Alhemo

Package leaflet: Information for the user

Alhemo 15 mg/1.5 mL solution for injection in pre-filled pen

concizumab
This medicinal product is subject to additional monitoring. This will allow for rapid identification of new safety information. You can help by reporting any side effects you experience while taking this medicine. See the end of section 4 for information on how to report side effects.
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet

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

1. What Alhemo is and what it is used for

What Alhemo is
Alhemo contains the active substance concizumab, which belongs to a group of medicines called
"monoclonal antibodies". Concizumab is a protein that recognises a target in the blood and binds to it. This target is involved in the blood clotting process.

What Alhemo is used for
Alhemo is used to prevent or reduce the frequency of bleeding episodes in adults and adolescents aged 12 years and older with:

• Haemophilia A with inhibitors.
• Severe haemophilia A (when blood levels of factor VIII are less than 1%) without inhibitors.
• Haemophilia B with inhibitors.
• Moderate/severe haemophilia B (when blood levels of factor IX are less than or equal to 2%) without inhibitors.

Haemophilia A is a congenital deficiency of blood coagulation factor VIII, and haemophilia B is a congenital deficiency of blood coagulation factor IX.

How Alhemo works
Concizumab blocks a natural factor in the blood that prevents blood from clotting. This factor is called tissue factor pathway inhibitor. By blocking this inhibitor, blood clotting becomes more effective, thereby helping to prevent or reduce bleeding when a coagulation factor is missing.

Alhemo works independently of factor VIII and factor IX, and independently of their inhibitors.

2. What you need to know before using Alhemo

Do not use Alhemo

• if you are allergic to concizumab or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Allergic reactions
You may be at risk of experiencing an allergic reaction. Stop treatment and contact your doctor if you develop symptoms of allergic reactions such as rash, redness, hives, or itching. You may also experience symptoms of severe allergic reactions such as:

• itching over large areas of the skin
• redness and/or swelling of the lips, tongue, face, or hands
• difficulty swallowing
• shortness of breath
• wheezing
• chest tightness
• paleness and cold skin
• rapid heartbeat
• dizziness due to low blood pressure.

Stop using Alhemo and seek immediate emergency medical help if you experience symptoms of severe allergic reactions.
Blood clots
Blood clots can form in any part of the body.
Stop using Alhemo and contact your doctor immediately if you experience symptoms of blood clots such as:

• Swelling, warmth, pain, or redness of the skin: these could be signs of a blood clot in the arms or legs.
• Feeling short of breath, severe chest pain: these could be signs of blood clots in the heart or lungs.
• Headache, feeling confused, difficulty speaking or moving, facial numbness, eye pain or swelling, or vision problems: these could be signs of a blood clot in the brain or eyes.
• Sudden stomach or lower back pain: these could be signs of blood clots in the intestines or kidneys.

Children and adolescents
Alhemo is not recommended for children under 12 years of age. The safety and benefit of this medicine have not yet been established in this population.
Other medicines and Alhemo
Tell your doctor if you are taking, have recently taken, or might take any other medicines.
Pregnancy and breastfeeding
Use a highly effective method of contraception during treatment with Alhemo and for 7 weeks after the last injection. Talk to your doctor to discuss which type of contraception is suitable for you.
If you are pregnant, think you might be pregnant, planning to become pregnant, or are breastfeeding, consult your doctor before using this medicine.
Driving and using machines
Alhemo is unlikely to affect your ability to drive or operate machinery.
Alhemo contains sodium and polysorbates
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e., essentially “sodium-free”.
This medicine contains 0.25 mg of polysorbate 80 per mL. Polysorbates may cause allergic reactions. Inform your doctor if you have known allergies.

3. How to use Alhemo

Before using the Alhemo pre-filled pen, consult the Instructions for Use detailed on the reverse side of
this leaflet. Speak to your doctor if you need to use alternative injection techniques; for example, thin patients and adolescents might need to inject into a skin fold held gently to avoid injecting too deeply (into the muscle).
Use this medicine exactly as directed by your doctor. If you have any doubts, consult your doctor, pharmacist, or nurse.
Management of sudden bleeding episodes
You may need to use factor VIII, factor IX, or bypassing agents to treat sudden bleeding episodes while using Alhemo. Follow your doctor’s instructions carefully regarding when and how to use these factor VIII, factor IX, or bypassing agent products.
Recommended dose for adults and adolescents is

• Initial dose on Day 1: 1 mg per kg of body weight.
• From Day 2 until the maintenance dose is established: 0.20 mg per kg of body weight once daily.
• Individual maintenance dose as determined by the doctor: 0.15, 0.20, or 0.25 mg per kg of body weight once daily.

Alhemo is injected under the skin of the abdomen or thigh and can be used at any time of day.
If you use more Alhemo than you should
Contact your doctor immediately.
If you forget to use Alhemo
Alhemo can be used at any time of day.
Missing one or more doses of Alhemo may affect the effectiveness of the medicine. It is important to take Alhemo every day.
If you miss a daily dose of Alhemo:
if you miss a dose during the first 4 weeks of treatment, contact your doctor to discuss how to resume treatment.
If you miss a dose after the maintenance dose has been established:

• If you missed 1 daily dose, resume your daily dose.
• If you missed 2 to 6 daily doses, take your daily dose twice (as two separate injections, each corresponding to the daily dose) and then continue taking your daily dose the next day.
• If you missed 7 or more daily doses, contact your doctor immediately, as you will need a new loading dose before continuing your daily dose the next day. If in doubt, consult your doctor.

If you stop treatment with Alhemo
You may no longer be protected against bleeding. Do not stop treatment with Alhemo without first consulting your doctor.
If you have any questions about using this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them.
Stop using Alhemo and contact your doctor immediately if you experience symptoms of severe allergic reactions or symptoms of blood clots. See “Warnings and precautions” in section 2.
Other side effects
Very common: may affect more than 1 in 10 people

• Injection site reactions such as redness, bleeding, itching, hives, swelling, pain, numbness.

Common: may affect up to 1 in 10 people

• Allergic reaction

Uncommon: may affect up to 1 in 100 people

• Blood clots

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects directly via the national reporting system detailed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Alhemo

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the pen label and on the box after “Exp.”. The expiry date refers to the last day of that month.
Do not use this medicine if you notice any change in the colour of the solution.

Before use

• Store unused Alhemo pens in a refrigerator at 2 °C - 8 °C.
• Store the new, unused pen with the cap attached.
• When stored in the refrigerator, do not place the pen directly next to the cooling element.
• Do not use Alhemo if it has been frozen or stored at temperatures above 30 °C.

After first use

• Store the Alhemo pen currently in use without the needle attached, for up to 28 days (4 weeks):
  • in a refrigerator at 2 °C - 8 °C. Do not place the pen directly next to the cooling element. Do not use Alhemo if it has been frozen. or
  • at room temperature below 30 °C. Discard the pen if it has been stored at a temperature above 30 °C. Do not store the pen in direct sunlight.
• Store the Alhemo pen in use with the cap attached.

