Product Information for the User

Nplate 250 micrograms powder and solvent for solution for injection

Nplate 500 micrograms powder and solvent for solution for injection

Romiplostim

Read this entire product information carefully before starting to use this medicine, as it contains important information for you.

• Keep this product information, as you may need to read it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.

• This medicine has been prescribed only for you, and you must not give it to other people even if they have the same symptoms as you, as it may harm them.

• If you experience any side effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this product information. See section 4.

1. What you need to know before starting to use Nplate
2. How to use Nplate
3. Possible side effects
4. Storage of Nplate
5. Contents of the pack and additional information
6. Instructions for preparing and administering a Nplate injection

The active ingredient of Nplate is romiplostim, which is a protein used to treat low platelet counts in patients with primary immune thrombocytopenia (PTI). PTI is a disease in which the body's immune system destroys its own platelets. Platelets are blood cells that help heal wounds and form blood clots. Very low platelet counts can cause severe bruises and bleeding.

Nplate is used in adult patients (18 years or older) with PTI who may or may not have had their spleen removed and who have been previously treated with corticosteroids or immunoglobulins that did not work for them.

Nplate works by stimulating the bone marrow (part of the bone that generates blood cells) to produce more platelets. This should help prevent bruises and bleeding related to PTI.

Do not use Nplate

• If you are allergic to romiplostim or any of the other components of this medication (listed in section 6).

• If you are allergic to other medications produced using DNA technology that utilizes the microorganismEscherichia coli(E. coli).

Warnings and precautions

• If you stop taking Nplate, it is likely that your platelet count will decrease again (thrombocytopenia). If you stop taking Nplate, your platelet count will need to be monitored, and your doctor will discuss the necessary precautions with you.

• If you have a risk of blood clots or if blood clots are frequent in your family. The risk of blood clots may also be increased if:
• • You have liver problems;
  • You are 65 years of age or older;
  • You are bedridden;
  • You have cancer;
  • You are taking birth control pills or hormone replacement therapy;
  • You have recently undergone surgery or have had an injury;
  • You are obese (overweight);
  • You are a smoker.

Consult your doctor, pharmacist, or nurse before starting to use Nplate.

If you have a very high platelet count, you may increase the risk of blood clots. Your doctor will adjust your Nplate dose to ensure that your platelet count is not too high.

Bone marrow changes(increase in reticulin and possible fibrosis in the bone marrow)

The long-term use of Nplate may cause changes in your bone marrow. These changes may lead to abnormal blood cells or your body producing fewer blood cells. The mild form of these changes in the bone marrow is called “increase in reticulin” and was observed in Nplate clinical trials. It is unknown if this could progress to a more severe form called “fibrosis”. Your blood tests may show signs of bone marrow changes such as abnormalities. Your doctor will decide if an abnormal blood test means that a bone marrow test should be done or if treatment with Nplate should be interrupted.

Worsening of blood cancer

Your doctor may decide to perform a bone marrow biopsy if they consider it necessary to ensure that you have PTI and not another disease such as Myelodysplastic Syndrome (MDS). If you have MDS and receive Nplate, you may experience an increase in blast cells and worsening of MDS to acute myeloid leukemia, which is a type of blood cancer.

Loss of response to romiplostim

If you experience a loss of response to romiplostim or inability to maintain a platelet response during treatment with romiplostim, your doctor will investigate the reasons, including if you are experiencing an increase in bone marrow fibers (reticulin) or if you have developed antibodies that neutralize the activity of romiplostim.

Children and adolescents

Nplate is not recommended for use in children under 18 years of age.

Other medications and Nplate

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication.

If you are also taking other medications that prevent blood clots (anticoagulant or antiplatelet therapy), there is a higher risk of bleeding. Your doctor will discuss this aspect with you.

If you are taking corticosteroids, danazol, and/or azathioprine, which you may be receiving to treat your PTI, you may need to reduce or discontinue their administration when combined with Nplate.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, or if you think you may be pregnant or intend to become pregnant, consult your doctor or pharmacist before using this medication. Nplate is not recommended during pregnancy unless your doctor advises it.

The excretion of romiplostim in human milk is unknown. Nplate is not recommended during breastfeeding. The decision to interrupt breastfeeding or interrupt romiplostim treatment should be made considering the benefits of breastfeeding for the baby and the benefits of romiplostim treatment for the patient.

Driving and operating machinery

Consult your doctor before driving or operating machinery, as some side effects (e.g., temporary episodes of dizziness) may impair your ability to perform these activities safely.

