Hemlibra 150 mg/ml solution for injection

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Hemlibra 150mg/ml solution for injection

emicizumab

Read all of this leaflet carefully before you start 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 pass it on to other people, even if they have the same symptoms as you, because it may harm them.
• If you get any side effects, talk to your doctor, pharmacist, or nurse, including any side effects not listed in this leaflet. See section 4.

In addition to this leaflet, your doctor will provide you with a patient information card and a guide (for patients/caregivers) containing important safety information you need to know. Always carry the card with you and show it to any healthcare professional, pharmacist, or laboratory professional you may consult.

Contents of this leaflet

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

1. What Hemlibra is and what it is used for

What Hemlibra is

Hemlibra contains the active substance “emicizumab”. This belongs to a group of medicines called “monoclonal antibodies”. Monoclonal antibodies are a type of protein that recognises and binds to a specific target in the body.

What Hemlibra is used for

Hemlibra is a medicine that can be used to treat patients of all ages with haemophilia A (congenital factor VIII deficiency):

• who have developed factor VIII inhibitors

• who have not developed factor VIII inhibitors with:

• severe disease (factor VIII level in blood is less than 1%)

• moderate disease (factor VIII level in blood is 1% to 5%) with severe bleeding phenotype.

Haemophilia A is an inherited condition caused by a lack of factor VIII, an essential substance required for blood to clot and to stop bleeding.

The medicine prevents bleeding or reduces bleeding episodes in people with this condition.

Some patients with haemophilia A may develop factor VIII inhibitors (antibodies against factor VIII), which prevent replacement factor VIII from working.

How Hemlibra works

Hemlibra restores the missing activated factor VIII function necessary for effective blood coagulation. Its structure is different from factor VIII, therefore, Hemlibra is not affected by factor VIII inhibitors.

2. What you need to know before using Hemlibra

Do not use Hemlibra

• if you are allergic to emicizumab or to any of the other ingredients of this medicine (listed in section 6). If you are unsure, consult your doctor, pharmacist, or nurse before starting Hemlibra.

Warnings and precautions

Before starting Hemlibra, it is very important that you consult your doctor about the use of “bypassing agents” (medicines that help blood to clot but work differently from factor VIII). This is because you may need to adjust your treatment with bypassing agents while receiving Hemlibra. Examples of bypassing agents include activated prothrombin complex concentrate (aPCC) and recombinant factor VIIa (rFVIIa). Serious and potentially fatal adverse effects may occur when aPCC is used in patients also receiving Hemlibra:

Potentially serious adverse effects of using aPCC while receiving Hemlibra

• Destruction of red blood cells (thrombotic microangiopathy)

• This is a serious and potentially life-threatening condition.

• In this condition, the lining of blood vessels may be damaged and blood clots may form in small blood vessels. In some cases, this may lead to damage in the kidneys or other organs.

• Exercise caution if you are at high risk of this condition (you have had this condition in the past, or a family member has had it), or if you are taking medicines that may increase the risk of developing this condition, such as cyclosporine, quinine, and tacrolimus.

• It is important to be aware of the symptoms of thrombotic microangiopathy in case you develop this condition (see section 4, “Possible side effects” for a list of symptoms).

Stop using Hemlibra and aPCC and contact your doctor immediately if you or your caregiver notice any symptoms of thrombotic microangiopathy.

• Blood clots (thromboembolism)

• Rarely, a blood clot may form within blood vessels and block them, which could potentially be life-threatening.

• It is important to be aware of the symptoms of such internal blood clots in case they form (see section 4, “Possible side effects” for a list of symptoms).

Stop using Hemlibra and aPCC and contact your doctor immediately if you or your caregiver notice any symptoms of blood clots in blood vessels.

Other important information about Hemlibra

• Formation of antibodies (immunogenicity)

• You may notice that your bleeding is not being controlled by the prescribed dose of this medicine. This may be due to the development of antibodies against this medicine.

Talk to your doctor immediately if you or your caregiver notice an increase in bleeding. Your doctor may decide to change your treatment if this medicine stops working for you.

Children under 1 year of age

In children under 1 year of age, the blood system is still developing. If your child is under one year of age, your doctor may prescribe Hemlibra only after carefully evaluating the expected benefits and risks of using Hemlibra.

