PROPLEX T, Factor IX Complex, Heat Treated is a sterile product prepared from pooled normal human plasma. It contains, in concentrated form, clotting Factors II (prothrombin), VII, IX, and X. Other proteins are also present in minimal amounts. The product also contains a small amount of heparin, 1.5 units or less per mL of reconstituted material, as a stabilizing agent. This amount does not affect the clinical usefulness of the complex in moderate dosage.

PROPLEX T, Factor IX Complex, Heat Treated must be administered intravenously. During the manufacturing process, this product was heat treated at 60 ± 1.0°C for 144-153 hours. This heating step was designed to reduce the risk of transmission of hepatitis and other viral infections. However, no procedure has been shown to be totally effective in removing viral infectivity from PROPLEX T, Factor IX Complex, Heat Treated.

Last updated on RxList: 3/5/2009

PROPLEX T, Factor IX Complex, Heat Treated is indicated for:

1. Factor IX deficiency (Hemophilia B, Christmas disease). The intravenous administration of PROPLEX T, Factor IX Complex, Heat Treated is intended to prevent or control bleeding episodes in patients with this deficiency. Factor IX Complex should not be used in patients with mild Factor IX deficiency for whom fresh frozen plasma is effective.
2. Bleeding episodes in patients with inhibitors to Factor VIII. Lusher, et al, have described the use of PROPLEX T, Factor IX Complex, Heat Treated in hemarthroses occurring in hemophiliacs with inhibitors to Factor VIII.¹²
3. Factor VII deficiency. The Factor VII content present in PROPLEX T, Factor IX Complex, Heat Treated has been shown to be effective in prevention or control of bleeding episodes in patients with Factor VII deficiency.¹³

Each bottle of PROPLEX T, Factor IX Complex, Heat Treated is labeled with both the Factor IX and Factor VII content. The Factor IX content is expressed in International Units per bottle and is traceable to the World Health Organization International Standard through a secondary concentrate standard. The Factor VII content is expressed in units per bottle and is traceable to pooled normal plasma through a secondary standard.

The amount of PROPLEX T, Factor IX Complex, Heat Treated required to restore normal hemostasis varies with the circumstances and with the patient. Dosage depends on the degree of deficiency and the desired hemostatic level of the deficient factor. As a guide to calculation of dosage, experience indicates that the following formulas may be used:^4,19

Factor IX Deficiency

Units required to raise blood level percentages:

1.0 unit/kg x body weight (in kg) x desired increase (% of normal)

If a 70 kg (154 lb) patient with a Factor IX level of 0% needs to be elevated to 25%, give 1.0 unit/kg x 70 kg x 25 = 1750 units

In preparation for and following surgery, levels above 25%, maintained for at least a week after surgery, are suggested. Laboratory control to assure such levels is recommended. To maintain levels above 25% for a reasonable time, each dose should be calculated to raise the level to 40% to 60% of normal. (See PRECAUTIONS.)

The preceding dosage formula for Factor IX deficiency is presented as a reference and a guideline. Exact dosage determinations should be made based on the medical judgment of the physician regarding circumstances, condition of patient, degree of deficiency, and the desired level of Factor IX to be achieved. If an inhibitor to Factor IX is present, sufficient additional dosage to overcome the inhibitor would be needed. For maintenance of an elevated level of the deficient factor, dosage may be repeated as often as needed. Clinical studies suggest that relatively high levels may be maintained by daily or twice-daily doses, while the lower effective levels may require injections only once every two or three days. A single dose may be sufficient to stop a minor bleeding episode.^20,21

Factor VIII Inhibitor

In using Factor IX Complex in the treatment of hemarthroses occurring in hemophiliacs with inhibitors to Factor VIII, dosage levels approximating 75 Factor IX units per kg of body weight have been employed successfully.¹²

AUTOPLEX T, Anti-Inhibitor Coagulant Complex, is recommended when hemarthroses occurring in hemophiliacs with inhibitors to Factor VIII cannot be resolved by administration of Factor IX complex, and in other types of bleeding episodes in Factor VIII-inhibitor patients.

