MARCAINA 5 mg /Ml Injectable Solution

Зміст інструкції

1. MARCAINA 5 mg/ml injectable solution
   1. What is Marcaina and what is it 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. Content of the pack and other information
2. MARCAINA 5 mg/ml hyperbaric injectable solution
   1. What is Marcaina and what is it used for
   2. What you need to know before you are given Marcaina
   3. How Marcaina will be administered to you
   4. Possible adverse effects
   5. How to store Marcaina
   6. Contents of the pack and other information

MARCAINA 5 mg/ml injectable solution

bupivacaine hydrochloride
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 pass it on to others, even if their symptoms are the same as yours, as it could be harmful.
• If you get any side effects, even 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 given to you
• 4. Possible side effects
• 5. How to store Marcaina
• 6. Contents of the pack and other information

1. What is Marcaina and what is it used for

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

• numbing parts of the body during surgery 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 anesthesia, i.e. elimination of pain in a
district of the body without loss of consciousness.
Marcaina is also indicated in surgical and dental procedures, either used alone or in association with
general anesthesia (narcosis).
Consult 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 other similar substances.
• If you are to undergo local anaesthesia in a vein. The blood circulation of an area of the body will be interrupted with the application of a tourniquet and the loss of sensitivity to pain will be limited to that area, as accidental loss 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 in the back to eliminate pain sensitivity) 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 carefully to reduce the risk of dangerous side effects: if you are elderly or debilitated;
• if you suffer from a disease of the electrical system of the heart (partial or complete heart block);
• if you suffer from advanced liver disease or severe kidney disease; alterations in liver enzymes (increased levels in the blood) may occur, especially with repeated injections and long-term treatment with this medicine;
• if you are in an advanced state of pregnancy (see Pregnancy and breastfeeding);
• if you are taking Class III antiarrhythmic drugs (e.g. amiodarone) to treat irregular heart rhythm (see Other medicines and Marcaina). Your doctor may also subject you to an ECG monitoring (electrocardiogram, an examination to assess heart function); if you have recently suffered a trauma to a joint (e.g. knee or elbow);
• if you are to undergo an anaesthesia called stellate ganglion block

Your doctor will monitor you during treatment with this medicine as some
local anaesthesia techniques can cause even serious side effects:
stellate ganglion block can give side effects similar to those of central nervous system block as well as cardiac toxicity with increased or decreased heart rate
up to cardiac arrest.

Children and adolescents

• In children under 12 years of age, the effects of Marcaina for numbing parts of the body 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 is Marcaina and what it is used for).

Other medicines and Marcaina
Tell your doctor or nurse if you are taking, have recently taken or might take
any other medicine.
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);
• MAO inhibitors or tricyclic antidepressants, used to treat depression.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, are planning to become pregnant, or are breastfeeding with
breast milk, ask your doctor or nurse for advice before you are given this
medicine.

Pregnancy
A large number of pregnant women and women of childbearing potential have been treated with bupivacaine and so far
no increase in the frequency of neonatal malformations has been reported.
If the foetus is reached by high concentrations of anaesthetic, it may experience a
decrease in heart rate.

Breastfeeding
Like other local anaesthetics, bupivacaine can pass into breast milk but in such a reduced amount that
there is generally no risk to the newborn.

Driving and using machines
Marcaina impairs the ability to drive vehicles or operate machinery.
Local anaesthetics can have a very mild effect on mental function and coordination,
and can temporarily negatively affect the ability to move and the degree of
vigilance.

3. How Marcaina will be administered to you

The dose will be established by the doctor based on your weight and your state of health.
Marcaina will be administered to you, in the affected part of the body, by a doctor specialized in the use
of this type of medicine, in adequately equipped facilities.
If a large part of your body needs to be anesthetized or you are administered a high dose of
medicine, the doctor will insert a small tube into a vein (catheter) before administering
Marcaina.
During the procedure, the doctor will carefully monitor your vital functions and talk to you.
If you need to undergo epidural anesthesia (administration of anesthetic drugs in the
back), the doctor will administer an initial dose of 3-5 ml of bupivacaine with another medicine
containing adrenaline, and subsequently the complete dose.

