Recombinate 220-400 Inj 1 Vial
It is used to treat or prevent bleeding in people with hemophilia.
Drug Class
Antihemophilic Agent
Pharmacologic Class
Coagulation Factor; Recombinant Factor VIII
Pregnancy Category
Category C
FDA Approved
Dec 1992
DEA Schedule
Not Controlled
Overview
What is this medicine?
Recombinate 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 needed for blood clotting.
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 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. Mixing is required before use; follow the instructions provided by your doctor. Avoid shaking the medication. Do not use the solution if it appears cloudy, is leaking, or contains particles. The medication should be colorless to faint yellow; discard it if the color changes. After mixing, do not refrigerate the medication.
Use the mixed medication within 3 hours of preparation. Discard any unused portion of the opened vial after use. 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, consult your doctor or pharmacist.
Storage and Disposal
If using this medication at home, store unopened containers at room temperature or in the refrigerator. Avoid freezing the medication.
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 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. Mixing is required before use; follow the instructions provided by your doctor. Avoid shaking the medication. Do not use the solution if it appears cloudy, is leaking, or contains particles. The medication should be colorless to faint yellow; discard it if the color changes. After mixing, do not refrigerate the medication.
Use the mixed medication within 3 hours of preparation. Discard any unused portion of the opened vial after use. 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, consult your doctor or pharmacist.
Storage and Disposal
If using this medication at home, store unopened containers at room temperature or in the refrigerator. Avoid freezing the medication.
Missed Dose
If you miss a dose, contact your doctor to determine the best course of action.
Lifestyle & Tips
- Avoid activities that carry a high risk of injury or bleeding (e.g., contact sports).
- Maintain good dental hygiene to prevent gum bleeding.
- Inform all healthcare providers (including dentists) about your hemophilia and medication.
- Carry identification indicating you have hemophilia.
- Learn how to self-administer the medication if prescribed for home use.
- Keep a detailed record of all infusions (date, time, dose, reason for infusion, lot number).
Available Forms & Alternatives
Dosing & Administration
Adult Dosing
Standard Dose:
Individualized based on Factor VIII deficiency, severity of hemorrhage, and patient's weight. Generally, 1 IU/kg increases Factor VIII activity by approximately 2 IU/dL (2%).
Condition-Specific Dosing:
onDemandTreatment:
Minor hemorrhage (e.g., early hemarthrosis, epistaxis): 15-25 IU/kg to achieve 30-50% Factor VIII activity. Moderate hemorrhage (e.g., significant hemarthrosis, muscle bleed): 25-50 IU/kg to achieve 50-100% Factor VIII activity. Major hemorrhage (e.g., life-threatening bleed, CNS bleed): 50 IU/kg initially, then 25-50 IU/kg every 8-12 hours to maintain 80-100% Factor VIII activity.
surgicalProphylaxis:
Pre-operative: 50 IU/kg to achieve 80-100% Factor VIII activity. Post-operative: Maintain Factor VIII activity >30-60% for 10-14 days depending on wound healing.
routineProphylaxis:
25-50 IU/kg 2-3 times per week.
Pediatric Dosing
Neonatal:
Not established, but used in neonates with hemophilia A. Dosing is individualized based on weight and Factor VIII levels, similar to older children.
Infant:
Dosing is individualized based on weight and Factor VIII levels, similar to adults. Prophylaxis often initiated early.
Child:
Dosing is individualized based on weight and Factor VIII levels, similar to adults. Prophylaxis often initiated early.
Adolescent:
Dosing is individualized based on weight and Factor VIII levels, similar to adults.
Dose Adjustments
Renal Impairment:
Mild:
No specific adjustment needed.
Moderate:
No specific adjustment needed.
Severe:
No specific adjustment needed.
Dialysis:
No specific adjustment needed. Factor VIII is a large protein and not significantly cleared by dialysis.
Hepatic Impairment:
Mild:
No specific adjustment needed.
Moderate:
No specific adjustment needed.
Severe:
No specific adjustment needed.
Pharmacology
Mechanism of Action
Antihemophilic Factor (Recombinant) is a glycoprotein that replaces the deficient endogenous coagulation Factor VIII in patients with hemophilia A. Factor VIII acts as a cofactor for Factor IXa in the activation of Factor X to Factor Xa, which is essential for the intrinsic coagulation pathway and subsequent thrombin generation and fibrin clot formation.
Pharmacokinetics
Absorption:
Bioavailability:
100%
Tmax:
Immediately after IV infusion
FoodEffect:
Not applicable (IV administration)
Distribution:
Vd:
Approximately 40-60 mL/kg (similar to plasma volume)
ProteinBinding:
Binds to von Willebrand factor (vWF) in plasma, which stabilizes Factor VIII and prolongs its half-life.