Other medicines and Hemlibra

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines.

• Use of a bypassing agent while receiving Hemlibra

• Before starting Hemlibra, consult your doctor and carefully follow their instructions regarding when to use a bypassing agent and the dose and regimen to follow. Hemlibra increases the blood's ability to clot. Therefore, the required dose of the bypassing agent may be lower than the dose you used before starting Hemlibra.

• Use aPCC only if no other treatment is available. If aPCC is needed, consult your doctor if you think you need more than 50 units/kg of aPCC in total. For further information on the use of aPCC while receiving Hemlibra, see section 2: Potentially serious adverse effects of using aPCC while receiving Hemlibra.

• Despite limited experience with concomitant administration of antifibrinolytics with aPCC or rFVIIa in patients treated with Hemlibra, you should be aware that thrombotic events could occur when intravenous antifibrinolytics are administered in combination with aPCC or rFVIIa.

Laboratory tests

Consult your doctor if you are using Hemlibra before undergoing blood tests to measure blood clotting ability. This is because the presence of Hemlibra in the blood may interfere with some of these laboratory tests and produce inaccurate results.

Pregnancy and breastfeeding

• You should use an effective method of birth control (contraception) during treatment with Hemlibra and for 6 months after the last injection of Hemlibra.
• If you are pregnant or breastfeeding, think you may be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before using this medicine. Your doctor will weigh the benefit of your taking Hemlibra against the risk to your baby.

Driving and using machines

It is unlikely that this medicine will affect your ability to drive or operate machinery.

3. How to use Hemlibra

Hemlibra is supplied in single-use vials as a ready-to-use solution that does not need to be diluted. A qualified physician experienced in the treatment of patients with hemophilia will teach you how to use Hemlibra therapy. Always follow exactly the administration instructions provided by your doctor. If in doubt, consult your doctor again.

Keep a record

Each time you use Hemlibra, record the name and batch number of the medicine.

How much Hemlibra to use

The dose of Hemlibra depends on your body weight, and your doctor will calculate the amount (in mg) and the corresponding volume of Hemlibra solution (in ml) to be injected:

• Loading dose regimen, weeks 1–4: the dose is 3 milligrams per kilogram of body weight, administered once weekly.

• Maintenance dose regimen, week 5 and onwards: the dose is either 1.5 milligrams per kilogram of body weight, administered once weekly; 3 milligrams per kilogram of body weight, administered every two weeks; or 6 milligrams per kilogram of body weight, administered every four weeks.

The decision on whether to use the maintenance dose of 1.5 mg/kg once weekly, 3 mg/kg every two weeks, or 6 mg/kg every four weeks should be discussed with your doctor and, where applicable, with your caregiver.

Different concentrations of Hemlibra (30 mg/ml and 150 mg/ml) must not be combined in a single injection to achieve the total volume to be administered.

No more than 2 ml of Hemlibra solution should be administered in a single injection.

How Hemlibra is administered

If you or your caregiver are administering a Hemlibra injection, you must carefully read and follow the instructions provided in section 7, “Instructions for use”.

• Hemlibra is administered as a subcutaneous injection (under the skin).
• Your doctor or nurse will teach you how to inject Hemlibra.
• Once you have received proper training, you may self-administer the medication at home, either alone or with the help of a caregiver.
• To correctly insert the needle under the skin, pinch a skin fold at the clean injection site with your free hand. It is important to form a skin fold to ensure that the injection is delivered under the skin (into the fatty tissue) and not deeper (into the muscle). An intramuscular injection could be uncomfortable.
• Prepare and administer the injection under clean, germ-free conditions using an aseptic technique. Your doctor or nurse will provide further information on this.

Where to inject Hemlibra

• Your doctor will instruct you on the appropriate body areas for Hemlibra injection.
• Recommended injection sites are: the front of the waist (lower abdomen), the outer upper arm, or the front of the thighs. Use only recommended injection sites.
• For each injection, use a different body area than the one used for your last injection.
• Do not administer injections in areas where the skin is red, bruised, tender, hardened, or in areas with moles or scars.
• When using Hemlibra, other subcutaneously injected medications should be administered in a different body region.

