NovoSeven

NovoSeven 1 mg (50 KIU) powder and solvent for injectable solution
NovoSeven 2 mg (100 KIU) powder and solvent for injectable solution
NovoSeven 5 mg (250 KIU) powder and solvent for injectable solution
NovoSeven 8 mg (400 KIU) powder and solvent for injectable solution
eptacog alfa (activated)
Please read this leaflet carefully before administering this injection, as it contains important
information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, consult your doctor.
• This medicine has been prescribed for you only. Never give it to others, even if their symptoms are the same as yours, as it could be dangerous.
• If any of the side effects occur, including those not listed in this leaflet, consult your doctor. See section 4.

Contents of this leaflet:

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

On the back of this page: instructions on how to use NovoSeven

1. What NovoSeven is and what it is used for

NovoSeven is a blood coagulation factor. When the coagulation factors present in the body do not function properly, this medicine promotes blood clotting at the site of bleeding.
NovoSeven is used to treat bleeding episodes and to prevent excessive bleeding following surgery or other major procedures. Early treatment with NovoSeven reduces both the amount and duration of bleeding, including joint bleeding. This reduces the need for hospitalization and time away from work or school.
It is used in certain patient groups:

• If you have congenital haemophilia and do not respond normally to treatment with coagulation factors VIII or IX
• If you have acquired haemophilia
• If you have Factor VII deficiency
• If you have Glanzmann's thrombasthenia (a coagulation disorder) and your condition cannot be effectively treated with platelet transfusion, or if platelets are not readily available.

NovoSeven may be administered by a physician for the treatment of severe postpartum hemorrhage, even if you do not have an underlying bleeding disorder.

2. What you need to know before using NovoSeven

Do not use NovoSeven

• If you are allergic to eptacog alfa (the active substance in NovoSeven) or to any of the other ingredients contained in the medicine (listed in section 6).
• If you are allergic to bovine, mouse, or hamster proteins (such as cow's milk).

► If any of these situations apply, do not use NovoSeven. Consult your doctor.
Warnings and precautions
Before treatment with NovoSeven, pay attention to what your doctor tells you:

• If you have recently undergone surgery
• If you have recently suffered a crush injury
• If the size of your arteries is reduced due to disease
• If you have an increased risk of blood clot formation (thrombosis)
• If you have severe liver disease
• If you have a severe blood infection
• If you are predisposed to disseminated intravascular coagulation (DIC, a condition in which clots develop in blood vessels), you must be closely monitored.

► If you fall into any of the conditions described, contact your doctor before administering the injection.
Other medicines and NovoSeven
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
Do not use NovoSeven together with prothrombin complex concentrate or rFXIII.
Talk to your doctor before using NovoSeven if you are also using products containing factor VIII and IX.
There is limited experience with the use of NovoSeven in combination with medicines called antifibrinolytic drugs (such as aminocaproic acid and tranexamic acid), which are also used to control bleeding. Talk to your doctor before taking NovoSeven with these medicines.
Pregnancy, breastfeeding and fertility
If you are pregnant, breastfeeding, or planning a pregnancy, ask your doctor for advice before using NovoSeven.
Driving and using machines
There are no studies on the effect of NovoSeven on the ability to drive and use machines.
However, there is no clinical reason to believe it may affect this ability.
NovoSeven contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per injection, i.e. it is practically "sodium-free".

3. How to use NovoSeven

NovoSeven powder must be reconstituted with the solvent and injected intravenously. For detailed instructions,
see the reverse of the package leaflet.
NovoSeven powder must be mixed with the solvent and injected intravenously. For detailed instructions,
see the reverse of the package leaflet.
When to treat
Begin treatment for bleeding as soon as possible, ideally within the first 2 hours.

• In case of mild or moderate bleeding, treat as soon as possible, ideally at home.
• In case of severe bleeding, contact your doctor. Severe bleeding is usually treated in hospital, and you may administer the first dose of NovoSeven during transport to the hospital.

Do not continue treatment for more than 24 hours without consulting your doctor:

• Each time you use NovoSeven, inform your doctor or hospital as soon as possible.
• If bleeding cannot be controlled within 24 hours, contact your doctor immediately. Hospital treatment will be required.

Dose
The first dose should be administered as soon as possible after the onset of bleeding. Consult your
doctor for information on when and for how long to administer doses.
The dose will be determined by your doctor, based on your body weight, your condition, and the type of
bleeding.
To achieve the best results, carefully follow the prescribed dose. Your doctor may adjust the dose.
If you have haemophilia:
The dose is usually 90 micrograms per kilogram of body weight; you may repeat the injection every 2–
3 hours until bleeding is under control.
Your doctor may recommend a single dose of 270 micrograms per kilogram of body weight.
There is no clinical experience regarding administration of this single dose in patients over 65 years of age.
If you have Factor VII deficiency:
The dose is usually between 15 and 30 micrograms per kilogram of body weight per injection.
If you have Glanzmann's thrombasthenia:
The usual dose is 90 micrograms (ranging between 80 and 120 micrograms) per kilogram of body weight,
per injection.
If you use more NovoSeven than you should
If you inject too much NovoSeven, consult your doctor immediately.
If you forget a dose of NovoSeven
If you have forgotten an injection of NovoSeven, or if you wish to discontinue treatment, consult your doctor immediately.

