Medtronic 7510050 Instructions for Use

Reduced Profile

X Small (1.4cc) & XX Small (0.7cc)

INFUSE® Bone Graft Kits ONLY

IMPORTANT MEDICAL INFORMATION

In USA

Customer Service Division Telephone: [phone]

Medtronic Sofamor Danek USA, Inc

. or

1800 Pyramid Place 901 396 3133
Memphis, Tennessee 38132 Telefax: 901 396 0356
USA

Supplied by
Medtronic Sofamor Danek USA, Inc.

2015-06-10

and XX Small (0.7cc) INFUSE® Bone Graft kit for the corresponding Medtronic Titanium Threaded
Interbody Fusion Device component size:

SINGLE CAGE USE

In the case of only one cage needing INFUSE® Bone Graft, due to the loss or contamination of a
sponge or sponges, single cages can be filled using the X Small (1.4cc) and/or XX Small (0.7cc)
kits as shown below:

INTER FIX™ Threaded Fusion Device Recommended INFUSE® Bone Graft Kit(s)

Part #

x length, mm)

Part #

Kit size

Reconstituted

graft volume

(cc)

890120 12x20 7510100 X Small 1.4

890125 12x25

7510100

INTER FIX™ and INTER FIX™ RP

Threaded Fusion Devices

Part # of

INTER FIX™

Devices

x length, mm)

Part #

Kit size

Reconstituted

graft volume (cc)

890120+9011221 12x20 7510100 X Small 1.4

890125+9011225 12x25

†

The INTER FIX™ Threaded Fusion Device is to be used with the corresponding size of the INTER FIX™ RP Threaded

Fusion Device.

Part #

x length, mm)

Part #

Kit size

Reconstituted

graft volume

(cc)

9011221 12x20 7510100 X Small 1.4

9011225 12x25

7510100

Part #

Size

x length, mm)

Part #

Kit size

Reconstituted

graft volume (cc)

8941420 14x20 7510100 X Small 1.4

8941423 14x23 7510100 X Small

8941620 16x20

7510050 +

INFUSE® Bone Graft/LT-CAGE® Lumbar Tapered Fusion Device Combinations

Single LT-CAGE® Device Fill

LT-CAGE® Lumbar

Tapered Fusion Device

Recommended INFUSE® Bone Graft Kit(s)

Part #

Size

(lead diameter, mm

x length, mm)

Part #

Kit size

Reconstituted

rhBMP-2/ACS

graft volume

(cc)

8941420

14x20

7510100

X Small

1.4

8941423

14x23

7510100

X Small

1.4

8941620

16x20

7510050 +

7510100

XX Small + X Small

2.1

8941623

16x23

7510050 +

7510100

XX Small + X Small

2.1

M705106B018E Rev. D

INFUSE

INFUSE

®

BONE GRAFT/INTER FIX™ RP THREADED FUSION DEVICE - REDUCED PROFILE

®

BONE GRAFT/LT-CAGE® LUMBAR TAPERED FUSION DEVICE

INFUSE

®

BONE GRAFT/INTER FIX™ THREADED FUSION DEVICE

X Small (1.4cc) & XX Small (0.7cc) INFUSE® Bone Graft Kits ONLY

GREFFON OSSEUX INFUSE®/DISPOSITIF CONIQUE DE FUSION LOMBAIRE LT-CAGE

GREFFON OSSEUX INFUSE®/DISPOSITIF DE FUSION FILETÉ INTER FIX™

®

GREFFON OSSEUX INFUSE®/DISPOSITIF DE FUSION FILETÉ À PROFIL RÉDUIT INTER FIX™ RP

Kits de greffon osseux INFUSE® XS (1,4 cc) et XXS (0,7 cc) UNIQUEMENT

IN USA

2015-06-10

Customer Service Division Telephone: [phone]
Medtronic Sofamor Danek USA or
1800 Pyramid Place 901-396-3133
Memphis, Tennessee 38132 Telefax: 901-396-0356
USA

ENGLISH

Supplied by
Medtronic Sofamor Danek USA, Inc.

IMPORTANT MEDICAL INFORMATION

CAUTION: Federal (USA) law restricts this device to sale by or on the order of a physician with

appropriate training.
The following contains important medical information on the use of INFUSE® Bone Graft with a variety

of Medtronic metallic interbody fusion cages. These interbody fusion devices include the LT-CAGE®
Lumbar Tapered Fusion Device, the INTER FIX™ Threaded Fusion Device, and the INTER FIX™
RP Threaded Fusion Device. Hereafter in this insert, these cages will be referred to collectively as
Medtronic Titanium Threaded Interbody Fusion Device.

DESCRIPTION

The INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody Fusion Device consists of two
components containing three parts – a metallic spinal fusion cage, a recombinant human bone
morphogenetic protein, and a carrier/scaffold for the bone morphogenetic protein and resulting bone.
The INFUSE® Bone Graft component is inserted into the Medtronic Titanium Threaded Interbody
Fusion Device component to form the complete INFUSE® Bone Graft/Medtronic Titanium Threaded
Interbody Fusion Device. These components must be used as a system for the prescribed

indication described below. The bone morphogenetic protein solution component must
not be used without the carrier/scaffold component or with a carrier/scaffold component
different from the one described in this document. The INFUSE® Bone Graft component must
not be used without the Medtronic Titanium Threaded Interbody Fusion Device component.

Medtronic Titanium Threaded Interbody Fusion Device Component

LT-CAGE® Lumbar Tapered Fusion Device

The LT-CAGE® Device consists of a hollow, perforated, machined cylinder with opposing flat sides.
The cage has a tapered design with an angle of 8.8° and is available in diameters ranging from
14mm to 18mm at the narrow end of the taper to 17mm to 22 mm at the wide end of the taper and
in lengths ranging from 20mm to 26mm. There are two holes on each of the two flat sides. On each
of the two rounded aspects, there is a single rounded slot. The implants have a helical screw thread
on the outer surface. One end of the device is closed. The other end is open to be filled with the
INFUSE® Bone Graft component.

The LT-CAGE® implants are made from implant-grade titanium alloy (Ti-6Al-4V) described by such
standards as ASTM F136 or its ISO equivalent.

in lengths ranging from 20mm to 26mm. There are two holes on each of the two flat sides. On each
of the two rounded aspects, there is a single rounded slot. The implants have a helical screw thread
on the outer surface. One end of the device is closed. The other end is open to be filled with the
INFUSE® Bone Graft component.

The LT-CAGE® implants are made from implant-grade titanium alloy (Ti-6Al-4V) described by such
standards as ASTM F136 or its ISO equivalent.

CONTRAINDICATIONS

• The INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody Fusion Device is contraindicated
for patients with a known hypersensitivity to recombinant human Bone Morphogenetic Protein-2,
bovine Type I collagen or to other components of the formulation.

!USA

Part #

x length, mm)

Part #

Kit size

Reconstituted

graft volume

(cc)

7510100

Part # of

Devices

x length, mm)

Part #

Kit size

Reconstituted

graft volume (cc)

Part #

x length, mm)

Part #

Kit size

Reconstituted

graft volume

(cc)

7510100

Part #

Size

x length, mm)

Part #

Kit size

Reconstituted

graft volume (cc)

8941420 14x20 7510100 X Small 1.4

8941423 14x23 7510100 X Small

8941620 16x20

7510050 +

8941623 16x23

7510100

INFUSE® Bone Graft/LT-CAGE® Lumbar Tapered Fusion Device Combinations

Single LT-CAGE® Device Fill

LT-CAGE® Lumbar

Tapered Fusion Device

Recommended INFUSE® Bone Graft Kit(s)

Part #

Size

(lead diameter, mm

x length, mm)

Part #

Kit size

Reconstituted

rhBMP-2/ACS

graft volume

(cc)

8941420

14x20

7510100

X Small

1.4

8941423

14x23

7510100

X Small

1.4

8941620

16x20

7510050 +

7510100

XX Small + X Small

2.1

8941623

16x23

7510050 +

7510100

XX Small + X Small

2.1

INTER FIX™ Threaded Fusion Device Recommended INFUSE® Bone Graft Kit(s)

Part #

x length, mm)

Part #

Kit size

Reconstituted

graft volume (cc)

890120 12x20 7510050 XX Small 0.7

890125 12x25 7510100 X Small 1.4

890140 14X20 7510100 X Small 1.4

890143 14X23 7510100 X Small 1.4

890146 14X26

7510050 +

890149 14X29

7510050 +

890160 16X20

7510050 +

890163 16X23

7510050 +

INTER FIX™ Threaded Fusion Device Recommended INFUSE® Bone Graft Kit(s)

Part #

x length, mm)

Part #

Kit size

Reconstituted

graft volume (cc)

9011221 12x20 7510050 XX Small 0.7

9011225 12x25 7510100 X Small 1.4

9011420 14X20 7510100 X Small 1.4

9011423 14X23 7510100 X Small 1.4

9011426 14X26

7510050 +

7510100

9011429 14X29

7510050 +

7510100

9011620 16X20

7510050 +

7510100

9011623 16X23

7510050 +

7510100

The LT-CAGE® Lumbar Tapered Fusion Device component is sold separately from the INFUSE®
Bone Graft component; however, these two components must be used together. The package
labeling for the LT-CAGE® Lumbar Tapered Fusion Device contains complete product information
for this component.