Factor VII Deficiency

Units required to raise blood level percentages:

0.5 unit/kg x body weight (in kg) x desired increase (% of normal)

Repeat dose every 4 to 6 hours as needed.

If a 70 kg (154 lb) patient with a Factor VII level of 0% needs to be elevated to 25%, give 0.5 unit/kg x 70 kg x 25 = 875 units.

In preparation for and following surgery, levels above 25%, maintained for at least a week after surgery, are suggested. Laboratory control to assure such levels is recommended. To maintain levels above 25% for a reasonable time, each dose should be calculated to raise the level to 40 to 60% of normal. (See PRECAUTIONS).

The preceding dosage formula for Factor VII deficiency is presented as a reference and a guideline. Exact dosage determinations should be made based on the medical judgment of the physician regarding circumstances, condition of patient, degree of deficiency, and the desired level of Factor VII to be achieved. If an inhibitor to Factor VII is present, sufficient additional dosage to overcome the inhibitor would be needed.^22,23

Reconstitution: Use Aseptic Technique

1. Bring PROPLEX T, Factor IX Complex, Heat Treated (dry concentrate) and Sterile Water for Injection, USP, (diluent) to room temperature.
2. Remove caps from concentrate and diluent bottles to expose central portions of rubber stoppers.
3. Cleanse stoppers with germicidal solution.
4. Remove protective covering from one end of double-ended needle and insert exposed needle through diluent stopper.
5. Remove protective covering from other end of double-ended needle. Invert diluent bottle over the upright concentrate bottle, then rapidly insert free end of the needle through the concentrate bottle stopper at its center. The vacuum in the concentrate bottle will draw in the diluent.
6. Disconnect the two bottles by removing needle from diluent bottle stopper, then remove needle from concentrate bottle. Swirl or rotate concentrate bottle until all material is dissolved. Be sure that the material is completely dissolved, otherwise active material will be removed by the filter.

Note: Do not refrigerate after reconstitution.

Rate of Administration

PROPLEX T, Factor IX Complex, Heat Treated should be infused slowly, at a rate of approximately two to three mL per minute. If headache, flushing, changes in pulse rate or blood pressure appear, the infusion rate should be decreased. In such instances it is advisable, initially, to stop the infusion until the symptoms disappear, then resume the infusion at a slower rate.

Administration: Use Aseptic Technique

When reconstitution of PROPLEX T, Factor IX Complex, Heat Treated is complete, its infusion should commence within three hours. However, it is recommended that the infusion begin as promptly as is practical.

The reconstituted material should be at room temperature during infusion. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Intravenous Drip Infusion

Follow directions for use printed on the administration set container. Make certain that the administration set contains an adequate filter.

Intravenous Syringe Injection

1. Attach filter needle to syringe and draw back plunger to admit air into the syringe.
2. Insert needle into the reconstituted PROPLEX T, Factor IX Complex, Heat Treated.
3. Inject air into bottle and then withdraw the reconstituted material into the syringe.
4. Remove and discard the filter needle from the syringe; attach a suitable needle and inject intravenously at a rate not exceeding 3 mL per minute.
5. If patient is to receive more than one bottle of concentrate, the contents of two bottles may be drawn into the same syringe by drawing up each bottle through a separate unused filter needle. This practice lessens the loss of concentrate. Please note: filter needles are intended to filter the contents of a single bottle of PROPLEX T, Factor IX Complex, Heat Treated only.

PROPLEX T, Factor IX Complex, Heat Treated is furnished with a suitable volume of Sterile Water for Injection, USP; a double-ended needle; a filter needle; and package insert.

