Xyntha: Package Insert and Label Information (Page 4 of 5)

15 REFERENCES

1.

Nilsson IM, Berntorp EE and Freiburghaus C. Treatment of patients with factor VIII and IX inhibitors. Thromb Haemost. 1993;70(1):56–59.

2.

Hoyer LW. Hemophilia A. N Engl J Med. 1994;330:38–47.

3.

Juhlin F. Stability and Compatibility of Reconstituted Recombinant Factor VIII SQ, 250 IU/ml, in a System for Continuous Infusion. Pharmacia Document 9610224, 1996.

4.

Ehrenforth S, Kreuz W, Scharrer I, et al. Incidence of development of factor VIII and factor IX inhibitors in hemophiliacs. Lancet. 1992;339:594–598.

5.

Lusher J, Arkin S, Abildgaard CF, Schwartz RS, the Kogenate PUP Study Group. Recombinant factor VIII for the treatment of previously untreated patients with hemophilia A. N Engl J Med. 1993;328:453–459.

6.

Bray GL, Gomperts ED, Courter S, et al. A multicenter study of recombinant factor VIII (Recombinate): safety, efficacy, and inhibitor risk in previously untreated patients with hemophilia A. Blood. 1994;83(9):2428–2435.

7.

Kessler C, Sachse K. Factor VIII:C inhibitor associated with monoclonal-antibody purified FVIII concentrate. Lancet. 1990;335:1403.

8.

Schwartz RS, Abildgaard CF, Aledort LM, et al. Human recombinant DNA-derived antihemophilic factor (factor VIII) in the treatment of hemophilia A. N Engl J Med. 1990;323:1800–1805.

9.

White GC II, Courter S, Bray GL, et al. A multicenter study of recombinant factor VIII (Recombinate™) in previously treated patients with hemophilia A. Thromb Haemost. 1997;77(4):660–667.

10.

Gruppo R, Chen H, Schroth P, et al. Safety and immunogenicity of recombinant factor VIII (Recombinate™) in previously untreated patients: A 7.3 year update. Haemophilia. 1998;4:228 (Abstract No. 291, XXIII Congress of the WFH, The Hague).

11.

Scharrer I, Bray GL, Neutzling O. Incidence of inhibitors in haemophilia A patients — a review of recent studies of recombinant and plasma-derived factor VIII concentrates. Haemophilia. 1999;5:145–154.

12.

Abshire TC, Brackmann HH, Scharrer I, et al. Sucrose formulated recombinant human antihemophilic Factor VIII is safe and efficacious for treatment of hemophilia A in home therapy: Results of a multicenter, international, clinical investigation. Thromb Haemost. 2000;83(6):811–816.

13.

Sandberg H, Almstedt A, Brandt J, Castro VM, Gray E, Holmquist L, et al. Structural and Functional Characterization of B-Domain Deleted Recombinant Factor VIII. Sem Hematol. 2001;38 (Suppl. 4):4–12.

14.

Kelley BD, Tannatt M, Magnusson R, Hagelberg S. Development and Validation of an Affinity Chromatography Step Using a Peptide Ligand for cGMP Production of Factor VIII. Biotechnol Bioeng. 2004;87(3):400–412.

15.

Mann KG and Ziedens KB. Overview of Hemostasis. In: Lee CA, Berntorp EE and Hoots WK, eds. Textbook of Hemophilia. USA, Blackwell Publishing; 2005:1–4.

16.

Recht M, Nemes L, Matysiak M et al. Clinical Evaluation of Moroctocog Alfa (AF-CC), a New Generation of B-Domain Deleted Recombinant Factor VIII (BDDrFVIII) for Treatment of Haemophilia A: Demonstration of Safety, Efficacy and Pharmacokinetic Equivalence to Full-length Recombinant Factor VIII. Haemophilia 2009; 1–12.

17.

Windyga J, Rusen L, Gruppo R, et al. BDDrFVIII (Moroctocog alfa [AF-CC]) for surgical haemostasis in patients with haemophilia A: results of a pivotal study. Haemophilia. 2010 Sep 1;16(5):731–9.

