Pharmavate

Poland
Brand name Pharmavate
Form solution for injection, powder and solvent for preparation of
Active substance / Dosage
human coagulation factor VIII · 50 j.m./ml
Prescription type Prescription only
ATC code
B02BD02
Registration number 100362510
Manufacturer Octapharma AB Octapharma Pharmaceuticals Production GmbH Octapharma SAS

Table of Contents

Patient Information Leaflet

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
Please read all of this leaflet carefully before using this medicine, as it contains important information for you.

  • Keep this leaflet, as you may need to read it again.
  • If you have any further questions, please consult your doctor, pharmacist, or nurse.
  • This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm other people, even if their symptoms are the same.
  • If any of the side effects worsens, or if you experience any side effects not listed in this leaflet, inform your doctor, pharmacist, or nurse.

Leaflet Contents:

  1. What Pharmavate is and what it is used for
  2. What you need to know 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 Pharmavate is and what it is 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 for the treatment and prevention of bleeding episodes in patients with haemophilia A. This is a condition characterized by prolonged bleeding compared to what is expected, caused by a congenital deficiency of coagulation 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 product name and batch number be recorded to maintain traceability of the batch used.
The physician may recommend considering vaccination against hepatitis A and B in patients receiving regular or repeated doses of human factor VIII products.

When not to use Pharmavate

  • if the patient is allergic to human blood coagulation factor VIII or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Before starting treatment with Pharmavate, consult a doctor, pharmacist, or nurse.
Pharmavate contains trace amounts of other human proteins. Any medicine containing proteins that is administered intravenously (given intravenously) may cause allergic reactions (see section 4. Possible side effects).
The development of inhibitors (antibodies) is a known complication that may occur during treatment with any factor VIII-containing medicines. These inhibitors, especially at high concentrations, may interfere with effective treatment, and the patient will be closely monitored for their development. If bleeding is not properly controlled with Pharmavate, inform the doctor immediately.

Information regarding blood and plasma used in the manufacture of Pharmavate

During the production of medicines derived from human blood or plasma, specific measures are taken to prevent the transmission of infections to patients. These include careful selection of blood and plasma donors to exclude those who may carry infections, as well as testing of all collected samples and plasma pools to detect the presence of viruses/infections. Manufacturers of these products have incorporated steps in the manufacturing process designed to inactivate or remove viruses. Despite these measures, when administering medicines prepared from human blood or plasma, it cannot be completely excluded that transmission of infection may occur. This also applies to unknown or newly emerging viruses or other types of infections.
The measures taken are considered effective against enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), and also against the non-enveloped hepatitis A virus (HAV). However, the methods used may have limited effectiveness against non-enveloped viruses such as parvovirus B19.
Parvovirus B19 infection may be dangerous for pregnant women (infection of the fetus) and for individuals with suppressed immune systems or those suffering from certain types of anemia (e.g., sickle cell anemia or abnormal red blood cell breakdown).

Other medicines and Pharmavate

Inform 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 factor VIII and other medicinal products are known.
However, Pharmavate must not be mixed with other medicines during infusion.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, suspect you may be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before using this medicine.

Driving and operating machinery

No effects on the ability to drive or operate machinery have been observed.

Pharmavate contains:

For the 250 IU vial, the product contains less than 1 mmol of sodium (23 mg) per dose, meaning the medicine is considered "sodium-free".
For the 500 IU and 1000 IU vials, the product contains up to 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 in patients on a sodium-controlled diet.

3. How to use Pharmavate

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

Dosing for prevention of bleeding:
For long-term prophylaxis of bleeding episodes in patients with severe haemophilia A, factor VIII should be administered at a dose of 20 to 40 IU per kilogram of body weight every 2 to 3 days.
The dose should be adjusted according to the clinical response. In some cases, more frequent administration or higher doses may be necessary.

Dose calculation:
Pharmavate should always be used as prescribed by the physician. In case of doubt, consult your doctor or pharmacist.

