Antihemophilic Factor (Human), Koatew-DVI, is a sterile, stable, purified, dried concentrate of human Antihemophilic Factor (AHF, factor VIII, AHG) which has been treated with tri-n-butyl phosphate (TNBP) and polysorbate 80 and heated in lyophilized form in the final container at 80°C for 72 hours. Koate-DVI is intended for use in therapy of classical hemophilia (hemophilia A).

Koate-DVI is purified from the cold insoluble fraction of pooled fresh-frozen plasma by modification and refinements of the methods first described by Hershgold, Pool, and Pappenhagen.¹ Koate-DVI contains purified and concentrated factor VIII. The factor VIII is 300–1000 times purified over whole plasma. Part of the fractionation may be performed by another licensed manufacturer. When reconstituted as directed, Koate-DVI contains approximately 50–150 times as much factor VIII as an equal volume of fresh plasma. The specific activity, after addition of Albumin (Human), is in the range of 9–22 IU/mg protein. Koate-DVI must be administered by the intravenous route.

Each bottle of Koate-DVI contains the labeled amount of antihemophilic factor activity in international units (IU). One IU, as defined by the World Health Organization standard for blood coagulation factor VIII, human, is approximately equal to the level of AHF found in 1.0 mL of fresh pooled human plasma. The final product when reconstituted as directed contains not more than (NMT) 1500 μg/mL polyethylene glycol (PEG), NMT 0.05 M glycine, NMT 25μg/mL polysorbate 80, NMT 5μg/g tri-n-butyl phosphate (TNBP), NMT 3 mM calcium, NMT 1μg/mL aluminum, NMT 0.06 M histidine, and NMT 10 mg/mL Albumin (Human).

REFERENCES

1. Hershgold EJ, Pool JG, Pappenhagen AR: The potent antihemophilic globulin concentrate derived from a cold insoluble fraction of human plasma: characterization and further data on preparation and clinical trial. J Lab Clin Med 67(1):23–32, 1966.

Last updated on RxList: 2/20/2009

Koate-DVI is indicated for the treatment of classical hemophilia (hemophilia A) in which there is a demonstrated deficiency of activity of the plasma clotting factor, factor VIII. Koate-DVI provides a means of temporarily replacing the missing clotting factor in order to control or prevent bleeding episodes, or in order to perform emergency and elective surgery on individuals with hemophilia.

Koate-DVI contains naturally occurring von Willebrand's factor, which is co-purified as part of the manufacturing process.

Koate-DVI has not been investigated for efficacy in the treatment of von Willebrand's disease, and hence is not approved for such usage.

Each bottle of Koate-DVI has the AHF(H) content in international units per bottle stated on the label of the bottle. The reconstituted product must be administered intravenously by either direct syringe injection or drip infusion. The product must be administered within 3 hours after reconstitution.

General Approach to Treatment and Assessment of Treatment Efficacy

The dosages described below are presented as general guidance. It should be emphasized that the dosage of Koate-DVI required for hemostasis must be individualized according to the needs of the patient, the severity of the deficiency, the severity of the hemorrhage, the presence of inhibitors, and the factor VIII level desired. It is often critical to follow the course of therapy with factor VIII level assays.

The clinical effect of Koate-DVI is the most important element in evaluating the effectiveness of treatment. It may be necessary to administer more Koate-DVI than would be estimated in order to attain satisfactory clinical results. If the calculated dose fails to attain the expected factor VIII levels, or if bleeding is not controlled after administration of the calculated dosage, the presence of a circulating inhibitor in the patient should be suspected. Its presence should be substantiated and the inhibitor level quantitated by appropriate laboratory tests.

When an inhibitor is present, the dosage requirement for AHF(H) is extremely variable and the dosage can be determined only by the clinical response. Some patients with low titer inhibitors, (10 Bethesda Units) can be successfully treated with factor VIII without a resultant anamnestic rise in inhibitor titer.¹² Factor VIII levels and clinical response to treatment must be assessed to insure adequate response. Use of alternative treatment products, such as Factor IX Complex concentrates, Antihemophilic Factor (Porcine) or Anti-Inhibitor Coagulant Complex, may be necessary for patients with high titer inhibitors. Immune tolerance therapy using repeated doses of FVIII concentrate administered frequently on a predetermined schedule may result in eradication of the FVIII inhibitor.^13,14 Most successful regimens have employed high doses of FVIII administered at least once daily, but no single dosage regimen has been universally accepted as the most effective. Consultation with a hemophilia expert experienced with the management of immune tolerance regimens is also advisable.