INTER FIX™ Threaded Fusion Device

The INTER FIX™ Device consists of a hollow, perforated, cylinder with parallel sides and an endcap.
The cage is available in diameters ranging from 12mm to 24mm and in lengths ranging from 20mm to
29mm. The endcaps of the INTER FIX™ cages are sized according to the diameter of the cylinders
and are applied to the open end of the cylinders after they are filled with INFUSE® Bone Graft.

The INTER FIX™ Threaded Fusion Device implants are made from implant-grade titanium alloy
(Ti-6Al-4V) described by such standards as ASTM F136 or its ISO equivalent.

The INTER FIX™ Threaded Fusion Device component is sold separately from the INFUSE® Bone
Graft component; however, these two components must be used together. The package labeling for
the INTER FIX™ Threaded Fusion Device contains complete product information for this component.

INTER FIX™ RP Threaded Fusion Device

The INTER FIX™ RP Device consists of a hollow, perforated, cylinder with a single, large, outer­radiused groove along the entire longitudinal axis that extends into the inside diameter of the device.
Both ends of the INTER FIX™ RP implant are closed. The cage is available in diameters ranging
from 12mm to 24mm and in lengths ranging from 20mm to 29mm.

The INTER FIX™ RP Threaded Fusion Device implants are made from implant-grade titanium alloy
(Ti-6Al-4V) described by such standards as ASTM F136 or its ISO equivalent.

The INTER FIX™ RP Threaded Fusion Device component is sold separately from the INFUSE® Bone
Graft component; however, these two components must be used together. The package labeling for the
INTER FIX™ RP Threaded Fusion Device contains complete product information for this component.

NOTE: The INTER FIX™ Threaded Fusion Device and the INTER FIX™ RP Threaded Fusion
Device may be used together to treat a spinal level. LT-CAGE® Lumbar Tapered Fusion Device
implants are not to be used in conjunction with either the INTER FIX™ OR INTER FIX™ RP
implants to treat a spinal level.

INFUSE® Bone Graft Component

INFUSE® Bone Graft consists of recombinant human Bone Morphogenetic Protein-2 (rhBMP-2,
known as dibotermin alfa) placed on an absorbable collagen sponge (ACS). The INFUSE® Bone
Graft component induces new bone tissue at the site of implantation. Based on data from non-clinical
studies, the bone formation process develops from the outside of the implant towards the center until
the entire INFUSE® Bone Graft component is replaced by trabecular bone.

rhBMP-2 is the active agent in the INFUSE® Bone Graft component. rhBMP-2 is a disulfide-linked
dimeric protein molecule with two major subunit species of 114 and 131 amino acids. Each subunit
is glycosylated at one site with high-mannose-type glycans. rhBMP-2 is produced by a genetically
engineered Chinese hamster ovary cell line.

rhBMP-2 and excipients are lyophilized. Upon reconstitution, each milliliter of rhBMP-2 solution
contains: 1.5 mg of rhBMP-2; 5.0 mg sucrose, NF; 25 mg glycine, USP; 3.7 mg L-glutamic acid,
FCC; 0.1 mg sodium chloride, USP; 0.1 mg polysorbate 80, NF; and 1.0 mL of sterile water. The
reconstituted rhBMP-2 solution has a pH of 4.5, and is clear, colorless to slightly yellow, and essentially
free from plainly visible particulate matter.

The ACS is a soft, white, pliable, absorbent implantable matrix for rhBMP-2. ACS is made from
bovine Type I collagen obtained from the deep flexor (Achilles) tendon. The ACS acts as a carrier
for the rhBMP-2 and acts as a scaffold for new bone formation.

implants are not to be used in conjunction with either the INTER FIX™ OR INTER FIX™ RP
implants to treat a spinal level.

INFUSE® Bone Graft Component

INFUSE® Bone Graft consists of recombinant human Bone Morphogenetic Protein-2 (rhBMP-2,
known as dibotermin alfa) placed on an absorbable collagen sponge (ACS). The INFUSE® Bone
Graft component induces new bone tissue at the site of implantation. Based on data from non-clinical
studies, the bone formation process develops from the outside of the implant towards the center until
the entire INFUSE® Bone Graft component is replaced by trabecular bone.

rhBMP-2 is the active agent in the INFUSE® Bone Graft component. rhBMP-2 is a disulfide-linked
dimeric protein molecule with two major subunit species of 114 and 131 amino acids. Each subunit
is glycosylated at one site with high-mannose-type glycans. rhBMP-2 is produced by a genetically
engineered Chinese hamster ovary cell line.

rhBMP-2 and excipients are lyophilized. Upon reconstitution, each milliliter of rhBMP-2 solution
contains: 1.5 mg of rhBMP-2; 5.0 mg sucrose, NF; 25 mg glycine, USP; 3.7 mg L-glutamic acid,
FCC; 0.1 mg sodium chloride, USP; 0.1 mg polysorbate 80, NF; and 1.0 mL of sterile water. The
reconstituted rhBMP-2 solution has a pH of 4.5, and is clear, colorless to slightly yellow, and essentially
free from plainly visible particulate matter.

The ACS is a soft, white, pliable, absorbent implantable matrix for rhBMP-2. ACS is made from
bovine Type I collagen obtained from the deep flexor (Achilles) tendon. The ACS acts as a carrier
for the rhBMP-2 and acts as a scaffold for new bone formation.

CONTRAINDICATIONS

• The INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody Fusion Device is contraindicated
for patients with a known hypersensitivity to recombinant human Bone Morphogenetic Protein-2,
bovine Type I collagen or to other components of the formulation.

• The INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody Fusion Device should not
be used in the vicinity of a resected or extant tumor, in patients with any active malignancy or
patients undergoing treatment for a malignancy.

• INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody Fusion Device should not be
used in patients who are skeletally immature (<18 years of age or no radiographic evidence of
epiphyseal closure).

• The INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody Fusion Device should not
be used in pregnant women. The potential effects of rhBMP-2 on the human fetus have not
been evaluated.

• The INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody Fusion Device should not be
implanted in patients with an active infection at the operative site or with an allergy to titanium
or titanium alloy.

WARNINGS

• In an experimental rabbit study, rhBMP-2 has been shown to elicit antibodies that are capable
of crossing the placenta. Reduced ossification of the frontal and parietal bones of the skull was
noted infrequently (<3%) in fetuses of rabbit dams immunized to rhBMP-2; however, there was
no effect noted in limb bud development. There are no adequate and well-controlled studies in
human pregnant women. Women of child bearing potential should be warned by their surgeon
of potential risk to a fetus and informed of other possible orthopedic treatments.

• Women of childbearing potential should be advised that antibody formation to rhBMP-2 or its
influence on fetal development has not been completely assessed. In the clinical trial supporting
the safety and effectiveness of the INFUSE® Bone Graft/LT-CAGE® Lumbar Tapered Fusion
Device, 2/277 (0.7%) patients treated with INFUSE® Bone Graft component and 1/127 (0.8%)
patients treated with autograft bone developed antibodies to rhBMP-2. The effect of maternal
antibodies to rhBMP-2, as might be present for several months following device implantation,
on the unborn fetus is unknown. Additionally, it is unknown whether fetal expression of BMP-2
could re-expose mothers who were previously antibody positive. Theoretically, re-exposure
may elicit a more powerful immune response to BMP-2 with possible adverse consequences
for the fetus. However, pregnancy did not lead to an increase in antibodies in the rabbit study.
Studies in genetically altered mice indicate that BMP-2 is critical to fetal development and that
a lack of BMP-2 activity may cause neonatal death or birth defects. It is not known if anti-BMP-2
antibodies may affect fetal development or the extent to which these antibodies may reduce
BMP-2 activity.

