Bupivacaine FisioPharma

Package leaflet: Information for the user

BUPIVACAINA FISIOPHARMA 2.5 mg/ml solution for injection, 5 mg/ml solution for injection

Bupivacaine hydrochloride
Please read this leaflet carefully before using this medicine because 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 give it to other people, even if their symptoms are the same as yours, because it could be harmful.
• If you experience any adverse reactions, including those not listed in this leaflet, contact your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

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

1. What BUPIVACAINA FISIOPHARMA is and what it is used for

BUPIVACAINA FISIOPHARMA 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.
BUPIVACAINA FISIOPHARMA is used to numb (anaesthetize) parts of the body in order to block or relieve pain.
BUPIVACAINA FISIOPHARMA can be used:

• to numb parts of the body during surgical procedures in adults and children over 12 years of age,
• to relieve pain in adults, infants, and children over 1 year of age.

BUPIVACAINA FISIOPHARMA can be used in the following peripheral anaesthesias (local infiltration, nerve block, locoregional anaesthesia, sympathetic block, caudal epidural, spinal -subarachnoid- anaesthesia).
BUPIVACAINA FISIOPHARMA is indicated, either alone or in combination with other anaesthetic medicines, for surgical procedures in:

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

Talk to your doctor if you do not feel better or if you feel worse.

2. What you need to know before using BUPIVACAINA FISIOPHARMA

Do not receive BUPIVACAINA FISIOPHARMA if:

• you are allergic to bupivacaine hydrochloride or to any of the other ingredients of this medicine (listed in section 6);
• you are allergic to other local anesthetics and/or substances similar to bupivacaine (amide-type anesthetics);
• you are pregnant or suspected of being pregnant and need to undergo certain types of anesthesia with bupivacaine. If you are pregnant, you must not receive cervical paracervical block anesthesia (a type of anesthesia at uterine level) and must not receive epidural anesthesia (administration of medication into the back to eliminate pain sensation) with bupivacaine 0.75% concentration; Bupivacaine 0.75% must not be used for epidural anesthesia during labor or pregnancy (obstetric epidural anesthesia) (see section on pregnancy and breastfeeding).
• the regional anesthesia you are scheduled to receive involves injection of the anesthetic into a vein (Bier Block);

Warnings and precautions
Talk to your doctor or nurse before receiving BUPIVACAINA FISIOPHARMA.
Serious adverse reactions, including death, have been reported following the use of similar medicines (local anesthetics). Therefore, this medicine will be administered to you only under strict medical supervision by trained personnel and in facilities equipped with emergency measures necessary for urgent treatment, immediately discontinuing administration at the first sign of warning, for example if you experience sensory disturbances or drowsiness (altered consciousness).
Before using this medicine, your doctor will check your blood circulation status.
Your doctor will administer this medicine to you with great caution to reduce the risk of dangerous adverse effects:

• if you are elderly or debilitated;
• if you suffer from a heart electrical system disorder (partial or complete heart block);
• if you have advanced liver disease or severe kidney disease; alterations in liver enzymes (increased blood levels) may occur, especially with repeated injections and long-term treatment with this medicine;
• if you are in an advanced stage of pregnancy (see Pregnancy and breastfeeding);
• if you are taking class III antiarrhythmic medicines (e.g., amiodarone) for irregular heart rhythm (see Other medicines and BUPIVACAINA FISIOPHARMA). Your doctor may also perform ECG monitoring (electrocardiogram, a test to assess heart function);
• if you are taking medicines used to treat mood disorders (MAOIs, tricyclic antidepressants);
• if you are scheduled to undergo a procedure called stellate ganglion block.

When performing local anesthesia in areas such as fingers or the base of the penis, bupivacaine without adrenaline will be administered to prevent tissue damage (ischemic necrosis).
Your doctor will monitor you during treatment with this medicine, as certain local anesthesia techniques may cause adverse effects, even serious ones:

• stellate ganglion block may cause adverse effects similar to those of central nervous block as well as cardiac toxicity, including increased or decreased heart rate up to cardiac arrest.

Children and adolescents

• In children under 12 years of age, the efficacy and safety of BUPIVACAINA FISIOPHARMA for numbing body parts during surgery (regional anesthesia for major nerve blocks) have not been established.
• In infants under 1 year of age, the safety and efficacy of BUPIVACAINA FISIOPHARMA have not been established. Therefore, the use of BUPIVACAINA FISIOPHARMA is not recommended in these age groups (see section 1. What BUPIVACAINA FISIOPHARMA is and what it is used for).