Calculation of Dosage

The in vivo percent elevation in factor VIII level can be estimated by multiplying the dose of AHF(H) per kilogram of body weight (IU/kg) by 2%. This method of calculation is based on clinical findings by Abildgaard et al,¹⁵ and is illustrated in the following examples:

Expected % factor VIII increase =	# units administered X 2%/IU/kg
	body weight (kg)

Example for a 70 kg adult:	1400 IU X 2%/IU/kg	= 40%
	70kg

or

Dosage required (IU) =	body weight (kg) X desired % factor VIII increase
	2%/IU/kg

Example for a 15 kg child:	15 kg X 100%	= 750 IU required
	2%/IU/kg

The dosage necessary to achieve hemostasis depends upon the type and severity of the bleeding episode, according to the following general guidelines:

Mild Hemorrhage

Mild superficial or early hemorrhages may respond to a single dose of 10 IU per kg,⁴ leading to an in vivo rise of approximately 20% in the factor VIII level. Therapy need not be repeated unless there is evidence of further bleeding.

Moderate Hemorrhage

For more serious bleeding episodes (e.g., definite hemarthroses, known trauma), the factor VIII level should be raised to 30%–50% by administering approximately 15 - 25 IU per kg. If further therapy is required, repeated doses of 10 - 15 IU per kg every 8-12 hours may be given.¹⁶

Severe Hemorrhage

In patients with life-threatening bleeding or possible hemorrhage involving vital structures (e.g., central nervous system, retropharyngeal and retroperitoneal spaces, iliopsoas sheath), the factor VIII level should be raised to 80% - 100% of normal in order to achieve hemostasis. This may be achieved in most patients with an initial AHF [Antihemophilic Factor (Human), Koatew-DVI] dose of 40-50 IU per kg and a maintenance dose of 20-25 IU per kg every 8-12 hours.17,18 For major surgical procedures, Factor VIII levels should be checked throughout the perioperative course to ensure adequate replacement therapy.

Surgery

For major surgical procedures, the factor VIII level should be raised to approximately 100% by giving a preoperative dose of 50 IU/kg. The factor VIII level should be checked to assure that the expected level is achieved before the patient goes to surgery. In order to maintain hemostatic levels, repeat infusions may be necessary every 6 to 12 hours initially, and for a total of 10 to 14 days until healing is complete. The intensity of factor VIII replacement therapy required depends on the type of surgery and postoperative regimen employed. For minor surgical procedures, less intensive treatment schedules may provide adequate hemostasis.^17,18

Prophylaxis

Factor VIII concentrates may also be administered on a regular schedule for prophylaxis of bleeding, as reported by Nilsson et al.¹⁹

Incorrect diagnosis, inappropriate dosage, method of administration, and biological differences in individual patients, could reduce the efficacy of this product or even result in an ill effect following its use. It is important that this product be stored properly, the directions for use be followed carefully during use, the risk of transmitting viruses be carefully weighed before the product is prescribed, and that plasma factor VIII levels be measured in initial treatment situations or if clinical response appears inadequate.

Reconstitution

Vacuum Transfer

Note: Aseptic technique should be carefully followed. All needles and vial tops that will come into contact with the product to be administered via the intravenous route should not come in contact with any non-sterile surface. Any contaminated needles should be discarded by placing in a puncture proof container, and new equipment should be used.

• After removing all items from the box, warm the sterile water (diluent) to room temperature (25°C, 77°F).
• Remove shrink band from product vial. If the shrink band is absent or shows signs of tampering, do not use the product and notify Talecris Biotherapeutics, Inc. immediately.
• Remove the plastic flip tops from each vial (Fig. A). Cleanse vial tops (grey stoppers) with alcohol swab and allow surface to dry. After cleaning, do not allow anything to touch the latex (rubber) stopper.
• Carefully remove the plastic sheath from the short end of the transfer needle. Insert the exposed needle into the diluent vial to the hub. (Fig. B)
• Carefully grip the sheath of the other end of the transfer needle and twist to remove it.
• Invert the diluent vial and insert the attached needle into the vial of concentrate at a 45° angle (Fig. C). This will direct the stream of diluent against the wall of the concentrate vial and minimize foaming. The vacuum will draw the diluent into the concentrate vial. **
• Remove the diluent bottle and transfer needle (Fig. D).
• Immediately after adding the diluent, agitate vigorously for 10–15 seconds, (Fig. E1) then swirl continuously until completely dissolved (Fig. E2). Some foaming will occur, but attempt to avoid excessive foaming. The vial should then be visually inspected for particulate matter and discoloration prior to administration.
• Clean the top of the vial of reconstituted Koate-DVI again with alcohol swab and let surface dry.
• Attach the filter needle (from the package) to a sterile syringe. Withdraw the Koate-DVI solution into the syringe through the filter needle (Fig. F).
• Remove the filter needle from the syringe and replace with an appropriate injection or butterfly needle for administration. Discard filter needle into a puncture proof container.
• If the same patient is using more than one vial of Koate-DVI, the contents of multiple vials may be drawn into the same syringe through the filter needles provided.

**If vacuum is lost in the concentrate vial, use a sterile syringe and needle to remove the sterile water from the diluent vial and inject it into the concentrate vial, directing the stream of fluid against the wall of the vial.

A number of factors beyond our control could reduce the efficacy of this product or even result in an ill effect following its use. These include improper storage and handling of the product after it leaves our hands, diagnosis, dosage, method of administration, and biological differences in individual patients. Because of these factors, it is important that this product be stored properly, that the directions be followed carefully during use, and that the risk of transmitting viruses be carefully weighed before the product is prescribed.

Rate of Administration

The rate of administration should be adapted to the response of the individual patient, but administration of the entire dose in 5 to 10 minutes is generally well-tolerated.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Koate-DVI is supplied in the following single dose bottles with the total units of factor VIII activity stated on the label of each bottle. A suitable volume of Sterile Water for Injection, USP, a sterile double-ended transfer needle, a sterile filter needle, and a sterile administration set are provided.

Approximate Factor VIII

NDC Number	Activity	Diluent
13533-665-20	250 IU	5 mL
13533-665-30	500 IU	5 mL
13533-665-50	1000 IU	10 mL

Storage

Koate-DVI should be stored under refrigeration (2–8°C; 36–46°F). Storage of lyophilized powder at room temperature (up to 25°C or 77°F) for 6 months, such as in home treatment situations, may be done without loss of factor VIII activity.

Freezing should be avoided as breakage of the diluent bottle might occur.

REFERENCES

4. Britton M, Harrison J, Abildgaard CF: Early treatment of hemophilic hemarthroses with minimal dose of new factor VIII concentrate. J Pediatr 85(2):245–7, 1974.

12. Kasper CK: Complications of hemophilia A treatment: factor VIII inhibitors. Ann NY Acad Sci 614:97–105, 1991.

13. Mariani G, Hilgartner M, Thompson AR, et al: Immune Tolerance to Factor VIII: International Registry Data. Adv Exp Med Biol 386:201–8, 1995.

14. DiMichele D: Hemophilia 1996, New Approach to an Old Disease. Pediatr Clin North Am 43(3):709–35, Jun 1995.

15. Abildgaard CF, Simone JV, Corrigan JJ, et al: Treatment of hemophilia with glycine-precipitated factor VIII. N Engl J Med 275(9):471–5, 1966.

16. Abildgaard CF: Current concepts in the management of hemophilia. Semin Hematol 12(3):223–32, 1975.

17. Hilgartner MW: Factor replacement therapy. In: Hilgartner MW, Pochedly C, eds.: Hemophilia in the child and adult. New York, Raven Press, 1989, pp 1–26.

18. Kasper CK, Dietrich SL: Comprehensive management of haemophilia. Clin Haematol 14(2):489–512, 1985.

19. Nilsson IM, Berntorp E, Löfqvist T, et al: Twenty-five years' experience of prophylactic treatment in severe haemophilia A and B. J Intern Med 232(1):25–32, 1992.

Talecris Biotherapeutics, Inc., Research Triangle Park, NC 27709 USA. Rev. September 2006.

Last updated on RxList: 2/20/2009

Allergic-type reactions may result from the administration of Antihemophilic Factor (Human) preparations.^10,11

Ten adverse reactions related to 7 infusions were observed during a total of 1053 infusions performed during the clinical study of Koate-DVI, for a frequency of 0.7% infusions associated with adverse reactions. All reactions were mild and included tingling in the arm, ear, and face, blurred vision, headache, nausea, stomach ache, and jittery feeling.²

No information provided.

REFERENCES

2. Data on file.

10. Eyster ME, Bowman HS, Haverstick JN: Adverse reactions to factor VIII infusions. [letter] Ann Intern Med 87(2):248, 1977.

11. Prager D, Djerassi I, Eyster ME, et al: Pennsylvania state-wide hemophilia program: summary of immediate reactions with the use of factor VIII and factor IX concentrate. Blood 53(5):1012–3, 1979.

Last updated on RxList: 2/20/2009

Koate-DVI 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. Despite these measures, because this product is made from human blood, it may carry a risk of transmitting infectious agents, e.g., viruses, and theoretically the Creutzfeldt-Jakob disease (CJD) agent. There is also the possibility that unknown infectious agents may be present in such products. 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 Talecris Biotherapeutics, Inc. [1-800-520-2807]. The physician should discuss the risks and benefits of this product with the patient, before prescribing or administering it to a patient.

Individuals who receive infusions of blood or plasma products may develop signs and/or symptoms of some viral infections, particularly hepatitis C. It is emphasized that hepatitis B vaccination is essential for patients with hemophilia and it is recommended that this be done at birth or diagnosis.^8,9 Hepatitis A vaccination is also recommended for hemophilic patients who are hepatitis A seronegative.

General

1. Koate-DVI is intended for treatment of bleeding disorders arising from a deficiency in factor VIII. This deficiency should be proven prior to administering Koate-DVI.
2. Administer within 3 hours after reconstitution. Do not refrigerate after reconstitution.
3. Administer only by the intravenous route.
4. Filter needle should be used prior to administering.
5. Koate-DVI contains levels of blood group isoagglutinins which are not clinically significant when controlling relatively minor bleeding episodes. When large or frequently repeated doses are required, patients of blood groups A, B, or AB should be monitored by means of hematocrit for signs of progressive anemia, as well as by direct Coombs' tests.
6. Product administration and handling of the infusion set and needles must be done with caution. Percutaneous puncture with a needle contaminated with blood can transmit infectious viruses including HIV (AIDS) and hepatitis. Obtain immediate medical attention if injury occurs.
   Place needles in sharps container after single use. Discard all equipment including any reconstituted Koate-DVI product in accordance with biohazard procedures.

Pregnancy Category C

Animal reproduction studies have not been conducted with Koate-DVI. It is also not known whether Koate-DVI can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Koate-DVI should be given to a pregnant woman only if clearly needed.

Pediatric Use

Koate-DVI has not been studied in pediatric patients. Koate-HP, solvent/detergent treated Antihemophilic Factor (Human), has been used extensively in pediatric patients.

Spontaneous adverse event reports with Koate-HP for pediatric use were within the experience of those reports for adult use.

REFERENCES

8. National Hemophilia Foundation Medical and Scientific Advisory Council. Hemophilia Information Exchange–AIDS Update: Recommendations concerning AIDS and the treatment of hemophilia HIV infection. Section I.G. (Rev. Jan., 1988).

9. Safety of therapeutic products used for hemophilia patients. MMWR 37(29):441–4, 449–50, 1988.

Last updated on RxList: 2/20/2009

No information provided.

None known.

Last updated on RxList: 2/20/2009

Hemophilia A is a hereditary bleeding disorder characterized by deficient coagulant activity of the specific plasma protein clotting factor, factor VIII. In afflicted individuals, hemorrhages may occur spontaneously or after only minor trauma. Surgery on such individuals is not feasible without first correcting the clotting abnormality. The administration of Koate-DVI provides an increase in plasma levels of factor VIII and can temporarily correct the coagulation defect in these patients.

After infusion of Antihemophilic Factor (Human), there is usually an instantaneous rise in the coagulant level followed by an initial rapid decrease in activity, and then a subsequent much slower rate of decrease in activity.^2-4 The early rapid phase may represent the time of equilibration with the extravascular compartment, and the second or slow phase of the survival curve presumably is the result of degradation and reflects the true biologic half-life of the infused Antihemophilic Factor (Human).³ The removal and inactivation of spiked relevant and model enveloped and non-enveloped viruses during the manufacturing process for Koate-DVI have been validated in laboratory studies at Talecris Biotherapeutics, Inc. Studies performed with the model enveloped viruses indicated that the greatest reduction was achieved by TNBP/polysorbate 80 treatment and 80°C heat. For this reason, VSV (Vesicular Stomatitis Virus, model for RNA enveloped viruses) and HIV-1 (Human Immunodeficiency Virus Type 1) were studied only at these two steps of the manufacturing process. The efficacy of the dry heat treatment was studied using all of the viruses, including BVDV (Bovine Viral Diarrheal Virus, model for hepatitis C virus) and Reo (Reovirus Type 3, model for viruses resistant to physical and chemical agents, such as hepatitis A), and the effect of moisture content on the inactivation of HAV (Hepatitis A Virus), PPV (Porcine Parvovirus, model for parvovirus B19), and PRV (Pseudorabies Virus, model for large enveloped DNA viruses) was investigated.

Table 1. Summary of In Vitro Log₁₀ Viral Reduction Studies

	Enveloped Model Viruses				Non-enveloped Model Viruses
	HIV-1	BVDV	PRV	VSV	Reo	HAV	PPV
Model for	HIV-1/2	HCV	Large enveloped DNA viruses	RNA enveloped viruses	HAV and viruses resistant to chemical and physical agents	HAV	B19
Global Reduction Factor	≥ 9.4	≥ 10.3	≥ 9.3	≥ 10.9	9.4	≥ 4.5	3.7

Similar studies have shown that a terminal 80°C heat incubation for 72 hours inactivates non-lipid enveloped viruses such as hepatitis A and canine parvovirus in vitro, as well as lipid enveloped viruses such as hepatitis C.^{5, 6, 7}

Koate-DVI is purified by a gel permeation chromatography step serving the dual purpose of reducing the amount of TNBP and polysorbate 80 as well as increasing the purity of the factor VIII.

A two-stage clinical study using Koate-DVI was performed in individuals with hemophilia A who had been previously treated with other plasma-derived AHF concentrates. In Stage 1 of the pharmacokinetic study with 19 individuals, statistical comparisons demonstrated that Koate-DVI is bioequivalent to the unheated product, Koatew-HP. The incremental in vivo recovery ten minutes after infusion of Koate-DVI was 1.90% IU/kg (Koate-HP 1.82% IU/kg). Mean biologic half-life of Koate-DVI was 16.12 hours (Koate-HP 16.13 hours). In Stage II of the study, participants received Koate-DVI treatments for six months on home therapy with a median of 54 days (range 24–93). No evidence of inhibitor formation was observed, either in the clinical study or in the preclinical investigations.²

REFERENCES

2. Data on file.

3. Aronson DL: Factor VIII (antihemophilic globulin). Semin Thromb Hemostas 6(1):12–27, 1979.

4. Britton M, Harrison J, Abildgaard CF: Early treatment of hemophilic hemarthroses with minimal dose of new factor VIII concentrate. J Pediatr 85(2):245–7, 1974.

5. Winkelman L., Feldman PA, Evan DR: Severe heat treatment of lyophilised coagulation factors in Virus Inactivation in Plasma Products. Curr Stud Hematol Blood Transfus. Morgenthaler J-J (ed.), Basel, Karger, 1989, No. 56, pp. 55-69.

6. Skidmore SJ, Pasi KJ, Mawson SJ, et al: Serological evidence that dry heating of clotting factor concentrates prevents transmission of non-A, non-B hepatitis. J. Med Virol. 30(1):50-2, 1990.

