ANNEX I
SUMMARY OF PRODUCT CHARACTERISTICS
1.
Osigraft 3.3 mg, powder for suspension for implantation
2.
Each vial contains 1g powder with 3.3 mg of eptotermin alfa*
* Human Osteogenic protein produced in Chinese hamster ovary (CHO) cells by recombinant DNA
technology
For a full list of excipients, see section 6.1.
3.
Powder for suspension for implantation.
Osigraft is a white to off-white granular powder.
4.
Treatment of nonunion of tibia of at least 9 month duration, secondary to trauma, in skeletally mature
patients, in cases where previous treatment with autograft has failed or use of autograft is unfeasible.
Osigraft should be used by an appropriately qualified surgeon.
Treatment requires a single surgery. Depending on the size of the defect, more than a single 1 g vial
of Osigraft may be required. The maximum human dose should not exceed 2 vials since efficacy in
the treatment on non-unions with gaps requiring higher doses has not been established.
Osigraft is contraindicated in children (see section 4.3).
Osigraft is administered by direct surgical placement at the defect site in contact with the prepared
bone surface. The surrounding soft tissues are then closed around the implant. Experience from
controlled clinical trials is limited to stabilisation of the fracture site using concomitant intramedullary
nailing.
Method of administration:
1.
Using sterile technique, remove the vial from its packaging.
2.
Lift the plastic flip-top and remove the crimp from the vial.
Handle the crimp with care. The edges of the crimp are sharp and may cut or damage gloves.
3.
Using your thumb, pry up the edge of the stopper. Once the vacuum is broken, remove the vial
stopper while holding the vial upright to prevent loss of Osigraft.
2
Do not insert a needle through the stopper. Puncture of the stopper with a needle may result in
particles of stopper material contaminating the Osigraft.
4.
Reconstitute the product as explained in section 6.6.
5.
Debride fibrous, necrotic or sclerotic tissue and appropriately decorticate bone so that the
reconstituted Osigraft is in direct contact with bleeding bone and viable osseous tissue.
6.
Provide adequate haemostasis to ensure that Osigraft is not dislodged from the surgical site.
Irrigate as necessary prior to the implantation of Osigraft. Where practical, surgical manipulations
to the site should be completed prior to implantation of Osigraft.
7.
Apply Osigraft to the prepared osseous tissue site using a sterile instrument such as a spatula or
curette. The amount of Osigraft used should approximate the size of the bone defect.
8.
Do not use suction or irrigation directly at the implant site as the particles of Osigraft may be
removed. Remove excess fluid if necessary by suctioning adjacent to the implant site or carefully
blotting the area with sterile sponge.
9.
Close soft tissues around the defect containing Osigraft using suture material of choice. Closure is
critical for containment of the implant in the area of the defect.
10.
After closure of the soft tissues around the defect, irrigate field, if necessary to remove any
Osigraft, which may have become dislodged during soft tissue closure.
11.
Do not place a drain directly in the implant site. If required, place it subcutaneously.
Osigraft must not be used in treating patients who:
have a known hypersensitivity to the active substance or to collagen;
have skeletal immaturity;
have known autoimmune disease, including rheumatoid arthritis, systemic lupus erythematosus,
scleroderma, Sjögren’s syndrome and dermatomyositis/polymyositis;
have active infection at the site of non-union or active systemic infection;
have inadequate skin coverage and vascularity of the non-union site;
have vertebral fractures;
have a non-union resulting from pathological fractures, metabolic bone disease or tumours;
have any tumour in the vicinity of the non-union site;
are receiving chemotherapy, radiation treatment or immunosuppression;
Osigraft does not provide any biomechanical strength and should be used with internal or external
fixation where initial mechanical stabilisation is required. However, external fixation may not provide
sufficient immobilisation. Motion in the non-union site may disrupt the fracture healing process.
Experience from controlled clinical trials is limited to stabilisation of tibial non-union site using
3
concomitant intramedullary nailing. Locking intramedullary rods have been used in the majority of
cases.
Use of Osigraft does not guarantee repair, additional surgeries may be required.
Any material dislodged from the non-union site can cause ectopic ossification in the surrounding
tissues with potential complications. Therefore, Osigraft may only be administered to the defect site
under adequate vision and with utmost care. Special care must be taken to prevent any leakage of
Osigraft due to irrigation, defective closure of surrounding tissue or inadequate haemostasis.
