Antihemophilic Factor (Human), Alphanate®, Solvent Detergent / Heat Treated, is a single dose, sterile, lyophilized concentrate of Factor VIII (AHF) intended for intravenous administration in the treatment of hemophilia A, or acquired Factor VIII deficiency.

Alphanate® is prepared from pooled human plasma by cryoprecipitation of the Factor VIII, fractional solubilization, and further purification employing heparin-coupled, cross-linked agarose which has an affinity to the heparin binding domain of vWf/FVIII:C complex.¹ The product is treated with a mixture of tri(n-butyl) phosphate (TNBP) and polysorbate 80 to reduce the risks of transmission of viral infection. In order to provide an additional safeguard against potential non-lipid enveloped viral contaminants, the product is also subjected to a 80 °C heat treatment step for 72 hours. However, no procedure has been shown to be totally effective in removing viral infectivity from coagulation factor products.

Alphanate® is labeled with the antihemophilic factor potency (Factor VIIIC activity) expressed in International Units (I U) per vial, which is referenced to the WHO International Standard.

Alphanate® contains Albumin (Human) as a stabilizer, resulting in a final container concentrate with a specific activity of at least 5 IU FVIII:C/mg total protein. Prior to the addition of the Albumin (Human) stabilizer, the specific activity is significantly higher.

When reconstituted with the appropriate volume of Sterile Water for Injection, USP, Alphanate® contains 0.3 - 0.9 g Albumin (Human)/100 mL; NMT 5 mmol calcium/L; NMT 750 µg glycine/IU FVIIIC; NMT 1.0 U heparin/mL; 10 - 40 mmol histidine/L; NMT 0.1 mg imidazole/mL; 50 - 200 mmol arginine/L; NMT 1.0 µg polyethylene glycol and polysorbate 80/IU FVIII:C; NMT 10 mEq sodium/vial; and NMT 0.1 µg TNBP/IU FVIIIC.

REFERENCES

1. Fujimura, Y., Titani, K., Holland, L.Z., Roberts, J.R., Kostel, P., Ruggeri, Z.M., Zimmerman, T.S. A Heparin-Binding Domain of Human Von Willebrand Factor: Characterization and Localization to a Tryptic Fragment Extending from Amino Acid Residue Val-449 to Lys-728. I Biol Chem 1987, 262(4): 1 734-1 739.

Last updated on RxList: 11/14/2008

Antihemophilic Factor (Human), Alphanate®, is indicated for the prevention and control of bleeding in patients with Factor VIII deficiency due to hemophilia A or acquired Factor VIII deficiency.⁷ No clinical trials have as yet been conducted using Alphanate® for treatment of von Willebrand's disease, therefore the product is not approved for this use.

For adult usage

Following reconstitution with the supplied diluent, Alphanate® should be administered intravenously within three hours after reconstitution to avoid the potential ill effect of any inadvertent bacterial contamination occurring during reconstitution. Alphanate® may be administered by injection (plastic disposable syringes are recommended). Administer at room temperature, do not refrigerate after reconstitution, and discard any unused contents into the appropriate safety container.

Antihemophilic factor potency (Factor VIII:C activity) is expressed in International Units (IU) on the product label. One unit approximates the activity in one mL of normal human plasma. Replacement therapy studies have shown a linear dose-response relationship with a 2.0-2.5% increase in Factor VIII activity for each unit of Factor VIII:C per kg of body weight transfused, from which an approximate factor of 0.5 lU/kg can be calculated.^15,16

The following formula provides a guide for dosage calculation (the plasma Factor VIII may vary depending upon the age, weight, severity of hemorrhage, or surgical procedure of the patient):

Bodyweight (in kg) X

0.50 lU/kg X

Factor VIII Increase Desired (Percent) =

Number of Factor VIII:C IU Required

Example:

50 kg X 0.50 lU/kg X 30 (% increase) = 750 IU Factor VIII:C

Mild to moderate hemorrhages can usually be treated with a single administration of Alphanate® sufficient to raise the plasma Factor VIII level to 20 to 30%. In the event of more serious hemorrhage, the patient's plasma Factor VIII level should be raised to 30 to 50%. Infusions are generally required at twice daily intervals over several days.¹⁶

