Pharmavate

Leaflet attached to the packaging: information for the user

Pharmavate, 50 IU/ml, powder and solvent for solution for injection

Human coagulation factor VIII Pharmavate, 100 IU/ml, powder and solvent for solution for injection

Human coagulation factor VIII

You should read the leaflet carefully before using the medicine, as it contains important information for the patient.

• You should keep this leaflet, so you can read it again if you need to.
• You should consult a doctor, pharmacist, or nurse if you have any further questions.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same as yours.
• If any of the side effects get worse or if you notice any side effects not listed in this leaflet, you should tell your doctor, pharmacist, or nurse.

Table of contents of the leaflet:

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

1. What is Pharmavate and what is it used for

Pharmavate belongs to a group of medicines called coagulation factors and contains human coagulation factor VIII. It is a special protein that increases the blood's ability to clot. Pharmavate is used to treat and prevent bleeding in patients with hemophilia A. This is a condition where bleeding is prolonged compared to what is expected. It results from a congenital deficiency of factor VIII in the blood.

2. Important information before using Pharmavate

It is strongly recommended that each time a dose of Pharmavate is administered to a patient, the name and batch number of the product should be recorded in order to maintain information about the batch used. The doctor may recommend considering vaccination against viral hepatitis A and B in case of regular or repeated administration of human factor VIII products.

When not to use Pharmavate

Warnings and precautions

Before starting treatment with Pharmavate, you should consult a doctor, pharmacist, or nurse. Pharmavate contains trace amounts of other human proteins. Any medicine that contains proteins and is administered intravenously (given into a vein) may cause allergic reactions (see section 4. Possible side effects). The formation of inhibitors (antibodies) is a known complication that may occur during treatment with all factor VIII medicines. These inhibitors, especially at high concentrations, disrupt proper treatment, and the patient will be closely monitored for the production of these inhibitors. If the patient's bleeding is not properly controlled with Pharmavate, you should immediately tell your doctor.

Information about blood and plasma used to manufacture Pharmavate

During the manufacture of medicines from human blood or plasma, certain measures are taken to prevent the transmission of infections to patients. These include careful selection of blood and plasma donors to ensure the exclusion of donors who may be carriers of infections, as well as testing all collected samples and plasma pools to detect the presence of viruses/infections. The manufacturers of these products have implemented virus inactivation or removal steps in the processing of blood or plasma. Despite these measures, when administering medicines prepared from human blood or plasma, it is not possible to completely exclude the possibility of transmitting an infection. This applies to both unknown or newly emerging viruses and other types of infections. The measures taken are considered effective against enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV), as well as the non-enveloped hepatitis A virus (HAV). The methods used may have limited effectiveness against non-enveloped viruses such as parvovirus B19. Parvovirus B19 infection can be hazardous for pregnant women (fetal infection) and for individuals whose immune system is suppressed or who suffer from certain types of anemia (e.g., sickle cell anemia or abnormal red blood cell breakdown).

Other medicines and Pharmavate

You should tell your doctor or pharmacist about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take, including those available without a prescription. No interactions between human coagulation factor VIII and other medicinal products are known. However, you should not mix Pharmavate with other medicines during infusion.

Pregnancy and breastfeeding

If you are pregnant, breastfeeding, or think you may be pregnant, or if you are planning to become pregnant, you should consult a doctor or pharmacist before using this medicine.

Driving and using machines

No effect on the ability to drive and use machines has been observed.

What Pharmavate contains

In the case of a 250 IU vial, the product contains less than 1 mmol of sodium (23 mg) per dose, which means that the medicine is considered "sodium-free". In the case of 500 IU and 1000 IU vials, the product contains a maximum of 1.75 mmol of sodium (40 mg) per dose. This corresponds to 2% of the maximum recommended daily intake of sodium for adults. This should be taken into account for patients on a controlled sodium diet.

