Indications and Limitation of Use: ADYNOVATE^® [Antihemophilic factor (Recombinant), PEGylated] is a human antihemophilic factor indicated for use in children and adults with hemophilia A for the control and prevention of bleeding episodes. ADYNOVATE is not indicated for the treatment of von Willebrand disease.¹

An established and consistent safety profile across clinical studies¹

study design

Pooled safety data evaluation
The safety of ADYNOVATE was evaluated in patients (children and adults) (N=365) with severe hemophilia A who received at least 1 dose of ADYNOVATE in 6 completed multicenter, prospective, open-label clinical studies and 1 ongoing clinical study.

Additional immunogenicity evaluations
Immunogenicity also evaluated the development of binding IgG and IgM antibodies against factor VIII, PEGylated (PEG)-factor VIII, and PEG and Chinese hamster ovary (CHO) protein.¹

Persistent treatment-emergent binding antibodies against FVIII, PEG-FVIII, or PEG were not detected.
Out of 365 patients, 36 patients in total showed pre-existing antibodies to factor VIII (n=5), PEG-factor VIII (n=31), and/or PEG (n=6) prior to the first exposure to ADYNOVATE
24 patients who tested negative at screening developed transient antibodies against factor VIII (n=10) or PEG-FVIII (n=16) and/or PEG (n=3) at 1 or 2 consecutive study visits¹
Antibodies were transient and not detectable at subsequent visits¹

SELECTED IMPORTANT RISK INFORMATION

WARNINGS & PRECAUTIONS

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.
See Detailed Important Risk Information below.

study results

Data from 7 clinical trials has shown¹

zero Inhibitors Seen in Previously Treated Patients at Completion of 6 Clinical Studies^†1,2

1 PTP developed a transient low-titer FVIII inhibitor at 0.6 BU while receiving more frequent dosing on ADYNOVATE in a randomized controlled trial comparing different dosing regimens^‡
1 PTP from an extension study developed a transient low titer (0.6 BU) FVIII inhibitor^‡
Persistent treatment emergent binding antibodies against FVIII and PEG-FVIII were not detected^‡

From an ongoing study in previously untreated patients < 6 years old with severe hemophilia A, 9 cases of FVIII inhibitor development associated with treatment with ADYNOVATE were reported.¹

^†Inhibitors defined as ≥0.6 BU using the Nijmegen modification of the Bethesda assay

^‡Repeat testing did not confirm the presence of inhibitor. Both of these patients continued treatment without change in the dose of ADYNOVATE

EDs=exposure days; IgG=immunoglobulin G; IgM=immunoglobulin M;

BU=Bethesda Unit; PTP=previously treated patient

SELECTED IMPORTANT RISK INFORMATION

WARNINGS & PRECAUTIONS

ADYNOVATE [Antihemophilic Factor (Recombinant), PEGylated] Important Information

Indications and Limitation of Use

ADYNOVATE is a human antihemophilic factor indicated in children and adults with hemophilia A (congenital factor VIII deficiency) for:

On-demand treatment and control of bleeding episodes
Perioperative management
Routine prophylaxis to reduce the frequency of bleeding episodes

ADYNOVATE is not indicated for the treatment of von Willebrand disease.

DETAILED IMPORTANT RISK INFORMATION

CONTRAINDICATIONS

Prior anaphylactic reaction to ADYNOVATE, to the parent molecule (ADVATE [Antihemophilic Factor (Recombinant)]), mouse or hamster protein, or excipients of ADYNOVATE (e.g. Tris, mannitol, trehalose, glutathione, and/or polysorbate 80).

WARNINGS & PRECAUTIONS

Hypersensitivity Reactions: Hypersensitivity reactions are possible with ADYNOVATE. Allergic-type hypersensitivity reactions, including anaphylaxis, have been reported with other recombinant antihemophilic factor VIII products, including the parent molecule, ADVATE. Early signs of hypersensitivity reactions that can progress to anaphylaxis may include angioedema, chest tightness, dyspnea, wheezing, urticaria, and pruritus. Immediately discontinue administration and initiate appropriate treatment if hypersensitivity reactions occur.

ADVERSE REACTIONS

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

Click here for ADYNOVATE Prescribing Information.
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ADVATE [Antihemophilic Factor (Recombinant)] Important Information

Indications

ADVATE is a recombinant antihemophilic factor indicated for use in children and adults with hemophilia A (congenital factor VIII deficiency) for:

Control and prevention of bleeding episodes
Perioperative management
Routine prophylaxis to prevent or reduce the frequency of bleeding episodes

ADVATE is not indicated for the treatment of von Willebrand disease.

DETAILED IMPORTANT RISK INFORMATION

CONTRAINDICATIONS

Patients who have life-threatening hypersensitivity reactions, including anaphylaxis, to mouse or hamster protein or other constituents of the product.

WARNINGS & 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.

Click here for ADVATE Prescribing Information.
Click here for ADVATE Prescribing Information en Español.

myPKFiT^® for ADYNOVATE Intended Use

The myPKFiT software is intended for use by licensed healthcare professionals (HCPs) who are familiar with hemophilia care. The myPKFiT software can be used to generate ADYNOVATE dosage amount and frequency recommendations for routine prophylaxis for an individual patient 12 years of age and older and body weight of 29 kg or greater, using that patient’s age and body weight information and local laboratory FVIII one-stage clotting activity measurements of sparse samples collected from that patient.
A minimum of two sparse sampling points are required at the recommended 3 hours (± 30 minutes) and at 48 hours (±2 hours) and/or 72 hours (±2 hours).
HCPs will also be able to evaluate various prophylaxis dose regimens tailored to an individual patient’s needs and treatment plan.
The software output may be used to guide decisions on appropriate ADYNOVATE dose and infusion intervals to maintain FVIII activity levels at or above a user-specified minimum FVIII activity level between 1% to 3% above natural baseline for an individual patient in accordance with the FDA-approved dosing recommendations provided in the ADYNOVATE Prescribing Information (PI).
myPKFiT should only be used to evaluate prophylactic dosing regimens for hemophilia A patients treated with ADYNOVATE, as per the ADYNOVATE Prescribing Information (PI).
myPKFiT for ADYNOVATE is not indicated for the treatment of von Willebrand disease. MyPKFiT for ADYNOVATE should not be used for patients who have developed neutralizing antibody (inhibitor) to FVIII products.

myPKFiT for ADYNOVATE is Rx only. For safe and proper use of the myPKFiT software, please refer to the complete instructions for use in the User Manual.

An established and consistent safety profile across clinical studies1

SELECTED IMPORTANT RISK INFORMATION

WARNINGS & PRECAUTIONS

Data from 7 clinical trials has shown1

SELECTED IMPORTANT RISK INFORMATION

WARNINGS & PRECAUTIONS

Hypersensitivity reactions

Adverse reactions

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An established and consistent safety profile across clinical studies¹

Data from 7 clinical trials has shown¹

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professional?