24 hours.
However, it is necessary to use the lowest doses and concentrations that can allow to obtain the desired effect.
Overdose What to do if you have taken an overdose of Bupivacaine - Generic Drug
Accidental intravascular injection of local anesthetics can cause immediate systemic toxic reactions (ranging from seconds to minutes). In case of overdose, systemic toxicity occurs later (15-60 minutes after injection) and this is due to a slowed increase in blood concentrations of local anesthetic (see "Adverse Effects - Acute Systemic Toxicity and Treatment of Acute Systemic Toxicity").
Hyperbaric Bupivacaine Angelini, under recommended conditions of use, is unlikely to promote blood levels high enough to cause systemic toxicity. However, if other local anesthetics are administered concomitantly, the toxic effects are additive and may cause systemic toxicity (see "Adverse Effects - Acute Systemic Toxicity and Treatment of Acute Systemic Toxicity").
When the first signs of overdose appear, stop the administration of the preparation and, placing the patient in a horizontal position, check that the airways are open. If breathing difficulties occur, assisted ventilation is required (the Ambu bag can also be used in an emergency). The use of bulbar analeptics is not recommended as they increase oxygen consumption. The onset of convulsive manifestations can be controlled with diazepam in the vein (10-20 mg), but barbiturates which can accentuate bulbar depression are not recommended.
To support the circulation, cortisone drugs can be used intravenously; dilute solutions of alpha-beta-stimulants with vasoconstrictive action (mefentermin, metaraminol and others) or of atropine sulphate can be added. The correction of any established acidic state can be corrected with the use of appropriate intravenous sodium bicarbonate solutions.
In case of accidental ingestion / intake of an excessive dose of Angelini Bupivacaine, notify your doctor immediately or contact the nearest hospital.
If you have any questions about the use of Bupivacaine Angelini, ask your doctor or pharmacist.
Side Effects What are the side effects of Bupivacaine - Generic Drug
Additional side effects in children and adolescents
Adverse reactions in children are similar to those in adults.
General
Like all medicines, Bupivacaine Angelini can cause side effects, although not everybody gets them.
The adverse reaction profile of Bupivacaine Angelini is comparable to that of other long-acting local anesthetics. The adverse drug reactions are difficult to distinguish from the physiological effects resulting from nerve conduction block (such as decrease in blood pressure, bradycardia, retention temporary urinary tract) and events caused directly by the injection (e.g. nerve fiber trauma, spinal hematoma) or indirectly (e.g. epidural abscess and meningitis) or events associated with cerebrospinal loss (e.g. post-dural puncture headache) The onset of neurological damage is a rare but well known consequence of regional anesthesia and in particular of epidural and spinal anesthesia.
Table of adverse drug reactions
- Vascular disorders: hypotension
- Gastrointestinal disorders: nausea.
- Heart Disorders: Bradycardia
- Vascular disorders: hypertension
- Gastrointestinal disorders: vomiting
- Urological and renal disorders: urinary retention, urinary incontinence.
- Nervous system disorders: signs and symptoms of CNS toxicity (convulsions, paraesthesia in the circumoral region, numbness of the tongue, hyperacusis, visual disturbances, loss of consciousness, tremor, light-headedness, tinnitus, dysarthria, paresis, dysesthesia)
- Disorders of the musculoskeletal system, connective tissue and bone tissue: muscle weakness, back pain.
- Immune system disorders: allergic reactions, anaphylactic reactions / shock
- Nervous system disorders: neuropathy, peripheral nerve injury, arachnoiditis, paresis, paraplegia, total spinal block (unintentional), paralysis
- Eye disorders: diplopia
- Cardiac disorders: cardiac arrest, cardiac arrhythmias
- Respiratory disorders: respiratory depression
Other reported side effects include phenomena of central nervous stimulation (excitement, disorientation, mydriasis, increased metabolism and body temperature, trismus, sweating, tachypnea, bronchodilation, vasodilation) and allergic reactions with local manifestations (urticaria, itching) or systemic (bronchospasm, laryngeal edema).
Compliance with the instructions contained in the package leaflet reduces the risk of undesirable effects.
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please inform your doctor or pharmacist.
Acute systemic toxicity
Systemic toxic reactions mainly affect the central nervous system and the cardiovascular system. These reactions are caused by high blood concentrations of the local anesthetic following accidental intravascular injection, overdose or exceptionally rapid absorption from highly vascularized areas (see "Precautions for use"). Reactions affecting the central nervous system are comparable to those of other local anesthetics of the amide type while cardiac reactions depend, both quantitatively and qualitatively, to a greater extent on the drug.