Plasma factor VIII activity corresponds to the concentration of factor VIII in plasma. It is expressed either as a percentage (relative 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 present in 1 ml of normal human plasma. An increase of 1 IU of factor VIII per kilogram of body weight raises plasma factor VIII activity by 1.5%–2% of normal activity. To calculate the required dose, determine the patient's plasma factor VIII activity. This will indicate by how much the activity needs to be increased. Consult your doctor if you are uncertain about the required increase in plasma factor VIII activity or how to calculate the appropriate dose.

The required dose is calculated using the following formula:
Required number of units = body weight (kg) × required increase in factor VIII activity (%) (IU/dl) × 0.5

The amount to be administered and the frequency of administration should always be adjusted according to the individual patient's clinical response.

In the following bleeding situations, plasma factor VIII activity should not fall below the indicated level (as % of normal values) for the specified period.

The following table may be helpful in determining doses for bleeding episodes or surgical procedures:

Bleeding severity /
Type of surgical procedure		Required factor VIII level (%)
(IU/dl)		Frequency of administration (hours) / Duration of therapy (days)
Bleeding
Early bleeding into joints, muscles or oral cavity20-40Repeat every 12 to 24 hours. At least 1 day until resolution of pain caused by bleeding or wound healing.
More severe bleeding into joints, muscles or hematoma30-60Repeat infusion every 12 to 24 hours for 3-4 days or more until resolution of pain and return of function.
Life-threatening bleeding60-100Repeat infusion every 8 to 24 hours until the threat is resolved.
Surgery
Minor
Including tooth extraction		30-60Every 24 hours, for at least 1 day until healing.
Major80-100
(pre- and postoperative)		Repeat infusion every 8 to 24 hours until adequate wound healing is achieved, then continue therapy for at least 7 additional days to maintain factor VIII activity at 30% to 60%.

The dose and frequency of administration of Pharmavate will be determined by the physician.
The response to factor VIII may vary among individual patients. Therefore, during treatment,
monitoring of factor VIII levels is recommended to determine the appropriate dose and frequency
of infusion.

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

Instructions for home use

  • Read all instructions carefully and follow them exactly!
  • Do not use Pharmavate after the expiry date stated on the label.
  • Aseptic conditions must be maintained during the procedure described below!
  • The solution in the syringe should be clear or slightly opalescent and shiny. Do not inject solutions that are cloudy or contain particulate matter.
  • The prepared solution should be used immediately to prevent microbiological contamination.
  • Use only the infusion set supplied. 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 directly after removing it from the refrigerator. Allow the diluent and powder vials to reach room temperature while still closed.
  2. Remove the caps from both vials and clean the rubber stoppers with one of the alcohol-impregnated swabs provided.
  3. The Mix2Vial™ system is shown in Fig. 1. Place the diluent vial on a flat surface and hold it firmly. Take the Mix2Vial™ and turn it. Place the blue part of the Mix2Vial™ onto the top of the diluent vial and press firmly until it clicks into place (Fig. 2 + 3).
Diagram showing screwing the upper component onto the lower part and placing the assembled unit over the vial labeled Solvent Schematic drawing of a medical device consisting of a white container labeled Solvent, a metal cap, and an upper component with a mesh Medical diagram showing a transparent powder adapter, integrated filter, and blue solvent adapter arranged vertically Diagram illustrating the process of connecting a powder vial with the upper vial containing solvent using a black downward-pointing arrow
  1. Place the vial containing the powder on a flat surface and hold it firmly. Take the diluent vial with the attached Mix2Vial™ and turn it upside down. Place the transparent part of the device onto the top of the powder vial and press firmly until it clicks into place (Fig. 4). The diluent will automatically flow into the powder vial.
Schematic showing unscrewing the solvent vial Solvent and connecting it to the vial containing powder Powder using a syringe
  1. With both vials connected, gently rotate the powder vial until the product is completely dissolved. Dissolution is completed in less than 10 minutes at room temperature. Slight foaming may occur during preparation. Unscrew the Mix2Vial™ into two parts (Fig. 5). The foam will disappear.

