Kogenate FS

Control And Prevention Of Bleeding Episodes

Kogenate® FS is an antihemophilic factor that is indicated for the control and prevention of bleeding episodes in adults and children (0-16 years) with hemophilia A.

Peri-operative Management

Kogenate FS is indicated for surgical prophylaxis in adults and children with hemophilia A.

Routine Prophylaxis In Children With Hemophilia A With No Pre-existing Joint Damage

Kogenate FS is indicated for routine prophylactic treatment to reduce the frequency of bleeding episodes and the risk of joint damage in children with no pre-existing joint damage.

Kogenate FS is not indicated for the treatment of von Willebrand's disease.

Kogenate is a prescription medication used to prevent bleeding episodes in children and adults with hemophilia A (also known as "classical hemophilia"). Kogenate can also be used to reduce the risk of joint damage in children who do not have any current joint damage.

Kogenate belongs to a group of drugs called clotting factors. It works by replacing a protein in the blood that is needed to control bleeding that people with hemophilia A are missing.

This medication comes in an injectable form to be given directly into a vein (IV) by a healthcare professional.

Common side effects of Kogenate include infusion site reactions, rash, and itching.

Medications can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of Kogenate, there are no specific foods that you must exclude from your diet when receiving this medication.

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Kogenate falls into category C. No studies have been done in animals, and no well-controlled studies have been done in pregnant women. Kogenate should be given to a pregnant woman only if clearly needed.

Kogenate comes in an injectable form to be given directly into a vein (IV) by a healthcare professional. Kogenate is given as an infusion over a period of 15 minutes or less.

Your doctor may allow you to infuse Kogenate at home if you are regularly receiving this medication. Follow your doctor's instructions exactly on how to mix and administer Kogenate.

If you miss an appointment to receive a dose of Kogenate, contact your healthcare provider for instructions on when to receive your next dose.

Use Kogenate FS as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• It is given as a shot into a vein.
• This medicine may be given at home.
• If you will be giving yourself the shot, your doctor or nurse will teach you how to give the shot.
• Follow how to use as you have been told by the doctor or read the package insert.
• Wash your hands before and after use.
• If stored in a refrigerator, let this medicine come to room temperature before mixing. Do not heat Kogenate FS.
• This medicine needs to be mixed before use. Follow how to mix as you were told by the doctor.
• Do not shake.
• Most products will be clear and colorless after mixing. Some products may be clear to slightly cloudy and colorless after mixing. Some products may be colorless to a faint yellow after mixing. Be sure you know what the product will look like after mixing.
• Do not use if the solution is cloudy, leaking, or has particles.
• Do not use if solution changes color.
• After mixing, do not refrigerate.
• Use within 3 hours of making.
• Throw away any part of opened vial not used after use.
• Throw away needles in a needle/sharp disposal box. Do not reuse needles or other items. When the box is full, follow all local rules for getting rid of it. Talk with a doctor or pharmacist if you have any questions.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

General

The clinical response to Kogenate FS may vary. If bleeding is not controlled with the recommended dose, the plasma level of factor VIII should be determined and a sufficient dose of Kogenate FS should be administered to achieve a satisfactory clinical response. If the patient’s plasma factor VIII level fails to increase as expected or if bleeding is not controlled after the expected dose, the presence of an inhibitor (neutralizing antibodies) should be suspected and appropriate testing performed. [See Warnings and Precautions (5.4).]

Anaphylaxis and Severe Hypersensitivity Reactions

Allergic-type hypersensitivity reactions including anaphylaxis have been reported with Kogenate FS and have manifested as pruritus, rash, urticaria, hives, facial swelling, dizziness, hypotension, nausea, chest discomfort, cough, dyspnea, wheezing, flushing, discomfort (generalized) and fatigue. Discontinue Kogenate FS if symptoms occur and seek immediate emergency treatment.

Kogenate FS contains trace amounts of mouse immunoglobulin G (MuIgG) and hamster (BHK) proteins. Patients treated with this product may develop hypersensitivity to these non-human mammalian proteins.

Neutralizing Antibodies

Patients treated with antihemophilic factor (AHF) products should be carefully monitored for the development of factor VIII inhibitors by appropriate clinical observations and laboratory tests.6 Inhibitors have been reported following administration of Kogenate FS predominantly in previously untreated patients. If expected plasma factor VIII activity levels are not attained, or if bleeding is not controlled with an expected dose, an assay that measures factor VIII inhibitor concentration should be performed.[See Warnings and Precautions (5.4).]