Hyperbaric Bupivacaine Angelini, under recommended conditions of use, is unlikely to promote blood levels high enough to cause systemic toxicity. However, if other local anesthetics are administered concomitantly, the toxic effects are additive and may cause systemic toxicity.
Central nervous system toxicity occurs gradually, with symptoms and signs of increasing severity. The first symptoms are usually paresthesia in the circumoral region, numbness of the tongue, light-headedness, hyperacusis, tinnitus and visual disturbances. Dysarthria, muscle spasm or tremor are more serious manifestations and precede the onset of generalized convulsions. These signs should not be confused with heretic behavior. Unconsciousness and seizures may follow which can last from a few seconds to several minutes. After the convulsions, a due to increased muscle activity, interference with breathing and the possible lack of airway patency, hypoxia and hypercapnia occur rapidly. In severe cases, apnea may occur. Acidosis, hyperkalaemia, hypocalcemia and hypoxia increase and amplify the toxic effects of local anesthetics.
The patient's return to initial clinical condition results from the redistribution of the local anesthetic from the central nervous system and subsequent metabolism and excretion. Recovery can be rapid if large quantities of the drug have not been administered.
In severe cases, cardiovascular effects may occur, usually preceded by signs of central nervous system toxicity. In patients who are deeply sedated or under general anesthesia, the effects on the cardiovascular system can arise without prodromal effects on the central nervous system. As a result of high systemic concentrations of local anesthetics, hypotension, bradycardia, arrhythmias and even cardiac arrest can be generated. but in rare cases cardiac arrest has arisen without prodromal effects of the central nervous system.
In children, early signs of local anesthetic systemic toxicity may be difficult to detect when the block is administered during general anesthesia.
Treatment of acute systemic toxicity
Administration of the local anesthetic should be discontinued immediately if signs of acute systemic toxicity or total spinal block appear. Symptoms of central nervous system toxicity (seizures, central nervous system depression) should be treated immediately with adequate support for patency. airways and breathing and with the administration of anticonvulsants, such as diazepam in a dose of 10-20 mg intravenously; however, barbiturates that can accentuate bulbar depression are not recommended. The circulation can be supported with the administration of cortisone. in appropriate intravenous doses; dilute solutions of alpha-beta-stimulants with vasoconstrictive action (mefentermin, metaraminol and others) or atropine sulphate can be added.
Should circulatory arrest occur, cardiopulmonary resuscitation should be performed immediately. It is vital to ensure optimal oxygenation, support ventilation and circulation, and treat acidosis.
If cardiovascular depression (hypotension, bradycardia) occurs, adequate treatment with intravenous fluids, vasopressors and / or inotropic agents should be considered. In children, dosage should be appropriate for age and weight. If cardiac arrest occurs, it may be necessary to prolong resuscitation maneuvers to achieve a favorable outcome.
Expiry and Retention
Expiry: see the expiry date indicated on the package.
The expiry date refers to the product in intact packaging, correctly stored.
Warning: Do not use the product after the expiry date shown on the package.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.
Keep this medicine out of the reach and sight of children.
Other information
COMPOSITION
Bupivacaine Angelini 2.5 mg / ml (0.25%) solution for injection
1 ml contains:
- Active ingredient: Bupivacaine 2.5 mg (as hydrochloride)
- Excipients: sodium chloride, water for injections
Bupivacaine Angelini 5 mg / ml (0.5%) solution for injection
1 ml contains:
- Active ingredient: Bupivacaine 5 mg (as hydrochloride)
- Excipients: sodium chloride, water for injections
Bupivacaine Angelini 5 mg / ml (0.5%) hyperbaric solution for injection
1 ml of hyperbaric solution contains:
- Active ingredient: Bupivacaine 5 mg (as hydrochloride)
- Excipients: anhydrous glucose, sodium hydroxide, water for injections
Bupivacaine Angelini 10 mg / ml (1%) hyperbaric solution for injection
1 ml of hyperbaric solution contains:
- Active ingredient: Bupivacaine 10 mg (as hydrochloride)
- Excipients: glucose monohydrate, water for injections.
PHARMACEUTICAL FORM AND CONTENT
Bupivacaine Angelini 2.5 mg / ml (0.25%) solution for injection
Solution for injection: pack of 1 or 5 type I 5 ml neutral glass ampoules; pack of 1, 5 or 10 type I neutral glass vials of 10 ml.
