Adynovate 750unit Inj, 1 Vial
It is used to treat or prevent bleeding in people with hemophilia.
Drug Class
Antihemophilic agent
Pharmacologic Class
Coagulation factor, recombinant, pegylated
Pregnancy 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. It works by replacing a missing protein in the blood called Factor VIII, which is essential for blood clotting. This specific type of Factor VIII is 'pegylated,' meaning it has been modified to stay in your body longer, allowing for less frequent injections compared to some other Factor VIII products.
How to Use This Medicine
Taking Your Medication Correctly
To ensure you get the most out of your treatment, it's essential to use this medication exactly as your doctor has prescribed. Carefully read all the information provided to you and follow the instructions closely.
This medication is administered as an intravenous injection. If you'll be self-administering the injection, your doctor or nurse will provide personalized guidance on the proper technique. Remember to wash your hands thoroughly before and after handling the medication.
Before mixing the medication, if it has been stored in the refrigerator, allow it to reach room temperature. You can do this by holding the vial in your hands until it feels as warm as your body temperature. Do not attempt to heat the medication. Once you're ready to mix it, follow the instructions provided by your doctor. It's crucial not to shake the vial after mixing.
After the medication has been mixed, it should not be refrigerated. Use the mixed solution within 3 hours of preparation. Before administering, inspect 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 it.
After using the medication, dispose of any unused portion from the opened vial. It's also important to properly dispose of needles and other sharp objects in a designated needle/sharp disposal box. Never reuse needles or any other items. Once the disposal box is full, follow local regulations for its safe disposal. If you have any questions or concerns, consult with your doctor or pharmacist.
Storing and Disposing of Your Medication
Store unopened vials of this medication in the refrigerator, but do not freeze them.
What to Do If You Miss a Dose
If you miss a dose, contact your doctor immediately to determine the best course of action.
To ensure you get the most out of your treatment, it's essential to use this medication exactly as your doctor has prescribed. Carefully read all the information provided to you and follow the instructions closely.
This medication is administered as an intravenous injection. If you'll be self-administering the injection, your doctor or nurse will provide personalized guidance on the proper technique. Remember to wash your hands thoroughly before and after handling the medication.
Before mixing the medication, if it has been stored in the refrigerator, allow it to reach room temperature. You can do this by holding the vial in your hands until it feels as warm as your body temperature. Do not attempt to heat the medication. Once you're ready to mix it, follow the instructions provided by your doctor. It's crucial not to shake the vial after mixing.
After the medication has been mixed, it should not be refrigerated. Use the mixed solution within 3 hours of preparation. Before administering, inspect 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 it.
After using the medication, dispose of any unused portion from the opened vial. It's also important to properly dispose of needles and other sharp objects in a designated needle/sharp disposal box. Never reuse needles or any other items. Once the disposal box is full, follow local regulations for its safe disposal. If you have any questions or concerns, consult with your doctor or pharmacist.
Storing and Disposing of Your Medication
Store unopened vials of this medication in the refrigerator, but do not freeze them.
What to Do If You Miss a Dose
If you miss a dose, contact your doctor immediately to determine the best course of action.
Lifestyle & Tips
- Maintain a regular treatment schedule as prescribed by your doctor (e.g., twice-weekly prophylaxis).
- Always carry your medication and supplies, especially when traveling.
- Wear medical alert identification (e.g., bracelet or necklace) indicating you have hemophilia A.
- Avoid activities that carry a high risk of injury or bleeding.
- Practice good dental hygiene to prevent gum bleeding.
- Report any new or worsening bleeding episodes, or signs of allergic reactions, to your healthcare provider immediately.
Available Forms & Alternatives
Dosing & Administration
Adult Dosing
Standard Dose:
Highly individualized based on Factor VIII levels, patient weight, and clinical response. Prophylaxis: 40-50 IU/kg twice weekly. On-demand treatment: 20-50 IU/kg for minor/moderate bleeds, 40-60 IU/kg for major bleeds, 50-60 IU/kg for surgery.
