Bupivacaine

Package leaflet: Information for the user

bupicain

2.5 mg/ml injection solution
5 mg/ml injection solution
10 mg/ml hyperbaric injection solution
bupivacaine hydrochloride
Generic medicine
Please read all of this leaflet carefully before you use this medicine as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not pass it on to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you get any side effects, including those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

1. What bupicain is and what it is used for
2. What you need to know before you are given bupicain
3. How to use bupicain
4. Possible side effects
5. How to store bupicain
6. Contents of the pack and other information

1. What is bupicain and what is it used for

Bupicain contains the active substance bupivacaine hydrochloride and belongs to a group of medicines called local anaesthetics, which are used before a surgical procedure to induce anaesthesia.
Bupicain can be used in all types of peripheral anaesthesia.
Bupicain is indicated, either alone or in combination with general anaesthesia (general anaesthesia), for procedures in:

• general surgery;
• bones and joints (orthopaedics);
• eyes (ophthalmology);
• ear, nose and throat (otorhinolaryngology);
• mouth and related structures (stomatology);
• genital organs and during childbirth (gynaecology-obstetrics);
• skin (dermatology).

Bupicain 2.5 mg/ml solution for injection and Bupicain 5 mg/ml solution for injection are indicated in adults and children above 12 years of age for surgical anaesthesia, and in adults and children above 1 year of age for acute pain.
Bupicain 10 mg/ml hyperbaric solution for injection is indicated in adults for spinal anaesthesia.

2. What you need to know before bupicain is administered to you

Do not be administered bupicain:

• if you are allergic to bupivacaine hydrochloride, to similar substances (such as amide-type local anesthetics), or to any of the other ingredients of this medicine (listed in section 6);
• if you are scheduled to undergo a type of regional anesthesia called a Bier Block.

If you are scheduled to undergo a type of anesthesia called intrathecal (bupicain 10 mg/ml
hyperbaric injectable solution), this medicine must not be administered to you if:

• you suffer from diseases of the central nervous system (such as meningitis, tumors, poliomyelitis, intracranial hemorrhage);
• you suffer from spinal diseases (such as spondylitis, tuberculosis, tumors), have an abnormally narrowed spinal canal (spinal stenosis) in any region of the spine, or have recently experienced trauma (such as fractures);
• you suffer from infections characterized by the presence of bacteria in the blood (septicemia);
• you have vitamin B12 deficiency (pernicious anemia), associated with spinal cord problems (subacute degeneration of the spinal cord);
• you have a bacterial skin infection (pyogenic) at or near the injection site;
• you have experienced heart function blockage (cardiogenic shock) or have reduced blood volume due to hemorrhage or fluid loss (hypovolemic shock);
• you suffer from coagulation disorders or are taking medicines used to prevent blood clotting (anticoagulants).

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before bupicain is administered to you.
Severe adverse effects, such as heart function blockage (cardiac arrest) or death, may occur with epidural anesthesia or peripheral nerve block.
Additionally, during treatment with bupicain, central nervous system, heart, and vascular problems (cardiovascular issues, ventricular arrhythmias, ventricular fibrillation, sudden cardiovascular collapse), and even death, may occur when this medicine is present in high concentrations in the blood—especially if accidentally injected into a blood vessel (intravascular injection) or into highly vascularized areas.
This medicine must be administered with great caution and under close medical supervision if:

• you are elderly or debilitated;
• you suffer from heart problems (partial or complete heart block), as this medicine may reduce heart contraction (cardiac conduction);
• you have advanced liver disease or severe kidney function impairment;
• you are in an advanced stage of pregnancy;
• you have reduced blood volume (hypovolemia), as this medicine, during intrathecal anesthesia (bupicain 10 mg/ml hyperbaric injectable solution), may cause a severe and sudden drop in blood pressure (hypotension);
• you are taking medicines used for heart rhythm disorders (class III antiarrhythmics), such as amiodarone; in this case, your doctor may decide to monitor heart function (via electrocardiogram) (see "Other medicines and bupicain");
• you suffer from nervous system disorders (multiple sclerosis, hemiplegia, paraplegia) or neuromuscular disorders and are scheduled for intrathecal anesthesia (bupicain 10 mg/ml hyperbaric injectable solution);
• you have experienced major joint trauma or undergone joint surgery and bupicain is to be administered intra-articularly;
• you have reduced cardiovascular function and bupicain is to be administered epidurally;
• you are taking medicines used to treat mood disorders (MAOIs, tricyclic antidepressants) (see "Other medicines and bupicain");
• you are scheduled for a procedure called stellate ganglion block.

