NPLATE

Package leaflet: Information for the user

Nplate 125 micrograms powder for solution for injection, 250 micrograms powder for solution for injection, 500 micrograms powder for solution for injection

romiplostim
Please 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 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, tell your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

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

1. What Nplate is and what it is used for

The active substance of Nplate is romiplostim, a protein used to treat low platelet counts in the blood of patients with primary immune thrombocytopenia, known as ITP. ITP is a condition in which the immune system destroys the body's platelets. Platelets are blood cells that help heal wounds and form blood clots. A very low platelet count can cause bruising and serious bleeding.
Nplate is used to treat adult patients with ITP who have or have not undergone splenectomy and who have previously been treated with corticosteroids or immunoglobulins, in cases where these treatments have not been effective. Nplate is also used to treat children from 1 year of age with chronic ITP who have or have not undergone splenectomy and who have previously been treated with corticosteroids or immunoglobulins, in cases where these treatments have not been effective.
Nplate works by stimulating the bone marrow (the part of the bone responsible for producing blood cells) to produce a greater number of platelets. This should help prevent the bruising and bleeding associated with ITP.

2. What you should know before using Nplate

Do not use Nplate
if you are allergic to romiplostim or to any of the other ingredients of this medicine
(listed in section 6).
if you are allergic to other medicines produced using recombinant DNA technology that use the bacterium
Escherichia coli (E. coli).

Warnings and precautions
If you stop taking Nplate, your platelet count is likely to become low again (thrombocytopenia). If you stop taking Nplate, your doctor will monitor your platelet count periodically and discuss with you the most appropriate precautionary measures.

If you are at risk of blood clots or have a family history of thrombosis, your risk of thrombosis may be increased if you:
have liver problems;
are elderly (over 65 years of age);
are bedridden;
have cancer;
are taking oral contraceptives or hormone replacement therapy;
have recently undergone surgery or sustained an injury;
are obese (overweight);
are a smoker.
Please consult your doctor before taking Nplate if you have any of these conditions.

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

Bone marrow changes (increased reticulin and possible bone marrow fibrosis)
Long-term use of Nplate may cause changes in the bone marrow. These changes may lead to abnormalities in blood cells or reduced production of blood cells.
A mild form of these bone marrow changes, called "increased reticulin," has been observed in clinical studies with Nplate. It is not known whether this may progress to a more severe condition known as "fibrosis." Signs of bone marrow changes may appear as abnormalities in blood tests. Your doctor will decide whether abnormal blood test results mean you need a bone marrow test or whether you should stop taking Nplate.

Worsening of blood cancers
Your doctor may decide to perform a bone marrow biopsy if they consider it necessary to confirm that you have ITP and not another condition such as myelodysplastic syndrome (MDS). If you have MDS and receive Nplate, you may experience an increase in malignant blood cells, and MDS may worsen and progress to acute myeloid leukemia, a type of blood cancer.

Loss of response to romiplostim
If you experience a loss of response or an inability to maintain a platelet response during treatment with romiplostim, your doctor will investigate the reasons, considering both possible increased bone marrow fibres (reticulin) and whether you have developed antibodies that neutralize the activity of romiplostim.

Children and adolescents
Nplate is not recommended for use in children under 1 year of age.

Other medicines and Nplate
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
If you are also taking medicines that prevent blood clotting (anticoagulant or antiplatelet therapy), your risk of bleeding is higher. Your doctor will discuss this with you.
If you are taking corticosteroids, danazol, and/or azathioprine—medicines you may receive to treat ITP—your doctor may reduce the dose or discontinue these medicines when used together with Nplate.

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, planning to become pregnant, or are breastfeeding, ask your doctor or pharmacist for advice before taking this medicine. The use of Nplate is not recommended during pregnancy unless specifically advised by your doctor.
It is not known whether romiplostim is excreted in breast milk. The use of Nplate is not recommended during breastfeeding. The decision whether to discontinue breastfeeding or to discontinue therapy with romiplostim should be based on the benefit of breastfeeding for the child and the benefit of romiplostim therapy for you.

Driving and using machines
Consult your doctor before driving or operating machinery, as certain side effects (e.g., transient episodes of dizziness) may impair your ability to do so safely.

3. How to use Nplate

Adults and children (1 to 17 years of age):
Nplate will be administered under the direct supervision of your doctor, who will closely monitor the amount of Nplate you are given.
Nplate is given once weekly as a subcutaneous injection (under the skin).
The starting dose is 1 microgram of Nplate per kilogram of body weight, administered once weekly. Your doctor will inform you of the amount of Nplate to be administered. Nplate must be injected once a week to maintain a high platelet count in the blood. Your doctor will regularly take blood samples to monitor how your platelets are responding and, if necessary, will adjust the dose accordingly.
Once the platelet count is under control, your doctor will continue to perform regular blood tests. The dose may be further adjusted to maintain long-term control of the platelet count in the blood.
Children (1 to 17 years of age): in addition to adjusting the dose based on platelet count, the doctor will regularly reassess body weight to adjust the dose.

If you use more Nplate than you should
Your doctor will ensure that you receive the correct amount of Nplate. If you have taken a higher dose than recommended, you may not experience any symptoms, but your platelet count could rise to high levels, which may increase the risk of blood clots. Therefore, if your doctor suspects that you have received an overdose of Nplate, monitoring for signs or symptoms of adverse effects is recommended, and immediate appropriate treatment should be administered.

If you use less Nplate than you should
Your doctor will ensure that you receive the correct amount of Nplate. If you have been given less Nplate than recommended, you may not experience physical symptoms, but your platelet count could decrease, which may increase the risk of bleeding. Therefore, if your doctor suspects that you have received an insufficient dose of Nplate, monitoring for any signs or symptoms of adverse effects is recommended, and immediate appropriate treatment should be administered.

