Haegarda 3000unit Inj, 1 Vial
It is used to prevent swelling attacks in people with hereditary angioedema (HAE).
Drug Class
Hereditary Angioedema (HAE) Prophylaxis
Pharmacologic Class
C1-esterase Inhibitor (Human)
Pregnancy Category
Not assigned by FDA (pre-2015 labeling system), consider risk/benefit
FDA Approved
Feb 2017
DEA Schedule
Not Controlled
Overview
What is this medicine?
Haegarda is a medicine made from human blood that helps prevent swelling attacks in people with a rare genetic condition called Hereditary Angioedema (HAE). It works by replacing a missing or faulty protein in your body that normally helps control swelling.
How to Use This Medicine
Proper Administration of This Medication
To use this medication correctly, follow your doctor's instructions and read all accompanying information carefully. This medication is administered via injection into the fatty tissue under the skin. If you will be self-administering the injection, your doctor or nurse will provide guidance on the proper technique.
Before use, this medication must be mixed according to the instructions provided by your doctor. Do not shake the medication. If it has been stored in the refrigerator, allow it to reach room temperature before mixing. Avoid heating the medication.
Inspect the solution before use; do not administer if it appears cloudy, is leaking, or contains particles. Discard any remaining medication after the dose has been administered. Only use the medication if the solution is clear and colorless. The mixed dose must be used within 8 hours.
To minimize the risk of injection site reactions, rotate the injection site with each administration. Dispose of used needles and syringes in a puncture-proof container. Do not reuse needles or other injectable devices. When the container is full, follow local regulations for disposal. If you have any questions or concerns, consult your doctor or pharmacist.
Storage and Disposal
Store this medication at room temperature or in the refrigerator, but do not freeze. Keep the medication in its original container to protect it from light. After mixing, do not refrigerate or freeze the medication.
Missed Dose
If you miss a dose, take it as soon as you remember. However, if it is close to the time for your next scheduled dose, skip the missed dose and resume your regular dosing schedule. Do not take two doses at the same time or take extra doses to make up for the missed dose.
To use this medication correctly, follow your doctor's instructions and read all accompanying information carefully. This medication is administered via injection into the fatty tissue under the skin. If you will be self-administering the injection, your doctor or nurse will provide guidance on the proper technique.
Before use, this medication must be mixed according to the instructions provided by your doctor. Do not shake the medication. If it has been stored in the refrigerator, allow it to reach room temperature before mixing. Avoid heating the medication.
Inspect the solution before use; do not administer if it appears cloudy, is leaking, or contains particles. Discard any remaining medication after the dose has been administered. Only use the medication if the solution is clear and colorless. The mixed dose must be used within 8 hours.
To minimize the risk of injection site reactions, rotate the injection site with each administration. Dispose of used needles and syringes in a puncture-proof container. Do not reuse needles or other injectable devices. When the container is full, follow local regulations for disposal. If you have any questions or concerns, consult your doctor or pharmacist.
Storage and Disposal
Store this medication at room temperature or in the refrigerator, but do not freeze. Keep the medication in its original container to protect it from light. After mixing, do not refrigerate or freeze the medication.
Missed Dose
If you miss a dose, take it as soon as you remember. However, if it is close to the time for your next scheduled dose, skip the missed dose and resume your regular dosing schedule. Do not take two doses at the same time or take extra doses to make up for the missed dose.
Lifestyle & Tips
- Administer Haegarda as prescribed, typically every 3 or 4 days, to maintain protection against HAE attacks.
- Learn to self-administer the injection correctly or ensure a caregiver is trained.
- Keep a diary of HAE attacks (frequency, severity, triggers) to monitor treatment effectiveness.
- Avoid known triggers for HAE attacks if identifiable (e.g., stress, certain medications, trauma).
- Carry an acute HAE attack medication (e.g., C1-INH concentrate for acute use, bradykinin receptor antagonist) as prescribed, even while on prophylaxis.