Condition-Specific Dosing:
prophylaxis:
40-50 IU/kg twice weekly
onDemandMinorBleed:
20-50 IU/kg
onDemandModerateBleed:
30-60 IU/kg
onDemandMajorBleed:
40-60 IU/kg
surgery:
50-60 IU/kg pre-op, then as needed to maintain FVIII levels
Pediatric Dosing
Neonatal:
Dosing individualized based on weight and Factor VIII levels, similar principles to older children/adults. Safety and efficacy established.
Infant:
Dosing individualized based on weight and Factor VIII levels, similar principles to older children/adults. Safety and efficacy established.
Child:
Prophylaxis: 40-50 IU/kg twice weekly. On-demand treatment: individualized based on bleed severity and FVIII levels.
Adolescent:
Prophylaxis: 40-50 IU/kg twice weekly. On-demand treatment: individualized based on bleed severity and FVIII levels.
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 considerations; not primarily renally cleared
Hepatic Impairment:
Mild:
No specific dose adjustment recommended
Moderate:
No specific dose adjustment recommended
Severe:
No specific dose adjustment recommended
Pharmacology
Mechanism of Action
Adynovate is a recombinant Factor VIII (rFVIII) covalently conjugated with one or more molecules of polyethylene glycol (PEG). It temporarily replaces the missing coagulation factor VIII that is needed for effective hemostasis. 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. The pegylation extends its half-life by reducing its clearance.
Pharmacokinetics
Absorption:
Bioavailability:
100%
Tmax:
Not applicable (peak immediately after IV infusion)
FoodEffect:
Not applicable
Distribution:
Vd:
Approximately plasma volume (e.g., 0.05-0.07 L/kg)
ProteinBinding:
Binds to von Willebrand factor (vWF)
CnssPenetration:
Limited
Elimination:
HalfLife:
Approximately 14.5 hours (terminal half-life, extended due to pegylation)
Clearance:
Approximately 3.7 dL/hr/kg
ExcretionRoute:
Catabolic degradation (no specific excretion route)
Unchanged:
Not applicable (protein degradation)
Pharmacodynamics
OnsetOfAction:
Immediate (upon infusion)
PeakEffect:
Immediately after infusion
DurationOfAction:
Extended due to pegylation, allowing for less frequent dosing (e.g., twice weekly prophylaxis)
Safety & Warnings
Side Effects
Serious Side Effects: Seek Medical Help 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 attention 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
+ 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 do not go away, contact your doctor or seek medical help:
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. If you have questions or concerns about side effects, contact 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 attention 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
+ 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 do not go away, contact your doctor or seek medical help:
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. If you have questions or concerns about side effects, contact 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:
- Unusual or prolonged bleeding from cuts or injuries
- Frequent nosebleeds or gum bleeding
- Joint pain, swelling, or warmth (signs of a joint bleed)
- Deep, spreading bruises
- Blood in urine or stool
- Severe headache or changes in vision (may indicate a head bleed)
- Signs of allergic reaction: hives, rash, itching, wheezing, difficulty breathing, dizziness, chest tightness, swelling of the face, lips, or tongue
- Signs that the medicine is not working as well (e.g., more frequent bleeds, bleeds that don't stop with treatment, needing higher doses)
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.
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
Any existing health problems, as these 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 and pharmacist will work together to verify that it is safe for you to take this medication in conjunction 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.
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
Any existing health problems, as these 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 and pharmacist will work together to verify that it is safe for you to take this medication in conjunction 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. 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. 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. 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. 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 products, as it is a protein. Extremely high levels are theoretically possible but unlikely to cause acute toxicity in hemophilia patients.
What to Do:
In case of suspected overdose, seek immediate medical attention. Management is supportive. Call 1-800-222-1222 (Poison Control Center) for advice.
Drug Interactions
Monitoring
Baseline Monitoring
Factor VIII activity levels
Rationale: To establish baseline and guide initial dosing.
Timing: Prior to initiation of therapy
Inhibitor screen (Bethesda assay)
Rationale: To detect pre-existing Factor VIII inhibitors.
Timing: Prior to initiation of therapy
Baseline bleeding history
Rationale: To assess severity of hemophilia A and guide treatment strategy.