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 Alhemo contains

• The active substance is concizumab. One millilitre of Alhemo 15 mg/1.5 mL contains 10 mg of concizumab.
• The other components are L-Arginine hydrochloride, L-histidine, sodium chloride, sucrose, polysorbate 80, phenol, hydrochloric acid and sodium hydroxide (for pH adjustment) and water for injections. See also section 2 “Alhemo contains sodium and polysorbates”.

Description of the appearance of Alhemo and contents of the pack
Alhemo is an injectable solution, from clear to slightly turbid and from colourless to slightly yellow,
in a single-use pre-filled pen. Transparent to white protein particles are acceptable.
Alhemo 15 mg/1.5 mL is available in single packs containing 1 pre-filled pen or in multiple packs containing 5 pre-filled pens (5 packs of 1). Not all pack sizes may be marketed.
Injection needles are not included.
Marketing Authorisation Holder and Manufacturer
Novo Nordisk A/S
Novo Alle 1
DK-2880 Bagsvaerd
Denmark
Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu

Instructions for use

Alhemo 15 mg/1.5 mL solution for injection in pre-filled pen

concizumab

What is contained in this pack?

• 1 Alhemo pre-filled pen
• Package leaflet

Needles not included.
Read the instructions and ensure you have received training from your doctor or nurse before using
the pen.
Follow your doctor's or nurse's instructions on how to use Alhemo and how often to inject it.
The pen is pre-filled with 15 mg of Alhemo for subcutaneous use only (injection under the skin). The
pen contains multiple doses of Alhemo.
The pen can deliver a maximum of 8 mg in a single injection. The dose counter increment is 0.1 mg. If
you require more than 8 mg, you must perform multiple injections. Other pens are available that can
administer the daily dose in a single injection. Please consult your doctor or nurse.
Safety information

The pen is for single-patient use only and must not be shared. Sharing the pen or needles may cause
infections and transmission of diseases.
Always use a new needle for each injection. Do not reuse needles, as they may become blocked,
infected, or deliver an incorrect dose.
The needle is covered by two caps: both must be removed. If you forget to remove both caps, no
solution will be injected.
Where should I inject the dose?
You may inject under the skin:

• of the abdomen OR
• of the thigh.

Inject at a 90° angle. The grey areas in the figure on the right indicate suitable injection sites. For each
injection, select a new site at least 5 cm away from the previous injection site.

Check the pen 1
Check the pen label
Look at the name and colour to ensure you have the correct medicine.
Inspect the medicine
Remove the pen cap and check that Alhemo in the viewing window appears as a solution ranging from
clear to slightly cloudy and from colourless to pale yellow. Transparent to white protein particles are
acceptable. Do not use the pen if Alhemo appears discoloured.
Check the expiry date
Check the expiry date on the pen label to ensure it has not passed. Do not use the pen if the expiry
date has passed.
If the pen is cold
You may inject Alhemo directly from the refrigerator or allow it to reach room temperature before
injection. You may warm the pen between your palms. Do not use any other warming method.
Attach a new needle 2
Take a new needle and remove the protective seal.

• Push the needle straight onto the pen. Rotate it until it is securely tightened. See A.
• Remove the outer needle cap and keep it. See B.
• Remove the inner needle cap and discard it. See B.

Never use a bent or damaged needle.
Use only needles recommended by your doctor or nurse. This pen is designed to be used with NovoFine Plus 32G x 4 mm or NovoFine 32G x 4 mm injection needles. If you use needles longer than 4 mm, consult your doctor or nurse for instructions on how to perform the injection.

Check the flow 3
A drop of Alhemo may appear at the needle tip, but you must still check the flow of Alhemo before each injection to avoid underdosing:
a. Rotate the dose selector one increment to select 0.1 mg. See A in the following figure. Hold the pen with the needle pointing upward.
b. Press the injection button. See B.
c. Check that a stream of Alhemo comes out from the needle tip. See B.
If no stream appears, refer to Troubleshooting if no stream appears during flow check.

Select the dose 4
Rotate the dose selector to select the prescribed dose.
Confirm that you have selected the correct dose.
You may adjust the dose by rotating the dose selector in either direction.
If you require a dose larger than the maximum single dose, you must perform multiple injections to
achieve the full dose. Other pens are available that can deliver the daily dose in a single injection.
Please consult your doctor or nurse. For further information, see section 6.
The pen contains 15 mg of Alhemo.
The pen can deliver a maximum of 8 mg in a single injection.

Inject the dose 5
To ensure you deliver the full dose,
read steps a. to e. before starting the injection.
a. Select the injection site. Refer to the section Where should I inject the dose?
b. Insert the needle directly into the abdomen or thigh at a 90° angle.
c. Keep pressing the injection button until the dose counter returns to <0>.
d. With the needle still in the skin, count slowly to 6 after the dose counter returns to <0>.
e. Remove the needle from the skin.
The pen will click during administration, and you may also hear a click when the dose counter returns
to <0>.

Remove the needle 6
Remove the needle from the pen after each injection by placing the needle tip into its outer cap without touching the needle or cap.
Once the needle is covered, fully insert the outer cap by pressing gently. Then unscrew the needle. Do not touch the back end of the needle.
Dispose of the needle according to instructions from your doctor, nurse, pharmacist, or local authorities.

Do you need a higher dose than the maximum single dose?
Your doctor may provide you with a pen capable of delivering the daily dose in a single injection.
If you require a dose larger than the maximum single dose, you must perform multiple injections to
achieve the full dose.
Repeat steps 1 to 6 until you have injected the full dose. Once the full dose has been administered, proceed to step 7.

• Always use a new needle for each injection.
• Check the flow of Alhemo before each injection.
• Accurately calculate the amount to inject in each injection to receive the full dose.

After the dose 7
Replace the pen cap to protect Alhemo from light.
The pen is now ready for storage until next use.
After first use, do not use the pen for more than 28 days.

How much Alhemo is left in the pen?
The pen scale shows approximately how much Alhemo remains in the pen.

To see more accurately how much Alhemo remains in the pen, rotate the dose selector until it stops. The dose indicator will align with the number of milligrams remaining in the pen. The number shown on the dose counter indicates the milligrams remaining in the pen.
If the dose counter shows 8, at least 8 mg remain in the pen. The example below shows 3.4 mg of Alhemo remaining in the pen.

Troubleshooting if no stream appears during flow check (step 3)

• If no stream appears, repeat step 3 up to six times until a stream is visible.
• If no stream still appears, prepare a new needle (step 2) and repeat the flow check (step 3).
• If no stream appears even after using a new needle, do not use that pen. Use a new pen instead.