Surgery in patients with Factor VIII deficiency requires that postoperatively the Factor VIII level be raised to 50 to 80% and maintained at or above 30% for approximately two weeks. For dental extractions, the Factor VIII level should be raised to 50% immediately prior to the procedure; additional Alphanate® may be given if bleeding recurs.¹⁷

In patients with severe Factor VIII deficiency who experience frequent hemorrhages, Antihemophilic Factor (Human), Alphanate®, may be administered prophy-lactically on a daily or every other day schedule to raise the Factor VIII level to approximately 15%.¹⁸

Factor VIII levels should be monitored periodically to evaluate individual patient response to the dosage regime.

For pediatric usage

See PRECAUTIONS

RECONSTITUTION

Always Use Aseptic Technique

1. Warm diluent (Sterile Water for Injection, USP) and concentrate (Alphanate®) to at least room temperature (but not above 37 °C).
2. Remove plastic caps from the diluent and concentrate vials.
3. Swab the exposed stopper surfaces with a cleansing agent such as alcohol. Do not leave excess cleansing agent on the stoppers.
4. Remove cover from one end of the double-ended transfer needle. Insert the exposed end of the needle through the center of the stopper in the DILUENT vial.
5. Remove plastic cap from the other end of the double-ended transfer needle now seated in the stopper of the diluent vial. To reduce any foaming, invert the vial of diluent and insert the exposed end of the needle through the center of the stopper in the CONCENTRATE vial at an angle, making certain that the diluent vial is always above the concentrate vial. The angle of insertion directs the flow of diluent against the side of the concentrate vial. Refer to Figure 1. There should be enough vacuum in the vial to transfer all of the diluent.
   

Figure 1
6. Disconnect the two vials by removing the transfer needle from the diluent vial stopper. Remove the double-ended transfer needle from the concentrate vial and discard the needle into the appropriate safety container.
7. Let the vial stand until contents are in solution, then GENTLY swirl until all concentrate is dissolved. Reconstitution requires less than 5 minutes.
8. DO NOT SHAKE THE CONTENTS OF THE VIAL. DO NOT INVERT THE CONCENTRATE VIAL UNTIL READY TO WITHDRAW CONTENTS.
9. Use as soon as possible after reconstitution.
10. After reconstitution, parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. When reconstitution procedure is strictly followed, a few small particles may occasionally remain. The microaggregate filter will remove particles and the labeled potency will not be reduced.

ADMINISTRATION BY SYRINGE

Use Aseptic Technique

1. Peel cover from microaggregate filter package and securely install the syringe into the exposed Luer inlet of the filter, using a slight clockwise twisting motion.
2. Remove filter from packaging. Remove protective cover from the spike end of the filter.
3. Pull back plunger drawing sufficient air into the syringe to allow reconstituted product to be withdrawn as described in the next step.
4. Insert the spike end of the filter into the reconstituted concentrate vial. Inject air (Figure 2a) and withdraw the reconstituted product from the vial into the syringe (Figure 2b).

Figure 2a               Figure 2b
5. Remove the filter from the syringe; discard the filter and the empty concentrate vial, into the appropriate safety container. Attach syringe to an infusion set, expel air from the syringe and infusion set. Perform venipuncture and administer slowly at a rate not exceeding 10 mL/minute.
6. If the patient is to receive more than one vial of concentrate, the infusion set will allow administration of multiple vials to be performed with a single venipuncture.
7. Discard all administration equipment after use into the appropriate safety container. Do not reuse.

Alphanate® is supplied in sterile, lyophilized form in single dose vials accompanied by a suitable volume of diluent (Sterile Water for Injection, USP), according to AHF potency. Each vial is labeled with the Factor VIIIC potency expressed in AHF International Units. Alphanate® is packaged with a double-ended transfer needle and microaggregate filter for use in administration.

Storage

Alphanate® should be stored at temperatures between 2 and 8 °C. Do not freeze to prevent damage to diluent vial. May be stored at room temperature not to exceed 30 °C for up to 2 months. When removed from refrigeration, record the date removed on the space provided on the carton.

