FDA label 7c490b0a-7412-407b-823e-e7e0e8ad4011

WARNINGS Hypersenitivity Allergic-type hypersensitivity reactions, including anaphylaxis, have been reported with HEMOFIL M and have been manifested by, for example, bronchospasm, dyspnea, hypotension, chest pain, facial edema, urticaria, rash, flushing, pruritus, nausea. Neutralizing Antibodies 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. Transmission of Infectious Agents HEMOFIL M 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. Appropriate vaccination (against hepatitis A and B) should be considered for patients in regular/repeated receipt of plasma-derived products including HEMOFIL M. Despite these measures, such products can still potentially transmit disease. Because this product is made from human plasma, a risk of transmitting infectious agents, e.g., viruses and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent, cannot be totally excluded. 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.). 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.

Hypersenitivity Allergic-type hypersensitivity reactions, including anaphylaxis, have been reported with HEMOFIL M and have been manifested by, for example, bronchospasm, dyspnea, hypotension, chest pain, facial edema, urticaria, rash, flushing, pruritus, nausea.

Neutralizing Antibodies 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.

Transmission of Infectious Agents HEMOFIL M 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. Appropriate vaccination (against hepatitis A and B) should be considered for patients in regular/repeated receipt of plasma-derived products including HEMOFIL M. Despite these measures, such products can still potentially transmit disease. Because this product is made from human plasma, a risk of transmitting infectious agents, e.g., viruses and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent, cannot be totally excluded. 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.). 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.

ADVERSE REACTIONS Adverse Reactions from Clinical Trials The adverse reactions presented in this section have been identified based on clinical trial experience with HEMOFIL M in patients previously treated with other Factor VIII concentrates or blood products (N = 74), and previously untreated patients (PUPs; N = 50). Clinical Trial Adverse Reactions System Organ Class (SOC) Preferred MedDRA Term Number of Cases (Frequency Percentage) BLOOD AND LYMPHATIC SYSTEM DISORDERS Factor VIII inhibition 3 (5.7%) In a study that included 43 evaluable PUPs and 10 minimally treated patients (MTPs), i.e., patients with a single exposure to other Factor VIII concentrates or blood products, 3 of the total of 53 patients (5.7%) developed an inhibitor while on study. NERVOUS SYSTEM DISORDERS Dizziness 1 (0.8%) Headache 1 (0.8%) Dysgeusia 1 (0.8%) GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS Pyrexia 1 (0.8%) Infusion site inflammation 2 (1.6%) HEMOFIL M was administered to 11 patients previously untreated with Antihemophilic Factor (Human). They have shown no signs of hepatitis or HIV infection following three to nine months of evaluation. A study of 25 patients treated with HEMOFIL M, and monitored for three to six months has demonstrated no evidence of antibody response to mouse protein. More than 1,000 infusions of HEMOFIL M have been administered during the clinical trials. Reported events included a single episode each of chest tightness, fuzziness and dizziness, and one patient reported an unusual taste after each infusion. Post-marketing Adverse Reactions In addition to clinical trials, the following adverse reactions have been reported in the post-marketing experience, listed by MedDRA System Organ Class (SOC), then by Preferred Term. IMMUNE SYSTEM DISORDERS: Anaphylaxis, Hypersensitivity reactions EYE DISORDERS: Visual impairment, Ocular hyperemia CARDIAC DISORDERS: Cyanosis, Bradycardia, Tachycardia VASCULAR DISORDERS: Hypotension, Flushing RESPIRATORY, THORACIC, AND MEDIASTINAL DISORDERS: Bronchospasm, Dyspnea, Cough, Hyperventilation GASTROINTESTINAL DISORDERS: Diarrhea, Vomiting, Nausea, Abdominal pain SKIN AND SUBCUTANEOUS TISSUE DISORDERS: Urticaria, Rash, Pruritus, Hyperhidrosis GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS: Facial edema, Edema, Chills, Fatigue, Chest pain, Musculoskeletal pain, Irritability

Adverse Reactions from Clinical Trials The adverse reactions presented in this section have been identified based on clinical trial experience with HEMOFIL M in patients previously treated with other Factor VIII concentrates or blood products (N = 74), and previously untreated patients (PUPs; N = 50). Clinical Trial Adverse Reactions System Organ Class (SOC) Preferred MedDRA Term Number of Cases (Frequency Percentage) BLOOD AND LYMPHATIC SYSTEM DISORDERS Factor VIII inhibition 3 (5.7%) In a study that included 43 evaluable PUPs and 10 minimally treated patients (MTPs), i.e., patients with a single exposure to other Factor VIII concentrates or blood products, 3 of the total of 53 patients (5.7%) developed an inhibitor while on study. NERVOUS SYSTEM DISORDERS Dizziness 1 (0.8%) Headache 1 (0.8%) Dysgeusia 1 (0.8%) GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS Pyrexia 1 (0.8%) Infusion site inflammation 2 (1.6%) HEMOFIL M was administered to 11 patients previously untreated with Antihemophilic Factor (Human). They have shown no signs of hepatitis or HIV infection following three to nine months of evaluation. A study of 25 patients treated with HEMOFIL M, and monitored for three to six months has demonstrated no evidence of antibody response to mouse protein. More than 1,000 infusions of HEMOFIL M have been administered during the clinical trials. Reported events included a single episode each of chest tightness, fuzziness and dizziness, and one patient reported an unusual taste after each infusion.