Nplate should be administered under the direct supervision of a doctor who will accurately control the amount of Nplate administered.

Nplate is administered once a week by subcutaneous injection.

The initial dose is 1 microgram of Nplate per kilogram of body weight once a week. Your doctor will tell you how much Nplate you should use. Nplate should be injected once a week for platelet count maintenance. Your doctor will regularly draw blood samples to evaluate how your platelets are responding and adjust the dose if necessary.

Once your platelet count is controlled, your doctor will continue to perform blood tests for monitoring. Your dose may be adjusted later to maintain long-term control of your platelet count.

Always follow exactly the Nplate administration instructions indicated by your doctor. In case of doubt, consult your doctor again on how to use Nplate.

Nplate administration instructions

After proper training, your doctor may also allow you to self-administer Nplate. Please read the instructions at the end of this prospectus on how to inject Nplate, as discussed with your doctor. If your doctor has allowed you to self-administer, you must follow up with them every month to determine if Nplate is working or if you should consider another treatment.

After the first month of self-administering Nplate, you will need to demonstrate that you can still prepare and inject Nplate correctly.

If you use more Nplate than you should

Your doctor will ensure that you receive the correct amount of Nplate. If you have received more Nplate than you should, you may not experience any physical symptoms, but your blood platelet levels may increase to very high levels and this may increase the risk of blood clotting. Therefore, if your doctor suspects that you have received more Nplate than you should, it is recommended that you be monitored for any signs or symptoms of side effects and that you receive the appropriate treatment immediately.

If your doctor has allowed you to self-administer and you use more Nplate than you should, inform your doctor immediately.

If you use less Nplate than you should

Your doctor will ensure that you receive the correct amount of Nplate. If you have received less Nplate than you should, you may not experience any physical symptoms, but your blood platelet levels may decrease to low levels and this may increase the risk of bleeding. Therefore, if your doctor suspects that you have received less Nplate than you should, it is recommended that you be monitored for any signs or symptoms of side effects and that you receive the appropriate treatment immediately.

If your doctor has allowed you to self-administer and you use less Nplate than you should, inform your doctor immediately.

If you forget to use Nplate

If you forget a dose of Nplate, your doctor will tell you when to receive the next dose.

If your doctor has allowed you to self-administer and you forgot to administer your injection, inform your doctor immediately.

If you interrupt Nplate treatment

If you stop using Nplate, it is likely that you will experience a low platelet count (thrombocytopenia) again. Your doctor will decide if you should stop taking Nplate.

Self-administering Nplate

Your doctor may decide that it is better for you to inject Nplate. Your doctor, nurse, or pharmacist will show you how to inject Nplate. Do not attempt to inject yourself if you have not been trained. It is very important that you prepare Nplate correctly and take the correct dose (see section 7. Nplate injection preparation and administration instructions, at the end of this prospectus).

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

Very common: may affect more than 1 in 10 people

• headache;

• allergic reaction;

• upper respiratory tract infection.

• Common: may affect up to 1 in 10 people

• bone marrow disorder, including an increase in bone marrow fibers (reticulina);

• difficulty falling asleep (insomnia);

• dizziness;

• tingling or numbness in the hands or feet (paresthesia);

• migraine;

• flushing of the skin (rubor);

• blood clot in a pulmonary artery (pulmonary embolism);

• nausea;

• diarrhea;

• abdominal pain;

• indigestion (dyspepsia);

• constipation;

• itching of the skin (pruritus);

• bruising under the skin (ecchymosis);

• hematomas (contusion);

• skin rash;

• joint pain (arthralgia);

• muscle pain or weakness (myalgia);

• pain in the hands and feet;

• muscle spasm;

• back pain;

• bone pain;

• fatigue (fatigue);

• reaction at the injection site;

• swelling in the hands and feet (peripheral edema);

• flu-like symptoms (influenza-like illness);

• pain;

• weakness (asthenia);

• fever (pyrexia);

• chills;

• contusion;

• swelling of the face, lips, mouth, tongue, or throat that may cause difficulty swallowing or breathing (angioedema);

• gastroenteritis;

• palpitations;
• sinusitis;
• bronchitis.

Common: may affect up to 1 in 10 people (may be observed in blood or urine tests)

• low platelet count in the blood (thrombocytopenia) and low platelet count in the blood (thrombocytopenia) after stopping treatment with Nplate;

• high platelet count (thrombocytosis);

• anemia.

