Adynovate 1500unit Inj, 1 Vial
It is used to treat or prevent bleeding in people with hemophilia.
Drug Class
Hemostatic Agent
Pharmacologic Class
Recombinant Coagulation Factor VIII (PEGylated)
Pregnancy Category
Not available
FDA Approved
Nov 2015
DEA Schedule
Not Controlled
Overview
What is this medicine?
Adynovate is a medicine used to treat and prevent bleeding in people with hemophilia A. Hemophilia A is a genetic bleeding disorder where the blood doesn't clot properly because of a missing or low amount of a protein called Factor VIII. Adynovate replaces this missing Factor VIII, helping your blood to clot normally and stop bleeding.
How to Use This Medicine
Proper Use of This Medication
To use this medication correctly, follow your doctor's instructions and read all the information provided. This medication is administered as an intravenous injection. If you will be self-administering the injection, your doctor or nurse will provide guidance on the proper technique. Before and after handling the medication, wash your hands thoroughly.
If the medication has been stored in the refrigerator, allow it to reach room temperature before mixing. Do not heat the medication. You can warm it to room temperature by holding the vial in your hands until it feels as warm as your body temperature.
Before use, this medication must be mixed according to the instructions provided by your doctor. Avoid shaking the vial. After mixing, do not refrigerate the medication. Use the mixed medication within 3 hours of preparation. Do not use the medication if the solution appears cloudy, is leaking, or contains particles. Additionally, do not use the medication if the solution has changed color.
After using the medication, discard any remaining contents of the opened vial. Dispose of needles and other sharp objects in a designated needle/sharp disposal box. Do not reuse needles or other items. When the disposal box is full, follow local regulations for proper disposal. If you have any questions or concerns, consult your doctor or pharmacist.
Storage and Disposal
Store unopened vials of this medication in the refrigerator, but do not freeze.
Missed Dose
If you miss a dose, contact your doctor to determine the best course of action.
To use this medication correctly, follow your doctor's instructions and read all the information provided. This medication is administered as an intravenous injection. If you will be self-administering the injection, your doctor or nurse will provide guidance on the proper technique. Before and after handling the medication, wash your hands thoroughly.
If the medication has been stored in the refrigerator, allow it to reach room temperature before mixing. Do not heat the medication. You can warm it to room temperature by holding the vial in your hands until it feels as warm as your body temperature.
Before use, this medication must be mixed according to the instructions provided by your doctor. Avoid shaking the vial. After mixing, do not refrigerate the medication. Use the mixed medication within 3 hours of preparation. Do not use the medication if the solution appears cloudy, is leaking, or contains particles. Additionally, do not use the medication if the solution has changed color.
After using the medication, discard any remaining contents of the opened vial. Dispose of needles and other sharp objects in a designated needle/sharp disposal box. Do not reuse needles or other items. When the disposal box is full, follow local regulations for proper disposal. If you have any questions or concerns, consult your doctor or pharmacist.
Storage and Disposal
Store unopened vials of this medication in the refrigerator, but do not freeze.
Missed Dose
If you miss a dose, contact your doctor to determine the best course of action.
Lifestyle & Tips
- Always carry your medication and supplies with you, especially when traveling.
- Maintain a medical alert identification (e.g., bracelet or necklace) indicating you have hemophilia A.
- Avoid activities that carry a high risk of injury or bleeding.
- Avoid medications that interfere with clotting, such as aspirin and NSAIDs (e.g., ibuprofen, naproxen), unless specifically approved by your doctor.
- Practice good dental hygiene to prevent gum bleeding.
- Follow your prescribed dosing schedule carefully, whether for prophylaxis or on-demand treatment.
Available Forms & Alternatives
Dosing & Administration
Adult Dosing
Standard Dose:
Prophylaxis: 40-50 IU/kg twice weekly. On-demand treatment: Dose varies based on severity of hemorrhage and target FVIII activity level (e.g., 10-20 IU/kg for minor, 30-40 IU/kg for moderate, 50 IU/kg for severe).
Dose Range:
10 - 50 mg
Condition-Specific Dosing:
prophylaxis:
40-50 IU/kg twice weekly
minor_hemorrhage:
10-20 IU/kg (target FVIII activity 20-40%)
moderate_hemorrhage:
30-40 IU/kg (target FVIII activity 60-80%)
severe_hemorrhage_or_surgery:
50 IU/kg (target FVIII activity 80-100%)
Pediatric Dosing
Neonatal:
Not established (limited data in neonates, generally not indicated for routine use)
Infant:
Prophylaxis: 40-50 IU/kg twice weekly. On-demand: Same as adult, based on bleed severity.
Child:
Prophylaxis: 40-50 IU/kg twice weekly. On-demand: Same as adult, based on bleed severity.
Adolescent:
Prophylaxis: 40-50 IU/kg twice weekly. On-demand: Same as adult, based on bleed severity.
Dose Adjustments
Renal Impairment:
Mild:
No adjustment needed
Moderate:
No adjustment needed
Severe:
No adjustment needed
Dialysis:
No specific considerations; not renally cleared.
Hepatic Impairment:
Mild:
No adjustment needed
Moderate:
No adjustment needed
Severe:
No adjustment needed
Pharmacology
Mechanism of Action
Adynovate is a recombinant, PEGylated human coagulation Factor VIII (FVIII) that temporarily replaces the missing coagulation Factor VIII needed for effective hemostasis in patients with hemophilia A. It binds to von Willebrand factor (vWF) and acts as a cofactor for activated Factor IX (FIXa), accelerating the conversion of Factor X (FX) to activated Factor X (FXa). FXa, in turn, converts prothrombin to thrombin, which then converts fibrinogen to fibrin, forming a stable clot.
Pharmacokinetics
Absorption:
Bioavailability:
100%
Tmax:
Not applicable (IV administration, immediate effect)
FoodEffect:
Not applicable
Distribution:
Vd:
Approximately 0.1 L/kg
ProteinBinding:
Binds to von Willebrand factor (vWF)
CnssPenetration:
Limited
Elimination:
HalfLife:
Approximately 14.2 to 15.7 hours (terminal half-life, prolonged due to pegylation)
Clearance:
Approximately 3.7 to 4.3 mL/hr/kg
ExcretionRoute:
Primarily via proteolytic degradation; not renally or hepatically excreted as intact protein.
Unchanged:
Not applicable (protein degradation)
Pharmacodynamics
OnsetOfAction:
Immediate (upon intravenous administration)
PeakEffect:
Immediate (within minutes of administration)
DurationOfAction:
Prolonged due to pegylation, allowing for less frequent dosing (e.g., twice weekly for prophylaxis).
Safety & Warnings
Side Effects
Urgent Side Effects: Seek Medical Help Right Away
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek immediate medical attention:
Signs of an allergic reaction, including:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin (with or without fever)
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Chest pain
Dizziness or fainting
Other Possible Side Effects
Like all medications, this drug can cause side effects. While many people may not experience any side effects or only minor ones, it's essential to discuss any concerns with your doctor. If you experience any of the following side effects or any other unusual symptoms that bother you or persist, contact your doctor for guidance:
Headache
Upset stomach
Diarrhea
* Irritation at the injection site (if applicable)
Reporting Side Effects
This list is not exhaustive, and you may experience other side effects not mentioned here. If you have questions or concerns about side effects, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek immediate medical attention:
Signs of an allergic reaction, including:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin (with or without fever)
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Chest pain
Dizziness or fainting
Other Possible Side Effects
Like all medications, this drug can cause side effects. While many people may not experience any side effects or only minor ones, it's essential to discuss any concerns with your doctor. If you experience any of the following side effects or any other unusual symptoms that bother you or persist, contact your doctor for guidance:
Headache
Upset stomach
Diarrhea
* Irritation at the injection site (if applicable)
Reporting Side Effects
This list is not exhaustive, and you may experience other side effects not mentioned here. If you have questions or concerns about side effects, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Signs of an allergic reaction: rash, hives, itching, facial swelling, difficulty breathing, chest tightness, dizziness, feeling faint. Seek immediate medical attention.
- Signs of bleeding that is not controlled by treatment: persistent bleeding, severe pain or swelling in joints/muscles, severe headache, blood in urine or stool. Contact your doctor or hemophilia treatment center immediately.
- Signs of inhibitor development: if your usual dose of Adynovate is no longer effective in controlling bleeding, or if you experience more frequent or severe bleeds.
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
If you have an allergy to hamster or mouse protein, as this may be relevant to your treatment.
Any potential interactions with other medications or health conditions. To ensure safe treatment, disclose all of your:
+ Prescription medications
+ Over-the-counter (OTC) medications
+ Natural products
+ Vitamins
All of your health problems, as they may affect the safety and efficacy of this medication.
Remember to consult with your doctor before making any changes to your medication regimen, including starting, stopping, or adjusting the dose of any medication. Your doctor will help you determine whether it is safe to take this medication in combination with your other medications and health conditions.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
If you have an allergy to hamster or mouse protein, as this may be relevant to your treatment.
Any potential interactions with other medications or health conditions. To ensure safe treatment, disclose all of your:
+ Prescription medications
+ Over-the-counter (OTC) medications
+ Natural products
+ Vitamins
All of your health problems, as they may affect the safety and efficacy of this medication.
Remember to consult with your doctor before making any changes to your medication regimen, including starting, stopping, or adjusting the dose of any medication. Your doctor will help you determine whether it is safe to take this medication in combination with your other medications and health conditions.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication.
Regular blood tests and other laboratory assessments should be conducted as directed by your doctor to monitor your condition.
If you experience unexplained bruising, bleeding, or if bleeding does not stop after taking this medication, contact your doctor immediately. This could be an indication that your current dosage is not effective.
Before traveling, consult with your doctor to ensure you have an adequate supply of this medication for the duration of your trip.
If you are pregnant, planning to become pregnant, or are breastfeeding, notify your doctor. It is crucial to discuss the potential benefits and risks of this medication to both you and your baby to make an informed decision.
Regular blood tests and other laboratory assessments should be conducted as directed by your doctor to monitor your condition.
If you experience unexplained bruising, bleeding, or if bleeding does not stop after taking this medication, contact your doctor immediately. This could be an indication that your current dosage is not effective.
Before traveling, consult with your doctor to ensure you have an adequate supply of this medication for the duration of your trip.
If you are pregnant, planning to become pregnant, or are breastfeeding, notify your doctor. It is crucial to discuss the potential benefits and risks of this medication to both you and your baby to make an informed decision.
Overdose Information
Overdose Symptoms:
- While overdose is unlikely to cause acute toxicity, very high Factor VIII levels could theoretically increase the risk of thrombotic events (blood clots).
- Symptoms of thrombosis could include pain, swelling, or redness in a limb; chest pain; shortness of breath; sudden vision changes.
What to Do:
In case of suspected overdose, contact your doctor or emergency services immediately. Management is supportive and may involve monitoring for thrombotic complications. Call 1-800-222-1222 (Poison Control) for advice.
Drug Interactions
Monitoring
Baseline Monitoring
Factor VIII activity levels
Rationale: To confirm diagnosis of hemophilia A and establish baseline levels.
Timing: Prior to initiation of therapy
Factor VIII inhibitor (neutralizing antibody) levels
Rationale: To screen for pre-existing inhibitors, which can render treatment ineffective.
Timing: Prior to initiation of therapy
Routine Monitoring
Factor VIII activity levels
Frequency: Periodically, especially after dose adjustments or in response to bleeding episodes. For surgical procedures, monitor pre- and post-operatively to ensure adequate hemostasis.
Target: Varies based on clinical situation (e.g., 20-40% for minor bleeds, 80-100% for severe bleeds/surgery).
Action Threshold: If levels are not within target range, adjust dose or frequency. If unexpected low levels, consider inhibitor development.
Factor VIII inhibitor (neutralizing antibody) levels
Frequency: Regularly (e.g., every 3-6 months, or more frequently in previously untreated patients or those with a history of inhibitors, or if treatment efficacy decreases).
Target: Negative or low titer (<0.6 BU/mL)
Action Threshold: If inhibitor titer rises above 0.6 BU/mL, consider alternative treatments (e.g., bypassing agents) and consult a hemophilia treatment center.
Signs and symptoms of allergic reactions
Frequency: During and immediately after infusion, and with subsequent doses.
Target: Absence of symptoms
Action Threshold: If symptoms occur (e.g., rash, hives, itching, facial swelling, dyspnea, chest tightness), stop infusion immediately and provide supportive care.
Symptom Monitoring
- Signs of bleeding (e.g., joint pain/swelling, bruising, prolonged bleeding from cuts, nosebleeds, blood in urine/stools, severe headache)
- Signs of allergic reaction (e.g., rash, hives, itching, facial swelling, dyspnea, chest tightness, dizziness, faintness)
- Signs of thrombosis (rare, but possible with very high FVIII levels or predisposing factors: pain, swelling, redness in limb; chest pain, shortness of breath)
Special Patient Groups
Pregnancy
Adynovate has not been studied in pregnant women. Animal reproduction studies have not shown evidence of fetal harm. Factor VIII is a normal component of human plasma. Use during pregnancy should only be considered if clearly needed and the potential benefits outweigh the potential risks. Consult with a hematologist and obstetrician.
Trimester-Specific Risks:
First Trimester:
No specific data, but generally considered low risk for a protein replacement therapy.
Second Trimester:
No specific data, but generally considered low risk.
Third Trimester:
No specific data, but generally considered low risk. May be used to manage bleeding risk during labor and delivery.
Lactation
It is not known whether Adynovate is excreted in human milk. However, Factor VIII is a normal component of human plasma, and large proteins are generally not excreted into breast milk in significant amounts. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Adynovate and any potential adverse effects on the breastfed infant from Adynovate or from the underlying maternal condition. Generally considered compatible with breastfeeding.
Infant Risk:
Low risk
Pediatric Use
Adynovate is approved for use in pediatric patients with hemophilia A, including those under 12 years of age. Dosing is weight-based and similar to adults. Clinical studies have demonstrated efficacy and safety in this population.
Geriatric Use
Clinical studies of Adynovate did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. However, no specific dose adjustment is generally required for elderly patients based on age alone. Dosing should be individualized based on clinical response and Factor VIII levels.
Clinical Information
Clinical Pearls
- Adynovate is a PEGylated Factor VIII, which provides a longer half-life compared to non-PEGylated recombinant Factor VIII products, allowing for less frequent dosing (e.g., twice weekly for prophylaxis).
- Proper reconstitution technique is crucial to ensure product integrity and patient safety. Always use the provided diluent and administration set.
- Patients should be educated on the signs and symptoms of allergic reactions and inhibitor development, and instructed to seek immediate medical attention if these occur.
- Regular monitoring of Factor VIII activity levels is important, especially during surgical procedures or if there is a change in bleeding patterns, to ensure adequate hemostasis.
- Inhibitor development is a serious complication of Factor VIII replacement therapy. Patients should be regularly screened for inhibitors, particularly in the first years of treatment or if treatment efficacy declines.
Alternative Therapies
- Other recombinant Factor VIII products (e.g., Advate, Eloctate, Jivi, Nuwiq, Recombinate, Xyntha)
- Plasma-derived Factor VIII products (e.g., Humate-P, Alphanate)
- Bypassing agents for patients with inhibitors (e.g., FEIBA, NovoSeven RT)
- Non-factor therapies (e.g., Emicizumab [Hemlibra] for prophylaxis in patients with or without inhibitors)
Cost & Coverage
Average Cost:
Highly variable, typically several thousand to tens of thousands of dollars per vial depending on strength and quantity purchased. per 1500 IU vial
Insurance Coverage:
Specialty Tier (requires prior authorization, often covered by major medical and pharmacy benefit plans for hemophilia A)
General Drug Facts
If your symptoms or health issues persist or worsen, it's essential to contact your doctor for further guidance. To ensure your safety, never share your medication with others or take someone else's medication. Some medications may come with an additional patient information leaflet, so be sure to check with your pharmacist for more information. If you have any questions or concerns about your medication, don't hesitate to reach out to your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek medical attention. When seeking help, be prepared to provide details about the medication taken, the amount, and the time it happened.