Haegarda

HAEGARDA is a human plasma-derived, purified, pasteurized, lyophilized concentrate of C1-INH to be reconstituted for S.C. administration. HAEGARDA is prepared from large pools of human plasma from U.S. donors. The potency of C1-INH is expressed in International Units (IU), which is related to the current WHO Standard for C1-INH products.

Reconstituted HAEGARDA has a concentration of 500 IU/mL C1-INH, 65 mg/mL total protein, 10 mg/mL glycine, 8.5 mg/mL sodium chloride and 2.7 mg/mL sodium citrate.

C1 Esterase Inhibitor

C1-INH is a soluble, single-chain highly glycosylated protein containing 478 amino acid residues which belongs to the serine protease inhibitor (serpin) family.

All plasma used in the manufacturing of C1-INH is obtained from U.S. donors and is tested using serological assays for hepatitis B surface antigen and antibodies to HIV-½ and HCV. Additionally, the plasma is tested with Nucleic Acid Testing (NAT) for HBV, HCV, HIV-1 and HAV and found to be non-reactive (negative). The plasma is also tested by NAT for Human Parvovirus B19. Only plasma that has passed virus screening is used for production, and the limit for Parvovirus B19 in the fractionation pool is set not to exceed 104 IU of Parvovirus B19 DNA per mL.

The manufacturing process for HAEGARDA includes multiple steps that reduce the risk of virus transmission. The virus inactivation/reduction capacity consists of three steps:

• Pasteurization in aqueous solution at 60°C for 10 hours
• Hydrophobic interaction chromatography
• Virus filtration (also called nanofiltration) by two filters, 20 nm and 15 nm, in series.

Viral inactivation and reduction were evaluated in a series of in vitro spiking experiments. The total mean cumulative virus inactivation/reduction is shown in Table 3.

Table 3: Mean Virus Inactivation/Reductions in HAEGARDA

Adverse reactions occurring in more than 4% of subjects treated with HAEGARDA were injection site reaction, hypersensitivity, nasopharyngitis and dizziness.

Clinical Trials Experience

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials o f a drug cannot be directly compared to rates in the clinical trials o f another drug and may not reflect the rates observed in practice.

Of the 90 subjects randomized in the double-blind, placebo-controlled, cross-over study [see Clinical Studies], 86 subjects received at least one dose of HAEGARDA and 86 subjects received at least one dose of placebo (Table 2). A total of 5081 injections of HAEGARDA and placebo were administered over a range of 3 to 19 weeks (median of 16.6 weeks for HAEGARDA; median of 16.3 weeks for placebo).

Table 2: Adverse Reactions in > 4% of Subjects Treated with HAEGARDA

Of the injection site reactions occurring after treatment with HAEGARDA, 95% were of mild intensity and 83% resolved within 1 day after onset.

Read the entire FDA prescribing information for Haegarda (C1 Esterase Inhibitor Subcutaneous [Human] Injection)

In the U.S.

• Berinert
• Cinryze
• Haegarda

Available Dosage Forms:

• Powder for Solution

Therapeutic Class: Immune Modulator

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur:

• Chest pain
• head congestion
• hoarseness or other voice changes
• nausea and vomiting
• pain or tenderness around the eyes and cheekbones
• rash
• sore throat
• tightness of the chest
• trouble breathing

• Flushing or redness of the skin
• itching
• unusually warm skin

• Confusion
• difficulty with speaking
• difficulty with swallowing
• dizziness
• double vision
• fast heartbeat
• general tiredness and weakness
• hives
• inability to move the arms, legs, or facial muscles
• numbness or tingling in the face, arms, or legs
• pain, redness, or swelling in the arm or leg
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• slow speech
• trouble speaking, thinking, or walking

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Diarrhea
• headache
• pain
• stomach pain

• Bleeding, blistering, burning, coldness, discoloration of skin, feeling of pressure, hives, infection, inflammation, itching, lumps, numbness, pain, rash, redness, scarring, soreness, stinging, swelling, tenderness, tingling, ulceration, or warmth at the injection site
• change in taste
• fever
• loss of taste
• muscle aches
• pain at the catheter site
• stuffy or runny nose
• unusual tiredness or weakness

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

• Tell all of your health care providers that you take Haegarda. This includes your doctors, nurses, pharmacists, and dentists.
• Keep epinephrine with you at all times.
• Unsafe allergic effects may rarely happen.
• Blood clots have happened with this medicine. The chance may be raised if you have a certain type of catheter or device in a vein or if you take certain drugs like estrogens or androgens. The chance may be raised if you have ever had heart or blood vessel disease, stroke, thick blood, or a blood clot. The chance may also be raised if you have not been able to move around for some time. Talk with your doctor.
• This medicine is made from human plasma (part of the blood) and may have viruses that may cause disease. This medicine is screened, tested, and treated to lower the chance that it carries an infection. Talk with the doctor.
• This medicine will not treat HAE attacks. This medicine is only used to prevent these health problems. Talk with the doctor to if you have questions about how to treat HAE attacks.
• Talk with the doctor before you travel. You will need to bring enough of Haegarda for use during travel.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this medicine while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Very bad dizziness or passing out.
• Change in color of mouth to blue.
• A fast heartbeat.
• Very bad headache.
• Weakness on 1 side of the body, trouble speaking or thinking, change in balance, drooping on one side of the face, or blurred eyesight.
• Call your doctor right away if you have signs of a blood clot like chest pain or pressure; coughing up blood; shortness of breath; swelling, warmth, numbness, change of color, or pain in a leg or arm; or trouble speaking or swallowing.

Applies to C1 esterase inhibitor (human): intravenous powder for solution

Along with its needed effects, C1 esterase inhibitor (human) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur while taking C1 esterase inhibitor (human):

• Chest pain
• head congestion
• hoarseness or other voice changes
• nausea and vomiting
• pain or tenderness around the eyes and cheekbones
• rash
• sore throat
• tightness of the chest
• trouble breathing

• Flushing or redness of the skin
• itching
• unusually warm skin

• Confusion
• difficulty with speaking
• difficulty with swallowing
• dizziness
• double vision
• fast heartbeat
• general tiredness and weakness
• hives
• inability to move the arms, legs, or facial muscles
• numbness or tingling in the face, arms, or legs
• pain, redness, or swelling in the arm or leg
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• slow speech
• trouble speaking, thinking, or walking

Some side effects of C1 esterase inhibitor (human) may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Diarrhea
• headache
• pain
• stomach pain

• Bleeding, blistering, burning, coldness, discoloration of skin, feeling of pressure, hives, infection, inflammation, itching, lumps, numbness, pain, rash, redness, scarring, soreness, stinging, swelling, tenderness, tingling, ulceration, or warmth at the injection site
• change in taste
• fever
• loss of taste
• muscle aches
• pain at the catheter site
• stuffy or runny nose
• unusual tiredness or weakness

Applies to C1 esterase inhibitor (human): intravenous kit, intravenous powder for injection

Respiratory

Respiratory side effects have included sinusitis, bronchitis, upper respiratory tract infection, and viral upper respiratory tract infection.[Ref]

Nervous system

Nervous system side effects have included headache.[Ref]

Musculoskeletal

Musculoskeletal side effects have included limb injury, back pain, and pain in extremity.[Ref]

Dermatologic

Dermatologic side effects have included pruritus.[Ref]

Cardiovascular

Cardiovascular side effects have included postmarketing reports of thrombotic events including deep vein thrombosis, myocardial infarction, and transient ischemic attack.[Ref]

Some side effects of Haegarda may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.