Merit Medical HepaSphere Microspheres(With Doxorubicin) IFU-Int'l: инструкция

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Instructions for use

Instructions d'utilisation

Gebrauchsanweisungen

Instrucciones de utilización

Istruzioni per l’uso

Instruções de utilização

Gebruiksaanwijzing

Brugsanvisning

Bruksanvisning

Käyttöohjeet

Instruksjoner for bruk

Οδηγίες χρήσης

Kullanma talimatları

Pokyny pro použití

Instrukcja stosowania

Instrucţiuni de utilizare

Инструкции за употреба

Használati útmutató

Lietošanas norādījumi

Naudojimo instrukcijos

Návod na použitie

Kasutusjuhised

Инструкции по применению

0459 - 2004

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English.........................................................................................................................3

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ENGLISH

c

aution should be used for any procedures involving the extracranial

INTENDED USE

c

irculation encompassing the head and neck, and the physician should

HepaSphere™ Microspheres are indicated for use in embolization of

carefully weigh the potential benefits of using embolization against the

b

lood vessels with or without delivery of doxorubicin HCl for therapeutic

risks and potential complications of the procedure. These complications

or preoperative purposes in the following procedures:

can include blindness, hearing loss, loss of smell, paralysis, and death.

• Embolization of hepatocellular carcinoma

• Serious radiation induced skin injury may occur to the patient due to

•

Embolization of metastases to the liver.

long periods of fluoroscopic exposure, large patient, angled x-ray

projections and multiple image recording runs or radiographs. Refer to

DESCRIPTION

your facility’s clinical protocol to ensure the proper radiation dose is

HepaSphere Microspheres are part of a family of embolic agents based

a

pplied for each specific type of procedure performed.

on proprietary technologies. They are designed for controlled, targeted

• Onset of radiation injury to the patient may be delayed. Patients

embolization. The HepaSphere Microspheres can be loaded with

should be counselled on potential radiation effects, what to look for and

d

oxorubicin HCl and are able to release the drug locally at the

w

ho to contact if symptoms occur.

embolization site. HepaSphere Microspheres are biocompatible,

• HepaSphere Microspheres MUST NOT be reconstituted in sterile

hydrophilic, non-resorbable, expandable, and conformable

water for injection. Reconstitution in sterile water results in extensive

microspheres. HepaSphere Microspheres swell upon exposure to

swelling that renders the injection of HepaSphere Microspheres very

aqueous solutions. They are available in a range of sizes.

difficult or may prevent injection.

• Do not reconstitute HepaSphere Microspheres with Lipiodol / Ethiodol.

Dry (µm)

• Pay careful attention for signs of mistargeted embolization. During

30-60

injection carefully monitor patient vital signs to include SaO

2

(e.g.

hypoxia, CNS changes). Consider terminating the procedure,

50-100

investigating for possible shunting, or increasing Microspheres size if

100-150

any signs of mistargeting occur or patient symptoms develop.

• Consider upsizing the Microspheres if angiographic evidence of

150-200

embolization does not quickly appear evident during injection of the

Microspheres.

DEVICE PACKAGING

HepaSphere Microspheres are contained in a sterile, 10 ml Cyclic Olefin

Copolymers (COC) vial,with a crimped cap,packaged in a sealed pouch.

Warnings about use of small microspheres:

Contents: 25 mg or 50 mg of dry HepaSphere Microspheres per vial to

• Careful consideration should be given whenever use is contemplated

be reconstituted before use.

of embolic agents that are smaller in diameter than the resolution

capability of your imaging equipment. The presence of arteriovenous

CONTRAINDICATIONS

anastomoses, branch vessels leading away from the target area or

• Patients intolerant to vascular occlusion procedures

emergent vessels not evident prior to embolization can lead to

• Vascular anatomy or blood flow precluding correct catheterplacement

mistargeted embolization and severe complications.