Rare: may affect up to 1 in 100 people

• bone marrow disorder; bone marrow disorder that causes scarring (myelofibrosis); enlargement of the spleen (splenomegaly); vaginal bleeding (vaginal hemorrhage), rectal bleeding (rectal hemorrhage); bleeding in the mouth (oral hemorrhage); bleeding at the injection site (hemorrhage at the injection site);

• heart attack (myocardial infarction); increased heart rate;

• dizziness or spinning sensation (vertigo);

• eye problems including: bleeding in the eyes (conjunctival hemorrhage); difficulty focusing or blurred vision (visual accommodation disorder, papilloedema, or eye disorder); blindness; itching in the eyes (ocular pruritus); increased tearing (excessive lacrimation); or visual disturbances;

• digestive problems including: vomiting; bad breath (halitosis); difficulty swallowing (dysphagia); indigestion or acid reflux (gastroesophageal reflux disease); blood in the stool (hematochezia); stomach discomfort; mouth ulcers or blisters in the mouth (stomatitis); tooth discoloration (dental discoloration);

• weight loss; weight gain; intolerance to alcohol; loss of appetite (anorexia or decreased appetite); dehydration;

• general feeling of discomfort (discomfort); chest pain; irritability; facial swelling (facial edema); feeling of heat; increased body temperature; nervous feeling;

• flu; localized infection; inflammation of the nasal passages and throat (nasopharyngitis);
• nasal and throat problems including: cough; nasal discharge (rhinorrhea); dry throat; shortness of breath or difficulty breathing (dyspnea); nasal congestion; chest pain when breathing (dyspnea);

• swollen, painful joints, caused by uric acid (a breakdown product of food) (gout);

• muscle stiffness; muscle weakness; shoulder pain; muscle cramps;

• nerve problems including involuntary muscle contractions (clonus); distorted sense of taste (dysgeusia); decreased sense of taste (hypogeusia); decreased sensitivity, especially in the skin (hypoaesthesia); nerve function disturbances in arms and legs (peripheral neuropathy); blood clot in the transverse sinus (transverse sinus thrombosis);

• depression; abnormal dreams;

• hair loss (alopecia); sensitivity to light (photosensitivity reaction); acne; allergic reaction in the skin from contact with allergens (contact dermatitis); skin manifestations with rash and blisters (eczema); dry skin; skin redness (erythema); severe peeling or exfoliative rash (exfoliative dermatitis); abnormal hair growth; skin thickening and itching from repeated scratching (prurigo); bruising under the skin or ecchymosis under the skin (purpura); skin rash with itching (papular eruption); skin rash with itching (pruriginous eruption); generalized itching rash (urticaria); skin nodule (skin nodule); abnormal skin odor (abnormal skin odor);

• circulation problems including blood clots in the hepatic vein (portal vein thrombosis); deep vein thrombosis; low blood pressure (hypotension); high blood pressure; peripheral embolism; reduced blood flow to the hands, ankles, or feet (peripheral ischemia); swelling and coagulation in a vein, which may be extremely soft to the touch (phlebitis or superficial thrombophlebitis); blood clot (thrombosis);

• a rare condition characterized by periods of burning pain, redness, and heat in the feet and hands (erythromelalgia).

Rare: may affect up to 1 in 100 people (may be observed in blood or urine tests)

• a rare type of anemia in which the red blood cells, white blood cells, and platelets are reduced in number (aplastic anemia);

• increased white blood cell count (leucocytosis);

• excessive production of platelets (thrombocytosis); increased platelet count; abnormal platelet count;

• abnormalities in some blood tests (increased transaminases; increased lactate dehydrogenase in the blood);

• multiple myeloma;

• proteins in the urine.

Reporting of side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through thenational notification system included in theAppendix V.By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the packaging and on the vial label after CAD. The expiration date is the last day of the month indicated.

Store in refrigerator (between 2°C and 8°C).

Do not freeze.

Store in the original packaging to protect it from light.

When stored in the original packaging, this medication may be kept at room temperature (up to 25°C) for a maximum period of 30 days.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the packaging and unused medications. This will help protect the environment.

Composition of Nplate

Each vial of Nplate 250 micrograms powder for injectable solution contains a total of 375 micrograms of romiplostim. An additional volume has been added to each vial to ensure that 250 micrograms of romiplostim can be administered. After dissolution, a volume of 0.5 ml of final product solution contains 250 micrograms of romiplostim (500 micrograms/ml).

