Prospect: information for the user

Factor IX Grifols 50 UI/mlpowder and solvent for injectable solution

Human coagulation factor IX

Read this prospect carefully before starting to use the medication, because it contains important information for you.

-Keep this prospect, as you may have to read it again.

-If you have any doubts, consult your doctor, pharmacist, or nurse.

-This medication has been prescribed only toyou,and you must not give it to other peoplealthough they may have the same symptoms as you, as it may harm them.

-Ifyou experience adverse effects, consult your doctor, pharmacist, or nurse, even if they are adverse effects that do not appear in this prospect. See section 4.

Content ofprospect

1.What isFactor IX Grifolsand what it is used for

2.What you need to know before starting to useFactor IX Grifols

3.How to useFactor IX Grifols

4.Possible adverse effects

5.Storage ofFactor IX Grifols

6.Contents of the package and additional information

Factor IX Grifolsis a medication that contains human coagulation factor IX.

Factor IX Grifolsbelongs to the group of medications known as antihemorrhagics: blood coagulation factors.

Factor IX Grifolsis indicated for the treatment andprophylaxis (prevention)of bleeding in patients with hemophilia B (congenital deficiency of factor IX). These patients do not have enough functional factor IX.Factor IX Grifolshelps to increase the amount of factor IX in the blood, allowing the blood to clot.

No useFactor IX Grifols

If you are allergicto the active ingredient or to any ofthe othercomponents of this medication (listed in section 6).See important information about some of the components ofFactor IX Grifolsat the end of this section.

If you have any doubts about the above, consult your doctor.

Warnings and precautions

Consult your doctor, pharmacist or nurse before starting to use Factor IX Grifols.

• There is a remote possibility that you may experience anaphylactic reaction (severe allergic reaction). If you feel chest tightness, dizziness, vertigo or nausea, or if you feel dizzy while standing, you may be experiencing an anaphylactic reaction to Factor IX Grifols. If this occurs, stop administering the product immediately and seek medical assistance.

• If hypersensitivity reactions (allergy, e.g. fever, generalized urticaria, chest tightness, shortness of breath, hypotension, and anaphylaxis) occur during the administration of Factor IX Grifols, the injection/infusion must be interrupted. Your doctor will decide on the appropriate treatment (e.g. antihistamines, shock therapy).

• Your doctor may want to perform some tests to ensure that the dose of Factor IX Grifols you receive is sufficient to achieve and maintain adequate factorIX levels.

• If your bleeding does not control with Factor IX Grifols, consult your doctor immediately. You may have developed inhibitors of factor IX, so your doctor will want to perform tests to confirm this. Factor IX inhibitors are antibodies present in the blood that block the factor IX you are using. This makes factor IX less effective in controlling bleeding.

• If you have a disease with a risk of thrombosis (history of heart disease or acute myocardial infarction, liver disease, thromboembolic disorders, coagulation disorders, or in newborns) and if you are administered high doses of factor IX in cases of major surgery. With adequate monitoring, possible complications can be detected in time and appropriate measures can be taken. Some of these complications are, for example, thromboembolism and consumption coagulopathy.

• If you are going to need a central venous access device (CVAD) for the administration of Factor IX Grifols, your doctor should consider the risk of complications related to the CVAD, including local infections, presence of bacteria in the blood (bacteremia), and the formation of a blood clot in the blood vessel (thrombosis) where the catheter is inserted.

When medications are prepared from blood or human plasma, a number of measures must be taken to prevent the possible transmission of infections to patients. These measures include:

• a careful selection of blood and plasma donors to ensure the exclusion of donors at risk of infection,
• the analysis of each donation and plasma mixtures to detect possible viruses or infections,
• the inclusion of a series of steps in the processing of blood or plasma that can inactivate or eliminate viruses.

Despite these measures, when medications prepared from blood or human plasma are administered, the possibility of transmission of infections cannot be completely ruled out. This also applies to unknown or emerging viruses and other types of infections.

The measures taken are considered effective for enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus, and hepatitis C virus, and for non-enveloped viruses such as hepatitis A virus. The measures taken may have limited value for non-enveloped viruses such as parvovirus B19.

Parvovirus B19 infection can be severe for a pregnant woman (fetal infection) and for peoplewhose immune system is depressed or who have some type of anemia(e.g. with sickle cell anemia or hemolytic anemia).

Your doctor may recommend that you consider vaccination against hepatitis A and B if you regularly/repeatedly receive factor IX concentrates derived from human plasma.

Each time you are administered a dose of Factor IX Grifols, it is recommended to record the name and batch number of the medication to maintain a record of the batches used.

There may be a possible connection between the appearance of factor IX inhibitors and allergic reactions. Patients with factor IX inhibitors may have a higher risk of anaphylactic reactions. Therefore, in patients who experience an allergic reaction, the presence of a factor IX inhibitor should be investigated.

Use of Factor IX Grifols with other medications

• Inform your doctor or pharmacist if you are using or have used recently or may need to use any other medication.