Bupivacaine Angelini 5 mg / ml (0.5%) solution for injection
Solution for injection: pack of 1 or 5 type I 5 ml neutral glass ampoules; pack of 1, 5 or 10 type I neutral glass vials of 10 ml.
Bupivacaine Angelini 5 mg / ml (0.5%) hyperbaric solution for injection
Solution for injection: pack of 10 type I neutral glass vials of 4 ml.
Bupivacaine Angelini 10 mg / ml (1%) hyperbaric solution for injection
Solution for injection: pack of 10 type I 2 ml neutral glass ampoules.
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
BUPIVACAINA ANGELINI
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
BUPIVACAINE ANGELINI 2.5 mg / ml solution for injection: 1 ml contains 2.5 mg bupivacaine (as hydrochloride).
BUPIVACAINE ANGELINI 5 mg / ml solution for injection: 1 ml contains 5 mg bupivacaine (as hydrochloride).
BUPIVACAINE ANGELINI 5 mg / ml hyperbaric solution for injection: 1 ml contains 5 mg bupivacaine (as hydrochloride).
BUPIVACAINE ANGELINI 10 mg / ml hyperbaric solution for injection: 1 ml contains 10 mg bupivacaine (as hydrochloride).
For the full list of excipients see section 6.1.
03.0 PHARMACEUTICAL FORM
Injectable solution
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Bupivacaina Angelini can be used in any type of peripheral anesthesia:
- local troncular, loco-regional infiltration
- sympathetic block
- retrograde intravenous block and intra-arterial block
- peridural, sacral
- subarachnoid spinal.
Bupivacaine Angelini is therefore indicated in all general surgery, orthopedics, ophthalmology, otolaryngology, stomatology, obstetrics and gynecology, dermatology, both used alone and associated with narcosis.
04.2 Posology and method of administration
Bupivacaine is usually used in minimum dosages, varying according to the indications, from 2-3 mg to 100-150 mg as indicated for guidance in the table:
(a): posology s "means for each intercostal space.
(b): starting with 10 ml then 3-5-8 ml every 4-6 hours, depending on the segments to be anesthetized and the age of the patient.
Warning: the vials do not contain preservatives, they must be used for a single administration. Any inventories will be discarded.
The maximum dosage for an adult and for a single administration should not exceed 150 mg, corresponding to 30 ml of the 0.50% solution and 60 ml of the 0.25% solution; more generally, the safety dose, both for adults and for children, which it is advisable not to exceed, is 2 mg / kg for a single administration.
In prolonged analgesic therapy, doses ranging from 0.25 to 1 mg / kg of body weight are usually used; the administration can be repeated 2-3 times in 24 hours.
N.B. When carrying out prolonged blocks for subsequent bolus administration, the risk of reaching toxic plasma concentrations or inducing neuronal damage locally must be considered.
The dose to be administered should be calculated based on the experience of the physician and knowledge of the patient's clinical status. It is necessary to use the lowest doses that can allow adequate anesthesia to be obtained. Individual variations may occur in relation to the start-up times and duration. In children with high body weight, a gradual reduction in dosage is often necessary and should be based on the ideal body weight. Reference texts should be consulted both on aspects that affect specific blocking techniques and on the individual needs of the patient. The degree of diffusion of anesthesia can be difficult to predict but is influenced by the volume of drug administered especially as regards isobaric solutions.
To prevent accidental intravascular injection, aspiration should be performed before and during administration of the main dose, which should be injected slowly or in increasing doses. During the procedure, carefully monitor the patient's vital functions and maintain verbal contact. In case epidural anesthesia is required, it is recommended to precede a test dose of 3-5 ml of bupivacaine with epinephrine. An "accidental intravascular injection can be recognized by a temporary increase in heart rate; an" accidental intrathecal injection is recognized by signs of spinal block. At the first sign of toxicity, discontinue administration immediately (see section 4.8 "Acute systemic toxicity" and "Treatment of acute systemic toxicity").
The specific gravity of Bupivacaine at 0.25% or 0.50% is 1.006 at 20 ° C and 0.997 at 37 ° C; Bupivacaine at 1% hyperbaric solution has a specific gravity of 1.045 at 20 ° C and of 1.035 at 37 ° C.
Any overdose of anesthetic should be avoided and never given two maximum doses of the latter without an interval of at least 24 hours.
However, it is necessary to use the lowest doses and concentrations that can allow to obtain the desired effect.
04.3 Contraindications
Hypersensitivity to the active ingredient, to any of the excipients or to other closely related substances from a chemical point of view; in particular towards local anesthetics of the same group (amide type).