CnssPenetration:
Limited
Elimination:
HalfLife:
Approximately 10-19 hours (mean ~14 hours), with significant inter-patient variability.
Clearance:
Approximately 2-5 mL/hr/kg
ExcretionRoute:
Metabolic degradation products are excreted.
Unchanged:
Not applicable (protein catabolism)
Pharmacodynamics
OnsetOfAction:
Immediate (upon completion of infusion)
PeakEffect:
Immediately after infusion
DurationOfAction:
Dependent on half-life and target Factor VIII levels; typically 8-24 hours for maintaining therapeutic levels, but clinical effect can last longer for minor bleeds.
Safety & Warnings
Side Effects
Serious Side Effects: Seek Medical Help Right Away
While rare, some people may experience severe and potentially life-threatening side effects when taking this medication. If you notice any of the following symptoms, contact your doctor or seek immediate medical attention:
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
Abnormal sensations, such as:
+ Burning
+ Numbness
+ Tingling
Change in mouth color to blue
Chest pain or pressure
Fast heartbeat
Dizziness or fainting
Feeling cold
Fever or chills
Flushing
Pale skin
Restlessness
Shortness of breath
Upset stomach or vomiting
Feeling extremely tired or weak
Other Possible Side Effects
Like all medications, this drug can cause side effects. However, many people do not experience any side effects or only have mild ones. If you are bothered by any of the following side effects or if they do not go away, contact your doctor:
Irritation at the injection site
Headache
This is not an exhaustive list of possible side effects. 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.
While rare, some people may experience severe and potentially life-threatening side effects when taking this medication. If you notice any of the following symptoms, contact your doctor or seek immediate medical attention:
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
Abnormal sensations, such as:
+ Burning
+ Numbness
+ Tingling
Change in mouth color to blue
Chest pain or pressure
Fast heartbeat
Dizziness or fainting
Feeling cold
Fever or chills
Flushing
Pale skin
Restlessness
Shortness of breath
Upset stomach or vomiting
Feeling extremely tired or weak
Other Possible Side Effects
Like all medications, this drug can cause side effects. However, many people do not experience any side effects or only have mild ones. If you are bothered by any of the following side effects or if they do not go away, contact your doctor:
Irritation at the injection site
Headache
This is not an exhaustive list of possible side effects. 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 bleeding: new or worsening joint pain/swelling, unusual bruising, prolonged bleeding from minor cuts, nosebleeds, blood in urine or stool, severe headache, vision changes, slurred speech (may indicate internal bleeding).
- Signs of allergic reaction: rash, hives, itching, facial swelling, difficulty breathing, wheezing, chest tightness, dizziness, feeling faint.
- Signs of inhibitor development: increased frequency or severity of bleeding episodes, or lack of response to usual doses of Recombinate.
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 symptoms you experienced as a result of the allergy.
If you have an allergy to cows, hamsters, or mice, as this may be relevant to your treatment.
Potential interactions with other medications or health conditions. To ensure safe treatment, disclose all of your current medications, including prescription and over-the-counter drugs, natural products, and vitamins, as well as any existing health problems.
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. Do not initiate, discontinue, or adjust the dosage 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 symptoms you experienced as a result of the allergy.
If you have an allergy to cows, hamsters, or mice, as this may be relevant to your treatment.
Potential interactions with other medications or health conditions. To ensure safe treatment, disclose all of your current medications, including prescription and over-the-counter drugs, natural products, and vitamins, as well as any existing health problems.
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. Do not initiate, discontinue, or adjust the dosage 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 work and laboratory tests should be conducted as directed by your doctor to monitor your condition.
If you experience unexplained bruising or 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 to last throughout 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.
If you experience unexplained bruising or 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 to last throughout 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:
- While acute overdose is unlikely to cause specific symptoms beyond potentially very high Factor VIII levels, extremely high levels could theoretically increase the risk of thrombosis (blood clots), though this is rare in hemophilia patients.
What to Do:
In case of suspected overdose or unusually high Factor VIII levels, consult a hematologist. Management would involve careful monitoring of coagulation parameters and clinical signs, and supportive care. Call 1-800-222-1222 (Poison Control).
Drug Interactions
Monitoring
Baseline Monitoring
Factor VIII activity levels
Rationale: To determine baseline deficiency and guide initial dosing.
Timing: Prior to first administration and periodically.
Inhibitor (neutralizing antibody) screen
Rationale: To detect the presence of antibodies that can neutralize Factor VIII, leading to treatment failure.
Timing: Prior to first administration, and regularly (e.g., every 3-6 months, or if clinical response is suboptimal).
Bleeding history and severity
Rationale: To assess the patient's clinical status and guide treatment strategy.
