Sergivell Plain/Sergivell Iso

Sergivell Plain: Each ampoule (4 mL) solution contains: Bupivacaine hydrochloride 20 mg.
Clear, colourless liquid, practically free from visible particles.
Sergivell Iso: Each ampoule (10 mL) solution contains: Bupivacaine hydrochloride Ph. Eur. 50mg, Sodium chloride 80 mg, Sodium hydroxide, as 0.1 M solution and/or hydrochloric acid, as 0.1M solution (for pH adjustment), Water for injections 10mL.
Clear colourless liquid.

Pharmacotherapeutic group: Local anesthetics, amides.
Pharmacology: Pharmacodynamics: Sergivell Plain: Bupivacaine is a long acting local anaesthetic agent of the amide type.
Moderate muscular relaxation of lower extremities.
Motor blockade of the abdominal muscles.
Bupivacaine Hydrochloride is hyperbaric and its initial spread in the intrathecal space is affected by gravity.
Sergivell Iso: Bupivacaine hydrochloride is a long-acting local anesthetic of the amide type with both anesthetic and analgesic effects. At high doses, it produces surgical anesthesia, at lower doses it produces sensory blockade (analgesia) with a less pronounced motor blockade.
Onset and duration of the local anesthetic effect of bupivacaine depend on the dose and the site of administration.
Bupivacaine, like other local anesthetics, causes a reversible blockade of impulse propagation along nerve fibers by preventing the inward movement of sodium ions through the cell membrane of the nerve fibers. The sodium channels of the nerve membrane are considered a receptor for local anesthetic molecules.
Local anesthetics may have similar effects on the other excitable membranes, e.g. in the brain and myocardium. If excessive amounts of the drug reach the systemic circulation, symptoms and signs of acute toxicity may occur, especially central and cardiovascular.
Central nervous system toxicity usually precedes the cardiovascular effects as central nervous system toxicity occurs at lower plasma concentrations of anesthetic. Direct effects of local anesthetics on the heart include negative dromotropic and negative inotropic effects and eventually cardiac arrest.
Indirect cardiovascular effects (hypotension, bradycardia) may occur after epidural administration depending on the extent of the concomitant sympathetic blockade.
Pharmacokinetics: Pediatric population: Pharmacokinetics of bupivacaine in children is similar to that in adults.
Sergivell Plain: Rapid onset of action and long duration i.e. T10-T12 segments-duration 2-3 hours.
Muscular relaxation of lower extremities lasts 2-2.5 hours.
Blockade of the abdominal muscles lasts 45-60 minutes. The duration of motor blockade does not exceed duration of analgesia.
Sergivell Iso: Bupivacaine has a value of dissociation constant (pKa)=8.2 and a value of partition coefficient (D)=348 (25°C n-octanol/phosphate buffer pH 7.4). The metabolites have less pharmacological activity than bupivacaine.
Absorption: The plasma concentration of bupivacaine depends on the administered dose, the route of administration, and vascularity in the injection site.
Bupivacaine shows complete biphasic absorption from the epidural space with half-lives in the order of 7 min and 6 h respectively. The slow absorption is rate-limiting in the elimination of bupivacaine, which explains why the apparent half-life after epidural administration is longer than that after intravenous administration.
Distribution: Bupivacaine has a total plasma clearance of 0.58 L/min, a volume of distribution at a steady state of 73 L, a terminal half-life (t_1/2) of 2.7 hours, and an intermediate hepatic extraction ratio of 0.38 after intravenous administration. It is mainly bound to alpha-acid glycoprotein with plasma binding of 96%. Clearance of bupivacaine is almost entirely due to liver metabolism and it is more sensitive to changes in intrinsic hepatic enzyme function than to liver perfusion.
An increase in total plasma concentration has been observed during continuous epidural infusion. It is a consequence of a postoperative increase in alpha 1-acid glycoprotein in plasma. The unbound, i.e. pharmacologically active, concentration is similar before and after surgery.
Bupivacaine readily crosses the placenta barrier and equilibrium with regard to the concentration of the unbound fraction is rapidly reached. The degree of plasma protein binding in the fetus is less than in the mother, which results in lower total plasma concentrations in the fetus.
Biotransformation: Bupivacaine is extensively metabolized in the liver, predominately by aromatic hydroxylation to 4 hydroxy bupivacaine and N-dealkylation to pipecoloxylidide (PPX), both mediated by cytochrome P450 3A4.
Elimination: About 1% of bupivacaine is excreted in the urine as an unchanged drug in 24 h and approximately 5% as PPX. The plasma concentrations of PPX and 4-hydroxy-bupivacaine during and after continuous administration are low compared to the parent medicine.