The use of bupivacaine should be avoided in patients with known or suspected pregnancy (see section 4.6).
Cases of cardiac arrest have been reported following the use of bupivacaine for epidural anesthesia in parturient women; in most cases this occurred following the use of the 0.75% solution. Therefore, the use of 0.75% bupivacaine should be avoided in epidural anesthesia in obstetrics. This concentration should be reserved for those surgical procedures in which a high degree of muscle relaxation and a prolonged effect are required.
The product is also contraindicated in paracervical block and regional intravenous anesthesia (Bier Block).
General contraindications should be considered in case of intrathecal anesthesia:
- acute active diseases of the central nervous system, such as meningitis, tumors,
poliomyelitis and intracranial hemorrhages
- spinal stenosis and active spinal disease (e.g. spondylitis, tuberculosis, tumor) or recent trauma (e.g. fractures)
- septicemia
- pernicious anemia combined with subacute degeneration of the spinal cord
- pyogenic skin infection at the injection site or surrounding area
- cardiogenic or hypovolemic shock
- coagulation disorders or anticoagulant treatments in progress.
04.4 Special warnings and appropriate precautions for use
The total posology must be correct in relation to the general conditions, age and relevant anamnestic data of the patient.
Cases of cardiac arrest or death have been reported following the use of bupivacaine for epidural anesthesia or peripheral nerve block. In some cases, resuscitation was difficult or impossible despite apparently adequate preparation and conduct of staff. In most cases of cases this occurred following the use of the 7.5 mg / ml solution.
Intrathecal anesthesia should only be performed by a physician or under the supervision of clinicians with the necessary expertise and experience.
Bupivacaine, like all local anesthetics, when used for local anesthetic procedures that result in high blood concentrations of the drug, can cause acute toxic effects on the central nervous system and cardiovascular system, especially in the case of accidental intravascular administration or injection into highly vascularized areas. Ventricular arrhythmia, ventricular fibrillation, sudden cardiovascular collapse and death have been reported following elevated systemic concentrations of bupivacaine. However, high systemic concentrations are not expected at doses typically used for intrathecal anesthesia.
Regional anesthesia procedures must always be performed in adequately equipped areas and by qualified personnel. It is necessary to have immediate availability of the equipment and drugs necessary for monitoring and emergency resuscitation.
In patients undergoing major blockade or receiving high doses of the drug, an intravenous catheter must be inserted before the administration of the local anesthetic. treatment of undesirable effects, systemic toxicity or other complications (see sections 4.8 and 4.9).
Blockade of the major peripheral nerves may involve the administration of a high volume of local anesthetic in highly vascularized areas, often near large vessels where there is an increased risk of intravascular injection and / or rapid systemic absorption, which can lead to elevated plasma concentrations .
Although regional anesthesia is frequently the anesthetic technique of choice, some patients require special attention to reduce the risk of dangerous side effects:
• elderly or debilitated patients;
• patients with partial or complete heart block as local anesthetics can depress cardiac conduction;
• patients with advanced liver disease or severe renal impairment;
• hypovolaemic patients can develop severe and sudden hypotension during intrathecal anesthesia, regardless of the local anesthetic used. Hypotension usually occurs after intrathecal block in adults;
• Patients being treated with class III antiarrhythmic drugs (eg amiodarone) should be closely monitored and ECG monitoring should be considered as cardiac effects can be additive.
Some local anesthetic techniques can be associated with severe adverse reactions, regardless of the local anesthetic used:
- Central nervous block: it can cause cardiovascular depression especially in the presence of hypovolemia. Epidural anesthesia should therefore be used with caution in patients with reduced cardiovascular function;
- Retrobulbar injections: they can, in very rare cases, reach the subarachnoid space of the brain causing temporary blindness, cardiovascular collapse, apnea, convulsions, etc. Such reactions must be diagnosed and treated immediately;
-Retro and peribulbar injections of local anesthetics: carry a low risk of persistent muscle dysfunction in the eye. Primary causes include trauma and / or local toxic effects on muscles and / or nerves. The severity of these tissue reactions is related to the extent of the trauma, the concentration of local anesthetic and the duration of tissue exposure to the local anesthetic. As with all local anesthetics, it is therefore necessary to use the lowest doses and concentrations. that can allow to obtain the desired effect. Vasoconstrictors can aggravate tissue reactions and should only be used if indicated. Accidental intra-arterial injections in the cranial and cervical region can cause immediate brain symptoms even at low doses.
