Hemofil M
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Questions & Answers
Side Effects & Adverse Reactions
Allergic-type hypersensitivity reactions, including anaphylaxis, have been reported with HEMOFIL M and have been manifested by bronchospasm, dyspnea, hypotension, chest pain, facial edema, urticaria, rash, flushing, pruritus, and nausea.
The development of neutralizing antibodies (inhibitors) to Factor VIII is a known complication of the treatment of patients with Hemophilia A. Inhibitors have predominantly been reported in previously untreated patients. The risk of developing inhibitors is correlated to the extent of exposure to Factor VIII, the risk being highest within the first 20 exposure days, and to other genetic and environmental factors. The risk for inhibitor development depends on a number of factors relating to the characteristics of the patient (e.g., type of the Factor VIII gene mutation, family history, ethnicity), which are believed to represent the most significant risk factors for inhibitor formation.
Because HEMOFIL M is made from human blood, it may carry a risk of transmitting infectious agents, e.g., viruses, the variant Creutzfeldt-Jakob disease (vCJD) agent and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent. This also applies to unknown or emerging viruses and other pathogens.
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 (in the U.S.) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. The physician should discuss the risks and benefits of this product with the patient.
Individuals who receive infusions of blood or plasma products may develop signs and/or symptoms of some viral infections, particularly non-A, non-B hepatitis. As indicated under Clinical Pharmacology, however, a group of such patients treated with HEMOFIL M did not demonstrate signs or symptoms of non-A, non-B hepatitis over observation periods ranging from three to nine months.
Allergic-type hypersensitivity reactions, including anaphylaxis, have been reported with HEMOFIL M and have been manifested by bronchospasm, dyspnea, hypotension, chest pain, facial edema, urticaria, rash, flushing, pruritus, and nausea.
Neutralizing AntibodiesThe development of neutralizing antibodies (inhibitors) to Factor VIII is a known complication of the treatment of patients with Hemophilia A. Inhibitors have predominantly been reported in previously untreated patients. The risk of developing inhibitors is correlated to the extent of exposure to Factor VIII, the risk being highest within the first 20 exposure days, and to other genetic and environmental factors. The risk for inhibitor development depends on a number of factors relating to the characteristics of the patient (e.g., type of the Factor VIII gene mutation, family history, ethnicity), which are believed to represent the most significant risk factors for inhibitor formation.
Transmission of Infectious AgentsBecause HEMOFIL M is made from human blood, it may carry a risk of transmitting infectious agents, e.g., viruses, the variant Creutzfeldt-Jakob disease (vCJD) agent and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent. This also applies to unknown or emerging viruses and other pathogens.
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 (in the U.S.) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. The physician should discuss the risks and benefits of this product with the patient.
Individuals who receive infusions of blood or plasma products may develop signs and/or symptoms of some viral infections, particularly non-A, non-B hepatitis. As indicated under Clinical Pharmacology, however, a group of such patients treated with HEMOFIL M did not demonstrate signs or symptoms of non-A, non-B hepatitis over observation periods ranging from three to nine months.
Legal Issues
There is currently no legal information available for this drug.
FDA Safety Alerts
There are currently no FDA safety alerts available for this drug.
Manufacturer Warnings
There is currently no manufacturer warning information available for this drug.
FDA Labeling Changes
There are currently no FDA labeling changes available for this drug.
Uses
HEMOFIL M is indicated in hemophilia A (classical hemophilia) for the prevention and control of hemorrhagic episodes.
HEMOFIL M is not indicated in von Willebrand's disease.
History
There is currently no drug history available for this drug.
