Opgenra - patient leaflet, side effects, dosage

Patient leaflet - Opgenra

B. PACKAGE LEAFLET

Package leaflet: Information for the patient

Opgenra 3.3 mg powder for implantation suspension eptotermin alfa

This medicine is subject to additional monitoring. This will allow quick identification of new safety information. You can help by reporting any side effects you may get. See end of section 4 for how to report side effects.

Read all of this leaflet carefully before you are administered this medicine because it contains important information for you.

– Keep this leaflet. You may need to read it again.
– If you have any further questions, ask your doctor.
– If you get any side effects talk to your doctor. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet :

1. What Opgenra is and what it is used for.
2. What you need to know before you are administered Opgenra.
3. How to use Opgenra.
4. Possible side effects.
5 How to store Opgenra.
6. Contents of the pack and other information.

1. What Opgenra is and what it is used for

Opgenra contains the active substance eptotermin alfa.

Opgenra is a type of medicine known as a bone morphogenetic protein (BMP). This group of medicines cause new bone to grow at the location where the surgeon has placed (implanted) it.

Opgenra is implanted in adult patients with slippage of the spine (spondylolisthesis) in cases where treatment with autograft (transplanted bone from your hip) has failed or must not be used.

2. What you need to know before you are administered Opgenra

Do not use Opgenra

– if you are allergic to eptotermin alfa or to any of the ingredients of this medicine (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, Sjogren’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).
– have had this medicine, eptotermin alfa or any similar medicine before.
– have any tumours in the area intended for surgery.
– if you require a spinal fusion because of a metabolic bone disease or tumours.
– if you are receiving chemotherapy, radiation treatment or immunosuppression.
- if you are a child (less than 12 years old).
- if you are an adolescent (12–18 years old) or your skeleton is not yet be fully formed (you are still growing).

Warnings and precautions

Talk to your doctor before you are administered this medicine.

Use of this medicine does not guarantee fusion. Additional surgeries may be needed.
There is a possibility that new antibodies can form in your body when this medicine is used. It

is possible they may impair the effectiveness of this medicine or cause an immune system response.

Inform your doctor or surgeon if you have been administered this medicine in the past. Repeated use of this medicine 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.
Inform your doctor if you have a history of liver or kidney disease.
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.

Opgenra has not been studied for use in cervical spine surgery. Use of this medicine in the cervical spine cannot be recommended.
Use of this medicine with synthetic bone substitutes is not recommended.

Talk to your doctor or surgeon about these precautions before you are administered this medicine.

Other medicines and Opgenra

Tell your doctor if you are taking or have recently taken any other medicines.

Use of this medicine with synthetic bone substitutes is not recommended. There have been reports of swelling and infection following the use of this medicine with synthetic bone substitutes.

Pregnancy and breast-feeding

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

Driving and using machines

It is unlikely that Opgenra will affect the ability to drive and use machines

3. How to use 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 anaesthetic so you will not be awake during the surgery.

A small quantity (one unit) of this medicine is reconstituted and 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 patient’s 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.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Talk to your doctor if you have any of the following:

– Common (may affect up to 1 in 10 people):

redness of the skin (erythema) ,
increased bone formation or bone formation outside of the fusion area (heterotopic bone formation),
failure of the spine to fuse (pseudarthrosis),
wound problems including infection, discharge and rupture.

– Uncommon (may affect up to 1 in 100 people):

localised swelling, swelling over the implant site,
collection of fluid in the tissues (seroma),
product migration (this has been observed when the product was mixed with a synthetic product used to fill the bone void)

– Not known (cannot be estimated from available data)

problems at the implant site (for example abscess, hardening, pain, swelling, or fever)
allergic reactions (for example rash or hives)
post-surgery problems (for example discharge, swelling or other wound complications)
resorption of bone (osteolysis).

Some patients that had a history of heart problems or were prone to frequent infections became worse after being administered this medicine. 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.

Reporting of side effects

If you get any side effects, talk to your doctor or surgeon.. 'This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Opgenra

Keep out of the sight and reach of children.

Do not use this medicine 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 this medicine both before and during its use, as well as for its correct disposal.

6. Contents of the pack and other information

What Opgenra contains

The active substance is eptotermin alfa (a recombinant human osteogenic protein 1 produced in a Chinese hamster ovary (CHO) cell line).

The other ingredients are bovine collagen and carmellose.

One vial of this medicine 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 powder for implantation suspension 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 × 1 vial containing 1g of powder (3.3 mg eptotermin alfa) and 2 × 1 vial containing 230 mg carmellose powder.

Annex IV

Grounds for one additional renewal

The CHMP recommend an additional five-year renewal based on the following pharmacovigilance grounds: the clinical experience with the product in the designated indication has been very limited in the EU during the first 5-year period of marketing authorisation. Indeed, there has been a limited exposure due to a recent and limited marketing of the product (launched in the EU only in August 2011 and marketed in only few Member States). In addition, results of the post-authorisation studies to investigate the long term safety and efficacy of Opgenra and also investigate the actual drug utilisation in ‘real life’ are needed to further characterise the safety and efficacy profile.