Paracervical block can sometimes cause fetal bradycardia / tachycardia. Careful monitoring of the fetal heart rate is therefore necessary.
A rare but serious adverse reaction following spinal anesthesia is total or high spinal block and subsequent cardiovascular and respiratory depression. Cardiovascular depression is caused by extensive sympathetic block resulting in profound hypotension and bradycardia or even cardiac arrest. Respiratory depression can be caused by blocking the innervation of the respiratory muscles, including the diaphragm. The risk of total or high spinal block is greater in elderly patients. The dose should therefore be reduced in these patients.
The onset of neurological damage is a rare consequence of intrathecal anesthesia and can lead to paraesthesia, anesthesia, motor weakness and paralysis. Occasionally such damage is permanent.
Caution is advised in patients with neurological disorders such as multiple sclerosis, hemiplegia, paraplegia and neuromuscular disorders even if it is believed that intrathecal anesthesia does not adversely affect these disorders. Before starting treatment, it should be considered whether the benefits are greater than the possible risks for the patient.
Epidural anesthesia can cause hypotension and bradycardia. The risk can be reduced by prefilling the circulation with solutions of crystalloids or colloids. Hypotension should be treated immediately with the administration, possibly repeated, of an intravenous sympathomimetic. In children, the dosage should be appropriate for age and weight.
When bupivacaine is administered intra-articularly, caution is advised if recent major intra-articular trauma is suspected or when surgery has resulted in extensive joint exposure as this may accelerate absorption and lead to plasma concentrations. higher.
If infiltrations by local anesthesia are practiced in areas without the possibility of collateral circulation (fingers, root of the penis, etc.) it is a precautionary measure to use the anesthetic without vasoconstrictor to avoid ischemic necrosis. use Bupivacaine Angelini 0.50% solution for injection with adrenaline. The product should be used with absolute caution in subjects undergoing treatment with MAOIs or tricyclic antidepressants. Before use, the doctor must ascertain the state of the circulatory conditions of the subjects to be treated. It is advisable to use an adequate dose-test, possibly in combination with adrenaline, in order to promptly avoid an accidental intravenous or intrathecal injection. The anesthetic solution. it must be injected with caution in small doses after about 10 seconds from a preventive aspiration .. Especially when very vascularized areas have to be infiltrated, it is advisable to allow about 2 minutes to elapse before proceeding with the actual loco-regional block.
The patient should be closely monitored by discontinuing administration immediately at the first sign of alarm (e.g., changes in the sensory).
It is necessary to have the immediate availability of equipment, drugs and personnel suitable for emergency treatment, since in rare cases, following the use of local anesthetics, serious reactions, sometimes with a fatal outcome, have been reported, even in the absence of individual hypersensitivity to the anamnesis.
04.5 Interactions with other medicinal products and other forms of interaction
Bupivacaine should be used with caution in patients being treated with other local anesthetics or substances structurally related to amide-type local anesthetics, e.g. certain antiarrhythmics such as lidocaine, mexiletine and tocainide as the systemic toxic effects are additive. Caution is advised in patients treated with class III antiarrhythmics (eg amiodarone) despite the absence of specific drug class interaction studies (see section 4.4).
The product should be used with absolute caution in subjects undergoing treatment with MAOIs or tricyclic antidepressants.
04.6 Pregnancy and breastfeeding
Pregnancy
Do not use the drug in known or suspected pregnancy (see section 4.3).
Feeding time
Like other local anesthetics, bupivacaine can be excreted in breast milk but in such small quantities that there is generally no risk to the newborn.
04.7 Effects on ability to drive and use machines
Local anesthetics, in addition to the direct anesthetic effect, can have a very mild effect on mental function and coordination, even in the absence of obvious central nervous system toxicity, and can temporarily adversely affect locomotion and the degree of alertness.
04.8 Undesirable effects
General
The adverse reaction profile of Bupivacaine Angelini is comparable to that of other long-acting local anesthetics. The adverse drug reactions are difficult to distinguish from the physiological effects resulting from nerve conduction block (such as decrease in blood pressure, bradycardia, temporary urinary retention) and by events directly caused by the injection (e.g. trauma of the nerve fiber, spinal hematoma) or indirectly (e.g. epidural abscess e meningitis) or events associated with cerebrospinal loss (e.g. post-dural puncture headache). The onset of neurological damage is a rare but well known consequence of regional anesthesia and in particular of epidural and spinal anesthesia.
