Bebulin

Name: Bebulin

Factor Ix Complex Dosage

Use exactly as prescribed by your doctor. Do not use in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

Factor IX is injected into a vein through an IV. You may be shown how to use an IV at home. Do not self-inject this medicine if you do not fully understand how to give the injection and properly dispose of used needles, IV tubing, and other items used to inject the medicine.

Always check the strength of the medicine on the label to be sure you are using the correct potency.

Always wash your hands before preparing and giving your injection.

Factor IX must be mixed with a liquid (diluent) before using it. If you are using the injections at home, be sure you understand how to properly mix and store the medicine. Take the medicine and diluent out of the refrigerator and allow them to reach room temperature before mixing your dose. Do not heat the medicine or diluent.

Each single-use vial (bottle) of this medicine is for one use only. Throw away after one use, even if there is still some medicine left in it after injecting your dose.

After mixing, gently swirl the mixture and allow the medicine to completely dissolve. The mixture should be kept at room temperature and must be used within 3 hours. Do not put mixed medicine into the refrigerator.

Prepare your dose in a syringe only when you are ready to give yourself an injection. Do not use the medication if it has changed colors or has particles in it. Call your pharmacist for new medication.

A single dose of factor IX may be enough to control minor bleeding. If you need another dose, wait at least 24 hours before using the medication again.

Check your pulse before and during your injection. If your pulse rate changes, slow or stop the injection until your pulse rate returns to normal.

Use a disposable needle only once. Throw away used needles in a puncture-proof container (ask your pharmacist where you can get one and how to dispose of it). Keep this container out of the reach of children and pets.

Wear a medical alert tag or carry an ID card stating that you have hemophilia. Any medical care provider who treats you should know that you have a bleeding or blood-clotting disorder.

If you need any type of surgery or dental work, tell the surgeon or dentist ahead of time that you have hemophilia.

You may need regular medical tests to be sure this medication is not causing harmful effects. Visit your doctor regularly.

Store the medication and the diluent in the refrigerator and do not allow them to freeze.

Throw away any unused medicine or diluent after the expiration date on the label has passed.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Factor IX is sometimes used only when needed, so you may not be on a dosing schedule. If you are using the medication regularly, use the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not use extra medicine to make up the missed dose.

Pharmacology

Mechanism of Action

Mixture of vitamin K-dependent clotting factors; temporarily increases the plasma levels of Factor IX, thus minimizing the hazards of hemorrhage in patients with hemophilia B

Bebulin Drug Class

Bebulin is part of the drug class:

  • Blood coagulation factors

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

  • The condition for which you are using this medicine.
  • Your body weight.
  • The amount of factor IX your body is able to make.
  • How much, how often, and where in your body you are bleeding.
  • Whether or not your body has built up a defense (antibody) against this medicine.

Missed Dose

Call your doctor or pharmacist for instructions.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Before Using Bebulin

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Blood clots may be especially likely to occur in premature and newborn babies, who are usually more sensitive than adults to the effects of injections of factor IX.

Geriatric

This medicine has been tested and has not been shown to cause different side effects or problems in older people than it does in younger adults.

Pregnancy

Pregnancy Category Explanation
All Trimesters C Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women.

Breast Feeding

Coagulation Factor IX RecombinantFactor IX Fc Fusion Protein RecombinantFactor IX Albumin Fusion Protein RecombinantCoagulation Factor IX Recombinant, GlycoPEGylated

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Factor IX

Studies in women suggest that this medication poses minimal risk to the infant when used during breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. Tell your healthcare professional if you are taking any other prescription or nonprescription (over-the-counter [OTC]) medicine.

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

  • Blood clots or a history of medical problems caused by blood clots or
  • Liver disease—Risk of bleeding or developing blood clots may be increased

Consumer Information Use and Disclaimer

  • If your symptoms or health problems do not get better or if they become worse, call your doctor.
  • Do not share your drugs with others and do not take anyone else's drugs.
  • Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
  • Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Check with your pharmacist about how to throw out unused drugs.
  • Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about Bebulin, please talk with your doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about Bebulin. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using Bebulin.

Review Date: October 4, 2017

Bebulin Description

Bebulin (Factor IX Complex), Nanofiltered and Vapor Heated, is a purified, sterile, stable, freeze-dried concentrate of the Coagulation Factor IX (Christmas Factor) as well as Factor II (Prothrombin) and Factor X (Stuart Prower Factor) and low amounts of Factor VII. In addition, the product contains small amounts of heparin (≤ 0.15 IU heparin per IU Factor IX).