Antibodies to OP-1 protein were detected in 66% of patients in the tibial non-union study following
the administration of Osigraft. Analysis of these antibodies showed that 9% had neutralizing capacity.
However, no association with clinical outcome or adverse event could be observed in clinical studies.
An immune response to Osigraft should be considered and appropriate tests for the presence of
antibodies in serum should be performed in cases where an immune-mediated undesirable effect is
suspected, including cases where Osigraft is ineffective.
Repeated use of Osigraft cannot be recommended. Studies with anti-OP-1 antibodies demonstrated
some cross-reactivity with closely related BMP proteins BMP-5 and BMP-6. Anti-OP-1 antibodies
have the ability to neutralise the
in vitro
biological activity of at least
BMP-6. Therefore, upon re-
administration of Osigraft, a risk of developing autoimmunity towards the endogenous BMP proteins
may exist.
The use of Osigraft with a synthetic bone void filler may lead to a risk of increase in local
inflammation,
infection and occasional migration of the implanted materials and is therefore not
recommended.
The pivotal clinical trial supporting the approval of Osigraft did not include the use of synthetic bone
void fillers. Post market surveillance data has signaled that the use of Osigraft in combination with a
synthetic bone void filler may lead to an increase in local inflammation infection and occasional
migration of the implanted materials.
Animal studies have been conducted that cannot rule out effects of anti-OP-1 antibodies on embryo-
foetal development (see section 5.3). Due to the unknown risks to the foetus associated with the
potential development of neutralizing antibodies to OP-1 protein, Osigraft should not be used during
pregnancy unless the potential benefit justifies the potential risks to the foetus (see section 4.4 &
section 5.3). Women of childbearing potential should be advised to use effective contraception up to at
least 12 months after treatment. Women of child-bearing potential should inform their surgeon of the
possibility of pregnancy prior to treatment with Osigraft.
In animal studies, excretion of IgG class anti-OP-1 antibodies into milk has been shown. As human
IgG is secreted into human milk, and the potential for harm to the infant is unknown, women should
not breast-feed during Osigraft therapy (see Section 5.3). Osigraft should be given to breast-feeding
women only when the attending physician decides that the benefits outweigh the risks. It is
recommended that breast-feeding be discontinued following treatment.
Not relevant.
4
Osigraft is implanted by an invasive surgical procedure, for example during open reduction of a
fracture site. Adverse events following such surgery and not specifically associated with the product
may include wound infection, osteomyelitis, mechanical complications of mechanical support,
hematoma, dehiscence, nausea, fever and pain. The incidence of these events in clinical studies was
>10%. However, there were no differences in the incidence of these adverse events compared with
patients who received bone autograft, except in the case of osteomyelitis for which the incidence of
osteomyelitis was statistically higher in the autograft group.
The following undesirable effects were commonly (>1/100, <1/10) reported in clinical trials:
erythema, tenderness, swelling over the implant site, and heterotopic ossification/myositis ossificans.
No case of overdose has been reported.
5.
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Bone Morphogenetic Proteins, ATC code: M05BC02
It is an osteoinductive and osteoconductive medicinal product.
Eptotermin alfa, the active substance, initiates bone formation through the induction of cellular
differentiation in mesenchymal cells, which are recruited to the implant site from bone marrow,
periosteum and muscle. Once bound at the cell surface, the active substance induces a cascade of
cellular events leading to the formation of chondroblasts and osteoblasts, which play a key role in the
bone formation process. The collagen matrix is insoluble and consists of particles with a size range of
75-425µm. This provides an appropriate bioresorbable scaffold for the anchorage dependent cell
proliferation and differentiation processes induced by the active substance. The cellular events
induced by the active substance take place within the collagen matrix. The matrix is also
osteoconductive and it allows bone in-growth into the defect area from the surrounding healthy bone.
The new bone formed is mechanically and radiographically comparable to normal bone. The new
bone remodels naturally, cortices are formed and marrow elements are generated. However, use of
Osigraft does not guarantee repair; additional surgery may be required.
The Tibial Nonunion pivotal trial compared Osigraft with autograft, with a primary efficacy endpoint
at 9 months post-treatment. Clinical outcomes of pain and weight-bearing were comparable to the
autograft (81% success in the Osigraft group, 77% success in the autograft goup). The radiographic
healing results of the Osigraft treatment group were slightly inferior compared to the autograft control
group (68% and 79% respectively).