3. How to use Pharmavate

Pharmavate should be administered intravenously after reconstitution with the supplied solvent. Treatment should be initiated under medical supervision.

Dosing for prophylaxis:

In long-term prophylaxis of bleeding in patients with severe hemophilia A, factor VIII should be administered at a dose of 20 to 40 IU per kilogram of body weight at intervals of 2 to 3 days. The dose should be adjusted according to the clinical response. In some cases, it may be necessary to administer the medicine at shorter intervals or in higher doses.

Dose calculation:

Pharmavate should always be used according to the doctor's recommendations. In case of doubts, you should consult your doctor or pharmacist again. The activity of factor VIII in plasma corresponds to the factor VIII content in plasma. It is expressed either as a percentage (compared to normal human plasma) or in international units (IU). The dose of factor VIII is expressed in IU. One International Unit (IU) of factor VIII activity is equivalent to the amount of factor VIII in 1 ml of normal human plasma. 1 IU of factor VIII per kilogram of body weight increases the activity of plasma factor VIII by 1.5% to 2% of normal activity. To calculate the required dose, you should determine the activity of factor VIII in the patient's plasma. This will allow you to determine how much the activity should be increased. You should consult a doctor in case of uncertainty about how much the activity of factor VIII in plasma should be increased and how to calculate the required dose. The required dose is calculated using the following formula: required number of units = body weight (kg) x required increase in factor VIII activity (%) (IU/dl) x 0.5. The amount to be administered and the frequency of administration of the product should always be adjusted according to the individual patient's clinical efficacy. In the following cases of bleeding, the activity of factor VIII should not fall below the specified level of plasma activity (as a percentage of normal values) during the given period. The following table may be helpful in determining doses in cases of bleeding or surgical procedures:

The dose and frequency of administration of Pharmavate will be determined by your doctor. The response to factor VIII may vary between patients. Therefore, during treatment, it is recommended to determine the levels of factor VIII to establish the appropriate dose and frequency of infusion administration.

Use in children

Clinical trials have not identified any special requirements for dosing in children. Dosing is the same for adults and children, both for treatment and prophylaxis.

Home administration instructions

• You should read all instructions and follow them carefully!
• Do not use the Pharmavate product after the expiration date stated on the label.
• During the procedure described below, you should maintain sterile conditions!
• The solution in the syringe should be clear or slightly pearlescent, shiny. Do not inject solutions that are cloudy or contain solid particles.
• The prepared solution should be used immediately to prevent microbial contamination.
• Only use the supplied injection set. Using other injection/infusion equipment may cause additional risks and treatment failure.

Instructions for preparing the solution using the Mix2Vial system:

• 1. Do not use the product immediately after removal from the refrigerator. Leave the solvent and powder in closed vials until they reach room temperature.
• 2. Remove the caps from both vials and clean the rubber stoppers with one of the enclosed alcohol swabs.
• 3. The Mix2Vial system is shown in Fig. 1. Place the vial with the solvent on a flat surface and hold it firmly. Take the Mix2Vial system and turn it. Place the blue part of the Mix2Vial on top of the vial with the solvent and press firmly until it clicks (Fig. 2 + 3).

• 4. Place the vial with the powder on a flat surface and hold it firmly. Take the vial with the solvent with the attached Mix2Vial system and turn it upside down. Place the transparent part of the set on top of the vial with the powder and press firmly until it clicks (Fig. 4). The solvent flows automatically into the vial with the powder.

• 5. With both vials connected, gently rotate the vial with the powder until the product is dissolved. Dissolution is completed in less than 10 minutes at room temperature. During preparation, a slight foam may form. Unscrew the Mix2Vial system into two parts (Fig. 5). The foam will disappear.

Discard the empty vial with the solvent and the blue part of the Mix2Vial system.

Instructions for performing the injection:

As a precaution, you should check your pulse before and during the injection. If you notice a significant increase in heart rate, you should reduce the injection rate or interrupt the administration of the medicine for a short time.

