Alphanine

Package leaflet: Information for the user

AlphaNine 500 IU, 1000 IU and 1500 IU Powder and solvent for solution for infusion

Coagulation factor IX
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 further questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others, even if their symptoms seem identical to yours, as it may be harmful.
• If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any side effects not listed in this leaflet. See section 4.

Contents of this leaflet:

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

1. What AlphaNine is and what it is used for

AlphaNine is supplied as a powder and solvent for solution for infusion containing 500, 1000 or
1500 IU per vial of highly purified human coagulation factor IX, produced from plasma of human donors,
with dual viral inactivation. (Note that IU means International Units, which is a standardized measure of activity.)
After reconstitution with 10 ml of water for injections (solvent), each vial contains approximately 50, 100 or 150 IU of factor IX/ml.
AlphaNine belongs to a group of medicines called coagulation factors.
AlphaNine is used for the treatment and prevention of bleeding in patients with Haemophilia B (congenital factor IX deficiency) and in patients with acquired factor IX deficiency.

2. What you need to know before using AlphaNine

Do not use AlphaNine

• If you are allergic to human coagulation factor IX or to any of the other ingredients of this medicine (listed in section 6) (see important information on certain excipients of AlphaNine at the end of this section).

Consult your doctor for more detailed information.
Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using AlphaNine.

• Rarely, anaphylactic reactions (sudden and severe allergic reactions) may occur, such as skin rash, feeling of tightness in the chest, dizziness, vertigo, nausea, or feeling faint when standing up. If these symptoms occur, you must stop using the product immediately and contact your doctor.

• Your doctor should perform certain tests to ensure that the dose of AlphaNine is sufficient to achieve and maintain adequate levels of factor IX and thus stop any bleeding.

• If your bleeding is not controlled with AlphaNine, consult your doctor immediately. You may have developed factor IX inhibitors: these are antibodies that block the clotting effect of factor IX. Your doctor will perform tests to confirm whether such inhibitors are present in your blood.

• Due to the possibility of blood clotting, factor IX must be used with caution in patients with liver disease, after surgery, in newborns, or in patients at risk of blood clots or disseminated intravascular coagulation (DIC).

• In patients with cardiovascular risk factors, replacement therapy with factor IX may increase cardiovascular risk.

• If a central venous access device (CVAD) is required for administration of AlphaNine, your doctor should consider the risk of CVAD-related complications, including: local infections, bacteria in the blood (bacteremia), and formation of blood clots in the blood vessel (thrombosis) where the catheter is inserted.

Viral safety
When medicines are produced from human blood or plasma, specific measures are taken
to prevent transmission of infections to patients. These measures include:

• Careful selection of blood and plasma donors to ensure potentially infected donors are excluded.
• Testing of each donation and plasma pool to detect possible presence of viruses/infections.
• Inclusion of certain steps in the processing of blood or plasma capable of inactivating or removing viruses. Despite these measures, when administering medicinal products prepared from human blood or plasma, the possibility of transmitting infectious agents cannot be completely ruled out. This also applies to emerging or unknown viruses or other types of infectious agents.

The measures taken are considered effective against lipid-enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV). However, they may have limited effectiveness against non-enveloped viruses such as hepatitis A virus and parvovirus B19. Infection with parvovirus B19 can be serious for pregnant women (fetal infection) and for immunocompromised individuals or those with certain types of anemia (e.g., sickle cell anemia or hemolytic anemia).
Your doctor may recommend that you consider vaccination against hepatitis A and B if you regularly/repeatedly receive doses of factor IX derived from human plasma.
It is strongly recommended that each time you receive a dose of AlphaNine, both the name and the batch number of the product are recorded, in order to maintain traceability of the batch used.
See section 4.
Children and adolescents
The warnings and precautions listed apply to both adults and children.
Other medicines and AlphaNine
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
No interactions between AlphaNine and other medicines are known.
Do not mix AlphaNine with other injectable medicines.
Pregnancy and breastfeeding
Because haemophilia B is rare in women, there are no data on the use of factor IX during pregnancy or breastfeeding. Therefore, factor IX may be used during pregnancy and breastfeeding only if clearly indicated.
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before using this medicine.
Driving and using machines
No effects on the ability to drive vehicles or use machines have been observed.
AlphaNine contains sodium and heparin
The residual sodium content in AlphaNine, originating from the manufacturing process, ranges from 1.3 to 3.0 millimoles (from 29.9 mg to 69 mg) per 10 milliliters of solution (volume after reconstitution of the powder contained in a single AlphaNine package). This corresponds to 1.49% and 3.45% of the maximum daily recommended intake for an adult. However, depending on the patient's body weight and dosage, the patient may receive more than one vial. This should be taken into account by patients on a sodium-controlled diet.
AlphaNine contains small amounts of heparin. Heparin may cause allergic reactions and reduced platelet count, which may affect the blood coagulation system. Patients with a history of allergic reactions to heparin should avoid using medicines containing heparin.

3. How to use AlphaNine

Use this medicine exactly as instructed by your doctor. If you have any doubts, consult your doctor or pharmacist.
Reconstitute the product as described at the end of this leaflet (see pictograms on the back of the leaflet). The product must be administered intravenously. The infusion rate must never exceed 10 ml/min to avoid unwanted side effects. Inject AlphaNine immediately after reconstitution.
The amount of AlphaNine you should use depends on several factors, such as body weight, clinical condition, and the type and severity of bleeding. Your doctor will calculate the dose, frequency, and dosing intervals of AlphaNine required to achieve the necessary factor IX level in the blood.
Your doctor will inform you about the duration of treatment with AlphaNine.