Use in children and adolescents
Marcaina is injected slowly into the epidural space (part of the spinal column) or in other
parts of the body by an anesthesiologist experienced in pediatric anesthesia techniques. The dosage depends on the age
and weight of the patient and will be determined by the anesthesiologist.

If you are given more Marcaina than you should
In case of accidental intake of an excessive dose of Marcaina, immediately inform your
doctor or go to the nearest hospital.
Accidental injection into a blood vessel of local anesthetics can cause immediate general adverse effects
(from a few seconds to a few minutes). In case of an overdose, the adverse effects manifest later (15-20 minutes after the injection) and this is due to a
slowed increase in blood concentrations of local anesthetic.
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 the following seriousside effects during the administration of Marcaina, the
doctor will IMMEDIATELY STOPadministration at the first sign of warning and will
administer, when possible, the appropriate therapy to treat these symptoms:

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

Immediate availability of equipment, medications and qualified personnel for emergency treatment is
necessary, as rare cases of severe allergic reactions, sometimes fatal, have been reported following the use of
local anesthetics, even in the absence of a known allergy.

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 (paresthesia), dizziness
• decreased heart rate (bradycardia)
• increased blood pressure (hypertension)
• vomiting
• inability to urinate (urinary retention)

uncommon (may affect up to 1 in 100 people)

• uncontrolled body movements (convulsions)
• numbness of the area around the mouth (paresthesia in the circumoral region)
• tongue insensitivity
• increased sensitivity to sounds (hyperacusis)
• visual disturbances
• loss of consciousness
• tremor
• feeling 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 a meninges, the lining of the brain (arachnoiditis)
• decreased ability to move (paresis)
• loss of ability to move the lower part of the body (paraplegia)
• block of sensation and ability to move (unintentional total spinal block)
• irregular heartbeats (cardiac arrhythmias).

Other adverse effects reported include:

effects involving the central nervous system

• excitement, disorientation,
• pupil dilation (mydriasis),
• increased metabolism and body temperature,
• jaw clenching that makes it impossible to open the mouth (trismus),
• sweating,
• increased respiratory rate (tachypnea), increased diameter of the bronchi that promotes the passage of air into the lungs (bronchodilation),
• increased diameter of blood vessels (vasodilation),
• oxygen deficiency throughout the body (hypoxia),
• increased carbon dioxide in the blood (hypercapnia),
• temporary interruption of breathing (apnea),
• increased acids in the blood (acidosis),
• increased potassium levels in the blood (hyperpotassemia),
• decreased calcium levels in the blood (hypocalcemia)

allergic reactions

• urticaria, itching
• temporary narrowing of the bronchi that prevents air from entering the lungs (bronchospasm)

effects involving the heart

• decreased blood circulation, causing tissues to no longer receive oxygen due to reduced 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 get any side effects, talk to your doctor or pharmacist. This includes any side effects not listed in
this leaflet. You can also report side effects directly through the national 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 at a temperature above 25 °C.
The solutions do not contain preservatives, are for single use only and must be used immediately
after opening. Any residual medicine must be discarded.
Do not resterilize vials of Marcaina.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the pack after Exp.
The expiry date refers to the last day of that month.
Do not use this medicine if you notice visible signs of deterioration.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how
to dispose of medicines you no longer use. This will help protect the environment.

6. Content of the pack and other information

What MARCAINA contains

• The active ingredient is bupivacaine hydrochloride 5 mg.
• The other ingredients are sodium chloride, sodium hydroxide (pH adjuster), hydrochloric acid (pH adjuster), water for injections.

Description of the appearance of MARCAINA and contents of the pack
Marcaina presents as a clear and colorless injectable solution.
It is available in packs of 5 vials of 5 ml.