REFERENCES

7. Eyster, M.E. Hemophilia: A Guide for the Primary Care Physician. Postgraduate Medicine 1978, 64:75-81.

15. Shanbrom, E., Thelin, M. Experimental Prophylaxis of Severe Hemophilia with a Factor VIII Concentrate. JAM A 1969, 208(9): 1 853-1 856.

16. Levine, P.H. Hemophilia and Allied Conditions. In: Current Therapy in Hematology-On-cology: 1983-1984. Brain, M.C. (ed) New York: BC Decker, 1983, pp. 147-152.

17. Kasper, C.K. Hemophilia and Hemophilioid Disorders. In: Conn, H.F., ed. Current Therapy, 4th ed., Philadelphia: Saunders, 1974, pp. 258-263.

18. Kasper, C.K., Dietrich, S.L., Rapaport, S.I. Hemophilia Prophylaxis with Factor VIII Concentrate. Arch Intern Med 1970, 125:1004-1009.

Manufactured by: Grifols Biologicals Inc., Los Angeles, CA 90032, USA. Revised January 2004. FDA rev date: n/a

Last updated on RxList: 11/14/2008

Adverse reactions may include urticaria, fever, chills, nausea, vomiting, headache, somnolence, or lethargy.

Occasionally, mild reactions occur following the administration of Antihemophilic Factor (Human)¹³, such as allergic reactions, chills, nausea, or stinging at the infusion site. If a reaction is experienced, and the patient requires additional Antihemophilic Factor (Human), product from a different lot should be administered.

Massive doses of Antihemophilic Factor (Human) have rarely resulted in acute hemolytic anemia, increased bleeding tendency or hyperfibrinogenemia.¹⁴ Alphanate® contains blood group specific isoagglutinins and, when large and/or frequent doses are required in patients of blood groups A, B, or AB, the patient should be monitored for signs of intravascular hemolysis and falling hematocrit. Should this condition occur, thus leading to progressive emolytic anemia, the administration of serologically compatible type O red blood cells should be considered or the administration of Antihemophilic Factor (Human) produced from group-specific plasma should be considered.

No information provided.

REFERENCES

13. Rizza, C.R., Biggs, R. Blood Products in the Management of Haemophilia and Christmas Disease. In: Poller, L, ed. Recent Advances in Blood Coagulation, Boston: Little Brown, 1969, pp.1 79-1 95.

14. Hathaway, W.E., Mahasandana, C, Clarke, S. Alteration of Platelet Function After Transfusion in Hemophilia. Proc 14th Ann Mtg, Am Soc Hematol 1971, Abstracts, 58, No. 88.

Last updated on RxList: 11/14/2008

Because Antihemophilic Factor (Human), Alphanate® is made from pooled human plasma, it may carry a risk of transmitting infectious agents, e.g., viruses, and theoretically, the Creutzfeldt-Jakob disease (CJD) agent. Stringent procedures designed to reduce the risk of adventitious agent transmission have been employed in the manufacture of this product, from the screening of plasma donors and the collection and testing of plasma, through the application of viral elimination/reduction steps such as solvent detergent and heat treatment in the manufacturing process. Despite these measures, such products can still potentially transmit disease; therefore, the risk of infectious agents cannot be totally eliminated. All infections thought by a physician possibly to have been transmitted by this product should be reported to the manufacturer at 1-888-675-2762 (US) or 1-323-225-9735 (International). The physician should weigh the risks and benefits of the use of this product and should discuss these with the patient.

Individuals who receive infusions of blood or plasma products may develop signs and/or symptoms of some viral infections, particularly hepatitis C.^8-9 Incubation in a solvent detergent mixture during the manufacturing process is designed to reduce the risk of transmitting viral infection.^8,9 However, scientific opinion encourages hepatitis A and hepatitis B vaccinations for patients with hemophilia at birth or at the time of diagnosis.

General

Antihemophilic Factor (Human), Alphanate®, should not be administered at a rate exceeding 10 mL/minute. Rapid administration of a Factor VIII concentrate may result in vasomotor reactions.

