Marcaina

Package leaflet: Information for the patient

MARCAINA 5 mg/ml injectable solution

bupivacaine hydrochloride
Please read this leaflet carefully before you are given 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 or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as you, because it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

1. What Marcaina is and what it is used for
2. What you need to know before you are given Marcaina
3. How Marcaina will be administered to you
4. Possible side effects
5. How to store Marcaina
6. Package contents and other information

1. What Marcaina is and what it is used for

Marcaina contains bupivacaine hydrochloride, a medicine belonging to the group of local anaesthetics.
Marcaina is used to numb (anaesthetize) parts of the body.
It is used to block or relieve pain.
Marcaina can be used for:

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

Marcaina can be used in any type of local anaesthesia, that is, elimination of pain in a specific area of the body without loss of consciousness.
Marcaina is also indicated for surgical and dental procedures, either used alone or in combination with general anaesthesia (anaesthesia).
Talk to your doctor if you do not feel better or if you feel worse.

2. What you need to know before you are given Marcaina

You will not be given Marcaina

• If you are allergic to bupivacaine hydrochloride or to any of the other ingredients of this medicine (listed in section 6).
• If you are allergic to other local anaesthetics and/or to similar substances.
• If you are due to receive local anaesthesia into a vein. Blood flow to a part of the body will be interrupted by applying a tourniquet, and loss of pain sensation will be limited to that area, as accidental leakage of bupivacaine into the bloodstream could cause toxic reactions. The use of bupivacaine 7.5 mg/ml is contraindicated in epidural anaesthesia (administration of drugs into the back to block pain sensation) in obstetrics (e.g. during labour and/or delivery).

Warnings and precautions
Talk to your doctor or nurse before you are given Marcaina.

• Your doctor will monitor you closely to reduce the risk of serious side effects: if you are elderly or debilitated;
• if you suffer from a disease affecting the heart's electrical system (partial or complete heart block);
• if you have advanced liver disease or severe kidney disease; changes 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) to treat irregular heart rhythm (see Other medicines and Marcaina). Your doctor may also perform ECG monitoring (electrocardiogram, a test to assess heart function);
• if you have recently suffered trauma to a joint (e.g. knee or elbow);
• if you are due to receive an anaesthetic procedure called stellate ganglion block.

Your doctor will monitor you during treatment with this medicine, as certain local anaesthetic techniques may cause serious adverse effects:
the stellate ganglion block may cause side effects similar to those of central nervous system blockade, as well as cardiac toxicity with increased or decreased heart rate, potentially leading to cardiac arrest.

Children and adolescents

• In children under 12 years of age, the effects of Marcaina in numbing body parts during surgery (local anaesthesia) have not been established.
• In children under 1 year of age, the safety and efficacy of Marcaina for pain treatment have not been established. Therefore, the use of Marcaina is not recommended in these age groups (see section 1. What Marcaina is and what it is used for).

Other medicines and Marcaina
Inform your doctor or nurse if you are taking, have recently taken, or might take any other medicines.
Tell your doctor if you are taking:

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

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, planning to become pregnant, or breastfeeding, please consult your doctor or nurse before you are given 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 the fetus is exposed to high concentrations of anaesthetic, it may develop a reduced heart rate.

Breastfeeding
Like other local anaesthetics, bupivacaine may pass into breast milk, but in such small amounts that there is generally no risk to the newborn.

Driving and using machines
Marcaina may impair your ability to drive or operate machinery.
Local anaesthetics may have a very mild effect on mental function and coordination, and may temporarily negatively affect motor ability and level of alertness.

3. How Marcaina will be administered to you

The dose will be determined by your doctor based on your weight and your state of health.
Marcaina will be administered by a doctor specialized in the use of this type of medicine, in appropriately equipped facilities, into the affected part of your body.
If a large area of your body needs to be anesthetized or if a high dose of the medicine is required, your doctor will insert a small tube into a vein (catheter) before administering Marcaina.
During the procedure, your doctor will carefully monitor your vital functions and will talk to you.
If you are to receive epidural anaesthesia (administration of anaesthetic medicines into the back), your doctor will first administer an initial dose of 3–5 ml of bupivacaine with another medicine containing adrenaline, followed by the full dose.
Use in children and adolescents
Marcaina is slowly injected into the epidural space (an area of the spine) or into other parts of the body by an anaesthetist experienced in paediatric anaesthetic techniques. The dosage depends on the patient's age and weight and will be determined by the anaesthetist.
If you are given more Marcaina than you should
In case of accidental administration of an excessive dose of Marcaina, inform your doctor immediately or go to the nearest hospital.
Accidental intravascular injection of local anaesthetics may cause immediate general adverse effects (occurring within seconds to a few minutes). In cases of overdose, adverse effects appear later (15–20 minutes after injection), due to a slower rise in blood concentrations of the local anaesthetic.
If you have any doubts about how to use this medicine, consult your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
If you experience any of the following serious side effects while receiving Marcaina, your doctor will IMMEDIATELY STOP administration at the first warning sign and will, whenever possible, administer appropriate therapy to treat these symptoms:

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

Immediate availability of appropriate emergency equipment, medications, and trained personnel is essential, as severe allergic reactions, sometimes fatal, have been reported following the use of local anaesthetics, even in the absence of known allergies.

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 (circumoral 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 injury
• inflammation of a meninge, the lining of the brain (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 bronchial diameter facilitating airflow into the lungs (bronchodilation)
• increased blood vessel diameter (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
• 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 impaired heart function (sudden cardiovascular collapse or shock)

Additional 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, consult your doctor. You may 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 MARCAINA

Do not store above 25 °C.
The solutions do not contain preservatives, are for single use only, and must be used immediately
after opening. Any unused medicinal product should be discarded.
Marcaina vials must not be resterilized.
Keep this medicinal product out of the sight and reach of children.
Do not use this medicinal product after the expiry date stated on the packaging after "Exp.".
The expiry date refers to the last day of that month.
Do not use this medicinal product if you notice any visible signs of deterioration.
Do not dispose of any medicinal product via wastewater or household waste. Ask your pharmacist how
to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What MARCAINA contains

• The active substance is bupivacaine hydrochloride 5 mg.
• The other components are sodium chloride, sodium hydroxide (pH regulator), hydrochloric acid (pH regulator), water for injectable preparations.

Description of the appearance of MARCAINA and contents of the pack
Marcaina is a clear, colourless injectable solution.
It is available in packs of 5 vials containing 5 ml each.
Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Aspen Pharma Trading Limited
3016 Lake Drive
Citywest Business Campus
Dublin 24
Ireland
Tel: +39 0687 502 429
Manufacturer
CENEXI
52 Rue Marcel et Jacques Gaucher
94120 FONTENAY SOUS BOIS
France

---

The following information is intended for healthcare professionals only:
The solubility of bupivacaine at pH values above 6.5 is limited. This should be taken into account when alkaline solutions such as carbonates are added, which may cause precipitation of the solution.
The solutions contain no preservatives, are for single use only, and must be used immediately after opening. Any unused medicinal product should be discarded.
Marcaina vials must not be re-sterilized.
Regional anaesthesia procedures must always be performed in properly equipped areas and by qualified personnel. Immediate availability of equipment and drugs necessary for monitoring and emergency resuscitation is required.
The physician must have received complete and adequate training in the procedure to be used and must be experienced in the diagnosis and management of adverse reactions, systemic toxicity, or other complications (see "Undesirable effects" and "Management in case of overdose").
Peripheral major nerve blocks may involve administration of a large volume of local anaesthetic into highly vascularized areas, often near large blood vessels, where there is an increased risk of intravascular injection and/or rapid systemic absorption, potentially leading to high plasma concentrations.
Marcaina is usually administered in minimal doses, varying according to indication, from 2–3 mg to 100–150 mg, as indicated in the following table:

Warning: Vials do not contain antimicrobial preservatives and must be used for a single
administration only. Any remaining solution must be discarded.
The maximum dose for an adult and per single administration should not exceed 150 mg,
corresponding to 30 ml of the 5 mg/ml solution; more generally, the recommended safe dose for both
adults and children, which should not be exceeded, is 2 mg/kg per single administration.
In prolonged analgesic therapy, usual doses range between 0.25 and 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 reaching
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. Individual variations in onset time and duration of effect may occur.
In children with high body weight, a gradual dose reduction based on ideal body weight is often
necessary. Reference textbooks should be consulted regarding both factors influencing specific block
techniques and individual patient requirements. The extent of anesthesia spread is difficult to predict
but is influenced by the volume of drug administered, especially with isobaric solutions.
It is advisable to use an adequate test dose, preferably combined with adrenaline, to promptly avoid
accidental intravenous or intrathecal injection.
The anesthetic solution should be injected cautiously in small increments after approximately 10 seconds
of prior aspiration. Especially when infiltrating highly vascularized areas, it is advisable to wait
approximately 2 minutes before proceeding with the actual loco-regional block.