Storage

PROPLEX T, Factor IX Complex, Heat Treated should be stored under ordinary refrigeration (2° to 8°C, 36° to 46°F). Avoid freezing to prevent damage to the diluent bottle.

To enroll in the confidential, industry-wide Patient Notification System, call 1-888-UPDATE U (1-888-873-2838).

REFERENCES

4. Zauber NP, Levin J: Factor IX levels in patients with hemophilia B (Christmas disease) following transfusion with concentrates of Factor IX or fresh frozen plasma (FFP). Medicine 56:213-224, 1977

12. Lusher JM, Shapiro SS, Palascak JE, et al: Efficacy of prothrombin-complex concentrates in hemophiliacs with antibodies to Factor VIII. A multicenter therapeutic trial. New Eng J Med 303:421-425, 1980

13. Ragni MV, Lewis JH, Spero JA, et al: Factor VII deficiency. Am J Hemotology 10: 79-88, 1981

19. Levine PH: Hemophilia and allied conditions, in Current Therapy, 1979. Conn HF (ed), Philadelphia, W.B. Saunders Co., 1979, pp 268-275

20. Nilsson IM: Clinical experience with a Swedish Factor IX concentrate, in Haemophilia. Ala F, Denson KWE(eds), Amsterdam, Excerpta Medica, 1973, pp 249-253

21. Owen CA Jr, Bowie EJW: Infusion therapy in hemophilia A and B, in Handbook of Hemophilia. Brinkhous KM, Hemker HC (eds), Amsterdam, Excerpta Medica, 1975, pp 449-473

22. Hoag MS, Aggeler PM, Fowell AH: Disappearance rate of concentrated proconvertin extracts in congenital and acquired hypoproconvertinemia. J Clin Invest 39:554-563, 1960

23. Bedizel M, Albers R: Hereditary Factor VII deficiency in newborns. Clinical Pediatrics 22:774-775, 1983

Baxter Healthcare Corporation, Westlake Village, CA 91362, USA. Revised November 2002.

Last updated on RxList: 3/5/2009

As with other plasma preparations, reactions manifested by chills and fever may occasionally be seen, particularly when large doses of PROPLEX T, Factor IX Complex, Heat Treated are administered.^17,18 A rate of infusion that is too rapid may cause headache, flushing, and changes in pulse rate and blood pressure. In such instances, stopping the infusion allows the symptoms to disappear promptly. With all but the most reactive individuals, the infusion may be resumed at a slower rate. (See Rate of Administration.) The risk of thrombosis is present with the administration of PROPLEX T, Factor IX Complex, Heat Treated.

No information provided.

REFERENCES

17. Hutchison JL, Freedman SO, Richards BA, et al: Plasma volume expansion and reactions after infusion of autologous and nonautologous plasma in man. J Lab Clin Med 56:734-746, 1960

18. Mollison PL: Some unfavourable effects of transfusion (Ch 15) in Blood Transfusion in Clinical Medicine, Sixth Edition. Oxford, Blackwell Scientific Publications, 1979, p 626

Last updated on RxList: 3/5/2009

PROPLEX T, Factor IX Complex, Heat Treated, is made from human plasma. Products made from human plasma may contain infectious agents, such as viruses, that can cause disease. The risk that such products will transmit an infectious agent has been reduced by screening plasma donors for prior exposure to certain viruses, by testing for the presence of certain current virus infections, and by inactivating and/or removing certain viruses (See CLINICAL PHARMACOLOGY). Despite these measures, such products can still potentially transmit disease. There is also the possibility that unknown infectious agents may be present in such products. Because this product is made from human blood, it may carry a risk of transmitting infectious agents, e.g., viruses, and theoretically, the Creutzfeldt-Jacob disease (CJD) agent. ALL infections thought by a physician possibly to have been transmitted by this product should be reported by the physician or other healthcare provider to Baxter Healthcare Corporation at 1-800-423-2862. The physician should discuss the risks and benefits of this product with the patient.