5.2 Pharmacokinetic properties
There are no data on the pharmacokinetics of the active substance in man. However, results from
Osigraft implantation studies in animals demonstrate that the active substance eptotermin alfa is
largely unavailable systemically.
5.3 Preclinical safety data
Single dose and repeat dose studies in a range of animal models (rats, dogs and primates) were
performed. The results of these showed no unanticipated or systemic effects of toxicity during the
observation period and after administration.
5
In a 2 year subcutaneous implantation study in rats, heterotopic bone formation was observed, as
expected. Sarcoma was associated with the long-term presence of the heterotopic bone. This effect,
termed solid state carcinogenicity, frequently has been observed in rats where solid materials (plastics
or metals) were implanted subcutaneously.
Heterotopic ossification commonly occurs in humans following accidental or surgical trauma.
Heterotopic ossification may also occur following use. (See Section 4.8 Undesirable Effects.)
However, there is evidence to suggest that heterotopic ossification is not linked to sarcoma in humans.
The effect of anti-OP-1 antibodies on the bone healing process was studied in dogs following two long
bone defects treated with repeat implantations. The results of radiological and histological
examinations in this non-clinical study showed bone healing with the initial and repeat exposure in the
same animal. Antibodies to OP-1 and bovine bone collagen type 1 were found after both exposures;
the antibody peak concentration was higher after the second implantation. The antibody levels
declined towards baseline during the follow-up period.
Controlled studies of the effects of exposure to eptotermin alfa on pre and postnatal development were
performed in rabbit models. Eptotermin alfa in Freund’s adjuvant was first administered
subcutaneously with booster doses given after 14 and 28 days. Blood and milk samples were collected
at regular intervals and analysed using a solid phase enzyme-linked immunoassay (ELISA) test.
Detectable levels of IgG and IgM antibodies to eptotermin alfa developed and were found in the serum
of all exposed adult animals. Antibodies to eptotermin alfa were found in sera from pooled foetal and
umbilical cord blood at levels that correlated to that of the maternal blood. Antibodies were detectable
in adults and offspring during the gestation and lactation periods. Significantly high titers of IgG class
anti-OP-1 antibodies were detected in milk throughout the whole post-natal phase study until the
lactation day 28 (see section 4.6).
A statistically significant increase in foetal malformations (misaligned sternabrae) was seen in litters
of the OP-1 immunized group. In another study a difference in body weight gain was seen in the
immunized adult females between lactation days 14 to 21 when compared to the control animals. The
weight of the offspring in the treated group was noted to be less than that of the control group during
the observation period. The clinical implications of these observations for human use of the finished
product remain uncertain. (See 4.6 Pregnancy & Lactation).
6.
6.1 List of excipients
Bovine collagen (vacuum dried)
6.2 Incompatibilities
In the absence of comparability studies, this medicinal product must not be mixed with other
medicinal products.
6.3 Shelf life
2 years
The reconstituted product should be used immediately.
6.4 Special precautions for storage
Store in a refrigerator (2°C - 8°C)
Keep the blister pack in the outer carton
6
6.5 Nature and contents of container
Osigraft is supplied in a glass vial (Type 1, borosilicate) containing 1 g of powder, sealed with a
stopper (butyl rubber) and a crimp cap (aluminium).
The primary package is maintained sterile within a blister pack, comprised of two (inner and outer)
plastic trays and lids.
Pack size of 1 vial.
6.6 Special precautions for disposal and other handling
Reconstitution with the solvent (not provided).
Each vial of Osigraft is reconstituted with 2 to 3 ml of sterile 9 mg/ml sodium chloride solution
(0.9% w/v) prior to use. Sterile sodium chloride solution for injection and contents of the Osigraft vial
are transferred to a sterile bowl and mixed with a sterile spatula or curette. To avoid breakage, do not
tap the bottom of the vial when transferring contents. After reconstitution, the single use suspension
for implantation should be used immediately.
Administration
When reconstituted, Osigraft has the consistency of wet sand, which facilitates its implantation and
placement at bone site defects.
Disposal
Any unused product or waste material should be disposed of in accordance with local requirements.
7.
Howmedica International S. de R. L.
Division of Stryker Corporation
Raheen Industrial Estate
Raheen
Limerick
Ireland
Tel +353-61-498200
Fax +353-61-498247
8.
EU/1/01/179/001
9.
Date of first authorisation: 17 May 2001
Date of latest renewal: 17 May 2006
7
Detailed information on this medicinal product is available on the website of the European Medicines
Agency (EMEA)
http://www.emea.europa.eu/
8
ANNEX II
A.
MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE
SUBSTANCE(S) AND MANUFACTURING AUTHORISATION
HOLDER(S) RESPONSIBLE FOR BATCH RELEASE
B. CONDITIONS OF THE MARKETING AUTHORISATION
9
A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE(S) AND
MANUFACTURING AUTHORISATION HOLDER(S) RESPONSIBLE FOR BATCH
RELEASE
Name and address of the manufacturer(s) of the biological active substance
Stryker Biotech
9 Technology Drive
West Lebanon
NH 03784
USA
Name and address of the manufacturer(s) responsible for batch release
Howmedica International S. de R. L.
Raheen Industrial Estate
Raheen
Limerick
Ireland
B. CONDITIONS OF THE MARKETING AUTHORISATION
•
Medicinal product subject to restricted medical prescription (See Annex I: Summary of Product
Characteristics, section 4.2).
•
OTHER CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND
EFFECTIVE USE OF THE MEDICINAL PRODUCT
Not applicable.
•
OTHER CONDITIONS
The Marketing Authorisation Holder will continue to submit yearly PSURs.
10
ANNEX III
LABELLING AND PACKAGE LEAFLET
11
A. LABELLING
12
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
OUTER CARTON
1.
Osigraft 3.3 mg, powder for suspension for implantation.
eptotermin alfa.
2.
STATEMENT OF ACTIVE SUBSTANCE(S)
1 g powder contains 3.3 mg eptotermin alfa* .
*
Human Osteogenic protein produced in Chinese hamster ovary (CHO) cells by recombinant DNA
technology.
3.
LIST OF EXCIPIENTS
Bovine collagen.
4.
Powder for suspension for implantation, (1 g in a vial - Pack size of 1).
5.
METHOD AND ROUTE(S) OF ADMINISTRATION
For intraosseous implantation.
Read the package leaflet before use.
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight of children.
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
8.
EXPIRY DATE
EXP MM/YYYY
9.
SPECIAL STORAGE CONDITIONS
Store in a refrigerator.
Keep the blister packs in the outer carton.
13
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
Any unused product or waste material should be disposed of in accordance with local requirements.
Howmedica International S. de R. L.
Division of Stryker Corporation
Raheen Business Park
Limerick
Ireland
Tel +353-61-498200
Fax +353-61-498247
EU/1/01/179/001
13. BATCH NUMBER
Lot {number}
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription.
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
Justification for not including Braille accepted
14
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS
FOIL FOR THE BLISTER PACK (OUTER) FOR THE VIAL
1.
Osigraft 3.3 mg, powder for suspension for implantation.
eptotermin alfa.
Intraosseous use.
2.
METHOD OF ADMINISTRATION
Read the package leaflet before use.
3.
EXPIRY DATE
EXP MM/YYYY
4.
BATCH NUMBER
Lot {number}
5.
CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT
3.3 mg
6.
OTHER
Do not open before use.
15
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS
VIAL
1.
Osigraft
eptotermin alfa
2.
METHOD OF ADMINISTRATION
3.
EXPIRY DATE
4.
BATCH NUMBER
Lot {number}
5.
CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT
3.3 mg
6.
OTHER
16
B. PACKAGE LEAFLET
17
PACKAGE LEAFLET: INFORMATION FOR THE USER
Osigraft 3.3 mg, powder for suspension for implantation
eptotermin alfa
Read all of this leaflet carefully before you start using this medicine.
-
Keep this leaflet. You may need to read it again.
-
If you have further questions, ask your doctor.
-
If any of the side effects gets serious, or if you notice any side effect not listed in this leaflet,
please tell your doctor.
In this leaflet
:
1.
What Osigraft is and what it is used for
2.
Before you use Osigraft
3.
How to use Osigraft
5
How to store Osigraft
6.
Further information
1.
WHAT OSIGRAFT IS AND WHAT IT IS USED FOR
Osigraft contains eptotermin alfa, a bone morphogenetic protein that induces new bone formation as
part of the healing process.
Osigraft is used in the treatment of nonunion (fractures which have failed to heal) of tibia of at least 9
month duration, secondary to trauma (following injury), in skeletally mature patients, in cases where
previous treatment with autograft (transplanted bone from your hip) has failed or use of autograft is
not feasible.
2.
BEFORE YOU USE OSIGRAFT
Do not use Osigraft
-
If you are allergic to eptotermin alfa or collagen, the other ingredient of Osigraft.
-
If you are skeletally immature (still growing).
-
If you have an autoimmune disease (disease arising from or directed against your own tissues),
including rheumatoid arthritis, systemic lupus erythematosus, scleroderma, Sjögren’s syndrome
and dermatomyositis/ polymyositis.
-
If you have active infection at the site of non-union (inflammation and drainage at the site of
injury) or active systemic infection.
-
If your doctor determines that you have inadequate skin coverage (at the fracture site) and
inadequate blood supply at the non-union site.
-
For vertebral (spine) fractures.
-
For treating non-union resulting from pathological (disease-related) fractures, metabolic bone
disease or tumours.
-
When there are any tumours in the area of the non-union site.
-
If you are receiving chemotherapy, radiation treatment or immunosuppression
Take special care with Osigraft
The following are precautions for use of Osigraft to be discussed with your doctor.
18
4.
Possible side effects
Osigraft does not aid in the support of weight and does not stabilise the fracture. Therefore, it should
be used with internal or external bone fixation devices. However, external fixation may not provide
sufficient stability. Motion in the non-union site may prevent the fracture healing process. Experience
from controlled clinical trials is limited to stabilisation of the tibial non-union site (lower leg) using
intramedullary nailing (internal fixation device). Locking intramedullary nails have been used in the
majority of cases.
Use of Osigraft does not guarantee repair; additional surgeries may be required.
Any material dislodged from the non-union site can cause bone formation (ectopic ossification) in the
surrounding tissues with potential complications. Therefore, Osigraft may only be administered to the
defect site under adequate vision and with utmost care. Special care must be taken to prevent any
leakage of Osigraft due to irrigation, defective closure of surrounding tissue or inadequate haemostasis
(control of bleeding).
Antibodies to OP-1 protein were detected in 66% of patients in the tibial non-union study following
the administration of Osigraft. Analysis of these antibodies showed that 9% had neutralizing capacity.
However, no association with clinical outcome or adverse event could be observed in clinical studies.
An immune response to Osigraft should be considered and appropriate tests for the presence of
antibodies in serum should be performed in cases where an immune-mediated undesirable effect is
suspected, including cases where Osigraft is ineffective.
Repeated use of Osigraft cannot be recommended. Studies with anti-OP-1 antibodies demonstrated
some cross-reactivity with closely related BMP proteins BMP-5 and BMP-6. Anti-OP-1 antibodies
have the ability to neutralize the in vitro biological activity of at least BMP-6. Therefore, upon re-
administration of Osigraft, a risk of developing autoimmunity towards the endogenous BMP proteins
may exit.
The use of Osigraft with a synthetic bone void filler may lead to a risk of increase in local
inflammation,
infection and occasional migration of the implanted materials and is therefore not
recommended.
Using other medicines
Please tell your doctor if you are taking or have recently taken any other medicines, including
medicines obtained without a prescription.
Pregnancy and breast-feeding
Osigraft should not be used during pregnancy unless the benefits outweigh the risks to the foetus.
Women of child-bearing potential should inform their surgeon of the possibility of pregnancy prior to
treatment with Osigraft. Women of childbearing potential should be advised to use effective
contraception up to at least 12 months after treatment.
Do not breast-feed your baby during Osigraft therapy. In animal studies, excretion of IgG class anti-
OP-1 antibodies into milk has been shown. As human IgG is secreted into human milk, and the
potential for harm to the infant is unknown, women should not breast-feed during Osigraft therapy.
If
you are nursing you should use Osigraft only if your treating physician considers the benefits
outweigh the risks.
Driving and using machines
Not relevant
Important information about some of the ingredients of Osigraft
Do not use Osigraft if you have a known hypersensitivity to collagen.
3.
HOW TO USE OSIGRAFT
19
Treatment requires a single surgery. Depending on the size of the defect (gap of bone break), more
than a single 1g unit of Osigraft may be required. The maximum human dose should not exceed 2
vials (2g) since its effectiveness in the treatment on non-unions with gaps requiring higher doses has
not been established.
Osigraft is administered by your doctor during your surgery. It is placed directly at the defect (injury)
site in contact with the prepared bone surface. The surrounding soft tissues (muscle and skin) are then
closed around the implant.
Method of administration:
You will be asleep during this procedure. The following are directions for the use of Osigraft by your
doctor.
1.
Using sterile technique, remove the vial from its packaging.