Post-marketing Adverse Reactions In addition to clinical trials, the following adverse reactions have been reported in the post-marketing experience, listed by MedDRA System Organ Class (SOC), then by Preferred Term. IMMUNE SYSTEM DISORDERS: Anaphylaxis, Hypersensitivity reactions EYE DISORDERS: Visual impairment, Ocular hyperemia CARDIAC DISORDERS: Cyanosis, Bradycardia, Tachycardia VASCULAR DISORDERS: Hypotension, Flushing RESPIRATORY, THORACIC, AND MEDIASTINAL DISORDERS: Bronchospasm, Dyspnea, Cough, Hyperventilation GASTROINTESTINAL DISORDERS: Diarrhea, Vomiting, Nausea, Abdominal pain SKIN AND SUBCUTANEOUS TISSUE DISORDERS: Urticaria, Rash, Pruritus, Hyperhidrosis GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS: Facial edema, Edema, Chills, Fatigue, Chest pain, Musculoskeletal pain, Irritability

<table ID="id_df22e3e4-1b99-42a8-b3dd-f8f65cbeeb19" border="single" width="442"> <col width="44.1%"/> <col width="31.0%"/> <col width="24.9%"/> <tbody> <tr ID="id_3355a9c5-3e74-46d4-8c07-6e4e885cafbd"> <td align="center" colspan="3" styleCode="Lrule Botrule Rrule" valign="top"> <content styleCode="bold">Clinical Trial Adverse Reactions</content> </td> </tr> <tr ID="id_d496723a-fca1-42c8-8fc8-944dc0f8c3e1"> <td align="center" styleCode="Lrule Botrule Rrule" valign="middle"> <content styleCode="bold">System Organ Class (SOC)</content> </td> <td align="center" styleCode="Botrule Rrule" valign="middle"> <content styleCode="bold">Preferred MedDRA Term</content> </td> <td align="center" styleCode="Botrule Rrule" valign="top"> <paragraph> <content styleCode="bold">Number of Cases</content> </paragraph> <paragraph> <content styleCode="bold">(Frequency</content> </paragraph> <content styleCode="bold">Percentage)</content> </td> </tr> <tr ID="id_2478225d-62fa-4ea0-a3bc-a6bfe802d9d0"> <td align="left" styleCode="Lrule Botrule Rrule" valign="top"> <paragraph> <content styleCode="bold">BLOOD AND LYMPHATIC</content> </paragraph> <content styleCode="bold">SYSTEM DISORDERS</content> </td> <td align="left" styleCode="Botrule Rrule" valign="middle">Factor VIII inhibition</td> <td align="center" styleCode="Botrule Rrule" valign="middle">3 (5.7%)<footnote ID="id-0b1990e4-31fa-4641-b20f-acab3f077453">In a study that included 43 evaluable PUPs and 10 minimally treated patients (MTPs), i.e., patients with a single exposure to other Factor VIII concentrates or blood products, 3 of the total of 53 patients (5.7%) developed an inhibitor while on study.</footnote> </td> </tr> <tr ID="id_3a244d17-ad56-4d38-8c27-a2ffb3f011cd"> <td align="left" rowspan="3" styleCode="Lrule Botrule Rrule" valign="top"> <content styleCode="bold">NERVOUS</content> <content styleCode="bold">SYSTEM DISORDERS</content> </td> <td align="left" styleCode="Botrule Rrule" valign="top">Dizziness</td> <td align="center" styleCode="Botrule Rrule" valign="top">1 (0.8%)</td> </tr> <tr ID="id_b61e5459-ca0a-4a72-b608-637a8fd81e17"> <td align="left" styleCode="Lrule Botrule Rrule" valign="top">Headache</td> <td align="center" styleCode="Botrule Rrule" valign="top">1 (0.8%)</td> </tr> <tr ID="id_1a306d56-0441-4fa9-9cab-e5e10584c9b0"> <td align="left" styleCode="Lrule Botrule Rrule" valign="top">Dysgeusia</td> <td align="center" styleCode="Botrule Rrule" valign="top">1 (0.8%)</td> </tr> <tr ID="id_6e139373-79e1-4450-a609-4a9912b3c96d"> <td align="left" rowspan="2" styleCode="Lrule Botrule Rrule" valign="top"> <content styleCode="bold">GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS</content> </td> <td align="left" styleCode="Botrule Rrule" valign="top">Pyrexia</td> <td align="center" styleCode="Botrule Rrule" valign="top">1 (0.8%)</td> </tr> <tr ID="id_1e5456a9-bf46-4f2d-89b4-04167b8fa67a"> <td align="left" styleCode="Lrule Botrule Rrule" valign="top">Infusion site inflammation</td> <td align="center" styleCode="Botrule Rrule" valign="top">2 (1.6%)</td> </tr> </tbody> </table>