Use of syringes and needles

• To withdraw Hemlibra solution from the vial, transfer it into the syringe, and inject it subcutaneously, you will need a syringe, a 5-micron filter transfer needle or a 5-micron filter vial adapter, and an injection needle.

• Syringes, filter transfer needles or filter vial adapters, and injection needles are not included in the package. For more information, refer to section 6, “What is needed for Hemlibra administration that is not included in the package”.

• Always use a new injection needle for each injection and dispose of it after a single use.

• For an injection of up to 1 ml of Hemlibra solution, use a 1 ml syringe.

• For an injection greater than 1 ml and up to 2 ml of Hemlibra solution, use a 2–3 ml syringe.

Use in children and adolescents

Hemlibra can be used in children and adolescents of all ages.

• A child may self-inject the medication provided that the healthcare professional, parent, or caregiver agrees. Self-injection is not recommended in children under 7 years of age.

If you use more Hemlibra than you should

If you use more Hemlibra than prescribed, inform your doctor immediately. This is because you may be at risk of experiencing adverse effects such as blood clots. Always follow exactly the administration instructions provided by your doctor. If in doubt, consult your doctor, pharmacist, or nurse.

If you forget to use Hemlibra

• If you miss a scheduled injection, administer the missed dose as soon as possible before the day of your next scheduled dose. Then continue with your regular dosing schedule. Do not inject two doses on the same day to make up for a missed dose.
• If in doubt, consult your doctor, pharmacist, or nurse.

If you stop using Hemlibra

Do not stop treatment with Hemlibra without consulting your doctor. If you discontinue Hemlibra treatment, you may no longer be protected against bleeding episodes.

If you have any further questions about the use of 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.

Serious side effects of using concomitant clotting factor (CCF) while receiving Hemlibra

Stop using Hemlibra and CCF and consult your doctor immediately if you or your caregiver notice any of the following side effects:

• Destruction of red blood cells (thrombotic microangiopathy):

• confusion, weakness, swelling of arms and legs, yellowing of the skin and eyes, abdominal or back pain, feeling dizzy (nausea), feeling unwell (vomiting), or urinating less than usual: these symptoms could be signs of thrombotic microangiopathy.

• Blood clots (thromboembolism):

• swelling, warmth, pain or redness: these symptoms could be signs of a blood clot in a vein near the skin surface.

• headache, facial numbness, pain or swelling in the eyes or vision problems: these symptoms could be signs of a blood clot in a vein behind the eye.

• skin darkening: this symptom could be a sign of serious skin tissue damage.

Other side effects when using Hemlibra

Very common: may affect more than 1 in 10 people

• reaction at the injection site (redness, itching, pain)
• headache
• joint pain

Common: may affect up to 1 in 10 people

• fever
• muscle pain
• diarrhea
• itchy rash or hives (urticaria)
• skin rash

Uncommon: may affect up to 1 in 100 people

• destruction of red blood cells (thrombotic microangiopathy)
• blood clot in a vein behind the eye (cavernous sinus thrombosis)
• serious skin tissue damage (cutaneous necrosis)
• blood clot in a vein near the skin surface (superficial thrombophlebitis)
• swelling of the face, tongue and/or throat and/or difficulty swallowing, or hives, together with breathing difficulties, which are indicative of angioedema
• lack of effect or reduced response to treatment
• allergic reaction

Reporting of side effects

If you experience any type of side effect, talk to your doctor, pharmacist or nurse, even if it is a side effect not listed in this leaflet. You can also report them directly through the national reporting system detailed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Hemlibra

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the carton and vial after “EXP”. The expiry date refers to the last day of the month indicated.

Store in a refrigerator (between 2 °C and 8 °C). Do not freeze.

Keep in the original packaging to protect from light.

After removal from the refrigerator, unopened vials may be stored at room temperature (below 30 °C) for a maximum of 7 days. After storage at room temperature, unopened vials may be returned to the refrigerator. The total storage time of the medicine at room temperature must not exceed 7 days.

Discard vials that have been stored at room temperature for more than 7 days or that have been exposed to temperatures above 30 °C.

Once the solution has been transferred from the vial to the syringe, use Hemlibra immediately. Do not refrigerate the solution in the syringe.

