INSTRUCTIONS FOR USE

INTENDED USE

HepaSphere™ Microspheres are indicated

for use in embolization of blood vessels

with or without delivery of doxorubicin HCl

for therapeutic or preoperative

purposes in the following procedures:

• Embolization of hepatocellular

carcinoma

• Embolization of metastases to the liver.

HepaSphere Microspheres loaded with

irinotecan are indicated for use in:

• Embolization of metastatic colorectal

cancer (mCRC) to the liver.

DESCRIPTION

HepaSphere Microspheres are part of a

family of embolic agents based on pro-

prietary technologies. They are designed

for controlled, targeted embolization. The

HepaSphere Microspheres can be loaded

with doxorubicin HCl or irinotecan, and are

able to release the drug locally at the em-

bolization site. HepaSphere Microspheres

are biocompatible, hydrophilic, non-re-

sorbable, expandable, and conformable

microspheres. HepaSphere Microspheres

swell upon exposure to aqueous solutions.

They are available in a range of sizes.

DEVICE PACKAGING

HepaSphere Microspheres are contained

in a sterile, 10 ml vial, with a crimped cap,

packaged in a sealed pouch.

Contents: 25 mg or 50 mg of dry

HepaSphere Microspheres per vial to be

reconstituted before use.

CONTRAINDICATIONS

• Patients intolerant to vascular occlusion

procedures

• Vascular anatomy or blood ow pre-

cluding correct catheter placement or

embolic injection

• Presence or suspicion of vasospasm

• Presence or likely onset of haemorrhage

• Presence of severe atheromatous

disease

• Presence of collateral vessel pathways

potentially endangering normal territo-

ries during embolization

• High ow arteriovenous shunts or

stulae with luminal diameter greater

than the selected size of HepaSphere

Microspheres

• Vascular resistance peripheral to the

feeding arteries precluding passage

of HepaSphere Microspheres into the

lesion

• Do not use in pulmonary vasculature,

coronary and central nervous system

vasculature

• Known sensitivity to poly vinyl alco-

hol-co-sodium acrylate

WARNINGS

• HepaSphere Microspheres size must be

chosen after consideration of the arte-

riovenous angiographic appearance.

HepaSphere Microspheres size should

be selected both to be appropriate for

the size of the vessel feeding the target

and to prevent passage from artery

to vein.

• Some of the HepaSphere Microspheres

may be slightly outside of the range,

so the physician should be sure to

carefully select the size of HepaSphere

Microspheres according to the size of

the target vessels at the desired level of

occlusion in the vasculature and after

consideration of the arteriovenous

angiographic appearance.

• Because of the signicant compli-

cations of untargeted embolization,

extreme caution should be used for any

procedures involving the extracranial

circulation encompassing the head

and neck, and the physician should

carefully weigh the potential benets

of using embolization against the risks

and potential complications of the

procedure. These complications can

include blindness, hearing loss, loss of

smell, paralysis, and death.

• Serious radiation induced skin injury

may occur to the patient due to long

periods of uoroscopic exposure, large

patient, angled x-ray projections and

multiple image recording runs or radio-

graphs. Refer to your facility’s clinical

protocol to ensure the proper radiation

dose is applied for each specic type of

procedure performed.

• Onset of radiation injury to the patient

may be delayed. Patients should be

counselled on potential radiation

eects, what to look for and whom to

contact if symptoms occur.

• HepaSphere Microspheres MUST NOT

be reconstituted in sterile water for

injection. Reconstitution in sterile

INSTRUCTIONS FOR USE

English

Dry(μm) 30-60 50-100 100-150 150-200

730142001_001_hepasphere_irinotecan.indd 1 1/7/16 8:22 AM

water results in extensive swelling that

renders the injection of HepaSphere

Microspheres very dicult or may

prevent injection.

• Do not reconstitute HepaSphere Micro-

spheres with Lipiodol / Ethiodol.

• Pay careful attention for signs of untar-

geted embolization. During injection

carefully monitor patient vital signs to

include SaO

(e.g. hypoxia, CNS chang-

es). Consider terminating the procedure,

investigating for possible shunting, or

increasing Microspheres size if any signs

of untargeted embolization occur or

patient symptoms develop.