Table of adverse drug reactions
Other reported side effects include phenomena of central nervous stimulation (excitement, disorientation, mydriasis, increased metabolism and body temperature, trismus, sweating, tachypnea, bronchodilation, vasodilation) and allergic reactions with local manifestations (urticaria, itching) or systemic (bronchospasm, laryngeal edema).
Acute systemic toxicity
Systemic toxic reactions mainly affect the central nervous system and the cardiovascular system. These reactions are caused by high blood concentrations of the local anesthetic following accidental intravascular injection, overdose or exceptionally rapid absorption from highly vascularized areas (see section 4.4). The central nervous system reactions are comparable to those of other local anesthetics. of the amide type while cardiac reactions depend, both quantitatively and qualitatively, to a greater extent on the drug.
Hyperbaric Bupivacaine Angelini, under recommended conditions of use, is unlikely to promote blood levels high enough to cause systemic toxicity. However, if other local anesthetics are administered concomitantly, the toxic effects are additive and may cause systemic toxicity.
Central nervous system toxicity occurs gradually, with symptoms and signs of increasing severity. The first symptoms are usually paresthesia in the circumoral region, numbness of the tongue, light-headedness, hyperacusis, tinnitus and visual disturbances. Dysarthria, muscle spasm or tremor are more serious manifestations and precede the onset of generalized convulsions. These signs should not be confused with heretic behavior. Unconsciousness and seizures may follow which can last from a few seconds to several minutes. After the convulsions, a due to increased muscle activity, interference with breathing and the possible lack of airway patency, hypoxia and hypercapnia occur rapidly. In severe cases, apnea may occur. Acidosis, hyperkalaemia, hypocalcemia and hypoxia increase and amplify the toxic effects of local anesthetics.
The patient's return to initial clinical condition results from the redistribution of the local anesthetic from the central nervous system and subsequent metabolism and excretion. Recovery can be rapid if large quantities of the drug have not been administered.
In severe cases, cardiovascular effects may occur, usually preceded by signs of central nervous system toxicity. In patients who are deeply sedated or under general anesthesia, the effects on the cardiovascular system can arise without prodromal effects on the central nervous system. As a result of high systemic concentrations of local anesthetics, hypotension, bradycardia, arrhythmias and even cardiac arrest can be generated. but in rare cases cardiac arrest has arisen without prodromal effects of the central nervous system.
In children, early signs of local anesthetic systemic toxicity may be difficult to detect when the block is administered during general anesthesia.
Treatment of acute systemic toxicity
Administration of the local anesthetic should be discontinued immediately if signs of acute systemic toxicity or total spinal block appear. Symptoms of central nervous system toxicity (seizures, central nervous system depression) should be treated immediately with adequate support for patency. airways and breathing and with the administration of anticonvulsants, such as diazepam in a dose of 10-20 mg intravenously; however, barbiturates that can accentuate bulbar depression are not recommended. The circulation can be supported with the administration of cortisone. in appropriate intravenous doses; dilute solutions of alpha-beta-stimulants with vasoconstrictive action (mefentermin, metaraminol and others) or atropine sulphate can be added.
Should circulatory arrest occur, cardiopulmonary resuscitation should be performed immediately. It is vital to ensure optimal oxygenation, support ventilation and circulation, and treat acidosis.
If cardiovascular depression (hypotension, bradycardia) occurs, adequate treatment with intravenous fluids, vasopressors and / or inotropic agents should be considered. In children, the dosage should be appropriate for age and weight.
If cardiac arrest occurs, it may be necessary to prolong resuscitation maneuvers to achieve a favorable outcome.
04.9 Overdose
Accidental intravascular injection of local anesthetics can cause immediate systemic toxic reactions (ranging from seconds to minutes). In case of overdose, systemic toxicity occurs later (15-60 minutes after injection) and this is due to a slowed increase in blood concentrations of local anesthetic (see section 4.8 "Acute systemic toxicity" and "Treatment of acute systemic toxicity").
Hyperbaric Bupivacaine Angelini, under recommended conditions of use, is unlikely to promote blood levels high enough to cause systemic toxicity. However, if other local anesthetics are administered concomitantly, the toxic effects are additive and may cause systemic toxicity (see section 4.8 "Acute systemic toxicity" and "Treatment of acute systemic toxicity").
When the first signs of overdose appear, stop the administration of the preparation and, placing the patient in a horizontal position, check that the airways are open. If breathing difficulties occur, assisted ventilation is required (the Ambu bag can also be used in an emergency). The use of bulbar analeptics is not recommended as they increase oxygen consumption. The onset of convulsive manifestations can be controlled with diazepam in the vein (10-20 mg), but barbiturates which can accentuate bulbar depression are not recommended.