4. Possible side effects

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

Serious side effects

Rare ( may affect up to 1 in 1,000 treatment episodes )

• Allergy, hypersensitivity or anaphylactic reactions. Signs may include skin rash, itching, redness, urticaria; difficulty in breathing; feeling weak and dizzy; severe swelling of the tongue, lips or injection site.
• Blood clots in the arteries or heart (which may cause a heart attack or angina pectoris), in the brain (which may cause stroke), or in the intestines and kidneys. Signs may include severe chest pain, shortness of breath, confusion, difficulty speaking or moving (paralysis), or abdominal pain.

Uncommon ( may affect up to 1 in 100 treatment episodes )

• Blood clots in the veins of the lungs, legs, liver, kidneys or at the injection site. Signs may include difficulty in breathing, painful swelling and redness in the legs, or abdominal pain.
• Lack of response or reduced response to treatment.

► If you experience any of these side effects, contact your doctor immediately.
Inform your doctor that you are using NovoSeven.
Tell your doctor if you have previously had allergic reactions, as you may need to be monitored more closely. In the vast majority of blood clotting cases, patients had a predisposition to thrombotic events.

Other side effects
( may affect up to 1 in 1,000 treatment episodes )

• Nausea
• Headache
• Changes in certain haematological and liver values.

Other uncommon side effects
( may affect up to 1 in 100 treatment episodes )

• Allergic reactions such as skin rash, itching and urticaria.
• Fever.

Reporting of side effects

If you notice any side effects, inform your doctor. This includes any side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store NovoSeven

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date stated on the outer carton and labels. The expiry date refers to the last day of the month.
• Store powder and solvent at a temperature below 25°C.
• Store powder and solvent protected from light.
• Do not freeze.
• Use NovoSeven immediately after reconstituting the powder with the solvent to avoid infection. If not used immediately after reconstitution, the vial with adapter and syringe still attached must be stored in a refrigerator at 2°C to 8°C for no more than 24 hours. Do not freeze the mixed NovoSeven solution and protect it from light. Do not store the solution without consulting your doctor or nurse.
• Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package Contents and Other Information

What NovoSeven Contains

• The active substance is recombinant coagulation factor VIIa (eptacog alfa [activated]).
• The other components in the powder are sodium chloride, calcium chloride dihydrate, glycylglycine, polysorbate 80, mannitol, sucrose, methionine, hydrochloric acid, sodium hydroxide. The components of the solvent are histidine, hydrochloric acid, sodium hydroxide, water for injections.

The powder for injectable solution contains: 1 mg/vial (equivalent to 50 KIU/vial), 2 mg/vial (equivalent to 100 KIU/vial), 5 mg/vial (equivalent to 250 KIU/vial), or 8 mg/vial (equivalent to 400 KIU/vial).
After reconstitution, 1 ml of solution contains 1 mg of eptacog alfa (activated).
1 KIU equals 1000 IU (International Units).

Description of the Appearance of NovoSeven and Package Contents
The powder vial contains white powder and the pre-filled syringe contains a clear, colourless solution. The reconstituted solution is colourless. Do not use the reconstituted solution if particles are observed or if there is any change in colour.

Each package of NovoSeven contains:

• 1 vial with white powder for injectable solution
• 1 vial adapter
• 1 pre-filled syringe with solvent for reconstitution
• 1 plunger

Pack sizes: 1 mg (50 KIU), 2 mg (100 KIU), 5 mg (250 KIU), and 8 mg (400 KIU).
Please refer to the outer carton for information on the contents of each package in use.

Marketing Authorisation Holder and Manufacturer
Novo Nordisk A/S
Novo Allé
DK-2880 Bagsværd, Denmark

Other Sources of Information
More detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu

Instructions on How to Use NovoSeven
READ THESE INSTRUCTIONS CAREFULLY BEFORE USING NOVOSEVEN

NovoSeven is supplied as a powder. Before injection (administration), you must reconstitute it with the solvent provided in the pre-filled syringe. The solvent is a histidine solution. Reconstituted NovoSeven must be administered intravenously (intravenous injection). The materials included in this package are designed for reconstituting and injecting NovoSeven.

You will also need an administration set (infusion tubing and butterfly needle, sterile alcohol swabs, gauze, and adhesive bandages).
These devices are not included in the NovoSeven package.

Do not use the materials without adequate training from your doctor or nurse.
Always wash your hands and ensure the surrounding area is clean.
When preparing and injecting the medicine directly into a vein, it is important to use an aseptic, germ-free technique. Inappropriate technique may introduce germs that could cause infections.
Do not open the materials until you are ready to use them.
Do not use the materials if they have been dropped or are damaged. Instead, use a new package.
Do not use the materials after the expiry date. Instead, use a new package. The expiry date is printed after 'EXP' on the outer carton, vial, vial adapter, and pre-filled syringe.
Do not use the materials if you suspect contamination. Instead, use a new package.
Do not discard any components until after the reconstituted solution has been injected.
The materials are for single use only.

