Adynovate 1000unit Inj, 1 Vial
It is used to treat or prevent bleeding in people with hemophilia.
Drug Class
Antihemophilic Agent
Pharmacologic Class
Coagulation Factor VIII (Recombinant, Pegylated)
Pregnancy Category
Category C
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 (a bleeding disorder where blood does not clot properly). It works by replacing a missing protein in the blood called Factor VIII, which is needed for blood clotting. This version of Factor VIII is designed to stay in the body longer, allowing for less frequent injections.
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 injection into a vein. If you will be self-administering the injection, your doctor or nurse will instruct you on the proper technique. Be sure to wash your hands before and after handling the medication.
Preparing the Medication
If the medication has been stored in the refrigerator, allow it to come to room temperature before mixing. You can do this by holding the vial in your hands until it feels as warm as your body temperature. Do not heat the medication. Once you are ready to mix the medication, follow the instructions provided by your doctor. Do not shake the vial after mixing.
Important Safety Precautions
After mixing, do not refrigerate the medication. Use the medication within 3 hours of preparation. Before administering the injection, check the solution for any signs of cloudiness, leakage, or particles. If you notice any of these issues or if the solution has changed color, do not use the medication. Dispose of any unused portion of the medication from the opened vial after use.
Disposing of Needles and Supplies
Dispose of used 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 with your doctor or pharmacist.
Storage and Disposal
Store unopened vials of this medication in the refrigerator, but do not freeze. 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 injection into a vein. If you will be self-administering the injection, your doctor or nurse will instruct you on the proper technique. Be sure to wash your hands before and after handling the medication.
Preparing the Medication
If the medication has been stored in the refrigerator, allow it to come to room temperature before mixing. You can do this by holding the vial in your hands until it feels as warm as your body temperature. Do not heat the medication. Once you are ready to mix the medication, follow the instructions provided by your doctor. Do not shake the vial after mixing.
Important Safety Precautions
After mixing, do not refrigerate the medication. Use the medication within 3 hours of preparation. Before administering the injection, check the solution for any signs of cloudiness, leakage, or particles. If you notice any of these issues or if the solution has changed color, do not use the medication. Dispose of any unused portion of the medication from the opened vial after use.
Disposing of Needles and Supplies
Dispose of used 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 with your doctor or pharmacist.
Storage and Disposal
Store unopened vials of this medication in the refrigerator, but do not freeze. If you miss a dose, contact your doctor to determine the best course of action.
Lifestyle & Tips
- Maintain a regular treatment schedule as prescribed by your doctor (prophylaxis).
- Administer the medication exactly as instructed, typically intravenously.
- Learn to recognize signs of bleeding and administer on-demand treatment promptly.
- Avoid activities that carry a high risk of injury or bleeding.
- Wear medical alert identification indicating hemophilia A.
- Maintain good dental hygiene to prevent gum bleeding.
- Discuss all medications, including over-the-counter drugs and supplements, with your healthcare provider, especially those that affect blood clotting (e.g., aspirin, NSAIDs).
Available Forms & Alternatives
Dosing & Administration
Adult Dosing
Standard Dose:
Individualized based on patient's Factor VIII level, type of bleeding, and clinical condition. For prophylaxis: 40-50 IU/kg every 3-4 days. For on-demand treatment: 10-60 IU/kg depending on severity of bleeding.
Dose Range:
10 - 60 mg
Condition-Specific Dosing:
prophylaxis:
40-50 IU/kg every 3-4 days
on_demand_minor_bleeding:
10-20 IU/kg (target FVIII 20-40%)
on_demand_moderate_bleeding:
20-40 IU/kg (target FVIII 40-80%)
on_demand_major_bleeding:
30-60 IU/kg (target FVIII 60-120%)
Pediatric Dosing
Neonatal:
Not established
Infant:
Dosing individualized based on patient's Factor VIII level, type of bleeding, and clinical condition. Similar to older children/adults, but close monitoring is crucial.
Child:
Dosing individualized based on patient's Factor VIII level, type of bleeding, and clinical condition. For prophylaxis: 40-50 IU/kg every 3-4 days. For on-demand treatment: 10-60 IU/kg depending on severity of bleeding.
Adolescent:
Dosing individualized based on patient's Factor VIII level, type of bleeding, and clinical condition. For prophylaxis: 40-50 IU/kg every 3-4 days. For on-demand treatment: 10-60 IU/kg depending on severity of bleeding.
Dose Adjustments
Renal Impairment:
Mild:
No specific dose adjustment recommended.
Moderate:
No specific dose adjustment recommended.
Severe:
No specific dose adjustment recommended.