Available Forms & Alternatives
Available Strengths:
Dosing & Administration
Adult Dosing
Standard Dose:
6000 units (2 vials) administered subcutaneously every 3 or 4 days
Dose Range:
40 - 40 mg
Condition-Specific Dosing:
prophylaxis:
40 units/kg administered subcutaneously every 3 or 4 days. For patients weighing less than 50 kg, the recommended dose is 40 units/kg. For patients weighing 50 kg or more, the recommended dose is 6000 units.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Approved for patients 6 years of age and older: 40 units/kg administered subcutaneously every 3 or 4 days. For patients weighing less than 50 kg, the recommended dose is 40 units/kg. For patients weighing 50 kg or more, the recommended dose is 6000 units.
Adolescent:
Approved for patients 6 years of age and older: 40 units/kg administered subcutaneously every 3 or 4 days. For patients weighing less than 50 kg, the recommended dose is 40 units/kg. For patients weighing 50 kg or more, the recommended dose is 6000 units.
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; C1-INH is a large protein and not significantly removed 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
C1 Inhibitor (Human) is a plasma-derived concentrate of C1-esterase inhibitor (C1-INH), a normal constituent of human plasma. It functions as a serine protease inhibitor, primarily inhibiting the activated C1s and C1r components of the classical complement pathway, as well as kallikrein and Factor XIIa in the contact system. In hereditary angioedema (HAE), a deficiency or dysfunction of C1-INH leads to uncontrolled activation of the kallikrein-kinin system, resulting in excessive bradykinin production, which causes increased vascular permeability and angioedema attacks. Haegarda replaces the deficient or dysfunctional C1-INH, thereby restoring the regulation of the contact system and reducing bradykinin generation, preventing HAE attacks.
Pharmacokinetics
Absorption:
Bioavailability:
Not applicable (administered subcutaneously, not 100% like IV, but directly absorbed)
Tmax:
Approximately 131 hours (median) after subcutaneous administration
FoodEffect:
Not applicable (parenteral administration)
Distribution:
Vd:
Approximately 2.1 L (based on population PK analysis)
ProteinBinding:
Not applicable (it is a protein itself)
CnssPenetration:
Limited (large protein, does not readily cross intact blood-brain barrier)
Elimination:
HalfLife:
Approximately 70 hours (median) after subcutaneous administration
Clearance:
Approximately 0.02 L/hour (based on population PK analysis)
ExcretionRoute:
Proteolytic degradation products are excreted via renal and fecal routes.
Unchanged:
Not applicable (metabolized)
Pharmacodynamics
OnsetOfAction:
Not immediately for acute attacks; for prophylaxis, sustained C1-INH levels are achieved over time.
PeakEffect:
Steady-state C1-INH levels are typically achieved after approximately 12 days of twice-weekly dosing.
DurationOfAction:
Sustained C1-INH levels maintained with every 3 or 4 day dosing for prophylaxis.
Safety & Warnings
Side Effects
Urgent Side Effects: Seek Medical Help Right Away
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 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
Severe dizziness or fainting
Discoloration of the mouth, turning blue
Rapid heartbeat
Severe headache
Weakness on one side of the body
Difficulty speaking or thinking
Changes in balance
Drooping on one side of the face
Blurred vision
Signs of a blood clot, including:
+ Chest pain or pressure
+ Coughing up blood
+ Shortness of breath
+ Swelling, warmth, numbness, color change, or pain in a leg or arm
+ Difficulty speaking or swallowing
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 symptoms that bother you or do not go away, contact your doctor:
Irritation at the injection site
Nose or throat irritation
Dizziness
Reporting Side Effects
This list is not exhaustive, and you may experience other 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.
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 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
Severe dizziness or fainting
Discoloration of the mouth, turning blue
Rapid heartbeat
Severe headache
Weakness on one side of the body
Difficulty speaking or thinking
Changes in balance
Drooping on one side of the face
Blurred vision
Signs of a blood clot, including:
+ Chest pain or pressure
+ Coughing up blood
+ Shortness of breath
+ Swelling, warmth, numbness, color change, or pain in a leg or arm
+ Difficulty speaking or swallowing
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 symptoms that bother you or do not go away, contact your doctor:
Irritation at the injection site
Nose or throat irritation
Dizziness
Reporting Side Effects
This list is not exhaustive, and you may experience other 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 an allergic reaction: hives, rash, itching, flushing, swelling of the face, lips, tongue, or throat, difficulty breathing, wheezing, dizziness, fainting. Seek immediate medical attention.
