Nplate 250 micrograms powder and solvent for solution for injection (Reconstitution Pack)

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

1. What Nplate is and what it is used for
2. What you need to know before you use 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 giving an injection of Nplate

• if you are allergic to romiplostim or any of the other ingredients of this medicine (listed in section 6).
• if you are allergic to other medicines that are produced by DNA technology using the micro-organism Escherichia coli (E. coli).

• If you stop taking Nplate a low blood platelet count (thrombocytopenia) is likely to reoccur. If you stop taking Nplate your platelet count will have to be monitored, and your doctor will discuss appropriate precautions with you.
• If you are at risk of blood clots or if blood clots are common in your family. The risk of blood clotting may also be increased if you:
  • have liver problems;
  • are elderly (≥ 65 years);
  • are bedridden;
  • have cancer;
  • are taking the contraceptive pill or hormone replacement therapy;
  • have recently had surgery or suffered an injury;
  • are obese (overweight);
  • are a smoker.

Talk to your doctor, pharmacist or nurse before using Nplate.

If you have very high blood platelet counts this may increase the risk of blood clotting. Your doctor will adjust your dose of Nplate to ensure that your platelet count does not become too high.

Bone marrow changes (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 your body making less blood cells. The mild form of these bone marrow changes is called “increased reticulin” and has been observed in Nplate clinical trials. It is not known if this may progress to a more severe form called “fibrosis.” Signs of bone marrow changes may show up as abnormalities in your blood tests. Your doctor will decide if abnormal blood tests mean that you should have bone marrow tests or if you should stop taking Nplate.

Worsening of blood cancers

Your doctor may decide to take a bone marrow biopsy if they decide it is necessary to ensure that you have ITP, and not another condition such as Myelodysplastic Syndrome (MDS). If you have MDS and receive Nplate you may have an increase in your blast cell counts and your MDS condition may worsen to become an acute myeloid leukaemia, which is a type of cancer of the blood.

Loss of response to romiplostim

If you experience a loss of response or failure to maintain a platelet response with romiplostim treatment, your doctor will investigate the reasons why including whether you are experiencing increased bone marrow fibres (reticulin) or have developed antibodies which neutralise romiplostim’s activity.

Nplate is not recommended for use in children below age 18.

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

If you are also taking medicines which prevent blood clots (anticoagulants or anti-platelet therapy) there is a greater 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, these may be reduced or stopped when given together with Nplate.

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine. Nplate is not recommended for use if you are pregnant unless indicated by your doctor.

It is not known whether romiplostim is present in human milk. Nplate is not recommended for use if you are breast-feeding. A decision on whether to discontinue breast-feeding or discontinue therapy with romiplostim should be made taking into account the benefit of breast-feeding to your child and the benefit of romiplostim therapy to you.

You should speak with your doctor before driving or using machines, as some side effects (e.g. temporary bouts of dizziness) may impair your ability to do so safely.

After suitable training, your doctor may also allow you to inject Nplate yourself. Please read the instructions at the end of this leaflet on how to inject Nplate, as discussed with your doctor. If your doctor has allowed you to self-inject, you should follow up with your doctor every month to have the doctor determine if Nplate is working for you or if another treatment needs to be considered.

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

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

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

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

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

If you have missed a dose of Nplate, your doctor will discuss with you when you should have your next dose.

If your doctor has allowed you to self-inject and you forget to give yourself an injection, you should inform your doctor immediately.

If you stop using Nplate, your low blood platelet count (thrombocytopenia) is likely to reoccur. Your doctor will decide if you should stop using Nplate.

Your doctor may decide that it is best for you to inject Nplate. Your doctor, nurse or pharmacist will show you how to inject yourself with Nplate. Do not try to inject yourself if you have not been trained. It is very important that you prepare Nplate properly and take the correct dose (see section 7. Instructions for preparing and giving an injection of Nplate, at the end of this leaflet).

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly (see details below). By reporting side effects you can help provide more information on the safety of this medicine.

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• The active substance is romiplostim.
  Each vial of Nplate 250 micrograms powder for solution for injection contains a total of 375 micrograms of romiplostim. An additional overfill is included in each vial to ensure that 250 micrograms of romiplostim can be delivered. After dissolving, a deliverable amount of 0.5 mL solution contains 250 micrograms of romiplostim (500 micrograms/mL).
  Each vial of Nplate 500 micrograms powder for solution for injection contains a total of 625 micrograms of romiplostim. An additional overfill is included in each vial to ensure that 500 micrograms of romiplostim can be delivered. After dissolving, a deliverable amount of 1 mL solution contains 500 micrograms of romiplostim (500 micrograms/mL).
• The other ingredients are:
  Powder: mannitol (E421), sucrose, L-histidine, hydrochloric acid (for pH adjustment) and polysorbate 20.
  Solvent: water for injections.