Dialysis:
No specific dose adjustment recommended; Factor VIII is a large protein and not significantly cleared by dialysis.
Hepatic Impairment:
Mild:
No specific dose adjustment recommended.
Moderate:
No specific dose adjustment recommended.
Severe:
No specific dose adjustment recommended.
Pharmacology
Mechanism of Action
Antihemophilic Factor (Recombinant [Pegylated]) is a recombinant DNA-derived, pegylated human coagulation Factor VIII. It temporarily replaces the deficient coagulation Factor VIII that is needed for effective hemostasis in patients with hemophilia A. Factor VIII acts as a cofactor for Factor IXa in the activation of Factor X to Factor Xa, which ultimately leads to the formation of a stable fibrin clot. Pegylation extends the half-life of Factor VIII.
Pharmacokinetics
Absorption:
Bioavailability:
100% (intravenous administration)
Tmax:
Not applicable (IV administration, immediate effect)
FoodEffect:
Not applicable
Distribution:
Vd:
Approximately 40-60 mL/kg
ProteinBinding:
Binds to von Willebrand factor (vWF) in circulation, which stabilizes Factor VIII and protects it from premature degradation.
CnssPenetration:
Limited
Elimination:
HalfLife:
Approximately 14.5 hours (terminal half-life, extended due to pegylation compared to non-pegylated FVIII)
Clearance:
Approximately 2.9 mL/hr/kg
ExcretionRoute:
Metabolized and eliminated via protein degradation pathways; no specific excretion route.
Unchanged:
Not applicable (protein degradation)
Pharmacodynamics
OnsetOfAction:
Immediate (upon intravenous administration)
PeakEffect:
Within minutes of administration (peak Factor VIII activity)
DurationOfAction:
Extended due to pegylation, allowing for less frequent dosing (e.g., 3-4 days for prophylaxis).
Safety & Warnings
Side Effects
Urgent Side Effects: Seek Medical Help Right Away
If you experience any of the following symptoms, call your doctor immediately or seek emergency medical attention, as they may be signs of a severe and potentially life-threatening reaction:
- Signs of an allergic reaction, such as 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, or 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, although not everyone will experience them. Many people have either no side effects or only mild ones. If you encounter any of the following side effects, or if you have any other concerns, contact your doctor for advice:
- Headache
- Upset stomach
- Diarrhea
- Irritation at the site where the drug is administered
Reporting Side Effects
This list does not include all possible side effects. If you have questions or concerns about side effects, discuss them with your doctor. For medical advice about side effects, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
If you experience any of the following symptoms, call your doctor immediately or seek emergency medical attention, as they may be signs of a severe and potentially life-threatening reaction:
- Signs of an allergic reaction, such as 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, or 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, although not everyone will experience them. Many people have either no side effects or only mild ones. If you encounter any of the following side effects, or if you have any other concerns, contact your doctor for advice:
- Headache
- Upset stomach
- Diarrhea
- Irritation at the site where the drug is administered
Reporting Side Effects
This list does not include all possible side effects. If you have questions or concerns about side effects, discuss them with your doctor. For medical advice about side effects, contact 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 allergic reaction: rash, hives, itching, facial swelling, shortness of breath, wheezing, dizziness, fainting.
- Signs of inhibitor development: increased frequency or severity of bleeding, bleeding that does not stop with usual doses of Adynovate.
- Signs of serious bleeding: severe pain or swelling in joints/muscles, severe headache, vision changes, slurred speech, weakness, blood in urine or stool, prolonged bleeding from minor cuts.
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, your doctor and pharmacist need to know about all the medications you are taking, including:
+ Prescription medications
+ Over-the-counter (OTC) medications
+ Natural products
+ Vitamins
Any health problems you have, as these may affect the safety and efficacy of this medication.
Remember to check with your doctor before starting, stopping, or changing the dose of any medication to ensure your safety.
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, your doctor and pharmacist need to know about all the medications you are taking, including:
+ Prescription medications
+ Over-the-counter (OTC) medications
+ Natural products
+ Vitamins
Any health problems you have, as these may affect the safety and efficacy of this medication.
Remember to check with your doctor before starting, stopping, or changing the dose of any medication to ensure your safety.
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 evaluations 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. These symptoms may indicate 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. You and your doctor will need to discuss the potential benefits and risks of this medication to both you and your baby.
Regular blood tests and other laboratory evaluations 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. These symptoms may indicate 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. You and your doctor will need to discuss the potential benefits and risks of this medication to both you and your baby.
