25 U / ml, 50 U / ml. Powder and solvent for solution for infusion.
Factor VIII Inhibitor Bypassing Activity
1. What Feiba is and what it is used for
Feiba is a preparation made from human plasma that allows the blood to stop, even when individual coagulation factors are reduced or absent.
Feiba is used to treat bleeding in hemophilia A patients with inhibitors.
Feiba is used to treat bleeding in hemophilia B patients with inhibitors if no other specific treatment is available.
Feiba is also used to prevent bleeding in hemophilia A patients with inhibitors who have experienced major bleeding or are at high risk for major bleeding.
Feiba can also be used to treat non- hemophilia patients who have acquired factor VIII inhibitors.
2. What you need to know before using Feiba
Tell your doctor if you have a known allergy.
Tell your doctor if you are on a low sodium diet.
Do not use Feiba
In the following situations, Feiba should only be used if, for example, due to the very high titer of inhibitors, a response to the expected coagulation factor concentrate cannot be obtained as expected.
- if you are allergic (hypersensitive) to any of the ingredients in Feiba.
- if you have disseminated intravascular coagulation ( DIC ), a life-threatening condition in which extensive blood clotting with the pronounced formation of blood clots forms in the blood vessels. This then leads to a coagulation factor being consumed in the body.
- in case of myocardial infarction, acute thrombosis ( thrombosis ), and/or flushing of the bloodstream (embolism): Feiba should only be used in life-threatening bleeding.
Warnings and cautions
Talk to your doctor before using Feiba as hypersensitivity reactions may occur, as with any intravenously administered plasma product. To recognize an allergic reaction as soon as possible, you should be aware of potential early signs of a hypersensitivity reaction, such as
- erythema (reddening of the skin)
- rash
- hives on the skin ( urticaria )
- itching all over the body
- swelling of the lips and tongue
- difficulty breathing/dyspnoea
- pressure over the chest
- general malaise
- dizziness
- decreased blood pressure
Other symptoms of hypersensitivity reactions to products made from plasma are persistent unconsciousness ( lethargy ) and restlessness.
If you notice any of these symptoms occurring, stop the infusion immediately and consult a doctor. The above symptoms may be early signs of anaphylactic shock. Severe symptoms require immediate emergency treatment.
Your doctor will only treat you again if you suspect hypersensitivity to the product or any of its components after carefully considering the expected benefit against the risk of reintroduction and/or if no reaction can be expected with other preventive treatment or alternative medicines.
- If you experience major changes in blood pressure or pulse, difficulty breathing, cough, or chest pain, stop the infusion immediately and consult a doctor. Your doctor will put in place appropriate diagnostic and therapeutic measures.
- In patients who have hemophilia with inhibitors or acquired inhibitors of coagulation factors. During treatment with Feiba, these patients may have an increased bleeding tendency and an increased risk of thrombosis at the same time.
The occurrence of blood clots that may end up in the bloodstream (thrombotic and thromboembolic events), including multiple intravascular coagulation ( DIC ), blockages in the veins due to blood clots ( venous thrombosis ), blood clots in the lung ( pulmonary embolism ), heart attack and stroke have occurred during treatment with Feiba. Concomitant use of recombinant factor VIIa is likely to increase the risk of developing a blood clot that enters the bloodstream (thromboembolic event). Some of the thromboembolic events have occurred during treatment with high doses of Feiba.
In a study conducted by another company, which examined emicizumab (a drug to prevent bleeding in patients with hemophilia A), some patients suffering from breakthrough bleeding were treated with Feiba to control the bleeding, and a few of these patients developed thrombotic microangiopathy. (TMA). TMA is a serious and potentially life-threatening condition. When you have this condition, the walls of the blood vessels can be damaged and blood clots form in small blood vessels. In some cases, this can damage the kidneys and other organs. If you experience breakthrough bleeding when using emicizumab as preventative medicine, contact your hemophilia doctor or hemophilia center immediately.
When medicines are made from human blood or plasma, special measures are taken to prevent the transmission of infection to patients. This includes a careful selection of blood and plasma donors to ensure that those at risk of carrying an infection are excluded and that each plasma pool donation is tested for signs of virus/infection. The manufacturers of these products also include steps in the processing of blood and plasma that can inactivate or secrete viruses. Nevertheless, the risk of transmission of infection can not be completely ruled out when drugs are made from human blood or human plasmas. This also applies to new, hitherto unknown viruses and other types of infection.