• Consider upsizing the Microspheres if

angiographic evidence of embolization

does not quickly appear evident during

injection of the Microspheres.

Warnings about use of small micro-

spheres:

• Careful consideration should be given

whenever use is contemplated of em-

bolic agents that are smaller in diameter

than the resolution capability of your

imaging equipment. The presence of

arteriovenous anastomoses, branch ves-

sels leading away from the target area

or emergent vessels not evident prior

to embolization can lead to untargeted

embolization and severe complications.

• Microspheres smaller than 100 microns

are more likely to terminate circulation

to distal tissue. Greater potential of isch-

emic injury results from use of smaller

sized microspheres and consideration

must be given to the consequence of

this injury prior to embolization. The

potential consequences include swell-

ing, necrosis, paralysis, abscess and/or

stronger post-embolization syndrome.

• Post embolization swelling may result

in ischemia to tissue adjacent to target

area. Care must be given to avoid

ischemia of intolerant, non targeted

tissue such as nervous tissue.

PRECAUTIONS

HepaSphere Microspheres must only be

used by physicians trained in vascular

embolization procedures. The size and

quantity of microspheres must be carefully

selected according to the lesion to be

treated and the potential presence of

shunts. Only the physician can decide the

most appropriate time to stop the injection

of HepaSphere Microspheres.

Do not use if the vial, cap, or pouch

appear damaged.

For single patient use only - Contents

supplied sterile - Never reuse, reprocess,

or resterilize the contents of a vial that

has been opened. Reusing, reprocessing or

resterilizing may compromise the structural

integrity of the device and or lead

to device failure, which in turn may result

in patient injury, illness or death. Reusing,

reprocessing or resterilizing may also

create a risk of contamination of the device

and or cause patient infection or cross

infection including, but not limited to,

the transmission of infectious disease(s)

from one patient to another. Contamina-

tion of the device may lead to injury,

illness or death of the patient. All proce-

dures must be performed according to

accepted aseptic technique.

HepaSphere Microspheres MUST NOT be

used in their original dry state. They must

be reconstituted before use. HepaSphere

Microspheres swell in aqueous solution.

The magnitude of swelling depends on the

ionic concentration of the solution. The

microspheres swell to approximately four

times their diameter in 0.9% NaCl aqueous

solution and nonionic contrast media, as

compared to their initial dry diameter. The

magnitude of swelling when loaded with

doxorubicin HCl is dependent upon the

amount of drug with which the product is

loaded. Lyophilized doxorubicin HCl must

be reconstituted in NaCl 0.9 % solution.

HepaSphere Microspheres undergo a

size decrease of about 20% when loaded

with doxorubicin HCl, and 30% when

loaded with irinotecan compared to the

size in pure NaCl 0.9 % aqueous solution.

HepaSphere Microspheres are compress-

ible and can be injected easily through

microcatheters. However, injection of the

HepaSphere Microspheres before they are

fully expanded could result in failure to

reach the intended embolization target

and possible embolization of a larger tissue

area.

Note: Maximum recommended concen-

tration of doxorubicin HCl is 5mg/ml.

Concentrations of doxorubicin HCl above

5mg/ml substantially increase the solution

viscosity and make it dicult to handle

with HepaSphere Microspheres.

Maximum recommended concentration of

irinotecan is 20 mg/ml.

730142001_001_hepasphere_irinotecan.indd 2 1/7/16 8:22 AM

Patients with known allergies to non-ionic

contrast media may require corticosteroids

prior to embolization. Additional evalua-

tions or precautions may be necessary in

managing periprocedural care for patients

with the following conditions:

• Bleeding diathesis or hypercoagulative

state

• Immunocompromise

Note: If loading HepaSphere Microspheres

with doxorubicin HCl or irinotecan, refer to

the appropriate drug IFU for information

concerning contraindications, warnings,

precautions, potential complications, dos-

age, and patient management before use.