• INFUSE® Bone Graft should not be used immediately prior to or during pregnancy. Women of
childbearing potential should be advised not to become pregnant for one year following treatment
with the INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody Fusion Device.

!USA

Part #

x length, mm)

Part #

Kit size

Reconstituted

graft volume

(cc)

7510100

Part # of

Devices

x length, mm)

Part #

Kit size

Reconstituted

graft volume (cc)

Part #

x length, mm)

Part #

Kit size

Reconstituted

graft volume

(cc)

7510100

Part #

Size

x length, mm)

Part #

Kit size

Reconstituted

graft volume (cc)

7510050 +

7510100

INFUSE® Bone Graft/LT-CAGE® Lumbar Tapered Fusion Device Combinations

Single LT-CAGE® Device Fill

LT-CAGE® Lumbar

Tapered Fusion Device

Recommended INFUSE® Bone Graft Kit(s)

Part #

Size

(lead diameter, mm

x length, mm)

Part #

Kit size

Reconstituted

rhBMP-2/ACS

graft volume

(cc)

8941420

14x20

7510100

X Small

1.4

8941423

14x23

7510100

X Small

1.4

8941620

16x20

7510050 +

7510100

XX Small + X Small

2.1

8941623

16x23

7510050 +

7510100

XX Small + X Small

2.1

Part #

x length, mm)

Part #

Kit size

Reconstituted

graft volume (cc)

7510050 +

7510050 +

7510050 +

7510050 +

Part #

x length, mm)

Part #

Kit size

Reconstituted

graft volume (cc)

9011221 12x20 7510050 XX Small 0.7

9011225 12x25 7510100 X Small 1.4

9011420 14X20 7510100 X Small 1.4

9011423 14X23 7510100 X Small 1.4

9011426 14X26

7510050 +

7510100

9011429 14X29

7510050 +

7510100

9011620 16X20

7510050 +

7510100

9011623 16X23

7510050 +

7510100

Bone Graft. See the insert for the other INFUSE® Bone Graft kits (Small, Medium, Large, and Large

• The safety and effectiveness of the INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody
Fusion Device in nursing mothers has not been established. It is not known if BMP-2 is excreted
in human milk.

General

• The INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody Fusion Device should not
be used in patients suspected of having a malignancy at the site of application.

• The safety and effectiveness of the use of the INFUSE® Bone Graft component with other spinal
implants, implanted at locations other than the lower lumbar spine, or used in surgical techniques
other than anterior open (LT-CAGE®, INTER FIX™, INTER FIX™ RP Devices) or anterior
laparoscopic (LT-CAGE® Device) approaches have not been established.

• The implantation of the INFUSE® Bone Graft/LT-CAGE® Lumbar Tapered Fusion Device
using an anterior laparoscopic surgical approach is associated with a higher incidence of
retrograde ejaculation (10.5%, 6/57 male patients) when compared to implantation using an
anterior open surgical approach (6.4%, 5/78 male patients). Both of these rates are greater

The tables provided in the “Directions for Use” of this insert describe how to use the X Small (1.4cc)
& XX Small (0.7cc) kits to fill smaller single cages if the need arises during surgery. For larger size
cages, the following is recommended: If a Large kit was used originally to fill two cages, use a Small
plus an X Small (1.4cc) kit to fill a single cage; if a Medium kit was used originally, use a Small kit
to fill a single cage; if a Small kit was used originally, use an X Small (1.4cc) kit to fill a single cage;
and if an X Small (1.4cc) kit was used originally, use an XX Small (0.7cc) kit to fill a single cage.

Each kit contains all the components necessary to prepare the INFUSE® Bone Graft component:
the rhBMP-2, which must be reconstituted; sterile water; absorbable collagen sponge; syringe(s) with
needle(s); this package insert; and instructions for preparation. The number of each item may vary
depending on the size of the kit. If two kits are going to be used (e.g., X Small (1.4cc) & XX Small
(0.7cc)), open both kits simultaneously and mix each according to the directions.

The rhBMP-2 is provided as a lyophilized powder in vials delivering 1.05 mg of protein for the X
Small and XX Small kits. After appropriate reconstitution, the configuration results in the formulation
and concentration (1.5 mg/mL) of rhBMP-2. The solution is then applied to the provided absorbable
collagen sponge. The INFUSE® Bone Graft component is prepared at the time of surgery and
allowed a prescribed amount of time (no less than 15 minutes) before placement inside of the
Medtronic Titanium Threaded Interbody Fusion Device component(s). The Instructions for Preparation
contain complete details on preparation of the INFUSE® Bone Graft/Medtronic Titanium Threaded
Interbody Fusion Device.

Implied warranties of merchantability and fitness for a particular purpose or use are specifically
excluded. See the MDT Catalog or price list for further information about warranties and limitations
of liability.

INDICATIONS

The INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody Fusion Device is indicated for
spinal fusion procedures in skeletally mature patients with degenerative disc disease (DDD) at one
level from L2-S1. DDD is defined as discogenic back pain with degeneration of the disc confirmed
by patient history and radiographic studies. These DDD patients may also have up to Grade I
spondylolisthesis or Grade 1 retrolisthesis at the involved level. Patients receiving the INFUSE® Bone
Graft/Medtronic Titanium Threaded Interbody Fusion Device should have had at least six months of
nonoperative treatment prior to treatment with the INFUSE® Bone Graft/Medtronic Titanium Threaded
Interbody Fusion Device. The INFUSE® Bone Graft with the LT-CAGE® Lumbar Tapered Fusion
Device is to be implanted via an anterior open or an anterior laparoscopic approach. The INFUSE®
Bone Graft with either the INTER FIX™ or the INTER FIX™ RP Threaded Fusion Device is to be
implanted via an anterior open approach.

DIRECTIONS FOR USE

The INFUSE® Bone Graft component is prepared at the time of surgery in the surgical suite by
reconstituting the lyophilized rhBMP-2 with sterile water (See Instructions for Preparation) and
then uniformly applying the reconstituted rhBMP-2 solution to the ACS. The INFUSE® Bone
Graft component is then inserted into the Medtronic Titanium Threaded Interbody Fusion Device
component. The complete device is then implanted through an anterior surgical approach. (See the
Surgical Technique manual.) If the INFUSE® Bone Graft component is not used within two hours
after reconstitution, it must be discarded.

The INFUSE® Bone Graft component must not be sterilized by the hospital. The Medtronic
Titanium Threaded Interbody Fusion Device component, if not supplied sterile, should be sterilized
before insertion of the INFUSE® Bone Graft component. Please refer to the specific Medtronic
Titanium Threaded Interbody Fusion Device package insert for information on packaging, cleaning/
decontamination, and sterilization of this component and its instruments.

This insert describes only the use of the X Small (1.4cc) and XX Small (0.7cc) kit sizes of INFUSE®

Bone Graft. See the insert for the other INFUSE® Bone Graft kits (Small, Medium, Large, and Large II)

DIRECTIONS FOR USE

The INFUSE® Bone Graft component is prepared at the time of surgery in the surgical suite by
reconstituting the lyophilized rhBMP-2 with sterile water (See Instructions for Preparation) and
then uniformly applying the reconstituted rhBMP-2 solution to the ACS. The INFUSE® Bone
Graft component is then inserted into the Medtronic Titanium Threaded Interbody Fusion Device
component. The complete device is then implanted through an anterior surgical approach. (See the
Surgical Technique manual.) If the INFUSE® Bone Graft component is not used within two hours
after reconstitution, it must be discarded.

The INFUSE® Bone Graft component must not be sterilized by the hospital. The Medtronic
Titanium Threaded Interbody Fusion Device component, if not supplied sterile, should be sterilized
before insertion of the INFUSE® Bone Graft component. Please refer to the specific Medtronic
Titanium Threaded Interbody Fusion Device package insert for information on packaging, cleaning/
decontamination, and sterilization of this component and its instruments.

This insert describes only the use of the X Small (1.4cc) and XX Small (0.7cc) kit sizes of INFUSE®
Bone Graft. See the insert for the other INFUSE® Bone Graft kits (Small, Medium, Large, and Large
II) for instructions for use on those size kits. The tables below list the appropriate X Small (1.4cc)

• The safety and effectiveness of the INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody
Fusion Device in nursing mothers has not been established. It is not known if BMP-2 is excreted
in human milk.