Timing: Prior to initiation of therapy
Routine Monitoring
Factor VIII activity levels
Frequency: Periodically, especially for dose adjustments, before surgery, or if clinical response is inadequate.
Target: Varies by indication (e.g., >1% for prophylaxis, higher for bleeds/surgery)
Action Threshold: Levels below target range or inadequate clinical response may require dose adjustment.
Inhibitor screen (Bethesda assay)
Frequency: Regularly (e.g., every 6-12 months), or if there is decreased clinical response to treatment.
Target: <0.6 Bethesda Units (BU)/mL
Action Threshold: Detection of inhibitors (≥0.6 BU/mL) requires specialized management.
Clinical response to treatment
Frequency: Continuously
Target: Resolution of bleeding episodes, absence of new bleeds (prophylaxis)
Action Threshold: Persistent or recurrent bleeding despite adequate dosing may indicate inhibitor development or other issues.
Symptom Monitoring
- Signs of bleeding (e.g., joint pain/swelling, unusual bruising, prolonged bleeding from cuts, nosebleeds, blood in urine/stool)
- Signs of allergic/hypersensitivity reaction (e.g., hives, rash, itching, wheezing, difficulty breathing, dizziness, chest tightness, swelling of face/lips/tongue)
- Signs of inhibitor development (e.g., increased frequency or severity of bleeding, decreased response to treatment, requiring higher doses to control bleeding)
Special Patient Groups
Pregnancy
Pregnancy Category C. Use only if clearly needed and the potential benefit justifies the potential risk to the fetus. There are no adequate and well-controlled studies in pregnant women. Animal reproduction studies have not shown adverse effects, but human data is insufficient. Factor VIII levels naturally increase during pregnancy, which may influence dosing.
Trimester-Specific Risks:
First Trimester:
Limited data, theoretical risk of adverse effects on organogenesis, but no direct evidence.
Second Trimester:
Limited data, no specific risks identified.
Third Trimester:
Limited data, no specific risks identified. Factor VIII levels typically rise in the third trimester.
Lactation
It is unknown 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. Use with caution.
Infant Risk:
Not available
Pediatric Use
Adynovate is safe and effective for use in pediatric patients with hemophilia A, including neonates, infants, children, and adolescents. Dosing is individualized based on weight, Factor VIII levels, and clinical response, similar to adult dosing principles.
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. No specific dose adjustments are recommended for geriatric patients; dosing should be individualized based on Factor VIII levels and clinical response.
Clinical Information
Clinical Pearls
- Adynovate's pegylation extends its half-life, allowing for less frequent prophylactic dosing (typically twice weekly) compared to non-pegylated recombinant Factor VIII products.
- Dosing is highly individualized; regular monitoring of Factor VIII activity levels is crucial to ensure adequate therapeutic levels, especially for prophylaxis or before surgical procedures.
- Patients should be closely monitored for the development of Factor VIII inhibitors, particularly in the first 50 exposure days or if there is a sudden decrease in treatment efficacy. Inhibitor development is the most serious complication of Factor VIII replacement therapy.
- Patients and caregivers should be thoroughly trained on proper reconstitution and intravenous administration techniques.
- Always store Adynovate according to package insert instructions (refrigerated, but can be stored at room temperature for a limited period).
Alternative Therapies
- Emicizumab (Hemlibra) - a bispecific antibody that mimics Factor VIIIa, used for prophylaxis in patients with or without inhibitors.
- Bypassing agents (e.g., FEIBA, NovoSeven RT) - used for bleeding episodes in patients with Factor VIII inhibitors.
- Gene therapy (e.g., Roctavian) - for long-term Factor VIII expression in eligible patients.
Cost & Coverage
Average Cost:
Highly variable, typically several thousand to tens of thousands of USD per vial depending on unit strength and quantity. per vial
Insurance Coverage:
Specialty drug, typically Tier 4 or 5. Requires prior authorization and is often covered under medical benefit.
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 emergency medical attention. When seeking help, be prepared to provide details about the medication taken, including the amount and time of ingestion.