EXPAREL 133 mg /10 Ml Prolonged-Release Injectable Dispersion

Зміст інструкції

1. EXPAREL liposomal 133 mg/10 mL dispersion for injectable preparation with prolonged
2. EXPAREL liposomal 266 mg/20 mL dispersion for injectable preparation with prolonged
   1. What is EXPAREL liposomal and what it is used for
   2. What you need to know before you receive EXPAREL liposomal
   3. How EXPAREL liposomal will be administered to you
   4. Possible side effects
   5. How to store EXPAREL liposomal
   6. Contents of the pack and other information

EXPAREL liposomal 133 mg/10 mL dispersion for injectable preparation with prolonged

release

EXPAREL liposomal 266 mg/20 mL dispersion for injectable preparation with prolonged

release
bupivacaine

Read this leaflet carefully before using this medicine as it contains important
information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or nurse.
• If any side effects occur, including those not listed in this leaflet, ask your doctor or nurse. See section 4.

Contents of this leaflet

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

1. What is EXPAREL liposomal and what it is used for

EXPAREL liposomal is a local anesthetic that contains the active substance bupivacaine.
EXPAREL liposomal is used in adults to reduce the pain felt in a specific part of the body
after a surgical procedure (for example, surgery on the knee or
shoulder joint).
EXPAREL liposomal is also used in adults and children aged 6 years and older to reduce
the pain felt in small to medium-sized wounds after a surgical procedure.

2. What you need to know before you receive EXPAREL liposomal

DO NOTreceive this medicine if:

• you are allergic to bupivacaine (or to other similar local anesthetics) or to any of the other
• you are pregnant and need to have a local anesthetic injected into the upper part of the vagina near the cervix. Bupivacaine can cause serious harm to the unborn child if used for this purpose;
• into a blood vessel or into the joints.

Warnings and precautions
EXPAREL liposomal should not be used in extensive abdominal, blood vessel and
chest surgeries.
Contact your doctor or nurse before receiving EXPAREL liposomal if:

• you have a heart problem;
• you have liver or kidney problems.

The use of EXPAREL liposomal may cause temporary loss of sensation or movement.
You may notice a difference in your ability to perceive things or to move normally for
a period of up to 5 days after the medicine is administered.
The following conditions have sometimes been reported with the use of other local anesthetics:

• Allergic reactions

Allergic reactions can occur in rare cases after the administration of a local anesthetic. Signs of allergic reactions to watch out for include: hives or skin rash, swelling around the eyes, swelling of the face, lips, mouth or throat, shortness of breath or
difficulty breathing, feeling dizzy or fainting, or fever. If you notice any of these symptoms after the
administration of EXPAREL liposomal, seek urgent medical attentionas these reactions can become

• Neurological conditions

Central nervous system toxicity can also occur occasionally. Early signs of this may include: restlessness, anxiety, difficulty speaking, feeling lightheaded, nausea or
vomiting, numbness and tingling of the mouth and lips, metallic taste, tinnitus (i.e.
ringing in the ears), dizziness, blurred vision, tremors or convulsions, depression,
drowsiness. Seek urgent medical attentionif you notice any of these symptoms after the administration of
EXPAREL liposomal. More serious adverse effects due to
excessive administration of bupivacaine include seizures (convulsions),

• Cardiovascular conditions

Cardiovascular conditions can also occur sometimes after the use of local anesthetics. The
signs to watch out for include: abnormal/irregular heartbeat, low blood pressure, fainting, dizziness or feeling lightheaded, fatigue (tiredness), shortness of breath or chest pain. A heart attack can also occur sometimes. Seek
urgent medical attentionif you notice

• Metahemoglobinemia

Metahemoglobinemia is a blood disorder that affects red blood cells. This condition
can occur immediately or several hours after the use of local anesthetics. Signs and symptoms
to watch out for include: pale skin or bluish/grayish skin color, shortness of breath,
feeling dizzy or fainting, confusion, palpitations or chest pain. Seek
urgent medical attentionif you notice any of these symptoms after the administration of EXPAREL liposomal. Metahemoglobinemia can sometimes cause more serious
symptoms such as irregular heartbeat, seizures, coma and even death (see also section 4

• Chondrolysis

Chondrolysis (destruction of cartilage of the bony joints) has been observed in patients who have received local anesthetics for intra-articular infusion. EXPAREL liposomal
should not be used for intra-articular infusion.

Children and adolescents
EXPAREL liposomal should not be used in children under 6 years of age to reduce pain
felt in small-to-medium-sized wounds after surgery. This medicine has not
been studied in this age group.
EXPAREL liposomal should not be used in children and adolescents under 18 years of age
to reduce pain in a specific part of the body after surgery (e.g.
surgery on the knee or shoulder joint). This medicine has not
been studied in this age group.