If you forget to use Nplate
If you have missed a dose of Nplate, your doctor will discuss with you when the next dose should be administered.

If you stop using Nplate
If you stop taking Nplate, thrombocytopenia (low platelet count in the blood) is likely to recur. Your doctor will decide whether you should stop using Nplate.

4. Possible side effects

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

Possible side effects in adults with ITP

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, increase in bone marrow fibres (reticulin);
• insomnia;
• dizziness;
• tingling or numbness in hands and feet (paraesthesia);
• migraine;
• skin redness (flushing);
• blood clot in the pulmonary artery (pulmonary embolism);
• nausea;
• diarrhoea;
• abdominal pain;
• indigestion (dyspepsia);
• constipation;
• itching (pruritus);
• bleeding under the skin (bruising);
• bruises (contusions);
• rash;
• joint pain (arthralgia);
• muscle pain or weakness (myalgia);
• pain in hands and feet;
• muscle spasm;
• back pain;
• bone pain;
• tiredness (fatigue);
• injection site reactions;
• swelling of hands and feet (peripheral oedema);
• flu-like symptoms (influenza);
• pain;
• weakness (asthenia);
• fever (pyrexia);
• chills;
• contusion;
• swelling of the face, lips, mouth, tongue or throat which may cause difficulty swallowing or breathing (angioedema);
• gastroenteritis;
• palpitations;
• inflammation of the sinuses (sinusitis);
• inflammation of the airways to the lungs (bronchitis);
• blood clot in veins (deep vein thrombosis).

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

• low platelet count in the blood (thrombocytopenia) and low platelet count in the blood (thrombocytopenia) after stopping Nplate;
• platelet count higher than normal (thrombocytosis);
• anaemia.

Uncommon: may affect up to 1 in 100 people

• inability of the bone marrow to produce normal numbers of blood cells (bone marrow failure); bone marrow changes leading to fibrosis (myelofibrosis); enlargement of the spleen (splenomegaly); vaginal bleeding; rectal bleeding; mouth bleeding; bleeding at injection site;
• heart attack (myocardial infarction); increased heart rate;
• dizziness or sensation of spinning (vertigo);
• eye disorders including: bleeding in the eye (conjunctival haemorrhage); blurred vision or difficulty focusing (accommodation disorders, papilledema or eye disorders); blindness; eye itching; increased tear production; or visual disturbances;
• gastrointestinal problems including: vomiting; bad breath (halitosis); difficulty swallowing (dysphagia); indigestion or heartburn (gastroesophageal reflux disease); blood in stools (haematochezia); gastric discomfort; mouth ulcers or mouth sores (stomatitis); tooth discoloration;
• weight loss; weight gain; alcohol intolerance; loss of appetite (anorexia or decreased appetite); dehydration;
• general feeling of being unwell; chest pain; irritability; facial swelling (facial oedema); hot flushes; fever; jaundice;
• influenza; localized infection; inflammation of nasal passages and throat (nasopharyngitis);
• nose and throat problems including: cough; runny nose (rhinorrhoea); dry throat; shortness of breath or difficulty breathing (dyspnoea); nasal congestion; painful breathing;
• joint pain and swelling due to uric acid (a by-product of food metabolism) (gout);
• muscle tension; muscle weakness; shoulder pain; muscle twitching (fasciculations);
• nervous system problems including involuntary muscle contractions (clonus); altered taste (dysgeusia); reduced sense of taste (hypogeusia); reduced sensitivity, especially of the skin (hypoesthesia); nerve function impairment in arms and legs (peripheral neuropathy); blood clot in the cerebral venous system (transverse sinus thrombosis);
• depression; abnormal dreams;
• hair loss (alopecia); sensitivity to light (photosensitivity reactions); acne; allergic skin reaction following contact with an allergen (contact dermatitis);

skin manifestations with rash and blisters (eczema); dry skin; red skin (erythema);
severe peeling or shedding of the skin (exfoliative rash); abnormal hair growth;
thickening and itching of the skin due to repeated scratching (prurigo); bleeding under
the skin or bruising (purpura); irregular skin rash (papular rash); itchy rash (pruritic rash);
generalized itchy rash (urticaria); skin bump (skin nodule); unpleasant odour of the skin (abnormal skin odour);

• circulatory problems including blood clots in the liver vein (portal vein thrombosis); low blood pressure (hypotension); increased blood pressure; blockage of blood vessels (peripheral embolism); reduced blood flow to hands, ankles or feet (peripheral ischaemia); swelling and clotting in a vein, which may be extremely painful when touched (phlebitis or superficial thrombophlebitis); blood clot (thrombosis);
• a rare condition characterised by episodes of burning pain, redness and increased temperature in the hands and feet (erythromelalgia).

Uncommon: may affect up to 1 in 100 people (may be detected during urine or blood tests)

• a rare type of anaemia in which red blood cells, white blood cells and platelets are all reduced in number (aplastic anaemia);
• increased number of white blood cells (leucocytosis);
• excessive platelet production (thrombocythaemia); increased number of platelets; abnormal number of blood cells that prevent bleeding (abnormal platelet count);
• changes in certain blood tests (increased transaminases; increased lactate dehydrogenase);
• tumour of white blood cells (multiple myeloma);
• protein in urine.

Possible side effects in children with ITP

Very common: may affect more than 1 in 10 people

• upper respiratory tract infection;
• pain in mouth and throat (oropharyngeal pain);
• itchy nose, runny nose or blocked nose (rhinitis);
• cough;
• upper abdominal pain;
• diarrhoea;
• rash;
• fever (pyrexia);
• bruises (contusions).

Common: may affect up to 1 in 10 people

• gastroenteritis;
• sore throat and discomfort when swallowing (pharyngitis);
• eye inflammation (conjunctivitis);
• ear infection;
• inflammation of the sinuses (sinusitis);
• swelling of limbs/hands/feet;
• bleeding under the skin surface or bruising under the skin (purpura);
• itchy rash (urticaria).