Each vial of Nplate 500 micrograms powder for injectable solution contains a total of 625 micrograms of romiplostim. An additional volume has been added to each vial to ensure that 500 micrograms of romiplostim can be administered. After dissolution, a volume of 1 ml of final product solution contains 500 micrograms of romiplostim (500 micrograms/ml).

Powder: mannitol (E421), sucrose, L-histidine, hydrochloric acid (for pH adjustment), and polisorbate 20.

Solvent: water for injectable preparations.

Appearance of the product and contents of the package

Nplate is a white powder for injectable solution that is supplied in a single-dose glass vial of 5 ml.

Nplate is supplied in a single-use or multiple-use package with 4 packages. Each package contains:

1 vial of 250 micrograms or 500 micrograms of romiplostim.

1 pre-loaded syringe containing 0.72 ml or 1.2 ml of water for injectable preparations for reconstitution.

1 plunger for the pre-loaded syringe.

1 sterile vial adapter.

1 sterile 1 ml syringe with Luer lock.

1 safety needle.

4 alcohol wipes.

It may only be marketed in some package sizes.

Marketing authorization holder and responsible manufacturer

Amgen Europe B.V.

Minervum 7061

4817 ZK Breda

Netherlands

Marketing authorization holder

Amgen Europe B.V.

Minervum 7061

4817 ZK Breda

Netherlands

Responsible manufacturer

Amgen Technology (Ireland) Unlimited Company

Pottery Road

Dun Laoghaire

Co Dublin

Ireland

Responsible manufacturer

Amgen NV

Telecomlaan 5-7

1831 Diegem

Belgium

You can request more information about this medicine by contacting the local representative of the marketing authorization holder.

België/Belgique/BelgienLietuva

s.a. Amgen n.v.Amgen Switzerland AG Vilniaus filialas

Tel/Tél: +32 (0)2 7752711Tel: +370 5 219 7474

????????Luxembourg/Luxemburg

?????? ???????? ????s.a. Amgen

???.: +359 (0)2 424 7440Belgique/Belgien

Tel/Tél: +32 (0)2 7752711

Ceská republikaMagyarország

Amgen s.r.o.Amgen Kft.

Tel: +420 221 773 500Tel.: +36 1 35 44 700

DanmarkMalta

Amgen filial af Amgen AB, SverigeAmgen B.V.

Tlf: +45 39617500The Netherlands

Tel: +31 (0)76 5732500

DeutschlandNederland

AMGEN GmbHAmgen B.V.

Tel.: +49 89 1490960Tel: +31 (0)76 5732500

EestiNorge

Amgen Switzerland AG Vilniaus filialasAmgen AB

Tel: +372 586 09553Tel: +47 23308000

Ελλ?δαÖsterreich

Amgen Ελλ?ς Φαρμακευτικ? Ε.Π.Ε.Amgen GmbH

Τηλ.: +30 210 3447000Tel: +43 (0)1 50 217

EspañaPolska

Amgen S.A.Amgen Biotechnologia Sp. z o.o.

Tel: +34 93 600 18 60Tel.: +48 22 581 3000

FrancePortugal

Amgen S.A.S.Amgen Biofarmacêutica, Lda.

Tél: +33 (0)9 69 363 363Tel: +351 21 4220606

HrvatskaRomânia

Amgen d.o.o.Amgen România SRL

Tel: +385 (0)1 562 57 20Tel: +4021 527 3000

IrelandSlovenija

Amgen Ireland LimitedAMGEN zdravila d.o.o.

Tel: +353 1 8527400Tel: +386 (0)1 585 1767

ÍslandSlovenská republika

Vistor hf.Amgen Slovakia s.r.o.

Sími: +354 535 7000Tel: +421 2 321 114 49

ItaliaSuomi/Finland

Amgen S.r.l.Amgen AB, sivuliike Suomessa/Amgen AB, filial

Tel: +39 02 6241121i Finland

Puh/Tel: +358 (0)9 54900500

K?προςSverige

C.A. Papaellinas LtdAmgen AB

Τηλ.: +357 22741 741Tel: +46 (0)8 6951100

LatvijaUnited Kingdom

Amgen Switzerland AG Rigas filialeAmgen Limited

Tel: +371 257 25888Tel: +44 (0)1223 420305

Date of the last review of this leaflet in

Other sources of information

The detailed information on this medicine is available on the European Medicines Agency websitehttp://www.ema.europa.eu

1. Instructions for the preparation and administration of a Nplate injection

This section contains information on how to self-inject Nplate. It is essential that you do not attempt to self-administer the injection if you have not received training from your doctor, nurse, or pharmacist. If you have questions about how to put the injection, consult your doctor, nurse, or pharmacist. It is crucial that the product is prepared correctly and that the dose administered is correct.