Other Information
HEMOFIL M, Antihemophilic Factor (Human) (AHF), Method M, Monoclonal Purified, is a sterile, nonpyrogenic, dried preparation of antihemophilic factor (Factor VIII, Factor VIII:C, AHF) in concentrated form with a specific activity range of 2 to 22 AHF International Units/mg of total protein. HEMOFIL M contains a maximum of 12.5 mg/mL Albumin, and per AHF International Unit, 0.07 mg polyethylene glycol (3350), 0.39 mg histidine as stabilizing agents, not more than 0.1 mg glycine, 0.1 ng mouse protein, 18 ng organic solvent (tri-n-butyl phosphate) and 50 ng detergent (octoxynol 9). In the absence of the added Albumin (Human), the specific activity is approximately 2,000 AHF International Units/mg of protein. [see Clinical Pharmacology]
HEMOFIL M is prepared by the Method M process from pooled human plasma by immunoaffinity chromatography utilizing a murine monoclonal antibody to Factor VIII:C, followed by an ion exchange chromatography step for further purification. Source material may be provided by other US licensed manufacturers. HEMOFIL M also includes an organic solvent (tri-n-butyl phosphate) and detergent (octoxynol 9) virus inactivation step designed to reduce the risk of transmission of hepatitis and other viral diseases. The process further includes a nanofiltration step between immunoaffinity chromatography and ion-exchange chromatography as an additional viral clearance step to further improve the viral safety margin of the final product.
Use of an organic solvent (tri-n-butyl phosphate; TNBP) in the manufacture of Antihemophilic Factor (Human) has little or no effect on AHF activity, while lipid enveloped viruses, such as hepatitis B and human immunodeficiency virus (HIV) would be inactivated.1 The nanofiltration step integrated into the manufacture of AHF-M further enhances the safety margin with respect to adventitious viruses.
Each bottle of HEMOFIL M is labeled with the AHF activity expressed in International Units (IU) per bottle. This potency assignment is referenced to the World Health Organization International Standard.
The purity of HEMOFIL M has been thought to influence the difficulty of producing an accurate potency measurement. Experiments have shown that to achieve accurate activity levels, such a potency assay should be conducted using plastic test tubes and pipets as well as substrate containing normal levels of von Willebrand's Factor.
In vitro studies demonstrate that the HEMOFIL M manufacturing process provides for viral reduction. These reductions are achieved through a combination of process chemistry, partitioning and/or inactivation during solvent/detergent treatment, and immunoaffinity chromatography. Introduction of a nanofiltration step with the 0.1µm prefilter and the ASAHI Planova 20N nanofilter provides a virus removal capacity for human immunodeficiency virus, Type 1 (HIV-1), hepatitis A virus (HAV), bovine viral diarrhea virus (BVDV), pseudorabies virus (PRV), mice minute virus (MMV), and human parvovirus B19 (B19V) in the order of four (4) logs or higher. B19V removal data were obtained with a Polymerase Chain Reaction (PCR) assay not correlated to an infectivity assay.
Studies for nanofiltration and other process steps, summarized in Table 1, demonstrate virus clearance during the HEMOFIL M manufacturing process using HIV-1; BVDV, a generic model for lipid enveloped RNA viruses, such as hepatitis C virus (HCV); PRV, a model for lipid enveloped DNA viruses, such as hepatitis B virus (HBV); canine parvovirus (CPV), a model for non-lipid enveloped DNA viruses, such as B19V, HAV, and MMV.
|
||||||
| Process Step Evaluated |
Virus Clearance, log 10 |
|||||
| Lipid-enveloped |
Non-Lipid enveloped |
|||||
| HIV-1 |
BVDV |
PRV |
HAV |
CPV |
MMV |
|
| Solvent/Detergent Treatment |
>4.8 |
>6.8 |
>6.9 |
NT* |
NT* |
NT* |
| Immunoaffinity Chromatography |
N.A.† |
N.A.† |
N.A.† |
≥4.5 |
≥3.9 |
NT |
| Nanofiltration |
>5.5 |
>4.6 |
>4.4 |
>5.4 |
NT |
>5.0 |
| Cumulative Total, log10 |
>10.3 |
>11.4 |
>11.3 |
>9.9 |
≥3.9 |
>5.0 |
Sources
Hemofil M Manufacturers
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Baxter Healthcare Corporation
![Hemofil M (Antihemophilic Factor Human) Kit [Baxter Healthcare Corporation]](/wp-content/themes/bootstrap/assets/img/loading2.gif)
Hemofil M | Baxter Healthcare Corporation
For intravenous use only.
