Nplate 250 micrograms powder for injection solution

Package leaflet: Information for the user

Introduction

Package leaflet: 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 all of this leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet, as 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, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.

• If you experience any side effects, talk to your doctor, pharmacist or nurse, even if they are side effects not listed in this leaflet. 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 in Nplate is romiplostim, a protein used to treat low platelet counts in patients with primary immune thrombocytopenia (ITP). ITP is a condition in which your 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 serious bruising and bleeding.

Nplate is used in adult patients with ITP who may or may not have had their spleen removed and who have previously been treated with corticosteroids or immunoglobulins that did not work. Nplate is also used in children aged 1 year and older with chronic ITP who may or may not have had their spleen removed and who have previously been treated with corticosteroids or immunoglobulins that were ineffective.

Nplate works by stimulating the bone marrow (the part of the bone responsible for producing blood cells) to produce more platelets. This should help prevent 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 uses the microorganism 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 platelet count will need to be monitored, and your doctor will advise you on appropriate precautions.
• If you are at risk of developing blood clots or if blood clots run in your family. The risk of blood clots may also be increased if:
  • you have liver problems;
  • you are an elderly person (≥ 65 years);
  • you are bedridden;
  • you have cancer;
  • you are taking contraceptive pills or hormone replacement therapy;
  • you have recently undergone surgery or suffered an injury;
  • you are obese (overweight);
  • you are a smoker.

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

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

Changes in bone marrow (increased reticulin and possible bone marrow fibrosis)

Long-term use of Nplate may cause changes in your bone marrow. These changes may lead to abnormal blood cells or reduced production of blood cells. A mild form of these bone marrow changes is called "increased reticulin," which has been observed in clinical trials of Nplate. It is unknown whether this may progress to a more severe condition called "fibrosis." Abnormal blood test results may show signs of bone marrow changes. Your doctor will decide whether an abnormal blood test means that a bone marrow examination should be performed or whether treatment with Nplate should be discontinued.

Worsening of blood cancer

Your doctor may decide to perform a bone marrow biopsy if it is 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 blast cell count and worsening of MDS, which could progress to acute myeloid leukemia, a type of blood cancer.

Loss of response to romiplostim

If you lose response to romiplostim or are unable to maintain a platelet response during treatment with romiplostim, your doctor will investigate the reasons, including whether you are developing increased bone marrow fibers (reticulin) or have developed antibodies that neutralize the activity of romiplostim.

Children and adolescents

The use of Nplate is not recommended 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 need to take any other medicines.

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

If you are taking corticosteroids, danazol, and/or azathioprine, which you may be receiving to treat your ITP, your doctor may need to reduce or discontinue these medications when used in combination with Nplate.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before using this medicine. Nplate is not recommended during pregnancy unless specifically advised by your doctor.

It is unknown whether romiplostim is excreted in human milk. The use of Nplate during breastfeeding is not recommended. The decision to discontinue breastfeeding or to discontinue romiplostim treatment should take into account the benefits of breastfeeding for the infant and the benefits of romiplostim treatment for the patient.

Driving and using machines

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

3. How to use Nplate

Adults and children (1 to 17 years of age):

Nplate must be administered under the direct supervision of a physician who will carefully control the amount of Nplate given.

Nplate is administered once weekly by subcutaneous injection (under the skin).

The starting dose is 1 microgram of Nplate per kilogram of body weight once weekly. Your doctor will determine the amount of Nplate you should use. Nplate should be injected once weekly to maintain platelet counts. Your doctor will take blood samples regularly to assess how your platelets are responding and to adjust the dose if necessary.

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

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

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 have, you may not experience any physical symptoms, but your blood platelet levels may rise to very high levels, which may increase the risk of blood clots. Therefore, if your doctor suspects that you have received too much Nplate, you should be monitored for any signs or symptoms of side effects and appropriate treatment should be administered 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 have, you may not experience any physical symptoms, but your blood platelet levels may drop to low levels, which may increase the risk of bleeding. Therefore, if your doctor suspects that you have received less Nplate than you should have, you should be monitored for any signs or symptoms of side effects and appropriate treatment should be administered immediately.

