Adynovate 500unit Inj, 1 Vial
It is used to treat or prevent bleeding in people with hemophilia.
Drug Class
Antihemophilic Agent
Pharmacologic Class
Coagulation Factor VIII
Pregnancy Category
Not assigned (older categories)
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 the blood does not clot properly). It works by replacing a missing protein in the blood called Factor VIII, which is essential for blood clotting. This version of Factor VIII is made in a lab and has a special attachment (PEGylation) that helps it stay in the body longer, so it doesn't need to be given as often.
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. 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 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 balance in 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 injection into a vein. If you will be self-administering the injection, your doctor or nurse will instruct you 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 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 balance in 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
- Maintain a regular treatment schedule as prescribed by your doctor, especially for prophylaxis.
- Always carry your medication and supplies, especially when traveling.
- Avoid activities that carry a high risk of injury or bleeding.
- Inform all healthcare providers (dentists, surgeons, etc.) that you have hemophilia and are on Factor VIII replacement therapy.
- Wear medical alert identification (e.g., bracelet or necklace).
Available Forms & Alternatives
Dosing & Administration
Adult Dosing
Standard Dose:
Prophylaxis: 40 IU/kg intravenously twice weekly. On-demand: Dose varies based on severity of hemorrhage and target FVIII activity level.
Dose Range:
10 - 50 mg
Condition-Specific Dosing:
prophylaxis:
40 IU/kg IV twice weekly
onDemandMinorBleed:
10-20 IU/kg IV to achieve 20-40% FVIII activity
onDemandModerateBleed:
20-40 IU/kg IV to achieve 40-80% FVIII activity
onDemandMajorBleed:
30-50 IU/kg IV to achieve 60-100% FVIII activity
surgicalMinor:
Pre-operative dose to achieve 60-80% FVIII activity
surgicalMajor:
Pre-operative dose to achieve 80-100% FVIII activity
Pediatric Dosing
Neonatal:
Not established (limited data, use with caution and individualized dosing)
Infant:
Not established (limited data, use with caution and individualized dosing)
Child:
Prophylaxis (0 to <12 years): 50 IU/kg intravenously twice weekly. On-demand: Dosing similar to adults, adjusted for weight and target FVIII activity.
Adolescent:
Prophylaxis (>=12 years): 40 IU/kg intravenously twice weekly. On-demand: Dosing similar to adults, adjusted for weight and target FVIII activity.
Dose Adjustments
Renal Impairment:
Mild:
No specific adjustment recommended
Moderate:
No specific adjustment recommended
Severe:
No specific adjustment recommended
Dialysis:
No specific adjustment recommended; Factor VIII is a large protein not removed by dialysis.
Hepatic Impairment:
Mild:
No specific adjustment recommended
Moderate:
No specific adjustment recommended
Severe:
No specific adjustment recommended
Pharmacology
Mechanism of Action
Antihemophilic Factor (Recombinant [Pegylated]) is a recombinant DNA-derived, PEGylated coagulation Factor VIII. It temporarily replaces the deficient endogenous Factor VIII, which is necessary for effective hemostasis. Factor VIII acts as a cofactor for activated Factor IX (Factor IXa) in the activation of Factor X to Factor Xa, which ultimately leads to the conversion of prothrombin to thrombin and the formation of a stable fibrin clot.
Pharmacokinetics
Absorption:
Bioavailability:
100% (intravenous administration)
Tmax:
Not applicable (immediate distribution after IV bolus)
FoodEffect:
Not applicable (intravenous administration)
Distribution:
Vd:
Approximately 40-60 mL/kg (similar to plasma volume)
ProteinBinding:
Binds to von Willebrand factor (vWF) in plasma
CnssPenetration:
Limited (large protein molecule)
Elimination:
HalfLife:
Approximately 14.5 hours (adults), 11.5 hours (pediatrics)
Clearance:
Approximately 3.5-4.5 mL/hr/kg
ExcretionRoute:
Primarily through protein degradation pathways; no specific excretion route
Unchanged:
Not applicable (metabolized)
Pharmacodynamics
OnsetOfAction:
Immediate (upon intravenous administration)
PeakEffect:
Within minutes of administration (peak FVIII activity)
DurationOfAction:
Extended due to pegylation, allowing for twice-weekly dosing in prophylaxis (maintains therapeutic levels for several days)
Safety & Warnings
Side Effects
Urgent Side Effects: Seek Medical Attention Immediately
Although rare, this medication can cause severe and potentially life-threatening side effects. If you experience any of the following symptoms, contact your doctor or seek medical help right away:
- 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. While many people may not experience any side effects or only minor ones, it's essential to discuss any concerns with your doctor. Contact your doctor or seek medical help if you experience any of the following side effects or if they bother you or do not go away:
- Headache
- Upset stomach
- Diarrhea
- Irritation at the site where the drug is administered
Additional Information
This list does not include all possible side effects. If you have questions or concerns about side effects, consult your doctor for medical advice. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Although rare, this medication can cause severe and potentially life-threatening side effects. If you experience any of the following symptoms, contact your doctor or seek medical help right away:
- 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. While many people may not experience any side effects or only minor ones, it's essential to discuss any concerns with your doctor. Contact your doctor or seek medical help if you experience any of the following side effects or if they bother you or do not go away:
- Headache
- Upset stomach
- Diarrhea
- Irritation at the site where the drug is administered
Additional Information
This list does not include all possible side effects. If you have questions or concerns about side effects, consult your doctor for medical advice. 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 bleeding: new or worsening joint pain, swelling, bruising, prolonged bleeding from cuts, nosebleeds, blood in urine or stool, severe headache.