Uncommon: may affect up to 1 in 100 people

• platelet count higher than normal (thrombocytosis).

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

5. How to store Nplate

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 carton and on the label of the
vial after EXP. The expiry date refers to the last day of that month.
Store in a refrigerator (2°C - 8°C).
Do not freeze.
Keep in the original packaging to protect the medicine from light.
This medicine may be removed from the refrigerator and stored at room temperature (up to 25°C) for a period of 30 days, provided it is kept in the original packaging.
Do not dispose of medicines 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 Nplate contains

• The active substance is romiplostim.

Each Nplate vial containing 125 micrograms of powder for injectable solution contains a total of 230 micrograms of romiplostim. An additional amount is included to ensure the availability of 125 micrograms of romiplostim per vial. After reconstitution, an extractable volume of 0.25 mL of solution contains 125 micrograms of romiplostim (500 micrograms/mL).
Each Nplate vial containing 250 micrograms of powder for injectable solution contains a total of 375 micrograms of romiplostim. An additional amount is included to ensure the availability of 250 micrograms of romiplostim per vial. After reconstitution, an extractable volume of 0.5 mL of solution contains 250 micrograms of romiplostim (500 micrograms/mL).
Each Nplate vial containing 500 micrograms of powder for injectable solution contains a total of 625 micrograms of romiplostim. An additional amount is included to ensure the availability of 500 micrograms of romiplostim per vial. After reconstitution, an extractable volume of 1 mL of solution contains 500 micrograms of romiplostim (500 micrograms/mL).

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

Description of the appearance of Nplate and package contents
Nplate is a white powder for injectable solution supplied in a single-dose glass vial.
Pack: containing 1 or 4 vials of 125 micrograms (beige cap), 250 micrograms (red cap), or 500 micrograms (blue cap) of romiplostim.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Amgen Europe B.V.
Minervum 7061
4817 ZK Breda
The Netherlands

Marketing Authorisation Holder
Amgen Europe B.V.
Minervum 7061
4817 ZK Breda
The Netherlands

Manufacturer
Amgen Technology (Ireland) Unlimited Company
Pottery Road
Dun Laoghaire
Dublin
Ireland

Manufacturer
Amgen NV
Telecomlaan 5-7
1831 Diegem
Belgium

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder.

België/Belgique/Belgien Lietuva
s.a. Amgen n.v. Amgen Switzerland AG Vilniaus filialas
Tél/Tel: +32 (0)2 7752711 Tel: +370 5 219 7474

България Luxembourg/Luxemburg
Амджен България ЕООД s.a. Amgen
Тел.: +359 (0)2 424 7440 Belgique/Belgien
Tél/Tel: +32 (0)2 7752711

Česká republika Magyarország
Amgen s.r.o. Amgen Kft.
Tel: +420 221 773 500 Tel.: +36 1 35 44 700

Danmark Malta
Amgen, filial af Amgen AB, Sverige Amgen S.r.l.
Tlf.: +45 39617500 Italy
Tel: +39 02 6241121

Deutschland Nederland
Amgen GmbH Amgen B.V.
Tel.: +49 89 1490960 Tel: +31 (0)76 5732500

Eesti Norge
Amgen Switzerland AG Vilniaus filialas Amgen AB
Tel: +372 586 09553 Tlf: +47 23308000

Ελλάδα Österreich
Amgen Ελλάς Φαρμακευτικά Ε.Π.Ε. Amgen GmbH
Τηλ.: +30 210 3447000 Tel: +43 (0)1 50 217

España Polska
Amgen S.A. Amgen Biotechnologia Sp. z o.o.
Tel: +34 93 600 18 60 Tel.: +48 22 581 3000

France Portugal
Amgen S.A.S. Amgen Biofarmacêutica, Lda.
Tél: +33 (0)9 69 363 363 Tel: +351 21 4220606

Hrvatska România
Amgen d.o.o. Amgen România SRL
Tel: +385 (0)1 562 57 20 Tel: +4021 527 3000

Ireland Slovenija
Amgen Ireland Limited AMGEN zdravila d.o.o.
Tel: +353 1 8527400 Tel: +386 (0)1 585 1767

Ísland Slovenská republika
Vistor hf. Amgen Slovakia s.r.o.
Sími: +354 535 7000 Tel: +421 2 321 114 49

Italia Suomi/Finland
Amgen S.r.l. Amgen AB, sivuliike Suomessa/Amgen AB, filial i Finland
Tel: +39 02 6241121 Puh/Tel: +358 (0)9 54900500

Kύπρος Sverige
C.A. Papaellinas Ltd Amgen AB
Τηλ.: +357 22741 741 Tel: +46 (0)8 6951100

Latvija
Amgen Switzerland AG Rīgas filiāle
Tel: +371 257 25888

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

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The following information is intended for healthcare professionals only:

Reconstitution:
Nplate is a sterile product without preservatives and is for single use only. Nplate must be reconstituted according to the principles of good aseptic technique.
Nplate 125 micrograms powder for solution for injection must be reconstituted with 0.44 mL of sterile water for injectable preparations, resulting in a total extractable volume of 0.25 mL. Each vial contains an overage to ensure the availability of 125 mcg of romiplostim (see vial content in the table below).
or
Nplate 250 micrograms powder for solution for injection must be reconstituted with 0.72 mL of sterile water for injectable preparations, resulting in a total extractable volume of 0.5 mL. Each vial contains an overage to ensure the availability of 250 mcg of romiplostim (see vial content in the table below).
or
Nplate 500 micrograms powder for solution for injection must be reconstituted with 1.2 mL of sterile water for injectable preparations, resulting in a total extractable volume of 1 mL. Each vial contains an overage to ensure the availability of 500 mcg of romiplostim (see vial content in the table below).
Vial content:

When reconstituting the medicinal product, only sterile water for injections should be used. Sodium chloride solutions or bacteriostatic water must not be used for reconstitution.