To support the circulation, cortisone drugs can be used intravenously; dilute solutions of alpha-beta-stimulants with vasoconstrictive action (mefentermin, metaraminol and others) or of atropine sulphate can be added. The correction of any established acidic state can be corrected with the use of appropriate intravenous sodium bicarbonate solutions.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: local anesthetics of the amide type (bupivacaine).
ATC code: N01BB01.
Bupivacaine hydrochloride or (N-butyl-2-piperidincarbon) -2-6-dimethylanilide is a long-acting amide-type local anesthetic similar to Mepivacaine. Its anesthetic effect is longer lasting than that obtained with others. local anesthetics being able to be maintained, in consideration of the doses used, up to 20 hours.
The onset of activity and the duration of the local anesthetic effect of bupivacaine depend on the dose and site of administration.
Like other local anesthetics, bupivacaine reversibly blocks nerve conduction and prevents sodium ions from entering through the nerve fiber cell membrane. The sodium channel of the nerve fiber membrane is considered the receptor on which local anesthetics act.
Local anesthetics can have similar effects on other excitable membranes such as the brain and myocardium. Excessive amounts of the drug at the systemic level can cause symptoms and signs of toxicity mainly affecting the central nervous and cardiovascular systems.
Central nervous system toxicity occurs at lower plasma concentrations and generally precedes cardiovascular effects (see section 4.8 "Treatment of acute systemic toxicity"). Direct effects of local anesthetics on the myocardium include slow conduction, negative inotropism up to cardiac arrest.
Indirect cardiovascular effects (hypotension, bradycardia) may occur after epidural administration and are related to the extension of the concomitant sympathetic block.
Bupivacaine Angelini 5 mg / ml Hyperbaric and Bupivacaine Angelini 10 mg / ml Hyperbaric are hyperbaric solutions (relative to cerebrospinal fluid) and their initial diffusion into the intrathecal space is influenced by gravity. In view of the low dose administered, intrathecal distribution results in relatively low drug concentrations and the duration of the local anesthetic effect tends to be relatively short. Compared to hyperbaric solutions, glucose-free solutions produce less predictable but longer-lasting block levels. .
05.2 Pharmacokinetic properties
Bupivacaine has a pKa of 8.2 and a partition coefficient of 346 (n-octanol / phosphate buffer at pH 7.4 at 25 ° C). The pharmacological activity of the metabolites is lower than that of bupivacaine.
The plasma concentration of bupivacaine depends on the dose, route of administration and vascularity of the injection site.
Bupivacaine shows complete and biphasic absorption from the epidural space, with half-lives of the order of 7 minutes and 6 hours, respectively. Hyperbaric bupivacaine also has complete and biphasic absorption from the subarachnoid space, with half-life of the two phases of the order of 50 and 408 minutes. Slow absorption is the limiting factor in the elimination of bupivacaine; this explains why the apparent half-life after epidural or subarachnoid administration is longer than that after intravenous administration.
In view of the low dose required for intrathecal administration, plasma concentrations of bupivacaine after intrathecal blockade are low compared to those found after other regional anesthesia procedures. Normally, the increase in maximum plasma concentrations is approximately 0.4 mg / liter for every 100 mg injected. This means that after a 20 mg administration, plasma levels would be approximately 0.1 mg / liter.
Bupivacaine exhibits a total plasma clearance of 0.58 liters / minute, a steady state volume of distribution of 73 liters, a terminal half-life of 2.7 hours and an intermediate hepatic extraction ratio of 0.38 after intravenous administration. It is mainly bound to alpha-1-acid glycoprotein, with a plasma binding of 96%.
The clearance of bupivacaine occurs via metabolic processes almost exclusively in the liver and is more sensitive to changes in the intrinsic function of liver enzymes than to hepatic perfusion.
During continuous epidural infusion, an increase in total plasma concentration was detected which can be correlated with a post-operative increase in alpha-1-acid glycoprotein. The concentration of the unbound, pharmacologically active fraction was similar before and after surgery. .
Bupivacaine crosses the placenta rapidly and equilibrium between the bound and free fractions is readily achieved. The degree of plasma protein binding in the fetus appears to be less than that observed in the mother, which probably results in a lower total plasma concentration in the fetus.