Monitoring Laboratory Tests

• Monitor plasma factor VIII activity levels by the one-stage clotting assay to confirm the adequate factor VIII levels have been achieved and maintained, when clinically indicated. [See Dosage and Administration (2).]
• Monitor for development of factor VIII inhibitors. Perform assay to determine if factor VIII inhibitor is present. If expected factor VIII activity plasma levels are not attained, or if bleeding is not controlled with the expected dose of Kogenate FS. Use Bethesda Units ( BU) to titer inhibitors.
  • If the inhibitor is less than 10 BU per mL, the administration of additional Kogenate FS concentrate may neutralize the inhibitor, and may permit an appropriate hemostatic response.

Adequate hemostasis may not be achieved if inhibitor titers are above 10 BU per mL. The inhibitor titer may rise following Kogenate FS infusion as a result of an anamnestic response to factor VIII. The treatment or prevention of bleeding in such patients requires the use of alternative therapeutic approaches and agents.

Preclinical studies evaluating Kogenate FS in hemophilia A with mice, rats, rabbits, and dogs demonstrated safe and effective restoration of hemostasis. Doses several fold higher than the recommended clinical dose (related to body weight) did not demonstrate any acute or subacute toxic effect for Kogenate FS in laboratory animals.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No studies have been conducted with Kogenate FS to assess its mutagenic or carcinogenic potential and impairment of fertility. Kogenate FS has been shown to be comparable to the predecessor product with respect to its biochemical and physiochemical properties, as well as its non-clinical in vivo pharmacology and toxicology. By inference, the predecessor product and Kogenate FS would be expected to have equivalent mutagenic and carcinogenic potential.

The predecessor product did not demonstrate reverse mutation or chromosomal aberrations at doses substantially greater than the maximum expected clinical dose. In vivo evaluation with the predecessor product in animals using doses ranging between 10 and 40 times the expected clinical maximum also indicated that the predecessor product did not possess a mutagenic potential. Long-term investigations of carcinogenic potential in animals have not been performed due to the immune response to heterologous proteins in all non-human mammalian species.

How Supplied

Kogenate FS Antihemophilic Factor (Recombinant) with BIO-SET®, a needleless self-contained system, is supplied in the following single use glass vial sizes. A prefilled diluent syringe containing sterile water (meets USP chemistry requirements Sterile Water for Injection, except for pH) for reconstitution, an administration set, two alcohol swabs, one bandage, and one cotton pad are also provided.

Actual factor VIII activity in IU is stated on the label of each Kogenate FS Vial.

Storage and Handling

• Store Kogenate FS at +2°C to +8°C (36°F to 46°F) for up to 30 months from the date of manufacture. Within this period, Kogenate FS may be stored for a period of up to 12 months at temperatures up to +25°C or 77°F, such as in home treatment situations.
• The starting date of room temperature storage should be clearly recorded on the unopened product carton. Once stored at room temperature, the product must not be returned to the refrigerator. The shelf-life then expires after the storage at room temperature, or the expiration date on the product vial, whichever is earlier.
• Do not use Kogenate FS after the expiration date indicated on the vial.
• Do not freeze.
• Protect from extreme exposure to light and store the lyophilized powder in the carton prior to use.

• Administer Kogenate FS within 3 hours after reconstitution.
• It is recommended to use the administration set provided.

See Patient Product Information and Instructions for Use

Advise patients to report any adverse reactions or problems following Kogenate FS administration to their physician or healthcare provider.

• Allergic-type hypersensitivity reactions have been reported with Kogenate FS. Warn patients of the early signs of hypersensitivity reactions [including hives (rash with itching), generalized urticaria, tightness of the chest, wheezing, hypotension] and anaphylaxis. Advise patients to discontinue use of the product if these symptoms occur and seek immediate emergency treatment with resuscitative measures such as the administration of epinephrine and oxygen.
• In clinical studies with Kogenate FS, a 15% incidence of inhibitor development was observed in PUPs/MTPs and zero de-novo inhibitors were observed with the PTPs. Inhibitor formation may occur at any time in the treatment of a patient with hemophilia A. Advise patients to contact their physician or treatment center for further treatment and/or assessment, if they experience a lack of clinical response to factor VIII replacement therapy, as this may be a manifestation of an inhibitor.
• Advise patients to consult with their healthcare provider prior to travel. While traveling advise patients to bring an adequate supply of Kogenate FS based on their current regimen of treatment.