General

Some viruses, such as parvovirus B19 or hepatitis A, are particularly difficult to remove or inactivate at this time. Parvovirus B19 most seriously affects pregnant women, or immune-compromised individuals. Symptoms of parvovirus B19 infection include fever, drowsiness, chills and runny nose followed about two weeks later by a rash, and joint pain. Evidence of hepatitis A may include several days to weeks of poor appetite, tiredness, and low-grade fever followed by nausea, vomiting, and pain in the belly. Dark urine and a yellowed complexion are also common symptoms. Patients should be encouraged to consult their physician if such symptoms appear.

Certain components used in the packaging of this product contain natural rubber latex.

Identification of the deficiency as one of either Factor IX, Factor VII or Factor VIII with inhibitors is essential before administration of the PROPLEX T, Factor IX Complex, Heat Treated is initiated.

With the exception of its use in treating hemarthroses occurring in Factor VIII-inhibitor patients, no benefits may be expected from this product in treating deficiencies other than those of Factor IX or Factor VII.

Caution: It is important that the dosage regimen chosen is carefully evaluated with respect to the entire spectrum of factors present in this product. Levels of Factors II, IX and X should be monitored during therapy to prevent unnecessarily high levels of these factors, which may increase the risk of intravascular coagulation. PROPLEX T, Factor IX Complex, Heat Treated is prepared by calcium phosphate absorption of cold ethanol precipitated material and therefore, contains higher ratios of Factor VII and Factor X to Factor IX than products prepared by cationic exchange.¹⁴

The use of high doses of prothrombin complex concentrates has been reported to be associated with instances of myocardial infarction, disseminated intravascular coagulation, venous thrombosis and pulmonary embolism.^{1, 12, 15, 16}

If signs of intravascular coagulation, thrombosis, or emboli occur, which include changes in blood pressure and pulse rate, respiratory distress, chest pain and cough, the infusion should be stopped promptly. In general, the risk of enhancing DIC may be reduced by raising the patient's Factor VII or Factor IX level to not more than about 50% of normal. If the need exists to raise the patient's Factor IX or Factor VII level higher than 50% of normal, the physician should monitor infusion of material to detect signs and symptoms of DIC.

Special caution should be taken in the use of this concentrate in newborns, where a higher morbidity and mortality may be associated with hepatitis, and in individuals with pre-existing liver disease.

Laboratory Tests

Since the dosage of PROPLEX T, Factor IX Complex, Heat Treated is calculated on the basis of its potency, frequent laboratory tests to monitor the effectiveness of treatment usually are unnecessary. This is particularly true for single dose treatment of an uncomplicated hemarthrosis. However, if a major bleeding episode is being treated in the hospital, or if adequate hemostatic levels of Factor VII or Factor IX are needed to permit performance of surgery, Factor VII or Factor IX assays should be performed at least once a day, prior to infusion, to ensure that the daily dose of PROPLEX T, Factor IX Complex, Heat Treated is sufficient to maintain adequate levels of the desired clotting factor.

Pregnancy

Pregnancy (Category C). Animal reproduction studies have not been conducted with PROPLEX T, Factor IX Complex, Heat Treated. It is also not known whether PROPLEX T, Factor IX Complex, Heat Treated can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. PROPLEX T, Factor IX Complex, Heat Treated should be given to a pregnant woman only if clearly needed.

REFERENCES

1. White GC, Lundblad RL, Kingdon HS: Prothrombin complex concentrates: Preparation, properties and clinical uses. Curr Top Hematol 2:203-244, 1979

12. Lusher JM, Shapiro SS, Palascak JE, et al: Efficacy of prothrombin-complex concentrates in hemophiliacs with antibodies to Factor VIII. A multicenter therapeutic trial. New Eng J Med 303:421-425, 1980

14. Aronson DL: Factor IX complex. Semin Thromb Hemostas VI:28-43, 1979

15. Fuerth JH, Mahrer P: Myocardial infarction after Factor IX therapy. JAMA 214: 1455-1456, 1981

16. Abildgaard CF: Hazards of prothrombin-complex concentrates in treatment of hemophilia. New Eng J Med 304:670, 1981

Last updated on RxList: 3/5/2009

No information provided.