POTENTIAL COMPLICATIONS

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 from

adjacent tissue oedema

• Undesirable reux or passage of

HepaSphere Microspheres into normal

arteries adjacent to the targeted lesion

or through the lesion into other arteries

or arterial beds, such as the internal

carotid artery, pulmonary, or coronary

circulation

• Pulmonary embolism due to arteriove-

nous shunting

• Ischemia at an undesired location,

including ischemic stroke, ischemic

infarction (including myocardial infarc-

tion), and tissue necrosis

• Capillary bed occlusion and tissue

damage

• Vasospasm

• Recanalisation

• Blindness, hearing loss, and loss of smell

• Foreign body reactions necessitating

medical intervention

• Infection necessitating medical inter-

vention

• Complications related to catheterization

(e.g. haematoma at the site of entry, clot

formation at the tip of the catheter and

subsequent dislodgement, and nerve

and/or circulatory injuries which may

result in leg injury)

• Allergic reaction to medications (e.g.

analgesics)

• Allergic reaction to non-ionic contrast

media or embolic material

• Vessel or lesion rupture and hemor-

rhage

• Death

• Additional information is found in the

Warnings section

SWELLING BEHAVIOR

HepaSphere Microspheres swell during

reconstitution with NaCl 0.9% aqueous

solution and non-ionic contrast media.

When hydrated in 100% NaCl 0.9% aque-

ous solution or non-ionic contrast medium,

or 50% non-ionic contrast and 50% NaCl

0.9% aqueous solution, HepaSphere Micro-

spheres swell approximately 4 times their

original dry diameter in approximately 10

minutes. For example, HepaSphere Micro-

spheres with a diameter of approximately

50-100 microns in their dry state will

expand to approximately 200-400 microns

during reconstitution as recommended

below. Because of the inherent variabil-

ity of the swelling process, some of the

HepaSphere Microspheres will be slightly

outside of this range after reconstitution,

so the physician should be sure to carefully

select the size of HepaSphere Microspheres

according to the size of the target vessels

at the desired level of occlusion in the

vasculature and the nature of the aqueous

solution.

Note: To expand properly HepaSphere

Microspheres need to be exposed to a

minimum of 10 ml of solution for doxoru-

bicin HCl or saline and a minimum of 5 ml

for irinotecan. The magnitude of swelling

when loaded with doxorubicin HCl is

dependent upon the amount of drug with

which the product is loaded. HepaSphere

Microspheres undergo a size decrease of

about 20% when loaded with doxorubicin

HCl compared to the size in pure NaCl 0.9%

aqueous solution and about 30 % when

loaded with irinotecan.

CATHETER COMPATIBILITY

HepaSphere Microspheres can be injected

with microcatheters with the following

specications:

Dry

(μm)

Approximate

Reconstituted

Size range (μm)

Catheter

Size ID(in.)

30-60 120-240 ≥0.021

50-100 200-400 ≥0.021

100-150 400-600 ≥0.024

150-200 600-800 ≥0.027

730142001_001_hepasphere_irinotecan.indd 3 1/7/16 8:22 AM

INSTRUCTIONS

HepaSphere Microspheres must be recon-

stituted with 100% NaCl 0.9% aqueous

solution or non-ionic contrast medium,

or 50% non-ionic contrast medium and

50% NaCl 0.9% aqueous solution if using

without delivery of doxorubicin HCl or

irinotecan, or loaded with doxorubicin

HCl solution or irinotecan solution before

positioning the catheter.

• Carefully select the size of HepaSphere

Microspheres according to the size of

the target vessels at the desired level

of occlusion in the vasculature and the

nature of the aqueous solution. See the

description of “SWELLING BEHAVIOR”.

• HepaSphere Microspheres may be

present outside the vial. Therefore, the

vial must be aseptically handled away

from the main sterile eld.

• Ensure the compatibility of the

HepaSphere Microspheres with the

intended size of catheter to be used.

See the table above.

• Inspect the packaging to conrm that

it is intact. Remove the vial from the

pouch. The external surface of the vial

is sterile.

• To prevent coring the rubber stopper,

insert the injection needle as follows:

1. Hold the needle so that the bevel

faces upwards and position the tip

diagonally to the insertion site. Press

the tip against the centre of the

insertion site.

2. Apply a gentle force to the needle in

the opposite direction to the bevel

to ease the needle into the insertion

site until the heel section of the

needle is no longer visible. Be careful

not to scrape o the upper-facing

surface of the rubber cap with the

heel of the needle tip.