- Signs of allergic reaction: hives, rash, itching, swelling of the face/lips/tongue, difficulty breathing, wheezing, dizziness, fainting.
- Signs of inhibitor development: increased frequency or severity of bleeding, or if your usual dose of Adynovate does not stop a bleed as expected.
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 other medications you are taking, including prescription and over-the-counter (OTC) drugs, natural products, and vitamins. This is crucial because this medication may interact with other drugs or health conditions.
Any existing health problems you have, as these may affect the safety and efficacy of this medication.
To ensure your safety, it is crucial to discuss all your medications and health conditions with your doctor and pharmacist. They will help you determine whether it is safe to take this medication with your other drugs and health problems. Never start, stop, or change the dose of any medication without first consulting 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 other medications you are taking, including prescription and over-the-counter (OTC) drugs, natural products, and vitamins. This is crucial because this medication may interact with other drugs or health conditions.
Any existing health problems you have, as these may affect the safety and efficacy of this medication.
To ensure your safety, it is crucial to discuss all your medications and health conditions with your doctor and pharmacist. They will help you determine whether it is safe to take this medication with your other drugs and health problems. Never start, stop, or change the dose of any medication without first consulting your doctor.
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:
- No specific symptoms of overdose are known for Factor VIII. Very high levels of Factor VIII may theoretically increase the risk of thrombosis, but this is rare.
What to Do:
In case of suspected overdose, contact your healthcare provider or emergency services immediately. Call 911 or the Poison Control Center at 1-800-222-1222. Management is supportive.
Drug Interactions
Monitoring
Baseline Monitoring
Factor VIII activity level
Rationale: To establish baseline and guide initial dosing, especially for on-demand treatment or surgery.
Timing: Prior to initiation of therapy or before a new treatment regimen.
Inhibitor (neutralizing antibody) screen
Rationale: To detect pre-existing inhibitors to Factor VIII, which can render treatment ineffective.
Timing: Prior to initiation of therapy.
Routine Monitoring
Factor VIII activity level
Frequency: Periodically during prophylaxis, before and after surgery, and to guide dosing for on-demand treatment of bleeds.
Target: Varies based on indication (e.g., >1% for prophylaxis, 20-100% for bleeds/surgery)
Action Threshold: If levels are not within target range, adjust dose or frequency; if unexpectedly low, consider inhibitor development.
Inhibitor (neutralizing antibody) assay (Bethesda assay)
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: <0.6 Bethesda Units (BU)/mL
Action Threshold: If >0.6 BU/mL, indicates inhibitor presence; requires alternative treatment strategies.
Clinical response to treatment
Frequency: Continuously
Target: Resolution of bleeding episodes, absence of spontaneous bleeds (prophylaxis)
Action Threshold: Persistent or recurrent bleeding despite adequate dosing suggests inadequate FVIII levels or inhibitor development.
Symptom Monitoring
- Signs of bleeding (e.g., joint pain/swelling, muscle pain, bruising, prolonged bleeding from minor cuts, nosebleeds, blood in urine/stools)
- Signs of allergic reaction (e.g., rash, hives, itching, facial swelling, shortness of breath, wheezing, dizziness, fainting)
- Signs of inhibitor development (e.g., decreased effectiveness of treatment, increased frequency or severity of bleeding episodes)
Special Patient Groups
Pregnancy
There are no adequate and well-controlled studies of Adynovate in pregnant women. Use only if clearly needed and the potential benefit justifies the potential risk to the fetus. Hemophilia A is rare in women, but if a pregnant woman has hemophilia A, treatment should be managed by a specialist.
Trimester-Specific Risks:
First Trimester:
Risk unknown; no human data.
Second Trimester:
Risk unknown; no human data.
Third Trimester:
Risk unknown; no human data.
Lactation
It is not known whether Adynovate is excreted in human milk. 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. Large protein molecules are generally not expected to pass into breast milk in significant amounts.
Infant Risk:
Risk unknown; likely low due to large molecular size.
Pediatric Use
Adynovate is approved for use in pediatric patients, including those under 12 years of age. Dosing for prophylaxis in pediatric patients (<12 years) is 50 IU/kg twice weekly, which is higher than for adults/adolescents due to faster Factor VIII clearance in younger children. Close monitoring of FVIII activity and inhibitor development is crucial.
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, which provides an extended half-life compared to conventional recombinant Factor VIII products, allowing for less frequent dosing (e.g., twice weekly for prophylaxis).
- Individualize dosing based on patient's Factor VIII levels, clinical response, and pharmacokinetic parameters if available.
- Patients should be educated on proper reconstitution and administration techniques for home use.
- Regular monitoring for Factor VIII inhibitors is critical, especially in previously untreated patients (PUPs) and those with a history of inhibitors, as inhibitor development can lead to treatment failure.
- Always confirm the specific unit strength of the vial before reconstitution and administration to avoid dosing errors.
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 replacement therapies (e.g., Emicizumab [Hemlibra])
Cost & Coverage
Average Cost:
Highly variable, typically several thousand to tens of thousands USD per vial depending on unit strength and quantity. per vial
Insurance Coverage:
Specialty Tier (requires prior authorization, often covered under medical benefit for hemophilia)
General Drug Facts
If your symptoms or health issues persist or worsen, it is essential to contact your doctor promptly. To ensure safe and effective treatment, never share your medication with others or take someone else's medication. Some medications may come with an additional patient information leaflet, so it's a good idea 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 emergency medical attention. When reporting the incident, be prepared to provide details about the medication taken, the amount, and the time it occurred.