7. Hart HF, Hart WG, Crossley J, et al: Effect of terminal (dry) heat treatment on non-enveloped viruses in coagulation factor concentrates. Vox Sang 67(4): 345-50, 1994.

Last updated on RxList: 2/20/2009

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 2 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.

Last updated on RxList: 2/20/2009

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.

ANTIHEMOPHILIC FACTOR (FACTOR VIII), HUMAN - INJECTION

(AN-tee-he-mow-FILL-ick factor)

COMMON BRAND NAME(S): Alphanate

USES: This medication is used to control and prevent bleeding episodes in people with low levels of factor VIII (hemophilia A). It is also used in these patients before surgery to prevent bleeding. People with low factor VIII levels are at risk for bleeding longer after an injury/surgery and for bleeding inside the body (especially into the joints and muscles). This product contains human factor VIII, also called antihemophilic factor. This product is used to temporarily replace the missing factor VIII, a protein (clotting factor) that is normally in the blood, so that the blood can clot and the bleeding can stop.

HOW TO USE: This medication is given by injection into a vein, usually over 5 to 10 minutes or as directed by your doctor. The medication may need to be given more slowly over a longer time depending on your dose and how you respond to it.

After first receiving this medication in a hemophilia treatment center or hospital, some patients may be able to give this medication to themselves at home. If your doctor directs you to give this medication at home, read the product information available from your pharmacist before you start using this medication and each time you get a refill. Learn all preparation and usage instructions in the product package. If you have any questions, ask your health care professional.

If the medication and the solution used to mix it have been refrigerated, bring both to room temperature before combining. After adding the solution to the powder, gently swirl the vial to completely dissolve the powder. Do not shake the vial. Before using this product, check it visually for particles or discoloration. If either is present, do not use the liquid. Use immediately (See also Storage).

The dosage is based on your medical condition, weight, blood test results, and response to treatment. Follow your doctor's instructions closely. Ask your doctor or pharmacist if you have any questions.

Learn how to store and discard needles and medical supplies safely. Consult your pharmacist.

Tell your doctor if your condition does not improve or if it worsens.

SIDE EFFECTS: Flushing of the face, nausea, vomiting, and fast heartbeat may sometimes occur and can be lessened by giving this medication more slowly. Burning/redness/irritation at the injection site, fever, chills, and headache may also 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: signs of anemia (e.g., tiredness, low energy, pale skin color, shortness of breath), new or worsening bleeding/bruising.

This medication is made from human blood. There is a very small chance that you may get infections from this medication (e.g., viral infections such as hepatitis), even though careful screening of blood donors, special manufacturing processes, and many tests are all used to reduce this risk. Discuss the benefits and risks of treatment with your doctor. Tell your doctor immediately if you develop any signs of hepatitis or other infection, including fever, persistent sore throat, unusual tiredness, unusual drowsiness, joint pain, persistent nausea/vomiting, stomach/abdominal pain, 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, chest discomfort/tightness.

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 this medication, tell your doctor or pharmacist if you are allergic to any antihemophilic factor (factor VIII) products; or to animal proteins (e.g., mouse); or to natural rubber/latex (found in the packaging of some brands); or if you have any other allergies.

Before using this medication, tell your doctor or pharmacist your medical history.

Manufacturers of some brands of this medication recommend that you monitor your heartbeat during treatment. If your heart starts to beat faster, it is recommended that you give this medication more slowly or temporarily stop the infusion until your heart rate returns to normal. Consult your doctor for more details.

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 virus 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 drug 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.

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 blood tests (e.g., factor VIII levels) should be performed frequently to determine your dosage and to check how well this medication is working. Consult your doctor for more details.

MISSED DOSE: It is important to follow the dosing schedule as directed by your doctor. If you miss a dose, contact your doctor to establish a new dosing schedule. Do not double the dose to catch up.

STORAGE: Store the medication according to the manufacturer's instructions. Some brands of this medication are good for only several months if stored at room temperature. Ask your pharmacist for more details. Do not freeze this product or store it in the bathroom. Protect the product from light. After mixing, do not refrigerate the liquid. Use it within 3 hours (unless the product instructions direct you otherwise) and 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.