Discard the empty diluent vial with the blue part of the Mix2Vial™.
Instructions for administering the injection:
As a precaution, monitor the pulse before and during the injection.
If a significant increase in pulse rate occurs, reduce the injection speed or temporarily interrupt
administration of the medicine.

  1. Attach the syringe to the transparent part of the Mix2Vial™. Turn the vial upside down and draw the solution into the syringe (Fig. 6). The solution in the syringe should be clear or slightly opalescent and shiny. After transferring the solution, firmly hold the plunger of the syringe (with the syringe pointing downward) and remove the syringe from the Mix2Vial™ (Fig. 7). Discard the Mix2Vial™ and the empty vial.
Schematic illustration showing a white container labeled powder connected to a transparent syringe with a black downward-pointing arrow Exploded schematic of the medical device showing the upper container labeled powder and the lower syringe with plunger and base
  1. Clean the selected injection site with one of the alcohol-impregnated swabs provided.
  2. Attach the supplied administration needle to the syringe.
  3. Insert the needle into the selected vein. If a tourniquet was used to visualize the vein, release it before starting the injection of Pharmavate. Blood must not enter the syringe due to the risk of fibrin clot formation.
  4. Inject the solution slowly into the vein, no faster than 2–3 ml per minute.

When more than one vial of Pharmavate powder is used during a single administration, the same needle and syringe may be reused. The Mix2Vial™ set 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 directly after removing it from the refrigerator. Warm the powder and diluent in their closed vials to room temperature. Maintain this temperature during preparation. If a water bath is used for warming, ensure that water does not come into contact with the rubber stoppers (non-latex) or the caps of the vials. The water bath temperature must not exceed +37°C.
  2. Remove the caps from the powder vial and the diluent vial (Fig. 1) and clean the rubber stoppers with one of the alcohol-impregnated swabs provided (Fig. 2).
Line drawing showing two hands firmly holding and stabilizing a small medicinal vial in an upright position Two hands holding a medicinal vial, one hand removing the white protective cap or seal to prepare for use

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

  1. Remove the protective cover from the short end of the double-ended needle (Fig. 3), taking care not to touch the exposed needle tip. Then pierce the center of the rubber stopper of the diluent vial vertically with the needle (Fig. 4). To completely withdraw the liquid from the diluent vial, insert the needle through the rubber stopper so that it penetrates fully and is visible inside the vial.
Two hands holding a syringe with needle, one hand stabilizing the barrel while the other applies or removes the protective cap indicated by an arrow One hand holding a medicinal vial while the other presses a dropper vertically downward onto its stopper, indicating direction of movement

Fig. 4
Fig.3 Fig.4

  1. Remove the protective cover from the other, longer end of the double-ended needle, taking care not to touch the exposed needle tip (Fig. 5). Hold the diluent vial with the inserted needle upside down above the powder vial and quickly pierce the center of the rubber stopper of the powder vial with the needle (Fig. 6). The vacuum inside the vial causes the diluent to flow into the powder vial.
One hand holding a glass vial while the other decisively removes the plastic needle shield upward from the syringe Hands holding a liquid vial and another hand pressing a smaller vial downward onto the stopper of the first vial indicated by an arrow

Fig.6
Fig.5 Fig.6

  1. Remove the double-ended needle together with the empty diluent vial (Fig. 7), then slowly rotate the vial containing the powder and diluent until the product is completely dissolved. Pharmavate dissolves rapidly at room temperature into a clear solution (Fig. 8).
Hand holding a glass bottle with liquid performing a rotational movement indicated by a curved arrow at the bottom of the container Hands holding a medicinal vial and a syringe with needle directed toward the vial's stopper to withdraw the medication

Fig.8
Fig.7 Fig.8

Instructions for administering the injection:
As a precaution, monitor the pulse before and during the injection.
If a significant increase in pulse rate occurs, reduce the injection speed or temporarily interrupt
administration of the medicine.

