Bupivacaine 5 mg / mL Solution for injection – Summary of Product Characteristics (SmPC) for healthcare professionals

1 NAME OF THE MEDICINAL PRODUCT

Bupivacaine 5 mg / mL Solution for injection

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each mL contains 5 mg bupivacaine hydrochloride anhydrous. Each 5-mL ampoule contains bupivacaine hydrochloride monohydrate equivalent to 25 mg bupivacaine hydrochloride anhydrous. Each 10-mL ampoule contains bupivacaine hydrochloride monohydrate equivalent to 50 mg bupivacaine hydrochloride anhydrous. Each 20-mL ampoule contains bupivacaine hydrochloride monohydrate equivalent to 100 mg bupivacaine hydrochloride anhydrous.

Excipient with known effect:

Each mL of Bupivacaine 5 mg / mL Solution contains 0.144 mmol (3.31 mg) of sodium.

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Solution for injection.

Clear, colourless solution.

pH: 4.0-6.5

Osmolality: 270 – 320 mOsm / kg

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Bupivacaine is indicated for:

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4.2 Posology and method of administration

Posology

The dosage varies and depends upon the area to be anaesthetised, the vascularity of the tissues, the number of neuronal segments to be blocked, individual tolerance and the technique of anaesthesia used.

Experience to date indicates a single dose of up to 150 mg bupivacaine hydrochloride. Doses of up to 50 mg 2-hourly may subsequently be used. A maximum dose of 2 mg / kg should not be exceeded in any four-hour period.

Adults and children above 12 years of age

The following table is a guide to dosage for the more 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 is important in calculating the required dose. The lowest dose required for adequate anaesthesia should be used. Individual variations in onset and duration occur.

Table 1 Dosage recommendations for adults

1. 1. Dose includes test dose.
2. 2. The dose for a major nerve block must be adjusted according to site of administration and patient status. Interscalene and supraclavicular brachial plexus blocks may be associated with a higher frequency of serious adverse reactions, regardless of the local anaesthetic used, see also section 4.4.
3. 3. In total ≤ 400 mg / 24 h.
4. 4. This solution is often used for epidural administration in combination with a suitable opioid for pain management. In total ≤ 400 mg / 24 h.
5. 5. If additional bupivacaine is used by any other techniques in the same patient, an overall dose limit of 150 mg should not be exceeded.
6. 6. There have been post-marketing reports of chondrolysis in patients receiving post-operative intra-articular continuous infusion of local anaesthetics. Bupivacaine is not approved for this indication (see also section 4.4).
7. 7.

   Bupivacaine without adrenaline.

   In general, surgical anaesthesia (e.g. epidural administration) requires the use of higher concentrations and doses. When a less intense block is required (e.g. in the relief of labour pain), the use of a lower concentration is indicated. The volume of drug used will affect the extent of spread of anaesthesia.

   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 recognised 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 (See section 4.8).

   Experience to date indicates that 400 mg administered over 24 hours is well tolerated in the average adult.

   Paediatric patients 1 to 12 years of age

   Paediatric regional anaesthetic procedures should be performed by qualified clinicians who are familiar with this population and the technique.

   The doses in the table should be regarded as guidelines for use in paediatrics. Individual variations occur. In children with a high body weight a gradual reduction of the dosage is often necessary and should be based on 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.

Table 2 Dosage recommendations for children 1 to 12 years of age

1. a) Thoracic epidural blocks need to be given by incremental dosage until the desired level of anaesthesia is achieved.
2. b)

   The onset and duration of peripheral nerve blocks depend on the type of block and the dose administered.

   In children the dosage should be calculated on a weight basis up to 2 mg / kg.

   In order to avoid intravascular injection, aspiration should be repeated prior to and during administration of the main dose. This 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. Children aged 5 years or older have received bupivacaine 5 mg / mL at a dose of 1.25 – 2 mg / kg.

   For penile blocks bupivacaine 5 mg / mL has been used at total doses of 0.2 – 0.5 mL / kg equivalent to 1 - 2.5 mg / kg.

   The safety and efficacy of Bupivacaine with and without adrenaline in children aged < 1 year of age have not been established. Only limited data are available.

   Safety and efficacy of intermittent epidural bolus injection or continuous infusion have not been established. Only limited data is available.

4.3 Contraindications

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4.4 Special warnings and precautions for use

t responded. However, in some instances resuscitation has proven impossible despite apparently adequate preparation and appropriate management.

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fibrillation, sudden cardiovascular collapse and death have been reported in connection with high systemic concentrations of bupivacaine.

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necessary precautions to avoid intravascular injection (see section 4.2).

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d appropriate training in the procedure to be performed and should be familiar

Major peripheral nerve blocks may require the administration of a large volume of local anaesthetic in areas of high vascularity, often close to large

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• The elderly and patients in poor general condition should be given reduced doses commensurate with their physical status.