Pediatric patients aged 1 to 12 years
Pediatric regional anesthesia procedures must be performed by qualified physicians familiar with this
patient population and the technique.
The doses in the table should be considered as guidelines for pediatric use. Individual variations may
occur.
In children with high body weight, a gradual dose reduction based on ideal body weight is often
necessary. Reference textbooks should be consulted regarding both factors influencing specific block
techniques and individual patient requirements.
The lowest effective dose required to achieve adequate anesthesia must be used.

Recommended dose for children aged 1 to 12 years
Conc. Volume Dose Onset Duration
mg/ml ml/kg mg/kg min of effect
hours
ACUTE PAIN (peri- and post-operative)
Surgical Field Block 5.0 0.5–2.0
(e.g., minor nerve blocks and infiltration)
Peripheral Nerve Blocks 5.0 0.5–2.0 a)
(e.g., ilioinguinal, iliohypogastric)
The onset and duration of peripheral nerve block depend on the type of block and the dose administered.
In children, dosing should be calculated based on body weight up to a maximum of 2 mg/kg.

The adverse reaction profile of Marcaine is similar to that of other long-acting local anesthetics. Drug-related adverse reactions are difficult to distinguish from 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 epidural and spinal anesthesia.

Some local anesthesia techniques may be associated with severe adverse reactions, regardless of the 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. Such reactions must be diagnosed and treated immediately.
• Retrobulbar and peribulbar injections of local anesthetics: carry a low risk of persistent ocular muscle 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, the lowest doses and concentrations that provide the desired effect should be used. Vasoconstrictors may worsen tissue reactions and should be used only when indicated.
• Local anesthetics, even at low doses, when injected into the head and neck (e.g., during stellate ganglion block), may cause systemic toxicity due to unintentional intra-arterial injection, intravascular absorption, or entry into the subarachnoid space.
• Paracervical block may occasionally cause fetal bradycardia/tachycardia. Therefore, careful monitoring of fetal heart rate is necessary.
• Continuous intra-articular infusion is not an approved indication for Marcaine. However, post-marketing cases of chondrolysis have been reported, exclusively in North America, in patients who received continuous post-operative intra-articular infusion of local anesthetics. The majority of reported chondrolysis cases involved the shoulder joint. A causal relationship has not been established.

Acute systemic toxicity
Systemic toxic reactions primarily affect the central nervous system and 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, while cardiac reactions depend more significantly on the specific drug, both quantitatively
and qualitatively.

EXPIRY AND STORAGE
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.

Patient information leaflet: information for the patient

MARCAINA 5 mg/ml hyperbaric injectable solution

bupivacaine hydrochloride
Please read this leaflet carefully before this medicine is administered to you, 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 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, as it could be dangerous.
• If you experience any side effect, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet:

1. What Marcaina is and what it is used for
2. What you need to know before Marcaina is administered to you
3. How Marcaina will be administered to you
4. Possible side effects
5. How to store Marcaina
6. Contents of the pack and other information

1. What Marcaina is and what it is used for

Marcaina contains bupivacaine hydrochloride, a medicine belonging to the group of local anaesthetics.
Marcaina is used to numb (anaesthetize) parts of the body during surgical procedures, by injecting the medicine into the back, in adults and children from 0 to 18 years of age, either alone or in combination with general anaesthesia.
Talk to your doctor if you do not feel better or if you feel worse.

2. What you should know before being given Marcaina

Marcaina must not be administered to you 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 to similar substances.
• You have diseases of the central nervous system (meningitis, tumors, poliomyelitis, or intracranial hemorrhage).
• You have spinal canal narrowing (spinal stenosis) and spinal disease (e.g., spondylitis, tuberculosis, tumor) or recent trauma (e.g., fractures).
• You have a blood infection (septicemia).
• You have impaired vitamin B12 absorption (pernicious anemia) and spinal cord damage.
• You have a skin infection at the injection site or in the surrounding area.
• You have reduced blood flow to the body due to impaired heart function (cardiogenic shock) or reduced circulating blood volume (hypovolemic).
• You have blood coagulation disorders or are taking medications to thin the blood (anticoagulants).