2.
Lift the plastic flip-top and remove the crimp from the vial.
Handle the crimp with care. The edges of the crimp are sharp and may cut or damage gloves.
3.
Using your thumb, pry up the edge of the stopper. Once the vacuum is broken, remove the vial
stopper while holding the vial upright to prevent loss of product.
Do not insert a needle through the stopper. Puncture of the stopper with a needle may result in
particles of stopper material contaminating Osigraft.
4.
Carefully transfer contents of the Osigraft vial to a suitable container such as a sterile bowl.
Warning: To avoid breakage do not tap the bottom of the vial when transferring contents.
5.
Reconstitute Osigraft with 2 to 3 ml of sterile 9 mg/ml sodium chloride solution for injection
(0.9% w/v) prior to use. When reconstituted, Osigraft has the consistency of wet sand, which
facilitates its implantation and placement at bone site defects. Once the implant is prepared it
should be used immediately. Any unused Osigraft should be disposed together with surgical
waste in accordance with local requirements.
6.
Debride fibrous, necrotic or sclerotic tissue and appropriately decorticate bone so that Osigraft
is in direct contact with bleeding bone and viable osseous tissue.
7.
Provide adequate haemostasis to ensure that material is not dislodged from the surgical site.
Irrigate as necessary prior to the implantation of Osigraft. Where practical, surgical
manipulations to the site should be completed prior to product implantation.
8.
Apply Osigraft to the prepared osseous tissue site using a sterile instrument such as a spatula or
curette. The amount of Osigraft used should approximate the size of the bone defect.
9.
Do not use suction or irrigation directly at the implant site as the particles of Osigraft may be
removed. Remove excess fluid if necessary by suctioning adjacent to the implant site or
carefully blotting the area with sterile sponge.
10.
Close soft tissues around the defect containing Osigraft using suture material of choice. Closure
is critical for containment of the implant in the area of the defect.
11.
After closure of the soft tissues around the defect, irrigate field, if necessary to remove any
product, which may have become dislodged during soft tissue closure.
20
12.
Do not place a drain directly in the implant site. If required, place it subcutaneously.
4.
POSSIBLE SIDE EFFECTS
Like all medicines, Osigraft can have side effects, although not everybody gets them.
Administration of Osigraft requires surgery. Adverse events following such surgery and not
specifically associated with the product may include wound infection, osteomyelitis (infection of the
bone), complications of mechanical support (such as the metal rod or plate used for stabilisation),
bleeding at the wound site, failure of the wound to heal, nausea, fever and pain. The incidence of these
events in clinical studies was >10%. However, there were no differences in the incidence of these
adverse events compared with patients who received bone autograft (transplanted bone) instead of
Osigraft, except in the case of osteomyelitis (infection of the bone) for which the incidence of
osteomyelitis was statistically higher in the autograft group.
In clinical studies, the following undesirable effects have been reported as related to Osigraft
discoloration of the wound site, erythema (redness of the skin), tenderness, and swelling over the
implant site, and heterotopic ossification / myositis ossificans (bone formation outside of the fracture
area). None of these events were classified as serious.
If any of the side effects gets serious, or if you notice any side effect not listed in this leaflet, please
tell your doctor.
5.
HOW TO STORE OSIGRAFT
Keep out of the reach and sight of children.
Store in a refrigerator at (2°C - 8°C)
Keep the blister pack in the outer carton
Any unused product or waste material should be disposed of in accordance with local requirements
Do not use after the expiry date which is stated on the label. The expiry date refers to the last day of
that month.
6.
FURTHER INFORMATION
What Osigraft contains
The active substance is eptotermin alfa (3.3 mg in 1 g of powder), produced by recombinant DNA
technology in Chinese Hamster Ovary (CHO) cells.
The other ingredient is vacuum dried bovine collagen, (1 g of powder in a vial).
What Osigraft looks like and contents of the pack
Osigraft is supplied as white to off-white powder packaged in an amber colored glass vial (pack size of
1) within a blister pack, comprised of a plastic tray and lid, in a carton.
Marketing Authorisation Holder and Manufacturer
Howmedica International S. de R. L.
Division of Stryker Corporation
Raheen Business Park
Limerick
Ireland
21
Tel +353-61-498200
Fax +353-61-498247
This leaflet was last approved in
Detailed information on this medicine is available on the European Medicines Agency (EMEA) web site:
http://www.emea.europa.eu
22
Source: European Medicines Agency
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