FDA-Approved Patient Labeling

Kogenate FS (kō-jen-ate)

Antihemophilic Factor (Recombinant)

Formulated with Sucrose

This leaflet summarizes important information about Kogenate FS with BIO-SET, a needleless self-contained reconstitution system. Please read it carefully before using this medicine. This information does not take the place of talking with your healthcare provider, and it does not include all of the important information about Kogenate FS. If you have any questions after reading this, ask your healthcare provider.

Do not attempt to self-infuse unless you have been taught how by your healthcare provider or hemophilia center.

What is Kogenate FS?

Kogenate FS is a medicine used to replace clotting factor (factor VIII or antihemophilic factor) that is missing in people with hemophilia A (also called “classic” hemophilia). Hemophilia A is an inherited bleeding disorder that prevents blood from clotting normally.

Kogenate FS is used to prevent and control bleeding in adults and children (0-16 years) with hemophilia A. Your healthcare provider may give you Kogenate FS when you have surgery. Kogenate FS can reduce the number of bleeding episodes when used regularly and reduce the risk of joint damage in children.

Kogenate FS is not used to treat von Willebrand's Disease.

Who should not use Kogenate FS?

You should not use Kogenate FS if you

• are allergic to rodents (like mice and hamsters).
• are allergic to any ingredients in Kogenate FS.

Tell your healthcare provider if you are pregnant or breast-feeding because Kogenate FS may not be right for you.

What should I tell my healthcare provider before I use Kogenate FS?

Tell your healthcare provider about all of your medical conditions.

Tell your healthcare provider and pharmacist about all of the medicines you take, including all prescription and non-prescription medicines, such as over-the-counter medicines, supplements, or herbal remedies.

Tell your healthcare provider if you have been told that you have inhibitors to factor VIII (because Kogenate FS may not work for you).

What are the possible side effects of Kogenate FS?

You could have an allergic reaction to Kogenate FS. Call your healthcare provider right away and stop treatment if you get

• rash or hives
• itching
• tightness of the chest or throat
• difficulty breathing
• light-headed, dizziness
• nausea
• decrease in blood pressure

Your body can also make antibodies, called “inhibitors,” against Kogenate FS, which may stop Kogenate FS from working properly. Consult with your healthcare provider to make sure you are carefully monitored with blood tests for the development of inhibitors to factor VIII.

Other common side effects of Kogenate FS are

• Local injection site reactions (pain, swelling, irritation at infusion site)
• Infections from implanted injection device

Tell your healthcare provider about any side effect that bothers you or does not go away.

Finding veins for injections may be difficult in young children. When frequent injections are required your child's healthcare provider may propose to have a device surgically placed under the skin to facilitate access to the bloodstream. These devices may result in infections.

These are not all the possible side effects with Kogenate FS. You can ask your healthcare provider for information that is written for healthcare professionals.

How do I store Kogenate FS?

Do not freeze Kogenate FS.

Store Kogenate FS at +2°C to +8°C (36°F to 46°F) for up to 30 months from the date of manufacture. Within this period, Kogenate FS may be stored for a period of up to 12 months at temperatures up to +25°C or 77°F.

The starting date of room temperature storage should be clearly recorded on the unopened product carton. Once stored at room temperature, the product must not be returned to the refrigerator. The shelf-life then expires after the storage at room temperature, or the expiration date on the product vial, whichever is earlier. Store vials in their original carton and protect them from extreme exposure to light.

Reconstituted product (after mixing dry products with wet diluent) must be used within 3 hours and cannot be stored.

Throw away any unused Kogenate FS after the expiration date.

Do not use reconstituted Kogenate FS if it is not clear to slightly cloudy and colorless.

What else should I know about Kogenate FS and hemophilia A?

Medicines are sometimes prescribed for purposes other than those listed here. Do not use Kogenate FS for a condition for which it is not prescribed. Do not share Kogenate FS with other people, even if they have the same symptoms that you have.

This leaflet summarizes the most important information about Kogenate FS. If you would like more information, talk to your healthcare provider. You can ask your healthcare provider or pharmacist for information about Kogenate FS that was written for healthcare professionals.

Instructions for use

How should I take Kogenate FS?

Do not attempt to self-infuse unless you have been taught how by your healthcare provider or hemophilia center.

See the step-by-step instructions for reconstituting Kogenate FS with BIO-SET at the end of this leaflet and the specific infusion instruction leaflet provided.