Other medicines and BUPIVACAINA FISIOPHARMA
Inform your doctor or nurse if you are taking, have recently taken, or might take any other medicines.
In particular, inform your doctor if you are taking:

• other local anesthetics or similar substances used to numb body parts (e.g., lidocaine, mexiletine, and tocainide);
• class III antiarrhythmic medicines used to treat irregular heart rhythm (e.g., amiodarone);
• medicines used to treat depression (MAOIs, tricyclic antidepressants).

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or are breastfeeding, consult your doctor or nurse before receiving this medicine.
Pregnancy
A large number of pregnant women and women of childbearing age have been treated with bupivacaine, and to date no increase in the frequency of neonatal malformations has been reported.
If you are confirmed or suspected to be pregnant, bupivacaine must not be administered for a procedure called paracervical block and/or must not be administered at a concentration of 0.75% for epidural anesthesia. If the fetus is exposed to high concentrations of anesthetic, it may develop a reduced heart rate (see section “Do not receive BUPIVACAINA FISIOPHARMA”).
Breastfeeding
Like other local anesthetics, bupivacaine may pass into breast milk, but in such small amounts that there is generally no risk to the newborn.
Driving and using machines
BUPIVACAINA FISIOPHARMA may impair your ability to drive or operate machinery.
Local anesthetics may have a very mild effect on mental function and coordination and may temporarily negatively affect motor ability and level of alertness.
BUPIVACAINA FISIOPHARMA 2.5 mg/ml and 5 mg/ml injectable solution contains sodium
This medicine contains 17.7 mg of sodium (the main component of table salt) per 5 ml vial.
This corresponds to 0.9% of the maximum daily recommended dietary intake for an adult.
This medicine contains 35.4 mg of sodium (the main component of table salt) per 10 ml vial.
This corresponds to 1.8% of the maximum daily recommended dietary intake for an adult.

3. How to use BUPIVACAINA FISIOPHARMA

This medicine will be administered to you by a doctor during surgical procedures. If you have any doubts, consult your doctor or nurse.
The dose and route of administration will be determined by the doctor according to your needs, age, and health condition.
BUPIVACAINA FISIOPHARMA will be administered by a specialist experienced in the use of this type of medicine, in appropriately equipped facilities, directly into the affected area of the body.
If a large area of the body needs to be anaesthetized or if a high dose of the medicine is required, the doctor will insert a flexible needle into a vein (venous cannula) before administering BUPIVACAINA FISIOPHARMA.
During the procedure, the doctor will carefully monitor your vital functions and will talk to you.
If you are to receive epidural anaesthesia (administration of anaesthetic drugs into the back), the doctor will administer an initial dose of 3–5 ml of bupivacaine, possibly with adrenaline, followed by the full dose.

Use in children and adolescents aged 12 years and older
BUPIVACAINA FISIOPHARMA is slowly injected into the epidural space (part of the spinal column) or into other areas of the body by an anaesthetist experienced in paediatric anaesthetic techniques.
The doctor will adjust the dose according to age and body weight.

If you are given more BUPIVACAINA FISIOPHARMA than you should
This medicine will be administered by trained medical personnel; therefore, it is unlikely that you will receive an excessive dose.
Accidental injection of local anaesthetics into a blood vessel may cause immediate general toxic effects (occurring within seconds to minutes).
Following administration of an excessive dose of this medicine, adverse effects may appear approximately 15–20 minutes after injection (e.g., numbness of the lips, dizziness, breathing difficulties, tremors, hearing and/or vision disturbances).
If you think you have been given too much of this medicine or experience any toxic symptoms, contact your doctor or nurse immediately, as administration must be stopped and corrective treatment initiated.
If you have any doubts about the use of this medicine, consult your doctor or nurse.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them.
If you experience any of the following serious side effects during administration of BUPIVACAINA FISIOPHARMA, your doctor will IMMEDIATELY STOP the administration at the first warning sign and will provide, whenever possible, appropriate treatment to manage these symptoms:

• cardiac arrest
• low blood pressure (hypotension)
• decreased heart rate (bradycardia)
• increased heart rate (tachycardia)
• loss of sensation and movement
• difficulty breathing
• loss of consciousness
• uncontrolled body movements (convulsions)
• reduced brain activity

Immediate availability of emergency equipment, medications, and trained personnel is essential,
as rare but serious, sometimes fatal, allergic (even in the absence of known allergy) or toxic reactions have been reported following the use of local anaesthetics.