The measures taken are considered effective for enveloped viruses, e.g. human immunodeficiency virus ( HIV ), hepatitis B virus, and hepatitis C virus and for the non-enveloped hepatitis A virus et. The measures may be of limited value against non-enveloped viruses such as parvovirus B19. Parvovirus B19 infection can be serious in pregnant women ( fetal infection ) and individuals with a weakened immune system or patients with certain anemia (eg sickle cell disease or hemolytic anemia ).
Your doctor may recommend that you consider hepatitis A and B vaccination if you regularly or repeatedly receive factor VIII inhibitors derived from human plasma.
Following administration of high doses of Feiba, a transient increase in passively transmitted hepatitis B surface antibodies may lead to misinterpretation of positive results in serological tests.
Feiba is a product made from plasma and may contain substances that react when given to a patient, which can lead to the formation of isohemagglutinins ( antibodies that cause red blood cells from another person to clot). This can lead to misleading results on blood tests.
It is strongly recommended that you note the name and batch number of Feiba at each treatment session to maintain a connection between you and the product batch number.
Other drugs and Feiba
Tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.
No adequate and well-controlled studies of the combined or sequential use of Feiba and recombinant factor VIIa, antacids (antifibrinolytics), or emicizumab have been performed. The possibility of blood clots should be considered when using systemic antifibrinolytics such as tranexamic acid and aminocaproic acid during treatment with Feiba. Therefore antifibrinolytics not be used for about 6 to 12 hours after administration of Feiba.
When co-administered with rFVIIa, potential drug interaction cannot be ruled out according to available in vitro data and clinical observations, which could potentially lead to a thromboembolic event. Tell your doctor if you are to be treated with Feiba after receiving emicizumab (a medicine that prevents bleeding in patients with hemophilia A) as certain warnings and precautions must be followed. Your doctor must monitor you closely.
Like all blood coagulation preparations, Feiba should not be mixed with other medicinal products before administration, as the efficacy and tolerance of the preparation may be impaired. It is recommended that joint vein access be flushed with physiological saline before and after administration of Feiba.
Pregnancy, breastfeeding, and fertility
Doctors decide if Feiba can be used during pregnancy and breast-feeding. Due to the increased risk of thrombosis during pregnancy, Feiba should only be administered under close medical supervision and only if necessary. Information on parvovirus B19 infection is provided in the Warnings and Precautions section.
Driving and using machines
There is no evidence that Feiba can affect the ability to drive and use machines.
Feiba contains sodium
Feiba 25 U / ml:
500 U
This medicine contains 80 mg of sodium (the main ingredient in table salt/table salt) per vial. This corresponds to 4% of the maximum recommended daily intake of sodium for adults.
Feiba 50 U / ml:
500 U
This medicine contains 40 mg sodium (the main ingredient in table salt/table salt) per vial. This corresponds to 2% of the maximum recommended daily sodium intake for adults.
1000 U
This medicine contains 80 mg of sodium (the main ingredient in table salt/table salt) per vial. This corresponds to 4% of the maximum recommended daily intake of sodium for adults.
2500 U
This medicine contains 200 mg of sodium (the main ingredient in table salt/table salt) per vial. This corresponds to 10% of the maximum recommended daily intake of sodium for adults.
3. How to use Feiba
Reconstitute the lyophilized Feiba powder in the supplied diluent and administer the solution intravenously.
Always use Feiba exactly as your doctor has told you. Ask your doctor or pharmacist if you are unsure.
Your doctor will decide on the dosage one, how often you should be treated and the duration of the treatment, depending on the severity of your coagulation disorder, the location, and extent of the bleeding, and the condition. Do not change the dosage prescribed by your doctor and do not stop using the preparation on your own.
Talk to your doctor or pharmacist if you have the impression that the effect of Feiba is too strong or too weak.
Warm the product to room or body temperature before administering one if necessary.
Feiba should be reconstituted immediately before administration. The solution should be used immediately (as the preparation does not contain any preservative ).
Gently swirl the bottle until all the powder has dissolved. Make sure that Feiba dissolves completely, otherwise fewer Feiba units will pass through the device’s filter.
Solutions that are cloudy or have precipitated material should be disposed of appropriately.
Do not reuse opened containers.
Use only the supplied water for injections and the kit provided for reconstitution.
If devices other than those provided are used, check that a suitable filter with a pore size of at least 149 µm is used.
Do not use the product if the sterile barrier has been broken, the packaging is damaged, or if it shows signs of deterioration.