or embolic injection

• Microspheres smaller than 100 microns will generally migrate distal

• Presence or suspicion of vasospasm

to anastomotic feeders and therefore are more likely to terminate

• Presence or likely onset of haemorrhage

circulation to distal tissue. Greater potential of ischemic injury results

• Presence of severe atheromatous disease

from use of smaller sized microspheres and consideration must be

• Feeding arteries too small to accept the selected HepaSphere

given to the consequence of this injury prior to embolization. The

Microspheres

potential consequences include swelling, necrosis, paralysis, abscess

• Presence of collateral vessel pathways potentially endangering

and/or stronger post-embolization syndrome.

normal territories during embolization

• Post embolization swelling may result in ischemia to tissue adjacent

• High flow arteriovenous shunts or fistulae with luminal diameter

to target area. Care must be given to avoid ischemia of intolerant, non

greater than the selected size of HepaSphere Microspheres

targeted tissue such as nervous tissue.

• Vascular resistance peripheral to the feeding arteries precluding

passage of HepaSphere Microspheres into the lesion

PRECAUTIONS

• Presence of arteries supplying the lesion not large enough to accept

HepaSphere Microspheres must only be used by physicians trained in

HepaSphere Microspheres

vascular embolization procedures. The size and quantity of

• Do not use in pulmonary vasculature, coronary and central nervous

microspheres must be carefully selected according to the lesion to be

system vasculature

treated and the potential presence of shunts. Only the physician can

• Known sensitivity to poly vinyl alcohol-co-sodium acrylate

decide the most appropriate time to stop the injection of HepaSphere

Microspheres.

WARNINGS

• HepaSphere Microspheres size must be chosen after consideration of

Do not use if the vial, cap, or pouch appear damaged.

the arteriovenous angiographic appearance. HepaSphere Microspheres

For single patient use only - Contents supplied sterile - Never reuse,

size should be selected to prevent passage from any artery to vein.

reprocess, or resterilize the contents of a vial that has been opened.

• Some of the HepaSphere Microspheres may be slightly outside of the

Reusing, reprocessing or resterilizing may compromise the structural

range, so the physician should be sure to carefully select the size of

integrity of the device and or lead to device failure, which in turn may

HepaSphere Microspheres according to the size of the target vessels at

result in patient injury, illness or death. Reusing, reprocessing or

the desired level of occlusion in the vasculature and after consideration

resterilizing may also create a risk of contamination of the device and or

of the arteriovenous angiographic appearance.

cause patient infectionor cross infection including,but not limited to,the

• Because of the significant complications of misembolization, extreme

transmission of infectious disease(s) from one patient to another.

3

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C

ontamination of the device may lead to injury, illness or death of the

M

icrospheres swell approximately 4 times their original dry diameter in

patient.All procedures must be performed according to accepted aseptic

approximately 10 minutes. For example, HepaSphere Microspheres with

technique.

a diameter of approximately 50-100 microns in their dry state will

e

xpand to approximately 200-400 microns during reconstitution as

HepaSphere Microspheres MUST NOT be used in their original

recommended below. Because of the inherent variability of the swelling

dry state.

They must be reconstituted before use. HepaSphere

process, some of the HepaSphere Microspheres will be slightly outside

M

icrospheres swell in aqueous solution. The magnitude of swelling

o

f this range after reconstitution, so the physician should be sure to

depends on the ionic concentration of the solution. The microspheres

carefully select the size of HepaSphere Microspheres according to the

swell to approximately four times their diameter in 0.9% NaCl aqueous

size of the target vessels at the desired level of occlusion in the

solution and non-ionic contrast media, as compared to their initial dry

vasculature and the nature of the aqueous solution.

diameter. The magnitude of swelling when loaded with doxorubicin HCl

Note:

To expand properly HepaSphere Microspheres need to be exposed

is dependent upon the amount of drug with which the product is loaded.

to a minimum of 10ml solution.

L

yophilized doxorubicin HCl must be reconstituted in NaCl0.9 % solution.