Sterile water for injections should be injected into the vial. The vial contents may be gently swirled and inverted during dissolution. Do not shake or vigorously agitate the vial. Dissolution of Nplate generally takes less than 2 minutes. Prior to administration, visually inspect the solution for the presence of particles and discoloration. The reconstituted solution must be clear and colorless; it must not be administered if particles or discoloration are observed.

From a microbiological standpoint, the medicinal product should be used immediately. If not used immediately, the user is responsible for the storage times and conditions after preparation, which normally should not exceed 24 hours at 25°C or 24 hours in a refrigerator (2°C–8°C), protected from light.

Any unused medicinal product and waste material derived from this medicinal product must be disposed of in accordance with local regulations.

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

Initial reconstitution of romiplostim with the specified volumes of sterile water for injections results in a concentration of 500 mcg/mL in all vial sizes. If the calculated individual patient dose is less than 23 mcg, an additional dilution step to 125 mcg/mL with injection solution of sodium chloride, sterile, preservative-free, 9 mg/mL (0.9%) is required to ensure accurate dosing (see table below).

Dilution guidelines:

Sterile, preservative-free 9 mg/mL (0.9%) sodium chloride injectable solution should be used
only for dilution. Dextrose (5%) in water or sterile water for injectable preparations must not be used for dilution. Other diluents have not been tested.
From a microbiological standpoint, the diluted medicinal product should be used immediately. If not used immediately, the times and conditions of in-use storage prior to use are the responsibility of the user and normally should not exceed 4 hours at 25°C in disposable syringes, or 4 hours in a refrigerator (2°C - 8°C) in the original vials, protected from light.

Package leaflet: Information for the user

Nplate 250 micrograms powder and solvent for injectable solution, 500 micrograms powder and solvent for injectable solution

romiplostim
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 others, even if they have the same symptoms as yours, because it could be dangerous.
• If you experience any side effect, including those not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

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

1. What Nplate is and what it is used for

The active substance in Nplate is romiplostim, a protein used to treat low platelet counts in the blood of patients with primary immune thrombocytopenia, known as ITP. ITP is a condition in which the immune system destroys the body's own platelets. Platelets are blood cells that help heal wounds and form blood clots. A very low platelet count can cause bruising and serious bleeding.
Nplate is used to treat adult patients (aged 18 years and older) with ITP who have either undergone or not undergone splenectomy, and who have previously been treated with corticosteroids or immunoglobulins, in cases where these treatments have not been effective.
Nplate works by stimulating the bone marrow (the part of the bone responsible for producing blood cells) to produce a greater number of platelets. This should help prevent the bruising and bleeding associated with ITP.

2. What you need to know before using Nplate

Do not use Nplate
if you are allergic to romiplostim or to any of the other ingredients of this medicine
(listed in section 6).
if you are allergic to other medicines produced using DNA technology that use the bacterium
Escherichia coli (E. coli).

Warnings and precautions
If you stop taking Nplate, your platelet count is likely to become low again (thrombocytopenia). If you discontinue Nplate, your doctor will monitor your platelet count periodically and discuss with you the most appropriate precautionary measures to take.

If you are at risk of blood clots or have a family history of thrombosis, your risk of thrombosis may be increased if you:

• have liver problems;
• are elderly (over 65 years of age);
• are bedridden;
• have cancer;
• are taking oral contraceptives or hormone replacement therapy;
• have recently undergone surgery or sustained an injury;
• are obese (overweight);
• are a smoker.
  Please consult your doctor before taking Nplate if you have any of these conditions.

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

Bone marrow changes (increased reticulin and possible bone marrow fibrosis)
Long-term use of Nplate may cause changes in the bone marrow. These changes may lead to abnormalities in blood cells or reduced production of blood cells.
A mild form of these bone marrow changes, called “increased reticulin,” has been observed in clinical studies with Nplate. It is not known whether this may progress to a more severe condition called “fibrosis.” Signs of bone marrow changes may appear as abnormalities in blood tests. Your doctor will decide whether abnormal blood test results mean you need a bone marrow test or whether you should stop taking Nplate.

Worsening of blood cancers
Your doctor may decide to perform a bone marrow biopsy if they consider it necessary to confirm that you have ITP and not another condition such as myelodysplastic syndrome (MDS). If you have MDS and receive Nplate, you may experience an increase in malignant blood cells, and MDS may worsen and progress to acute myeloid leukemia, a type of blood cancer.

Loss of response to romiplostim
If you experience a loss of response or inability to maintain a platelet response during treatment with romiplostim, your doctor will investigate the reasons, considering both possible increases in bone marrow fibres (reticulin) and whether 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 medicines and Nplate
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

If you are also taking medicines that prevent blood clots (anticoagulant or antiplatelet therapy), your risk of bleeding may be higher. Your doctor will discuss this with you.

If you are taking corticosteroids, danazol, and/or azathioprine—medicines you may receive to treat ITP—your doctor may reduce the dose or discontinue them when used together with Nplate.

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, ask your doctor or pharmacist for advice before taking this medicine.
The use of Nplate is not recommended during pregnancy unless specifically indicated by your doctor.
It is not known whether romiplostim is excreted in human breast milk. The use of Nplate is not recommended during breastfeeding. The decision whether to discontinue breastfeeding or to stop treatment with romiplostim should be based on the benefits of breastfeeding for the child and the benefits of romiplostim therapy for you.

Driving and using machines
Consult your doctor before driving or operating machinery, as certain side effects (e.g., transient episodes of dizziness) may impair your ability to do so safely.