General

• The INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody Fusion Device should not
be used in patients suspected of having a malignancy at the site of application.

• The safety and effectiveness of the use of the INFUSE® Bone Graft component with other spinal
implants, implanted at locations other than the lower lumbar spine, or used in surgical techniques
other than anterior open (LT-CAGE®, INTER FIX™, INTER FIX™ RP Devices) or anterior
laparoscopic (LT-CAGE® Device) approaches have not been established.

• The implantation of the INFUSE® Bone Graft/LT-CAGE® Lumbar Tapered Fusion Device
using an anterior laparoscopic surgical approach is associated with a higher incidence of
retrograde ejaculation (10.5%, 6/57 male patients) when compared to implantation using an
anterior open surgical approach (6.4%, 5/78 male patients). Both of these rates are greater
than that for a control group implanted using an open anterior approach who did not receive
INFUSE® Bone Graft (1.5%, 1/68 male patients). In the randomized study of the anterior open
surgical approach, retrograde ejaculation occurred in the INFUSE® Bone Graft group in 17.6%
(3/17) of the male patients who underwent the surgery with a transperitoneal approach, as

Graft component is then inserted into the Medtronic Titanium Threaded Interbody Fusion Device
component. The complete device is then implanted through an anterior surgical approach. (See the
Surgical Technique manual.) If the INFUSE® Bone Graft component is not used within two hours
after reconstitution, it must be discarded.

The INFUSE® Bone Graft component must not be sterilized by the hospital. The Medtronic
Titanium Threaded Interbody Fusion Device component, if not supplied sterile, should be sterilized
before insertion of the INFUSE® Bone Graft component. Please refer to the specific Medtronic
Titanium Threaded Interbody Fusion Device package insert for information on packaging, cleaning/
decontamination, and sterilization of this component and its instruments.

This insert describes only the use of the X Small (1.4cc) and XX Small (0.7cc) kit sizes of INFUSE®
Bone Graft. See the insert for the other INFUSE® Bone Graft kits (Small, Medium, Large, and Large
II) for instructions for use on those size kits. The tables below list the appropriate X Small (1.4cc)
and XX Small (0.7cc) INFUSE® Bone Graft kit for the corresponding Medtronic Titanium Threaded
Interbody Fusion Device component size:

SINGLE CAGE USE

In the case of only one cage needing INFUSE® Bone Graft, due to the loss or contamination of a
sponge or sponges, single cages can be filled using the X Small (1.4cc) and/or XX Small (0.7cc)
kits as shown below:

General

• The INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody Fusion Device should not
be used in patients suspected of having a malignancy at the site of application.

• The safety and effectiveness of the use of the INFUSE® Bone Graft component with other spinal
implants, implanted at locations other than the lower lumbar spine, or used in surgical techniques
other than anterior open (LT-CAGE®, INTER FIX™, INTER FIX™ RP Devices) or anterior
laparoscopic (LT-CAGE® Device) approaches have not been established.

• The implantation of the INFUSE® Bone Graft/LT-CAGE® Lumbar Tapered Fusion Device
using an anterior laparoscopic surgical approach is associated with a higher incidence of
retrograde ejaculation (10.5%, 6/57 male patients) when compared to implantation using an
anterior open surgical approach (6.4%, 5/78 male patients). Both of these rates are greater
than that for a control group implanted using an open anterior approach who did not receive
INFUSE® Bone Graft (1.5%, 1/68 male patients). In the randomized study of the anterior open
surgical approach, retrograde ejaculation occurred in the INFUSE® Bone Graft group in 17.6%
(3/17) of the male patients who underwent the surgery with a transperitoneal approach, as
compared to 3.2% (2/ 61) of the males with a retroperitoneal approach. In the control group,
the retrograde ejaculation rate was 7.6% (1/13) in the males with a transperitoneal approach,
as compared to 0% (0/55) in the males with a retroperitoneal approach. With the two treatment
groups pooled, retrograde ejaculation occurred in 13.3% (4/30) of the males who underwent a
transperitoneal approach and in 1.8% (2/116) of the males who underwent a retroperitoneal
approach. This difference is statistically significant (p=0.017, Fisher exact test). Male patients
should be informed of this potential risk prior to considering the use of INFUSE® Bone Graft.

• The safety and effectiveness of the use of INFUSE® Bone Graft implanted in the cervical
spine has not been established. This product is only approved for use in the lumbar spine as
indicated above.

− When anterior cervical spinal fusions were performed using the INFUSE® Bone Graft

component, some cases of edema have been reported within the first postoperative week. In
some of these cases, this swelling has been severe enough to produce airway compromise,
sometimes requiring emergency surgery.

− In a clinical trial comparing single-level anterior cervical fusion using INFUSE® Bone Graft

to a control that did not use INFUSE® Bone Graft, 16.4% of patients treated with INFUSE®
Bone Graft reported dysphagia, compared to 7.3% of control patients. Most of the dysphagia
events occurred within the first four weeks after surgery, and most of these events were
classified as non-serious (e.g., non-life-threatening events not requiring hospitalization). While
dysphagia may occur following anterior cervical procedures, it may occur more frequently or
to a greater extent in the presence of INFUSE® Bone Graft.

− When anterior cervical fusions were performed using INFUSE® Bone Graft, the radiographic

appearance of anterior heterotopic ossification (HO) was noted in some patients, most commonly
observed anterior and superior to the treated level. In some of the cases of severe HO, adjacent-
level fusion and reduced motion were also noted. HO may occur more frequently or to a greater
extent with the use of INFUSE® Bone Graft.

Bone Formation

• Posterior bone formation outside of the disc space was observed in some patients when
degenerative disc disease was treated by a posterior lumbar interbody fusion procedure. Although
it was not clearly associated with key clinical outcome measures (e.g., leg pain) in most of the
cases, bone formation outside of the disc space is not desirable and may potentially lead to nerve
compression, requiring surgical intervention.

• Inappropriate use of the product, such as preparing it differently than prescribed, compressing
the rhBMP-2/ACS implant more than necessary, or overfilling the volume intended for new bone
formation, may change the concentration of the rhBMP-2, which may inhibit the ability of the
rhBMP-2/ACS to convert to bone and/or cause complications. Such use of the rhBMP-2/ACS
implant may result in radiographic evidence of resorption. These findings may be asymptomatic
or symptomatic. A sheep model developed to test the hypothesis that volume overfilling and/or
hyperconcentration of the rhBMP-2 solution results in radiographic evidence of bone resorption
has preliminarily been evaluated and appears to be supportive of the hypothesized mechanism.

• Placement of rhBMP-2/ACS can cause initial resorption of trabecular bone that may be transient.

Part #

x length, mm)

Part #

Kit size

Reconstituted

graft volume

(cc)

Part # of

Devices

x length, mm)

Part #

Kit size

Reconstituted

graft volume (cc)

Part #

x length, mm)

Part #

Kit size

Reconstituted

graft volume

(cc)

INFUSE® Bone Graft/LT-CAGE® Lumbar Tapered Fusion Device Combinations

Single LT-CAGE® Device Fill

for instructions for use on those size kits. The tables below list the appropriate X Small (1.4cc

and XX Small (0.7cc) INFUSE® Bone Graft kit for the corresponding Medtronic Titanium Threaded
Interbody Fusion Device component size:

INTER FIX™ Threaded Fusion Device Recommended INFUSE® Bone Graft Kit(s)

INFUSE® Bone Graft/INTER FIX™ Threaded Fusion Device Combinations

Dual INTER FIX™ Devices

Size

(diameter, mm

rhBMP-2/ACS

890120 12x20 7510100 X Small 1.4

890125 12x25

INTER FIX™ and INTER FIX™ RP

INTER FIX™

890120+9011221 12x20 7510100 X Small 1.4

890125+9011225 12x25

†

The INTER FIX™ Threaded Fusion Device is to be used with the corresponding size of the INTER FIX™ RP Threaded

Fusion Device.