3. Continuing to apply a gentle force to

the needle in the opposite direction

to the bevel, slowly insert the needle

vertically through the rubber cap.

4. After preparation, carefully examine

the solution to determine if there are

any rubber impurities present. If the

solution appears contaminated, do

not use it.

HEPASPHERE MICROSPHERES CAN BE

USED WITH OR WITHOUT LOADING OF

DOXORUBICIN HCl OR IRINOTECAN.

OPTION 1: PREPARATION FOR EMBOLI-

ZATION WITHOUT DRUG (BLAND)

The approximate reconstitution time when

used without loading of a drug is 10 min.

• Fill a 10ml syringe with 100% NaCl 0.9%

aqueous solution or non-ionic contrast

medium (or 50% NaCl 0.9% aqueous

solution and 50% contrast). Connect

the syringe to a needle of 20 gauge

diameter or larger.

• To ensure proper reconstitution of

the HepaSphere Microspheres, grasp

the vial horizontally in your ngertips

and roll the vial several times. This will

transfer the dry contents of the vial to

the sidewall.

Note: Pull back only the ip-top cap; do

not remove the crimp ring or the stopper

from the vial.

• Carefully insert the needle from the

syringe through the stopper of the

vial. Continue rolling the vial in your

ngertips and inject the full amount

(10ml) of reconstitution medium into

the vial, then place the vial vertically

and carefully remove the syringe with

the needle attached.

Note: The vial is hermetically closed. If

aspiration from the syringe into the vial

does not automatically occur, then, using

caution, manually aspirate air from the

vial into the syringe prior to injecting the

reconstitution uid. Proper aspiration and/

or venting techniques, as approved by

the healthcare facility, may be used for

easier injection of reconstitution medium

into vial. If aspiration of air from the vial is

performed prior to reconstitution, exercise

caution not to remove the spheres from

the vial.

• To ensure a homogeneous reconstitu-

tion of the HepaSphere Microspheres,

gently invert the vial back and forth

so that the liquid contacts the stopper

5-10 times.

• Note: Vigorous shaking may introduce

micro bubbles, which can cause the

microspheres to aggregate.

• Wait a minimum of 10 minutes to

allow the HepaSphere Microspheres to

reconstitute and expand fully.

• Use a 30ml syringe and 20 gauge or

larger needle to aspirate the contents

of the vial. Rotate the vial to a vertical

position with the bottom of the vial

facing upward. Pull the needle back so

(3)

(1)

(2)

DIRECTION OF FORCE

(3)

(1)

(2)

DIRECTION OF FORCE

(3)

(1)

(2)

DIRECTION OF FORCE

730142001_001_hepasphere_irinotecan.indd 4 1/7/16 8:22 AM

that it is submerged in the liquid but

not occluded by the stopper. Gently

aspirate the entire contents of the vial

into the syringe.

Note: If the air was previously aspirated

from the vial, gentle injection of air using

the syringe prior to aspirating the contents

of the vial will ensure an easier aspiration of

vial contents into the syringe. If all contents

are not withdrawn, introduce an additional

volume of air and repeat the aspiration

process. It is possible to add an additional

amount of non-ionic contrast or NaCl 0.9%

aqueous solution into the syringe in order

to get a higher dispersion of microspheres.

Note: HepaSphere Microspheres reconsti-

tuted as described above can be used in

the presence of chemotherapeutic agents

such as cisplatin, epirubicin, doxorubicin

HCl, uorouracil, irinotecan and mitomycin

after hydration. However for drug delivery,

HepaSphere Microspheres are only

indicated for use with doxorubicin HCl (see

below Option 2) or irinotecan (see below

Option 3).

• If microspheres were reconstituted

using 100% NaCl 0.9%, non-ionic

contrast medium must be added to

the syringe containing the HepaSphere

Microspheres for visualization under

uoroscopy. If non-ionic contrast

medium was used to reconstitute the

microspheres, additional non-ionic

contrast medium may be added.

OPTION 2: PREPARATION FOR

EMBOLIZATION LOADED WITH

DOXORUBICIN HCl

WARNING: Liposomal formulations of

doxorubicin HCl are not suitable for loading

into HepaSphere Microspheres.

