1 ml solution for injection contains: bupivacaine hydrochloride 5 mg.
Excipients/Inactive Ingredients: Glucose monohydrate 80 mg, sodium hydroxide/hydrochloric acid (to pH 4.0-6.0), water for injections to 1 ml.
Pharmacotherapeutic group (ATC code): N01B B01.
Pharmacology: Pharmacodynamics: Marcain Spinal Heavy contains bupivacaine, which is a long-acting local anaesthetic of the amide type. Bupivacaine reversibly blocks impulse conduction in the nerves by inhibiting the transport of sodium ions through the nerve membrane. Similar effects can also be seen on excitatory membranes in the brain and myocardium.
Marcain Spinal Heavy is intended for hyperbaric spinal anaesthesia. The relative density of the solution for injection is 1.026 at 20°C (equivalent to 1.021 at 37°C) and the initial distribution into the subarachnoid space is markedly influenced by gravity.
For administration into the spine, a small dose is given, which gives a relatively low concentration and short duration of effect.
Pharmacokinetics: Bupivacaine is very liposoluble with an oil/water distribution coefficient of 27.5.
Bupivacaine displays complete and bi-phasic absorption from the subarachnoid space, with half-lives for the two phases of approx. 50 and approx. 400 minutes, with large variations. The slow absorption phase is the rate-determining factor in the elimination of bupivacaine, which explains why the apparent half-life is longer than after intravenous administration.
Absorption from the subarachnoid space is relatively slow, which, in combination with the low dose required for spinal anaesthesia, gives a relatively low plasma concentration (approx. 0.4 mg/ml per 100 mg injected).
After intravenous administration, total plasma clearance is approx. 0.58 l/min, the volume of distribution in steady state is approx. 73 l, the elimination half-life is 2.7 hours, and the hepatic extraction ratio is approx. 0.40. Bupivacaine is metabolised almost completely in the liver, predominantly through aromatic hydroxylation to 4-hydroxybupivacaine and N-dealkylation to PPX, both of which are mediated by cytochrome P450 3A4. Clearance is thus dependent on hepatic perfusion and the activity of the metabolising enzyme.
Bupivacaine crosses the placenta and the concentration of free bupivacaine is the same in the mother and the foetus. However, the total plasma concentration is lower in the foetus, which has a lower degree of protein binding.
Toxicology: Pre-Clinical Safety Data: There are no preclinical data of relevance for an evaluation of safety other than what has already been mentioned in this monograph.
Spinal anaesthesia for surgery, e.g. urological surgery and surgery on the lower limbs lasting 2-3 hours, abdominal surgery lasting 45-60 minutes.
Marcain Spinal Heavy should only be used by clinicians with experience of regional anaesthesia or under their supervision. The lowest possible dose for adequate anaesthesia should be used.
The doses given as follows are guides for adults and the dosage should be adjusted to the individual patient.
The dose should be reduced in the elderly and in patients in the late stages of pregnancy. (See Table 1).
Click on icon to see table/diagram/image
The recommended site of injection is below L3-L4 intervertebral space. There is currently no experience of doses higher than 20 mg.
A spinal injection is given only after the subarachnoid space has been clearly identified by means of lumbar puncture (clear cerebrospinal fluid runs out via the spinal needle or is seen on aspiration). In the event of unsuccessful anaesthesia, a new attempt to administer the drug should only be made by injecting at a different level and with a smaller volume. One cause of lack of effect may be poor intrathecal distribution of the drug, and this can be helped by altering the patient's position.
Symptoms and Signs: Bupivacaine can cause acute toxic effects of a central nervous and cardiovascular nature if it is given in high doses, especially if it is administered intravascularly. However, the dose used in spinal anaesthesia is low (≤20 % of the dose used for epidural anaesthesia) and thus the risk of overdosage is unlikely. In cases of concomitant administration with other local anaesthetics, however, systemic toxic effects may occur, as the toxic effects are additive.
Treatment: In cases of total spinal blockade adequate ventilation must be ensured (patent airways, oxygen, intubation and controlled ventilation if necessary). If there is a fall in blood pressure a vasopressor (preferably with an inotropic effect) should be given, e.g. ephedrine 5-10 mg intravenously.
If signs of acute systemic toxicity occur the administration of local anaesthetics must be stopped immediately. Treatment must be given to maintain good ventilation, oxygenation and circulation. Oxygen must always be given, and assisted ventilation if necessary. If convulsions do not cease spontaneously within 15-20 seconds, thiopentone sodium 1-3 mg/kg should be given intravenously to facilitate ventilation or diazepam 0.1 mg/kg intravenously (acts rather more slowly). Prolonged seizures jeopardise the patient's respiration and oxygenation. Injection of muscle relaxants (e.g. suxamethonium 1 mg/kg) creates more favourable conditions for ventilation and oxygenation of the patient, but requires experience of tracheal intubation and controlled ventilation. In cases of a fall in blood pressure/bradycardia, a vasopressor should be given (e.g. ephedrine 5-10 mg intravenously, which may be repeated after 2-3 minutes).