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 doctors or healthcare professionals:
The solubility of bupivacaine at a pH higher than 6.5 is limited. This should be taken into consideration when
alkaline solutions, such as carbonates, are added, which may cause the solution to precipitate.
The solutions do not contain preservatives, are for single use and must be used immediately
after opening. Any remaining drug must be discarded.
The vials of Marcaina must not be resterilized.
Regional anesthesia procedures must always be performed in adequately equipped areas and
by qualified personnel. Immediate availability of equipment and
drugs necessary for monitoring and emergency resuscitation must be ensured.
The doctor must have undergone complete and adequate training in the procedure to be used and
must be experienced in the diagnosis and treatment of adverse effects, systemic toxicity or other
complications (see “Undesirable effects” and “Overdose”).
Blocking of major peripheral nerves may involve the administration of a high 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, which may lead to
high plasma concentrations.
Marcaina is usually used in minimum dosages, varying according to the indications, from 2-3 mg to 100-150

Warning: the vials, not containing preservatives, must be used for a single
administration. Any remaining product must be discarded.
The maximum dose for an adult and for single administration should not exceed 150 mg,
corresponding to 30 ml of the 5 mg/ml solution; more generally, the safety dose for both adults
and children, which is advisable not to exceed, is 2 mg/kg for single administration.
In prolonged pain therapy, doses usually ranging from 0.25 to 1 mg/kg of body weight are used;
administration can be repeated 2-3 times within 24 hours.

N.B. When performing prolonged blocks for successive bolus administration, the risk of reaching toxic plasma concentrations or inducing local neuronal damage must be
considered.
The dose to be administered must be calculated based on the doctor's experience and on
knowledge of the patient's clinical condition. The lowest doses that can
allow adequate anesthesia should be used. Individual variations may occur regarding
the onset and duration of action. In children with high body weight, a
gradual reduction of the dosage based on ideal body weight is often necessary. Reference texts should
be consulted both regarding aspects that affect specific blocking techniques and
regarding individual patient needs. The degree of anesthesia spread can be
difficult to predict but is influenced by the volume of drug administered, especially
with regard to isobaric solutions.
It is advisable to use an adequate dose-test, possibly in association with adrenaline, in order to
promptly avoid accidental intravenous or intrathecal injection.
The anesthetic solution should be injected with caution in small doses after about 10 seconds from a
preliminary aspiration. Especially when infiltrating highly vascularized areas, it is
advisable to wait about 2 minutes before proceeding with the actual loco-regional block.

Paediatric patientsfrom 1 to 12 years of age
Paediatric regional anesthesia procedures must be performed by qualified doctors who are familiar with this population and with the technique.
The doses in the table should be considered as guidelines for use in paediatrics. Individual
variations may occur.
In children with high body weight, a gradual reduction of the dosage based on ideal body weight is often necessary. Reference texts should be consulted both regarding
aspects that affect specific blocking techniques and regarding individual patient
needs.
The lowest dose necessary for adequate anesthesia should be used.

Recommended dose for children from 1 to 12 years of age
Conc.
mg/ml
Volume
ml/kg
Dose
mg/kg
Onset
min
Duration
of effect
hours
ACUTE PAIN(peri- and post-operative)

Surgical field block
(e.g., minor nerve block and
infiltration)

• 5.0 0.5-2.0

Peripheral Nerve Block
(e.g. ilioinguinal-iliohypogastric)

• 5.0 0.5-2.0 a)

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

• Central nervous system block: may cause cardiovascular depression, especially in the presence of hypovolemia. Epidural anesthesia should therefore be used with caution in patients with reduced cardiovascular function.
• Retrobulbar injections: may, in very rare cases, reach the cerebral subarachnoid space causing temporary blindness, cardiovascular collapse, apnea, convulsions, etc. Such reactions must be diagnosed and treated immediately.
• Retro- and peribulbar injections of local anesthetics: involve a low risk of persistent muscle dysfunction at the ocular level. Primary causes include trauma and/or local toxic effects on muscles and/or nerves. The severity of such reactions to the tissues is correlated with 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 that can allow to obtain the desired effect. Vasoconstrictors may worsen tissue reactions and should be used only if indicated.
• Local anesthetics, even at low doses, injected into the head and neck, as in the performance of stellate ganglion blocks, can produce systemic toxicity due to unintentional intra-arterial injection or intravascular absorption or into the subarachnoid space.
• Paracervical block may sometimes cause fetal bradycardia/tachycardia. Therefore, careful monitoring of fetal heart rate is necessary.
• Continuous intra-articular infusion is not an approved indication for Marcaina. However, cases post-marketing have been reported, exclusively in North America, of chondrolysis in patients who received post-operative continuous intra-articular infusion of local anesthetics. The majority of chondrolysis cases reported involved the shoulder joint. No causal relationship has been established.