Other medicines and EXPAREL liposomal
Tell your doctor if you are taking or have recently taken any other medicines.
Taking some medicines at the same time may be harmful. In particular, tell your doctor
if you are taking any of the following:

• nitrates/nitrites - medicines used to dilate blood vessels and improve blood flow, especially for heart conditions, such as nitroglycerin, nitroprusside, nitric oxide, nitrous oxide;
• local anesthetics - benzocaine, lidocaine, bupivacaine, mepivacaine, tetracaine, prilocaine, procaine, articaine, ropivacaine;
• antiarrhythmics - medicines used to treat an irregular heartbeat (arrhythmia) such as lidocaine and mexiletine;
• anticancer medicines - cyclophosphamide, flutamide, rasburicase, isofamide, hydroxyurea;
• antibiotics - dapsone, sulfonamides, nitrofurantoin, para-aminosalicylic acid;
• antimalarials - chloroquine, primaquine, quinine;
• anticonvulsants - phenytoin, valproic acid, phenobarbital;
• other medicines - acetaminophen (paracetamol), metoclopramide (for stomach problems and against nausea), sulfasalazine (for inflammatory conditions), povidone-iodine (topical antiseptic).

If you have any doubts about any of these medicines, ask your doctor.

Pregnancy and breastfeeding
EXPAREL liposomal IS NOTrecommended during pregnancy and in women of childbearing potential who are not
using contraceptive measures. If you are pregnant, suspect you are pregnant or are planning a
pregnancy, tell your doctor or nurse before receiving this medicine.
EXPAREL liposomal passes into breast milk at very low levels and may cause serious adverse
reactions in the baby. Ask your doctor for advice before breastfeeding. The doctor will decide whether you should
stop breastfeeding or whether this medicine should not be given to you.

Driving and using machines
EXPAREL liposomal may alter your ability to perceive things or to move normally for
a period of up to 5 days after the medicine is administered. If you experience any of these
adverse effects, you should not drive vehicles or use tools or machinery.

EXPAREL liposomalcontains sodium
This medicine contains 21 mg of sodium (the main component of table salt) in each
10 mL vial and 42 mg in each 20 mL vial. This is equivalent to 1.1% and
2.1% of the recommended maximum daily intake with the diet of an adult, respectively.

3. How EXPAREL liposomal will be administered to you

EXPAREL liposomal will be administered to you by the doctor during the surgical procedure.
The recommended dose you will receive will be decided by the doctor, based on the type of pain relief you
need and the part of the body into which the medicine will be injected. The dose will also depend on the
size of the surgical site and your physical condition.
EXPAREL liposomal will be administered by injection. The doctor will inject EXPAREL
liposomal into one of the following sites:

• the site of the surgical procedure;
• near the nerves that support the area of the body affected by the surgery.

If you receive more EXPAREL liposomal than you should
EXPAREL liposomal must be used by experienced doctors who will monitor your blood pressure,
heart rate, respiratory rate and state of consciousness and monitor you for any signs
indicating that you have received an excessive amount of bupivacaine after the administration
of EXPAREL liposomal.

Seek urgent medical assistanceif after the administration of EXPAREL liposomal you notice
These are signs that indicate you have received an excessive dose of bupivacaine.

• Seizures (convulsions)
• Loss of consciousness
• Feeling of restlessness or anxiety
• Difficulty speaking
• Feeling dizzy or lightheaded
• Nausea or vomiting
• Numbness and tingling of the mouth and lips
• Changes in vision, hearing or taste
• Tremors or contractions
• Feeling sleepy, confused or not fully alert
• Increase or decrease in blood pressure
• Increase or decrease in heart rate.

If you miss a dose of EXPAREL liposomal
It is unlikely that you will miss a dose. EXPAREL liposomal will be administered to you by the doctor only once
(during the surgical procedure).
If you have any questions about the use of this medicine, ask your doctor, pharmacist or
nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Seek urgent medical assistanceif you develop any of the following serious side effects reported with the use of other local anesthetics (see section 2):

• abnormal/irregular heartbeat, low blood pressure, fainting, dizziness or lightheadedness, fatigue, shortness of breath, chest pain, cardiac arrest (symptoms of cardiovascular reaction);
• restlessness, anxiety, difficulty speaking, feeling lightheaded, nausea or vomiting, numbness or tingling of the mouth and lips, metallic taste, tinnitus (ringing in the ears), dizziness, blurred vision, tremors or spasms, depression, drowsiness, seizures (symptoms of central nervous system reaction);
• hives or rash, swelling around the eyes, swelling of face, lips, mouth or throat, shortness of breath or difficulty breathing, fast heartbeat, nausea, vomiting, feeling dizzy or fainting, or fever (symptoms of allergic reaction);
• pale skin or grey/bluish skin color, shortness of breath, feeling lightheaded or fainting, confusion, palpitations, chest pain, irregular heartbeat, convulsions or coma (symptoms of methemoglobinemia).