Storage
See section 5 “How to store Alhemo” on the back of this leaflet.
Caring for the pen
Handle the pen with care. Improper or careless use may lead to inaccurate dosing, which could result in the medicine not having the intended effect.
Do not expose the pen to dust, dirt, or liquids.
Do not wash, immerse in liquid, or lubricate the pen. If necessary, clean it with a neutral detergent on a damp cloth.
Always keep the pen out of sight and reach of others, especially children.
Disposal of Alhemo pens, needles, and packaging materials
When the pen is empty, dispose of it according to local regulations.
The pen cannot be refilled.
To reduce the risk of needlestick injury, dispose of used needles immediately as instructed by your doctor, nurse, pharmacist, or local authorities.
[Text for the first page of the folded leaflet]
Package leaflet and Instructions for use

Package leaflet: information for the user

Alhemo 60 mg/1.5 mL solution for injection in pre-filled pen

concizumab
This medicinal product is subject to additional monitoring. This will allow rapid identification of new safety information. You can help by reporting any side effects you experience while taking this medicine. See the end of section 4 for information on how to report side effects.
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

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

1. What Alhemo is and what it is used for

What Alhemo is
Alhemo contains the active substance concizumab, which belongs to a group of medicines called
"monoclonal antibodies". Concizumab is a protein that recognises a target in the blood and binds to it. This target is involved in the blood clotting process.

What Alhemo is used for
Alhemo is used to prevent or reduce the frequency of bleeding episodes in adults and adolescents aged 12 years and older with:

• haemophilia A with inhibitors.
• severe haemophilia A (when blood levels of factor VIII are less than 1%) without inhibitors.
• haemophilia B with inhibitors.
• moderate/severe haemophilia B (when blood levels of factor IX are less than or equal to 2%) without inhibitors.

Haemophilia A is a congenital deficiency of blood clotting factor VIII, and haemophilia B is a congenital deficiency of blood clotting factor IX.

How Alhemo works
Concizumab blocks a natural factor in the blood that prevents blood from clotting. This factor is called tissue factor pathway inhibitor. By blocking this inhibitor, blood clotting becomes more effective, thereby helping to prevent or reduce bleeding when a clotting factor is missing.

Alhemo works independently of factor VIII and factor IX, and independently of their inhibitors.

2. What you need to know before using Alhemo

Do not use Alhemo

• if you are allergic to concizumab or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Allergic reactions
You may be at risk of experiencing an allergic reaction. Stop treatment and contact your doctor immediately if you develop symptoms of allergic reactions such as rash, redness, hives, or itching. You may also experience symptoms of severe allergic reactions such as:

• itching over large areas of the skin
• redness and/or swelling of the lips, tongue, face, or hands
• difficulty swallowing
• shortness of breath
• wheezing
• chest tightness
• paleness and cold skin
• rapid heartbeat
• dizziness due to low blood pressure.

Stop using Alhemo and seek immediate emergency medical assistance if you experience symptoms of severe allergic reactions.
Blood clots
Blood clots can form in any part of the body.
Stop using Alhemo and contact your doctor immediately if you experience symptoms of blood clots such as:

• Swelling, warmth, pain, or redness of the skin: these could be signs of a blood clot in the arms or legs.
• Feeling short of breath, severe chest pain: these could be signs of blood clots in the heart or lungs.
• Headache, confusion, difficulty speaking or moving, facial numbness, eye pain or swelling, or vision problems: these could be signs of a blood clot in the brain or eyes.
• Sudden stomach or lower back pain: these could be signs of blood clots in the intestines or kidneys.

Children and adolescents
Alhemo is not recommended for children under 12 years of age. The safety and benefits of this medicine have not yet been established in this population.
Other medicines and Alhemo
Tell your doctor if you are taking, have recently taken, or might take any other medicines.
Pregnancy and breastfeeding
Use a highly effective method of contraception during treatment with Alhemo and for 7 weeks after the last injection. Talk to your doctor about which type of contraception is suitable for you.
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or are breastfeeding, consult your doctor before using this medicine.
Driving and using machines
It is unlikely that Alhemo will affect your ability to drive or operate machinery.
Alhemo contains sodium and polysorbates
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. essentially "sodium-free".
This medicine contains 0.25 mg of polysorbate 80 per mL. Polysorbates may cause allergic reactions. Inform your doctor if you have known allergies.

3. How to use Alhemo

Before using the Alhemo pre-filled pen, consult the Instructions for Use detailed on the reverse of
this leaflet. Speak to your doctor if you need to use alternative injection techniques; for example,
thin patients and adolescents may need to inject into a skin fold gently pinched to avoid injecting too
deeply (into the muscle).
Use this medicine exactly as instructed by your doctor. If you have any doubts, consult your doctor,
pharmacist, or nurse.
Management of sudden bleeding episodes
You may need to use factor VIII, factor IX, or bypassing agents to treat sudden bleeding episodes while
using Alhemo. Follow your doctor’s instructions carefully regarding when and how to use these
factor VIII-, factor IX-, or bypassing agent-based products.
Recommended dose for adults and adolescents is

• Initial dose on Day 1: 1 mg per kg body weight.
• From Day 2 until the maintenance dose is established: 0.20 mg per kg body weight once daily.
• Individual maintenance dose as determined by the doctor: 0.15, 0.20, or 0.25 mg per kg body weight once daily.

Alhemo is injected under the skin of the abdomen or thigh and may be used at any time of day.
If you use more Alhemo than you should
Contact your doctor immediately.
If you forget to use Alhemo
Alhemo may be used at any time of day.
Missing one or more doses of Alhemo may affect the medicine’s effectiveness. It is important to take
Alhemo every day.
If you miss a daily dose of Alhemo:
if you miss a dose during the first 4 weeks of treatment, contact your doctor to discuss how to
resume treatment.
If you miss a dose after the maintenance dose has been established:

• If you missed 1 daily dose, resume the daily dose.
• If you missed 2 to 6 daily doses, take the daily dose twice (as two separate injections, each corresponding to the daily dose), then continue taking the daily dose the next day.
• If you missed 7 or more daily doses, contact your doctor immediately, as you will need a new loading dose before continuing with the daily dose the next day. If you have any doubts, consult your doctor.

If you stop treatment with Alhemo
You may no longer be protected against bleeding. Do not stop treatment with Alhemo without first
consulting your doctor.
If you have any questions about the use of this medicine, speak to your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Stop using Alhemo and contact your doctor immediately if you experience symptoms of severe allergic reactions or symptoms of blood clots. See "Warnings and precautions" in section 2.
Other side effects
Very common: may affect more than 1 in 10 people

• Reactions at the injection site such as redness, bleeding, itching, hives, swelling, pain, numbness.

Common: may affect up to 1 in 10 people

• Allergic reaction

Uncommon: may affect up to 1 in 100 people

• Blood clots

Reporting of side effects
If you get any side effects, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects directly through the national reporting system detailed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Alhemo

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the pen label and on the
carton after “Expiry”. The expiry date refers to the last day of that month.
Do not use this medicine if you notice any change in the colour of the solution.

Before use

• Store unused Alhemo pens in a refrigerator at 2 °C - 8 °C.
• Store the new, unused pen with the cap attached.
• When storing in the refrigerator, do not place the pen directly next to the cooling element.
• Do not use Alhemo if it has been frozen or stored at temperatures above 30 °C.

After first use

• Store the Alhemo pen currently in use without the needle attached, for up to 28 days (4 weeks):
  • in the refrigerator at 2 °C - 8 °C. Do not store the pen directly next to the cooling element. Do not use Alhemo if it has been frozen. or
  • at room temperature below 30 °C. Dispose of the pen if it has been stored at temperatures above 30 °C. Do not store the pen in direct sunlight.
• Store the Alhemo pen in use with the cap attached.

Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Alhemo contains

• The active substance is concizumab. One millilitre of Alhemo 60 mg/1.5 mL contains 40 mg of concizumab.
• The other components are L-Arginine hydrochloride, L-histidine, sodium chloride, sucrose, polysorbate 80, phenol, hydrochloric acid and sodium hydroxide (for pH adjustment) and water for injections. See also section 2 “Alhemo contains sodium and polysorbates”.

Description of the appearance of Alhemo and contents of the pack
Alhemo is an injectable solution ranging from clear to slightly cloudy and from colourless to slightly yellow, in a single-use pre-filled pen. Transparent to white protein particles are acceptable.
Alhemo 60 mg/1.5 mL is available in single packs containing 1 pre-filled pen or in multiple packs containing 5 pre-filled pens (5 packs of 1). Not all pack sizes may be marketed.
Injection needles are not included.

Marketing Authorisation Holder and Manufacturer
Novo Nordisk A/S
Novo Alle 1
DK-2880 Bagsvaerd
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 for use

Alhemo 60 mg/1.5 mL solution for injection in pre-filled pen

concizumab

What does this pack contain?

• 1 pre-filled Alhemo pen
• Package leaflet
  Needles not included.

Read the instructions and make sure you have received training from your doctor or nurse before using the pen.
Follow your doctor’s or nurse’s instructions on how to use Alhemo and how often to inject it.
The pen is pre-filled with 60 mg of Alhemo for subcutaneous use only (injection under the skin). The pen contains multiple doses of Alhemo.
The pen can deliver up to 32 mg in a single injection. The dose counter increments in 0.4 mg steps. If you require more than 32 mg, you must perform multiple injections. Other pens are available that can deliver the daily dose in a single injection. Please consult your doctor or nurse.

Safety information
The pen is for single-patient use only and must not be shared. Sharing the pen or needles may cause infections and transmission of diseases.
Always use a new needle for each injection. Do not reuse needles, as they may become blocked, infected, or deliver an incorrect dose.
The needle is covered by two caps: both must be removed. If you forget to remove both caps, no solution will be injected.

Where should I inject the dose?
You may inject the dose under the skin:

• of the abdomen OR
• of the thigh

Inject at a 90° angle. The grey areas in the figure on the right indicate the injection sites. For each injection, select a new site at least 5 cm away from the previous injection site.

Check the pen 1
Check the pen label
Look at the name and colour to ensure you have the correct medicine.
Inspect the medicine
Remove the pen cap and check that Alhemo in the viewing window appears as a solution from clear to slightly cloudy and colourless to pale yellow. Transparent to white protein particles are acceptable. Do not use the pen if Alhemo appears discoloured.
Check the expiry date
Check the expiry date on the pen label to ensure it has not passed. Do not use the pen if the expiry date has passed.
If the pen is cold
You may inject Alhemo directly from the refrigerator or allow it to reach room temperature before injection. You may warm the pen between your palms. Do not use any other method to warm it.

Attach a new needle 2
Take a new needle and remove the protective seal.

• Push the needle straight onto the pen. Rotate it until it is firmly secured. See A.
• Remove the outer needle cap and keep it. See B.
• Remove the inner needle cap and discard it. See B.

Never use a bent or damaged needle.
Use only needles recommended by your doctor or nurse. This pen is designed to be used with NovoFine Plus 32G x 4 mm or NovoFine 32G x 4 mm injection needles. If you use needles longer than 4 mm, consult your doctor or nurse for injection instructions.

Check the flow 3
A drop of Alhemo may appear at the needle tip, but you must still check the flow of Alhemo before every injection to avoid underdosing:
a. Turn the dose selector one click to select 0.4 mg. See A in the figure below. Hold the pen with the needle pointing upward.
b. Press the injection button. See B.
c. Check that a stream of Alhemo comes out of the needle tip. See B.
If no stream appears, refer to Troubleshooting if no stream appears during flow check.

Select the dose 4
Turn the dose selector to select the prescribed dose.
Confirm that you have selected the correct dose.
You may adjust the dose by turning the dose selector in either direction.
If you require a dose larger than can be selected, you must perform multiple injections to achieve the full dose. Other pens are available that can deliver the daily dose in a single injection. Consult your doctor or nurse. For more information, see section 6.
The pen contains 60 mg of Alhemo.
The pen can deliver up to 32 mg in a single injection.

Inject the dose 5
To ensure you deliver the full dose,
read steps a. to e. before starting the injection.
a. Select the injection site. Refer to the section Where should I inject the dose?
b. Insert the needle directly into the abdomen or thigh at a 90° angle.
c. Keep pressing the injection button until the dose counter returns to <0>.
d. With the needle still in the skin, count slowly to 6 after the dose counter returns to <0>.
e. Remove the needle from the skin.
The pen will click during delivery, and you may hear another click when the dose counter returns to <0>.

Remove the needle 6
Remove the needle from the pen after each injection by placing the needle tip into its outer cap without touching the needle or cap.
When the needle is covered, press the outer cap fully on carefully. Then unscrew the needle. Do not touch the back end of the needle.
Dispose of the needle according to instructions from your doctor, nurse, pharmacist, or local authorities.

Do you need a higher dose than you can select?
Your doctor will provide you with a pen capable of delivering the daily dose in a single injection.
If you require a dose larger than can be selected, you must perform multiple injections to achieve the full dose.
Repeat steps 1 to 6 until you have injected the full dose. Once the full dose is injected, proceed to step 7.

• Always use a new needle for each injection.
• Check the flow of Alhemo before each injection.
• Accurately calculate the amount to inject in each injection to receive the full dose.

After the dose 7
Replace the pen cap to protect Alhemo from light.
The pen is now ready for storage until next use.
After first use, do not use the pen for more than 28 days.

How much Alhemo is left in the pen?
The pen scale shows approximately how much Alhemo remains in the pen.

To see more accurately how much Alhemo remains in the pen, turn the dose selector until it stops. The dose indicator will align with the number of milligrams remaining in the pen. The number shown on the dose counter is the number of milligrams left in the pen.
If the dose counter shows 32, there are 32 mg or more remaining in the pen.
The example below shows 13.6 mg of Alhemo remaining in the pen.

Troubleshooting if no stream appears during flow check (step 3)

• If no stream appears, repeat step 3 up to six times until a stream is seen.
• If still no stream appears, attach a new needle (step 2) and repeat the flow check (step 3).
• If no stream appears even after using a new needle, do not use that pen. Use a new pen.
  Storage See section 5 "How to store Alhemo" on the back of this leaflet.

Taking care of the pen
Handle the pen with care. Improper or careless use may lead to inaccurate dosing, which could result in not achieving the intended effect of the medicine.
Do not expose the pen to dust, dirt, or liquids.
Do not wash, immerse in liquid, or lubricate the pen. If necessary, clean it with a neutral detergent on a damp cloth.
Always keep the pen out of sight and reach of others, especially children.

Disposal of Alhemo pens, needles, and packaging materials
When the pen is empty, dispose of it according to local regulations.
The pen cannot be refilled.
To reduce the risk of needlestick injury, dispose of used needles immediately as instructed by your doctor, nurse, pharmacist, or local authorities.