Bebulin is standardized in terms of Factor IX content and each vial is labeled for the Factor IX content indicated in International Units (IU). One International Unit of Factor IX (according to the current International Standard for Human Blood Coagulation Factors II, IX, and X in Concentrates) corresponds to the activity of Factor IX in 1 mL of fresh normal human plasma.

Bebulin is manufactured from large plasma pools of human plasma. Screening against potentially infectious agents begins with the donor selection process and continues throughout plasma collection and plasma preparation. Each individual plasma donation used in the manufacture of Bebulin is collected only at FDA approved blood establishments and is tested by FDA licensed serological tests for Hepatitis B Surface Antigen (HBsAg), and for antibodies to Human Immunodeficiency Virus (HIV-1/HIV-2) and Hepatitis C Virus (HCV) in accordance with U.S. regulatory requirements. As an additional safety measure, mini-pools of the plasma are tested for the presence of HIV-1 and HCV by FDA licensed Nucleic Acid Testing (NAT) and found negative. In addition, two dedicated and independent virus removal/inactivation steps have been integrated into the manufacturing process, namely 35 nm nanofiltration1 and a vapor heat treatment process2 [10 hours at 60°C and subsequent 1 hour at 80°C under the condition of 7-8% (w/v) residual moisture]. In addition, the DEAE-Sephadex adsorption contributes to the virus safety profile of Bebulin. Despite these measures, such products can still potentially transmit disease (see WARNINGS).

In vitro spiking studies have been used to validate the capability of the manufacturing process to remove and inactivate viruses. To establish virus clearance capacity of the manufacturing process, these virus clearance studies were performed in accordance with good laboratory practices under extreme conditions (e.g. at minimum incubation times and temperatures below specifications for vapor –heat treatment). The in vitro viral reduction studies performed on nanofiltered Bebulin are summarized in Table 1 .

Table 1: Mean log10 Reduction Factors (RFs) For Each Virus and Manufacturing Step*  
* Reduction factors < 1 log are not used for calculation of the overall reduction factor. † Studies on B19V, which are considered experimental in nature, have demonstrated a virus reduction factor of not more than 3.6 log10 and 4.6 log10 by DEAE-Sephadex adsorption and vapor -heat treatment, respectively. ‡ HIV-1, Human Immunodeficiency Virus Type 1
BVDV, Bovine Viral Diarrhea Virus (model for Hepatitis C Virus and other lipid enveloped RNA viruses)
PRV, Pseudorabies Virus (model for lipid enveloped DNA viruses including Hepatitis B Virus)
HAV, Hepatitis A Virus
MMV, Mice Minute Virus (model for non-lipid enveloped DNA viruses, including human parvovirus B19 [B19V]) § n.d.: Not done ¶ Studies on West Nile Virus (WNV), have demonstrated a virus reduction factor of 3.1 log10 by the 35 nm nanofiltration step.
Virus Type Enveloped RNA Enveloped DNA Non-enveloped RNA Non-enveloped DNA
Virus Family Retroviridae Flaviviridae Herpesviridae Picornaviridae Parvoviridae†
Virus‡ HIV-1 BVDV PRV HAV MMV
DEAE Sephadex Adsorption n.d§ n.d n.d 1.4 1.3
35 nm Nanofiltration¶ > 6.4 2.0 > 6.0 1.7 ≤1.0
Vapor-Heat Treatment > 6.8 > 7.1 > 7.4 > 4.5 ≤1.0
Overall log reduction factor (ORF) > 13.2 > 9.1 > 13.4 > 7.6 1.3

Contraindications

None known.

Warnings

Contraindications

Hypersensitivity

Bebulin, Bebulin VH: Known allergy to heparin or history of heparin-induced thrombocytopenia

Cautions

Made from pooled human plasma, it may carry a risk of transmitting infectious agents (eg, viruses), and theoretically, the Creutzfeldt-Jakob disease (CJD) agent

Thromboembolic events (DVT, PE, thrombotic stroke) as well as DIC reported

Factor IX complex products may partically counteract the effect of warfarin treatment; does NOT include adequate FVII levels to be used to reverse warfarin-induced bleeding

Formation of circulating antibodies inhibiting Factor IX reported

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