Overdose Information
Overdose Symptoms:
- No specific symptoms of overdose have been reported with Factor VIII products. High levels of Factor VIII may theoretically increase the risk of thrombosis, but this is rare in hemophilia A patients.
What to Do:
In case of suspected overdose, contact your healthcare provider or emergency services immediately. Management is generally supportive. Call 1-800-222-1222 (Poison Control).
Drug Interactions
Monitoring
Baseline Monitoring
Diagnosis of Hemophilia A
Rationale: Confirm Factor VIII deficiency.
Timing: Prior to initiation of therapy
Baseline Factor VIII activity level
Rationale: To guide initial dosing and assess response.
Timing: Prior to initiation of therapy
Inhibitor (neutralizing antibody) screen
Rationale: To detect pre-existing inhibitors, which can render treatment ineffective.
Timing: Prior to initiation of therapy
Routine Monitoring
Factor VIII activity levels
Frequency: Periodically, especially after initial dosing, during acute bleeding episodes, or if clinical response is suboptimal.
Target: Depends on clinical situation (e.g., 1-5% for prophylaxis trough, 20-40% for minor bleeding, 60-120% for major bleeding).
Action Threshold: Suboptimal Factor VIII levels or inadequate clinical response may require dose adjustment or investigation for inhibitors.
Inhibitor (neutralizing antibody) testing (Bethesda assay)
Frequency: Regularly (e.g., every 3-6 months for the first few years, then annually, or if bleeding episodes are not controlled with expected doses).
Target: Negative (<0.6 Bethesda Units/mL)
Action Threshold: Positive inhibitor titer requires specialized management by a hematologist.
Clinical response to treatment
Frequency: Continuously during therapy.
Target: Cessation of bleeding, prevention of bleeding episodes.
Action Threshold: Persistent or recurrent bleeding despite adequate dosing may indicate inhibitor development or other complications.
Symptom Monitoring
- Signs of bleeding (e.g., joint pain/swelling, muscle pain, bruising, prolonged bleeding from cuts, nosebleeds, blood in urine/stool)
- Signs of allergic reaction (e.g., rash, hives, itching, facial swelling, shortness of breath, wheezing, dizziness, fainting)
- Signs of inhibitor development (e.g., increased frequency or severity of bleeding, lack of response to usual doses of Adynovate)
Special Patient Groups
Pregnancy
Use only if clearly needed. Animal reproduction studies have not been conducted with Adynovate. It is not known whether Adynovate can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Factor VIII is a normal component of human plasma. The potential benefit should justify the potential risk to the fetus.
Trimester-Specific Risks:
First Trimester:
Risk unknown, consider benefit vs. risk.
Second Trimester:
Risk unknown, consider benefit vs. risk.
Third Trimester:
Risk unknown, consider benefit vs. risk.
Lactation
It is not known whether Adynovate is excreted in human milk. Factor VIII is a large protein and unlikely to be absorbed intact by the infant. 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 of adverse effects to the breastfed infant.
Pediatric Use
Adynovate is approved for use in pediatric patients, including neonates, for prophylaxis and on-demand treatment of bleeding. Dosing is individualized based on weight and Factor VIII levels. Close monitoring for inhibitor development is crucial, especially in previously untreated patients (PUPs).
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. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
Clinical Information
Clinical Pearls
- Adynovate is a pegylated Factor VIII product, offering an extended half-life compared to conventional Factor VIII, allowing for less frequent prophylactic dosing (e.g., every 3-4 days).
- Individualized pharmacokinetic (PK) assessment can help optimize dosing regimens for prophylaxis.
- Patients should be educated on proper aseptic technique for reconstitution and administration to prevent infections.
- Prompt treatment of bleeding episodes is crucial to prevent long-term joint damage.
- Regular monitoring for Factor VIII inhibitors is essential, as their development can render treatment ineffective and requires alternative management strategies.
Alternative Therapies
- Other recombinant Factor VIII products (e.g., Advate, Eloctate, Jivi, Nuwiq, Xyntha)
- Plasma-derived Factor VIII products
- Emicizumab (Hemlibra) - a bispecific antibody mimicking FVIIIa, for prophylaxis in Hemophilia A with or without inhibitors
- Gene therapy for Hemophilia A (e.g., Roctavian)
- Bypassing agents (e.g., FEIBA, NovoSeven RT) for patients with inhibitors
Cost & Coverage
Average Cost:
Extremely high (e.g., thousands to tens of thousands of USD per vial depending on unit strength) per vial
Insurance Coverage:
Specialty Tier (requires prior authorization, often covered by major medical plans for approved indications)
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 details. 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 emergency medical attention. When seeking help, be prepared to provide information about the medication taken, the amount, and the time it happened.