Some patients develop inhibitors to Factor VIII. Factor VIII inhibitors are circulating antibodies (i.e., globulins) that neutralize the procoagulant activity of Factor VIII. No studies have been conducted with Alphanate® to evaluate inhibitor formation. Therefore, it is not known whether there are greater, lesser or the same risks of developing inhibitors due to the use of this product than there are with other antihemophilic factor preparations. Patients with these inhibitors may not respond to treatment with Antihemophilic Factor (Human), or the response may be much less than would otherwise be expected; therefore, larger doses of Antihemophilic Factor (Human) are often required. The management of bleeding in patients with inhibitors requires careful monitoring, especially if surgical procedures are indicated.^10-12

Nursing personnel, and others who administer this material, should exercise appropriate caution when handling due to the risk of exposure to viral infection. Discard any unused contents into the appropriate safety container. Discard administration equipment after single use into the appropriate safety container. Do not resterilize components.

Pregnancy Category C

Animal reproduction studies have not been conducted with Alphanate®. Therefore, it is not known whether it can cause fetal harm when administered to a pregnant woman or affect the reproductive capacity of a woman. Alphanate® should be given to a pregnant woman only if clearly needed.

Pediatric Use

Clinical trials for safety and effectiveness in pediatric patients 16 years of age and younger have not been conducted. Across well controlled half-life and recovery clinical trial in patients previously treated with Factor VIII concentrates for Hemophilia A, the one pediatric patient receiving Alphanate® (solvent detergent) responded similarly when compared with 12 adult patients.⁴ No adverse events were reported in either pediatric or adult patients with Alphanate®.⁴

REFERENCES

4. Data on file at Grifols Biologicals Inc.

8. Biggs, R. Jaundice and Antibodies Directed Against Factors VIII and IX in Patients Treated for Haemophilia or Christmas Disease in the United Kingdom. Br J Haematol 1974, 26:313-329.

9. Kasper, C.K., Kipnis, S.A. Hepatitis and Clotting Factor Concentrates. JAMA 1972,221:510.

10. Kasper, C.K. Incidence and Course of Inhibitors Among Patients with Classic Hemophilia. Thromb Diath Haemorrh (Stuttg) 1973, 30:263-271.

11. Rizza, C.R., Biggs, R. The Treatment of Patients Who Have Factor VIII Antibodies. Br ] Haematol 1973, 24:65-82.

12. Roberts, H.R., Knowles, M.R., Jones, T.L., McMillan, C. The Use of Factor VIII in the Management of Patients with Factor VIII Inhibitors. In: Brinkhous, K.M., ed. Hemophilia and New Hemorrhagic States, International Symposium, New York, University of North Carolina Press, 1970, pp.152-163.

Last updated on RxList: 11/14/2008

No information provided.

None known.

Last updated on RxList: 11/14/2008

Antihemophilic Factor (Human) is a constituent of normal plasma and is required for clotting. The administration of Alphanate® temporarily increases the plasma level of this clotting factor, thus minimizing the hazard of hemorrhage.^2-3 Following the administration of Alphanate® during clinical trials, the mean in vivo half-life of Factor VIII observed in 12 adult subjects with severe hemophilia A was 17.9 ± 9.6 hours. In this same study, the In vivo recovery was 96.7 ± 14.5% at 10 minutes postinfusion.⁴ Recovery at 10 minutes postinfusion was also determined as 2.4 ± 0.4 IU FVIII rise/dL plasma per IU FVIII infused/kg body weight.⁴

The solvent detergent treatment process has been shown by Horowitz, et al., to provide a high level of virus kill without compromising protein structure and function.⁵ The susceptibility of human pathogenic viruses such as the human immunodeficiency viruses, hepatitis viruses, as well as marker viruses such as sindbis virus and vesicular stomatitis virus (VSV), to inactivation by organic solvent detergent treatment has been discussed in the literature.⁶

In vitro inactivation studies to evaluate the solvent detergent treatment step used in the manufacture of Alphanate® employed an assay with a sensitivity of 2 logs of virus for the marker viruses, vesicular stomatitis virus (VSV) and sindbis virus. The studies demonstrated a log kill of ≥ 4.1 for VSV and ≥ 4.7 for sindbis virus. Greater than or equal to 11.1 logs of HIV-1 and greater than or equal to 6.1 logs of HIV-2 were inactivated by the solvent detergent treatment step. The number of viral particles inactivated by the process represents the maximum amount of virus added initially to the sample, thus the results of the study indicate that all the added HIV virus was killed.⁴

In another study, the dry heat cycle of 80 °C for 72 hours of the Alphanate® manufacturing process was shown to inactivate greater than or equal to 5.8 logs of hepatitis A virus (HAV).