This section is divided into the following sub-sections:

Before starting

Step 1. Place the injection materials

Step 2. Prepare the vial for use, place the vial adapter

Step 3. Prepare the sterile water syringe

Step 4. Dissolve Nplate by injecting water into the vial

Step 5. Prepare a new syringe for the injection

Step 6. Prepare the safety needle for the injection

Step 7. Choose and prepare the injection site

Step 8. Inject the Nplate liquid

Step 9. Disposal of supplies

Before starting

Read all the usage instructions carefully.These instructions are for patients who have alreadybeen trained by their healthcare professional, such as their doctor, nurse, or pharmacist, in self-injection. If you have not been trained, please contact your healthcare professional.

The Nplate auto-injection kit should be kept in the original packaging until use to protect the Nplate vial from light. Keep the Nplate auto-injection kit refrigerated between 2°C and 8°C.

Once Nplate has been dissolved, inject immediately.

You may be left with excess Nplate after administering the prescribed dose. Do not reuse Nplate! Any excess dissolved Nplate must be disposed of immediately after completing the injection process. The excess Nplate from the vial MUST NOT be reused for another injection.

Step 1. Place the injection materials

Do the following:

• Select a flat and well-lit work surface, such as a table.

• Take the Nplate auto-injection kit from the refrigerator.Do not use if frozen.If you have any doubts about storage, contact your healthcare professional for further instructions.

Check the expiration date included in the auto-injection kit. If the expiration date has passed, do not use it.Do not continue and inform your healthcare professional.

• Nota:If your doctor has prescribed a dose of Nplate that requires more than one injection,you will need to use more than one auto-injection kit. Follow the steps described in this leaflet and use as many auto-injection kits as necessary to complete the prescribed dose of Nplate.

• Ensure that you have the following components:

Alcohol wipes packagex4

Plunger for sterile water syringex1Sterile water syringex1

Syringe of 1 ml with Luer lockx1Safety needle for injectionx1

• Do notopen the components until indicated in the instructions.

• Do notuse components that have been altered or damaged.

• Do notreuse the components.

Step 2. Prepare the vial for use, place the vial adapter

Use:2 alcohol wipes, 1 vial, and 1 vial adapter package.

Do the following:

Step 3. Prepare the sterile water syringe

Use:The pre-loaded sterile water syringe and plunger.

Before starting Step 3, please note the following:

• The transparent plastic plunger must always be connected before breaking the white tip of the syringe. Carry out Step 3a before Step 3b.

Do the following:

Step 4. Dissolve Nplate, inject water into the vial

Use:The pre-loaded sterile water syringe and vial with vial adapter attached.

Before starting Step 4, please note the following:

• Dissolveslowly and carefully. It is a protein and, as such, can be easily damagedby inadequate and excessive mixing of the solution.

Do the following:

Before continuing:

• Ensurethat all the water is injected from the syringe into the vial before dissolving it.

Before continuing:

• Inspectvisually the dissolved liquid in the vial for particles and/or discoloration. It should beclear and colorless and completely dissolved.

• Nota:If there isany color or particles in the liquid,contact your healthcare professional.

• Ensurethat the liquid is completely dissolved before removing the syringe.

• Dispose of the empty syringein a sharp object container. Keep the dissolved Nplate vial. Immediately prepare a new syringe for the injection.

• Do notdelay the injection of Nplate

Step 5. Prepare a new syringe for the injection

Use:A new 1 ml syringe from the package and the vial with dissolved and transparent Nplate.

Before continuing:

• Reviewyour dose before starting this step.
• Nota:Nplate liquid is very potent, so the accuracy and measurement of the dose areimportant.

• Ensurethat all air bubbles have been removed before the injection.

Do the following:

• Make a final check to ensure that the correct amount of liquid for your dose is in the syringeandthat all air bubbles have been removed.

Before continuing:

• Ensurethat the correct amount of liquid for your dose remains in the syringe.

• Ensurethat all air bubbles have been removed from the syringe.

Step 6. Prepare the safety needle for the injection

Use:The syringe full of the measured dose of Nplate and the safety needle.

Do the following:

Step 7. Choose and prepare the injection site

Use:New alcohol wipes.

Do the following:

Step 8. Inject the Nplate liquid

Use:The syringe full and the safety needle.

Do the following: