(antihemophilic factor [Recombinant])
The most common adverse reactions (≥10%) with XYNTHA in adult and pediatric previously treated patients (PTPs) were headache, arthralgia, pyrexia, and cough.
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
XYNTHA was evaluated in five completed clinical studies (N=178), comprising four studies with adult and pediatric PTPs.
The safety and efficacy of XYNTHA was evaluated in two completed pivotal studies. In the first study (n=94), safety and efficacy were examined in PTPs with severe to moderately severe hemophilia A (factor VIII activity in plasma [FVIII:C] ≤2%) who received XYNTHA for routine prophylaxis and on-demand treatment. Ninety-four subjects received at least one dose of XYNTHA, resulting in a total of 6,775 infusions [see Clinical Studies (14)]. The second study (n=30) examined the use of XYNTHA for surgical prophylaxis in PTPs with severe to moderately severe hemophilia A (FVIII:C ≤2%) who required elective major surgery and were expected to receive XYNTHA replacement therapy for at least 6 days post-surgery. All subjects received at least one dose of XYNTHA, resulting in 1,161 infusions. One subject received XYNTHA for a pre-surgery pharmacokinetic assessment only and did not undergo surgery [see Clinical Studies (14)].
Across all studies, safety was evaluated in 72 pediatric PTPs <17 years of age (46 subjects, <6 years of age (4 subjects were 0 to <2 years of age), 4 subjects 6 to <12 years of age, and 22 adolescents, 12 to <17 years of age). A total of 13,109 infusions of XYNTHA were administered with a median dose per infusion of 28 IU/kg (min-max: 6–108 IU/kg).
Across all studies, the most common adverse reactions (≥10%) with XYNTHA in adult and pediatric PTPs were headache (24%), arthralgia (23%), pyrexia (23%), and cough (12%). Other adverse reactions reported in ≥5% of subjects were: diarrhea (8%), vomiting (8%), and asthenia (6%).
There is a potential for immunogenicity with therapeutic proteins. The development of factor VIII inhibitors with XYNTHA was evaluated in 167 adult and pediatric PTPs with at least 50 exposure days (EDs). Laboratory-based assessments for FVIII inhibitor (partial Nijmegen modification of the Bethesda inhibitor assay) were conducted in the clinical studies. The criterion for a positive FVIII result test result was ≥0.6 BU/mL. Across all studies, 4 subjects developed factor VIII inhibitors (2.4%).
The completed clinical studies for XYNTHA examined 178 subjects (30 for surgical prophylaxis) who had previously been treated with factor VIII (PTPs). In the first safety and efficacy study, factor VIII inhibitors were detected in two of 89 subjects (2.2%) who completed ≥50 EDs. In a Bayesian statistical analysis, results from this study were used to update PTP results from a prior supporting study using XYNTHA manufactured at the initial facility (with one de novo and two recurrent inhibitors observed in 110 subjects) and the experience with predecessor product (with one inhibitor observed in 113 subjects). The Bayesian analysis indicated that the population inhibitor rate for XYNTHA, an estimate of the 95% upper limit of the true inhibitor rate, was 4.17%.
None of the PTPs developed anti-CHO (Chinese hamster ovary) or anti-TN8.2 antibodies. One PTP developed anti-FVIII antibodies; but, this subject did not develop an inhibitor.
In the surgery study, one low titer persistent inhibitor and one transient false-positive inhibitor were reported. In this study, one surgical subject developed anti-CHO cell antibodies with no associated allergic reaction. One subject developed anti-FVIII antibodies; but, this subject did not develop an inhibitor.
Across all studies, immunogenicity was evaluated in 64 pediatric PTPs <17 years of age with at least 50 EDs (43 children <6 years of age, 4 subjects 6 to <12 years of age, and 17 adolescents, 12 to <17 years of age). Of these, 2 pediatric subjects developed an inhibitor.
The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody, including neutralizing antibody, positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparisons of the incidence of antibodies to XYNTHA with the incidence of antibodies to other products may be misleading.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
The following postmarketing adverse reaction has been reported for XYNTHA:
Inadequate therapeutic response
Patient Information
XYNTHA® SOLOFUSE® /ZIN-tha/
[Antihemophilic Factor (Recombinant)]
Please read this patient information carefully before using XYNTHA and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your healthcare provider about your medical problems or your treatment.
What is XYNTHA?
XYNTHA is an injectable medicine that is used to help control and reduce bleeding in people with hemophilia A. Hemophilia A is also called classic hemophilia. Your healthcare provider may give you XYNTHA when you have surgery.
XYNTHA is not used to treat von Willebrand's disease.
What should I tell my healthcare provider before using XYNTHA?
Tell your healthcare provider about all of your medical conditions, including if you:
Tell your healthcare provider about all of the medicines you take, including all prescription and non-prescription medicines, such as over-the-counter medicines, supplements, or herbal remedies.
How should I infuse XYNTHA?
Step-by-step instructions for infusing with XYNTHA SOLOFUSE are provided at the end of this leaflet.
The steps listed below are general guidelines for using XYNTHA SOLOFUSE. Always follow any specific instructions from your healthcare provider. If you are unsure of the procedures, please call your healthcare provider before using.
Call your healthcare provider right away if bleeding is not controlled after using XYNTHA.
Call your healthcare provider right away if you take more than the dose you should take.
Talk to your healthcare provider before traveling. Plan to bring enough XYNTHA SOLOFUSE for your treatment during this time.
What are the possible side effects of XYNTHA?
Call your healthcare provider or go to the emergency department right away if you have any of the following symptoms because these may be signs of a serious allergic reaction:
Common side effects of XYNTHA are
Your body can make antibodies against XYNTHA (called "inhibitors") that may stop XYNTHA from working properly. Your healthcare provider may need to take blood tests from time to time to monitor for inhibitors.
Talk to your healthcare provider about any side effect that bothers you or that does not go away. You may report side effects to FDA at 1-800-FDA-1088.
How should I store XYNTHA SOLOFUSE?
Store in the refrigerator at 36° to 46°F (2° to 8°C).
Do not freeze.
Protect from light.
XYNTHA SOLOFUSE can last at room temperature (below 77°F) for up to 3 months. If you store XYNTHA SOLOFUSE at room temperature, carefully write down the date you put XYNTHA SOLOFUSE at room temperature, so you will know when to throw it away. There is a space on the carton for you to write the date.
Throw away any unused XYNTHA SOLOFUSE after the expiration date.
Infuse within 3 hours after reconstitution or after removal of the grey rubber tip cap from the prefilled dual-chamber syringe. You can keep the reconstituted solution at room temperature before infusion for up to 3 hours. If it is not used in 3 hours, throw it away.
Do not use reconstituted XYNTHA if it is not clear to slightly opalescent and colorless.
Dispose of all materials, whether reconstituted or not, in an appropriate medical waste container.
What else should I know about XYNTHA?
Medicines are sometimes prescribed for purposes other than those listed here. Talk to your healthcare provider if you have any concerns. You can ask your healthcare provider for information about XYNTHA SOLOFUSE that was written for healthcare professionals.
Do not share XYNTHA SOLOFUSE with other people, even if they have the same symptoms that you have.
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