As a general guideline the loading of

lyophilized doxorubicin HCl solubilized in

NaCl 0.9% solution into HepaSphere Micro-

spheres will take one hour. The HepaSphere

Microspheres should not be used before

they are fully hydrated and expanded.

Loading kinetics of pre-solubilized doxo-

rubicin HCI may vary, depending on the

concentration and pH of the solution.

• Choose the appropriate dose of doxo-

rubicin HCl to load into the HepaSphere

Microspheres.

Note: A maximum dose of doxorubicin HCl

75mg can be loaded into each vial of 25 mg

HepaSphere Microspheres. Solubilize the

desired dose of lyophilized doxorubicin HCl

in 20ml of NaCl 0.9% solution for injection.

NEVER USE PURE WATER

Note: Maximum recommended concen-

tration of doxorubicin HCl is 5mg/ml.

Concentrations of doxorubicin HCl above

5mg/ml substantially increase the solution

viscosity and make it dicult to handle

with HepaSphere Microspheres.

• Aspirate the 20ml of doxorubicin HCl

solution into two separate 30ml syring-

es. Each 30ml syringe should contain

10ml of doxorubicin HCl solution.

• Connect one of the 30ml syringes

containing 10ml of the doxorubicin

HCl solution to a needle of 20 gauge

diameter or larger.

• To ensure proper reconstitution of the

HepaSphere Microspheres, grasp the

HepaSphere Microspheres vial horizon-

tally in your ngertips and roll the vial

several times. This will transfer the dry

contents of the vial to the sidewall.

• Note: Pull back only the ip-top cap;

do not remove the crimp ring or the

stopper from the vial.

• Carefully insert the needle of one of

the 30ml syringes containing 10ml of

doxorubicin HCl solution through the

stopper of the vial. Continue rolling the

vial in your ngertips and inject the full

10ml of doxorubicin HCl solution into

the vial.

• Place the HepaSphere Microspheres vial

vertically. Carefully remove the syringe

with the needle attached, and allow the

vial to stand for 10 minutes in order to

completely hydrate the spheres.

• During the 10 minutes hydration period,

shake the HepaSphere Microspheres

vial several times back and forth so that

the liquid contacts the grey stopper.

Repeat this process every 2-3 minutes

to ensure a homogenous reconstitution

of the HepaSphere Microspheres.

Note: The vial is hermetically closed. If

aspiration from the syringe into the vial

does not automatically occur, then, using

caution, manually aspirate air from the

vial into the syringe prior to injecting the

reconstitution uid. Proper aspiration and/

or venting techniques, as approved by the

healthcare facility, may be used for easier

injection of reconstitution media into

the vial. If aspiration of air from the vial is

performed prior to reconstitution, exercise

caution not to remove the spheres from

the vial.

• After the 10 minutes hydration period,

attach a 20 gauge or larger needle to

the second 30ml syringe containing

730142001_001_hepasphere_irinotecan.indd 5 1/7/16 8:22 AM

the remaining 10ml of doxorubicin HCl

solution and insert into the HepaSphere

Microspheres vial. Aspirate the contents

of the HepaSphere Microspheres vial

into the 30ml syringe containing the

remaining 10 ml of doxorubicin HCl

solution. Rotate the vial to a vertical

position with the bottom of the vial

facing upward. Pull the needle back so

that it is submerged in the liquid but

not occluded by the stopper. Gently

aspirate the entire contents of the vial

into the syringe.

• Prior to removing the needle from the

HepaSphere Microspheres vial, while

holding the syringe vertically, gently

pull the plunger of the syringe down,

removing any solution that may be in

the hub of the needle.

• Replace the needle with a syringe cap

and invert the syringe back and forth

to disperse the contents within the

syringe.

• Wait a minimum of 60 minutes to

allow the HepaSphere Microspheres to

expand fully and load the doxorubicin

HCl. During the 60 minutes, the syringe

should be inverted every 10 – 15

minutes in order to optimize the drug

distribution into the spheres.

• After 60 minutes, let the syringe stand

for the spheres to settle down and

purge all supernatant and discard it

following facility approved standards.

• Add a minimum of 20ml of non-ionic

contrast medium to the 30ml syringe

containing the doxorubicin HCl loaded

HepaSphere Microspheres, however

larger volume of solution can provide

better control during embolization.