The use of Factor IX Complex is potentially hazardous in patients with signs of fibrinolysis and in patients with disseminated intravascular coagulation (DIC).

Last updated on RxList: 3/5/2009

PROPLEX T, Factor IX Complex, Heat Treated is a combination of vitamin K-dependent clotting factors found in normal plasma. The administration of PROPLEX T, Factor IX Complex, Heat Treated provides an increase in plasma levels of Factor VII and Factor IX and can temporarily correct the coagulation defect of patients with deficiencies in these factors. Plasma levels of Factors II and X will also be increased.

The half-life of Factor VII in non-treated Factor IX Complex, administered to Factor VII deficient patients, has been found to range from 3 to 6 hours.^1,2

The half-life of Factor IX in non-treated Factor IX Complex, administered to Factor IX deficient patients, has been found to range from 24 to 32 hours.^3,4

PROPLEX T, Factor IX Complex, Heat Treated is manufactured by the modified Cohn-Oncley cold ethanol fractionation process which includes a series of cold-ethanol precipitation, centrifugation and/or filtration of human plasma. PROPLEX T, Factor IX Complex, Heat Treated solution is then lyophilized and heat treated at 60 ± 1.0°C for 144-153 hours. This process accomplishes both purification of PROPLEX T, Factor IX Complex, Heat Treated and reduction of viruses.

The PROPLEX T, Factor IX Complex, Heat Treated manufacturing process provides a significant viral reduction in in vitro studies.¹⁰ These viral reduction studies, summarized in Table 1, demonstrate viral clearance during the PROPLEX T, Factor IX Complex, Heat Treated manufacturing process using bovine diarrhea virus (BVD) as a model for lipid enveloped RNAviruses such as hepatitis C virus (HVC); human immunodeficiency virus, type 1 (HIV-1), a relevant blood borne pathogen; and a herpes virus, pseudorabies virus (PRV) as a model for lipid enveloped DNAviruses. Studies were also performed with two non-lipid enveloped viruses: hepatitis A(HAV) virus, a relevant non-lipid enveloped RNAvirus; and porcine parvovirus (PPV), as a model for non-lipid enveloped DNAviruses. These studies indicate that specific steps in the manufacture of PROPLEX T, Factor IX Complex, Heat Treated are capable of eliminating/ inactivating a wide range of relevant and model viruses exhibiting diverse physicochemical properties.

Table 1 : In Vitro Virus Clearance During the Fractionation Process of PROPLEX T

Process Step Evaluated	Viral Reduction Factor (log10)
	Lipid-enveloped			Non-lipid enveloped
	PRV	BVD	HIV-1	HAV	PPV
Cohn-Oncley Cold Ethanol Fractionation Process	4.6	1.2	8.2	1.9	1.4

The effectiveness of the heating step in reducing viral infectivity was assessed by in vitro viral inactivation studies using, as markers, viruses not commonly found in plasma and the results are listed in Table 2 for PROPLEX T, Factor IX Complex, Heat Treated. The model viruses used were sindbis virus (SIN), a lipid enveloped RNA virus; vesicular stomatitis virus (VSV), an enveloped RNAvirus and pseudo rabies virus (PRV), a lipid enveloped DNAvirus. When known quantities of these viruses were added to the product, the heat treatment employed inactivated the following quantities of virus (Table 2):

Table 2 : In Vitro Virus Clearance During the Lyophilization and Heat Treatment of PROPLEX T

Process Step Evaluated	Viral Reduction Factor (log10)
	Lipid-enveloped
	SIN	PRV	VSV
Lyophilization and Heat Treatment Cycle	10.5	1.4	5.6

In addition, it has been shown that cytomegalo virus does not survive the manufacturing process. As these data indicate, all viruses are not equally affected by the heat treatment. Work by Colombo, et al with first-exposure hemophiliacs who received heat treated Antihemophilic Factor (Human) showed that while some reduction of hepatitis infectivity may have been achieved by heat treatment, a substantial portion of the patients who had not previously received blood products developed signs and/or symptoms of hepatitis.⁵ (See WARNINGS).