If you forget to use Nplate

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

If you stop using Nplate

If you stop using Nplate, you are likely to develop a low platelet count again (thrombocytopenia). Your doctor will decide whether you should stop taking Nplate.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone gets them.

Possible adverse 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, including increase in bone marrow fibres (reticulin);
• difficulty sleeping (insomnia);
• dizziness;
• tingling or numbness in the hands or feet (paraesthesia);
• migraine;
• skin redness (flushing);
• blood clot in an artery of the lung (pulmonary embolism);
• nausea;
• diarrhoea;
• abdominal pain;
• indigestion (dyspepsia);
• constipation;
• itching of the skin (pruritus);
• bleeding under the skin (ecchymosis);
• bruising (contusion);
• skin rash;
• joint pain (arthralgia);
• muscle pain or weakness (myalgia);
• pain in hands and feet;
• muscle spasm;
• back pain;
• bone pain;
• tiredness (fatigue);
• reaction at injection site;
• swelling in hands and feet (peripheral oedema);
• flu-like symptoms (influenza-like illness);
• pain;
• weakness (asthenia);
• fever (pyrexia);
• chills;
• bruising;
• 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 leading to the lungs (bronchitis);
• blood clotting in veins (deep vein thrombosis).

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

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

Uncommon: may affect up to 1 in 100 people

• bone marrow disorder; disorder of the bone marrow causing scarring (myelofibrosis); enlargement of the spleen (splenomegaly); vaginal bleeding (vaginal haemorrhage); bleeding from the rectum (rectal haemorrhage); bleeding from the mouth (oral haemorrhage); bleeding at injection site (injection site haemorrhage);
• heart attack (myocardial infarction); increased heart rate;
• dizziness or spinning sensation (vertigo);
• eye problems including: bleeding in the eyes (conjunctival haemorrhage); difficulty focusing or blurred vision (visual accommodation disorder, papilloedema or eye disorder); blindness; itching in the eyes (ocular pruritus); increased tearing (increased lacrimation); or visual disturbances;
• digestive system problems including: vomiting; bad breath (halitosis); difficulty swallowing (dysphagia); indigestion or heartburn (gastroesophageal reflux disorder); blood in stools (haematochezia); stomach discomfort; mouth ulcers or blisters in the mouth (stomatitis); discoloured teeth (dental discolouration);
• weight loss; weight gain; alcohol intolerance; loss of appetite (anorexia or decreased appetite); dehydration;
• general feeling of discomfort (malaise); chest pain; irritability; facial swelling (facial oedema); sensation of heat; increased body temperature; nervous sensation;
• flu; localized infection; inflammation of the nose 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 (painful respiration);
• painful swollen joints caused by uric acid (breakdown product of food) (gout);
• muscle stiffness; muscle weakness; shoulder pain; muscle contractions;
• nervous system problems including involuntary muscle contractions (clonus); distorted sense of taste (dysgeusia); reduced sense of taste (hypogeusia); sensation of reduced sensitivity, especially in the skin (hypoesthesia); nerve function disorders 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 skin reaction due to contact with allergens (contact dermatitis); skin manifestations with rash and blisters (eczema); dry skin; skin redness (erythema); severe peeling or exfoliative rash (exfoliative rash); abnormal hair growth; thickening and itching of the skin due to repeated scratching (prurigo); bleeding under the skin surface or bruising under the skin (purpura); itchy skin rash (papular rash); itchy skin rash (pruritic rash); generalized itchy rash (urticaria); skin lump (skin nodule); abnormal odour of the skin (abnormal skin odour);
• circulation problems including blood clots in the liver vein (portal vein thrombosis); low blood pressure (hypotension); increased blood pressure; blockage of a blood vessel (peripheral embolism); reduced blood flow in hands, ankles or feet (peripheral ischaemia); swelling and clotting in a vein, which may feel extremely soft to touch (phlebitis or superficial thrombophlebitis); blood clotting (thrombosis);
• a rare condition characterized by episodes of burning pain, redness and warmth in the feet and hands (erythromelalgia).