Other side effects may include:
Common(may affect up to 1 in 10 people):

• altered sense of taste;
• constipation;
• nausea or vomiting;
• loss of oral sensitivity.

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

• feeling of warmth;
• general bruising or falls;
• abnormal blood test results;
• joint pain;
• reduced mobility or involuntary/uncontrolled body movements;
• trauma, pain, spasms, contractions or muscle weakness;
• burning sensation;
• headache;
• loss of sensitivity;
• itchy skin or skin irritation.

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

• abdominal discomfort, abdominal bloating or indigestion;
• diarrhea;
• dry mouth, difficulty or pain when swallowing;
• itching inside the mouth;
• excess saliva in the mouth;
• chills;
• pain (in the abdomen, at the wound site, at the level of the muscles, groin, hands or feet);
• swelling of the ankles, feet, legs or joints;
• joint stiffness;
• ECG abnormalities;
• fresh blood from the anus, usually with stools;
• feeling tired;
• partial paralysis;
• difficulty breathing;
• redness of the skin or the area around the wound;
• complications (e.g., redness, swelling, pain) at the wound site;
• excessive sweating;
• discoloration of the nails.

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

• inability to urinate (completely or partially empty the bladder);
• ineffectiveness of EXPAREL liposomal.

Some of the above side effects may be observed more frequently in children and adolescents aged 6 years and older.

Additional side effects observed in children and adolescents aged 6 years and older
Very common(may affect more than 1 in 10 people):

• anemia

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

• feeling of tingling;
• hearing loss;
• fastened breathing;
• delayed awakening from anesthesia.

Reporting of side effects
If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly through the national reporting system listed in Annex V. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store EXPAREL liposomal

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 vial label after
Exp. The expiry date refers to the last day of that month.
Store in a refrigerator (2°C – 8°C). Do not freeze.
EXPAREL liposomal can also be stored at room temperature (at a temperature below
25°C) for a maximum of 30 days in closed and sealed vials. The vials must not be
returned to the refrigerator.
After first opening
The chemical and physical stability during use of EXPAREL liposomal withdrawn from the vials and transferred into
polypropylene syringes has been demonstrated for 48 hours if stored in a refrigerator (2°C – 8°C) or for
6 hours if stored at room temperature (below 25°C). From a microbiological point of view, the
product must be used immediately. If not used immediately, the in-use storage times and conditions prior to use are the responsibility of the user and must not
exceed 24 hours at a temperature of 2°C – 8°C unless the opening has been carried out under controlled and validated aseptic conditions.
After dilution
The chemical and physical stability during use of EXPAREL liposomal when mixed with other
formulations of bupivacaine has been demonstrated for 24 hours at room temperature (at a temperature
below 25°C). When mixed with sodium chloride 9 mg/mL (0.9%) solution or Ringer’s
lactate, the chemical and physical stability during use has been demonstrated for 4 hours when stored in a refrigerator
(2°C – 8°C) and at room temperature (at a temperature below 25°C). From a microbiological point of view, unless the method of dilution precludes the risk of microbial contamination, the
product must be used immediately. If not used immediately, the in-use storage times and conditions prior to use are the responsibility of the user.

6. Contents of the pack and other information

What EXPAREL liposomal contains
The active ingredient is bupivacaine. Each mL contains 13.3 mg of bupivacaine in a liposomal dispersion
for injectable prolonged-release preparation.
Each vial of 10 mL of prolonged-release injectable dispersion contains
133 mg of bupivacaine as a free base.
Each vial of 20 mL of prolonged-release injectable dispersion contains
266 mg of bupivacaine as a free base.
The other ingredients are: dipalmitoylphosphatidylcholine (DEPC), dipalmitoylphosphatidylglycerol (DPPG),
cholesterol for parenteral use, tricaprilin, sodium chloride, phosphoric acid and water for injections.