- Signs of a blood clot: pain or swelling in an arm or leg, sudden chest pain, shortness of breath, numbness or weakness on one side of the body. Seek immediate medical attention.
- Any new or worsening HAE attacks despite regular use of Haegarda.
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.
Potential interactions with other medications or health conditions. This medication may affect or be affected by other drugs or health problems, so it is crucial to disclose this information.
To ensure safe treatment, provide your doctor and pharmacist with a comprehensive list of:
All prescription and over-the-counter (OTC) medications you are taking
Natural products and vitamins you are using
* Any health problems you have
Carefully review your medications and health conditions to confirm that it is safe to take this medication in conjunction with them. Never start, stop, 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.
Potential interactions with other medications or health conditions. This medication may affect or be affected by other drugs or health problems, so it is crucial to disclose this information.
To ensure safe treatment, provide your doctor and pharmacist with a comprehensive list of:
All prescription and over-the-counter (OTC) medications you are taking
Natural products and vitamins you are using
* Any health problems you have
Carefully review your medications and health conditions to confirm that it is safe to take this medication in conjunction with them. Never start, stop, 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. Your doctor will prescribe an additional medication called epinephrine, which you should carry with you at all times while taking this drug. Make sure you understand how and when to use epinephrine, and seek immediate medical attention after administering it.
There is a risk of blood clots associated with this medication. Your risk may be increased if you have a certain type of catheter or device in a vein, or if you are taking other medications such as estrogens or androgens. Additionally, your risk may be higher if you have a history of heart or blood vessel disease, stroke, thick blood, or a previous blood clot. Prolonged periods of immobility may also increase your risk. Discuss these factors with your doctor.
As this medication is derived from human plasma, a component of blood, there is a potential risk of transmitting viruses that can cause disease. Although the medication is thoroughly screened, tested, and treated to minimize this risk, it is crucial to discuss this with your doctor.
It is important to note that this medication is used to prevent certain health problems, but it will not treat acute HAE attacks. If you have questions about managing HAE attacks, consult your doctor.
Before traveling, consult your doctor to ensure you have an adequate supply of this medication. If you experience any changes in weight, inform your doctor, as your dosage may need to be adjusted.
If you are pregnant, planning to become pregnant, or breastfeeding, inform your doctor. It is essential to discuss the potential benefits and risks of this medication to both you and your baby.
There is a risk of blood clots associated with this medication. Your risk may be increased if you have a certain type of catheter or device in a vein, or if you are taking other medications such as estrogens or androgens. Additionally, your risk may be higher if you have a history of heart or blood vessel disease, stroke, thick blood, or a previous blood clot. Prolonged periods of immobility may also increase your risk. Discuss these factors with your doctor.
As this medication is derived from human plasma, a component of blood, there is a potential risk of transmitting viruses that can cause disease. Although the medication is thoroughly screened, tested, and treated to minimize this risk, it is crucial to discuss this with your doctor.
It is important to note that this medication is used to prevent certain health problems, but it will not treat acute HAE attacks. If you have questions about managing HAE attacks, consult your doctor.
Before traveling, consult your doctor to ensure you have an adequate supply of this medication. If you experience any changes in weight, inform your doctor, as your dosage may need to be adjusted.
If you are pregnant, planning to become pregnant, or breastfeeding, inform your doctor. It is essential to discuss the potential benefits and risks of this medication to both you and your baby.
Overdose Information
Overdose Symptoms:
- Symptoms of overdose are not well-defined for C1 Inhibitor (Human) as it is a protein. High doses may theoretically increase the risk of thromboembolic events, but clinical data are limited.
What to Do:
In case of suspected overdose, contact a poison control center (e.g., 1-800-222-1222) or seek emergency medical attention. Management is supportive and symptomatic.