Sergivell Plain: Bupivacaine Hydrochloride (Sergivell Plain) 5 mg/mL solution for injection is indicated in adults and children of all ages for intrathecal (subarachnoid) spinal anaesthesia for surgery (urological and lower limb surgery lasting 2-3 hours, abdominal surgery lasting 45-60 minutes).
Bupivacaine is a long-acting anaesthetic agent of the amide type. Bupivacaine Hydrochloride has a rapid onset of action and long duration. The duration of analgesia in the T10-T12 segments is 2-3 hours.
Bupivacaine Hydrochloride produces a moderate muscular relaxation of the lower extremities lasting 2-2.5 hours. The motor blockade of the abdominal muscles makes the solution suitable for the performance of abdominal surgery lasting 45-60 minutes. The duration of the motor blockade does not exceed the duration of analgesia. The cardiovascular effects of Bupivacaine Hydrochloride are similar to or less than those seen with other spinal agents. Bupivacaine 5 mg/mL with glucose 80 mg/mL is exceptionally well tolerated by all tissues with which it comes in contact.
Sergivell Iso: Bupivacaine hydrochloride is used for the production of local anesthesia by percutaneous infiltration, peripheral nerve block(s), and central neural block (caudal or epidural), that is, for specialist use in situations where prolonged anesthesia is required because sensory nerve block is more marked than motor block, Bupivacaine hydrochloride is especially useful in the relief of pain, e.g. during labor. Bupivacaine hydrochloride is indicated for: Surgical anesthesia in adults and children above 12 years of age.
Management of acute pain in adults and children above 1 year of age.

Sergivell Plain: Adults and children above 12 years of age: The dose recommended below should be regarded as a guide for use in the average adult.
The figures reflect the expected average dose range needed. Standard textbooks should be consulted for factors affecting specific block techniques and for individual patient requirements.
The clinician's experience and knowledge of the patient's physical status are of importance in calculating the required dose. The lowest dose required for adequate anaesthesia should be used. Individual variations in onset and duration occur, and the extent of the spread of anaesthesia may be difficult to predict, but will be affected by the volume of the drug used, especially with isobaric (plain) solution.
Dosage recommendations: Intrathecal anaesthesia for surgery: 2-4mL (10-20 mg bupivacaine hydrochloride).
The dose should be reduced in elderly patients and patients in the late stages of pregnancy (see Precautions).
Paediatric population: Neonates, infants and children up to 40 kg: One of the differences between young children and adults is a relatively large volume of CSF in infants and neonates, requiring relatively higher dose/kg to produce the same level of nerve block as compared to adults.
Procedures of regional anaesthesia in children should be performed by qualified clinicians who are familiar with this population and techniques. The doses in the table 1 should be regarded as guidelines for use in paediatric patients. There are individual variations. Standard textbooks should be consulted for factors affecting specific block technique and for individual patient requirements. The lowest dose required for adequate anaesthesia should be used. (See Table 1.)

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The spread of anaesthesia obtained with Bupivacaine Hydrochloride depends on several factors including the volume of solution and the position of the patient during and following the injection.
When injected at the L3-L4 intervertebral space, with the patient in the sitting position, 3 mL of Bupivacaine Hydrochloride spreads to the T7-T10 spinal segments. With the patient receiving the injection in the horizontal position and then turned supine, the blockade spreads to T4-T7 spinal segments. It should be understood that the level of spinal anaesthesia achieved with any local anaesthetic can be unpredictable in a given patient. The recommended site of injection is below L3.
The effects of injections of Bupivacaine Hydrochloride exceeding 4 mL have not yet been studied and such volumes can therefore not be recommended.
Mode of administration: For intrathecal use.
Sergivell Iso: Adults and children above 12 years of age: The following Table 1 is a guide to dosage for the most commonly used techniques in the average adult. The figures reflect the expected average dose range needed. Standard textbooks should be consulted for factors affecting specific block techniques and for individual patient requirements.
N.B. When prolonged blocks are used, either by continuous infusion or by repeated bolus administration, the risks of reaching a toxic plasma concentration or inducing a local neural injury must be considered.
The clinician's experience and knowledge of the patient's physical status are important in calculating the required dose. The lowest dose required for adequate anesthesia should be used. Individual variations in onset and duration occur.
Warning: There is a risk of systemic effects of adrenaline in the case of a case of administration of high volumes of solutions of anesthetic with adrenaline. (See Table 2.)