In a different study, the following steps in the manufacturing process of Alphanate® were evaluated for virus reduction/removal capability: precipitation with 3.5% polyethylene glycol (PEG), solvent detergent treatment with 0.3% tri-n-butyl phosphate and 1.0% polysorbate 80, heparin-actigel-ALD chromatography, lyophilization of Factor VIM and heat treatment at 80 °C for 72 hours. The following viruses were used in these studies: bovine herpes (BHV), bovine viral diarrhea virus (BVD), human poliovirus Sabin type 2 (POL), canine parvovirus (CPV) and human immunodeficiency virus, type 1 (HIV-1).

Table 1 summarizes the reduction factors for each virus evaluated for each viral inactivation/removal step validated in the manufacturing process of Alphanate®.⁴

However, no treatment method has yet been shown capable of totally eliminating all potential infective virus in preparations of coagulation factor concentrates.

Table 1

Virus Reduction (log10)	Processing Step
	3.5% PEG Precipitation	Solvent Detergent treatment	Column chromatography	Lyophilization of Factor VIII	Dry heat Cycle (80 °C, 72h)	Total Log Removal
BHV	< 1.0	≥ 8.0	7.6	1.3	2.1	≥ 19.0
BVD	< 1.0	≥ 4.5	< 1.0	< 1.0	≥ 4.9	≥ 9.4
POL	3.3	_	< 1.0	3.4	≥ 2.5	≥ 9.2
CPV	1.2	-	< 1.0	< 1.0	4.1	5.3
VSV	-	≥ 4.1	-	-	-	≥ 4.1
Sindbis	-	≥ 4.7	-	-	-	≥ 4.7
HIV-1	< 1.0	≥ 11.1	≥ 2.0	-	-	≥ 13.1
HIV-2	-	≥ 6.1	-	-	-	≥ 6.1
HAV	-			2.1	> 5.8	≥ 7.9

REFERENCES

1. Fujimura, Y., Titani, K., Holland, L.Z., Roberts, J.R., Kostel, P., Ruggeri, Z.M., Zimmerman, T.S. A Heparin-Binding Domain of Human Von Willebrand Factor: Characterization and Localization to a Tryptic Fragment Extending from Amino Acid Residue Val-449 to Lys-728. I Biol Chem 1987, 262(4): 1 734-1 739.

2. Hershgold, E.J. Properties of Factor VIII (Antihaemophilic Factor). In: Spaet, T.H., ed. Progress in Hemostasis and Thrombosis, Grune and Stratton Publisher, 1974, 2:99-139.

3. Ashenhurst, J.B., Langehenning, P.L., Seeier, R.A. Early Treatment of Bleeding Episodes with 10 U/Kgof Factor VIII. Blood 1977, 50:181.

4. Data on file at Grifols Biologicals Inc.

5. Edwards, C.A., Piet, M.P.J., Chin, S., Horowitz, B. Tri(n-Butyl) Phosphate/Detergent Treatment of Licensed Therapeutic and Experimental Blood Derivatives. Vox Sang 1987, 52:53-59.

6. Horowitz, B. Investigations into the Application of Tri(n-Butyl) Phosphate/Detergent Mixture to Blood Derivatives. In: Morgenthaler, J-J. ed. Viral Inactivation in Plasma Products, Karger, 1989, 56:83-96.

Last updated on RxList: 11/14/2008

Patients should be informed of the early symptoms and signs of hypersensitivity reaction, including hives, generalized urticaria, chest tightness, dyspnea, wheezing, faintness, hypotension, and anaphylaxis. Patients should be advised to discontinue use of the product and contact their physician and/or seek immediate emergency care, depending on the severity of the reaction, if these symptoms occur.

Some viruses, such as parvovirus B19 or hepatitis A, are particularly difficult to remove or inactivate at this time. Parvovirus B19 may most seriously affect seronegative pregnant women, or immunocompromised individuals. The majority of parvovirus B19 and hepatitis A infections are acquired by environmental (natural) sources.

Last updated on RxList: 11/14/2008

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.