HEMOFIL M Solution for infusion Ref.[50465] Active ingredients: Coagulation factor VIII

Hypersensitivity

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 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

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 CreutzfeldtJakob 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 Baxalta US Inc. at 1-800-423-2090 (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.

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:

^* In a study that included 4 3 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.

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: anaphylactic reaction, hypersensitivity

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

Musculoskeletal and Connective Tissue Disorders: musculoskeletal pain

General Disorders and Administration Site Conditions: facial edema, edema, chills, fatigue, chest pain, irritability

Identification of the clotting defect as a Factor VIII deficiency is essential before the administration of HEMOFIL M is initiated.

Factor VIII Inhibitors

Evaluate patients for the development of Factor VIII inhibitors if the expected plasma Factor VIII activity levels are not attained or if bleeding is not controlled with an appropriate dose.

No benefit may be expected from this product in treating other deficiencies.

Formation of Antibodies to Mous e Protein

HEMOFIL M contains trace amounts of mouse protein (less than 0.1 ng/AHF activity units). The possibility exists that patients treated with HEMOFIL M may develop hypersensitivity to the mouse proteins. There have been no cases of hypersensitivity to the mouse proteins reported.

Increase in Pulse Rate

Determine the pulse rate before and during administration of HEMOFIL M. Should a significant increase occur, reduce the rate of administration or temporarily halt the injection to allow the symptoms to disappear promptly.

Perform appropriate laboratory tests on the patient’s plasma at suitable intervals to ensure that adequate AHF levels have been reached and are maintained.

If the AHF content of the patient’s plasma fails to reach expected levels or if bleeding is not controlled after apparently adequate dosage, the presence of inhibitor should be suspected. By appropriate laboratory procedures, the presence of inhibitor can be demonstrated and quantified in terms of AHF units neutralized by each mL of plasma or by the total estimated plasma volume.

If the inhibitor is at low levels (i.e., <10 Bethesda units per mL), after administration of sufficient AHF units to neutralize the inhibitor, additional AHF units will elicit the predicted response.

Animal reproduction studies have not been conducted with HEMOFIL M. The safety of HEMOFIL M for use in pregnant women has not been established. It is not known whether HEMOFIL M can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. HEMOFIL M should be given to a pregnant woman only if clearly needed.

The safety of HEMOFIL M for use in nursing mothers has not been established. It is not known whether this drug is excreted into human milk. Physicians should carefully consider the potential risks and benefits for each specific patient before prescribing HEMOFIL M. HEMOFIL M should be given to nursing mothers only if clinically indicated.