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In general, surgical anesthesia (e.g. epidural administration) requires a higher concentration and dose of a local anesthetic. When a less intense nerve block is required (e.g.in the relief of labor pain), the use of a lower concentration of anesthetic is indicated. The volume of medicinal products will affect the extent of the spread of anesthesia.
In order to avoid intravascular injection, aspiration should be repeated prior to and during administration of the main dose, which should be injected slowly or in incremental doses, at a rate of 25-50 mg/min, while closely observing the patient's vital functions and maintaining verbal contact. An inadvertent intravascular injection may be recognized by a temporary increase in heart rate and an accidental intrathecal injection by signs of a spinal block. If toxic symptoms occur, the injection should be stopped immediately.
Current experience indicates that 400 mg of bupivacaine administered over 24 hours is well-tolerated dose in the average adult.
Pediatric population 1 to 12 years of age: Pediatric regional anesthetic techniques should be performed by a qualified physician who is familiar with this population and the technique.
The doses listed in Table 2 should be regarded as guidelines for use in pediatrics. There are individual variations. In children with a high body weight is often necessary to reduce the dose gradually working with the assumption of the ideal body weight. Standard textbooks should be consulted for factors affecting specific block techniques and for individual patient requirements.
The lowest dose required for adequate analgesia should be used. (See Table 3.)

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The dose required for children should be calculated on the basis of knowledge of body weight up to a dose of 2 mg/kg.
In order to avoid intravascular injection, aspiration should be repeated prior to and during the administration of the main dose. The dose should be injected slowly in incremental doses, particularly in the lumbar and thoracic epidural routes, constantly and closely observing the patient's vital functions.
Peritonsillar infiltration has been performed in children above 2 years of age with bupivacaine 2.5 mg/mL at a dose of 7.5-12.5 mg per tonsil.
Ilioinguinal-iliohypogastric blocks have been performed in children aged 1 year or older with bupivacaine 2.5 mg/mL at a dose of 0.1-0.5 mL/kg, equivalent to 0.25-1.25 mg/kg. In children aged 5 years or older bupivacaine 5 mg/mL was administered at a dose of 1.25-2 mg/kg.
For penile blocks bupivacaine 5 mg/mL has been used at a total dose of 0.2-0.5 mL/kg, equivalent to 1-2.5 mg/kg.
Safety and efficacy of this medicine with or without adrenaline in children aged up to 1 year have not been established. Only limited data are available.
Safety and efficacy of intermittent epidural bolus injections or continuous epidural infusion have not been established. Only limited data are available.
Mode of administration: For peripheral nerve block, caudal block, and lumbar epidural block.

Sergivell Plain: At the recommended use of the medicine, it is unlikely to reach toxic systemic concentrations of the active ingredient. However, when administered concurrently to other local anaesthetics there is a summation of toxic effects and systemic toxic reactions may occur (see Acute systemic toxicity and Treatment of acute systemic toxicity under Adverse Reactions).
Sergivell Iso: Accidental intravascular injections of local anesthetics may cause immediate (within seconds to a few minutes) systemic toxic reactions. In the event of an overdose, systemic toxicity appears later (15-60 minutes after injection) due to the slower increase in local anesthetic blood concentration.