Any unused product or waste material should be disposed of by local requirements.
Reconstitution of the powder to prepare an infusion solution with BaxJect II Hi-Flow:
- Heat the unopened vial of diluent (water for injections) to room temperature or not more than + 37 ° C) if necessary, e.g. in a water bath for a few minutes.
- Remove the caps from the bottles of powder and water and disinfect the rubber stoppers. Place the bottles on a flat surface.
- Open the package with BAXJECT II Hi-Flow by pulling off the protective foil without touching the contents of the package (Figure a). Do not remove the accessory from the package.
- Turn the package over and push the clear plastic tip through the rubber stopper of the water bottle (Fig. B). Grasp the edges of the package and pull the package away from the BAXJECT II Hi-Flow (Figure c). Do not remove the blue cover from the BAXJECT II Hi-Flow.
- Turn the entire system over with the BAXJECT II Hi-Flow attached to the water bottle so that the water bottle ends up on top. Push the purple plastic tip through the rubber stopper of the powder bottle. The water will be sucked into the Feiba bottle by vacuum (Pictured which can be found under the information for “Infusion”).
- Rotate the bottle gently, (do not shake), until all the powder is completely dissolved. Check that Feiba is completely dissolved, otherwise, an active substance may get stuck in the filter.
Infusion
Use aseptic technique throughout the procedure!
- Remove the blue cover from the BAXJECT II Hi-Flow. Take the syringe and connect it to the BAXJECT II Hi-Flow. DO NOT draw air into the syringe. (Picture e). The use of a Luer lock syringe is recommended to ensure a tight connection between the syringe and the Baxject II Hi-Flow (turn the syringe clockwise until it stops).
- Turn the system upside down so that the bottle of dissolved Feiba ends up on top. SLOWLY pull the solution into the syringe by carefully pulling out the syringe plunger and making sure that a proper connection between the BAXJECT II Hi-Flow and the syringe is maintained throughout the application process (Fig. F).
- Remove the syringe.
- If foaming occurs, wait until the foam has disappeared. Administer the solution slowly intravenously with the supplied infusion set (or a single-use needle).
Do not exceed the infusion rate of 2 units Feiba / kg body weight per minute.
If you use more Feiba than you should:
Tell your doctor immediately. Overdose of Feiba may increase the risk of side effects, e.g. thromboembolism (the formation of a blood clot that flushes into the blood vessels), consumption coagulopathy (pronounced blood clot formation in the blood vessels, DIC ), or heart attack. Some of the reported thromboembolic events occurred at doses above 200 units/kg daily or in patients with other risk factors for thromboembolic events. If signs or symptoms of thrombotic and thromboembolic events are observed, the infusion should be stopped immediately, and appropriate diagnostic and therapeutic measures instituted.
4. Possible side effects
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Common side effects are (may affect up to 1 in 10 people):
Hypersensitivity, headache, dizziness, low blood pressure, rash, a positive test for hepatitis B surface antibodies.
Adverse reactions with unknown frequency (cannot be calculated from the available data)
Blood and lymphatic system disorders: DIC, severe coagulation disorder ( DIC ), the increased titer of inhibitors
Immune system disorders: Anaphylactic reactions, hives all over the body ( urticaria )
Central and peripheral nervous system: Numbness in arms and legs ( hypoesthesia ), abnormal or impaired sensation ( paresthesia ), stroke (thrombotic stroke, embolic stroke ), drowsiness (insomnia), altered taste sensation ( dysgeusia )
Heart: Myocardial infarction (myocardial infarction), rapid heartbeat ( tachycardia )
Blood vessels: Blood clots that are flushed into vessels (thromboembolic events, venous and arterial thrombosis ), increased blood pressure ( hypertension ), redness
Respiratory, thoracic, and mediastinal disorders (space between the lungs, eg trachea, esophagus, heart, etc.): Obstruction of the pulmonary artery ( pulmonary embolism ), contractions of the airways ( bronchospasm ), wheezing, cough, shortness of breath ( dyspnoea )
Gastrointestinal disorders: Vomiting, diarrhea, abdominal pain, malaise (nausea)
Skin and subcutaneous tissue disorders: Numbness of the face, swelling of the face, tongue, and lips ( angioedema ), hives all over the body ( urticaria ), pruritus ( pruritus )
General disorders and administration site conditions: Injection site pain, malaise, fever, chills, fever, chest pain, chest discomfort
Examinations: Decreased blood pressure
A rapid intravenous infusion may cause stabbing pain and numbness in the face, arms, and legs as well as a drop in blood pressure.