T

he magnitude of swelling when loaded with doxorubicin HCl is

HepaSphere Microspheres undergo a slight size decrease of about 20%

dependent upon the amount of drug with which the product is loaded.

w

hen loaded with doxorubicin HCl compared to the size in pure NaCl 0.9

H

epaSphere Microspheres undergo a slight size decrease of about 20%

% aqueous solution. HepaSphere Microspheres are compressible and

when loaded with doxorubicin HCl compared to the size in pure NaCl

can be injected easily through microcatheters. However, injection of the

0.9% aqueous solution.

HepaSphere Microspheres before they are fully expanded could result in

failure to reach the intended embolization target and possible

CATHETER COMPATIBILITY

embolization of a larger tissue area.

HepaSphere Microspheres can be injected with microcatheters with the

Note:

Maximum recommended concentration of doxorubicin HCl is

following specifications:

5mg/ml. Concentrations of doxorubicin HCl above 5mg/ml substantially

increase the solution viscosity and make it difficult to handle with

Approximate

HepaSphere Microspheres.

Catheter Size

Dry (µm)

Reconstituted

Patients with known allergies to non-ionic contrast media may require

ID (in.)

Size range (µm)

corticosteroids prior to embolization.

Additional evaluations or precautions may be necessary in managing

30-60 120 - 240

≥ 0.021

periprocedural care for patients with the following conditions:

• Bleeding diathesis or hypercoagulative state

50-100 200 - 400

≥ 0.021

• Immunocompromise

100-150 400 - 600

≥ 0.024

POTENTIAL COMPLICATIONS

150-200 600 - 800

≥ 0.027

Vascular embolization is a high-risk procedure. Complications may occur

at any time during or after the procedure, and may include, but are not

limited to, the following:

• Paralysis resulting from untargeted embolization or ischemic injury

INSTRUCTIONS

from adjacent tissue oedema

HepaSphere Microspheres must be reconstituted with 100% NaCl 0.9%

• Undesirable reflux or passage of HepaSphere Microspheres into

aqueous solution or non-ionic contrast medium, or 50% non-ionic

normal arteries adjacent to the targeted lesion or through the lesion into

contrast medium and 50% NaCl 0.9% aqueous solution if using without

other arteries or arterial beds, such as the internal carotid artery,

delivery of doxorubicin HCl, or loaded with doxorubicin HCl solution

pulmonary, or coronary circulation

before positioning the catheter.

• Pulmonary embolism due to arteriovenous shunting

• Carefully select the size of HepaSphere Microspheres according to the

• Ischemia at an undesired location, including ischemic stroke, ischemic

size of the target vessels at the desired level of occlusion in the

infarction (including myocardial infarction), and tissue necrosis

vasculature and the nature of the aqueous solution. See the description

• Capillary bed occlusion and tissue damage

of “SWELLING BEHAVIOR”.

• Vasospasm

• HepaSphere Microspheres may be present outside the vial.Therefore,

• Recanalisation

the vial must be aseptically handled away from the main sterile field.

• Blindness, hearing loss, and loss of smell

• Ensure the compatibility of the HepaSphere Microspheres with the

• Foreign body reactions necessitating medical intervention

intended size of catheter to be used. See the table above.

• Infection necessitating medical intervention

• Inspect the packaging to confirm that it is intact. Remove the vial from

• Complications related to catheterization (e.g. haematoma at the site of

the pouch.The external surface of the vial is sterile.

entry, clot formation at the tip of the catheter and subsequent

dislodgement, and nerve and/or circulatory injuries which may result in

HEPASPHERE MICROSPHERES CAN BE USED WITH OR WITHOUT

leg injury)

LOADING OF DOXORUBICIN HCL.

• Allergic reaction to medications (e.g. analgesics)

• Allergic reaction to non-ionic contrast media or embolic material

OPTION 1: PREPARATION FOR EMBOLIZATION WITHOUT

• Vessel or lesion rupture and haemorrhage

DOXORUBICIN HCL (BLAND)

• Death

The approximate reconstitution time when used without loading of

• Additional information is found in the Warnings section

doxorubicin HCl is 10 min.