Nplate is a white powder for solution for injection supplied in a 5 mL single-dose glass vial.

Nplate is supplied as a 1 pack or multipack comprising 4 packs. Each pack contains:

1 vial of 250 micrograms or 500 micrograms of romiplostim.

1 pre-filled syringe containing 0.72 or 1.2 mL of water for injections.

1 plunger rod for pre-filled syringe.

1 sterile vial adapter.

1 sterile 1 mL Luer lock syringe.

1 sterile safety needle.

4 alcohol swabs.

Not all pack sizes may be marketed.

Manufacturer

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

The Nplate self injection kit must be kept in the original package until use in order to protect the Nplate vial from light. Keep the Nplate self injection kit refrigerated at 2°C to 8°C.

Once Nplate has been dissolved, inject immediately.

You may have excess Nplate left over after administering your prescribed dose. Do not re-use Nplate!

Any excess dissolved Nplate must be thrown away immediately after completing the injection process. Left over Nplate in vial must NEVER be re-used for another injection.

Do the following:

• Select a well lit, flat work surface, such as a table.
• Take the Nplate self injection kit out of the refrigerator. Do not use if frozen. If you have any questions about storage, contact your healthcare professional for further instructions. Check the expiry date on the self injection kit. If the expiry date has passed, do not use. Stop and contact your healthcare professional.
• Note: If your healthcare professional has instructed you that your Nplate dose requires more than one injection of Nplate, 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 complete your prescribed dose of Nplate.
• Make sure you have the following items:

Alcohol swab package x4

A vial of powder, either 250 micrograms OR 500 micrograms x1

13 mm vial adapter x1

Plunger rod for pre-filled sterile water syringe x1

Pre-filled sterile water syringe x1

1 mL Luer-lock tip syringe x1

Injection safety needle x1

• Do not open items until directed in instructions.
• Do not use components that have evidence of tampering or damage.
• Do not re-use items.

Using: 2 alcohol swab packages, 1 vial, and 1 vial adapter package.

Do the following:

• Wash your hands with soap and warm water.
• Clean the flat work surface with a new alcohol swab.
• Remove red (250 micrograms) or blue (500 micrograms) plastic cap from vial.
• Using a new alcohol swab clean vial stopper.
• Do not touch vial stopper after cleaning it.

• Peel off paper backing slowly from vial adapter while keeping vial adapter in the plastic package.
• Do not touch vial stopper or spike of vial adapter.

• Keeping the vial on a table, and keeping the vial adapter in the plastic packaging, line up spike on the vial adapter to the centre of the stopper on the vial.

• Push the vial adapter down onto the vial until it is firmly in place and you can’t push down any more.

• Lift off plastic vial adapter packaging, leaving vial adapter on vial.
• Do not touch the top of vial adapter.

Using: Pre-filled sterile water syringe and plunger rod.

Before you begin Step 3 please note the following:

• The clear plastic plunger rod MUST always be attached first before breaking the white tip off of the pre-filled water syringe. Perform step 3a before step 3b.

Do the following:

• Step 3a: Attach clear plastic plunger rod to pre-filled sterile water syringe by placing the threaded end of the plunger rod into the syringe and carefully twisting the rod clockwise onto the grey syringe plunger, until you feel a slight resistance. Do not over tighten.

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

• Once the seal is broken, pull the white plastic cover off. You will see grey rubber in the cap.

Using: Pre-filled sterile water syringe and vial with vial adapter attached.

Before you begin Step 4 please note the following:

• Do dissolve slowly and carefully. This is a protein product and proteins can be easily damaged by improper mixing and excessive shaking.

Do the following:

• Keeping the vial on the table, attach water-filled syringe to vial adapter by holding the side of the vial adapter with one hand and twisting the syringe tip clockwise onto the adapter with the other hand until you feel a slight resistance.

• Very slowly and gently push down on plunger rod to inject all water in the syringe into the vial. Water must flow slowly onto powder.
• Do not force the water into the vial.
• Note: After injecting the water into the vial it is common for the plunger to move back up. You do not have to maintain pressure on the plunger for the rest of Step 4.

Before continuing:

• Do ensure that all water is injected from the syringe into the vial before dissolving.
• Holding the area where the vial and vial adapter connect between your fingers, gently swirl the vial by rotating your wrist until all of the powder has dissolved and the liquid in the vial is clear and colourless.
• Do gently swirl the vial.
• Do not shake the vial.
• Do not roll vial between palms.
• Note: It may take up to 2 minutes for the powder to completely dissolve.