Contents
The package contains:

• 1 vial with NovoSeven powder
• 1 vial adapter
• 1 pre-filled syringe with solvent
• 1 plunger (placed under the syringe)

Plunger
Thread
Tip end

1. Prepare the vial and syringe • Take out the number of NovoSeven packages you need. • Check the expiration date. • Check the name, dosage, and color of the packaging to make sure it contains the correct product. • Wash your hands and dry them thoroughly with a clean towel or hand dryer. • Take the vial, vial adapter, and pre-filled syringe from the box. Leave the plunger in its packaging. • Bring the vial and pre-filled syringe to room temperature (not above 37°C). You can do this by holding them in your hands until they feel as warm as your hands. • Do not use any other method to heat the vial or pre-filled syringe.	A
Remove the plastic cap from the vial. If the rubber stopper is loose or missing, do not use the vial. • Clean the rubber stopper with a sterile alcohol swab and let it air dry for a few seconds before use to ensure it is as germ-free as possible. • Do not touch the rubber stopper with your fingers to avoid transferring germs.	B
2. Attach the vial adapter • Remove the protective seal from the vial adapter. If the protective seal is not tightly closed or is broken, do not use the adapter. Do not remove the adapter from the protective cap with your fingers. If you touch the end of the vial adapter, germs may be transferred.	C
Place the vial on a flat, solid surface. • Twist the protective seal to attach the adapter onto the vial. Once attached, do not remove the adapter from the vial.	D
Gently press the protective cap with your thumb and index finger as shown. Remove the protective cap from the adapter. Do not lift the adapter from the vial when removing the protective cap.	E
3. Attach the plunger and syringe • Take the plunger from the end and remove it from its packaging. Do not touch the sides or threaded part of the plunger. If you touch these parts, germs may be transferred. • Immediately insert the plunger into the syringe, screwing it clockwise into the pre-filled syringe until you feel resistance.	F
Remove the syringe cap from the pre-filled syringe by bending it downward until it breaks off. Do not touch the tip of the syringe under the syringe cap. If you touch the syringe tip, germs may be transferred. If the syringe cap is loose or missing, do not use the pre-filled syringe.	G
Screw the pre-filled syringe carefully onto the adapter until you feel resistance.	H
4. Reconstitute the powder with the solvent • Hold the pre-filled syringe slightly tilted with the vial pointing downward. • Push the plunger to inject all the solvent into the vial.	I
Keep the plunger fully depressed and gently rotate the vial until the powder dissolves. Do not shake the vial, as this may cause foaming. • Check the reconstituted solution. It should be colorless. If you see visible particles or discoloration, do not use it. Instead, use a new package.	J
Use reconstituted NovoSeven immediately to avoid infection. If you cannot use it immediately, see section 5 "How to store NovoSeven" on the other side of this leaflet. Do not store the reconstituted solution without the advice of your doctor or nurse. (I) If your dose requires more than one vial, repeat steps A to J with additional vials, adapters, and pre-filled syringes until you reach the required dose.
Keep the plunger fully depressed. • Rotate the syringe with the vial pointing downward. • Stop pushing the plunger and let it return on its own as the reconstituted solution fills the syringe. • Gently pull back the plunger to draw the reconstituted solution into the syringe. • If you need only part of the reconstituted solution, use the scale on the syringe to measure the amount drawn, as instructed by your doctor or nurse. • If there is too much air in the syringe at this point, inject the air back into the vial.	K
With the vial held downward, gently tap the syringe to allow any air bubbles to rise to the top. • Slowly push the plunger until all air bubbles have risen.
Unscrew the adapter with the vial. • Do not touch the tip of the syringe. If you touch the syringe tip, germs may be transferred.	L
Inject NovoSeven using the pre-filled syringe through needle-free connectors for central venous catheters. Warning: The pre-filled syringe is made of glass and is designed to be compatible with standard luer-lock connectors. Some needle-free connectors with an internal tip are incompatible with pre-filled syringes. This incompatibility may prevent drug administration and/or damage the needle-free connector. Follow the instructions for use of needle-free connectors. Administration through a needle-free connector may require transferring the reconstituted solution into a standard 10 ml luer-lock plastic syringe. This step must be performed after step J.
5. Inject the reconstituted solution. NovoSeven is now ready to be injected intravenously. • Inject the reconstituted solution according to the instructions of your doctor or nurse. • Inject slowly over 2–5 minutes. Administer the solution through a central venous access system (CVC), such as a central venous catheter or implanted port: • Use an aseptic, germ-free technique. Follow the instructions for use of the connector and central venous catheter (CVC) as provided by your doctor or nurse. • Injection via a CVC requires the use of a sterile 10 ml syringe to withdraw the reconstituted solution. • If the CVC line needs to be flushed before or after injection with NovoSeven, use an injectable sodium chloride solution 9 mg/ml.
Disposal • After injection, dispose of the syringe with the administration set, the vial with the adapter, unused NovoSeven, and other waste materials as instructed by your doctor or nurse. • Do not dispose of them with household waste.	M
Do not disassemble the materials before disposal. Do not reuse any materials.