16 HOW SUPPLIED/STORAGE AND HANDLING

How Supplied

Each XYNTHA SOLOFUSE Kit contains: one plunger rod for assembly, one sterile infusion set, two alcohol swabs, one bandage, one gauze pad, one vented sterile cap, and one package insert. The drug product, diluents for injection and the rest of components included within the XYNTHA 250, 500, 1000, 2000, or 3000 International Units kit are free from natural rubber and natural rubber latex.

XYNTHA SOLOFUSE is supplied in a kit that includes the XYNTHA lyophilized powder containing nominally 250, 500, 1000, 2000 or 3000 IU and 4 mL 0.9 % Sodium Chloride solution for reconstitution in a prefilled dual-chamber syringe:

XYNTHA SOLOFUSE Kit

Nominal Strength	Fill Size Color Indicator	Kit NDC #
250 International Units	Yellow	58394-022-03
500 International Units	Blue	58394-023-03
1000 International Units	Green	58394-024-03
2000 International Units	Red	58394-025-03
3000 International Units	Gray	58394-016-03

Actual factor VIII activity in International Units is stated on the label of each XYNTHA SOLOFUSE.

Storage and Handling

Product as Packaged for Sale:

•

Store XYNTHA SOLOFUSE under refrigeration at a temperature of 2° to 8°C (36° to 46°F) for up to 36 months from the date of manufacture until the expiration date stated on the label.

•

Within the expiration date, XYNTHA SOLOFUSE also may be stored at room temperature not to exceed 25°C (77°F) for up to 3 months.

•

Clearly record the starting date at room temperature storage in the space provided on the outer carton. At the end of the 3-month period, immediately use or discard the product. Do not put the product back into the refrigerator.

•

Do not use XYNTHA SOLOFUSE after the expiration date stated on the label or after 3 months when stored at room temperature, whichever is earlier.

•

Do not freeze. (Freezing may damage the XYNTHA SOLOFUSE.)

•

During storage, avoid prolonged exposure of XYNTHA SOLOFUSE to light.

•

Store the reconstituted solution at room temperature prior to administration. Administer XYNTHA SOLOFUSE within 3 hours after reconstitution or after removal of the grey rubber tip cap from the product.

17 PATIENT COUNSELING INFORMATION

Advise patients to:

•

read the FDA-approved patient labeling (Patient Information and Instructions for Use).

•

report any adverse reactions or problems that concern them when taking XYNTHA to their healthcare provider.

•

discontinue use of the product, call their healthcare provider, and go to the emergency department if any allergic-type hypersensitivity reactions occur. Inform patients of the early signs of hypersensitivity reactions (including hives [rash with itching]), generalized urticaria, tightness of the chest, wheezing, hypotension) and anaphylaxis.

•

contact their healthcare provider if they experience a lack of a clinical response to factor VIII replacement therapy, as this may be a manifestation of an inhibitor.

•

notify their healthcare provider if they become pregnant or intend to become pregnant during therapy, or if they are breastfeeding.

•

Local irritation may occur when infusing XYNTHA SOLOFUSE.

For Medical Information about XYNTHA, please visit www.pfizermedinfo.com or call 1-800-438-1985.

FDA-Approved Patient Labeling

Patient Information

XYNTHA^® SOLOFUSE^® /ZIN –tha /
[Antihemophilic Factor (Recombinant)]

Please read this patient information carefully before using XYNTHA and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your healthcare provider about your medical problems or your treatment.

What is XYNTHA?

XYNTHA is an injectable medicine that is used to help control and reduce bleeding in people with hemophilia A. Hemophilia A is also called classic hemophilia. Your healthcare provider may give you XYNTHA when you have surgery.

XYNTHA is not used to treat von Willebrand’s disease.

What should I tell my healthcare provider before using XYNTHA?

Tell your healthcare provider about all of your medical conditions, including if you:

•

have any allergies, including allergies to hamsters.

•

are pregnant or planning to become pregnant. It is not known if XYNTHA may harm your unborn baby.

•

are breastfeeding. It is not known if XYNTHA passes into your milk and if it can harm your baby.