9011221 12x20 7510100 X Small 1.4

9011225 12x25

INFUSE® Bone Graft/INTER FIX™ and INTER FIX™ RP Threaded Fusion Device Combinations

INTER FIX™ RP Device with INTER FIX™ Device

Threaded Fusion Devices

Size

†

INTER FIX™ RP

Threaded Fusion Device

(diameter, mm

INFUSE® Bone Graft/INTER FIX™ RP Threaded Fusion Device Combinations

Size

(Diameter, mm

7510050 +

7510100

7510050 +

7510100

Dual INTER FIX™ RP Devices

7510050 +

7510100

XX Small + X Small 2.1

Recommended INFUSE® Bone Graft Kit(s)

XX Small + X Small 2.1

Recommended INFUSE® Bone Graft Kit(s)

XX Small + X Small 2.1

rhBMP-2/ACS

rhBMP-2/ACS

appearance of anterior heterotopic ossification (HO) was noted in some patients, most commonly
observed anterior and superior to the treated level. In some of the cases of severe HO, adjacent-
level fusion and reduced motion were also noted. HO may occur more frequently or to a greater
extent with the use of INFUSE® Bone Graft.

Bone Formation

• Posterior bone formation outside of the disc space was observed in some patients when
degenerative disc disease was treated by a posterior lumbar interbody fusion procedure. Although
it was not clearly associated with key clinical outcome measures (e.g., leg pain) in most of the
cases, bone formation outside of the disc space is not desirable and may potentially lead to nerve
compression, requiring surgical intervention.

• Inappropriate use of the product, such as preparing it differently than prescribed, compressing
the rhBMP-2/ACS implant more than necessary, or overfilling the volume intended for new bone
formation, may change the concentration of the rhBMP-2, which may inhibit the ability of the
rhBMP-2/ACS to convert to bone and/or cause complications. Such use of the rhBMP-2/ACS
implant may result in radiographic evidence of resorption. These findings may be asymptomatic
or symptomatic. A sheep model developed to test the hypothesis that volume overfilling and/or
hyperconcentration of the rhBMP-2 solution results in radiographic evidence of bone resorption
has preliminarily been evaluated and appears to be supportive of the hypothesized mechanism.

• Placement of rhBMP-2/ACS can cause initial resorption of trabecular bone that may be transient.

• Device migration has been reported with use of rhBMP-2/ACS in spinal fusion surgery. Device
migration has been reported in the presence and absence of bone resorption.

• Nerve compression associated with heterotopic bone formation has been reported in patients
undergoing spine surgery with rhBMP-2/ACS. Surgical intervention may be required to address
the symptoms.

Fluid Collection/Edema

• The formation of fluid collections (sometimes encapsulated) in some cases resulted in nerve
compression and pain, which may require clinical intervention (aspiration and/or surgical
removal) if symptoms persist. Many of these reports have occurred when rhBMP-2/ACS was
used in conjunction with unapproved approaches/devices or in a manner inconsistent with the
instructions for use.

• While there are currently anecdotal and literature evidence to suggest that volume overfilling and/
or hyperconcentration of the rhBMP-2 solution may lead to fluid formation and/or edema, animal
models for scientifically evaluating these events do not presently exist.

PRECAUTIONS

PHYSICIAN NOTE: Although the physician is the learned intermediary between the company and the

patient, the important medical information given in this document should be conveyed to the patient.

!USA

FOR US AUDIENCES ONLY

General

• The safety and effectiveness of repeat applications of the INFUSE® Bone Graft component
has not been established.

• The INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody Fusion Device should only
be used by surgeons who are experienced in spinal fusion procedures and have undergone
adequate training with this device, for anterior laparoscopic and/or anterior open procedures.

• Two Medtronic Titanium Threaded Interbody Fusion Device components should be implanted
side by side at the surgical level whenever possible.

• The Medtronic Titanium Threaded Interbody Fusion Device components and instruments must
be sterilized prior to use according to the sterilization instructions provided in the package insert
for that component, unless supplied sterile and clearly labeled as such.

• When using this device at spinal levels between L2 and L4, the potential impact of anatomical
structures (e.g., the aorta) on implant placement must be considered.

• The formation of exuberant or heterotopic bone growth at the upper lumbar levels (L2- L4) may
have a deleterious impact on certain neurovascular structures (e.g., the aorta and sympathetic
nerve chain).

Part #

x length, mm)

Part #

Kit size

Reconstituted

graft volume

(cc)

7510100

Part # of

INTER FIX™

Devices

†

(diameter, mm

x length, mm)

Part #

Kit size

Reconstituted

rhBMP-2/ACS

graft volume (cc)

890120+9011221 12x20 7510100 X Small 1.4

890125+9011225 12x25

7510050 +

7510100

XX Small + X Small 2.1

†

The INTER FIX™ Threaded Fusion Device is to be used with the corresponding size of the INTER FIX™ RP Threaded

Fusion Device.

INFUSE® Bone Graft/INTER FIX™ RP Threaded Fusion Device Combinations

Dual INTER FIX™ RP Devices

INTER FIX™ RP

Threaded Fusion Device

Recommended INFUSE® Bone Graft Kit(s)

Part #

Size

(Diameter, mm

x length, mm)

Part #

Kit size

Reconstituted

rhBMP-2/ACS

graft volume

(cc)

9011221 12x20 7510100 X Small 1.4

9011225 12x25

7510050 +

7510100

XX Small + X Small 2.1

Part #

x length, mm)

Part #

Kit size

Reconstituted

graft volume (cc)

INFUSE® Bone Graft/LT-CAGE® Lumbar Tapered Fusion Device Combinations

Single LT-CAGE® Device Fill

LT-CAGE® Lumbar

Tapered Fusion Device

Recommended INFUSE® Bone Graft Kit(s)

Part #

Size

(lead diameter, mm

x length, mm)

Part #

Kit size

Reconstituted

rhBMP-2/ACS

graft volume

(cc)

8941420

14x20

7510100

X Small

1.4

8941423

14x23

7510100

X Small

1.4

8941620

16x20

7510050 +

7510100

XX Small + X Small

2.1

8941623

16x23

7510050 +

7510100

XX Small + X Small

2.1

Part #

x length, mm)

Part #

Kit size

Reconstituted

graft volume (cc)

DIRECTIONS FOR USE

The INFUSE® Bone Graft component is prepared at the time of surgery in the surgical suite by
reconstituting the lyophilized rhBMP-2 with sterile water (See Instructions for Preparation) and
then uniformly applying the reconstituted rhBMP-2 solution to the ACS. The INFUSE® Bone
Graft component is then inserted into the Medtronic Titanium Threaded Interbody Fusion Device
component. The complete device is then implanted through an anterior surgical approach. (See the
Surgical Technique manual.) If the INFUSE® Bone Graft component is not used within two hours
after reconstitution, it must be discarded.

The INFUSE® Bone Graft component must not be sterilized by the hospital. The Medtronic
Titanium Threaded Interbody Fusion Device component, if not supplied sterile, should be sterilized
before insertion of the INFUSE® Bone Graft component. Please refer to the specific Medtronic
Titanium Threaded Interbody Fusion Device package insert for information on packaging, cleaning/
decontamination, and sterilization of this component and its instruments.

This insert describes only the use of the X Small (1.4cc) and XX Small (0.7cc) kit sizes of INFUSE®
Bone Graft. See the insert for the other INFUSE® Bone Graft kits (Small, Medium, Large, and Large
II) for instructions for use on those size kits. The tables below list the appropriate X Small (1.4cc)
and XX Small (0.7cc) INFUSE® Bone Graft kit for the corresponding Medtronic Titanium Threaded
Interbody Fusion Device component size:

• The safety and effectiveness of the INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody
Fusion Device in nursing mothers has not been established. It is not known if BMP-2 is excreted
in human milk.

General

• The INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody Fusion Device should not
be used in patients suspected of having a malignancy at the site of application.

• The safety and effectiveness of the use of the INFUSE® Bone Graft component with other spinal
implants, implanted at locations other than the lower lumbar spine, or used in surgical techniques
other than anterior open (LT-CAGE®, INTER FIX™, INTER FIX™ RP Devices) or anterior
laparoscopic (LT-CAGE® Device) approaches have not been established.