Gently invert the syringe 2 or 3 times

and wait 5 min until solution homoge-

neity is reached.

• Before any injection, check the spheres

are in suspension, if not, invert the

syringe back and forth to disperse

contents within the syringe.

OPTION 3: PREPARATION FOR

EMBOLIZATION LOADED WITH

IRINOTECAN

HepaSphere Microspheres loaded with

irinotecan are only applicable to the 30-60μ

and 50-100μ sizes.

As a general guideline the loading of

irinotecan into HepaSphere Microspheres

will take 30 minutes. The HepaSphere Mi-

crospheres should not be used before they

are fully hydrated and expanded.

• Choose the appropriate dose of

irinotecan solution to load into the

HepaSphere Microspheres. A maximum

dose of 100 mg irinotecan can be load-

ed in each vial of 25 mg HepaSphere

MicroSpheres. Irinotecan solution is

typically available in a concentration of

20 mg/ml.

• Aspirate the irinotecan into a syringe

connected to a needle of 20 gauge

diameter or larger.

• To ensure proper reconstitution of the

HepaSphere Microspheres, grasp the

HepaSphere Microspheres vial horizon-

tally in your ngertips and roll the vial

several times. This will transfer the dry

contents of the vial to the sidewall.

Note: Pull back only the ip-top cap; do

not remove the crimp ring or the stopper

from the vial.

• Carefully insert the needle of the

syringe containing the irinotecan

solution through the stopper of the vial.

Continue rolling the vial in your nger-

tips and inject the irinotecan solution

into the vial.

• Place the HepaSphere Microspheres vial

vertically. Carefully remove the syringe

with the needle attached, and allow the

vial to stand for 30 minutes in order to

completely hydrate the spheres.

• During those 30 minutes, shake the

HepaSphere Microspheres vial several

times back and forth so that the liquid

contacts the grey stopper. Repeat this

process every 2-3 minutes to ensure

a homogenous reconstitution of the

HepaSphere Microspheres.

Note: The vial is hermetically closed. If

aspiration from the syringe into the vial

does not automatically occur, then, using

caution, manually aspirate air from the

vial into the syringe prior to injecting the

reconstitution uid. Proper aspiration

and/or venting techniques, as approved

by the healthcare facility, may be used for

easier injection of reconstitution media

into the vial. If aspiration of air from the

vial is performed prior to reconstitution,

exercise caution not to remove the spheres

from the vial.

• After the 30 minutes hydration and

loading period, attach a 20 gauge

or larger needle to an appropriately

sized syringe and insert it into the

HepaSphere Microspheres vial. Aspirate

the contents of the HepaSphere Mi-

crospheres vial into the syringe. Rotate

the vial to a vertical position with the

730142001_001_hepasphere_irinotecan.indd 6 1/7/16 8:22 AM

bottom of the vial facing upward. Pull

the needle back so that it is submerged

in the liquid but not occluded by the

stopper. Gently aspirate the entire con-

tents of the vial into the syringe.

• Prior to removing the needle from the

HepaSphere Microspheres vial, while

holding the syringe vertically, gently

pull the plunger of the syringe down,

removing any solution that may be in

the hub of the needle.

• Replace the needle with a syringe cap

and invert the syringe back and forth

to disperse the contents within the

syringe.

• Add an equal volume of non-ionic

contrast medium to the syringe contain-

ing the irinotecan loaded HepaSphere

Microspheres immediately before use.

• Larger volume of non-ionic contrast me-

dia can lead to irinotecan release into

the supernatant.

• Gently invert the syringe 2 or 3 times

and wait 5 min until solution homoge-

neity is reached.

• Before any injection, check that the

microspheres are in suspension. If not,

invert the syringe back and forth to

disperse contents within the syringe.

• Do not remove the supernatant.

DELIVERY INSTRUCTIONS

• Carefully evaluate the vascular network

associated with the target lesion utiliz-

ing high resolution imaging.

Note: It is important to determine if any

arteriovenous shunts are present before

beginning embolization.

• Using standard techniques, position

the delivery catheter within the target

vessel and the catheter tip as close as

possible to the embolization target.

• Use an injection syringe no larger than

3ml for the delivery of doxorubicin/

irinotecan/bland loaded HepaSphere

Microspheres. Use of a 1ml injection

syringe is recommended.