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

How should I infuse XYNTHA?

Step-by-step instructions for infusing with XYNTHA SOLOFUSE are provided at the end of this leaflet.

The steps listed below are general guidelines for using XYNTHA SOLOFUSE. Always follow any specific instructions from your healthcare provider. 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 XYNTHA.

Call your healthcare provider right away if you take more than the dose you should take.

Talk to your healthcare provider before traveling. Plan to bring enough XYNTHA SOLOFUSE for your treatment during this time.

What are the possible side effects of XYNTHA?

Call your healthcare provider or go to the emergency department right away if you have any of the following symptoms because these may be signs of a serious allergic reaction:

•

wheezing

•

difficulty breathing

•

chest tightness

•

turning blue (look at lips and gums)

•

fast heartbeat

•

swelling of the face

•

faintness

•

rash

•

hives

Common side effects of XYNTHA are

•

headache

•

joint pain

•

fever

•

cough

•

vomiting

•

diarrhea

•

weakness

Your body can make antibodies against XYNTHA (called “inhibitors”) that may stop XYNTHA from working properly. Your healthcare provider may need to take blood tests from time to time to monitor for inhibitors.

Talk to your healthcare provider about any side effect that bothers you or that does not go away. You may report side effects to FDA at 1-800-FDA-1088.

How should I store XYNTHA SOLOFUSE?

Store in the refrigerator at 36° to 46°F (2° to 8°C).

Do not freeze.

Protect from light.

XYNTHA SOLOFUSE can last at room temperature (below 77°F) for up to 3 months. If you store XYNTHA SOLOFUSE at room temperature, carefully write down the date you put XYNTHA SOLOFUSE at room temperature, so you will know when to throw it away. There is a space on the carton for you to write the date.

Throw away any unused XYNTHA SOLOFUSE after the expiration date.

Infuse within 3 hours after reconstitution or after removal of the grey rubber tip cap from the prefilled dual-chamber syringe. You can keep the reconstituted solution at room temperature before infusion for up to 3 hours. If it is not used in 3 hours, throw it away.

Do not use reconstituted XYNTHA if it is not clear to slightly opalescent and colorless.

Dispose of all materials, whether reconstituted or not, in an appropriate medical waste container.

What else should I know about XYNTHA?

Medicines are sometimes prescribed for purposes other than those listed here. Talk to your healthcare provider if you have any concerns. You can ask your healthcare provider for information about XYNTHA SOLOFUSE that was written for healthcare professionals.

Do not share XYNTHA SOLOFUSE with other people, even if they have the same symptoms that you have.

Instructions for Use

XYNTHA^® SOLOFUSE^® /ZIN –tha /
[Antihemophilic Factor (Recombinant)]

XYNTHA SOLOFUSE is supplied as a pre-filled dual-chamber syringe with lyophilized XYNTHA powder in one chamber and 0.9% sodium chloride solution in the other chamber. Before you can infuse it (intravenous injection), you must reconstitute the powder by mixing it with the sodium chloride solution.

Reconstitute and infuse XYNTHA SOLOFUSE using the infusion set provided in this kit. Please follow the directions below for the proper use of this product.

PREPARATION AND RECONSTITUTION OF XYNTHA SOLOFUSE

Preparation

1.

Always wash your hands before doing the following steps.

2.

Keep everything clean and germ-free while you are reconstituting XYNTHA SOLOFUSE.

3.

Once the syringes are open, finish reconstituting XYNTHA SOLOFUSE as soon as possible. This will help to keep them germ-free.

4.

For additional instructions on the use of a XYNTHA SOLOFUSE and a XYNTHA vial or multiple XYNTHA SOLOFUSE, see the detailed information provided after INFUSION OF XYNTHA section.

Reconstitution

1.

Allow the XYNTHA SOLOFUSE to reach room temperature.

2.

Remove the contents of the XYNTHA SOLOFUSE Kit and place on a clean surface, making sure you have all the supplies you will need.

3.

