Label: Information for the User

Nplate 125 micrograms Powder for Solution for Injection

Nplate 250 micrograms Powder for Solution for Injection

Nplate 500 micrograms Powder for Solution for Injection

Romiplostim

Read this label carefully before you start using this medicine, because it contains important information for you.

• Keep this label, 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 should not give it to others 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 label. See section 4.

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 immune system of your body destroys your own platelets. Platelets are the blood cells that help to heal wounds and form blood clots. Very low platelet counts can cause severe bruises and bleeding.

Nplate is used in adult patientswith PTIwho may or may not have had their spleen removed and who have been previously treated with corticosteroids or immunoglobulins, when these treatments have not worked. Nplate is also used in children1year or older with chronic PTI who may or may not have had their spleen removed and who have been previously treated with corticosteroids or immunoglobulins that have not worked.

Nplate works by stimulating the bone marrow (part of the bone that generates blood cells) to produce more platelets. This should help to prevent the bruises and bleeding associated with 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 Escherichia coli (E. coli) microorganism.

Warnings and precautions

• If you stop taking Nplate, it is likely that your platelet count will return to low levels (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 suffered 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(increased 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 a reduced production of blood cells. The mild form of these bone marrow changes is called "increased reticulin" and was observed in Nplate clinical trials. It is unknown if this could progress to a more severe form called "fibrosis". Abnormalities in your blood tests may indicate changes in the bone marrow. Your doctor will decide if an abnormal blood test means that a bone marrow test should be performed 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 a 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 1 year.

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 plan to become pregnant, consult your doctor or pharmacist before using this medication. Nplate is not recommended during pregnancy unless your doctor advises otherwise.

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

Adults and children (1 to 17 years):

Nplate must 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 indicate the amount of Nplate you should use. Nplate must be injected once a week for the maintenance of platelet counts. 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 control. Your dose may be adjusted later to maintain long-term control of your platelet count.

Children (1 to 17 years): in addition to adjusting the dose based on platelet counts, your doctor will also regularly review your weight to adjust your dose.

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 present 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 to observe any signs or symptoms of side effects and that you be administered the appropriate treatment 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 present any physical symptoms, but your blood platelet levels may decrease to low levels and this may produce a risk of bleeding. Therefore, if your doctor suspects that you have received less Nplate than you should, it is recommended that you be monitored to observe any signs or symptoms of side effects and that you be administered the appropriate treatment immediately.

If you forget to use Nplate

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

If you interrupt treatment with Nplate

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

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

Possible side effects in adults with PTI

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 fibres (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 (asthenia);

• 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 (bleeding 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;

• gastrointestinal 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 mouth sores (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 sensation;

• flu; localized infection; inflammation of the nasal passages and throat (nasopharyngitis);

• nasal and throat problems including: cough; nasal secretion (rhinorrhea); dry throat; shortness of breath or difficulty breathing (dyspnea); nasal congestion; pain on breathing (respiratory pain);

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

• muscle stiffness; muscle weakness; shoulder pain; muscle contractions;

• neurological 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; redness of the skin (erythema); severe peeling or exfoliative rash (exfoliative dermatitis); abnormal hair growth; thickening and itching of the skin from repeated scratching (prurigo); bruising under the skin or purpura 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);

• or multiple myeloma;

• proteins in the urine.

Possible side effects in children with PTI

Very common: may affect more than 1 in 10 people

• upper respiratory tract infection;

• mouth and throat pain (oropharyngeal pain);

• itching, nasal secretion, or blocked nose (rhinitis);

• cough;

• abdominal pain;

• diarrhea;

• rash;

• fever (pyrexia);

• hematoma (contusion).

Common: may affect up to 1 in 10 people

• gastroenteritis;

• throat pain and discomfort swallowing (pharyngitis);

• conjunctivitis;

• ear infection;

• sinusitis;

• swelling in the extremities, hands/feet;

• bruising under the skin or hematomas under the skin (purpura);

• urticaria.

Rare: may affect up to 1 in 100 people

• high platelet count (thrombocytosis).

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 out of the refrigerator for a maximum period of 30 days at room temperature (up to 25°C).

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the packaging and medications that you no longer need. This will help protect the environment.

Composition of Nplate

• The active ingredient is romiplostim.

