Opgenra 3.3 mg powders for suspension for implantation

Opgenra must not be used

• if you are allergic (hypersensitive) to eptotermin alfa or to any of the ingredients of Opgenra (see section 6).
• if you have an autoimmune disease (disease arising from or directed against your own tissues), including Crohn?s disease, rheumatoid arthritis, systemic lupus erythematosus, scleroderma, Sjögren?s syndrome and dermatomyositis/ polymyositis.
• if you have an active infection in your spine or have been told that you have an active internal (systemic) infection.
• if you have inadequate skin coverage and inadequate blood supply at the site of surgery (your doctor should have told you if this is the case).
• if you require a spinal fusion because of a metabolic bone disease or tumours
• have any tumours in the area intended for surgery.
• if you are receiving chemotherapy, radiation treatment or immunosuppression .
• have had Opgenra, eptotermin alfaor any similar medicine before.
• if you are a child.
• if you are an adolescent and your skeleton is not yet be fully formed (you are still growing).

Take special care with Opgenra:

The following are precautions for use of Opgenra to be discussed with your doctor.

• There is a possibility that new antibodies can form in your body when Opgenra is used. Your doctors will monitor you if they suspect this is the case.
• Inform your doctor or surgeon if you have a history of heart problems or are prone to frequent infections so that they can closely monitor you.
• Repeated use of Opgenra cannot be recommended. Laboratory studies have demonstrated that there is a theoretical risk of developing autoimmunity towards the natural (endogenous) BMP proteins in your body following repeat exposure to this medicine.

Use of Opgenra does not guarantee fusion; additional surgeries may be required.

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

Opgenra should not be used during pregnancy unless the benefits to the mother outweigh the risks to the unborn child. Women of child-bearing potential should inform their surgeon of the possibility of pregnancy before undergoing treatment with Opgenra. Women of childbearing potential are advised to use effective contraception for a period of 2 years after their treatment.

Do not breast-feed your baby during Opgenra therapy. As the potential for harm to the breast fed infant is unknown, women should not breast-feed during the period immediately following treatment with Opgenra. If you are nursing, you should receive Opgenra only if your treating physician or surgeon considers the benefits to you outweigh the risks to your child.

Driving and using machines

Studies on the effects on the ability to drive and use machines have not been performed with Opgenra.

Opgenra is only used by an appropriately qualified surgeon during the course of spinal fusion surgery. This is normally done under a full general anasethetic so you will not be awake during the surgery.

A small quantity (one unit) of Opgenra is placed directly on each side of the spine at the site requiring fusion. The surrounding muscle tissue is then closed around the implanted medicine as is the skin on top of the muscle. This specialised medicine is used instead of autograft bone (some of a patients own bone taken from the hip) to fuse the spine.

The maximum dose of this medicine should not exceed 2 units (6.6 mg eptotermin alfa) since its effectiveness and safety in higher doses has not been studied.

Like all medicines, Opgenra can cause side effects, although not everybody gets them. These side effects may occur with certain frequencies, which are defined as follows: common: affects 1 to 10 users in 100
uncommon: affects 1 to 10 users in 1,000

In clinical studies, the following side effects were reported:
Common reported side effects included:

• erythema (redness of the skin),
• tenderness and swelling over the implant site,
• heterotopic ossification (bone formation outside of the fusion area),
• pseudarthrosis (failure of the spine to fuse),
• wound infections. Uncommon reported side effects included:
• localised swelling
• seroma (a collection of fluid in the tissues)
• product migration (this has been observed when the product was mixed with a synthetic product used to fill the bone void)

Some common undesirable side effects can follow spine surgery itself and these include:

• wound infection,
• osteomyelitis (infection of the bone),
• complications of mechanical support (such as instruments used for stabilisation),
• bleeding at the wound site,
• failure of the wound to heal,
• nausea,
• fever and
• pain.

If the side effects gets serious or you notice any side effects not listed in this leaflet, please tell your doctor.

Like all medicines, Opgenra can cause side effects, although not everybody gets them. These side effects may occur with certain frequencies, which are defined as follows: common: affects 1 to 10 users in 100
uncommon: affects 1 to 10 users in 1,000

In clinical studies, the following side effects were reported:
Common reported side effects included:

• erythema (redness of the skin),
• tenderness and swelling over the implant site,
• heterotopic ossification (bone formation outside of the fusion area),
• pseudarthrosis (failure of the spine to fuse),
• wound infections. Uncommon reported side effects included:
• localised swelling
• seroma (a collection of fluid in the tissues)
• product migration (this has been observed when the product was mixed with a synthetic product used to fill the bone void)

Some common undesirable side effects can follow spine surgery itself and these include:

• wound infection,
• osteomyelitis (infection of the bone),
• complications of mechanical support (such as instruments used for stabilisation),
• bleeding at the wound site,
• failure of the wound to heal,
• nausea,
• fever and
• pain.

If the side effects gets serious or you notice any side effects not listed in this leaflet, please tell your doctor.

Keep out of the reach and sight of children.

Do not use Opgenra after the expiry date which is stated on the carton and blisters. The expiry date refers to the last day of the month. Opgenra should be used immediately after reconstitution.

Store in a refrigerator (2°C - 8-C).
Keep the blisters in the outer carton.

The hospital pharmacist or surgeon is responsible for the correct storage of the product both before and during its use, as well as for the correct disposal.

What Opgenra contains

The active substance is eptotermin alfa (a recombinant human Osteogenic protein 1 produced in a recombinant Chinese hamster ovary (CHO) cell line). One vial of Opgenra contains 1 g of powder including 3,3 mg of eptotermin alfa and the excipient bovine collagen. The other vial contains the excipient carmellose.

What Opgenra looks like and contents of the pack

One unit of Opgenra powders for suspension for implantation comes as two separate powders. The powder containing the active substance and the excipient bovine collagen has the appearance of a white to off-white granular powder; the carmellose powder is a yellowish white powder.

The powders come in glass vials. Each vial is secured in a sterile blister. Each outer carton contains one 3.3 mg eptotermin alfa vial containing 1 g of powder and one carmellose powder vial containing 230 mg powder.

Pack sizes:
-a single unit pack with 1 vial containing 1g of powder (3.3 mg eptotermin alfa) and 1 vial containing 230 mg carmellose powder
-a pack of two units with 2 x 1 vial containing 1g of powder (3.3 mg eptotermin alfa) and 2 x 1vial containing 230 mg carmellose powder.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Howmedica International S. de R. L.
Raheen Business Park
Limerick
Ireland

Tel +353-61-498200
Fax +353-61-498247

This leaflet was last approved in .