Warnings and precautions
Please speak with your doctor or nurse before receiving Marcaina.
Your doctor will closely monitor you to reduce the risk of serious adverse effects:

• if you are elderly or debilitated;
• if you have a disease of the heart's electrical system (partial or complete heart block);
• if you have advanced liver disease or severe kidney disease;
• if you are in an advanced stage of pregnancy (see section “Pregnancy and breastfeeding”);
• if you have reduced circulating blood volume. You may experience a severe and sudden drop in blood pressure during spinal anesthesia, regardless of the local anesthetic used;
• if you are taking class III antiarrhythmic drugs (e.g., amiodarone) to treat irregular heart rhythm (see section “Other medicines and Marcaina”). Your doctor may also perform ECG monitoring (electrocardiogram, a test to assess heart function);
• if you have an immune system disorder, the body's defense system, which destroys nerves (multiple sclerosis);
• if you have loss of motor function on one side of the body or in the lower part of the body (hemiplegia, paraplegia) or nerve and muscle disorders. If you are elderly or in an advanced stage of pregnancy, your doctor may reduce your dose.

Other medicines and Marcaina
Inform your doctor or nurse if you are taking, have recently taken, or might take any other medicine.
Inform your doctor if you are taking:

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

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breastfeeding, please 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 in an advanced stage of pregnancy, your doctor will reduce your dose (see also “Warnings and precautions”).
If the fetus is exposed to high concentrations of anesthetic, it may experience a decreased heart rate.
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
Marcaina 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.

3. How Marcaine will be administered to you

The dose will be determined by your doctor based on your weight and health condition.
Marcaine will be administered into your back by a doctor specialized in the use of this type of medicine.
During the procedure, your doctor will carefully monitor your vital functions and will talk to you.

Use in children and adolescents
Marcaine will be slowly injected into the child's back by an anaesthetist experienced in paediatric anaesthetic techniques. The dose will be determined by the anaesthetist based on the child's age and weight.

If you are given more Marcaine than you should
It is highly unlikely that you will receive more solution than required, as your doctor will monitor you during treatment.
Accidental injection of local anaesthetics into a blood vessel can cause immediate general adverse effects (occurring within a few seconds to several minutes). In cases of overdose, adverse effects appear later (15–20 minutes after injection), due to a delayed rise in blood concentrations of the local anaesthetic.
When used under the recommended conditions, Marcaine hyperbaric is unlikely to reach blood levels high enough to cause general adverse effects. However, if other local anaesthetics are administered concomitantly, their adverse effects are additive and may lead to general adverse effects.
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 gets them.
If you experience any of the following serious side effects while receiving Marcaina, your doctor will IMMEDIATELY STOP administration at the first sign of warning and will give you, when possible, appropriate treatment to manage these symptoms:

• death
• blockage of nerves from the neck downwards (total or high spinal block)
• cessation of heart and lung function (cardiovascular and respiratory depression)
• severe drop in blood pressure (profound hypotension)
• decreased heart rate (bradycardia)
• cardiac arrest (when the heart stops beating)
• increased heart rate
• 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 necessary, as rare but severe allergic reactions, sometimes fatal, have been reported with local anesthetics, even in the absence of known allergies.

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
• headache
• decreased heart rate (bradycardia)
• high blood pressure (hypertension)
• vomiting
• inability to urinate (urinary retention)
• inability to control urination (urinary incontinence)

Uncommon (may affect up to 1 in 100 people)

• uncontrolled body movements (convulsions)
• numbness around the mouth (circumoral 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)
• reduced motor function (paresis)
• sensory disturbance (dysaesthesia)
• muscle weakness, back pain

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

• allergic reactions
• nerve disease (neuropathy)
• nerve damage
• inflammation of a meningeal membrane covering the brain (arachnoiditis)
• loss of motor function in the lower part of the body (paraplegia)
• unintentional blockage of sensation and motor function (unintentional total spinal block)
• loss of motor function (paralysis)
• double vision (diplopia)
• 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 bronchial diameter facilitating airflow into the lungs (bronchodilation)
• increased blood vessel diameter (vasodilation)
• lack of oxygen throughout the body (hypoxia)
• increased carbon dioxide levels in the blood (hypercapnia)
• temporary cessation of breathing (apnea)
• increased acid levels in the blood (acidosis)
• increased potassium levels in the blood (hyperkalemia)
• decreased calcium levels in the blood (hypocalcemia)
• numbness (paraesthesia)
• loss of pain sensation (anesthesia)
• motor weakness

Allergic reactions

• hives, itching
• temporary narrowing of the airways 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)

Generally, with spinal anesthesia, side effects related to the heart are not expected.