• The implantation of the INFUSE® Bone Graft/LT-CAGE® Lumbar Tapered Fusion Device
using an anterior laparoscopic surgical approach is associated with a higher incidence of
retrograde ejaculation (10.5%, 6/57 male patients) when compared to implantation using an
anterior open surgical approach (6.4%, 5/78 male patients). Both of these rates are greater
than that for a control group implanted using an open anterior approach who did not receive
INFUSE® Bone Graft (1.5%, 1/68 male patients). In the randomized study of the anterior open
surgical approach, retrograde ejaculation occurred in the INFUSE® Bone Graft group in 17.6%
(3/17) of the male patients who underwent the surgery with a transperitoneal approach, as
compared to 3.2% (2/ 61) of the males with a retroperitoneal approach. In the control group,
the retrograde ejaculation rate was 7.6% (1/13) in the males with a transperitoneal approach,
as compared to 0% (0/55) in the males with a retroperitoneal approach. With the two treatment
groups pooled, retrograde ejaculation occurred in 13.3% (4/30) of the males who underwent a

SINGLE CAGE USE

In the case of only one cage needing INFUSE® Bone Graft, due to the loss or contamination of a
sponge or sponges, single cages can be filled using the X Small (1.4cc) and/or XX Small (0.7cc)
kits as shown below:

8941420 14x20 7510100 X Small 1.4

8941423 14x23 7510100 X Small

8941620 16x20

8941623 16x23

INTER FIX™ Threaded Fusion Device Recommended INFUSE® Bone Graft Kit(s)

890120 12x20 7510050 XX Small 0.7

890125 12x25 7510100 X Small 1.4

890140 14X20 7510100 X Small 1.4

890143 14X23 7510100 X Small 1.4

890146 14X26

890149 14X29

890160 16X20

890163 16X23

INFUSE® Bone Graft/LT-CAGE® Lumbar Tapered Fusion Device Combinations

LT-CAGE® Lumbar

Tapered Fusion Device

Size

(lead diameter, mm

INFUSE® Bone Graft/INTER FIX™ Threaded Fusion Device Combinations

Size

(diameter, mm

Single LT-CAGE® Device Fill

7510050 +

7510100

7510050 +

7510100

Single INTER FIX™ Device Fill

7510050 +

7510100

7510050 +

7510100

7510050 +

7510100

7510050 +

7510100

Recommended INFUSE® Bone Graft Kit(s)

XX Small + X Small

XX Small + X Small

XX Small + X Small 2.1

XX Small + X Small 2.1

XX Small + X Small 2.1

XX Small + X Small 2.1

rhBMP-2/ACS

1.4

2.1

2.1

rhBMP-2/ACS

!USA

FOR US AUDIENCES ONLY

General

• The safety and effectiveness of repeat applications of the INFUSE® Bone Graft component
has not been established.

• The INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody Fusion Device should only
be used by surgeons who are experienced in spinal fusion procedures and have undergone
adequate training with this device, for anterior laparoscopic and/or anterior open procedures.

• Two Medtronic Titanium Threaded Interbody Fusion Device components should be implanted
side by side at the surgical level whenever possible.

• The Medtronic Titanium Threaded Interbody Fusion Device components and instruments must
be sterilized prior to use according to the sterilization instructions provided in the package insert
for that component, unless supplied sterile and clearly labeled as such.

• When using this device at spinal levels between L2 and L4, the potential impact of anatomical
structures (e.g., the aorta) on implant placement must be considered.

• The formation of exuberant or heterotopic bone growth at the upper lumbar levels (L2- L4) may
have a deleterious impact on certain neurovascular structures (e.g., the aorta and sympathetic
nerve chain).

• The safety and effectiveness of the device at spinal levels L2- L4 or in patients with up to Grade
1 retrolisthesis has not been established.

• The INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody Fusion Device is intended
for single use only. Discard unused product and use a new device for subsequent applications.

• Prior to use, inspect the packaging, vials, and stoppers for visible damage. If damage is visible,
do not use the product. Retain the packaging and vials and contact a Medtronic representative.

• Do not use after the printed expiration date on the label.

Hepatic and Renal Impairment

• The safety and effectiveness of the INFUSE® Bone Graft/Medtronic Titanium Threaded
Interbody Fusion Device in patients with hepatic or renal impairment has not been established.
Pharmacokinetic studies of rhBMP-2 indicate that the renal and hepatic systems are involved
with its clearance.

Geriatrics

• Clinical studies of the INFUSE® Bone Graft/LT-CAGE® Lumbar Tapered Fusion Device did not
include sufficient numbers of patients 65 years and older to determine whether they respond
differently from younger subjects.

Bone Formation

• The safety and effectiveness of the INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody
Fusion Device has not been demonstrated in patients with metabolic bone diseases.

• The potential for heterotopic or undesirable exuberant bone formation exists.

.

Antibody Formation/Allergic Reactions

• The safety and effectiveness of the INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody
Fusion Device has not been demonstrated in patients with autoimmune disease.

• The safety and effectiveness of the INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody
Fusion Device has not been demonstrated in patients with immunosuppressive disease or
suppressed immune systems resulting from radiation therapy, chemotherapy, steroid therapy, or
other treatments.

Immunogenicity

• As with all therapeutic proteins, there is a potential for immune responses to be generated
to the INFUSE® Bone Graft component. The immune response to the INFUSE® Bone Graft
components was evaluated in 349 investigational patients and 183 control patients receiving
lumbar interbody fusions.

– Anti-rhBMP-2 antibodies: 2/349 (0.6%) patients receiving the INFUSE® Bone Graft

component developed antibodies vs. 1/183 (0.5%) in the control group.

– Anti-bovine Type I collagen antibodies: 18.1% of patients receiving the INFUSE® Bone Graft

Part #

x length, mm)

Part #

Kit size

Reconstituted

graft volume

(cc)

7510100

Part # of

Devices

x length, mm)

Part #

Kit size

Reconstituted

graft volume (cc)

Part #

x length, mm)

Part #

Kit size

Reconstituted

graft volume

(cc)

7510100

Part #

Size

x length, mm)

Part #

Kit size

Reconstituted

graft volume (cc)

7510050 +

7510100

INFUSE® Bone Graft/LT-CAGE® Lumbar Tapered Fusion Device Combinations

Single LT-CAGE® Device Fill

LT-CAGE® Lumbar

Tapered Fusion Device

Recommended INFUSE® Bone Graft Kit(s)

Part #

Size

(lead diameter, mm

x length, mm)

Part #

Kit size

Reconstituted

rhBMP-2/ACS

graft volume

(cc)

8941420

14x20

7510100

X Small

1.4

8941423

14x23

7510100

X Small

1.4

8941620

16x20

7510050 +

7510100

XX Small + X Small

2.1

8941623

16x23

7510050 +

7510100

XX Small + X Small

2.1

Part #

Size

(diameter, mm

x length, mm)

Part #

Kit size

Reconstituted

rhBMP-2/ACS

graft volume (cc)

890120 12x20 7510050 XX Small 0.7

890125 12x25 7510100 X Small 1.4

890140 14X20 7510100 X Small 1.4

890143 14X23 7510100 X Small 1.4

890146 14X26

7510050 +

7510100

XX Small + X Small 2.1

890149 14X29

7510050 +

7510100

XX Small + X Small 2.1

890160 16X20

7510050 +

7510100

XX Small + X Small 2.1

890163 16X23

7510050 +

7510100

XX Small + X Small 2.1

Part #

x length, mm)

Part #

Kit size

Reconstituted

graft volume (cc)

7510100

7510100

INTER FIX™ Threaded Fusion Device Recommended INFUSE® Bone Graft Kit(s)

9011221 12x20 7510050 XX Small 0.7

9011225 12x25 7510100 X Small 1.4

9011420 14X20 7510100 X Small 1.4

9011423 14X23 7510100 X Small 1.4

9011426 14X26

9011429 14X29

9011620 16X20

9011623 16X23

INFUSE® Bone Graft/INTER FIX™ RP Threaded Fusion Device Combinations

Single INTER FIX™ RP Device Fill

Size

(diameter, mm

7510050 +

7510050 +

7510050 +

7510050 +

7510100

7510100

XX Small + X Small 2.1

XX Small + X Small 2.1

XX Small + X Small 2.1

XX Small + X Small 2.1

rhBMP-2/ACS

CONTRAINDICATIONS

• The INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody Fusion Device is contraindicated
for patients with a known hypersensitivity to recombinant human Bone Morphogenetic Protein-2,
bovine Type I collagen or to other components of the formulation.

• The INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody Fusion Device should not
be used in the vicinity of a resected or extant tumor, in patients with any active malignancy or
patients undergoing treatment for a malignancy.

• INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody Fusion Device should not be
used in patients who are skeletally immature (<18 years of age or no radiographic evidence of
epiphyseal closure).

• The INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody Fusion Device should not
be used in pregnant women. The potential effects of rhBMP-2 on the human fetus have not
been evaluated.