In the event of circulatory arrest, cardiopulmonary resuscitation should be instituted immediately. It is important to maintain good oxygenation, respiration and circulation, and to treat acidosis.
Children must be given doses in proportion to their age and bodyweight for treatment of systemic toxicity.
Hypersensitivity to local anaesthetics of the amide type, or to any of the excipients.
General contraindications related to intrathecal anaesthesia should be taken into account.
Acute active disease of the central nervous system, such as meningitis, tumours, poliomyelitis and cranial haemorrhage.
Spinal stenosis and active disease (e.g., spondylitis, tumour) or recent trauma (e.g., fracture) in the vertebral column.
Pernicious anaemia with subacute combined degeneration of the Spinal cord.
Pyogenic infection of the skin at or adjacent to the site of puncture.
Cardiogenic or hypovolaemic shock.
Coagulation disorders or ongoing anticoagulant treatment.
One should be aware that spinal anaesthesia can sometimes lead to major blocks, with paralysis of intercostal muscles and the diaphragm, especially in pregnant women.
Caution should be exercised in patients with degree II or III AV block since local anaesthetics can lower the conduction capacity of the myocardium.
Elderly patients and patients with severe hepatic disease, severely impaired renal function or in poor general condition also require special attention.
Patients treated with class III anti-arrhythmic drugs (e.g. amiodarone) should be closely observed and ECG monitoring should be considered, since the cardiac effects of bupivacaine and class III anti-arrhythmic drugs can be additive.
Intrathecal anaesthesia can lead to hypotension and bradycardia. The risk of such effects can be reduced by e.g. injection of a vasopressor. Hypotension should be treated immediately with administration of an intravenous sympathomimetic, and repeated if required.
Like all local anaesthetic drugs, bupivacaine can cause acute central nervous and cardiovascular toxic effects in cases of use leading to high concentrations in the blood. This applies particularly after inadvertent intravascular administration.
Ventricular arrhythmia, ventricular fibrillation, sudden cardiovascular collapse and death have been reported in association with high systemic concentrations of bupivacaine. However, with the doses normally used for spinal anaesthesia high systemic concentrations are uncommon.
An uncommon, but dangerous, side effect in spinal anaesthesia is extensive or total spinal blockade, which results in cardiovascular depression and respiratory depression. The cardiovascular depression is caused by extensive sympathetic blockade, which can result in hypotension and bradycardia, or even cardiac arrest. Respiratory depression can be caused by blockade of the innervation of the respiratory muscles, including the diaphragm.
There is an increased risk of extensive or total spinal blockade in elderly patients and patients in late stages of pregnancy. The dose should therefore be reduced for these patients.
In rare cases spinal anaesthesia can cause neurological damage, resulting in paraesthesia, anaesthesia, motor weakness and paralysis. Neurological disorders, such as multiple sclerosis, hemiplegia, paraplegia and neuromuscular disturbances are not thought to be adversely affected by spinal anaesthesia, but caution should be exercised.
Effects on Ability to Drive and Use Machines: Depending on the dose and method of administration, bupivacaine can have a transient effect on movement and coordination.
Pregnancy: No known risks for the foetus from use during pregnancy.
However, note that the dose should be reduced for patients in late stages of pregnancy. (See also Precautions.)
Lactation: Bupivacaine passes into breast milk, but the risk of this affecting the child appears unlikely with therapeutic doses.
Undesirable effects caused by the product itself can be difficult to distinguish from the physiological effects of the nerve block (e.g., fall in blood pressure, bradycardia, temporary urinary retention), events caused directly by the needle puncture (e.g., spinal haematoma) or caused indirectly by the needle puncture (e.g., meningitis, epidural abscess) or events associated with leakage of cerebrospinal leakage (e.g., post lumbar puncture headache). (See Table 2).
Click on icon to see table/diagram/image
Bupivacaine should be used with caution in patients receiving other local anaesthetics or agents structurally similar to local anaesthetics, i.e. class IB anti-arrhythmic drugs, as the systemic toxic effects are additive.
Specific interaction studies with bupivacaine and anti-arrhythmic drugs class III (e.g., amiodarone) have not been performed, but caution should be advised (see also Precautions).
Instructions for Use/Handling: The solution must be used as soon as possible after the ampoule has been opened.
Incompatibilities: Additions to Spinal solutions are not recommended.
Store below 30°C.
Do not freeze.
N01BB01 - bupivacaine ; Belongs to the class of amides. Used as local anesthetics.
Soln for inj 5 mg/mL (clear, colourless solution in amp) x 4 mL x 5's.