Grasp the plunger rod as shown in the following diagram. Do not touch the shaft of the plunger rod. Screw the plunger rod firmly into the opening in the finger rest of the XYNTHA SOLOFUSE by pushing and turning firmly until resistance is felt (approximately 2 turns). Throughout the reconstitution process, it is important to keep the XYNTHA SOLOFUSE upright to prevent possible leakage.

4.

Holding the XYNTHA SOLOFUSE upright, remove the white tamper-evident seal by bending the seal right to left (or a gentle rocking motion) to break the perforation of the cap and expose the grey rubber tip cap of the XYNTHA SOLOFUSE.

5.

Remove the protective blue vented sterile cap from its package. While holding the XYNTHA SOLOFUSE upright, remove the grey rubber tip cap and replace it with the protective blue vented cap (prevents pressure build-up). Avoid touching the open end of both the syringe and the protective blue vented cap.

(click image for full-size original)

6.

Gently and slowly push the plunger rod until the two stoppers inside the XYNTHA SOLOFUSE meet, and all of the diluent is transferred to the chamber containing the XYNTHA powder.
Note: To prevent the escape of fluid from the tip of the syringe, do not push the plunger rod with excessive force.

7.

With the XYNTHA SOLOFUSE remaining upright, swirl gently several times until the powder is dissolved.Look carefully at the solution in the XYNTHA SOLOFUSE. The solution should be clear to slightly opalescent and colorless. If it is not, throw away the solution and use a new kit.

8.

Holding the XYNTHA SOLOFUSE in an upright position, slowly advance the plunger rod until most, but not all, of the air is removed from the drug product chamber.

Note:

•

If you are not using the solution immediately, store the syringe upright and keep the protective blue vent cap on the XYNTHA SOLOFUSE until ready to infuse.

•

Infuse XYNTHA solution within 3 hours after reconstitution or removal of the grey tip cap from the XYNTHA SOLOFUSE. The reconstituted solution may be kept at room temperature for up to 3 hours prior to infusion. If you have not used it in 3 hours, throw it away.

•

If more than one XYNTHA SOLOFUSE is needed for each infusion, a luer-to-luer syringe connector can be used (not included in this kit). Please contact your doctor or healthcare provider, or call the Wyeth Medical Information Department at 1-800-438-1985, for additional information.

INFUSION OF XYNTHA

Your healthcare provider will teach you how to infuse XYNTHA yourself. Once you learn how to do this, you can follow the instructions in this insert.

Before XYNTHA can be infused, you must reconstitute it as instructed above in the PREPARATION AND RECONSTITUTION OF XYNTHA SOLOFUSE section.

After reconstitution, be sure to look carefully at the XYNTHA solution. The solution should be clear to slightly opalescent and colorless. If it is not, throw away the solution and use a new kit.

Use the infusion set included in the kit to infuse XYNTHA. Do not infuse XYNTHA in the same tubing or container with other medicines.

1.

After removing the protective blue vented cap, firmly attach the intravenous infusion set provided in the kit onto the XYNTHA SOLOFUSE.

(click image for full-size original)

2.

Apply a tourniquet and prepare the injection site by wiping the skin well with an alcohol swab provided in the kit.

3.

Remove the protective needle cover and insert the butterfly needle of the infusion set tubing into your vein as instructed by your healthcare provider. Remove the tourniquet. Verify proper needle placement.

4.

Infuse the reconstituted XYNTHA product over several minutes. Your comfort level should determine the rate of infusion.

5.

After infusing XYNTHA, remove the infusion set and throw it away. The amount of liquid left in the infusion set will not affect your treatment.

Note:

•

Dispose of all unused solution, the empty XYNTHA SOLOFUSE, and other used medical supplies in an appropriate container.

•

It is a good idea to record the lot number from the XYNTHA SOLOFUSE label every time you use XYNTHA. You can use the peel-off label found on the XYNTHA SOLOFUSE to record the lot number.

ADDITIONAL INSTRUCTIONS

XYNTHA is also supplied in kits that include single-use vials with lyophilized powder and prefilled diluent syringes.