Description of the appearance of EXPAREL liposomal and contents of the pack
EXPAREL liposomal is a prolonged-release injectable dispersion of colour from
white to off-white.
It is available in single-use type I glass vials of 10 mL or 20 mL, with a grey butyl rubber stopper
coated with ethylene tetrafluoroethylene and a tear-off aluminium/polypropylene seal.
Each pack contains 4 or 10 vials.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Pacira Ireland Ltd
Unit 13
Classon House
Dundrum Business Park
Dundrum,
Dublin 14
D14W9Y3
Ireland

Manufacturer
Millmount Healthcare Limited
Block-7, City North Business Campus
Stamullen, Co. Meath
K32 YD60
Ireland
For further information on this medicinal product, contact the local representative of the marketing
authorisation holder:
More detailed information on this medicine is available on the website of the European Medicines
Agency: http://www.ema.europa.eu .
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The following information is intended exclusively for healthcare professionals:
Important: Before using the medicine, consult the Summary of Product Characteristics
(SmPC).
Each vial of EXPAREL liposomal is for single use only.
Unopened vials of EXPAREL liposomal must be stored in a refrigerator at a temperature
between 2°C and 8°C. EXPAREL liposomal must not be frozen.
Unopened and sealed vials of EXPAREL liposomal may also be stored at room temperature (below 25°C) for a maximum of 30 days. The vials must not be returned
to the refrigerator.
After first opening
The chemical and physical stability in use of EXPAREL liposomal drawn from vials and transferred into
polypropylene syringes has been demonstrated for 48 hours if stored in a refrigerator (2°C – 8°C) or for
6 hours if stored at room temperature (below 25°C). From a microbiological point of view, the
product must be used immediately. If not used immediately, storage times in use and conditions prior to use are the responsibility of the user and must not exceed 24 hours at a temperature of 2°C – 8°C unless the opening has been carried out under controlled and validated aseptic conditions.
After dilution
The chemical and physical stability in use of EXPAREL liposomal when mixed with other
bupivacaine formulations has been demonstrated for 24 hours at room temperature (at a temperature
below 25°C). When mixed with sodium chloride 9 mg/mL (0.9%) solution or Ringer’s
lactate, the chemical and physical stability in use has been demonstrated for 4 hours when stored in a refrigerator
(2°C – 8°C) and at room temperature (at a temperature below 25°C). From a microbiological point of
view, unless the dilution method precludes the risk of microbial contamination, the
product must be used immediately. If not used immediately, storage times in use and conditions prior to use are the responsibility of the user.
Vials of EXPAREL liposomal must be visually inspected before
administration. They must be gently inverted to re-suspend the
particles in the dispersion immediately before withdrawal from the vial. If the contents have
settled, it may be necessary to invert the vial several times.
EXPAREL liposomal is intended for single-dose administration only. The maximum dose must not exceed 266 mg (20 mL). The recommended dose for local infiltration depends
on the size of the surgical site, the volume needed to cover the area and patient-specific factors that may affect the safety of an amidic-type local anaesthetic (see
section 4.2 of the SmPC).
EXPAREL liposomal can be administered in the ready-to-use dispersion or diluted up to a
concentration of 0.89 mg/mL (i.e. 1:14 dilution by volume) with sodium chloride
9 mg/mL (0.9%) solution or Ringer’s lactate. EXPAREL liposomal must not be mixed with other
medicines, nor diluted with water or other hypotonic agents, as this causes destruction of the
liposomal particles.
EXPAREL liposomal is a liposomal formulation and must not be used interchangeably with
other bupivacaine formulations. Bupivacaine hydrochloride (immediate-release formulations) and
EXPAREL liposomal can be administered concurrently in the same syringe provided that
the ratio between the dose in milligrams of bupivacaine solution and EXPAREL liposomal is not
greater than 1:2. The total amount of bupivacaine HCl and EXPAREL liposomal in co-
administration must not exceed the equivalent of 400 mg of bupivacaine HCl in adults. The
amount of bupivacaine present in EXPAREL liposomal is expressed as bupivacaine free base, therefore when calculating the total dose of bupivacaine for co-administration, the amount of
bupivacaine from EXPAREL liposomal must be converted to bupivacaine HCl equivalent by
multiplying the EXPAREL liposomal dose by a factor of 1.128.
Caution is advised when co-administering EXPAREL liposomal and bupivacaine HCl,
especially in highly vascular areas where higher systemic absorption is expected
(see section 4.4 of the SmPC).
EXPAREL liposomal can be administered after lidocaine with a delay of at least
20 minutes.
When applying a topical antiseptic such as povidone-iodine, allow it to dry before
administering EXPAREL liposomal at the same site. EXPAREL liposomal must not come into
contact with povidone-iodine solutions.
EXPAREL liposomal must be injected slowly (generally 1-2 mL per injection) using a
needle with a diameter of 25 gauge or higher. During administration, the surgical site should be
frequently aspirated, when clinically appropriate, to ensure that no blood is present and
to minimise the risk of accidental intravascular injection.
Unused medicine and waste materials derived from such medicine must be disposed of in accordance
with local regulations.