3. How to use Nplate

Nplate will be administered under the direct supervision of your doctor, who will closely monitor the amount of Nplate you are given.
Nplate is administered once weekly as a subcutaneous injection (under the skin).
The initial dose is 1 microgram of Nplate per kilogram of body weight, given once a week. Your doctor will inform you of the amount of Nplate to be administered. Nplate must be injected once a week to maintain an adequate platelet count in the blood. Your doctor will regularly take blood samples to monitor how your platelets are responding and, if necessary, will adjust the dose accordingly.
Once the platelet count is under control, your doctor will continue to perform regular blood tests. The dose may be further adjusted to maintain long-term control of the platelet count in the blood.
Always use Nplate exactly as instructed by your doctor. If you have any doubts, consult your doctor or pharmacist if you are unsure about how to use Nplate.

Instructions for preparing and administering an injection of Nplate
After appropriate training, your doctor may allow you to self-inject Nplate. As discussed with your doctor, please read the instructions at the end of this leaflet on how to inject Nplate. If your doctor has permitted you to perform self-injection, you must be monitored monthly by your doctor so that they can determine whether Nplate is effective for you or whether another treatment should be considered.
After the first month of self-injecting Nplate, you will be required to demonstrate that you are still able to correctly prepare and administer the injection.

If you use more Nplate than you should
Your doctor will ensure that you receive the correct amount of Nplate. If you have taken a higher dose of Nplate than you should have, you may not experience any symptoms, but your platelet count could rise to high levels, which may increase the risk of blood clotting. Therefore, if your doctor suspects that you have taken more Nplate than you should, monitoring for signs or symptoms of adverse effects is recommended, and appropriate treatment should be administered immediately.
If your doctor has allowed you to self-inject and you have used 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 been given less Nplate than you should have received, you may not experience physical symptoms, but your platelet count could decrease, which may increase the risk of bleeding. Therefore, if your doctor suspects that you have received less Nplate than required, monitoring for any signs or symptoms of adverse effects is recommended, and appropriate treatment should be administered immediately.
If your doctor has allowed you to self-inject and you have used less Nplate than you should, inform your doctor immediately.

If you forget to use Nplate
If you have missed a dose of Nplate, your doctor will discuss with you when the next dose should be administered.
If your doctor has allowed you to self-inject and you forget to give yourself the injection, inform your doctor immediately.

If you stop using Nplate
If you stop taking Nplate, thrombocytopenia (low platelet count in the blood) is likely to recur. Your doctor will decide whether you should stop using Nplate.

Self-injecting Nplate
Your doctor may decide that it is best for you to self-inject Nplate. Your doctor, nurse, or pharmacist will show you how to self-inject Nplate. Do not attempt to self-inject Nplate unless you have received adequate training. It is very important that you properly prepare Nplate and administer the correct dose (see section 7. Instructions for preparing and administering an injection of Nplate, at the end of this leaflet).

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets 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, increase in bone marrow fibres (reticulin);
• insomnia;
• dizziness;
• tingling or numbness in hands and feet (paraesthesia);
• migraine;
• skin redness (flushing);
• blood clot in the pulmonary artery (pulmonary embolism);
• nausea;
• diarrhoea;
• abdominal pain;
• indigestion (dyspepsia);
• constipation;
• itching (pruritus);
• bleeding under the skin (ecchymosis);
• bruising (contusions);
• rash;
• joint pain (arthralgia);
• muscle pain or weakness (myalgia);
• pain in hands and feet;
• muscle spasm;
• back pain;
• bone pain;
• fatigue (tiredness);
• injection site reactions;
• swelling of hands and feet (peripheral oedema);
• flu-like symptoms (influenza);
• pain;
• weakness (asthenia);
• fever (pyrexia);
• chills;
• contusion;
• swelling of the face, lips, mouth, tongue or throat which may cause difficulty in swallowing or breathing (angioedema);
• gastroenteritis;
• palpitations;
• inflammation of the sinuses (sinusitis);
• inflammation of the airways leading to the lungs (bronchitis);
• blood clot in veins (deep vein thrombosis).

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

• low platelet count in the blood (thrombocytopenia) and low platelet count in the blood (thrombocytopenia) after stopping Nplate;
• platelet count higher than normal (thrombocytosis);
• anaemia.

Uncommon: may affect up to 1 in 100 people

• inability of the bone marrow to produce normal numbers of blood cells (bone marrow failure);
• changes in the bone marrow leading to fibrosis (myelofibrosis);
• enlargement of the spleen (splenomegaly);
• vaginal bleeding;
• rectal bleeding;
• mouth bleeding;
• bleeding at injection site;
• heart attack (myocardial infarction);
• increased heart rate;
• vertigo or sensation of spinning;
• eye disorders including: bleeding in the eye (conjunctival haemorrhage); blurred vision or difficulty focusing (accommodation disorders, papilloedema or eye disorders); blindness; eye itching; increased tear production; or visual disturbances;
• gastrointestinal problems including: vomiting; bad breath (halitosis); difficulty swallowing (dysphagia); indigestion or heartburn (gastroesophageal reflux disease); blood in stool (haematochezia); gastric disturbances; mouth ulcers or canker sores (stomatitis); tooth discoloration;
• weight loss; weight gain; alcohol intolerance; loss of appetite (anorexia or decreased appetite); dehydration;
• general malaise; chest pain; irritability; facial swelling (facial oedema); hot flushes; fever; jaundice;
• influenza; localized infection; inflammation of nasal passages and throat (nasopharyngitis);
• nose and throat problems including: cough; runny nose (rhinorrhoea); dry throat; shortness of breath or difficulty breathing (dyspnoea); nasal congestion; painful breathing;
• joint pain and swelling caused by uric acid (a by-product of food metabolism) (gout);
• muscle tension; muscle weakness; shoulder pain; muscle fasciculations;
• nervous system disorders including involuntary muscle contractions (clonus); altered taste (dysgeusia); reduced sense of taste (hypogeusia); reduced sensation, especially of the skin (hypoesthesia); nerve dysfunction in arms and legs (peripheral neuropathy); blood clot in the cerebral venous system (transverse sinus thrombosis);
• depression; abnormal dreams;
• hair loss (alopecia); sensitivity to light (photosensitivity reactions); acne; skin allergy after contact with an allergen (contact dermatitis); skin manifestations with rash and blisters (eczema); dry skin; red skin (erythema); severe peeling or shedding of the skin (exfoliative rash); abnormal hair growth; thickening and itching of the skin due to repeated scratching (pruritus); bleeding under the skin or bruising (purpura); irregular skin rash (papular rash); itchy skin rash (pruritic rash); generalized itchy rash (urticaria); skin bump (skin nodule); unpleasant odour of the skin (abnormal skin odour);
• circulatory problems including blood clots in the liver vein (portal vein thrombosis); low blood pressure (hypotension); increased blood pressure; blockage of blood vessels (peripheral embolism); reduced blood flow to hands, ankles or feet (peripheral ischaemia); swelling and clotting in a vein, which may be extremely painful when touched (phlebitis or superficial thrombophlebitis); blood clot (thrombosis);
• a rare condition characterized by episodes of burning pain, redness and increased temperature in the hands and feet (erythromelalgia).