Acute systemic toxicity
Toxic systemic reactions mainly affect the central nervous system and the cardiovascular system. Such reactions are caused by high blood concentrations of the local anesthetic
following accidental intravascular injection, overdose or exceptionally rapid absorption
from highly vascularized areas (see “Precautions for use”). Reactions to the central
nervous system are similar to those of other amid-type local anesthetics while
cardiac reactions depend, both quantitatively and qualitatively, to a greater extent on
the drug.

EXPIRY DATE AND STORAGE
The solubility of bupivacaine at a pH higher than 6.5 is limited. This should be taken into consideration when
alkaline solutions, such as carbonates, are added, which may cause the solution to precipitate.

MARCAINA 5 mg/ml hyperbaric injectable solution

bupivacaine hydrochloride
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 pass it on to others, even if their symptoms are the same as yours, as it could be harmful.
• If you get any side effects, even 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 given to you
• 4. Possible side effects
• 5. How to store Marcaina
• 6. Contents of the pack and other information

1. What is Marcaina and what is it used for

Marcaina contains bupivacaine hydrochloride, a medicine belonging to the group of local
anesthetics.
Marcaina is used to numb (anaesthetize) parts of the body during a surgical procedure,
with an injection of the medicine into the back, in adults and children from 0 to 18 years of age,
either used alone or in combination with general anesthesia (narcosis).
If you do not feel better or if you feel worse, please consult your doctor.

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

Marcaina will not be given to you

• 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 anesthetics and/or to other similar substances.
• If you suffer from diseases of the central nervous system (meningitis, tumors, poliomyelitis and intracranial hemorrhages).
• If you suffer from a narrowing of the spinal canal (spinal stenosis) and spinal disease (e.g. spondylitis, tuberculosis, tumor) or recent trauma (e.g. fractures).
• If you suffer from a blood infection (septicemia).
• If you suffer from decreased absorption of vitamin B12 (pernicious anemia) and spinal cord damage.
• If you suffer from a skin infection at the injection site or in the surrounding area.
• If you suffer from reduced blood flow to the body caused by decreased heart function (cardiogenic shock) or decreased blood volume (hypovolemic).
• If you suffer from blood clotting problems or are taking medicines to thin the blood (anticoagulants).

Warnings and precautions
Talk to your doctor or nurse before you are given Marcaina.
The doctor will monitor you carefully to reduce the risk of dangerous side effects:

• if you are elderly or debilitated;
• if you suffer from a disease of the electrical system of the heart (partial or complete heart block);
• if you suffer from advanced liver disease or severe kidney disease;
• if you are in advanced pregnancy (see section “Pregnancy and breastfeeding”);
• if you suffer from a reduced 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 heartbeat (see section “Other medicines and Marcaina”). The doctor may also subject you to an ECG monitoring (electrocardiogram, examination to assess heart function);
• if you suffer from a disease of the immune system, the body's defense system, that destroys nerves (multiple sclerosis);
• if you suffer from loss of movement on one side or the lower part of the body (hemiplegia, paraplegia) or nerve and muscle disorders; If you are elderly or in advanced pregnancy, the doctor may reduce your dose.

Other medicines and Marcaina
Tell your doctor or nurse if you are taking, have recently taken or might take any
other medicine.
Tell 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 medicines, used to treat irregular heartbeat (e.g. amiodarone);
• MAO inhibitors or tricyclic antidepressants, used to treat depression.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, are planning to become pregnant, or are breastfeeding with
breast milk, ask your doctor or nurse for advice before you are given this medicine.

Pregnancy
A large number of pregnant women and women of childbearing age have been treated with bupivacaine and so far no
increase in the frequency of neonatal malformations has been reported.
If you are in advanced pregnancy, the doctor will reduce the dose (see also “Warnings and precautions”).
If the fetus is reached by high concentrations of anesthetic, it may experience a decrease in
heart rate.

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

Driving and using machines
Marcaina impairs the ability to drive vehicles or use machines.
Local anesthetics can have a very mild effect on mental function and coordination, and
can temporarily negatively affect the ability to move and the level of alertness.