Your doctor will monitor you during treatment with this medicine, as certain local anesthetic techniques may cause even serious adverse effects:

• Central nerve block: may manifest as reduced heart and vascular function (cardiovascular depression), especially if you already have reduced blood volume (hypovolemia); therefore, caution is required if you have reduced cardiovascular function and are undergoing epidural anesthesia;
• Stellate ganglion block: may cause adverse effects similar to central nerve block, as well as cardiac toxicity with increased or decreased heart rate up to cardiac arrest;
• Epidural anesthesia: may cause decreased blood pressure (hypotension) and reduced heart rate (bradycardia); hypotension requires immediate intravenous administration of medicines used to stimulate the heart (sympathomimetics);
• Retrobulbar injections (behind the eyes): very rarely, temporary vision loss (temporary blindness), heart and circulation blockage (cardiovascular collapse), breathing difficulties (apnea), and seizures may occur, which must be treated immediately;
• Retrobulbar or peribulbar injections (behind or around the eyes): rare, long-lasting eye muscle disorders may occur; therefore, the lowest doses and concentrations of anesthetic should be used;
• Paracervical block: may cause decreased or increased fetal heart rate (bradycardia/tachycardia); therefore, fetal heart rate must be monitored during use of this medicine (see "Pregnancy and breastfeeding");
• Spinal anesthesia (bupicain 10 mg/ml hyperbaric injectable solution): may cause total or high spinal block, with reduced heart and circulatory function (cardiovascular depression) and reduced respiration (respiratory depression); these effects are more likely if you are elderly or in an advanced stage of pregnancy; in both cases, the dose should be reduced; additionally, with intrathecal anesthesia, rare but potentially permanent nerve and brain damage (paresthesia, anesthesia, motor weakness, and paralysis) may occur.

If local anesthesia is administered to areas such as fingers or the base of the penis, bupivacaine without adrenaline will be used to prevent tissue damage (ischemic necrosis).
Before administering this medicine, your doctor must assess your blood circulation status.
Your doctor may decide to use a test dose of this medicine combined with adrenaline to avoid accidental intravenous or intrathecal injection.
During administration, your doctor will closely monitor you and immediately discontinue treatment at the first sign of alarm, such as altered sensation or drowsiness (changes in consciousness).
Rare cases of severe reactions, even in non-allergic individuals, have been reported; therefore, immediate availability of emergency equipment, medicines, and trained personnel is required during use of this medicine.

Children
The safety and efficacy of bupivacaine hydrochloride in children under 1 year of age have not been established.
The use of bupivacaine hydrochloride for intra-articular block or major nerve block in children aged 1 to 12 years has not been documented.
For epidural anesthesia, the dose must be adjusted according to weight and age (see "Use in children aged 1 to 12 years").

Other medicines and bupicain
Inform your doctor, pharmacist, or nurse if you are currently using, have recently used, or might use any other medicines.
This medicine must be administered with caution if you are taking:

• other medicines used to reduce pain during surgery (local anesthetics);
• medicines similar to bupicain, such as certain antiarrhythmics (e.g., lidocaine, mexiletine, tocainide);
• class III antiarrhythmics, such as amiodarone (see "Warnings and precautions");
• MAOIs, tricyclic antidepressants (see "Warnings and precautions").

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, planning pregnancy, or breastfeeding, consult your doctor, pharmacist, or nurse before using this medicine.
Pregnancy
If you are in an advanced stage of pregnancy, the dose for spinal anesthesia (bupicain 10 mg/ml hyperbaric injectable solution) must be reduced.
Paracervical anesthesia is associated with a higher risk of adverse effects on the fetus (see "Warnings and precautions").
Breastfeeding
If you are breastfeeding, bupicain may pass into breast milk in very small amounts; generally, there is no risk to the newborn.