• 1. Connect the syringe to the transparent part of the Mix2Vial system. Turn the vial upside down and draw the solution into the syringe (Fig. 6). The solution in the syringe should be clear or slightly pearlescent, shiny. After transferring the solution, hold the syringe plunger firmly (with the plunger facing down) and remove the syringe from the Mix2Vial system (Fig. 7). Discard the Mix2Vial system and the empty vial.

• 2. Clean the selected injection site with one of the enclosed alcohol swabs.
• 3. Attach the supplied injection needle to the syringe.
• 4. Insert the needle into the selected vein. If a tourniquet is used to make the vein visible, it should be loosened before starting the injection of Pharmavate. Blood must not enter the syringe due to the risk of forming fibrin clots.
• 5. Inject the solution into the vein slowly, no faster than 2-3 ml per minute.

If you are using more than one vial of Pharmavate powder during a single administration, you can reuse the same injection needle and syringe. The Mix2Vial system is intended for single use only.

Instructions for preparing the solution using the transfer set (1 double-ended needle and 1 filter needle):

• 1. Do not use the product immediately after removal from the refrigerator. Warm the powder and solvent in closed vials to room temperature. This temperature should be maintained during preparation. If a water bath is used for warming, make sure the water does not come into contact with the rubber stoppers (latex-free) or the vial caps. The temperature of the water bath should not exceed +37°C.
• 2. Remove the caps from the vial with the powder and the vial with the solvent (Fig. 1) and clean the rubber stoppers with one of the enclosed alcohol swabs (Fig. 2).

Fig.1
Fig.2
Fig.1
Fig.2

• 3. Remove the protective cover from the short end of the double-ended needle (Fig. 3), making sure not to touch the exposed needle tip. Then, puncture the center of the rubber stopper of the vial with the solvent with the needle vertically (Fig. 4). To completely withdraw the liquid from the vial with the solvent, the needle should be inserted into the stopper so that it enters the vial and is visible.

Fig.4
Fig.3
Fig.4

• 4. Remove the protective cover from the other, longer end of the double-ended needle (Fig. 5), making sure not to touch the exposed needle tip. Take the vial with the solvent and the inserted needle and turn it upside down above the vial with the powder. Quickly puncture the center of the rubber stopper of the vial with the powder with the needle (Fig. 6). The vacuum inside the vial causes the solvent to flow into the vial with the powder.

Fig.6
Fig.5
Fig.6

• 5. Remove the double-ended needle along with the empty vial of solvent (Fig. 7), then slowly rotate the vial with the powder and solvent until the product is dissolved. Pharmavate dissolves quickly at room temperature into a clear solution (Fig. 8).

Fig.8
Fig.7
Fig.8

Instructions for performing the injection:

As a precaution, you should check your pulse before and during the injection. If you notice a significant increase in heart rate, you should reduce the injection rate or interrupt the administration of the medicine.

• 1. After preparing the powder as described above, remove the protective cover from the filter needle and puncture the rubber stopper of the vial with the prepared concentrate.
• 2. Remove the needle cap from the filter needle and attach the syringe.
• 3. Turn the vial with the attached syringe upside down and draw the solution into the syringe.
• 4. Clean the selected injection site with one of the enclosed alcohol swabs.
• 5. Remove the filter needle from the syringe and attach the injection needle to the syringe.
• 6. Inject the solution into the vein, no faster than 2-3 ml per minute.

Any unused medicinal product or waste materials should be disposed of in accordance with local regulations. Patients using more than one vial of Pharmavate concentrate may use the same injection needle and syringe for injection, but the filter needle is intended for single use only. When drawing the solution into the syringe, you should always use a filter needle.

Use of a higher than recommended dose of Pharmavate

No symptoms of overdose of human coagulation factor VIII have been observed. However, it is recommended not to exceed the recommended dose.