Before using the medicine, check that the solution is free from particles and discoloration. The solution should be colourless to slightly yellow. Do not use this medicine if it appears cloudy, has changed colour, or contains visible particles.

Dispose of unused solution properly. Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and containers you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Hemlibra

• The active substance is emicizumab. Each Hemlibra vial contains 60 mg (0.4 ml at a concentration of 150 mg/ml), 105 mg (0.7 ml at a concentration of 150 mg/ml), 150 mg (1 ml at a concentration of 150 mg/ml), or 300 mg (2 ml at a concentration of 150 mg/ml) of emicizumab.

• The other components are L-arginine, L-histidine, L-aspartic acid, poloxamer 188, and water for injections.

Appearance of Hemlibra and contents of the pack

Hemlibra is an injectable solution. It is a colourless or slightly yellowish liquid.

Each Hemlibra pack contains 1 glass vial.

Only certain pack sizes may be marketed.

What is needed for Hemlibra administration that is not included in the pack

To withdraw the Hemlibra solution from the vial, transfer it into a syringe, and inject it subcutaneously, a syringe, a filtered transfer needle or a filtered vial adapter, and an injection needle are required (see section 7, "Instructions for use").

Syringes

• 1 ml syringe: transparent polypropylene or polycarbonate syringe with Luer-lock tip, graduated in 0.01 ml increments or
• 2-3 ml syringe: transparent polypropylene or polycarbonate syringe with Luer-lock tip, graduated in 0.1 ml increments.

Note: Syringes with Low Dead Space (LDS) plungers must be used when using the filtered vial adapter.

Transfer devices and needles

• Filtered transfer needle: stainless steel with Luer-lock connection, 18 G, 35 mm (1½″) length, containing a 5-micron filter and preferably with a semi-regular tip or

• Filtered vial adapter: polypropylene with Luer-lock connection, integrated 5-micron filter, and 15 mm outer neck diameter fit and

• Injection needle: stainless steel with Luer-lock connection, 26 G (acceptable range: 25–27 G), preferably 9 mm (3/8″) in length or up to a maximum of 13 mm (½″), preferably with needle safety feature.

Marketing Authorization Holder

Roche Registration GmbH
Emil-Barell-Strasse 1
79639 Grenzach-Wyhlen
Germany

Manufacturer

Roche Pharma AG
Emil-Barell-Strasse 1
79639 Grenzach-Wyhlen
Germany

For more information about this medicinal product, please contact the local representative of the Marketing Authorization Holder:

Date of the most recent review of this leaflet

Other sources of information

Detailed information on this medicine is available on the website of the European Medicines Agency: http://www.ema.euopa.eu/

7. Instructions for use

Instructions for use

Hemlibra

Injection

Single-dose vial(s)

You must read, understand, and follow these instructions for use before injecting Hemlibra. Your healthcare provider should train you on how to properly prepare, measure, and inject Hemlibra before your first use. If you have any doubts, consult your healthcare provider.

Important information:

• Do not inject yourself or another person unless your healthcare professional has trained you to do so.

• Check that the name Hemlibra appears on the carton and on the vial label.

• Before opening the vial, read the label to confirm that you have the correct concentration of the medicine needed to administer your prescribed dose. You may need to use more than one vial to deliver the full prescribed dose.

• Check the expiration date printed on the carton and the vial label. Do not use after the expiration date.

• Use the vial only once. After injecting the dose, discard any remaining Hemlibra solution in the vial. Do not store unused medicine from the vial for later use.

• Use only the syringes, transfer needles, and injection needles prescribed by your healthcare professional.

• Use the syringes, transfer needles, and injection needles only once.

Dispose of used caps, vial(s), syringes, and needles.

• If your prescribed dose is greater than 2 ml, you will need to administer more than one subcutaneous injection of Hemlibra; contact your healthcare professional for appropriate injection instructions.

• Hemlibra must be injected only under the skin.

Storage of Hemlibra vials:

• Store the vial in the refrigerator (2 °C to 8 °C). Do not freeze.

• Keep the vial in the original packaging to protect the medicine from light.

• Once removed from the refrigerator, the unopened vial may be stored at room temperature (below 30 °C) for up to 7 days. After storage at room temperature, unopened vials may be returned to the refrigerator. The total time stored outside the refrigerator at room temperature must not exceed 7 days.