Driving and using machines
Bupicain may impair your ability to drive or operate machinery. Bupicain may cause mild disturbances in mental function and motor control (coordination) and may temporarily negatively affect mobility and level of alertness. If you experience these symptoms, avoid driving and operating machinery.

bupicain 2.5 mg/ml injectable solution and bupicain 5 mg/ml injectable solution contain sodium
5 ml vial: these medicines contain less than 1 mmol (23 mg) of sodium per vial, i.e., essentially 'sodium-free'.
10 ml vial: these medicines contain 31.5 mg of sodium (main component of table salt) per vial. This corresponds to 1.6% of the maximum daily recommended dietary intake for an adult.

3. How to use bupicain

This medicine will be administered to you by a doctor or trained medical personnel during surgical procedures. If you have any doubts, consult your doctor, pharmacist, or nurse.
The dose and route of administration will be determined by the doctor according to your needs and age.

Use in adults and children over 12 years of age
The dose should be the lowest possible that ensures adequate anaesthesia. The recommended dose ranges from 2–3 mg to 100–150 mg, depending on the type of anaesthesia.
The maximum dose for a single administration should not exceed 150 mg, corresponding to 30 ml of the 5 mg/ml solution and 60 ml of the 2.5 mg/ml solution.
In general, the recommended maximum dose is 2 mg per kg of body weight for a single administration.

Use in children from 1 to 12 years of age (bupicain 2.5 mg/ml injectable solution and bupicain 5 mg/ml
injectable solution)
The dose should be the lowest possible that ensures adequate anaesthesia.
The maximum dose is 2 mg per kg of body weight.
The doctor will adjust the dose according to body weight.
Children under 1 year of age: The safety and efficacy of bupivacaine have not been established (see “Children”).

If you use more bupicain than you should
Accidental intravascular injection may cause toxic effects within a few seconds or minutes.
Following administration of an excessive dose of this medicine, systemic toxic effects (systemic toxic reactions) may occur 15–60 minutes after injection.
Bupicain 10 mg/ml hyperbaric injectable solution, when administered under recommended conditions, is unlikely to cause general toxicity. However, if other local anaesthetics are administered concomitantly, toxic effects may be additive.
In case of accidental use or ingestion of an excessive dose of this medicine, contact your doctor immediately or go to the nearest hospital Emergency Department.

If you forget to use bupicain
This medicine will be administered by a doctor or nurse, so it is unlikely that a dose will be missed.
If you have any doubts about the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone experiences them.
The following side effects may occur:
Very common (may affect more than 1 in 10 people):

• reduction in blood pressure (hypotension);
• nausea.

Common (may affect up to 1 in 10 people):

• disturbances in sensation of legs, arms, or other body parts (paraesthesia), dizziness;
• reduction in heart rate (bradycardia);
• increase in blood pressure (hypertension);
• vomiting;
• inability of the bladder to empty (urinary retention).

Uncommon (may affect up to 1 in 100 people):

• seizures, altered sensation around the mouth (circumoral paraesthesia), tongue numbness, intolerance to sounds (hyperacusis), visual disturbances, loss of consciousness, tremor, sensation of emptiness in the head, perception of ringing in the ears (tinnitus), speech disturbances (dysarthria).

Rare (may affect up to 1 in 1,000 people):

• allergic reactions, severe allergic reaction (anaphylactic shock);
• disease characterized by impaired nerve function (neuropathy), nerve damage (peripheral nerve injury), inflammation of the membrane covering the brain and spinal cord (arachnoiditis), loss of ability to contract one or more muscles (paresis), movement and sensory disturbances in the lower limbs (paraplegia), unintentional total spinal block;
• double vision (diplopia);
• heart block (cardiac arrest), changes in heart rhythm (cardiac arrhythmias);
• breathing problems (respiratory depression).