The expected in vivo peak AHF level, expressed as IU/dL of plasma or % (percent) of normal, can be calculated by multiplying the dose administered per kg body weight (IU/kg) by two. This calculation is based on the clinical finding by Abildgaard, et al,2 which is supported by data from the collaborative study of in vivo recovery and survival with 15 different lots of HEMOFIL M on 56 hemophiliacs that demonstrated a mean peak recovery point above the mean pre-infusion baseline of about 2.0 IU/dL per infused IU/kg body weight.3
Examples:
(1) A dose of 1750 IU AHF administered to a 70 kg patient, i.e., 25 IU/kg (1750/70), should be expected to cause a peak post-infusion AHF increase of 25 x 2 = 50 IU/dL (50% of normal).
(2) A peak level of 70% is required in a 40 kg child. In this situation the dose would be 70/2 x 40 = 1400 IU.
Recommended Dosage Schedule
Physician supervision of the dosage is required. The following dosage schedule may be used as a guide.
HEMORRHAGE
Degree of hemorrhage
Required peak post-infusion AHF activity in the blood (as % of normal or IU/dL plasma)
Frequency of infusion
Early hemarthrosis or muscle bleed or oral bleed
20-40
Begin infusion every 12 to 24 hours for one-three days until the bleeding episode as indicated by pain is resolved or healing is achieved.
More extensive hemarthrosis, muscle bleed, or hematoma
30-60
Repeat infusion every 12 to 24 hours for usually three days or more until pain and disability are resolved.
Life threatening bleeds such as head injury, throat bleed, severe abdominal pain
60-100
Repeat infusion every 8 to 24 hours until threat is resolved.
SURGERY
Type of operation
Minor surgery, including tooth extraction
60-80
A single infusion plus oral antifibrinolytic therapy within one hour is sufficient in approximately 70% of cases.
Major surgery
80-100 (pre- and post-operative)
Repeat infusion every 8 to 24 hours depending on state of healing.
If bleeding is not controlled with the prescribed dose, determine the plasma level of Factor VIII and administer a sufficient dose of HEMOFIL M to achieve a satisfactory clinical response.
Under certain circumstances (e.g., presence of a low titer inhibitor) doses larger than those recommended may be necessary as per standard care. In patients with high titer Factor VIII inhibitors, HEMOFIL M therapy may not be effective and other therapeutic options should be considered.
The dosage and duration of treatment depend on the severity of Factor VIII deficiency, the location and extent of the bleeding, and the patient’s clinical condition. Careful control of replacement therapy is especially important in cases of major surgery or life threatening hemorrhages.
Reconstitution: Use Aseptic Technique 1. Bring HEMOFIL M (dry concentrate) and Sterile Water for Injection, USP, (diluent) to room temperature. 2. Remove caps from concentrate and diluent bottles to expose central portion 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 upright HEMOFIL M bottle, then rapidly insert free end of the needle through the HEMOFIL M bottle stopper at its center. The vacuum in the HEMOFIL M bottle will draw in the diluent. 6. Disconnect the two bottles by removing needle from diluent bottle stopper, then remove needle from HEMOFIL M bottle. Swirl gently until all material is dissolved. Be sure that HEMOFIL M is completely dissolved; otherwise active material will be removed by the filter.Note: Do not refrigerate after reconstitution.
Administration: Use Aseptic Technique • Intravenous administration only. • Administer at room temperature not more than 3 hours after reconstitution. • Record the name and batch number of the product in order to maintain a link between the patient and the batch of the product.Intravenous Syringe Injection
• Visually inspect parenteral product for particulate matter and discoloration prior to administration. The solution should be colorless in appearance. Do not administer if particulate matter or discoloration is found. • Plastic syringes are recommended for use with this product. The ground glass surface of all-glass syringes tend to stick with solutions of this type.1. Attach filter needle to a disposable syringe and draw back plunger to admit air into syringe.
2. Insert needle into reconstituted HEMOFIL M.
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 as instructed under Rate of Administration.
5. If a patient is to receive more than one bottle of HEMOFIL M, 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 HEMOFIL M. Filter needles are intended to filter the contents of a single bottle of HEMOFIL M only.
Rate of AdministrationAdminister HEMOFIL M at a rate of up to 10 mL per minute. Infuse HEMOFIL M at a rate of administration that ensures the comfort of the patient. [see Precautions: Increase of Pulse Rate]
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