Each vial of Nplate 125 micrograms powder for injection contains a total of 230 micrograms of romiplostim. An additional volume has been added to each vial to ensure that 125 micrograms of romiplostim can be administered. After dissolution, a final volume of 0.25 ml of solution contains 125 micrograms of romiplostim (500 micrograms/ml).

Each vial of Nplate 250 micrograms powder for injection 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 final volume of 0.5 ml of solution contains 250 micrograms of romiplostim (500 micrograms/ml).

Each vial of Nplate 500 micrograms powder for injection 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 final volume of 1 ml of solution contains 500 micrograms of romiplostim (500 micrograms/ml).

• The other components are mannitol (E421), sucrose, L-histidine, hydrochloric acid (for pH adjustment), and polisorbate 20.

Appearance of the product and contents of the pack

Nplate is a white powder for injection that is supplied in a single-dose glass vial.

Each pack contains 1 or 4 vials of 125 micrograms (beige cap), 250 micrograms (red cap), or 500 micrograms (blue cap) of romiplostim.

Only some pack sizes may be marketed.

Marketing authorization holder and responsible person for manufacturing

Amgen Europe B.V.

Minervum 7061

4817 ZK Breda

Netherlands

Marketing authorization holder

Amgen Europe B.V.

Minervum 7061

4817 ZK Breda

Netherlands

Responsible person for manufacturing

Amgen Technology (Ireland) Unlimited Company

Pottery Road

Dun Laoghaire

Co Dublin

Ireland

Responsible person for manufacturing

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 revision of this leaflet

Other sources of information

The detailed information on this medicine is available on the website of the European Medicines Agencyhttp://www.ema.europa.eu

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This information is intended solely for healthcare professionals:

Reconstitution:

Nplate is a sterile product without preservatives and is indicated for single use. Nplate should be reconstituted following good aseptic practice recommendations.

• Nplate 125 micrograms powder for injectionshould be reconstituted with 0.44 ml ofsterile water for injections to produce a final volume of 0.25 ml. Eachvial includes an additional amount to ensure that 125 mcg of romiplostim can be administered (see the table below for the contents of the vial).

• Nplate 250 micrograms powder for injectionshould be reconstituted with 0.72 ml ofsterile water for injections to produce a final volume of 0.5 ml. Each vial includes an additional amount to ensure that 250 mcg of romiplostim can be administered (see the table below for the contents of the vial).

• Nplate 500 micrograms powder for injectionshould be reconstituted with 1.2 ml ofsterile water for injections to produce a final volume of 1 ml. Each vial includes an additional amount to ensure that 500 mcg of romiplostim can be administered (see the table below for the contents of the vial).

Contents of the vial:

Only sterile water for injections should be used to reconstitute the medicine. Solutions of sodium chloride or bacteriostatic water should not be used to reconstitute the medicine.

Water for injections should be injected into the vial. During dissolution, a gentle circular motion should be made and the contents of the vial should be inverted. The vial should not be shaken or agitated vigorously. It usually takes less than 2 minutes to dissolve Nplate.No shaking or vigorous agitation of the vial is required.Inspect the solution visually for particles or discoloration before administration. The reconstituted solution should be transparent and colorless and should not be administered if particles and/or discoloration are observed.

From a microbiological point of view, the medicine should be used immediately. If not used immediately, the times and conditions of storage during use before use are the responsibility of the user and should not exceed 24 hours at 25°C or 24 hours in the refrigerator (between 2°C and 8°C), protected from light.

The disposal of unused medicine and all materials that have come into contact with it will be carried out in accordance with local regulations.

Dilution (required when the individual patient dose calculation is less than 23 mcg).

The initial reconstitution of romiplostim with designated volumes of sterile water for injections results in a concentration of 500 mcg/ml in all vial sizes. If the individual patient dose calculation is less than 23 mcg, additional dilution is required to achieve a concentration of 125 mcg/mlwith sterile sodium chloride 9 mg/ml (0.9%) solution, withoutpreservatives,to ensure an exact dose (see the table below).

Dilution guidelines:

The sterile sodium chloride 9 mg/ml (0.9%) solution, without preservatives, should only be used for dilution. Dextrose (5%) in water or sterile water for injections should not be used for dilution. No other diluent has been tested.

From a microbiological point of view, the diluted medicine should be used immediately. If not used immediately, the times and conditions of storage during use before use are the responsibility of the user and should not exceed 4 hours at 25°C in disposable syringes or 4 hours in the original vials in the refrigerator (between 2°C and 8°C), protected from light.