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• Bupivacaine hydrochloride should be used with caution in patients with epilepsy, patients with advanced liver disease or severe renal dysfunction
• Patients in the late stages of pregnancy

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• The physiological effects generated by a central neural blockade are more pronounced in the presence of hypotension. Patients with hypovolaemia

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• Retro- and peribulbar injections of local anaesthetics carry a low risk of

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• Small doses of local anaesthetics injected into the head and neck, including retrobulbar, dental and stellate ganglion blocks, may produce systemic toxicity due to inadvertent intra-arterial injection.

• Injection of adrenaline containing bupivacaine in areas of end arteries

  (e.g. penile block, Oberst block) may cause ischemic tissue necrosis.

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• Epidural anaesthesia can cause intercostal paralysis and patients with pleural effusions may suffer respiratory embarrassment. Septicaemia can

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raw surfaces within the joint have been created by the surgical procedure,

Paediatric population

The use of bupivacaine for major nerve block in children 1 to 12 years of age has not been documented.

thoracic level may result in severe hypotension and respiratory impairment.

5 mL ampoules:

This medicinal product contains less than 1 mmol sodium (23 mg) per ampoule, that is to say essentially ‘sodium-free’.

10 mL and 20 mL ampoules:

This medicinal product contains 3.31 mg sodium per 1 mL, equivalent to 0.17% of the WHO

recommended maximum daily intake of 2 g sodium for an adult.

4.5 Interaction with other medicinal products and other forms of interaction

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Paediatric population

4.6 Fertility, pregnancy and lactation

Pregnancy

Foetal adverse effects due to local anaesthetics, such as foetal bradycardia, acidosis and damping of the central nervous system seem to be most apparent in paracervical block anaesthesia. Such effects may be due to high concentrations of anaesthetic reaching the foetus. (See section 4.4).

Breastfeeding

Bupivacaine is excreted into the mother's milk in small amount and it is poorly absorbed orally, thus adverse effects in breastfed infants are not anticipated. It is therefore possible to breastfeed after anaesthesia with bupivacaine. Based on the

e given to premature infants and infants at risk for apnoe, hypotonia and hypotension,

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Fertility

There are no data on the effect of bupivacaine hydrochloride on human fertility.

4.7 Effects on ability to drive and use machines

4.8 Undesirable effects

distinguish from the physiological effects of the nerve block (e.g. decrease in blood pressure, bradycardia), events caused directly (e.g. nerve trauma) or indirectly (e.g. epidural abscess) by needle puncture.

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Tabulated list of adverse reactions

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< 1/100), rare (

1/10,000, < 1/1,000), very rare (< 1/10,000) or not known (cannot be estimated from the available data).

Table 3

Table of Adverse Drug Reactions (ADR)

Paediatric population

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9 Overdose

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Acute systemic toxicity

Systemic toxic reactions primarily involve the central nervous system (CNS) and the cardiovascularsystem. Such reactions are caused by high blood concentrations of a

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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.

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r. Acidosis, hyperkalaemia and hypoxia increase and extend the toxic effects of local anaesthetics.

Recovery is due to redistribution of the local anaesthetic drug from the central nervous system and subsequent metabolism and excretion. Recovery may be rapid unless large amounts of the drug 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

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Treatment of Acute Toxicity

Treatment of a patient with systemic toxicity consists of arresting convulsions and

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5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Phamacotherapeutic group: Anesthetics, local; Amides; ATC code: N01BB01

Mechanism of action and Pharmacodynamic effects

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5.2 Pharmacokinetic properties

Absorption

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Bupivacaine shows complete and biphasic absorption from the epidural space with

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Distribution and Elimination

Bupivacaine has a total plasma clearance of 0.58 l/min, a volume of distribution at

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In children the pharmacokinetics are similar to that in adults.

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5.3 Preclinical safety data

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6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

6.2 Incompatibilities

6.3 Shelf life

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6.4 Special precautions for storage

Do not refrigerate or freeze.

For storage conditions after first opening / dilution of the medicinal product, see section 6.3.

6.5 Nature and contents of container

Polypropylene ampoules of 5 mL, 10 mL or 20 mL. Ampoules are placed in cartons. Pack sizes of 5, 10, 20 and 50 ampoules.

Polypropylene ampoules of 5 mL, 10 mL or 20 mL. Each ampoule is placed individually in a plastic polypropylene blister. Blisters are placed in cartons.

Pack sizes of 5, 10, 20 and 50 ampoules.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

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7 MARKETING AUTHORISATION HOLDER

Noridem Enterprises Limited

Evagorou & Makariou,

Mitsi Building 3, Office 115,

1065 Nicosia, Cyprus

8 MARKETING AUTHORISATION NUMBER(S)

PL 24598/0086

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION

Date of first authorisation: 14/01/2021

Date of latest renewal:

10 DATE OF REVISION OF THE TEXT

10/09/2026