Takeda hematology product information and coding

WARNINGS AND PRECAUTIONS

Hypersensitivity Reactions

Allergic-type hypersensitivity reactions, including anaphylaxis, have been reported with ADVATE. Symptoms include dizziness, paresthesia, rash, flushing, facial swelling, urticaria, dyspnea, pruritus, and vomiting. Discontinue ADVATE if hypersensitivity symptoms occur and administer appropriate emergency treatment.

Neutralizing Antibodies

Neutralizing antibodies (inhibitors) have been reported following administration of ADVATE predominantly in previously untreated patients (PUPs) and previously minimally treated patients (MTPs). Monitor all patients for the development of factor VIII inhibitors by appropriate clinical observation and laboratory testing. If expected plasma factor VIII activity levels are not attained, or if bleeding is not controlled with an expected dose, perform an assay that measures factor VIII inhibitor concentration.

ADVERSE REACTIONS

• Serious adverse reactions seen with ADVATE are hypersensitivity reactions, including anaphylaxis, and the development of high-titer inhibitors necessitating alternative treatments to factor VIII.
• The most common adverse reactions observed in clinical trials (>5% of subjects) were pyrexia, headache, cough, nasopharyngitis, arthralgia, vomiting, upper respiratory tract infection, limb injury, nasal congestion, and diarrhea.

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WARNINGS AND PRECAUTIONS

Hypersensitivity Reactions

Hypersensitivity reactions, including anaphylaxis, have been reported with ADYNOVATE. Hypersensitivity reactions that can progress to anaphylaxis may include angioedema, chest tightness, dyspnea, wheezing, urticaria, pruritus, and nausea and vomiting. Immediately discontinue administration and initiate appropriate treatment if hypersensitivity reactions occur.

Neutralizing Antibodies

Formation of neutralizing antibodies (inhibitors) to factor VIII can occur following administration of ADYNOVATE. Monitor patients regularly for the development of factor VIII inhibitors by appropriate clinical observations and laboratory tests. Perform an assay that measures factor VIII inhibitor concentration if the plasma factor VIII level fails to increase as expected, or if bleeding is not controlled with expected dose.

ADVERSE REACTIONS

The most common adverse reactions (≥1% of subjects) reported in the clinical studies were headache, diarrhea, rash, nausea, dizziness and urticaria.

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WARNINGS AND PRECAUTIONS

Thromboembolic events (including venous thrombosis, pulmonary embolism, myocardial infarction, and stroke) can occur, particularly following the administration of high doses (>200 units/kg/day) and/or in patients with thrombotic risk factors.

Patients with DIC, advanced atherosclerotic disease, crush injury, septicemia, or concomitant treatment with recombinant factor VII have an increased risk of developing thrombotic events due to circulating tissue factor or predisposing coagulopathy. Potential benefit of treatment should be weighed against the potential risk of these thromboembolic events.

Infusion should not exceed a single dose of 100 units/kg and daily doses of 200 units/kg. Maximum injection or infusion rate must not exceed 2 units/kg/minute. Monitor patients receiving >100 units/kg for the development of DIC, acute coronary ischemia and signs and symptoms of other thromboembolic events. If clinical signs or symptoms occur, such as chest pain or pressure, shortness of breath, altered consciousness, vision, or speech, limb or abdomen swelling and/or pain, discontinue FEIBA and initiate appropriate diagnostic and therapeutic measures.

Safety and efficacy of FEIBA for breakthrough bleeding in patients receiving emicizumab has not been established. Cases of thrombotic microangiopathy (TMA) were reported in a clinical trial where subjects received FEIBA as part of a treatment regimen for breakthrough bleeding following emicizumab treatment. Consider the benefits and risks with FEIBA if considered required for patients receiving emicizumab prophylaxis. If treatment with FEIBA is required for patients receiving emicizumab, the hemophilia treating physician should closely monitor for signs and symptoms of TMA. In FEIBA clinical studies TMA has not been reported.