Uncommon: may affect up to 1 in 100 people (may be detected during urine or blood tests)

• a rare type of anaemia in which red blood cells, white blood cells and platelets are all reduced in number (aplastic anaemia);
• increased number of white blood cells (leucocytosis);
• excessive platelet production (thrombocythaemia); increased number of platelets; abnormal number of blood cells that prevent bleeding (abnormal platelet count);
• changes in certain blood tests (increased transaminases; increased lactate dehydrogenase);
• tumour of white blood cells (multiple myeloma);
• protein in urine.

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

5. How to store Nplate

Keep out of the sight and reach of children.
Do not use this medicinal product after the expiry date stated on the vial label after
EXP. The expiry date refers to the last day of that month.
Store in a refrigerator (2°C - 8°C).
Do not freeze.
Store in the original packaging to protect from light.
This medicinal product may be removed from the refrigerator and stored at
room temperature (up to 25°C) for a maximum of 30 days, provided it is kept in the
original packaging.
Do not dispose of medicines 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 Nplate contains

• The active substance is romiplostim.

Each 250 microgram vial of Nplate for injectable solution contains a total of 375 micrograms of romiplostim. An additional amount is included to ensure the availability of 250 micrograms of romiplostim in each vial. After reconstitution, an extractable volume of 0.5 mL of solution contains 250 micrograms of romiplostim (500 micrograms/mL).
Each 500 microgram vial of Nplate for injectable solution contains a total of 625 micrograms of romiplostim. An additional amount is included to ensure the availability of 500 micrograms of romiplostim in each vial. After reconstitution, an extractable volume of 1 mL of solution contains 500 micrograms of romiplostim (500 micrograms/mL).

• The other components are:
  Powder: mannitol (E421), sucrose, L-histidine, hydrochloric acid (for pH adjustment), and polysorbate 20.
  Solvent: water for injections.

Description of the appearance of Nplate and contents of the pack
Nplate is a white powder for injectable solution supplied in a single-dose 5 mL glass vial.
Nplate is supplied as a pack containing 1 piece or a multiple pack containing 4 pieces. Each pack contains:
1 vial containing 250 micrograms or 500 micrograms of romiplostim.
1 pre-filled syringe containing 0.72 mL or 1.2 mL of water for injections.
1 plunger for the pre-filled syringe.
1 sterile vial adapter.
1 sterile 1 mL syringe with Luer lock connector.
1 sterile safety needle.
4 alcohol swabs.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Amgen Europe B.V.
Minervum 7061
4817 ZK Breda
The Netherlands

Marketing Authorisation Holder
Amgen Europe B.V.
Minervum 7061
4817 ZK Breda
The Netherlands

Manufacturer
Amgen Technology (Ireland) Unlimited Company
Pottery Road
Dun Laoghaire
Dublin
Ireland

Manufacturer
Amgen NV
Telecomlaan 5-7
1831 Diegem
Belgium

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder.

België/Belgique/Belgien Lietuva
s.a. Amgen n.v. Amgen Switzerland AG Vilniaus filialas
Tél/Tel: +32 (0)2 7752711 Tel: +370 5 219 7474

България Luxembourg/Luxemburg
Амджен България ЕООД s.a. Amgen
Тел.: +359 (0)2 424 7440 Belgique/Belgien
Tél/Tel: +32 (0)2 7752711

Česká republika Magyarország
Amgen s.r.o. Amgen Kft.
Tel: +420 221 773 500 Tel.: +36 1 35 44 700

Danmark Malta
Amgen, filial af Amgen AB, Sverige Amgen S.r.l.
Tlf.: +45 39617500 Italy
Tel: +39 02 6241121

Deutschland Nederland
Amgen GmbH Amgen B.V.
Tel.: +49 89 1490960 Tel: +31 (0)76 5732500

Eesti Norge
Amgen Switzerland AG Vilniaus filialas Amgen AB
Tel: +372 586 09553 Tlf: +47 23308000

Ελλάδα Österreich
Amgen Ελλάς Φαρμακευτικά Ε.Π.Ε. Amgen GmbH
Τηλ: +30 210 3447000 Tel: +43 (0)1 50 217

España Polska
Amgen S.A. Amgen Biotechnologia Sp. z o.o.
Tel: +34 93 600 18 60 Tel.: +48 22 581 3000

France Portugal
Amgen S.A.S. Amgen Biofarmacêutica, Lda.
Tél: +33 (0)9 69 363 363 Tel: +351 21 4220606

Hrvatska România
Amgen d.o.o. Amgen România SRL
Tel: +385 (0)1 562 57 20 Tel: +4021 527 3000