3. How Marcaina will be administered to you

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

Use in children and adolescents
Marcaina will be injected slowly into the child's back by an experienced anesthesiologist in pediatric
anesthesia techniques. The dose will be determined by the anesthesiologist based on the child's age and weight.

If you are given more Marcaina than you should
It is very unlikely that you will be given more solution than necessary because your doctor will
monitor you during treatment.
Accidental injection into a blood vessel of local anesthetics can cause immediate general adverse effects
(ranging from a few seconds to a few minutes). In case of overdose, the adverse effects
manifest later (15-20 minutes after the injection) and this is due to a slowed increase
in blood concentrations of local anesthetic.
Hyperbaric Marcaina, under the recommended conditions of use, is unlikely to reach levels in the blood
sufficiently high to cause general adverse effects. However, if other local anesthetics are
administered together, the adverse effects are additive and can cause general adverse effects.
If you have any doubts about the use of this medicine, please contact your doctor or nurse.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everybody gets them.
If you experience the following seriousadverse effects during the administration of Marcaina, the
doctor will IMMEDIATELY STOPadministration at the first sign of warning and will administer, where
possible, the appropriate therapy to treat these symptoms:

• death
• nerve block from the neck down (total or high spinal)
• interruption of heart and lung function (cardiovascular and respiratory depression)
• severe drop in blood pressure (deep hypotension)
• decrease in heart rate (bradycardia)
• cardiac arrest (when the heart stops beating)
• increase in heart rate
• loss of sensation and movement
• difficulty breathing
• loss of consciousness
• uncontrolled body movements (convulsions)
• reduction of brain activity Immediate availability of equipment, drugs and personnel suitable for emergency treatment is necessary, as serious allergic reactions, sometimes with fatal outcome, have been reported in rare cases following the use oflocal anesthetics, even in the absence of a known allergy.

Possible adverse 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 (paresthesia), dizziness
• headache
• decrease in heart rate (bradycardia)
• increase in 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 (paresthesia in the circumoral region)
• tongue insensitivity
• increased sensitivity to sounds (hyperacusis)
• visual disturbances
• loss of consciousness
• tremor
• feeling of emptiness in the head
• ringing in the ears (tinnitus)
• difficulty speaking (dysarthria)
• decreased ability to move (paresis)
• sensory disturbance (dysesthesia)
• muscle weakness, back pain rare (may affect up to 1 in 1,000 people)
• allergic reactions
• nerve disease (neuropathy)
• nerve damage
• inflammation of a meninges, the lining of the brain (arachnoiditis)
• loss of motor ability in the lower body (paraplegia)
• block of sensation and ability to move (unintentional total spinal block)
• loss of motor ability (paralysis)
• double vision (diplopia)
• heart rhythm disturbances

Other adverse effects reported include:

effects involving the central nervous system

• excitement, disorientation,
• pupil dilation (mydriasis),
• increased metabolism and body temperature,
• jaw clenching making it impossible to open the mouth (trismus),
• sweating,
• increased respiratory rate (tachypnea), increased diameter of the bronchi which promotes the passage of air into the lungs (bronchodilation),
• increased diameter of blood vessels (vasodilation),
• oxygen deficiency throughout the body (hypoxia),
• increased carbon dioxide in the blood (hypercapnia),
• temporary interruption of breathing (apnea),
• increased acids in the blood (acidosis),
• increased potassium levels in the blood (hyperpotassemia),
• decreased calcium levels in the blood (hypocalcemia),
• numbness (paresthesia),
• loss of pain sensation (anesthesia),
• motor weakness allergic reactions
• hives, itching
• temporary narrowing of the bronchi preventing air from entering the lungs (bronchospasm) effects involving the heart
• decreased blood circulation whereby tissues no longer receive oxygen due to reduced heart function (sudden cardiovascular collapse or shock) Generally in the case of spinal anesthesia, no adverse effects involving the heart are expected.