You should always follow the specific instructions given by your healthcare provider. The steps listed below are general guidelines for using Kogenate FS. If you are unsure of the procedures, please call your healthcare provider before using.

Call your healthcare provider right away if bleeding is not controlled after using Kogenate FS.

Your healthcare provider will prescribe the dose that you should take.

Your healthcare provider may need to take blood tests from time to time.

Talk to your healthcare provider before traveling. You should plan to bring enough Kogenate FS for your treatment during this time.

Carefully handle Kogenate  FS. Dispose of all materials, including any leftover reconstituted Kogenate  FS product, in an appropriate container.

Reconstitution and use of Kogenate FS

Always work on a clean surface and wash your hands before performing the following procedures:

1. Prepare

A. Open

The easiest way to remove the cap from the vials is to move the top from side-to-side while pulling upward at the same time. This breaks the small plastic tabs that connect the cap to the top of the vial.

B. Remove Tip Cap

Remove the tamper-evident tip cap from the syringe. Separate the tip cap from the syringe by gently breaking it off. Hold the syringe in one hand while snapping off the tip cap with the other hand. Do not try to twist it off. Move it from side to side.

C. Connect Syringe

Connect the prefilled syringe to the powder vial by gently screwing it on clockwise on to the top of the vial until finger tight. Do not overtighten.

2. Activate

A. Activate (Spike the vial)

Place the vial on a solid, non-skid surface. Hold the vial firmly with one hand. With the other hand, place your thumb and forefinger on the fingerplate of the syringe and press down firmly on the fingerplate until it meets the top of the powder vial. This is the most critical step in the process. If the syringe is not pushed down firmly enough, the system will not be fully activated.

B. Connect Plunger Rod

Grasp the plunger rod at the top. Avoid contact with the rest of the plunger rod. Immediately connect it to the syringe by screwing the plunger rod clockwise into the rubber stopper.

C. Inject

Inject diluent into the vial by slowly pressing down the plunger rod. Pushing down the syringe too quickly may cause foaming in the vial. If this occurs, wait until the foam subsides before continuing.

D. Mix

Mix the diluent and powder by swirling gently and slowly. DO NOT SHAKE THE VIAL. Be sure the powder is completely dissolved before using.

3. Transfer

A. Transfer

Invert the vial, with the syringe still attached and smoothly draw all the solution into the syringe. Tilt the vial to the side and back to check that all remaining solution has been drawn into the large opening in the rubber stopper.

B. Disconnect

Disconnect the syringe from the empty vial by unscrewing it counterclockwise. DO NOT PULL THE SYRINGE FROM THE VIAL WITHOUT UNSCREWING IT FIRST.

C. Infuse

Attach the syringe to the butterfly set by screwing it in clockwise and follow the infusion instructions provided with Kogenate FS with BIO-SET.

Rate of administration

The entire dose of Kogenate  FS can usually be infused within 1 to 15 minutes. However, your healthcare provider will determine the rate of administration that is best for you.

Resources at Bayer available to the patient:

For Adverse Reaction Reporting contact:

Bayer Medical Communications 1-888-84-BAYER (1-888-842-2937)

Contact Bayer to receive more product information:

Kogenate FS Customer Service 1-888-606-3780

Bayer Reimbursement HELPline 1-800-288-8374

For more information, visit www.kogenatefs.com

Bayer HealthCare LLC Tarrytown, NY 10591 USA

U.S. License No. 8

(License Holder: Bayer Corporation)

Kogenate FS with BIO-SET Carton 250 IU

NDC 0026-3792-20

Kogenate FS

Antihemophilic

Factor

(Recombinant)

With BIO-SET

Formulated with

Sucrose

Kogenate FS with BIO-SET Carton 500 IU

NDC 0026-3793-30

Kogenate FS

Antihemophilic

Factor

(Recombinant)

With BIO-SET

Formulated with

Sucrose

Kogenate FS with BIO-SET Carton 1000 IU

NDC 0026-3795-50

Kogenate FS

Antihemophilic

Factor

(Recombinant)

With BIO-SET

Formulated with

Sucrose

Kogenate FS with BIO-SET Carton 2000 IU

NDC 0026-3796-60

Kogenate FS

Antihemophilic

Factor

(Recombinant)

With BIO-SET

Formulated with

Sucrose

Kogenate FS with BIO-SET Carton 3000 IU

NDC 0026-3797-70

Kogenate FS

Antihemophilic

Factor

(Recombinant)

With BIO-SET

Formulated with

Sucrose