Bupivacaine is extensively metabolised in the liver primarily by aromatic hydroxylation to 4-hydroxy-bupivacaine and by N-dealkylation to PPX, both mediated by cytochrome P450 3A4. Approximately 1% of bupivacaine is excreted as unchanged drug in the urine over 24 hours and approximately 5% as PPX. Plasma concentrations of PPX and 4-hydroxy-bupivacaine during and after continuous administration of bupivacaine are low compared to the parent compound .
05.3 Preclinical safety data
The LD50 calculated in the acute toxicity studies gave the following values: in mice i.v. 7.8 mg / kg and s.c. 82 mg / kg; in the guinea pig e.p. 50 mg / Kg. The chronic treatments performed on the rat (10 mg / kg s.c. for 90 days) did not show any alterations compared to the controls such as to be attributable to the toxic effects of the preparation.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Bupivacaine Angelini 2.5 mg / ml (0.25%) solution for injection and Bupivacaine Angelini 5 mg / ml (0.5%) solution for injection:
Sodium chloride, water for injections.
Bupivacaine Angelini 5 mg / ml (0.5%) hyperbaric solution for injection:
Anhydrous glucose, sodium hydroxide, water for injections.
Bupivacaine Angelini 10 mg / ml (1%) hyperbaric solution for injection:
Glucose monohydrate, water for injections.
06.2 Incompatibility
The product does not show incompatibility with other compounds.
06.3 Period of validity
Bupivacaina Angelini 2.5 mg / ml And 5 mg / ml: 3 years.
Bupivacaina Angelini 10 mg / ml hyperbaric injectable solution: 3 years.
Bupivacaina Angelini 5 mg / ml hyperbaric injectable solution: 24 months.
06.4 Special precautions for storage
This medicine does not require any special storage conditions
06.5 Nature of the immediate packaging and contents of the package
Bupivacaine Angelini 2.5 mg / ml (0.25%) solution for injection
Solution for injection: pack of 1 or 5 type I 5 ml neutral glass ampoules; pack of 1, 5 or 10 type I neutral glass vials of 10 ml.
Bupivacaine Angelini 5 mg / ml (0.5%) solution for injection
Solution for injection: pack of 1 or 5 type I 5 ml neutral glass ampoules; pack of 1, 5 or 10 type I neutral glass vials of 10 ml.
Bupivacaine Angelini 5 mg / ml (0.5%) hyperbaric solution for injection
Solution for injection: pack of 10 type I neutral glass vials of 4 ml.
Bupivacaine Angelini 10 mg / ml (1%) hyperbaric solution for injection
Solution for injection: pack of 10 type I 2 ml neutral glass ampoules.
06.6 Instructions for use and handling
Unused medicine and waste derived from this medicine must be disposed of in accordance with local regulations
07.0 MARKETING AUTHORIZATION HOLDER
Joint Chemical Companies Angelini Francesco - A.C.R.A.F. S.p.A.
Viale Amelia, 70 - 00181 ROME.
08.0 MARKETING AUTHORIZATION NUMBER
Bupivacaine Angelini 2.5 mg / ml solution for injection, 10 ampoules of 10 ml AIC n. 029232016
Bupivacaine Angelini 5 mg / ml solution for injection, 10 ampoules of 10 ml AIC n. 029232028
Bupivacaine Angelini 5 mg / ml hyperbaric solution for injection, 10 ampoules of 4 ml AIC n. 029232129
Bupivacaine Angelini 10 mg / ml hyperbaric solution for injection, 10 ampoules of 2 ml AIC n. 029232030
Bupivacaine Angelini 2.5 mg / ml solution for injection, 1 ampoule of 5 ml AIC n. 029232042
Bupivacaine Angelini 2.5 mg / ml solution for injection, 5 ampoules of 5 ml AIC n. 029232055
Bupivacaine Angelini 2.5 mg / ml solution for injection, 1 ampoule of 10 ml AIC n. 029232067
Bupivacaine Angelini 2.5 mg / ml solution for injection, 5 ampoules of 10 ml AIC n. 029232079
Bupivacaine Angelini 5 mg / ml solution for injection, 1 ampoule of 5 ml AIC n. 029232081
Bupivacaine Angelini 5 mg / ml solution for injection, 5 ampoules of 5 ml AIC n. 029232093
Bupivacaine Angelini 5 mg / ml solution for injection, 1 ampoule of 10 ml AIC n. 029232105
Bupivacaine Angelini 5 mg / ml solution for injection, 5 ampoules of 10 ml AIC n. 029232117
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
4.8.1995/4.8.2010
10.0 DATE OF REVISION OF THE TEXT
23.07.2009