• Discard vials that have been stored at room temperature for more than 7 days or that have been exposed to temperatures above 30 °C.

• Keep vials out of the sight and reach of children.

• Remove the vial from the refrigerator 15 minutes before use and allow it to reach room temperature (below 30 °C) before preparing the injection.

• Do not shake the vial.

Storage of needles and syringes:

• Keep the transfer needle, injection needle, and syringe dry.

• Keep the transfer needle, injection needle, and syringe out of the sight and reach of children.

Inspection of medicine and materials:

• Gather all the materials listed below to prepare and administer the injection.

• Check the expiration date printed on the carton, the vial label, and the materials listed below. Do not use after the expiration date.

• Do not use the vial if:

• the medicine is cloudy, discolored, or hazy.

• the medicine contains particles.

• the cap covering the stopper is missing.

• Inspect the materials for damage. Do not use if they appear damaged or have been dropped on the floor.

• Place the materials on a flat, clean, and well-lit work surface.

The carton contains:

The package does not include:

Get ready:

Selection and preparation of the injection site:

For the injection, you may use:

• The thigh (front and middle part).
• The stomach area (abdomen), except for the 5 cm around the navel.
• The outer area of the upper arm (only if the caregiver administers the injection).
• You should use a different injection site each time, at least 2.5 cm away from the site used in any previous injection.
• Do not inject into areas that might be irritated by a belt or girdle.
• Do not inject into moles, scars, bruises, or areas where the skin is tender, red, hard, or damaged.

Preparing the syringe for injection:

• Once the syringe has been filled with the medicine, it must be used immediately.

• Once the needle cap has been removed, the medicine must be injected under the skin within 5 minutes.

• Do not touch exposed needles or place them on any surface after removing the cap.

• Do not use the syringe if the needle touches any surface.

Important information after the injection:

• If you see drops of blood at the injection site, you may press it with sterile cotton or gauze for at least 10 seconds until bleeding stops.

• If you have a bruise (a small bleed under the skin), you may also apply ice with light pressure. If bleeding does not stop, contact a healthcare professional.

• Do not rub the injection site after the injection.

Disposal of medicine and materials:

Important: Always keep the sharps container out of the reach of children.

• Dispose of any cap(s), vial(s), needles, and syringes used in a sharps container. Discard used needles and syringes into a sharps container immediately after use. Do not dispose of loose caps, vials, needles, or syringes in household waste.

• If you do not have a sharps container, you may use a household waste container that:

• is made of puncture-resistant plastic.

• can be closed with a tight, puncture-resistant lid that prevents sharps from escaping.

• remains upright and stable during use.

• is leak-proof.

• is properly labeled as containing hazardous waste.

• When the sharps container is nearly full, you must follow local guidelines for proper disposal.

• Do not dispose of any used sharps container in household waste unless local guidelines permit it. Do not recycle your sharps container.

1. PREPARATION

Step 1. Remove the cap from the vial and clean the top

Step 2. Attach the transfer needle with filter to the syringe

Step 3. Remove the transfer needle cap

Step 4. Inject air into the vial

Step 5. Transfer the medication to the syringe

Step 6. Remove air bubbles

Do not use the transfer needle to inject the medicine, as it may cause pain and bleeding.

1. INJECTION

Step 7. Replace the cap on the transfer needle

Step 8. Clean the injection site

Step 9. Remove the used transfer needle from the syringe

Step 10. Attach the injection needle to the syringe

Step 11. Remove the safety protector

Step 12. Uncover the injection needle

Step 13. Adjust the plunger according to the prescribed dose

Step 14. Subcutaneous injection (under the skin)

Step 15. Inject the medication

1. DISPOSAL OF THE SYRINGE AND NEEDLE

Step 16. Secure the needle with the safety shield

Step 17. Dispose of the syringe and needle.

Combination of vials

If you need to use more than 1 vial to achieve the prescribed dose, follow these steps after withdrawing the medication from the first vial as described in step 5. You must use a new transfer needle for each vial.

Step A. Replace the cap on the transfer needle

Step B. Remove the used transfer needle from the syringe