SWELLING BEHAVIOR

• Fill a 10ml syringe with 100% NaCl 0.9% aqueous solution or non-

HepaSphere Microspheres swell during reconstitution with NaCl 0.9%

ionic contrast medium (or 50% NaCl 0.9% aqueous solution and 50%

aqueous solution and non-ionic contrast media.When hydrated in 100%

contrast). Connect the syringe to a needle of 20 gauge diameter or larger.

NaCl 0.9% aqueous solution or non-ionic contrast medium, or 50% non-

• To ensure proper reconstitution of the HepaSphere Microspheres,

ionic contrast and 50% NaCl 0.9% aqueous solution, HepaSphere

grasp the vial horizontally in your fingertips and roll the vial several times.

This will transfer the dry contents of the vial to the sidewall.

4

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N

ote:

P

ull back only the flip-top cap; do not remove the crimp ring or the

•

Connect one of the 30ml syringes containing 10ml of the doxorubicin

stopper from the vial.

HCl solution to a needle of 20 gauge diameter or larger.

• Carefully insert the needle from the syringe through the stopper of the

• To ensure proper reconstitution of the HepaSphere Microspheres,grasp

v

ial. Continue rolling the vial in your fingertips and inject the full amount

t

he HepaSphere Microspheres vial horizontally in your fingertips and roll

(10ml)

of reconstitution medium into the vial,then place the vial vertically

the vial several times.This will transfer the dry contents of the vial to the

and carefully remove the syringe with the needle attached.

sidewall.

N

ote:

T

he vial is hermetically closed. Proper aspiration and/or venting

N

ote:

P

ull back only the flip-top cap; do not remove the crimp ring or the

techniques,as approved by the healthcare facility, may be used for easier

stopper from the vial.

injection of reconstitution medium into vial.If aspiration of air from the vial

• Carefully insert the needle of one of the 30ml syringes containing 10ml

is performed prior to reconstitution, exercise caution not to remove the

of doxorubicin HCl solution through the stopper of the vial. Continue

spheres from the vial.

rolling the vial in your fingertips and inject the full 10ml of doxorubicin HCl

• To ensure a homogeneous reconstitution of the HepaSphere

solution into the vial.

M

icrospheres, gently invert the vial back and forth so that the liquid

•

Place theHepaSphere Microspheres vial vertically. Carefully removethe

contacts the stopper 5-10 times.

syringe with the needle attached, and allow the vial to stand for 10

N

ote:

V

igorous shaking may introduce micro bubbles, which can cause

m

inutes in order to completely hydrate the spheres.

the microspheres to aggregate.

• During the 10 minutes hydration period, shake the HepaSphere

• Wait a minimum of 10 minutes

to allow the HepaSphere Microspheres

Microspheres vial several times back and forth so that the liquid contacts

to reconstitute and expand fully.

the grey stopper. Repeat this process every 2-3 minutes to ensure a

• Use a 30ml syringe and 20 gauge or larger needle to aspirate the

homogenous reconstitution of the HepaSphere Microspheres.

contents of the vial. Rotate the vial to a vertical position with the bottom of

Note:

The vial is hermetically closed. Proper aspiration and/or venting

the vial facing upward.Pull the needle back so that it is submerged in the

techniques,as approved by the healthcare facility, may be used for easier

liquid but not occluded by the stopper. Gently aspirate the entire contents

injection of reconstitution media into the vial. If aspiration of air from the

of the vial into the syringe.

vial is performed prior to reconstitution, exercise caution not to remove

Note:

If the air was previously aspirated from the vial, gentle injection of

the spheres from the vial.

air using the syringe prior to aspirating the contents of the vial will ensure

• After the 10 minutes hydration period, attach a 20 gauge or larger

an easier aspiration of vial contents into the syringe.If all contents are not

needle to the second 30ml syringe containing the remaining 10ml of

withdrawn, introduce an additional volume of air and repeat the aspiration

doxorubicin HCl solution and insert into the HepaSphere Microspheres

process.It is possible to add an additional amount of non-ionic contrast or

vial. Aspirate the contents of the HepaSphere Microspheres vial into the

NaCl 0.9% aqueous solution into the syringe in order to get a higher

30ml syringe containing the remaining 10 ml of doxorubicin HCl solution.

dispersion of microspheres.