Hypersensitivity to the active substance or to any of the excipients.
Hypersensitivity to local anesthetics of the amide-type.
Intrathecal or Epidural anesthesia, regardless of the local anesthetic used, has its own contraindications which include: active disease of the central nervous system such as meningitis, poliomyelitis; intracranial hemorrhage: sub-acute combined degeneration of the spinal cord due to pernicious anemia and cerebral and spinal tumor; pyogenic infection of the skin at or adjacent to the site of lumbar puncture; cardiogenic or hypovolemic shock coagulation disorders or ongoing anticoagulation treatment.
Sergivell Plain: Spinal stenosis and active disease (e.g. spondylitis, tuberculosis, tumor) or recent trauma (e.g. fracture) in the vertebral column.
Sergivell Iso: This medicine is contraindicated for intravenous regional anesthesia (Bier's-block) because unintentional leakage of bupivacaine into the systemic circulation can cause manifestations of systemic toxicity. Tuberculosis of the spine.

Like all local anesthetics, bupivacaine may cause acute toxicity effects on the central nervous and cardiovascular systems if utilized for local anesthetic procedures resulting in high blood concentrations of the drug. This is especially the case after unintentional intravascular administration or injection into highly vascular areas. Ventricular arrhythmia, ventricular fibrillation, sudden cardiovascular collapse, and death have been reported in connection with high systemic concentrations of bupivacaine.
Adequate resuscitation equipment should be available whenever local or general anesthesia is administered. The clinician responsible should take the necessary precautions to avoid intravascular injection. Before any nerve block is attempted, intravenous access for resuscitation purposes should be established. Clinicians should have received adequate and appropriate training in the procedure to be performed and should be familiar with the diagnosis and treatment of side effects, systemic toxicity, or other complications.
Patients treated with anti-arrhythmic agents class III (e.g. amiodarone) should be under close surveillance and ECG monitoring, since cardiac effects may be additive.
The physiological effects generated by a central neural blockade are more pronounced in the presence of hypotension. Patients with hypovolemia due to any cause can develop sudden and severe hypotension during epidural anesthesia.
Effects on ability to drive and use machines: Bupivacaine hydrochloride has a minor influence on the ability to drive and use machines. Besides the direct anesthetic effect, local anesthetics may have a very mild effect on mental function and coordination even in the absence of overt CNS toxicity, and may temporarily impair locomotion and alertness.
Sergivell Plain: Intrathecal anaesthesia should only be undertaken by clinicians with the necessary knowledge and experience.
Should cardiac arrest occur, a successful outcome may require prolonged resuscitative efforts. High systemic concentrations are not expected with doses normally used for intrathecal anesthesia.
There is an increased risk of high or total spinal blockade, resulting in cardiovascular and respiratory depression, in the elderly and in patients in the late stages of pregnancy. The dose should therefore be reduced in these patients.
Intrathecal anaesthesia with any local anaesthetic can cause hypotension and bradycardia which should be anticipated and appropriate precautions taken. These may include preloading the circulation with crystalloid or colloid solution. If hypotension develops it should be treated with a vasopressor such as ephedrine 10-15 mg intravenously. Severe hypotension may result from hypovolaemia due to haemorrhage or dehydration, or aorto-caval occlusion in patients with massive ascites, large abdominal tumours or late pregnancy. Marked hypotension should be avoided in patients with cardiac decompensation.
Patients with hypovolaemia due to any cause can develop sudden and severe hypotension during intrathecal anaesthesia.
Intrathecal anaesthesia can cause intercostal paralysis and patients with pleural effusions may suffer respiratory embarrassment. Septicaemia can increase the risk of intraspinal abscess formation in the postoperative period.
Neurological injury is a rare consequence of intrathecal anaesthesia and may result in paraesthesia, anaesthesia, motor weakness and paralysis. Occasionally these are permanent.
Before treatment is instituted, consideration should be taken if the benefits outweigh the possible risks for the patient.
Patients in poor general condition due to ageing or other compromising factors such as partial or complete heart conduction block, advanced liver or renal dysfunction require special attention, although regional anaesthesia may be the optimal choice for surgery in these patients.
Sergivell Iso: There have been reports of cardiac arrest or death during the use of bupivacaine for epidural anesthesia or peripheral nerve blockade, we despite apparently adequate preparation and appropriate management.