Hypersensitivity and allergic reactions, including severe anaphylactoid reactions, can occur. Symptoms include urticaria, angioedema, gastrointestinal manifestations, bronchospasm, and hypotension. Reactions can be severe and systemic (e.g., anaphylaxis with urticaria and angioedema, bronchospasm, and circulatory shock). Other infusion reactions, such as chills, pyrexia, and hypertension have also been reported. If signs and symptoms of severe allergic reactions occur, immediately discontinue FEIBA and provide appropriate supportive care.

Because FEIBA is made from human plasma 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.

FEIBA contains blood group isohemagglutinins (anti-A and anti-B). Passive transmission of antibodies to erythrocyte antigens, e.g., A, B, D, may interfere with some serological tests for red cell antibodies, such as antiglobulin test (Coombs test).

ADVERSE REACTIONS

Most frequently reported adverse reactions observed in >5% of subjects in the prophylaxis trial were anemia, diarrhea, hemarthrosis, hepatitis B surface antibody positive, nausea, and vomiting.

Serious adverse reactions seen are hypersensitivity reactions and thromboembolic events, including stroke, pulmonary embolism and deep vein thrombosis.

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Neutralizing Antibodies

Formation of neutralizing antibodies (inhibitors) to factor VIII can occur following administration of HEMOFIL M. Monitor patients regularly for the development of factor VIII inhibitors by appropriate clinical observations and laboratory tests. Perform an assay that measures factor VIII inhibitor concentration if the plasma factor VIII level fails to increase as expected, or if bleeding is not controlled with expected dose.

Transmission of Infection

Because HEMOFIL M is made from human blood, it may carry a risk of transmitting infectious agents, such as viruses. These agents may include the parvovirus B19, hepatitis A, Creutzfeldt-Jakob disease agent or a variant of it, and other unknown or emerging viruses or disease causing agents. Discuss the risks and benefits of this product with the patient.

All infections thought by a physician possibly to have been transmitted by this product should be reported to Shire, at 1-800-999-1785 (Baxalta related products in the U.S.).

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.

ADVERSE REACTIONS

The adverse reactions (1 or more subjects) reported in the clinical studies were Factor VIII inhibition, infusion site inflammation, dizziness, headache, dysgeusia, and pyrexia.

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Inhibitory Antibodies

Inhibitory antibodies to OBIZUR have occurred in patients treated with OBIZUR. Lack of efficacy could be due to inhibitory antibodies to OBIZUR.

Anamnestic reactions with rise in human factor VIII and/or recombinant factor VIII porcine sequence inhibitors have also been reported in patients treated with OBIZUR. These anamnestic rises also may result in a lack of efficacy.

Consider evaluating for presence of anti-recombinant porcine factor VIII (anti-rpFVIII) antibodies prior to initiation of treatment with OBIZUR. In instances where positive anti-rpFVIII antibody results are detected after treatment with OBIZUR is initiated, factor VIII levels may be used to decide whether treatment with OBIZUR should be continued.

Monitor patients for the development of antibodies to OBIZUR by appropriate assays. If the plasma factor VIII level fails to increase as expected, or if bleeding is not controlled after OBIZUR administration, suspect the presence of an anti-porcine factor VIII antibody.

If such inhibitory antibodies are suspected and there is a lack of efficacy, consider management options such as discontinuing OBIZUR and initiating other therapeutics such as a factor VIII bypassing agent.

Monitoring Laboratory Tests

• Perform one-stage clotting assay to confirm that adequate factor VIII levels have been achieved and maintained - Monitor factor VIII activity 30 minutes and 3 hours after initial dose
  - Monitor factor VIII activity 30 minutes after subsequent doses
• Monitor the development of inhibitory antibodies to OBIZUR. Perform a Nijmegen Bethesda inhibitor assay with recombinant porcine factor VIII as substrate for recombinant porcine factor VIII antibodies if expected plasma factor VIII activity levels are not attained or if bleeding is not controlled with the expected dose of OBIZUR. Use Bethesda Units (BU) to report inhibitor levels. Contact Takeda at 1-877-TAKEDA-7 (1-877-825-3327) if additional information is needed regarding testing.