Additional adverse effects in children and adolescents
The adverse effects of the drug in children are similar to those in adults

Reporting of adverse effects
If you get any side effects, even those not listed in this leaflet, tell your
doctor. You can also report side effects directly through the national 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 at a temperature above 25 °C.
The solution does not contain preservatives, is for single use and must be used immediately after opening.
Any residual medicine must be discarded.
The vials of Marcaina must not be resterilized.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the pack after Scad.
The expiry date refers to the last day of that month.
Do not use this medicine if you notice visible signs of deterioration.
Do not dispose of any medicine in 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 Marcaina contains

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

Description of the appearance of Marcaina and contents of the pack
Marcaina presents as a clear and colourless solution for injection.
It is available in the following pack:

• 5 mg/ml pack of 5 vials of 4 ml

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 exclusively for doctors or healthcare professionals:
The solubility of bupivacaine at a pH higher than 6.5 is limited. This should be taken into consideration when
alkaline solutions, such as carbonates, are added, as they may cause the solution to precipitate.
The solution does not contain preservatives, is for single use and must be used immediately after opening.
Any remaining medicine must be discarded.
The vials of Marcaina must not be resterilized.
Regional anaesthesia procedures must always be performed in adequately equipped areas and by
qualified personnel. Immediate availability of equipment and medicines
necessary for monitoring and emergency resuscitation is required.
The doctor must have undergone complete and adequate training in the procedure to be used and must
be experienced in the diagnosis and treatment of adverse effects, systemic toxicity or other complications
(see “Adverse effects” and “Overdose”).
Blocking of major peripheral nerves may involve the administration of a large volume of
local anaesthetic in highly vascularized areas, often near large vessels where there is an increased risk
of intravascular injection and/or rapid systemic absorption, which can lead to elevated plasma concentrations.
Marcaina is usually used in minimum dosages, varying according to the indications, as indicated for guidance in the table:

Warning: the vials, not containing excipients for aseptic preservation, must be used for a single administration.
Any remaining contents must be discarded.
It is advisable to use an adequate dose-test, possibly in association with adrenaline, in order to avoid
promptly an accidental intravenous or intrathecal injection.
The anaesthetic solution must be injected with caution in small doses after about 10 seconds from a
preliminary aspiration. Especially when infiltrating highly vascularized areas, it is advisable to
allow about 2 minutes to elapse before proceeding with the actual loco-regional block.
The profile of adverse reactions of Marcaina is similar to that of other long-acting local anaesthetics. Drug adverse reactions are difficult to distinguish from the physiological effects
resulting from nerve conduction block (such as decreased blood pressure, bradycardia,
temporary urinary retention) and from events caused directly by the injection (e.g. nerve fibre 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 onset of neurological damage is a
rare but well-known consequence of regional anaesthesia and in particular, of epidural and spinal anaesthesia.

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 anaesthetic following accidental intravascular injection, overdose or exceptionally rapid absorption from highly vascularized areas (see “Precautions for use”). Reactions affecting the central nervous system
are similar to those of other amidic-type local anaesthetics while reactions at the cardiac level
depend, both quantitatively and qualitatively, to a greater extent on the drug.

Marcaina hyperbaric, under the recommended conditions of use, is unlikely to promote blood levels

sufficiently high to cause systemic toxicity. However, if other local anaesthetics are

administered concurrently, the toxic effects are additive and may cause systemic toxicity.
The patient's return to initial clinical conditions is consequent to the redistribution of the local anaesthetic
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, effects on the cardiovascular systemmay occur, generally preceded
by signs of central nervous system toxicity. In deeply sedated or anaesthetized patients, effects on the cardiovascular system may occur without prodromal effects of the central nervous system. As a result of high systemic concentrations of local anaesthetics, hypotension, bradycardia, arrhythmias and even cardiac arrest may occur, but in rare cases cardiac arrest has occurred without prodromal effects of the central nervous system.
In children, it may be difficult to detect the onset of early signs of local anaesthetic systemic toxicity when the block is administered during general anaesthesia.

Treatment of acute systemic toxicity
If cardiovascular depression (hypotension, bradycardia) occurs, appropriate treatment with intravenous fluids, vasopressors, inotropic agents and/or
lipid emulsion should be considered. In children, the dosage must be adjusted to age and weight.
If cardiac arrest occurs, immediate cardiopulmonary resuscitation must be performed. It is vital to ensure optimal oxygenation, support ventilation and
circulation and treat acidosis.
If cardiac arrest occurs, it may be necessary to prolong resuscitation maneuvers to
achieve a favourable 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 increasing doses. At the first
sign of toxicity, administration should be stopped immediately (see “Adverse effects”).