• Currently, there are no known interactions with other medications.
• Factor IX Grifolsshould not be mixed with other medications before administration, as it may adversely affect the efficacy and safety of the product.

Pregnancy, lactation and fertility

If you are pregnant or breastfeeding, or if you think you may be pregnant, consult your doctor or pharmacist before using this medication.

• Inform your doctor if you are pregnant or breastfeeding.

• Your doctor will decide if Factor IX Grifols can be used during pregnancy and lactation.
• Since hemophilia B is rare in women, there is no experience with the use of Factor IX Grifols during pregnancy and lactation.

Driving and operating machinery

There is no indication thatFactor IX Grifolsmay affect your ability to drive or operate machinery.

Sodium content

Factor IX Grifols contains 20.7 mg of sodium in the presentation of Factor IX Grifols 250 UI/5 ml, 41.4 mg of sodium in the presentation of Factor IX Grifols 500 UI/10 ml, 82.8 mg of sodium in the presentation of Factor IX Grifols 1000 UI/20 ml, and 124.2 mg of sodium in the presentation of Factor IX Grifols 1500 UI/30 ml. This is equivalent to 1.04%, 2.07%, 4.14%, and 6.21% respectively of the maximum daily sodium recommended by the WHO for an adult (2 g of sodium).

Reconstitute the product as described in this section. The product must be administered slowly, especially the first dose (approximately 3 ml/min) intravenously.

Follow exactly the administration instructions of this medication indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

Your doctor will decide the dose ofFactor IX Grifolsyou will receive. This dose and its duration will depend on your individual needs for factor IX substitution treatment and the pharmacokinetics (recovery and half-life), which must be checked regularly.

Your doctor may modify the dose ofFactor IX Grifolsyou receive over time.

Treatment dose

The required dose is determined using the following formula:

Required units = body weight (kg) x desired increase in factor IX (%) (UI/dl) x 0.8

Prophylaxis dose for bleeding

In routine prophylaxis to prevent bleeding in patients with severe hemophilia B, doses of 20 to 40 UI of factor IX/kg of body weight should be administered at intervals of 3 to 4 days. In some cases, especially in young patients, it may be necessary to shorten the administration intervals or administer higher doses.

Patients with inhibitors

If you have developed inhibitors ofFIX, you may need a higher amount ofFactor IX Grifolsto control bleeding. If this dose does not control bleeding, your doctor may consider the use of an alternative medication. Do not increase the total dose ofFactor IX Grifolsyou use to control bleeding without consulting your doctor.

Instructions for use/manipulation

Follow these instructions unless your doctor has given you different instructions.

For the reconstitution and administration ofFactor IX Grifols, presentation of 1500 UI/30 ml, withthe solvent presented in vials, the preparation of the solution is as follows:

1.Warm the vials without exceeding 37 °C.

2.Remove the label from the solvent vial, disinfecting the stopper with analcohol wipe.

3.Extract the double-pointed needle from the container. Separate one of the caps that protect the tips and pierce the stopper of the solvent vial.

4.Remove the label from the lyophilized product vial, disinfecting the stopper with analcohol wipe.

5.Separate the cap from the other tip of the needle.

6.Invert the solvent vial and pierce the lyophilized vial, ensuring that all the solvent is transferred and avoiding vacuum loss.

7.Separate the solvent vial with the double-pointed needle. Gently turn the vial to avoid foam formation until the solution is fully dissolved. Do not shake.

8.Remove the filter from the blister and insert it into the syringe, recirculate enough air for the total volume of the solution. Insert the needle into the filter and pierce the vial of the reconstituted product. Inject the preloaded air from the syringe, through the filter, to then invert the vial position and aspirate the contents into the syringe.

9.Remove the filter-needle assemblyand administer slowly intravenously using the butterfly needle provided at a rate of 3 ml/min.

For the reconstitution and administration ofFactor IX Grifols, presentations of 250 UI/5 ml, 500UI/10 ml, and 1000 UI/20 ml, in whichthe solvent is presented in preloaded syringes, the preparation of the solution is as follows:

1.Warm the vial and syringe of solvent without exceeding 37 °C.

2.Attach the plunger to the syringe of solvent.

3.Remove the label from the filter. Separate the stopper from the cone of the syringe of solvent and attach it to the filter.

4.Remove the label from the adapter and attach it to the filter-syringe assembly.

5.Remove the label from the vial, disinfecting the stopper with analcohol wipe.

6.Insert the spike of the adapter into the vial.

7.Transfer all the solvent from the syringe to the vial.

8.Gently turn the vial to avoid foam formation until the solution is fully dissolved. Do not shake.

9.Separate the filter-syringe assembly from the rest. Aspirate enough air for the total volume of the solution. Reattach the filter-syringe assembly to the vial.

10.Invert the vial and aspirate the contents into the syringe.

11.Separate the syringe and administer slowly intravenously using the butterfly needle provided at a rate of 3 ml/min.