Myocardial infarction has been observed after administration of doses above the daily maximum dose and/or prolonged use and/or the presence of risk factors for thromboembolism.
5. How to store Feiba
Keep out of sight and reach of children.
Do not store above 25 ° C. Do not freeze.
Store in the original package. Sensitive to light.
Do not use Feiba after the expiry date which is stated on the label and carton. The expiration date is the last day of the specified month.
The medicine should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.
6. Contents of the packaging and other information
Content declaration for Feiba 25 U / ml
Powder
- The active substance in each vial is factor VIII inhibitor bypass activity.
- One ml contains 25 units of factor VIII inhibitor bypass activity.
- One vial of Feiba 25 units/ml contains 500 units of factor VIII inhibitor bypassing activity.
- The human plasma protein content is 200-600 mg / 500 units.
Feiba also contains factor II, IX, and X, mainly in non-activated form, as well as activated factor VII. Factor VIII coagulation antigen (F VIII C: Ag) and the factors in the kallikrein-quinine system (a metabolic interaction system) are only present in traceable amounts, if at all. - The other ingredients are sodium chloride and sodium citrate.
Diluent
- Water for injections
Content declaration for Feiba 50 U / ml
Powder
- The active substance in each vial is factor VIII inhibitor bypass activity.
- One ml contains 50 units of factor VIII inhibitor bypassing activity.
- One vial of Feiba 50 units/ml contains 500 units of factor VIII inhibitor bypass activity.
- One vial of Feiba 50 units/ml contains 1000 units of factor VIII inhibitor bypassing activity.
- One vial of Feiba 50 units/ml contains 2500 units of factor VIII inhibitor bypassing activity.
- Human plasma protein content is 200–600 mg / 500 units and 400-1200 mg / 1000 units and 1000-3000 mg / 2500 units.
Feiba also contains factor II, IX, and X, mainly in non-activated form, as well as activated factor VII. Factor VIII coagulation antigen (F VIII C: Ag) and the factors in the kallikrein-quinine system (a metabolic interaction system) are only present in traceable amounts, if at all. - The other ingredients are sodium chloride and sodium citrate.
Diluent
- Water for injections
What the medicine looks like and the contents of the pack
The product is presented in the form of a lyophilized powder or a brittle solid with a white to almost white or pale green color. The ready solution pH is between 6.8 and 7.6.
The powder and solvent are supplied in glass vials sealed with rubber stoppers.
25 U / ml
Package type: 1 x 500 units
50 U / ml
Package type: 1 x 500 units, 1 x 1000 units, 1 x 2500 units.
Not all pack sizes may be marketed.
25 U / ml
Package contents:
- 1 vial with 500 units Feiba powder for infusion solution
- 1 vial with 20 ml of diluent (water for injections)
- 1 BAXJECT II Hi-Flow for reconstitution
- 1 disposable syringe
- 1 disposable needle
- 1 butterfly needle set with clamp
- 1 vial with 500 units Feiba powder for infusion solution
- 1 vial of 20 ml sterile water for injections
- 1 disposable syringe
- 1 disposable needle
- 1 butterfly needle set with clamp
- 1 filter cannula
- 1 transfer cannula
- 1 aeration cannula
50 U / ml
Package contents:
– 1 vial with 500, 1000 units, or 2500 units Feiba powder for infusion solution
– 1 vial with 10 ml, 20 ml alt. 50 ml diluent (water for injections)
– 1 BAXJECT II Hi-Flow for reconstitution
– 1 disposable syringe
– 1 disposable needle
– 1 butterfly needle set with clamp
– 1 vial with 500 units or 1000 units Feiba powder for infusion solution
– 1 vial with 10 ml, 20 ml sterile water for injections
– 1 disposable syringe
– 1 disposable needle
– 1 butterfly needle set with clamp
– 1 filter cannula
– 1 transfer cannula
– 1 aeration cannula
Marketing Authorisation Holder
Baxalta Innovations GmbH
Industriestrasse 67
1220 Vienna
Austria
Manufacturer
Baxter AG
Industriestrasse 67
1220 Vienna
Austria
Takeda Manufacturing Austria AG
Industriestrasse 67
1221 Vienna
Austria
Agent
Takeda Pharma AB
Vasagatan 7, 6 tr
111 20 Stockholm