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

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

Possible adverse 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);
• itching, runny nose or blocked nose (rhinitis);
• cough;
• pain in the upper abdomen;
• diarrhoea;
• rash;
• fever (pyrexia);
• bruising (contusion).

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 in 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

• higher than normal platelet count (thrombocytosis).

Reporting of adverse effects

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

5. Storage of Nplate

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

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

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

Do not freeze.

Store in the original packaging to protect from light.

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

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Nplate

• The active substance is romiplostim.

Each vial of Nplate 125 micrograms powder for injectable solution 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 reconstitution, a final product volume of 0.25 ml of solution contains 125 micrograms of romiplostim (500 micrograms/ml).

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 reconstitution, a final product volume of 0.5 ml of 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 reconstitution, a final product 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 polysorbate 20.

Nature of the medicinal product and contents of the container

Nplate is a white powder for injectable solution 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 certain pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder and Manufacturer:

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

Marketing Authorization Holder

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

Manufacturer

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

Manufacturer

Amgen NV
Telecomlaan 5-7
1831 Diegem
Belgium

Further information on this medicinal product is available upon request by contacting the local representative of the Marketing Authorization Holder.

Date of the most recent review of this leaflet:

Other sources of information

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

This information is intended for healthcare professionals only:

Reconstitution:

Nplate is a sterile, preservative-free product intended for single use. Nplate must be reconstituted following good aseptic practice.

• Nplate 125 micrograms powder for solution for injection must be reconstituted with 0.44 ml of sterile water for injection to yield a final volume of 0.25 ml. Each vial contains an overage to ensure that 125 µg of romiplostim can be administered (see the table below on vial content).

• Nplate 250 micrograms powder for solution for injection must be reconstituted with 0.72 ml of sterile water for injection to yield a final volume of 0.5 ml. Each vial contains an overage to ensure that 250 µg of romiplostim can be administered (see the table below on vial content).

• Nplate 500 micrograms powder for solution for injection must be reconstituted with 1.2 ml of sterile water for injection to yield a final volume of 1 ml. Each vial contains an overage to ensure that 500 µg of romiplostim can be administered (see the table below on vial content).

Vial content:

Sterile water for injectable preparations must be used only to reconstitute the medication. Sodium chloride solutions or bacteriostatic water must not be used for reconstitution.

Water for injectable preparations should be injected into the vial. During dissolution, gently swirl the vial and invert it several times. Do not shake or vigorously agitate the vial. Dissolution of Nplate usually takes less than 2 minutes. Visually inspect the solution for particles or discoloration prior to administration. The reconstituted solution should be clear and colorless; do not administer if particles or discoloration are observed.

From a microbiological standpoint, the medication should be used immediately. If not used immediately, the storage times and conditions prior to use are the responsibility of the user and must not exceed 24 hours at 25°C or 24 hours under refrigeration (between 2°C and 8°C), protected from light.

Disposal of unused medication and all materials that have come into contact with it must be carried out in accordance with local regulations.

Dilution (required when the patient's individual dose calculation is less than 23 µg).

Initial reconstitution of romiplostim with the designated volumes of sterile water for injectable preparations results in a concentration of 500 µg/mL in all vial sizes. If the patient's individual dose calculation is less than 23 µg, an additional dilution step is required to achieve a concentration of 125 µg/mL using sterile, preservative-free 9 mg/mL (0.9%) sodium chloride injectable solution, to ensure accurate dosing (see table below).

Dilution guidelines:

Sodium chloride 9 mg/ml (0.9%) sterile solution for injection, free from preservatives, should only be used for dilution. It should not be used for diluting dextrose (5%) in water or sterile water for injectable preparations. No other diluent has been tested.

From a microbiological standpoint, the diluted medicinal product should be used immediately. If not used immediately, the storage times and conditions of use prior to administration 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 refrigerated (between 2°C and 8°C), protected from light.