It is essential to use the injection equipment provided with the medication. In the event that medical perfusion equipment is used, check the compatibility of the system with the preloaded syringe. To ensure proper administration of the product, it may be necessary to use an adapter in some cases.

Reconstitution scheme for the solvent in syringes

If you use moreFactor IX Grifolsthan you should

No cases of overdose with factor IX coagulation human have been reported.However, if you have usedFactor IX Grifolsmore than you should, consult your doctor or pharmacist immediately.

In case of overdose or accidental administration, consult the Toxicological Information Service, phone 91 562 04 20.

If you forgot to use Factor IX Grifols

• Do not take a double dose to compensate for the missed doses.

• Continue with the next administration immediately and follow at regular intervals as indicated by your doctor.

Like all medications, this medicationmay produce adverse effects, although not all people will experience them.

In rare cases, you may notice one of these adverse effects after administration of Factor IX Grifols:

• Pruritus, local reactions at the injection site (e.g. burning sensation and transient redness)
• Allergic reactions (e.g. chest tightness/general feeling of discomfort, dizziness, nausea, and mild drop in blood pressure that may cause dizziness when standing)

The possibility of anaphylactic shock cannot be completely ruled out. If you notice any of the following symptomsduring injection/infusion

• Chest tightness/general feeling of discomfort
• Dizziness
• Mild hypotension (mild decrease in blood pressure with dizziness when standing)
• Nausea

may be an early sign of hypersensitivity and anaphylactic reaction. If an allergic or anaphylactic reaction occurs, the injection/infusion should be interrupted and your doctor should be consulted immediately.

However, the possibility of allergic reactions to the components of the preparation cannot be completely ruled out. The formation of factor IX-neutralizing antibodies (inhibitors) is a known complication in the treatment of patients with hemophilia B. The development of inhibitors should be carefully monitored through laboratory tests and appropriate clinical examinations to determine the formation of these inhibitors.

There is a risk of thromboembolic complications with Factor IX Grifols, particularly if you have a risk of thrombosis and/or receive high-dose therapy.

• For information on viral safety, seesection 2.

Reporting Adverse Effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect that does not appear in this prospectus. You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use:www.notificaRAM.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medication.

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

Do not usethis medicationafter the date that appears on the packaging after the abbreviation “CAD”. The expiration date is the last day of the month indicated.

Lyophilized powder vial (human coagulation factor IX):store between 2 °C and 8 °C (in the refrigerator).

Vial or syringe of solvent (injectable water): store between 2 °C and 30 °C.

When proceeding with outpatient administration, the product can be stored at room temperature (do not store above 25 °C) for a maximum period of 3 months.

The product should not be refrigerated again after being stored at room temperature.

Do not usethis medicationif you observe that the solution presents turbidity or sediments. The solution is generally clear or slightly opalescent.

Once reconstituted, the solution should be discarded if particles are observed inside or any type of discoloration.

The reconstituted solution must be used immediately or within a period of 3 hours.

All unused products and waste materials must be disposed of in accordance with local requirements.

Medications should not be thrown away through drains or in the trash. Ask your pharmacist how to dispose of packaging and medications that you no longer need. In this way, you will help protect the environment.

Composition ofFactor IX Grifols

The active ingredient is human coagulation factor IX.

Each vial ofFactor IX Grifolscontains lyophilized powder with 250 UI, 500 UI, 1000 UI or 1500 UI of human coagulation factor IX.Once reconstituted, the content of human factor IX is 50UI/ml (250 UI/5 ml, 500 UI/10 ml, 1000 UI/20 ml or 1500 UI/30 ml).

The other components are lysine, glycine, chloride, sodium, phosphate and citrate.

Each container of solvent contains 5 ml, 10 ml, 20 ml or 30 ml of injectable water.

See section 2 for important information about one of the components.

Appearance of the product and contents of the container

Vial containing white or pale yellow powder and vial/syringe with injectable water (solvent).

Each vial ofFactor IX Grifolsof the presentations of 250 UI/5 ml, 500 UI/10 ml and 1000UI/20ml is accompanied by a pre-loaded syringe with solvent containing 5 ml, 10 ml or 20ml of injectable water, along with the necessary accessories for its reconstitution and administration (vial adapter, filter, 2 alcohol wipes and butterfly needle).

Each vial ofFactor IX Grifolsof the 1500 UI/30 ml presentation is accompanied by a solvent vial with 30 ml of injectable water, along with the necessary accessories for its reconstitution and administration (double-pointed needle, filter, 2 alcohol wipes, butterfly needle and syringe with needle).

It may only be marketed in some sizes of containers.

Box contents: 1 lyophilized vial, 1 pre-loaded syringe/vial of solvent and accessories.

Marketing authorization holder and responsible manufacturer

Instituto Grifols, S.A.

Can Guasch, 2 - Parets del Vallès

08150 Barcelona - SPAIN

Last review date of this leaflet: April 2019

The detailed information of this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) (http://www.aemps.gob.es/).

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This information is intended solely for healthcare professionals:

The following table can be used as a dosing guide in bleeding episodes and surgery.