It has been reported that HIV is heat labile and that it is inactivated by treatment with 19-20% alcohol.^6,7,8 Lengthy exposure to 20% ethanol occurs in the Cohn cold ethanol fractionation procedure from which this product is derived. In a retrospective study conducted with patients receiving AUTOPLEX, Anti-Inhibitor Coagulant Complex which is also derived from the Cohn process, none of the patients who received AUTOPLEX, Anti-Inhibitor Coagulant Complex exclusively seroconverted for HIV antibodies, while 56% of those patients who received other treatment modalities seroconverted during the three year study.⁹ Heat treatment has also been shown to be an effective means of inactivating HIV.^10. In a study comparing heat treated HEMOFIL T, Antihemophilic Factor (Human), to untreated Antihemophilic Factor (Human) products, none of the patients receiving the heat treated product developed antibodies to HIV, while 17% of the patients receiving untreated products did seroconvert by the end of the study.¹¹

REFERENCES

1. White GC, Lundblad RL, Kingdon HS: Prothrombin complex concentrates: Preparation, properties and clinical uses. Curr Top Hematol 2:203-244, 1979

2. Marder VJ, Shulman NR: Clinical aspects of congenital Factor VII deficiency. Am J Med 37:182-192, 1964

3. Mollison PL: The transfusion of platelets, leucocytes and plasma components (Ch 3) in Blood Transfusion in Clinical Medicine, Sixth Ed. Oxford, Blackwell Scientific Publications, 1979, pp 103-113

4. Zauber NP, Levin J: Factor IX levels in patients with hemophilia B (Christmas disease) following transfusion with concentrates of Factor IX or fresh frozen plasma (FFP). Medicine 56:213-224, 1977

5. Colombo M, Carnelli V, Gazengel C, et al: Transmission of non-A, non-B hepatitis by heat-treated Factor VIII concentrate. Lancet 2:1-4, 1985

6. Update: Acquired immune deficiency syndrome (AIDS) in persons with hemophilia. Morbidity and Mortality Weekly Report 33:589-591, October 26, 1984

7. Spire B, Barre-Sinoussi F, Montagnier L, et al: Inactivation of lymphadenopathy associated virus by chemical disinfectants. Lancet 2:899-901, 1984

8. Piszkiewicz D, Kingdon H, Apfelzweig R, et al: Inactivation of HTLV-III/LAV during plasma fractionation. Lancet 2:1188-1189, 1985

9. Gazengel C, Larrieu MJ: Lack of seroconversion for LAV/HTLV-III in patients exclusively given unheated activated prothrombin complex prepared with ethanol step. Lancet 2:1189, 1985

10. Petricciani J, McDougal JS, Evatt BL: Case for concluding that heat-treated, licensed anti-haemophilic factor is free from HTLV-III. Lancet 2:890-891, 1985

11. Rouzioux C, Chamaret S, Montagnier L, et al: Absence of antibodies to AIDS virus in haemophiliacs treated with heat-treated Factor VIII concentrate. Lancet 1:271-272, 1985

Last updated on RxList: 3/5/2009

No information provided. Please refer to the WARNINGS and PRECAUTIONS sections.