• Aspirate the HepaSphere Microspheres

mixture into the injection syringe.

• Two methods for embolic aliquot

sequestering for injection may be used:

Option 1: Connect a 3way-stopcock to

the syringe containing the doxorubicin/

irinotecan/bland loaded HepaSphere

Microspheres to the infusion micro

catheter and use a 1ml syringe for

injection through the open port of the 3

way-stopcock.

Option 2: Serial aliquots of the

doxorubicin/irinotecan/bland loaded

HepaSphere Microspheres can be

drawn from the syringe into a 1ml

injection syringe through a 3 way-stop

cock that is not attached to the infusion

catheter. The 1ml syringe containing

each aliquot can be attached inde-

pendently to the infusion microcatheter

and injected.

• Invert the syringe back and forth to

maintain the homogenous suspen-

sion of the HepaSphere Microspheres

mixture.

• Under continuous uoroscopic guid-

ance, inject the aliquot of HepaSphere

Microspheres in a slow, non forceful,

pulsatile manner over a time period

of approximately 1 minute per ml of

microspheres solution. Always inject

under free-ow conditions and monitor

for reux.

Note: Reux of embolic spheres can induce

immediate ischemia of untargeted tissues

and vessels.

• When stasis in the feeding pedicle oc-

curs while delivering the doxorubicin/

irinotecan/bland loaded HepaSphere

Microspheres, wait a minimum of 5

minutes then perform a selective an-

giogram after the full 5 minutes wait to

verify the cessation of antegrade ow.

• If cessation of antegrade ow has not

occurred, continue infusion under

uoroscopic guidance until the desired

devascularization is obtained.

• After the HepaSphere Microsphere

infusion is completed, remove the

catheter while maintaining gentle aspi-

ration to avoid dislodging any residual

HepaSphere Microspheres that may still

be in the catheter lumen. Discard the

catheter after removal and do not reuse.

• Discard any open vial or unused

HepaSphere Microspheres.

CAUTION

In the event that the catheter becomes

obstructed or signicant infusion resistance

is encountered during injection, do not at-

tempt to ush the catheter with excessive

pressure because reux of embolic material

may occur resulting in untargeted emboli-

zation. Remove the catheter while applying

gentle aspiration and discard.

CONSERVATION AND STORAGE

HepaSphere Microspheres must be stored

in a dry, dark place in their original vials

and packaging. Use by the date indicated

on the labeling.

730142001_001_hepasphere_irinotecan.indd 7 1/7/16 8:22 AM

Size of dry

products (μm)

Colour code

(label borders)

Quantity of

microspheres (mg) Reference

30-60 Orange

V 225 HS

V 250 HS

50-100 Yellow

V 325 HS

V 350 HS

100-150 Blue

V 525 HS

V 550 HS

150-200 Red

V 725 HS

V 750 HS

When the procedure of reconstitution

is completed, store the solution of

HepaSphere Microspheres in 2 to 8°C con-

ditions and use within 24 hours, IF not used

immediately. Do not store HepaSphere

Microspheres after contrast medium has

been added.

730142001_001_hepasphere_irinotecan.indd 8 1/7/16 8:22 AM

Symbol Designation

Manufacturer: Name & Address

Use by date: year-month-day

LOT

Batch code

Catalog number

Do not resterilize

Do not use if package is damaged

Keep away from sunlight

Keep dry

Do not re-use

Caution: Consult accompanying documents

Non-pyrogenic

Sterilized using irradiation

EC mark logo - Notied body identication: 0459

Size of dry microspheres / Size of hydrated microspheres

All serious or life threatening adverse events or deaths associated with use of

HepaSphere Microspheres should be reported to the device manufacturer.

INFORMATION ON PACKAGING

Biosphere Medical, S.A.

Parc des Nations - Paris Nord 2

383 rue de la Belle Etoile

95700 Roissy en France

France

Manufactured for:

Merit Medical Systems, Inc.

1600 West Merit Parkway

South Jordan, Utah 84095, U.S.A.

1-801-253-1600

U.S.A. Customer Service 1-800-356-3748

www.merit.com

730142001_001 2015-11-24

0459_2004

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