Not known (frequency cannot be estimated from available data):

• excitement, disorientation, dilation of the pupil (mydriasis), increased metabolism and body temperature, contraction of the jaw muscles (trismus), sweating, increased respiratory rate (tachypnea), bronchial dilation (bronchodilation), increased blood vessel volume (vasodilation);
• allergic reactions with local manifestations such as skin irritations (urticaria, pruritus) or systemic manifestations such as contraction of bronchial muscles (bronchospasm).

Following administration of bupivacaine 10 mg/ml hyperbaric injectable solution, the following additional side effects may also occur:
Common (may affect up to 1 in 10 people):

• headache after dural puncture (post-dural puncture headache);
• involuntary loss of urine (urinary incontinence).

Uncommon (may affect up to 1 in 100 people):

• reduced ability to contract one or more muscles (paresis), disturbance of sensation (dysaesthesia);
• muscle weakness, back pain.

Rare (may affect up to 1 in 1,000 people):

• loss of contraction in one or more muscles (paralysis).

Possible side effects in children
Side effects that may occur in children are similar to those reported in adults. It may be difficult to detect the onset of early signs of toxicity of this medicine when used during general anaesthesia in children.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store bupivacaine

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the container after "Exp.". The expiry date refers to the last day of that month.
The solution must be used immediately after opening. Any unused medicine should be discarded.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What bupicain 2.5 mg/ml injectable solution contains

• The active substance is bupivacaine hydrochloride: 1 ml contains 2.5 mg of bupivacaine hydrochloride.
• The other components are: sodium chloride, water for injections.

What bupicain 5 mg/ml injectable solution contains

• The active substance is bupivacaine hydrochloride: 1 ml contains 5 mg of bupivacaine hydrochloride.
• The other components are: sodium chloride, water for injections.

What bupicain 10 mg/ml hyperbaric injectable solution contains

• The active substance is bupivacaine hydrochloride: 1 ml contains 10 mg of bupivacaine hydrochloride.
• The other components are: glucose monohydrate, water for injections.

Description of the appearance of bupicain and contents of the pack
Bupicain 2.5 mg/ml injectable solution and bupicain 5 mg/ml injectable solution:
pack of 10 vials of 5 ml or 10 ml.
Bupicain 10 mg/ml hyperbaric injectable solution:
pack of 10 vials of 2 ml.

Marketing Authorisation Holder and Manufacturer
Monico spa
Via Ponte di Pietra 7, 30173 Venezia Mestre - Italy

The following information is intended exclusively for healthcare professionals

Posology and method of administration
In adults, the recommended dose is indicated as a guideline in the following table:

In children aged 1 to 12 years, the recommended doses of bupicain 2.5 mg/ml injectable solution and bupicain 5 mg/ml injectable solution are reported in the following table:

a) The onset and duration of peripheral nerve blocks depend on the type of block and the dose administered.
b) Thoracic epidural blocks require incremental dosing until the desired level of anaesthesia is achieved.

Treatment of acute systemic toxicity
Administration of the local anaesthetic must be stopped immediately if signs of acute systemic toxicity or total spinal block occur. Symptoms of central nervous system toxicity must be treated immediately with appropriate airway and respiratory support, and with administration of anticonvulsants such as diazepam 10–20 mg intravenously. Barbiturates are not recommended, as they may worsen bulbar depression. Circulation may be supported by intravenous administration of corticosteroids in appropriate doses; diluted alpha- and beta-stimulating vasoconstrictor agents (mephentermine, metharaminol and others) or atropine sulphate may also be added.

If cardiovascular depression occurs, appropriate treatment with intravenous fluids, vasopressors, inotropic agents and/or lipid emulsion should be considered. In children, dosage must be adjusted according to age and body weight.

If circulatory arrest occurs, immediate cardiopulmonary resuscitation must be initiated. Ensuring optimal oxygenation, supporting ventilation and circulation, and treating acidosis are of vital importance.

In the event of cardiac arrest, resuscitation efforts may need to be prolonged to achieve a favourable outcome.

Incompatibilities
The solubility of bupivacaine at pH above 6.5 is limited. This should be taken into account when alkaline solutions such as carbonates are added, as they may cause precipitation of the solution.

For further information, refer to the Summary of Product Characteristics.