Timing: At diagnosis and ongoing.
Routine Monitoring
Factor VIII activity levels
Frequency: During treatment of acute bleeds or surgery (e.g., pre- and post-infusion, then daily or as needed); periodically for prophylaxis (e.g., trough levels).
Target: Dependent on clinical situation (e.g., 30-50% for minor bleed, 80-100% for major bleed/surgery).
Action Threshold: Adjust dose or frequency if levels are not within target range or if clinical response is inadequate.
Clinical response (cessation of bleeding)
Frequency: Continuously during treatment of bleeding episodes.
Target: Resolution of bleeding symptoms.
Action Threshold: If bleeding persists or recurs, re-evaluate Factor VIII levels, consider inhibitor testing, or adjust dose.
Inhibitor (neutralizing antibody) titers
Frequency: Every 3-6 months, or if there is a lack of expected clinical response or Factor VIII activity levels.
Target: Negative or low titer.
Action Threshold: If inhibitors develop, consider immune tolerance induction (ITI) or use bypassing agents.
Symptom Monitoring
- Signs of bleeding (e.g., joint pain/swelling, bruising, prolonged bleeding from cuts, blood in urine/stools, nosebleeds, headaches, vision changes)
- Signs of allergic reaction (e.g., rash, hives, itching, facial swelling, shortness of breath, chest tightness, dizziness, faintness)
- Signs of infusion-related reactions (e.g., chills, fever, flushing, headache, nausea, vomiting, tingling)
Special Patient Groups
Pregnancy
Recombinate is a Category C drug. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Hemophilia A is a genetic disorder, and management of bleeding during pregnancy and delivery is critical for affected women. Factor VIII replacement is often necessary.
Trimester-Specific Risks:
First Trimester:
Risk is generally considered low as Factor VIII is a naturally occurring protein, but use only if clearly needed.
Second Trimester:
Risk is generally considered low, continued use as needed for bleeding or prophylaxis.
Third Trimester:
Crucial for managing bleeding risk during labor and delivery. Factor VIII levels should be monitored closely.
Lactation
It is not known whether Recombinate is excreted in human milk. However, as Factor VIII is a large protein, its transfer into breast milk is likely minimal, and oral absorption by the infant is unlikely. The benefits of breastfeeding should be considered along with the mother's clinical need for Recombinate. Generally considered compatible with breastfeeding.
Infant Risk:
Low risk.
Pediatric Use
Recombinate is approved for use in pediatric patients with hemophilia A. Dosing is weight-based and individualized, similar to adults. Prophylaxis is often initiated early in life to prevent joint damage. Inhibitor development is more common in previously untreated patients (PUPs) and young children.
Geriatric Use
Clinical studies did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Dosing should be individualized based on Factor VIII levels and clinical response, similar to younger adults. No specific dose adjustments are generally required based solely on age.
Clinical Information
Clinical Pearls
- Recombinate is administered intravenously. Ensure proper aseptic technique during preparation and administration.
- Individualize dosing based on patient's Factor VIII levels, bleeding severity, and clinical response. Regular monitoring of Factor VIII activity is crucial, especially for major bleeds or surgery.
- Patients should be monitored for the development of Factor VIII inhibitors (neutralizing antibodies), which can lead to lack of efficacy. If inhibitors are suspected, perform a Bethesda assay.
- Infusion-related reactions (e.g., chills, fever, flushing) can occur; slow the infusion rate if these occur.
- Recombinate does not contain von Willebrand factor (vWF) in therapeutically significant quantities and is not indicated for von Willebrand disease.
- Patients should be educated on early signs of bleeding and the importance of prompt treatment.
Alternative Therapies
- Other recombinant Factor VIII products (e.g., Advate, Eloctate, Adynovate, Jivi, Nuwiq, Xyntha)
- Plasma-derived Factor VIII products (e.g., Hemofil M, Koate-DVI)
- Extended half-life Factor VIII products (e.g., Eloctate, Adynovate, Jivi)
- Bypassing agents for patients with inhibitors (e.g., activated prothrombin complex concentrate [aPCC], recombinant Factor VIIa [rFVIIa])
- Non-factor replacement therapies (e.g., Emicizumab - a bispecific antibody mimicking Factor VIIIa cofactor function)
Cost & Coverage
Average Cost:
Extremely high (e.g., thousands to tens of thousands of USD per vial depending on strength and quantity) per vial
Insurance Coverage:
Specialty Tier (requires prior authorization, often subject to high co-pays or co-insurance)
General Drug Facts
If your symptoms or health issues persist or worsen, it is 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 it's a good idea to check with your pharmacist for more information. If you have any questions or concerns about this 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 overdose, including the medication taken, the amount, and the time it occurred.