[Text for the first page of the folded package leaflet]
Package leaflet and Instructions for use

Package leaflet: Information for the user

Alhemo 150 mg/1.5 mL solution for injection in a pre-filled pen

concizumab
This medicinal product is subject to additional monitoring. This will allow for rapid identification of new safety information. You can help by reporting any side effects you experience while taking this medicine. See the end of section 4 for information on how to report side effects.
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

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

1. What Alhemo is and what it is used for

What Alhemo is
Alhemo contains the active substance concizumab, which belongs to a group of medicines called
"monoclonal antibodies". Concizumab is a protein that recognises a target in the blood and binds to it. This target is involved in the blood clotting process.
What Alhemo is used for
Alhemo is used to prevent or reduce the frequency of bleeding episodes in adults and adolescents aged 12 years and older with:

• haemophilia A with inhibitors.
• severe haemophilia A (when blood levels of factor VIII are less than 1%) without inhibitors.
• haemophilia B with inhibitors.
• moderate/severe haemophilia B (when blood levels of factor IX are less than or equal to 2%) without inhibitors.

Haemophilia A is a congenital deficiency of blood coagulation factor VIII, and haemophilia B is a congenital deficiency of blood coagulation factor IX.
How Alhemo works
Concizumab blocks a natural factor in the blood that prevents blood from clotting. This factor is called tissue factor pathway inhibitor. By blocking this inhibitor, blood clotting becomes more effective, thereby helping to prevent or reduce bleeding when a clotting factor is missing.
Alhemo works independently of factor VIII and factor IX, and independently of their inhibitors.

2. What you need to know before using Alhemo

Do not use Alhemo

• if you are allergic to concizumab or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Allergic reactions
You may be at risk of experiencing an allergic reaction. Stop treatment and contact your doctor if you develop symptoms of allergic reactions such as rash, redness, hives, or itching. You may also experience symptoms of severe allergic reactions such as:

• itching over large areas of the skin
• redness and/or swelling of the lips, tongue, face, or hands
• difficulty swallowing
• shortness of breath
• wheezing
• chest tightness
• paleness and cold skin
• rapid heartbeat
• dizziness due to low blood pressure.

Stop using Alhemo and seek immediate emergency medical help if you experience symptoms of severe allergic reactions.
Blood clots
Blood clots can form in any part of the body.
Stop using Alhemo and contact your doctor immediately if you experience symptoms of blood clots such as:

• Swelling, warmth, pain, or redness of the skin: these could be signs of a blood clot in the arms or legs.
• Feeling short of breath, severe chest pain: these could be signs of blood clots in the heart or lungs.
• Headache, feeling confused, difficulty speaking or moving, facial numbness, pain or swelling in the eyes, or vision problems: these could be signs of a blood clot in the brain or eyes.
• Sudden stomach or lower back pain: these could be signs of blood clots in the intestines or kidneys.

Children and adolescents
Alhemo is not recommended for children under 12 years of age. The safety and benefits of this medicine have not yet been established in this population.
Other medicines and Alhemo
Tell your doctor if you are taking, have recently taken, or might take any other medicines.
Pregnancy and breastfeeding
Use a highly effective method of contraception during treatment with Alhemo and for 7 weeks after the last injection. Talk to your doctor to discuss which type of contraception is suitable for you.
If you are pregnant, think you might be pregnant, are planning to become pregnant, or are breastfeeding, ask your doctor for advice before using this medicine.
Driving and using machines
It is unlikely that Alhemo will affect your ability to drive or operate machinery.
Alhemo contains sodium and polysorbates
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. essentially "sodium-free".
This medicine contains 0.25 mg of polysorbate 80 per mL. Polysorbates may cause allergic reactions. Inform your doctor if you have known allergies.

3. How to use Alhemo

Before using the Alhemo pre-filled pen, consult the Instructions for Use detailed on the reverse of
this leaflet. Speak to your doctor if you need to use alternative injection techniques; for example,
thin patients and adolescents may need to inject into a skin fold held gently to avoid injecting too
deeply (into the muscle).
Use this medicine exactly as your doctor has instructed. If you have any doubts, consult your
doctor, pharmacist, or nurse.
Management of sudden bleeding episodes
You may need to use factor VIII, factor IX, or bypassing agents to treat sudden bleeding episodes
while using Alhemo. Follow your doctor’s instructions carefully regarding when and how to use
these factor VIII- or factor IX-based products or bypassing agents.
Recommended dose for adults and adolescents

• Initial dose on Day 1: 1 mg per kg of body weight.
• From Day 2 until the maintenance dose is established: 0.20 mg per kg of body weight once daily.
• Individual maintenance dose as determined by the doctor: 0.15, 0.20, or 0.25 mg per kg of body weight once daily.

Alhemo is injected under the skin of the abdomen or thigh and can be used at any time of day.
If you use more Alhemo than you should
Contact your doctor immediately.
If you forget to use Alhemo
Alhemo can be used at any time of day.
Missing one or more doses of Alhemo affects the effectiveness of the medicine. It is important to take
Alhemo every day.
If you miss a daily dose of Alhemo:
if you miss a dose during the first 4 weeks of treatment, contact your doctor to discuss how to resume.
If you miss a dose after the maintenance dose has been established:

• If you missed 1 daily dose, resume the daily dose.
• If you missed 2 to 6 daily doses, take the daily dose twice (as two separate injections, each corresponding to the daily dose) and then continue with the daily dose the next day.
• If you missed 7 or more daily doses, contact your doctor immediately, as you will need a new loading dose before continuing with the daily dose the next day. If you have any doubts, consult your doctor.

If you stop treatment with Alhemo
You may no longer be protected against bleeding. Do not stop treatment with Alhemo without first
consulting your doctor.
If you have any questions about how to use this medicine, ask your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Stop using Alhemo and contact your doctor immediately if you experience symptoms of severe allergic reactions or symptoms of blood clots. See "Warnings and precautions" in section 2.
Other side effects
Very common: may affect more than 1 in 10 people

• Reactions at the injection site such as redness, bleeding, itching, hives, swelling, pain, numbness.

Common: may affect up to 1 in 10 people

• Allergic reaction

Uncommon: may affect up to 1 in 100 people

• Blood clots

Reporting of side effects
If you get any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects directly through 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 Alhemo

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the pen label and on the box after “Exp.”. The expiry date refers to the last day of that month.
Do not use this medicine if you notice any change in the colour of the solution.

Before use

• Store unused Alhemo pens in a refrigerator at 2 °C - 8 °C.
• Store the new, unused pen with the cap attached.
• When storing in the refrigerator, do not place the pen directly next to the cooling element.
• Do not use Alhemo if it has been frozen or stored at temperatures above 30 °C.

After first use

• Store the Alhemo pen currently in use without the needle attached, for up to 28 days (4 weeks):
  • in a refrigerator at 2 °C - 8 °C. Do not store the pen directly next to the cooling element. Do not use Alhemo if it has been frozen. or
  • at room temperature below 30 °C. Discard the pen if it has been stored at temperatures above 30 °C. Do not store the pen in direct sunlight.
• Store the Alhemo pen in use with the cap attached.