Missed dose of Pharmavate

You should not take a double dose to make up for a missed dose. You should immediately proceed to the next dose and continue dosing as recommended by your doctor or pharmacist. You should consult your doctor or pharmacist if you have any other questions about using this product.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. Although they are rare(may affect up to 1 in 1000 people), allergic or hypersensitivity reactions have been observed in patients treated with factor VIII products. You should consult a doctor if you experience any of the following symptoms: vomiting, burning sensation and stinging pain at the injection site, feeling of pressure in the chest, chills, tachycardia, nausea, tingling sensation, redness, headache, hives, decreased blood pressure, rash, restlessness, swelling of the face, lips, mouth, tongue, or throat, which may lead to difficulty swallowing or breathing (angioedema), fatigue (lethargy), wheezing. Very rarely(may affect up to 1 in 10,000 people), hypersensitivity may lead to a life-threatening allergic reaction called anaphylaxis, which may include shock, as well as any of the symptoms listed above. In such a case, you should immediately consult a doctor or call emergency services. Other rare side effects (may affect up to 1 in 1000 people) include fever. In previously untreated children with factor VIII products, inhibitory antibodies (see section 2) may occur very frequently (more than 1 in 10 patients). However, in patients who have previously been treated with factor VIII (more than 150 days of treatment), the risk is not very common (less than 1 in 100 patients). If this happens, the patient's medicines may stop working properly, and the patient may experience persistent bleeding. If this happens, you should immediately consult a doctor. Information related to viral safety, see section 2. (You should exercise particular caution when using Pharmavate).

Reporting side effects

If you experience any side effects, including any side effects not listed in this leaflet, you should tell your doctor or pharmacist. Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products, Medical Devices, and Biocidal Products, Al. Jerozolimskie 181C, PL - 02-222 Warsaw, tel.: +48 22 49 21 301, fax: +48 22 49 21 309, website: https://smz.ezdrowie.gov.pl. Side effects can also be reported to the marketing authorization holder. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Pharmavate

The medicine should be stored out of the sight and reach of children. Do not use this medicine after the expiration date stated on the label. The expiration date refers to the last day of the specified month. Store in a temperature below 25°C. Do not freeze. Store in the outer packaging to protect from light. The solution after reconstitution should be used immediately and only during a single administration. Do not use this medicine if you notice that the solution is cloudy or not completely dissolved. Medicines should not be disposed of via wastewater or household waste. You should ask your pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the pack and other information

What Pharmavate contains

The active substance of the medicine is human coagulation factor VIII.

Volume and concentrations

The other ingredients are: For the powder: sodium citrate, sodium chloride, calcium chloride, glycine For the solvent: water for injections

What Pharmavate looks like and contents of the pack

Pharmavate is a powder and solvent for solution for injection. White or light yellow powder, or brittle mass. The solvent is a clear, colorless liquid. 3 available pack sizes differ in factor VIII content and solvent: 250 IU/vial: after reconstitution in 5 ml, the strength is 50 IU/ml 500 IU/vial: after reconstitution in 10 ml, the strength is 50 IU/ml 1000 IU/vial: after reconstitution in 10 ml, the strength is 100 IU/ml All pack sizes contain: 1 Mix2Vial system, 1 syringe for single use, 1 injection needle, and 2 alcohol swabs or 1 transfer set (1 double-ended needle and 1 filter needle), 1 syringe for single use, 1 injection needle, and 2 alcohol swabs Not all pack sizes may be marketed.

Marketing authorization holder

Octapharma (IP) SPRL, Route de Lennik 451, 1070 Anderlecht, Belgium

Manufacturer

Octapharma Pharmazeutika Produktionsges.m.b.H, Oberlaaer Str. 235, 1100 Vienna, Austria Octapharma S.A.S, 72 Rue du Maréchal Foch, 67380 Lingolsheim, France Octapharma AB, 112 75 Stockholm, Sweden

Date of last revision of the leaflet: 01.01.2025