• The INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody Fusion Device should not be
implanted in patients with an active infection at the operative site or with an allergy to titanium
or titanium alloy.

CONTRAINDICATIONS

• The INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody Fusion Device is contraindicated
for patients with a known hypersensitivity to recombinant human Bone Morphogenetic Protein-2,
bovine Type I collagen or to other components of the formulation.

• The INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody Fusion Device should not
be used in the vicinity of a resected or extant tumor, in patients with any active malignancy or
patients undergoing treatment for a malignancy.

• INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody Fusion Device should not be
used in patients who are skeletally immature (<18 years of age or no radiographic evidence of
epiphyseal closure).

• The INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody Fusion Device should not
be used in pregnant women. The potential effects of rhBMP-2 on the human fetus have not
been evaluated.

• The INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody Fusion Device should not be
implanted in patients with an active infection at the operative site or with an allergy to titanium
or titanium alloy.

!USA

• Do not use after the printed expiration date on the label.

Hepatic and Renal Impairment

• The safety and effectiveness of the INFUSE® Bone Graft/Medtronic Titanium Threaded
Interbody Fusion Device in patients with hepatic or renal impairment has not been established.
Pharmacokinetic studies of rhBMP-2 indicate that the renal and hepatic systems are involved
with its clearance.

Geriatrics

• Clinical studies of the INFUSE® Bone Graft/LT-CAGE® Lumbar Tapered Fusion Device did not
include sufficient numbers of patients 65 years and older to determine whether they respond
differently from younger subjects.

Bone Formation

• The safety and effectiveness of the INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody
Fusion Device has not been demonstrated in patients with metabolic bone diseases.

• The potential for heterotopic or undesirable exuberant bone formation exists.

.

Antibody Formation/Allergic Reactions

• The safety and effectiveness of the INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody
Fusion Device has not been demonstrated in patients with autoimmune disease.

• The safety and effectiveness of the INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody
Fusion Device has not been demonstrated in patients with immunosuppressive disease or
suppressed immune systems resulting from radiation therapy, chemotherapy, steroid therapy, or
other treatments.

Immunogenicity

• As with all therapeutic proteins, there is a potential for immune responses to be generated
to the INFUSE® Bone Graft component. The immune response to the INFUSE® Bone Graft
components was evaluated in 349 investigational patients and 183 control patients receiving
lumbar interbody fusions.

– Anti-rhBMP-2 antibodies: 2/349 (0.6%) patients receiving the INFUSE® Bone Graft

component developed antibodies vs. 1/183 (0.5%) in the control group.

– Anti-bovine Type I collagen antibodies: 18.1% of patients receiving the INFUSE® Bone Graft

component developed antibodies to bovine Type I collagen vs. 14.2% of control patients. No
patients in either group developed anti-human Type I collagen antibodies.

– The presence of antibodies to rhBMP-2 was not associated with immune mediated adverse

events such as allergic reactions. The neutralizing capacity of antibodies to rhBMP-2 is not
known.

• The incidence of antibody detection is highly dependent on the sensitivity and specificity of the
assay. Additionally, the incidence of antibody detection may be influenced by several factors
including sample handling, concomitant medications and underlying disease. For these reasons,
comparison of the incidence of antibodies to the INFUSE® Bone Graft component with the
incidence of antibodies to other products may be misleading.

ADVERSE EVENTS

The INFUSE® Bone Graft/LT-CAGE® Lumbar Tapered Fusion Device was implanted in 288
investigational patients and compared to 139 control patients who received the LT-CAGE® Lumbar
Tapered Fusion Device filled with iliac crest autograft. The investigational patients were implanted with
the device via either an open anterior surgical approach or a laparoscopic anterior surgical approach.
The control patients were implanted via the open anterior surgical approach only.

Adverse event rates presented are based on the number of patients having at least one occurrence
for a particular adverse event divided by the total number of patients in that treatment group. Because
no control subjects were evaluated at the 48- and 72-month timepoints, the reported events at these
timepoints are only from the investigational subjects.

Part #

x length, mm)

Part #

Kit size

Reconstituted

graft volume

(cc)

7510100

Part # of

Devices

x length, mm)

Part #

Kit size

Reconstituted

graft volume (cc)

Part #

x length, mm)

Part #

Kit size

Reconstituted

graft volume

(cc)

7510100

Part #

Size

x length, mm)

Part #

Kit size

Reconstituted

graft volume (cc)

7510050 +

7510100

INFUSE® Bone Graft/LT-CAGE® Lumbar Tapered Fusion Device Combinations

Single LT-CAGE® Device Fill

LT-CAGE® Lumbar

Tapered Fusion Device

Recommended INFUSE® Bone Graft Kit(s)

Part #

Size

(lead diameter, mm

x length, mm)

Part #

Kit size

Reconstituted

rhBMP-2/ACS

graft volume

(cc)

8941420

14x20

7510100

X Small

1.4

8941423

14x23

7510100

X Small

1.4

8941620

16x20

7510050 +

7510100

XX Small + X Small

2.1

8941623

16x23

7510050 +

7510100

XX Small + X Small

2.1

Part #

x length, mm)

Part #

Kit size

Reconstituted

graft volume (cc)

7510050 +

7510050 +

7510050 +

7510050 +

Part #

x length, mm)

Part #

Kit size

Reconstituted

graft volume (cc)

9011221 12x20 7510050 XX Small 0.7

9011225 12x25 7510100 X Small 1.4

9011420 14X20 7510100 X Small 1.4

9011423 14X23 7510100 X Small 1.4

9011426 14X26

7510050 +

7510100

XX Small + X Small 2.1

9011429 14X29

7510050 +

7510100

XX Small + X Small 2.1

9011620 16X20

7510050 +

7510100

XX Small + X Small 2.1

9011623 16X23

7510050 +

7510100

XX Small + X Small 2.1

WARNINGS

• In an experimental rabbit study, rhBMP-2 has been shown to elicit antibodies that are capable
of crossing the placenta. Reduced ossification of the frontal and parietal bones of the skull was
noted infrequently (<3%) in fetuses of rabbit dams immunized to rhBMP-2; however, there was
no effect noted in limb bud development. There are no adequate and well-controlled studies in
human pregnant women. Women of child bearing potential should be warned by their surgeon
of potential risk to a fetus and informed of other possible orthopedic treatments.

• Women of childbearing potential should be advised that antibody formation to rhBMP-2 or its
influence on fetal development has not been completely assessed. In the clinical trial supporting
the safety and effectiveness of the INFUSE® Bone Graft/LT-CAGE® Lumbar Tapered Fusion
Device, 2/277 (0.7%) patients treated with INFUSE® Bone Graft component and 1/127 (0.8%)
patients treated with autograft bone developed antibodies to rhBMP-2. The effect of maternal
antibodies to rhBMP-2, as might be present for several months following device implantation,
on the unborn fetus is unknown. Additionally, it is unknown whether fetal expression of BMP-2

General

• The INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody Fusion Device should not

could re-expose mothers who were previously antibody positive. Theoretically, re-exposure
may elicit a more powerful immune response to BMP-2 with possible adverse consequences
for the fetus. However, pregnancy did not lead to an increase in antibodies in the rabbit study.
Studies in genetically altered mice indicate that BMP-2 is critical to fetal development and that
a lack of BMP-2 activity may cause neonatal death or birth defects. It is not known if anti-BMP-2
antibodies may affect fetal development or the extent to which these antibodies may reduce
BMP-2 activity.

• INFUSE® Bone Graft should not be used immediately prior to or during pregnancy. Women of
childbearing potential should be advised not to become pregnant for one year following treatment
with the INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody Fusion Device.

• The safety and effectiveness of the INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody
Fusion Device in nursing mothers has not been established. It is not known if BMP-2 is excreted
in human milk.

be used in patients suspected of having a malignancy at the site of application.

• The safety and effectiveness of the use of the INFUSE® Bone Graft component with other spinal
implants, implanted at locations other than the lower lumbar spine, or used in surgical techniques
other than anterior open (LT-CAGE®, INTER FIX™, INTER FIX™ RP Devices) or anterior
laparoscopic (LT-CAGE® Device) approaches have not been established.