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 Alhemo contains

• The active substance is concizumab. One millilitre of Alhemo 150 mg/1.5 mL contains 100 mg of concizumab.
• The other components are L-arginine hydrochloride, L-histidine, sodium chloride, sucrose, polysorbate 80, phenol, hydrochloric acid and sodium hydroxide (for pH adjustment) and water for injections. See also section 2 “Alhemo contains sodium and polysorbates”.

Description of the appearance of Alhemo and contents of the pack
Alhemo is a solution for injection, from clear to slightly opalescent and from colourless to slightly yellow, in a single-use pre-filled pen. Transparent to white protein particles are acceptable.
Alhemo 150 mg/1.5 mL is available in single packs containing 1 pre-filled pen or in multiple packs containing 5 pre-filled pens (5 packs of 1). Not all pack sizes may be marketed.
Needles for injection are not included.

Marketing Authorisation Holder and Manufacturer
Novo Nordisk A/S
Novo Alle 1
DK-2880 Bagsvaerd
Denmark

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

Instructions for use

Alhemo 150 mg/1.5 mL solution for injection in pre-filled pen

concizumab

What is contained in this pack?

• 1 Alhemo pre-filled pen
• Package leaflet

Needles not included.
Read the instructions and ensure you have received training from your doctor or nurse before using the pen.
Follow your doctor’s or nurse’s instructions on how to use Alhemo and how often to inject it.
The pen is pre-filled with 150 mg of Alhemo for subcutaneous use only (injection under the skin). The pen contains multiple doses of Alhemo.
The pen can deliver up to 80 mg in a single injection. The dose counter increments in 1 mg steps. If you require more than 80 mg, you must perform multiple injections.

Safety information
The pen is for single-patient use only and must not be shared. Sharing the pen or needles may cause infections and transmission of diseases.
Always use a new needle for each injection. Do not reuse needles, as they may become blocked, contaminated, or deliver an incorrect dose.
The needle is covered by two caps: both must be removed. If you forget to remove both caps, no solution will be injected.

Where should I inject the dose?
You may inject under the skin:

• of the abdomen OR
• of the thigh

Inject at a 90° angle. The grey areas in the figure on the right indicate suitable injection sites. For each injection, select a new site at least 5 cm away from the previous injection site.

Check the pen 1
Check the pen label
Look at the name and colour to ensure you have the correct medicine.
Inspect the medicine
Remove the pen cap and check that Alhemo in the viewing window appears as a solution ranging from clear to slightly cloudy and from colourless to pale yellow. Transparent to white protein particles are acceptable. Do not use the pen if Alhemo appears discoloured.
Check the expiry date
Check the expiry date on the pen label to ensure it has not passed. Do not use the pen if the expiry date has been exceeded.
If the pen is cold
You may inject Alhemo directly from the refrigerator or allow it to reach room temperature before injection. You may warm the pen between your palms. Do not use any other method of warming.

Attach a new needle 2
Take a new needle and remove the protective seal.

• Push the needle straight onto the pen. Rotate it until it is securely tightened. See A.
• Remove the outer needle cap and keep it. See B.
• Remove the inner needle cap and discard it. See B.

Never use a bent or damaged needle.
Use only needles recommended by your doctor or nurse. This pen is designed to be used with NovoFine Plus 32G x 4 mm or NovoFine 32G x 4 mm injection needles. If you use needles longer than 4 mm, consult your doctor or nurse for instructions on how to administer the injection.

Check the flow 3
A drop of Alhemo may appear at the needle tip, but you must still check the flow of Alhemo before every injection to avoid underdosing:
a. Turn the dose selector one notch to select 1 mg. See A in the figure below. Hold the pen with the needle pointing upwards.
b. Press the injection button. See B.
c. Check that a stream of Alhemo comes out from the needle tip. See B.
If no stream appears, refer to Troubleshooting if no stream appears during flow check.

Select the dose 4
Turn the dose selector to select the prescribed dose.
Confirm that you have selected the correct dose.
You may adjust the dose by turning the dose selector in either direction.
If you require a dose greater than what can be delivered in one injection, you must perform multiple injections to achieve the full dose. For more information, see point 6.
The pen contains 150 mg of Alhemo.
The pen can deliver up to 80 mg in a single injection.

Inject the dose 5
Read steps a. to e. before starting the injection.
a. Select your injection site. Refer to the section Where should I inject the dose?
b. Insert the needle directly into the abdomen or thigh at a 90° angle.
c. Keep pressing the injection button until the dose counter returns to <0>.
d. With the needle still in the skin, count slowly to 6 after the dose counter has returned to <0>.
e. Remove the needle from the skin.
The pen will click during delivery, and you may hear an additional click when the dose counter returns to <0>.

Remove the needle 6
Remove the needle from the pen after each injection by placing the needle tip into its outer cap without touching either the needle or the cap.
Once the needle is covered, fully push the outer cap on by pressing gently. Then unscrew the needle. Do not touch the back end of the needle.
Dispose of the needle according to instructions from your doctor, nurse, pharmacist, or local authorities.

Do you need a higher dose than can be selected?
If you require a dose greater than what can be delivered in one injection, you must perform multiple injections to achieve the full dose. Repeat steps 1 to 6 until the full dose has been administered. Once the full dose is injected, proceed to step 7.

• Always use a new needle for each injection.
• Check the flow of Alhemo before each injection.
• Accurately calculate the amount to inject in each injection to receive the full dose.

After the dose 7
Replace the pen cap to protect Alhemo from light.
The pen is now ready to be stored until next use.
After first use, do not use the pen for more than 28 days.

How much Alhemo is left in the pen?
The pen scale shows approximately how much Alhemo remains in the pen.

To see more accurately how much Alhemo remains in the pen, turn the dose selector until it stops. The dose indicator will align with the number of milligrams remaining in the pen. The number shown on the dose counter indicates the number of milligrams left in the pen.
If the dose counter shows 80, there are 80 mg or more remaining in the pen.
The example below shows 34 mg of Alhemo remaining in the pen.

Troubleshooting if no stream appears during flow check (step 3)

• If no stream appears, repeat step 3 up to six times until a stream is seen.
• If still no stream appears, prepare a new needle (step 2) and repeat the flow check (step 3).
• If no stream appears even after using a new needle, do not use that pen. Use a new pen.

Storage See section 5 “How to store Alhemo” on the back of this leaflet.

Caring for the pen
Handle the pen with care. Improper or careless use may lead to inaccurate dosing, which could result in not achieving the desired effect of the medicine.
Do not expose the pen to dust, dirt, or liquids.
Do not wash, immerse in liquid, or lubricate the pen. If necessary, clean it with a neutral detergent on a damp cloth.
Always keep the pen out of sight and reach of others, especially children.

Disposal of Alhemo pens, needles, and packaging materials
When the pen is empty, dispose of it according to local regulations.
The pen cannot be refilled.
To reduce the risk of needlestick injury, dispose of used needles immediately as instructed by your doctor, nurse, pharmacist, or local authorities.