Additional side effects in children and adolescents
Side effects of the medicine 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, consult your doctor. You may also report side effects directly via the national adverse reaction reporting system.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Marcaina

Do not store above 25 °C.
The solution contains no preservatives, is for single use only, and must be used immediately after opening.
Any unused medicinal product must be discarded.
Marcaina vials must not be resterilized.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton after "Exp".
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 dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Marcaina contains

• The active substance is bupivacaine hydrochloride 5 mg.
• The other components are monohydrate glucose, sodium hydroxide (pH regulator), hydrochloric acid (pH regulator), water for injections.

Description of the appearance of Marcaina and contents of the pack
Marcaina is a clear, colourless injectable solution.
It is available in the following pack:

• 5 mg/ml pack containing 5 vials of 4 ml each

Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder
Aspen Pharma Trading Limited
3016 Lake Drive
Citywest Business Campus
Dublin 24
Ireland
Tel: +39 0687 502 429
Manufacturer
CENEXI
52 Rue Marcel et Jacques Gaucher
94120 FONTENAY SOUS BOIS
France

---

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 account when alkaline solutions, such as carbonates, are added, as they may cause precipitation of the solution.
The solution contains no preservatives, is for single use only, and must be used immediately after opening.
Any unused medicinal product must be discarded.
Marcaina vials must not be resterilized.
Regional anaesthetic procedures must always be performed in adequately equipped areas by qualified personnel. Immediate availability of equipment and drugs 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 nerve blocks may involve the administration of a large volume of local anaesthetic in highly vascularized areas, often close to large vessels, where there is an increased risk of intravascular injection and/or rapid systemic absorption, which may lead to high plasma concentrations.
Marcaina is usually used in minimal dosages, varying according to the indication, as indicated in the following table (for guidance only):

Warning: The vials do not contain antimicrobial preservatives and must therefore be used for a single administration only.
Any unused portion must be discarded.
It is advisable to use an adequate test dose, preferably in combination with adrenaline, in order to promptly detect accidental intravenous or intrathecal injection.
The anesthetic solution must be injected cautiously in small increments after approximately 10 seconds of prior aspiration. Especially when infiltrating highly vascularized areas, it is recommended to wait approximately 2 minutes before proceeding with the actual loco-regional block.
The adverse reaction profile of Marcaina is similar to that of other long-acting local anesthetics. Drug-related adverse reactions are difficult to distinguish from the physiological effects resulting from nerve conduction blockade (such as decreased arterial pressure, bradycardia, temporary urinary retention) and from events directly caused by the injection (e.g., nerve fiber trauma, spinal hematoma) or indirectly (e.g., epidural abscess and meningitis), or from events associated with cerebrospinal fluid leakage (e.g., post-dural puncture headache). The occurrence of neurological damage is a rare but well-known consequence of regional anesthesia, particularly epidural and spinal anesthesia.

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 observed with other amide-type local anesthetics, whereas cardiac reactions depend more significantly on the specific drug, both quantitatively and qualitatively.

Marcaina hyperbaric, when used under recommended conditions, is unlikely to produce blood levels high enough to cause systemic toxicity. However, if other local anesthetics are administered concomitantly, toxic effects are additive and may lead to systemic toxicity.

Return of the patient to baseline clinical status follows redistribution of the local anesthetic from the central nervous system and subsequent metabolism and excretion. Recovery may be rapid if large amounts of the drug have not been administered.

In severe cases, cardiovascular system effects may occur, usually preceded by signs of central nervous system toxicity. In deeply sedated patients or those undergoing general anesthesia, cardiovascular effects may occur without preceding central nervous system prodromal signs. As a result of high systemic concentrations of local anesthetics, hypotension, bradycardia, arrhythmias, and even cardiac arrest may occur; in rare cases, cardiac arrest has occurred without preceding central nervous system prodromal symptoms.

In children, early signs of local anesthetic systemic toxicity may be difficult to detect when the block is administered during general anesthesia.

Treatment of acute systemic toxicity
If cardiovascular depression (hypotension, bradycardia) occurs, appropriate treatment should be considered, including intravenous fluids, vasopressors, inotropic agents, and/or lipid emulsion. In children, dosing must be adjusted according to age and 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.

If cardiac arrest occurs, resuscitation efforts may need to be prolonged to achieve a favorable outcome.

To prevent accidental intravascular injection, aspiration should be performed before and during administration of the main dose, which should be injected slowly or in incremental doses. At the first sign of toxicity, administration must be immediately discontinued (see “Undesirable effects”).