Ireland Slovenija
Amgen Ireland Limited AMGEN zdravila d.o.o.
Tel: +353 1 8527400 Tel: +386 (0)1 585 1767

Ísland Slovenská republika
Vistor hf. Amgen Slovakia s.r.o.
Sími: +354 535 7000 Tel: +421 2 321 114 49

Italia Suomi/Finland
Amgen S.r.l. Amgen AB, sivuliike Suomessa/Amgen AB, filial i Finland
Tel: +39 02 6241121 Puh/Tel: +358 (0)9 54900500

Kύπρος Sverige
C.A. Papaellinas Ltd Amgen AB
Τηλ: +357 22741 741 Tel: +46 (0)8 6951100

Latvija
Amgen Switzerland AG Rīgas filiāle
Tel: +371 257 25888

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

7. Instructions for preparing and administering an injection of Nplate

This section contains information on how to self-inject Nplate. It is important that you do not attempt
to administer the injection without having received training from your doctor, nurse, or
pharmacist. If you have any questions about how to administer the injection, contact your doctor, nurse, or
pharmacist for assistance. It is very important that the product is prepared correctly and that the
correct dose is administered.
This section is divided into the following subsections:
Before you begin
Step 1. Prepare the materials for an injection
Step 2. Prepare the vial for use, attach the vial adapter
Step 3. Prepare the syringe with sterile water
Step 4. Reconstitute Nplate by injecting water into the vial
Step 5. Prepare a new syringe for injection
Step 6. Prepare the injection needle
Step 7. Choose and prepare an injection site
Step 8. Inject the liquid Nplate
Step 9. Dispose of waste
Before you begin
Read all the instructions carefully. These instructions are intended for patients who have already
received training on how to perform self-injection from their healthcare provider, such as a doctor, nurse, or
pharmacist. If you have not received training, contact your healthcare provider.
The Nplate self-injection kit must be stored in its original packaging until use to protect the Nplate vial from light. Keep the Nplate self-injection kit refrigerated at 2°C to 8°C.
Once Nplate has been reconstituted, administer the injection immediately.
After administering the prescribed dose, there may be excess Nplate remaining. Do not reuse Nplate! Any excess reconstituted Nplate must be discarded immediately at the end of the injection process. Reconstituted Nplate remaining in the vial must NEVER be reused for another injection.
Step 1. Prepare the materials for an injection
Do the following:

• Choose a well-lit, flat work surface, such as a table.
• Remove the Nplate self-injection kit from the refrigerator. Do not use if it has been frozen. If you have any questions regarding storage, contact your healthcare provider for further instructions. Check the expiration date on the self-injection kit. If the expiration date has passed, do not use it. Stop and contact your healthcare provider.
• Note: If your healthcare provider has informed you that your Nplate dosage requires more than one Nplate injection, you will need to use more than one self-injection kit. Follow the steps as described in this leaflet and use as many self-injection kits as necessary to achieve the prescribed Nplate dose.
• Make sure you have the following items:

Pack of 4 alcohol swabs

1 vial of powder, 250 micrograms or 1 vial adapter, 13 mm
500 micrograms

1 plunger for the prefilled syringe with water 1 prefilled syringe with sterile water
sterile

1 syringe with 1 mL screw fitting (Luer lock) 1 safety needle for injection

• Do not open items until instructed to do so.
• Do not use components showing signs of tampering or damage.
• Do not reuse items.

Step 2. Prepare the vial for use, attach the vial adapter
Using: 2 alcohol swab packets, 1 vial, and 1 vial adapter.
Do the following:

Wash your hands with soap and warm water.

• Clean the flat working surface with a new alcohol swab.
• Remove the red plastic cap (250 micrograms) or blue (500 micrograms) from the vial.

Using a new alcohol swab,
clean the vial stopper.

• Do not touch the vial stopper after cleaning.

Slowly peel off the protective paper
from the vial adapter while holding
the vial adapter in the
plastic packaging.

• Do not touch the vial stopper or the tip of the vial adapter.

• Holding the vial on a table, and keeping the vial adapter in its plastic wrapper, align the tip of the vial adapter to the center of the vial stopper.

Push down the vial adapter onto the
vial until it is firmly in place and
cannot be pushed further down.

Leave the vial adapter’s plastic wrapper
over the vial.

• Do not touch the tip of the vial adapter.

Step 3. Prepare the syringe with sterile water
Using: Pre-filled syringe with sterile water and plunger.
Before starting Step 3, please note:

• The transparent plastic plunger MUST always be attached just before breaking the white tip of the pre-filled syringe with sterile water. Perform Step 3a before Step 3b.

Do the following:

Step 3a: Attach the plunger to the
pre-filled syringe with sterile water,
by placing the threaded end of the plunger into the syringe and gently rotating it until you feel slight resistance. Do not overtighten.

• Step 3b: Holding the syringe with one hand, bend downward the tip of the white plastic cap with the other hand. This will break the seal of the white plastic cap.

Once the seal is broken, remove the
white plastic cap. You will see gray
rubber in the stopper.
Step 4. Reconstitute Nplate by injecting water into the vial
Using: Pre-filled syringe with sterile water and a vial with attached vial adapter.
Before starting Step 4, note that:

• Reconstitute slowly and gently. This is a protein product and proteins can be easily damaged by improper mixing or excessive agitation.

Do the following:

• Holding the vial on the table, attach the pre-filled syringe of water to the vial adapter, using one hand to hold the outer edge of the vial adapter and the other hand to turn the syringe tip clockwise onto the adapter until you feel slight resistance.

Very slowly and gently push
the plunger down to inject
all the water from the syringe into the vial.
The water should flow slowly onto the powder.

• Do not force water into the vial.
• Note: After injecting water into the vial, it is common for the plunger to retract slightly. You do not need to maintain pressure on the plunger for the remainder of Step 4. Push slowly and gently.