Before continuing:

• Do visually inspect the dissolved liquid for particles and/or discolouration. It must be clear and colourless and fully dissolved.
• Note: If there is any colour or particles in the liquid, contact your healthcare professional.
• Do make sure liquid is fully dissolved before removing syringe.
• When Nplate is completely dissolved, remove the empty syringe by twisting it anti-clockwise off of the vial adapter.

• Discard the empty syringe into sharps or hazard container. Keep the dissolved Nplate Vial. Immediately prepare new syringe for injection.
• Do not delay injecting Nplate.

Using: A new 1 mL syringe package and the vial of dissolved, clear Nplate.

Before continuing:

• Do check your dose before starting this step.
• Note: The Nplate liquid is highly potent which is why accuracy and dose measurement are important.
• Do make sure that all air bubbles are removed before injection.

Do the following:

• Remove 1 mL syringe from package.
• Draw air into syringe to 1 mL marking.
• Do not pull plunger back to more than 1 mL.

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

A. Push air into vial.
B. Maintain pressure on plunger.
C. Turn vial assembly and syringe upside down, so the vial is directly above the syringe.

• Withdraw the full amount of liquid into the syringe.
  • The maximum deliverable volume for the 250 microgram vial is 0.5 mL and for the 500 microgram vial is 1 mL.
• Do not pull the plunger out of the back of the syringe.

• Do ensure that the plunger remains in the syringe.

• Check and remove all air bubbles in the syringe.
  • Gently tap the syringe with your fingers to separate the bubbles from the liquid.
  • Slowly push the plunger up to force the air bubbles out of the syringe.

• Slowly push back on the plunger to leave only the amount prescribed by your healthcare professional.
• Make sure the top of the plunger head lines up with the syringe marking that matches your prescribed dose. If necessary push liquid back into the vial to achieve the desired dose.

• Do a final check to ensure the correct amount of liquid for your dose is in the syringe and all air bubbles have been removed.

Before continuing:

• Do make sure the correct amount of liquid for your dose remains in the syringe.
• Do make sure all air bubbles are removed from the syringe.
• Once all air bubbles are removed and syringe is filled with your correct dose, twist off syringe from vial adapter.

• Keep filled syringe in your hand and do not touch syringe tip.
• Do not set filled syringe down after removing from vial.

Using: Filled syringe with measured Nplate dose and safety needle.

Do the following:

• Holding the syringe in the palm of your hand with the tip facing up, remove the safety needle from the package.

• Attach safety needle to filled syringe.
  Apply strong force while twisting to attach the safety needle onto syringe. Turn clockwise to lock into Luer lock tip.
• The product is now ready for injection. IMMEDIATELY continue to step 7.

Using: New alcohol swab.

Do the following:

• Select your injection site. Three recommended injection sites for Nplate include:
  • Front of the middle thighs
  • Abdomen, except for the 5 centimetre area right around the navel
  • If someone else is giving you the injection, they can also use the outer area of the upper arms
  • Do rotate the site for each injection.

• Do not inject into areas where the skin is tender, bruised and hard.
• Do not inject into areas with scars or stretch marks.
• Wipe the site where Nplate is to be injected with an alcohol swab, using a circular motion.
• Do not touch this area again before giving the injection.

Using: Filled syringe and needle assembly.

Do the following:

• Pull back on the pink safety cover (toward the syringe and away from the needle).

• Remove clear needle shield by holding syringe in one hand and carefully pulling shield straight off with the other hand.
• Do remove the clear needle shield before injecting.

• With one hand, gently pinch the cleaned 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 short, sharp motion, push the needle into the skin.

• Inject the prescribed dose subcutaneously as directed by your doctor, nurse or pharmacist.
• When the syringe is empty, pull the needle out of the skin, being careful to keep it at the same angle as inserted.
• There may be a little bleeding at the injection site. You can press a cotton ball or gauze over the injection site for 10 seconds.
• Do not rub the injection site. If needed, you may cover the injection site with a plaster.
• After injecting, use your thumb (or tip of your finger) to activate the pink safety cover by pushing the cover forward using the same hand until you hear and/or feel it click and lock into place over the needle.

• Visually confirm that the needle tip is covered. Always cover the needle with the pink safety cover before disposal.

Do the following:

• Immediately discard syringe with covered needle into a sharps container.
• Immediately discard used Nplate vial into an appropriate waste container.
• Make sure all other materials are discarded into proper containers.

The injection device and Nplate vial must NEVER be reused.

• Do dispose of the used needle and syringe in a puncture-resistant container.
• Do dispose of any left-over Nplate in proper waste container. Left over Nplate in the vial must NEVER be re-used for another injection.