[Text for the first page of the folded package leaflet]
Package leaflet and Instructions for use

Package leaflet: information for the user

Alhemo 300 mg/3 mL solution for injection in pre-filled pen

concizumab
This medicinal product is subject to additional monitoring. This will allow for rapid identification of new safety information. You can help by reporting any side effects you experience while taking this medicine. See the end of section 4 for information on how to report side effects.
Please read this leaflet carefully before using this medicine as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, contact your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

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

1. What Alhemo is and what it is used for

What Alhemo is
Alhemo contains the active substance concizumab, which belongs to a group of medicines called
"monoclonal antibodies". Concizumab is a protein that recognises a target in the blood and binds to it. This target is involved in the blood clotting process.

What Alhemo is used for
Alhemo is used to prevent or reduce the frequency of bleeding episodes in adults and adolescents aged 12 years and older with:

• haemophilia A with inhibitors.
• severe haemophilia A (when blood levels of factor VIII are less than 1%) without inhibitors.
• haemophilia B with inhibitors.
• moderate/severe haemophilia B (when blood levels of factor IX are less than or equal to 2%) without inhibitors.

Haemophilia A is a congenital deficiency of blood clotting factor VIII, and haemophilia B is a congenital deficiency of blood clotting factor IX.

How Alhemo works
Concizumab blocks a natural factor in the blood that prevents blood from clotting. This factor is called tissue factor pathway inhibitor. By blocking this inhibitor, blood clotting becomes more effective, thereby helping to prevent or reduce bleeding when a clotting factor is missing.

Alhemo works independently of factor VIII and factor IX, and independently of their inhibitors.

2. What you need to know before using Alhemo

Do not use Alhemo

• if you are allergic to concizumab or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Allergic reactions
There is a risk that you may experience an allergic reaction. Stop treatment and contact your
doctor if you develop symptoms of allergic reactions such as rash, redness, hives, or itching.
You may also experience symptoms of severe allergic reactions such as:

• itching over large areas of the skin
• redness and/or swelling of the lips, tongue, face, or hands
• difficulty swallowing
• shortness of breath
• wheezing
• chest tightness
• paleness and cold skin
• rapid heartbeat
• dizziness due to low blood pressure.

Stop using Alhemo and seek immediate emergency medical assistance if you experience symptoms
of severe allergic reactions.
Blood clots
Blood clots can form in any part of the body.
Stop using Alhemo and contact your doctor immediately if you experience symptoms of
blood clots such as:

• Swelling, warmth, pain, or redness of the skin: these could be symptoms of a blood clot in the legs or arms.
• Feeling short of breath, severe chest pain: these could be symptoms of blood clots in the heart or lungs.
• Headache, confusion, difficulty speaking or moving, facial numbness, eye pain or swelling, or vision problems: these could be symptoms of a blood clot in the brain or eyes.
• Sudden stomach or lower back pain: these could be symptoms of blood clots in the intestines or kidneys.

Children and adolescents
Alhemo is not recommended for children under 12 years of age. The safety and benefits of
this medicine have not yet been established in this population.
Other medicines and Alhemo
Inform your doctor if you are taking, have recently taken, or might take any other medicines.
Pregnancy and breastfeeding
Use a highly effective method of contraception during treatment with Alhemo and
for 7 weeks after the last injection. Consult your doctor to discuss the type of contraceptive to
use.
If you are pregnant, suspect you may be pregnant, plan to become pregnant, or are breastfeeding,
please consult your doctor before using this medicine.
Driving and using machines
It is unlikely that Alhemo will affect your ability to drive or operate machinery.
Alhemo contains sodium and polysorbates
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. essentially “sodium-free”.
This medicine contains 0.25 mg of polysorbate 80 per mL. Polysorbates may cause allergic reactions. Inform your doctor if you have known allergies.

3. How to use Alhemo

Before using the Alhemo pre-filled pen, please consult the Instructions for Use detailed on the reverse of
this leaflet. Speak to your doctor if you need to use alternative injection techniques; for example, thin patients and adolescents may need to inject into a skin fold, gently pinched, to avoid injecting too deeply (into the muscle).
Use this medicine exactly as instructed by your doctor. If you have any doubts, consult your doctor, pharmacist, or nurse.
Management of sudden bleeding episodes
You may need to use factor VIII, factor IX, or bypassing agents to treat sudden bleeding episodes while using Alhemo. Follow your doctor’s instructions carefully regarding when and how to use these factor VIII, factor IX, or bypassing agent products.
Recommended dose for adults and adolescents is

• Initial dose on Day 1: 1 mg per kg of body weight.
• From Day 2 until the maintenance dose is established: 0.20 mg per kg of body weight once daily.
• Individual maintenance dose as determined by the doctor: 0.15, 0.20, or 0.25 mg per kg of body weight once daily.

Alhemo is injected under the skin of the abdomen or thigh and may be used at any time of day.
If you use more Alhemo than you should
Contact your doctor immediately.
If you forget to use Alhemo
Alhemo may be used at any time of day.
Missing one or more doses of Alhemo may affect the effectiveness of the medicine. It is important to take Alhemo every day.
If you miss a daily dose of Alhemo:
If you miss a dose during the first 4 weeks of treatment, contact your doctor to discuss how to resume treatment.
If you miss a dose after the maintenance dose has been established:

• If you missed 1 daily dose, resume your daily dose.
• If you missed 2 to 6 daily doses, take the daily dose twice (as two separate injections, each corresponding to the daily dose), then continue with the daily dose the next day.
• If you missed 7 or more daily doses, contact your doctor immediately, as you will need a new loading dose before continuing with the daily dose the next day. If you have any doubts, consult your doctor.

If you stop treatment with Alhemo
You may no longer be protected against bleeding. Do not stop treatment with Alhemo without first consulting your doctor.
If you have any questions about using this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Stop using Alhemo and contact your doctor immediately if you experience symptoms of severe allergic reactions or symptoms of blood clots. See "Warnings and precautions" in section 2.
Other side effects
Very common: may affect more than 1 in 10 people

• Reactions at the injection site such as redness, bleeding, itching, hives, swelling, pain, numbness.

Common: may affect up to 1 in 10 people

• Allergic reaction

Uncommon: may affect up to 1 in 100 people

• Blood clots

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. You may also report side effects directly through 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 Alhemo

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the label of the pen and on the
box after “Exp.”. The expiry date refers to the last day of that month.
Do not use this medicine if you notice any change in the colour of the solution.

Before use

• Store unused Alhemo pens in a refrigerator at 2 °C - 8 °C.
• Store the new, unused pen with the cap attached.
• When stored in the refrigerator, do not place the pen directly next to the cooling element.
• Do not use Alhemo if it has been frozen or stored at temperatures above 30 °C.

After first use

• Store the Alhemo pen currently in use without the needle attached, for up to 28 days (4 weeks):
  • in a refrigerator at 2 °C - 8 °C. Do not store the pen directly next to the cooling element. Do not use Alhemo if it has been frozen. or
  • at room temperature below 30 °C. Discard the pen if it has been stored at a temperature above 30 °C. Do not store the pen in direct sunlight.
• Store the Alhemo pen in use with the cap attached.