Drug Interactions
Monitoring
Baseline Monitoring
Diagnosis of Hereditary Angioedema (HAE)
Rationale: Confirm appropriate indication for treatment.
Timing: Prior to initiation of therapy
Baseline C4 levels
Rationale: To establish baseline for HAE diagnosis, though C4 levels are not used to monitor treatment efficacy for Haegarda.
Timing: Prior to initiation of therapy
Routine Monitoring
Frequency and severity of HAE attacks
Frequency: Continuously, patient self-monitoring and clinician assessment at follow-up visits
Target: Reduction in attack frequency and severity
Action Threshold: If attack frequency does not decrease or worsens, reassess adherence, dosing, or consider alternative therapies.
Signs and symptoms of hypersensitivity reactions
Frequency: During and immediately after administration, and ongoing
Target: Absence of allergic reactions
Action Threshold: Discontinue infusion immediately if severe allergic reaction occurs; manage symptoms.
Signs and symptoms of thromboembolic events
Frequency: Periodically, especially in patients with risk factors
Target: Absence of thrombotic events
Action Threshold: Prompt medical evaluation if symptoms occur.
Symptom Monitoring
- Swelling (face, lips, tongue, throat, extremities, abdomen, genitals)
- Difficulty breathing or swallowing
- Abdominal pain, nausea, vomiting, diarrhea (during HAE attacks)
- Hives, rash, itching, flushing (hypersensitivity reaction)
- Chest pain, shortness of breath, swelling or pain in an arm or leg (thromboembolic events)
Special Patient Groups
Pregnancy
Use during pregnancy only if clearly needed and the potential benefits outweigh the potential risks. Human and animal data are limited. C1-INH is a normal component of human plasma.
Trimester-Specific Risks:
First Trimester:
Limited data; theoretical risk is low as it's a human protein.
Second Trimester:
Limited data; theoretical risk is low.
Third Trimester:
Limited data; theoretical risk is low.
Lactation
It is unknown if C1 Inhibitor is excreted in human milk. Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for Haegarda and any potential adverse effects on the breastfed infant from Haegarda or from the underlying maternal condition. C1-INH is a normal component of human plasma, and oral absorption by an infant is unlikely.
Infant Risk:
Low (L3-L4, but generally considered low due to protein nature and unlikely oral absorption)
Pediatric Use
Approved for patients 6 years of age and older. Dosing is weight-based for patients under 50 kg. Safety and effectiveness in pediatric patients younger than 6 years of age have not been established.
Geriatric Use
No specific dose adjustment is recommended for geriatric patients. Clinical studies 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
- Haegarda is for routine prophylaxis to prevent HAE attacks, not for acute treatment of attacks.
- Patients should be trained on proper subcutaneous administration technique, including reconstitution and injection.
- Store Haegarda refrigerated (2°C to 8°C [36°F to 46°F]). Do not freeze. Protect from light. Can be stored at room temperature (up to 25°C [77°F]) for up to 6 months, but must be used within that period or discarded.
- Ensure patients have access to and understand how to use their acute HAE attack medication.
- Monitor for hypersensitivity reactions, especially during the first few administrations. Have epinephrine and other supportive measures readily available.
- While rare, thrombotic events have been reported with C1-INH products. Consider risk factors (e.g., indwelling catheters, history of thrombosis, estrogen use) and monitor patients accordingly.
Alternative Therapies
- Cinryze (C1 Esterase Inhibitor [Human]) - IV prophylaxis
- Berinert (C1 Esterase Inhibitor [Human]) - IV acute treatment
- Ruconest (C1 Esterase Inhibitor [recombinant]) - IV acute treatment
- Takhzyro (lanadelumab) - SC prophylaxis
- Orladeyo (berotralstat) - Oral prophylaxis
- Kalbitor (ecallantide) - SC acute treatment
- Firazyr (icatibant) - SC acute treatment
Cost & Coverage
Average Cost:
Very high (e.g., thousands of dollars per vial) per 3000 unit vial
Insurance Coverage:
Specialty Tier (requires prior authorization, often subject to step therapy)
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 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 medication, including the amount taken and the time it happened, to ensure you receive the best possible care.