• The implantation of the INFUSE® Bone Graft/LT-CAGE® Lumbar Tapered Fusion Device
using an anterior laparoscopic surgical approach is associated with a higher incidence of
retrograde ejaculation (10.5%, 6/57 male patients) when compared to implantation using an
anterior open surgical approach (6.4%, 5/78 male patients). Both of these rates are greater
than that for a control group implanted using an open anterior approach who did not receive
INFUSE® Bone Graft (1.5%, 1/68 male patients). In the randomized study of the anterior open
surgical approach, retrograde ejaculation occurred in the INFUSE® Bone Graft group in 17.6%
(3/17) of the male patients who underwent the surgery with a transperitoneal approach, as
compared to 3.2% (2/ 61) of the males with a retroperitoneal approach. In the control group,
the retrograde ejaculation rate was 7.6% (1/13) in the males with a transperitoneal approach,
as compared to 0% (0/55) in the males with a retroperitoneal approach. With the two treatment
groups pooled, retrograde ejaculation occurred in 13.3% (4/30) of the males who underwent a
transperitoneal approach and in 1.8% (2/116) of the males who underwent a retroperitoneal
approach. This difference is statistically significant (p=0.017, Fisher exact test). Male patients
should be informed of this potential risk prior to considering the use of INFUSE® Bone Graft.

the retrograde ejaculation rate was 7.6% (1/13) in the males with a transperitoneal approach,
as compared to 0% (0/55) in the males with a retroperitoneal approach. With the two treatment
groups pooled, retrograde ejaculation occurred in 13.3% (4/30) of the males who underwent a
transperitoneal approach and in 1.8% (2/116) of the males who underwent a retroperitoneal
approach. This difference is statistically significant (p=0.017, Fisher exact test). Male patients
should be informed of this potential risk prior to considering the use of INFUSE® Bone Graft.

• The safety and effectiveness of the use of INFUSE® Bone Graft implanted in the cervical
spine has not been established. This product is only approved for use in the lumbar spine as
indicated above.

− When anterior cervical spinal fusions were performed using the INFUSE® Bone Graft

component, some cases of edema have been reported within the first postoperative week. In
some of these cases, this swelling has been severe enough to produce airway compromise,
sometimes requiring emergency surgery.

− In a clinical trial comparing single-level anterior cervical fusion using INFUSE® Bone Graft

to a control that did not use INFUSE® Bone Graft, 16.4% of patients treated with INFUSE®
Bone Graft reported dysphagia, compared to 7.3% of control patients. Most of the dysphagia
events occurred within the first four weeks after surgery, and most of these events were
classified as non-serious (e.g., non-life-threatening events not requiring hospitalization). While
dysphagia may occur following anterior cervical procedures, it may occur more frequently or
to a greater extent in the presence of INFUSE® Bone Graft.

− When anterior cervical fusions were performed using INFUSE® Bone Graft, the radiographic

appearance of anterior heterotopic ossification (HO) was noted in some patients, most commonly
observed anterior and superior to the treated level. In some of the cases of severe HO, adjacent­level fusion and reduced motion were also noted. HO may occur more frequently or to a greater
extent with the use of INFUSE® Bone Graft.

Bone Formation

• Posterior bone formation outside of the disc space was observed in some patients when
degenerative disc disease was treated by a posterior lumbar interbody fusion procedure. Although
it was not clearly associated with key clinical outcome measures (e.g., leg pain) in most of the
cases, bone formation outside of the disc space is not desirable and may potentially lead to nerve
compression, requiring surgical intervention.

• Inappropriate use of the product, such as preparing it differently than prescribed, compressing
the rhBMP-2/ACS implant more than necessary, or overfilling the volume intended for new bone
formation, may change the concentration of the rhBMP-2, which may inhibit the ability of the
rhBMP-2/ACS to convert to bone and/or cause complications. Such use of the rhBMP-2/ACS
implant may result in radiographic evidence of resorption. These findings may be asymptomatic
or symptomatic. A sheep model developed to test the hypothesis that volume overfilling and/or
hyperconcentration of the rhBMP-2 solution results in radiographic evidence of bone resorption
has preliminarily been evaluated and appears to be supportive of the hypothesized mechanism.

• Placement of rhBMP-2/ACS can cause initial resorption of trabecular bone that may be transient.

• Device migration has been reported with use of rhBMP-2/ACS in spinal fusion surgery. Device
migration has been reported in the presence and absence of bone resorption.

• Nerve compression associated with heterotopic bone formation has been reported in patients
undergoing spine surgery with rhBMP-2/ACS. Surgical intervention may be required to address
the symptoms.

Fluid Collection/Edema

• The formation of fluid collections (sometimes encapsulated) in some cases resulted in nerve
compression and pain, which may require clinical intervention (aspiration and/or surgical
removal) if symptoms persist. Many of these reports have occurred when rhBMP-2/ACS was
used in conjunction with unapproved approaches/devices or in a manner inconsistent with the
instructions for use.

• While there are currently anecdotal and literature evidence to suggest that volume overfilling and/
or hyperconcentration of the rhBMP-2 solution may lead to fluid formation and/or edema, animal
models for scientifically evaluating these events do not presently exist.

PRECAUTIONS

PHYSICIAN NOTE: Although the physician is the learned intermediary between the company and the

patient, the important medical information given in this document should be conveyed to the patient.

!USA

FOR US AUDIENCES ONLY

patient, the important medical information given in this document should be conveyed to the patient.

!USA

FOR US AUDIENCES ONLY

General

• The safety and effectiveness of repeat applications of the INFUSE® Bone Graft component
has not been established.

• The INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody Fusion Device should only
be used by surgeons who are experienced in spinal fusion procedures and have undergone
adequate training with this device, for anterior laparoscopic and/or anterior open procedures.

• Two Medtronic Titanium Threaded Interbody Fusion Device components should be implanted
side by side at the surgical level whenever possible.

• The Medtronic Titanium Threaded Interbody Fusion Device components and instruments must
be sterilized prior to use according to the sterilization instructions provided in the package insert
for that component, unless supplied sterile and clearly labeled as such.

• When using this device at spinal levels between L2 and L4, the potential impact of anatomical
structures (e.g., the aorta) on implant placement must be considered.

• The formation of exuberant or heterotopic bone growth at the upper lumbar levels (L2- L4) may
have a deleterious impact on certain neurovascular structures (e.g., the aorta and sympathetic
nerve chain).

• The safety and effectiveness of the device at spinal levels L2- L4 or in patients with up to Grade
1 retrolisthesis has not been established.

• The INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody Fusion Device is intended
for single use only. Discard unused product and use a new device for subsequent applications.

• Prior to use, inspect the packaging, vials, and stoppers for visible damage. If damage is visible,
do not use the product. Retain the packaging and vials and contact a Medtronic representative.

• Do not use after the printed expiration date on the label.

Hepatic and Renal Impairment

• The safety and effectiveness of the INFUSE® Bone Graft/Medtronic Titanium Threaded
Interbody Fusion Device in patients with hepatic or renal impairment has not been established.
Pharmacokinetic studies of rhBMP-2 indicate that the renal and hepatic systems are involved
with its clearance.

Geriatrics

• Clinical studies of the INFUSE® Bone Graft/LT-CAGE® Lumbar Tapered Fusion Device did not
include sufficient numbers of patients 65 years and older to determine whether they respond
differently from younger subjects.

Bone Formation

• The safety and effectiveness of the INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody
Fusion Device has not been demonstrated in patients with metabolic bone diseases.

• The potential for heterotopic or undesirable exuberant bone formation exists.

.

Antibody Formation/Allergic Reactions

• The safety and effectiveness of the INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody
Fusion Device has not been demonstrated in patients with autoimmune disease.

• The safety and effectiveness of the INFUSE® Bone Graft/Medtronic Titanium Threaded Interbody
Fusion Device has not been demonstrated in patients with immunosuppressive disease or
suppressed immune systems resulting from radiation therapy, chemotherapy, steroid therapy, or
other treatments.

Immunogenicity

• As with all therapeutic proteins, there is a potential for immune responses to be generated
to the INFUSE® Bone Graft component. The immune response to the INFUSE® Bone Graft
components was evaluated in 349 investigational patients and 183 control patients receiving
lumbar interbody fusions.

– Anti-rhBMP-2 antibodies: 2/349 (0.6%) patients receiving the INFUSE® Bone Graft

component developed antibodies vs. 1/183 (0.5%) in the control group.

– Anti-bovine Type I collagen antibodies: 18.1% of patients receiving the INFUSE® Bone Graft

component developed antibodies to bovine Type I collagen vs. 14.2% of control patients. No
patients in either group developed anti-human Type I collagen antibodies.