ADVERSE REACTIONS

Common adverse reactions observed in greater than 5% of subjects in the clinical trial were development of inhibitors to porcine factor VIII.

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Neutralizing Antibodies

Inhibitors have been reported following administration of RECOMBINATE predominantly in previously untreated and minimally treated patients. Patients treated with antihemophilic factor (AHF) products should be carefully monitored for the development of factor VIII inhibitors by appropriate clinical observations and laboratory tests. Perform an assay that measures factor VIII inhibitor concentration if the plasma factor VIII level fails to increase as expected, or if bleeding is not controlled with expected dose.

ADVERSE REACTIONS

The most common adverse reactions reported in clinical studies were chills, flushing, rash, and epistaxis.

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Inhibitors

Development of neutralizing antibodies (inhibitors) to RIXUBIS may occur. Regularly evaluate patients for the development of factor IX inhibitors by appropriate clinical observations and laboratory tests. If expected factor IX plasma activity levels are not attained, or if bleeding is not controlled with an expected dose, perform an assay that measures factor IX inhibitor concentration. Contact a specialized hemophilia treatment center if a patient develops an inhibitor.

Patients with factor IX inhibitors are at an increased risk of severe hypersensitivity reactions or anaphylaxis if re-exposed to RIXUBIS.

Nephrotic Syndrome

Nephrotic syndrome has been reported following attempted immune tolerance induction with factor IX products in hemophilia B patients that have factor IX inhibitors. The safety and efficacy of using RIXUBIS for immune tolerance induction have not been established.

Thromboembolic Complications

The use of factor IX containing products has been associated with the development of thromboembolic complications. Monitor patients for early signs of thromboembolic and consumptive coagulopathy, when administering RIXUBIS to patients with liver disease, with signs of fibrinolysis, peri- and post-operatively, or at risk for thromboembolic events or DIC. The benefit of treatment with RIXUBIS should be weighed against the risk of these complications in patients with DIC or those at risk for DIC or thromboembolic events.

ADVERSE REACTIONS

Common adverse reactions observed in >1% of subjects in clinical studies were: dysgeusia, pain in extremity, and positive test for furin antibody.

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Hypersensitivity Reactions

Hypersensitivity reactions have occurred with VONVENDI. These reactions can include anaphylactic shock, generalized urticaria, angioedema, chest tightness, hypotension, shock, lethargy, nausea, vomiting, paresthesia, pruritus, restlessness, blurred vision, wheezing and/or acute respiratory distress. Discontinue VONVENDI if hypersensitivity symptoms occur and administer appropriate emergency treatment.

Neutralizing Antibodies (Inhibitors)

Inhibitors to VWF and/or factor VIII can occur. If the expected plasma levels of VWF activity (VWF:RCo) are not attained, perform an appropriate assay to determine if anti-VWF or anti-factor VIII inhibitors are present. Consider other therapeutic options and direct the patient to a physician with experience in the care of either VWD or hemophilia A.

In patients with high levels of inhibitors to VWF or factor VIII, VONVENDI therapy may not be effective and infusion of this protein may lead to severe hypersensitivity reactions. Since inhibitor antibodies can occur concomitantly with anaphylactic reactions, evaluate patients experiencing an anaphylactic reaction for the presence of inhibitors.

ADVERSE REACTIONS

In clinical trials, the most common adverse reactions observed in ≥2% of subjects (n=100) were headache, vomiting, nausea, dizziness, arthralgia, joint injury, vertigo, ALT increased and generalized pruritus.

One subject treated with VONVENDI in perioperative setting developed deep vein thrombosis after total hip replacement surgery.

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