Merit Medical HepaSphere Microspheres(With Doxorubicin) IFU-Int'l User Manual

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Note: Pull back only the flip-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 fingertips 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: 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 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withdrawn, introduce an additional volume of air and repeat the aspiration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 reconstituted as described above can be
used in the presence of chemotherapeutic agents such as cisplatin,
epirubicin, doxorubicin HCl, fluorouracil, irinotecan and mitomycin after
hydration. However for drug delivery, HepaSphere Microspheres are only
indicated for use with doxorubicin HCl (see below Option 2).
• 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 fluoroscopy. 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 Microspheres will take one hour.
The HepaSphere Microspheres should not be used before they are fully
hydrated and expanded. Loading kinetics of pre-solubilized doxorubicin
HCI may vary, depending on the concentration and pH of the solution.
• Choose the appropriate dose of doxorubicin HCl to load into the
HepaSphere Microspheres.

Note:
• A maximum dose of doxorubicin HCl

75mg can be loaded into each vial

of 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 concentration of doxorubicin HCl is
5mg/ml. Concentrations of doxorubicin HCl above 5mg/ml substantially
increase the solution viscosity and make it difficult to handle with
HepaSphere Microspheres.
• Aspirate the 20ml of doxorubicin HCl solution into two separate 30ml
syringes. 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 horizontally in your fingertips and roll
the vial several times. This will transfer the dry contents of the vial to the
sidewall.

Note: Pull back only the flip-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 fingertips 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. 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 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 homogeneity 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.

DELIVERY INSTRUCTIONS
• Carefully evaluate the vascular network associated with the target lesion
utilizing 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 loaded HepaSphere Microspheres. Use of a 1ml injection
syringe is recommended.
• Aspirate 1ml of the HepaSphere Microspheres mixture into the injection
syringe.

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