Major peripheral nerve blocks may require the administration of a large volume of local anesthetic in highly vascularised areas and/or areas with a higher risk of systemic absorption which may lead to increased plasma concentration of the medicine.
Overdosage or accidental intravenous injection may give rise to toxic reactions.
Injection of repeated doses of bupivacaine hydrochloride may cause significant increases in blood levels with each repeated dose due to the slow accumulation of the drug. Tolerance varies with the status of the patient. Although regional anesthesia is frequently considered an optimal anesthetic technique, some patients require special attention in order to reduce the risk of serious side effects: The elderly and patients in poor general condition should be given reduced doses commensurate with their physical status.
Patients with partial or complete heart block due to the fact that local anesthetics may depress myocardial conduction.
Patients with advanced liver disease and severe renal dysfunction.
Patients in the late stages of pregnancy.
Patients allergic to ester-type local anesthetic drugs (procaine, tetracaine, benzocaine, etc.) have not shown cross-sensitivity to agents of the amide type such as bupivacaine.
Certain local anesthetic procedures may be associated with serious adverse reactions, regardless of the local anesthetics used.
Local anesthetics should be used with caution for epidural anesthesia in patients with impaired cardiovascular function since they may be less able to compensate for functional changes associated with the prolongation of A-V conduction produced by these drugs.
Epidural anesthesia should therefore be avoided or used with caution in patients with untreated hypovolemia or significantly impaired venous return. Retrobulbar injections may very rarely the cranial subarachnoid space causing temporary blindness, cardiovascular collapse, apnoea, convulsions, etc.
Retro-and perbulbar injections of local anesthetic may cause a low risk of persistent ocular muscle dysfunction. The primary causes include trauma and/or local toxic effects on muscles and/or nerves. The severity of such issue reaction is related to the degree of trauma, the concentration of the local anesthetic, and the duration of exposure of the tissue to the local anesthetic. For this reason, as with all local anesthetics, the lowest effective concentration and dose of local anesthetic should be used.
Vasoconstrictors may aggravate tissue reactions and should be used only when indicated.
Small doses of local anesthetics injected into the head and neck, including retrobulbar dental and stellate ganglion blocks, may produce systemic toxicity due to inadvertent intra-arterial injection.
Paracervical block may have a greater adverse effect on the fetus than other nerve blocks used in obstetrics. Due to the systemic toxicity of bupivacaine special care should be taken when using bupivacaine for paracervical block.
There have been post-marketing reports of chondrolysis in patients receiving post-operative intraarticular continuous infusion of local anesthetics. The majority of reported cases of chondrolysis have involved the shoulder joint. Due to multiple contributing factors and inconsistency in the scientific literature regarding the mechanism of this action, causality has not been established. Intraarticular continuous infusion is not an approved indication for Bupivacaine hydrochloride (Sergivell iso).
Epidural anesthesia with any local anesthetic can cause hypotension and bradycardia which should be anticipated and appropriate precautions are taken. The risk of such effects can be reduced, e.g. by injection of vasopressor agents.
Hypotension should be managed urgently by intravenous administration of sympathomimetic, repeated as necessary Severe hypotension may result from hypovolemia due to hemorrhage or dehydration, or aortocaval occlusion in patients with massive ascites, large abdominal tumors, or late pregnancy. Marked hypotension should be avoided in patients with cardiac decompensation.
Patients with hypovolaemia due to any cause can develop sudden and severe hypotension during epidural anesthesia.
Epidural anesthesia can cause intercostal paralysis and patients with pleural effusions may suffer respiratory embarrassment. Septicemia can increase the risk of intraspinal abscess formation in the postoperative period.
When bupivacaine is administered as an intraarticular injection, caution is advised when recent major intra-articular trauma is suspected or extensive raw surfaces within the joint have been created by the surgical procedure, as that may accelerate the absorption and result in higher plasma concentrations of the anesthetic.
Use in Children: Safety and efficacy of this medicine in children aged up to 1 year have not been established. Only limited data are available.
The use of bupivacaine for intraarticular block in children 1 to 12 years of age has not been documented.
The use of bupivacaine for major nerve blocks in children 1 to 12 years of age has not been documented.
Epidural anesthesia in children should be given by gradual doses corresponding with their age and body weight as especially epidural anesthesia at the thoracic route may result in severe hypotension and respiratory impairment.