If you use one XYNTHA vial and one XYNTHA SOLOFUSE for the infusion, reconstitute the XYNTHA vial and the XYNTHA SOLOFUSE according to the specific directions for that respective product kit. Use a separate, 10 milliliter or larger luer lock syringe (not included in this kit) to draw back the reconstituted contents of the XYNTHA vial and the XYNTHA SOLOFUSE.

If you use multiple XYNTHA SOLOFUSE kits for the infusion, reconstitute each XYNTHA SOLOFUSE according to the directions above. Use a separate, 10 milliliter or larger luer lock syringe (not included in this kit) to draw back the reconstituted contents of any additional XYNTHA SOLOFUSE.

Use of a XYNTHA Vial Kit with a XYNTHA SOLOFUSE Kit

These instructions are for the use of only one XYNTHA vial kit with one XYNTHA SOLOFUSE Kit. For further information, please contact your healthcare provider or call the Medical Information Department at Wyeth Pharmaceuticals, 1-800-438-1985.

1.

Reconstitute the XYNTHA vial using the instructions included with the kit. Detach the empty diluent syringe from the vial adapter by gently turning and pulling the syringe counterclockwise, leaving the contents in the XYNTHA vial with the vial adapter in place.

2.

Reconstitute the XYNTHA SOLOFUSE using the instructions included with the product kit, remembering to remove most, but not all, of the air from the syringe.

3.

After removing the protective blue vented cap, connect the XYNTHA SOLOFUSE to the vial adapter by inserting the tip into the adapter opening while firmly pushing and turning the syringe clockwise until secured.

4.

Slowly push the plunger rod of the XYNTHA SOLOFUSE to empty the contents into the XYNTHA vial. The plunger rod may move back slightly after release.

5.

Detach the empty XYNTHA SOLOFUSE from the vial adapter and throw it away. If the syringe turns without detaching from the vial adapter, grasp the white collar and turn.

6.

Connect a sterile 10 milliliter or larger luer lock syringe to the vial adapter. You may want to inject some air into the vial to make withdrawing the vial contents easier.

7.

Invert the XYNTHA vial and slowly draw the solution into the large luer lock syringe.

8.

Detach the large luer lock syringe from the vial adapter by gently turning and pulling the syringe counterclockwise. Throw away the empty XYNTHA vial with the adapter attached.

9.

Attach the infusion set to the large luer lock syringe as directed in the INFUSION OF XYNTHA section.

Note: Dispose of all unused solution, the empty XYNTHA SOLOFUSE, and other used medical supplies in an appropriate container.

Use of Multiple XYNTHA SOLOFUSE Kits

The instructions below are for the use of multiple XYNTHA SOLOFUSE kits with a 10 milliliter or larger luer lock syringe. For further information, please contact your healthcare provider or call the Medical Information Department at Wyeth Pharmaceuticals, 1-800-438-1985.

Note: Luer-to-luer syringe connectors are not provided in the kits. Contact your XYNTHA supplier to order.

1.

Reconstitute all XYNTHA SOLOFUSE according to instructions described in PREPARATION AND RECONSTITUTION OF XYNTHA SOLOFUSE section. Holding the XYNTHA SOLOFUSE in an upright position, slowly push the plunger rod until most, but not all, of the air is removed from the syringe.

2.

Remove the luer-to-luer syringe connector from its package.

3.

After removing the protective blue vented cap, connect a sterile 10 milliliter or larger luer lock syringe to one opening (port) in the syringe connector and the XYNTHA SOLOFUSE to the remaining open port on the opposite end.

(click image for full-size original)

4.

With the XYNTHA SOLOFUSE on top, slowly push the plunger rod to empty all the XYNTHA SOLOFUSE content into the large luer lock syringe.

5.

Remove the empty XYNTHA SOLOFUSE and repeat procedures 3 and 4 above for any additional XYNTHA SOLOFUSE.

6.

Remove the luer-to-luer syringe connector from the large luer lock syringe and attach the infusion set as directed in the INFUSION OF XYNTHA section.

Note: Dispose of all unused solution, the empty XYNTHA SOLOFUSE, and other used medical supplies in an appropriate container.

This product’s labeling may have been updated. For the most recent prescribing information, please visit www.pfizer.com.

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LAB-0500-13.0