Last updated on RxList: 3/5/2009

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

FACTOR IX, HUMAN - INJECTION

(FACK-ter nine)

COMMON BRAND NAME(S): Alphanine SD, Konyne 80, Proplex T

USES: This medication is used to prevent or control bleeding in people with little or no factor IX (due to hemophilia B, Christmas disease). Factor IX is a protein (clotting factor) in the blood that works with other clotting factors to help the blood clot and therefore stop bleeding. People with little or no factor IX are at risk for bleeding longer after an injury/surgery or bleeding suddenly (often in the joints/muscle) without an obvious cause.

This medication should not be used to reverse the effects of "blood thinners" (e.g., warfarin). Most types of this medication should not be used to treat other types of factor deficiencies (e.g., factors II, VII, VIII, X) or factor problems (e.g., inhibitor to factor XIII). If you are using this medication for one of these conditions, consult your doctor or pharmacist to make sure that you are using the right product.

HOW TO USE: This medication is given by injection into a vein by a health care professional. Learn all preparation and usage instructions for this product. Before using this product, check it visually for particles or discoloration. Do not use the liquid if it is discolored. Some forms of this medication must be completely mixed into the liquid so that the liquid contains no particles. In these cases, do not use the liquid if it contains particles. Other forms of this medication may occasionally contain a few small particles in the vial, even if the medication is mixed correctly. In these cases, the particles will not affect how well the medication works and will be removed by the filter. If you have questions about whether your form of this medication may be used if it contains particles, or if you have other questions about the use of this medication, consult the doctor or pharmacist.

Dosage is based on your medical condition (e.g., amount and location of bleeding), weight, and response to treatment.

The medication in the vial and the supplies that come with the medication should be used only once. Do not reuse. Learn how to store and discard needles and medical supplies safely.

Tell your doctor if your condition persists or worsens.

SIDE EFFECTS: Pain at injection site, chills, tingling, flushing, headache, nausea, or vomiting may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: swelling at injection site, fast heartbeat, shortness of breath, change in the amount of urine, swelling of the ankles/feet, pain/redness/swelling of arms or legs, new or increased bleeding/bruising.

Seek immediate medical attention if any of these rare but very serious side effects occur: chest pain, trouble breathing, bluish fingers.

This medication is made from human blood. Even though donors are carefully screened and this medication goes through a special manufacturing process, there is a very small chance that you may get infections from the medication (e.g., viral infections such as hepatitis). Tell your doctor immediately if you develop any signs of hepatitis/another infection, including fever, persistent sore throat, unusual tiredness, persistent nausea/vomiting, yellowing eyes/skin, dark urine.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before using factor IX, tell your doctor or pharmacist if you are allergic to factor IX products; or if you have any other allergies.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: other clotting disorders (e.g., disseminated intravascular coagulation-DIC), immune system problems, recent surgery/procedure, liver disease.

Before having surgery, tell your doctor or dentist that you are using this medication.

Since this medication is made from human blood, there is a very small chance that you may get infections from it (e.g., viral infections such as hepatitis). It is recommended that you get the appropriate vaccinations (e.g., for hepatitis A and B) and that people giving this medication handle the medication with special caution to prevent viral infections. Consult your doctor for more details.

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

It is not known whether this medication passes into breast milk. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor or pharmacist first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: drugs that help with clotting (e.g., tranexamic acid).

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center.

NOTES: Do not share this medication with others.

Laboratory and/or medical tests (e.g., factor IX activity) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

MISSED DOSE: If you miss a dose, contact your doctor or pharmacist immediately to establish a new dosing schedule.

STORAGE: This medication must be stored properly. Store vials of powder in the refrigerator between 36-46 degrees F (2-8 degrees C) away from light. Do not freeze. Review storage instructions for your specific product with the pharmacist. Check the expiration date before using. The vial of medication should only be used once. Throw away any unused portion. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

MEDICAL ALERT: Your condition can cause complications in a medical emergency. For information about enrolling in MedicAlert, call 1-800-854-1166 (USA) or 1-800-668-1507 (Canada).

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.