Pregnancy: There is no evidence of untoward effects in human pregnancy. In large doses, there is evidence of decreased pup survival in rats and an embryological effect in rabbits if bupivacaine is administered in pregnancy, Bupivacaine should not, therefore, be given in early pregnancy unless the benefits are considered to outweigh the risks.
Sergivell Plain: It should be noted that the dose should be reduced in patients in the late stages of pregnancy, see Precautions.
Sergivell Iso: Fetal adverse effects due to local anesthetics, such as fetal bradycardia (negative chronotropic effect of a local anesthetic on the myocardium of the fetus and vasoconstriction of uterine blood vessels) seem to be most apparent in paracervical block anesthesia. Such effects may be due to high concentrations of anesthetic reaching the fetus.
Lactation: Bupivacaine is excreted into the mother's milk but in such small quantifies that there is no risk of affecting the child at therapeutic dose levels.

Paediatric population: Adverse drug reactions in children are similar to those in adults, however, in children early signs of local anaesthetic toxicity may be difficult to detect in cases where the nerve block is given during sedation or general anaesthesia.
Sergivell Plain: Tabulated list of adverse reactions: Adverse effect profile of this medicine is similar to those for long acting local anaesthetics used for intrathecal technique.
Frequencies (see Table 4) are defined as very common (1/10), common (1/100 to <1/10), uncommon (1/1000 to <1/100), rare (1/10,000 to <1/1000), very rare (<1/10,000) or not known (cannot be estimated from the available data). (See Table 4.)

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Adverse reactions caused by the drug per se are difficult to distinguish from the physiological effects of the nerve block (e.g. decrease in blood pressure, bradycardia, temporary urinary retention), events caused directly (e.g. spinal haematoma) or indirectly (e.g. meningitis, epidural abscess) by needle puncture or events associated to cerebrospinal leakage (e.g. postdural puncture headache).
Acute systemic toxicity: Bupivacaine Hydrochloride, used as recommended, is unlikely to reach blood levels high enough to cause systemic toxicity. However, if other local anaesthetics are concomitantly administered, toxic effects are additive and may cause systemic toxic reactions.
Systemic toxicity is rarely associated with spinal anaesthesia but might occur after accidental intravascular injection. Systemic adverse reactions are characterised by numbness of the tongue, light-headedness, dizziness and tremors, followed by convulsions and cardiovascular disorders.
Treatment of acute systemic toxicity: No treatment is required for milder symptoms of systemic toxicity but if convulsions occur then it is important to ensure adequate oxygenation and to arrest the convulsions if they last more than 15-30 seconds. Oxygen should be given by face mask and the respiration assisted or controlled if necessary. Convulsions can be arrested by injection of thiopental 100-150 mg intravenously or with diazepam 5-10 mg intravenously. Alternatively, succinylcholine 50-100 mg intravenously may be given but only if the clinician has the ability to perform endotracheal intubation and to manage a totally paralysed patient.
High or total spinal blockade causing respiratory paralysis should be treated by ensuring and maintaining a patent airway and giving oxygen by assisted or controlled ventilation.
Hypotension should be treated by the use of vasopressors, e.g. ephedrine 10-15 mg intravenously and repeated until the desired level of arterial pressure is reached. Intravenous fluids, both electrolytes and colloids, given rapidly can also reverse hypotension.
Sergivell Iso: Accidental sub-arachnoid injection can lead to very high spinal anesthesia possibly with apnoea and severe hypotension.
Adverse drug reactions profile of this medicine is similar to those of other long-acting local anesthetics. Undesirable effects caused by the medicine per se are difficult to distinguish from the physiological manifestations of nerve blockade (e.g. decrease in blood pressure, bradycardia), from direct (e.g. traumatization of the nerve) or indirect effects (e.g. epidural abscess), caused by needle puncture. Neurological damage is a rare but well-known complication of regional, particularly epidural and spinal anesthesia. It may be due to several causes, e.g. direct injury to the spinal cord or spinal nerves, anterior spinal artery syndrome, injection of an irritant substance, or an injection of a non-sterile solution. These may result in localized areas of paraesthesia or anesthesia, motor weakness, loss of sphincter control, and paraplegia. Occasionally these are permanent.
Adverse drug reactions are presented in Table 5 according to the MedDRA system organ classes and MedDRA frequency convention: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000). (See Table 5.)