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. Pack contents and other information

What Alhemo contains

• The active substance is concizumab. One millilitre of Alhemo 300 mg/3 mL contains 100 mg of concizumab.
• The other components are L-arginine hydrochloride, L-histidine, sodium chloride, sucrose, polysorbate 80, phenol, hydrochloric acid and sodium hydroxide (for pH adjustment), and water for injections. See also section 2 “Alhemo contains sodium and polysorbates”.

Description of the appearance of Alhemo and pack contents
Alhemo is an injectable solution, from clear to slightly opalescent, colourless to slightly yellow,
supplied in a single-use, pre-filled pen. Transparent to white protein particles are acceptable.
Alhemo 300 mg/3 mL is available in a single pack containing 1 pre-filled pen.
Needles for injection are not included.
Marketing authorisation holder and manufacturer
Novo Nordisk A/S
Novo Alle 1
DK-2880 Bagsvaerd
Denmark
Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu

Instructions for use

Alhemo 300 mg/3 mL solution for injection in a prefilled pen

concizumab

What is included in this pack?

• 1 Alhemo prefilled pen
• Package leaflet

Needles not included.
Read the instructions and make sure you have received training from your doctor or nurse before using
the pen.
Follow your doctor’s or nurse’s instructions on how and how often to inject Alhemo.
The pen is prefilled with 300 mg of Alhemo for subcutaneous use only (injection under the skin). The
pen contains multiple doses of Alhemo.
The pen can deliver up to 80 mg in a single injection. The dose counter increments by 1 mg. If you need
more than 80 mg, you must perform multiple injections.

Safety information
The pen is for single-patient use only and must not be shared. Sharing the pen or needles may cause
infections and transmission of diseases.
Always use a new needle for each injection. Do not reuse needles, as they may become blocked, infected,
or deliver an incorrect dose.
The needle is covered by two caps: both must be removed. If you forget to remove both caps, no solution
will be injected.
Where should I inject the dose?
You may inject under the skin:

• of the abdomen OR
• of the thigh

Inject at a 90° angle. The grey areas in the figure on the right show the injection sites. For each
injection, select a new site at least 5 cm away from the previous injection site.

Check the pen 1
Check the pen label
Look at the name and colour to ensure you have the correct medicine.
Check the expiry date
Check the expiry date on the pen label to make sure it has not passed. Do not use the pen if the expiry
date has passed.
Inspect the medicine
Remove the pen cap and check that Alhemo in the viewing window appears as a solution ranging from
clear to slightly cloudy and from colourless to pale yellow. Transparent to white protein particles are
acceptable. If Alhemo appears discoloured, do not use the pen.
If the pen is cold
You may inject Alhemo directly from the refrigerator or allow it to reach room temperature before
injection. You may warm the pen between your palms. Do not use any other warming method.
Attach a new needle 2
Take a new needle and remove the protective seal.

• Push the needle straight onto the pen. Rotate it until it is firmly attached. See A.
• Remove the outer needle cap and keep it for later use. See B.
• Remove the inner needle cap and discard it. See B.

Never use a bent or damaged needle.
Use only needles recommended by your doctor or nurse. This pen is designed to be used with NovoFine
Plus 32G x 4 mm or NovoFine 32G x 4 mm injection needles. If you use needles longer than 4 mm,
consult your doctor or nurse for instructions on how to administer the injection.

Check the flow 3
A drop of Alhemo may appear at the needle tip, but you must still check the flow of Alhemo before
every injection to avoid underdosing:
a. Turn the dose selector one click to select 1 mg. See A in the figure below.
Hold the pen with the needle pointing upwards.
b. Press the injection button. See B.
c. Check that a stream of Alhemo comes out from the needle tip. See B.
If no stream appears, refer to Troubleshooting if no stream appears during flow check.

Select the dose 4
Turn the dose selector to select the prescribed dose.
Confirm that you have selected the correct dose.
You may adjust the dose by turning the dose selector in either direction.
If you need a dose larger than the maximum single injection, you must perform multiple injections to
achieve the full dose. For more information, see point 6.
The pen contains 300 mg of Alhemo.
The pen can deliver up to 80 mg in a single injection.

Inject the dose 5
To ensure you administer the full dose,
read steps a. to e. before starting the injection.
a. Select the injection site. Refer to the section Where should I inject the dose?
b. Insert the needle directly into the abdomen or thigh at a 90° angle.
c. Keep pressing the injection button until the dose counter returns to <0>.
d. With the needle still in the skin, count slowly to 6 after the dose counter returns to <0>.
e. Remove the needle from the skin.
The pen will click during delivery, and you may hear another click when the dose counter returns to <0>.

Remove the needle 6
Remove the needle from the pen after each injection by placing the needle tip into its outer cap without
touching the needle or the cap.
When the needle is covered, fully insert the outer cap by pressing carefully. Then unscrew the needle. Do
not touch the back end of the needle.
Dispose of the needle according to instructions from your doctor, nurse, pharmacist, or local authorities.

Do you need a dose larger than the maximum single dose?
If you need a dose larger than the maximum single dose, you must perform multiple injections to achieve
the full dose. Repeat steps 1 to 6 until the full dose has been injected.
Once the full dose has been injected, proceed to step 7.

• Always use a new needle for each injection.
• Check the flow of Alhemo before each injection.
• Accurately calculate the amount to inject in each injection to receive the full dose.

After the dose 7
Replace the pen cap to protect Alhemo from light.
The pen is now ready for storage until next use.
After first use, do not use the pen for more than 28 days.

How much Alhemo is left in the pen?
The pen scale shows approximately how much Alhemo remains in the pen.

If you wish to see more accurately how much Alhemo remains in the pen, turn the dose selector until it
stops. The dose indicator will align with the number of milligrams remaining in the pen. The number
shown on the dose counter indicates the number of milligrams left in the pen.
If the dose counter shows 80, there are 80 mg or more remaining in the pen.
The example below shows 34 mg of Alhemo remaining in the pen.

Troubleshooting if no stream appears during flow check (step 3)

• If no stream appears, repeat step 3 up to six times until a stream is visible.
• If still no stream appears, attach a new needle (step 2) and repeat the flow check (step 3).
• If no stream appears even after using a new needle, do not use that pen. Use a new pen instead.

Storage
See section 5 “How to store Alhemo” on the reverse of this leaflet.
Caring for the pen
Handle the pen with care. Improper or rough handling may lead to inaccurate dosing, which could
result in not achieving the intended effect of the medicine.
Do not expose the pen to dust, dirt, or liquids.
Do not wash, immerse in liquid, or lubricate the pen. If necessary, clean it with a neutral detergent on a
damp cloth.
Always keep the pen out of sight and reach of others, especially children.
Disposal of Alhemo pens, needles, and packaging materials
When the pen is empty, dispose of it according to local regulations.
The pen cannot be refilled.
To reduce the risk of needlestick injury, dispose of used needles immediately as instructed by your
doctor, nurse, pharmacist, or local authorities.
[Text for the first page of the folded package leaflet]
Package leaflet and Instructions for use