The possible side effects are listed below according to the following frequency:
Very common (may affect more than 1 in 10 people)

• low blood pressure (hypotension)
• nausea

Common (may affect up to 1 in 10 people)

• numbness (paraesthesia), dizziness
• decreased heart rate (bradycardia)
• high blood pressure (hypertension)
• vomiting
• inability to urinate (urinary retention)

Uncommon (may affect up to 1 in 100 people)

• uncontrolled body movements (convulsions)
• numbness around the mouth (perioral paraesthesia)
• tongue numbness
• increased sensitivity to sounds (hyperacusis)
• visual disturbances
• loss of consciousness
• tremor
• sensation of emptiness in the head
• ringing in the ears (tinnitus)
• difficulty speaking (dysarthria)
• muscle weakness, back pain

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

• allergic reactions, anaphylactic shock (severe allergic reaction)
• nerve disease (neuropathy)
• nerve damage
• inflammation of the membrane covering the brain called meninges (arachnoiditis)
• reduced ability to move (paresis)
• loss of movement in the lower part of the body (paraplegia)
• unintentional block of sensation and movement (unintentional total spinal block)
• irregular heartbeats (cardiac arrhythmias)

Other reported side effects include:
Effects on the central nervous system

• excitation, disorientation
• dilation of the pupil of the eye (mydriasis)
• increased metabolism and body temperature
• jaw muscle spasm making it impossible to open the mouth (trismus)
• sweating
• increased respiratory rate (tachypnea), increased diameter of the bronchi leading to greater airflow into the lungs (bronchodilation)
• increased diameter of blood vessels (vasodilation)
• lack of oxygen throughout the body (hypoxia)
• increased carbon dioxide levels in the blood (hypercapnia)
• temporary cessation of breathing (apnoea)
• increased acid levels in the blood (acidosis)
• increased potassium levels in the blood (hyperkalaemia)
• decreased calcium levels in the blood (hypocalcaemia)

Allergic reactions

• urticaria, itching (pruritus)
• temporary narrowing of the bronchi preventing airflow into the lungs (bronchospasm)

Effects on the heart

• reduced blood circulation leading to inadequate oxygen supply to tissues due to decreased heart function (sudden cardiovascular collapse or shock)

Side effects in children and adolescents
Adverse drug reactions in children are similar to those in adults.

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 BUPIVACAINA FISIOPHARMA

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after “Expiry”. The expiry date refers to the last day of that month.
Do not use this medicine if you notice any visible signs of deterioration.
Do not store above 25°C.
The vials do not contain preservatives, are intended for single use only, and must be used immediately after opening. Any remaining solution must 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. Package contents and other information

What BUPIVACAINA FISIOPHARMA 2.5 mg/ml injectable solution contains

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

What BUPIVACAINA FISIOPHARMA 5 mg/ml injectable solution contains

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

Description of the appearance of BUPIVACAINA FISIOPHARMA and pack contents
Bupivacaine Fisiopharma 2.5 mg/ml solution for injection
Pack of 10 vials containing 5 ml each
Pack of 10 vials containing 10 ml each

Bupivacaine Fisiopharma 5 mg/ml solution for injection
Pack of 10 vials containing 5 ml each
Pack of 10 vials containing 10 ml each

Marketing Authorization Holder and Manufacturer
Fisiopharma s.r.l. - Industrial Area - 84020 PALOMONTE (SA) - ITALY

The following information is intended exclusively for physicians or healthcare professionals

The solubility of bupivacaine at pH greater than 6.5 is limited. This should be taken into consideration when alkaline solutions, such as carbonates, are added, as they may cause precipitation of the solution.
The vials do not contain preservatives, are intended for single use only, and must be used immediately after opening. Any remaining solution must be discarded.
Regional anesthesia procedures must always be performed in properly equipped settings and by qualified personnel. Immediate availability of equipment and medications necessary for monitoring and emergency resuscitation must be ensured.
The physician must have received complete and adequate training in the procedure to be used and must be experienced in the diagnosis and treatment of adverse reactions, systemic toxicity, or other complications (see "Undesirable effects" and "Management in case of overdose").
Peripheral major nerve blocks may involve the administration of a large 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, potentially leading to high plasma concentrations.
Adults and children over 12 years of age
Bupivacaine Fisiopharma is usually administered in minimal dosages, varying according to indication, from 2–3 mg to 100–150 mg, as indicated in the following table for guidance:

The maximum dosage for an adult per single administration should not exceed 150 mg,
corresponding to 30 ml of the 5 mg/ml solution and to 60 ml of the 2.5 mg/ml solution; more generally, the recommended safety dose, for both adults and children, not to be exceeded, is 2 mg/kg per single administration.
In prolonged analgesic therapy, usual doses range from 0.25 to 1 mg/kg body weight; administration may be repeated 2–3 times within 24 hours.
N.B. When performing prolonged blocks with repeated bolus administrations, the risk of achieving toxic plasma concentrations or inducing local neurotoxicity must be considered.
The dose to be administered must be calculated based on the physician’s experience and knowledge of the patient’s clinical condition. It is necessary to use the lowest doses capable of providing adequate anesthesia. Individual variations in onset time and duration of effect may occur. In children with high body weight, a gradual dose reduction is often required, based on ideal body weight. Reference texts should be consulted regarding factors affecting specific block techniques as well as individual patient requirements. The extent of anesthesia spread may be difficult to predict but is influenced by the volume of drug administered.
The physician may decide to use a test dose of this medicinal product, possibly in combination with adrenaline, to avoid accidental intravenous injection.
Administration should be performed cautiously, in small increments, following an aspiration test after approximately 10 seconds. Especially when infiltrating highly vascularized areas, it is advisable to wait approximately 2 minutes before proceeding with the actual loco-regional block.
Paediatric patients aged 1 to 12 years
Paediatric regional anaesthesia procedures should be performed by qualified physicians familiar with this patient population and with the technique.
The doses listed in the table should be considered as guidelines for paediatric use. Individual variations may occur.
In children with high body weight, a gradual dose reduction is often required, based on ideal body weight. Reference texts should be consulted regarding factors affecting specific block techniques as well as individual patient requirements.
The lowest dose required to achieve adequate anaesthesia should be used.
Recommended dose for children aged 1 to 12 years

a) The onset and duration of peripheral nerve block depend on the type of block and the administered dose.
In children, the dosage should be calculated according to body weight, up to a maximum of 2 mg/kg.
The adverse reaction profile of Bupivacaine Fisiopharma is similar to that of other long-acting local anesthetics.
Drug-related adverse reactions are often difficult to distinguish from the physiological effects resulting from
nerve conduction block (such as decreased arterial pressure, bradycardia) and from events directly caused by
injection (e.g., nerve fiber trauma) or indirectly (e.g., epidural abscess). The occurrence of neurological damage
is a rare but well-known consequence of regional anesthesia, particularly of epidural and spinal anesthesia.
Some local anesthetic techniques may be associated with severe adverse reactions, regardless of the specific
local anesthetic used:

• Central nerve block: may cause cardiovascular depression, especially in the presence of hypovolemia. Epidural anesthesia should therefore be used with caution in patients with impaired cardiovascular function.
• Retrobulbar injections: in very rare cases, may reach the cerebral subarachnoid space, causing temporary blindness, cardiovascular collapse, apnea, seizures, etc. These reactions must be diagnosed and treated immediately.
• Retrobulbar and peribulbar injections of local anesthetics: carry a low risk of persistent ocular muscular dysfunction. Primary causes include trauma and/or local toxic effects on muscles and/or nerves. The severity of such tissue reactions is related to the extent of 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 capable of achieving the desired effect. Vasoconstrictors may worsen tissue reactions and should only be used when indicated.
• Local anesthetics, even at low doses, when injected in the head and neck region—such as during stellate ganglion block—may cause systemic toxicity due to unintentional intra-arterial injection or intravascular or subarachnoid absorption.
• Paracervical block may occasionally cause fetal bradycardia/tachycardia. Careful monitoring of fetal heart rate is therefore required.
• Continuous intra-articular infusion is not an approved indication for Bupivacaine Fisiopharma. Cases of chondrolysis, primarily affecting the shoulder joint, have been reported in patients receiving postoperative continuous intra-articular infusion of local anesthetics.

Acute systemic toxicity
Systemic toxic reactions primarily 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 unusually rapid absorption from highly vascularized areas (see “Precautions for use”).
Central nervous system reactions are similar to those of other amide-type local anesthetics, whereas cardiac
reactions depend more significantly—both quantitatively and qualitatively—on the specific drug.
Any overdose of local anesthetic must be avoided, and two maximum doses should never be administered
without an interval of at least 24 hours.
When performing infiltrations for local anesthesia in areas lacking collateral circulation (fingers, penile
base, etc.), it is advisable to use the anesthetic without vasoconstrictor to avoid ischemic necrosis.
During administration, the patient must be closely monitored, and administration should be stopped
immediately at the first sign of warning (e.g., changes in consciousness).
The specific gravity of bupivacaine 2.5 mg/ml or 5 mg/ml is 1.006 at 20°C and 0.997 at 37°C.
Overdose
At the first signs of overdose, discontinue administration of the drug immediately. Place the patient in a
horizontal position and ensure airway patency. If respiratory difficulties occur, initiate assisted ventilation
(in emergencies, a bag-valve mask such as the Ambu bag may be used).
The use of bulbar analeptics is not recommended, as they increase oxygen consumption. Convulsive
manifestations may be controlled with intravenous diazepam (10–20 mg); barbiturates are not recommended, as they may worsen bulbar depression.
To support circulation, corticosteroids may be administered intravenously; diluted solutions of α-adrenergic vasoconstrictor agents (methoxamine, metaraminol, and others) or atropine sulfate may be added. Correction of any established acidotic state may be achieved using appropriate intravenous solutions of sodium bicarbonate.
For further information, consult the Summary of Product Characteristics.