Use in children and adolescents
Clinical study data are insufficient to recommend the use of AlphaNine in children under 6 years of age.

If you use more AlphaNine than you should
Cases of overdose with human coagulation factor IX have not been reported. However, if you have used more AlphaNine than prescribed, consult your doctor or pharmacist immediately.

If you forget to use AlphaNine
Take the next dose as soon as possible and continue at regular intervals as directed by your doctor. Do not use a double dose to make up for a missed dose.

4. Possible side effects

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

Rarely, some of the following side effects may occur after administration of AlphaNine. Please contact your doctor immediately if you experience:

• itching, local reactions at the injection site (e.g.: transient burning and redness);
• allergic reactions (e.g.: chest tightness / feeling unwell, dizziness, nausea, and a slight drop in blood pressure which may cause dizziness when standing);
• fever;
• rapid heartbeat (tachycardia);
• chills;
• widespread hives;
• headache;
• drowsiness (lethargy);
• restlessness;
• tingling;
• vomiting;
• wheezing.

An anaphylactic shock may occasionally occur. If you notice any of the following symptoms during infusion/injection, stop the infusion/injection immediately and contact your doctor immediately:

• chest tightness / feeling unwell;
• dizziness;
• mild hypotension (slight drop in blood pressure with dizziness when standing);
• nausea.

Allergic reactions to the components of the product cannot be completely ruled out. In some cases, these reactions have led to severe anaphylaxis and have occurred concomitantly with the development of factor IX inhibitors. The formation of neutralizing antibodies to factor IX (inhibitors) is a well-known complication in the treatment of patients with haemophilia B. Study results show that those who use factor IX for the first time are more likely to be affected. You will be closely monitored for the development of these inhibitors.
Nephrotic syndrome has been reported following attempts to induce immunotolerance in patients with haemophilia B who have factor IX inhibitors and a history of allergic reactions.
There is a possibility of blood clot formation, particularly in the presence of clinical risk factors.

Additional side effects in children and adolescents
The frequency and severity of adverse reactions in children appear comparable to those in adults.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects directly via
http://www.agenziafarmaco.gov.it/it/responsabili. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store AlphaNine

Keep this medicine out of the sight and reach of children.
Store in a refrigerator (2-8 °C). Do not freeze. Protect from light.
Do not use this medicine after the expiry date stated on the vial label and on the carton after Exp.
Do not use this medicine if you notice that the solution is cloudy or contains deposits. The solution is usually clear or slightly opalescent. If the solution is discoloured or cloudy, discard it.
After reconstitution, the product must be used immediately.
Any unused medicine or waste material must be disposed of in accordance with local regulations.
Do not dispose of any medicine 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 AlphaNine contains
The active substance is human coagulation Factor IX.
AlphaNine is available as a powder and solvent for solution for infusion, containing 500, 1000, or
1500 IU of human coagulation Factor IX per vial. The contents of one powder vial are reconstituted with 10 ml of water for injections.
The other components are heparin and dextrose (see section 2, "What you need to know before using
AlphaNine", for further information on other components).

Description of the appearance of AlphaNine and contents of the package
Vial containing a hygroscopic powder or a pale yellow to white friable solid, and a pre-filled syringe with water for injections (solvent).
Pack: 1 lyophilized vial, 1 pre-filled syringe with solvent, and accessories (one vial adapter, one microfilter, 2 disinfectant swabs, and an infusion set).
Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer
Marketing Authorization Holder:
Grifols Italia S.p.A.
Viale Enrico Forlanini, 23
20134 Milano - ITALY

Manufacturer:
Instituto Grifols, S.A.
Can Guasc, 2 - Parets del Vallès
08150 Barcelona - SPAIN

Instructions for use / handling
Follow these instructions unless otherwise directed by your doctor.
Any unused portion of the product must never be stored for later use, nor refrigerated.
Reconstitution and withdrawal must be performed under aseptic conditions.

To prepare the solution:

1. Warm the vial and the syringe, without exceeding 30 °C.
2. Insert the plunger into the syringe containing the solvent.
3. Remove the filter from its packaging. Remove the cap from the syringe connector and attach the syringe to the filter.
4. Remove the vial adapter from its packaging and connect it to the filter on the syringe.
5. Remove the plastic protector from the vial and clean the stopper with the provided disinfectant swab.
6. Pierce the vial stopper with the needle of the vial adapter.
7. Transfer all the solvent from the syringe into the vial.
8. Gently rotate the vial without shaking until the product is completely dissolved. As this is a parenteral solution, do not use the product if it is not fully dissolved or if particles are visible.
9. Quickly disconnect the syringe with the filter from the vial adapter to release the vacuum. Proceed immediately to steps 10 and 11.
10. With the vial held upright, draw the solution into the syringe.
11. Prepare the injection site, disconnect the syringe, and inject the product using the butterfly needle infusion set provided. Inject slowly into a vein at a rate not exceeding 10 ml/min.

Do not reuse administration sets.
It is important to use the infusion set supplied with the medicinal product. If other medical infusion systems are used, compatibility with the pre-filled syringe must be verified. Adapters should be used when necessary to ensure proper administration of the product.