Rotate the vial to a vertical position with the bottom of the vial facing

Note:

HepaSphere Microspheres reconstituted as described abovecan be

upward. Pull the needle back so that it is submerged in the liquid but not

used in the presence of chemotherapeutic agents such as cisplatin,

occluded bythe stopper.Gently aspirate the entire contents ofthe vial into

epirubicin, doxorubicin HCl, fluorouracil, irinotecan and mitomycin after

the syringe.

hydration. However for drug delivery, HepaSphere Microspheres are only

• Prior to removing the needle from the HepaSphere Microspheres vial,

indicated for use with doxorubicin HCl (see below Option 2).

while holding the syringe vertically, gently pull the plunger of the syringe

• If microspheres were reconstituted using 100% NaCl 0.9%, non-ionic

down, removing any solution that may be in the hub of the needle.

contrast medium must be added to thesyringecontainingthe HepaSphere

• Replace the needle with a syringe cap and invert the syringe back and

Microspheres for visualization under fluoroscopy. If non-ionic contrast

forth to disperse the contents within the syringe. Wait a minimum of 60

medium was used to reconstitute the microspheres, additional non-ionic

minutes to allow the HepaSphere Microspheres to expand fully and load

contrast medium may be added.

the doxorubicin HCl. During the 60 minutes, the syringe should be

inverted every 10 – 15 minutes in order to optimize the drug distribution

OPTION 2: PREPARATION FOR EMBOLIZATION LOADED WITH

into the spheres.

DOXORUBICIN HCL

• After 60 minutes, let the syringe stand for the spheres to settle down

and purge all supernatant and discard it following facility approved

WARNING:

Liposomal formulations of doxorubicin HCl are not suitable for

standards.

loading into HepaSphere Microspheres.

• Add a minimum of 20ml of non-ionic contrast medium to the 30ml

syringe containingthe doxorubicin HCl loaded HepaSphere Microspheres,

As a general guideline the loadingof lyophilizeddoxorubicin HCl solubilized

however larger volume of solution can provide better control during

in NaCl 0.9% solution into HepaSphere Microspheres will take one hour.

embolization. Gently invert the syringe 2 or 3 times and wait 5 min until

The HepaSphere Microspheres should not be used before they are fully

solution homogeneity is reached.

hydrated and expanded. Loading kinetics of pre-solubilized doxorubicin

• Before any injection, check the spheres are in suspension, if not invert

HCI may vary, depending on the concentration and pH of the solution.

the syringe back and forth to disperse contents within the syringe.

• Choose the appropriate dose of doxorubicin HCl to load into the

HepaSphere Microspheres.

DELIVERY INSTRUCTIONS

Note:

• Carefully evaluate the vascularnetworkassociated with the target lesion

• A maximum dose of doxorubicin HCl

75mg

can be loaded into each vial

utilizing high resolution imaging.

of HepaSphere Microspheres. Solubilize the desired dose of lyophilized

Note:

It is important to determine if any arteriovenous shunts are present

doxorubicin HCl in 20ml

of NaCl 0.9% solution for injection. NEVER USE

before beginning embolization.

PURE WATER

• Using standard techniques, position the delivery catheter within the

Note:

Maximum recommended concentration of doxorubicin HCl is

target vessel and the catheter tip as close as possible to the embolization

5mg/ml. Concentrations of doxorubicin HCl above 5mg/ml substantially

target.

increase the solution viscosity and make it difficult to handle with

• Use an injection syringe no larger than 3ml for the delivery of

HepaSphere Microspheres.

doxorubicin loaded HepaSphere Microspheres. Use of a 1ml injection

• Aspirate the 20ml of doxorubicin HCl solution into two separate 30ml

syringe is recommended.

syringes. Each 30ml syringe should contain 10ml of doxorubicin HCl

• Aspirate 1ml of the HepaSphere Microspheres mixture into the injection

solution.

syringe.

5