  1. After preparing the powder as described above, remove the protective cover from the filter needle and pierce the rubber stopper of the vial containing the prepared concentrate.
  2. Remove the cap from the filter needle and attach the syringe.
  3. Invert the vial with the attached syringe and draw the solution into the syringe.
  4. Clean the selected injection site with one of the alcohol-impregnated swabs provided.
  5. Remove the filter needle from the syringe and attach the infusion needle to the syringe.
  6. Inject the solution into the vein at a rate not exceeding 2–3 ml per minute.

Any unused portions of the medicinal product or waste materials must be disposed of in accordance
with local regulations.
Patients using more than one vial of Pharmavate concentrate may reuse the same infusion needle and
syringe, but the filter needle is intended for single use only.
Always use a filter needle when drawing the solution into the syringe.

Use of a higher than recommended dose of Pharmavate
Symptoms of overdose with human coagulation factor VIII have not been observed. However, it is
recommended not to exceed the recommended dose.

Missed dose of Pharmavate
Do not administer a double dose to make up for a missed dose. Proceed promptly to the next dose and continue dosing as prescribed by the physician or pharmacist.
Contact your physician or pharmacist if you have any further questions regarding the use of this product.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
Although rare (may occur in 1 out of 1,000 people), hypersensitivity or allergic reactions have been observed in patients treated with products containing factor VIII.
You should contact your doctor if any of the following symptoms occur:
vomiting, burning or scalding pain at the infusion site, chest tightness, chills, tachycardia, nausea, tingling sensation, flushing, headache, urticaria, hypotension, rash, restlessness, facial swelling, swelling of the lips, oral cavity, tongue or throat, which may lead to difficulty swallowing or breathing (angioedema), fatigue (lethargy), wheezing.
Very rarely (may occur in 1 out of 10,000 people), hypersensitivity may lead to a life-threatening allergic reaction called anaphylaxis, which may include shock and some or all of the symptoms described above. In such a case, you should contact your doctor immediately or call emergency services.
Other rare adverse reactions (may occur in 1 out of 1,000 people):
Fever
In children who have not previously been treated with factor VIII-containing medicines, inhibitory antibodies (see section 2) may develop very commonly (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 uncommon (less than 1 in 100 patients). If this occurs, the patient's medicine may no longer work properly and persistent bleeding may occur. If this happens, contact your doctor immediately.
Viral safety information, see section 2. (Special caution should be exercised when using Pharmavate).
Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor or pharmacist.
Adverse reactions can be reported directly to the Department of Monitoring of Adverse Drug Reactions of the Office for Registration 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
Adverse reactions may also be reported to the marketing authorization holder.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Pharmavate

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label. The expiry date refers to the last day of the stated month.
Store 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 for a single administration.
Do not use this medicine if the solution appears cloudy or not completely dissolved.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures help protect the environment.

6. Contents of the pack and other information

What Pharmavate contains
The active substance is human coagulation factor VIII.
Volume and concentrations

Pharmavate® powder vial size (IU of factor VIII)Solvent vial size (to be added to the Pharmavate® powder vial) (ml)Approximate concentration of the solution after reconstitution (IU of factor VIII/ml)
250 IU550
500 IU1050
1,000 IU10100

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 available as a powder and solvent for solution for injection.
White or pale yellow powder, or friable mass.
The solvent is a clear, colourless liquid.
Three pack sizes differing in the content of factor VIII and solvent are available:

  • 250 IU/vial: after reconstitution in 5 ml, the concentration is 50 IU/ml
  • 500 IU/vial: after reconstitution in 10 ml, the concentration is 50 IU/ml
  • 1000 IU/vial: after reconstitution in 10 ml, the concentration is 100 IU/ml

All pack sizes contain:
1 Mix2Vial transfer system, 1 single-use syringe, 1 injection needle,
and 2 alcohol-impregnated swabs
or
1 transfer set (1 double-ended needle and 1 filter needle), 1 single-use syringe,
1 injection needle and 2 alcohol-impregnated swabs.
Not all pack sizes may be marketed.
Marketing Authorisation 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