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Hepatic dysfunction, with reversible increases of SGOT (serum glutamic-oxaloacetic transaminase), SGPT (serum glutamic pyruvic transaminase), alkaline phosphates, and bilirubin, has been observed following repeated injections or long-term infusions of bupivacaine. If signs of hepatic dysfunction are observed during treatment with bupivacaine, the medicine should be discontinued.
Acute systemic toxicity: Systemic toxic reactions primarily involve the central nervous system (CNS) and the cardiovascular system. Such reactions are caused by high plasma concentrations of a local anesthetic, which may appear due to accidental intravascular injection, overdose, or exceptionally rapid absorption from highly vascularised areas. CNS reactions are similar for all local anesthetics of the amide type, while cardiac reactions are more dependent on the type of medicine, both qualitatively and quantitatively.
Central manifestations of toxicity usually come before cardiovascular manifestations. The exceptions are patients under general anesthesia or patients under sedation with barbiturates or benzodiazepines. Central nervous system toxicity is a graded response with symptoms and signs of escalating severity The first symptoms are usually light-headedness, circumoral paraesthesia, numbness of the tongue, hyperacusis, tinnitus, and visual disturbances. Dysarthria, muscular twitching, or tremors are more serious and precede the onset of generalized convulsions. These signs must not be mistaken for neurotic behavior. Unconsciousness and grand mal convulsions may follow, which may last from a few seconds to several minutes. Hypoxia and hypercarbia occur rapidly following convulsions due to increased muscular activity, together with interference with respiration and possible loss of functional airways. In severe cases, apnoea may occur Acidosis, hyperkalemia, and hypoxia increase and extend the toxic effect of local anesthetics.
Recovery is due to the redistribution of the local anesthetic drug from the central nervous system and subsequent metabolism and excretion. Recovery may be rapid unless large amounts of the medicine have been injected.
Cardiovascular system toxicity may be seen in severe cases and is generally preceded by signs of toxicity in the central nervous system. In patients under heavy sedation or receiving a general anesthetic, prodromal CNS symptoms may be absent. Hypotension, bradycardia, arrhythmia, and even cardiac arrest may occur as a result of high systemic concentrations of local anesthetics, but in rare cases, cardiac arrest has occurred without prodromal CNS effects.
Treatment of acute toxicity: If signs of acute systemic toxicity appear, injection of the local anesthetic should be discontinued immediately.
Treatment of a patient with systemic toxicity consists of arresting convulsions and ensuring adequate ventilation with oxygen, if necessary by assisted or controlled ventilation (respiration).
Once convulsions have been controlled and adequate ventilation of the lungs is ensured, no other treatment is generally required.
If cardiovascular depression occurs (hypotension, bradycardia) appropriate treatment with intravenous fluids, vasopressor, inotropic agents, and/or lipid emulsion should be considered. Children should be given doses commensurate with age and weight.
If a circulatory arrest should occur, immediate cardiopulmonary resuscitation should be instituted. Optimal oxygenation and ventilation and circulatory support as well as treatment of acidosis are of vital importance.
Cardiac arrest due to bupivacaine can be resistant to electrical defibrillation and resuscitation must be continued energetically for a prolonged period.
High or total spinal blockade causing respiratory paralysis and hypotension during epidural anesthesia should be treated by ensuring and maintaining a patent airway and giving oxygen by assisted or controlled ventilation.

Bupivacaine should be used with caution in patients receiving other local anesthetics or pharmaceuticals structurally similar to amide-type local anesthetics, e.g. certain antiarrhythmics, such as lidocaine and mexiletine since the systemic toxic effects are additive. Specific interaction studies with bupivacaine and anti-arrhythmic drugs class II (e.g. amiodarone) have not been performed, but caution should be advised.

Sergivell Iso: Discard unused portion.

Store at temperatures not exceeding 30°C. Do not freeze.
Shelf-life: 3 years.

Anaesthetics - Local & General

N01BB01 - bupivacaine ; Belongs to the class of amides. Used as local anesthetics.

Rx