Before continuing:

• Ensure that all water from the syringe has been injected into the vial before reconstitution.

• Hold between your fingers the area connecting the vial and the vial adapter, gently rotate the vial by turning your wrist until all the powder is dissolved and the liquid in the vial is clear and colorless.
• Rotate the vial slowly. Correct
• Do not shake the vial.

• Do not roll the vial between the palms of your hands.
• Note: Complete dissolution of the powder may take up to 2 minutes.

Incorrect
Before continuing:

• Visually inspect the reconstituted liquid for the presence of particles and/or discoloration. It should be clear, colorless, and completely dissolved.
• Note: If discoloration or particles are observed in the liquid, contact healthcare personnel.
• Ensure that the liquid is completely dissolved before removing the syringe.

When Nplate is completely dissolved,
remove the empty syringe from the
vial adapter by rotating it
counterclockwise.

• Dispose of the empty syringe in a sharps or hazardous waste container. Keep the reconstituted Nplate vial. Immediately prepare a new syringe for injectable preparation.
• Do not delay the injection of Nplate.

Step 5. Prepare a new syringe for injection
Using: A new 1 mL syringe from its packaging and the reconstituted, clear Nplate vial.
Before continuing:

• Check your dosage before starting this step.
• Note: Nplate liquid is very potent; therefore, accurate dose calculation and measurement are important.
• Ensure all air bubbles are removed before injection.

Do the following:

Remove the 1 mL syringe
from its packaging.

• Draw air into the syringe up to the 1 mL mark.
• Do not pull the plunger beyond 1 mL.

Draw air into the syringe up to the 1 mL mark

• Attach the 1 mL syringe to the vial adapter of the reconstituted Nplate by turning the syringe tip clockwise onto the vial adapter until you feel slight resistance.

A. Push air into the vial.
B. Maintain pressure on the plunger.
C. Invert the assembled unit
vial-syringe, so that the vial is directly above the syringe.
A. B. C.
Invert

• Withdraw the entire liquid volume into the syringe.
  • The maximum extractable volume is 0.5 mL for the 250 microgram vial and 1 mL for the 500 microgram vial.
• Do not detach the plunger from the back of the syringe.

Ensure that the plunger remains in the syringe.
Correct

• Check and remove all air bubbles from the syringe.
  • Gently tap the syringe with your fingers to dislodge bubbles from the liquid.
  • Slowly push the plunger upward to expel air bubbles from the syringe.

Air bubbles: Correct
Incorrect

• Slowly pull the plunger to fill the syringe with only the amount prescribed by the healthcare provider.
• Ensure that the top of the plunger head is aligned with the syringe mark indicating the prescribed dose. If needed, return liquid to the vial to achieve the desired dose.

Ensure the content matches the
prescribed dose

• Perform a final check to confirm the correct amount of liquid is in the syringe and that all air bubbles have been removed.

Before continuing:

• Ensure the correct amount of liquid for your dose remains in the syringe.
• Ensure all air bubbles have been removed from the syringe.

Once all air bubbles are removed and the syringe is filled with the correct dose, remove
the syringe from the vial adapter.

Hold the filled syringe in your hand and
do not touch the syringe tip.

• Do not hold the filled syringe upside down after removing it from the vial.

Step 6. Prepare the needle for injection
Using: Pre-filled syringe with a measured dose of Nplate and safety needle.
Do the following:

Holding the syringe in your palm with
the tip pointing upward, remove the safety
needle from its packaging.

Attach the safety needle to the filled syringe. Apply firm pressure while rotating to attach the safety needle to the syringe. Turn clockwise to lock it into the Luer lock fitting.

• The product is now ready for injection. IMMEDIATELY proceed to Step 7.

Step 7. Choose and prepare an injection site
Using: A new alcohol swab.
Do the following:
Injection site

• Select the injection site. The three recommended injection sites for Nplate are:

• The central front area of the thighs
• The abdomen, except for the 5 cm area around the navel
• If someone is assisting you with the injection, the outer upper arm may also be used
• Change the site for each injection Front Back
• Do not inject into areas where the skin is tender, bruised, or hard.

• Do not inject into areas with scars or stretch marks.
• Disinfect the site where Nplate will be injected using an alcohol swab with a circular motion.
• Do not touch this area again before administering the injection.

Step 8. Inject liquid Nplate
Using: Assembled unit of filled syringe and needle.
Do the following:

Fold back the pink safety cap
(toward the syringe and away from the needle).

• Remove the transparent needle protector by holding the syringe in one hand and carefully pulling off the protector with the other hand.
• Remove the transparent needle protector before injection.

With one hand, gently pinch the disinfected
area of skin and hold it firmly. With the other hand, hold the syringe (like a pencil) at a 45-degree angle to the skin.

• With a quick, short motion, push the needle into the skin.
• Inject the prescribed dose under the skin as directed by your doctor, nurse, or pharmacist.

When the syringe is empty, withdraw the needle from the skin, taking care to
maintain the same angle
as during insertion.

• There may be minor bleeding at the injection site. You may apply a cotton ball or gauze pad to the site for 10 seconds.
• Do not rub the injection site. If needed, you may cover the injection site with a bandage.

After the injection, use your thumb (or fingertip) to activate the pink safety cap by pushing it forward with the same hand until you hear/feel a click and the needle is locked.

• Visually confirm that the needle tip is covered. Before disposal, always cover the needle with the pink safety cap.

Step 9. Dispose of waste
Do the following:

• Immediately dispose of the syringe with covered needle into a sharps container.
• Immediately dispose of the used Nplate vial into an appropriate waste container.
• Ensure all other materials are disposed of in appropriate containers.

The injection device and Nplate vial must NEVER be reused.

• Dispose of used needles and syringes in a puncture-resistant container.
• Dispose of any unused Nplate in an appropriate waste container. Unused Nplate in the vial must NEVER be reused for another injection.