Hizentra

Primary Immunodeficiency (PI)

Hizentra is used to treat adults and children 2 years of age and older who have primary immunodeficiency. This is a group of rare, chronic disorders where part of the body's immune system is missing or does not function properly, making it difficult to fight off infections. The medication provides antibodies that the body cannot produce on its own. Specific types of PI treated include:

• X-linked agammaglobulinemia
• Common variable immunodeficiency
• Congenital agammaglobulinemia
• Wiskott-Aldrich syndrome
• Severe combined immunodeficiencies

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

Hizentra is also used as a maintenance treatment for adults with chronic inflammatory demyelinating polyneuropathy. CIDP is a neurological disorder that causes progressive weakness and impaired sensory function in the arms and legs. The medication is used to help prevent the return of neuromuscular disability and physical impairment in people with this condition.

Antibody Replacement

Hizentra is a solution made of human antibodies called immunoglobulin G (IgG). These are proteins that the immune system typically uses to find and destroy germs like bacteria and viruses. For people with primary immunodeficiency, the body does not produce enough of these antibodies. Hizentra works by replacing the missing IgG, which helps the body defend itself against infections.

Immune Regulation

In the treatment of chronic inflammatory demyelinating polyneuropathy (CIDP), the immune system mistakenly attacks the nerves. While the exact way Hizentra works for this condition is not fully understood, it is believed to help regulate the immune system. By introducing healthy antibodies, the medication may help prevent the immune system from attacking the protective covering of the nerves.

Subcutaneous Delivery

The medication is injected into the fatty tissue directly under the skin. It is then slowly absorbed into the bloodstream. This method of delivery allows the antibodies to enter the system gradually, which helps maintain a steady level of protection in the body between doses.

Common Side Effects

Many people using Hizentra experience mild side effects. These often occur at the site where the medicine is injected and may include:

• Injection site reactions: Redness, swelling, itching, warmth, or a small lump.
• Headache or migraine.
• Nausea, vomiting, or diarrhea.
• Fatigue or tiredness.
• Back pain or joint pain.
• Mild fever or chills.

Serious Side Effects

While less common, Hizentra can cause serious or life-threatening conditions. Seek medical attention immediately if you experience:

• Blood clots: Symptoms include sudden shortness of breath, chest pain, swelling or warmth in an arm or leg, or sudden weakness.
• Kidney problems: Signs include decreased urination, rapid weight gain, or swelling in the feet and ankles.
• Aseptic meningitis: This is an inflammation of the brain lining characterized by a severe headache, stiff neck, fever, and sensitivity to light.
• Lung issues: Difficulty breathing or a blue tint to the lips or skin.
• Hemolysis: The breakdown of red blood cells, which may cause fatigue, dark urine, or yellowing of the skin and eyes.
• Severe allergic reactions: Hives, swelling of the face or throat, and dizziness.

Boxed Warning: Thrombosis

Blood clots (thrombosis) may occur with immune globulin products, including Hizentra. Risk factors include advanced age, prolonged periods of inactivity, a history of blood clots, use of estrogens, or certain cardiovascular conditions. For patients at risk, the product should be administered at the minimum dose and infusion rate practicable. Adequate hydration is recommended before administration.

Contraindications

Hizentra should not be used by patients who have had a history of anaphylactic or severe systemic reactions to human immune globulin or its components, such as polysorbate 80. It is also contraindicated in patients with selective IgA deficiency who have known antibodies against IgA and a history of hypersensitivity.

Hypersensitivity and Allergic Reactions

Severe hypersensitivity reactions can occur. If a reaction happens, the infusion must be stopped immediately and appropriate treatment started. Patients with antibodies to IgA are at a higher risk for severe hypersensitivity. Epinephrine should be available for immediate use in case of a severe reaction.

Kidney Function

Acute kidney failure and other renal complications have been reported with the use of human immune globulin products. Monitoring of kidney function and urine output is important, especially for those at increased risk of renal failure, such as patients with pre-existing kidney disease or diabetes.

Aseptic Meningitis Syndrome (AMS)

AMS has been reported in association with immune globulin treatment. Symptoms typically begin within several hours to two days after treatment and include severe headache, neck stiffness, drowsiness, fever, and sensitivity to light. Discontinuing treatment may result in the resolution of symptoms within several days.

Hemolysis and Lung Injury

Hizentra may contain blood group antibodies that can cause the breakdown of red blood cells (hemolysis). Additionally, some patients may experience transfusion-related acute lung injury (TRALI), a condition characterized by severe breathing distress, low oxygen levels, and pulmonary edema, typically occurring within one to six hours after infusion.

Infectious Agents

Because Hizentra is made from human plasma, it may carry a risk of transmitting infectious agents, such as viruses or the agent that causes Creutzfeldt-Jakob disease. The manufacturing process includes steps to reduce this risk, such as screening donors and using viral inactivation steps, but the risk cannot be entirely eliminated.

Interference with Laboratory Tests

The passive transfer of antibodies through Hizentra may result in misleading positive results in serological tests. Healthcare providers should be aware of this potential interference when interpreting laboratory results.

Pregnancy

There are no adequate and well-controlled studies of Hizentra in pregnant women. It is unknown whether the medication can cause harm to a developing fetus or affect reproductive capacity. Animal reproduction studies have not been conducted with this drug.

Immune globulins are known to cross the placenta, especially during the third trimester. Because of the lack of specific data, Hizentra should only be given to a pregnant woman if it is clearly needed and recommended by a doctor.

Breastfeeding

It is not known if Hizentra is excreted in human breast milk. Because many medications can be passed through milk, caution should be used when administering Hizentra to someone who is nursing. Patients should talk to their healthcare provider about the potential risks and benefits of breastfeeding while using this medication.

Available Forms

Hizentra is a sterile liquid solution intended for subcutaneous infusion. It is provided in ready-to-use formats to be administered under the skin.

The medication is available in the following forms:

• Single-use vials: These containers are intended for one-time use and do not contain preservatives.
• Prefilled syringes: These are ready-to-use syringes designed for subcutaneous administration.

The solution is clear and may range in color from colorless to pale yellow or light brown. Because it is a biological product, it must be inspected for particles or discoloration before use.

FDA Approval Status

Hizentra (Immune Globulin Subcutaneous [Human], 20% Liquid) was first approved by the U.S. Food and Drug Administration (FDA) in March 2010. It was the first 20% subcutaneous immunoglobulin (SCIg) therapy available in the United States.

Approved Indications

The FDA has approved Hizentra for the following uses:

• Primary Immunodeficiency (PI): For the treatment of adults and pediatric patients 2 years of age and older.
• Chronic Inflammatory Demyelinating Polyneuropathy (CIDP): For the treatment of adults as maintenance therapy to prevent relapse of neuromuscular disability and impairment.

Boxed Warning

Hizentra contains a boxed warning from the FDA regarding the risk of thrombosis (blood clots). Thrombosis may occur even in the absence of known risk factors. For patients at risk, the drug should be administered at the minimum dose and infusion rate practicable. Patients should be well hydrated before administration.

Regulatory History and Safety

Since its initial approval for primary immunodeficiency, the FDA expanded Hizentra's indications in 2018 to include the treatment of CIDP. The product is subject to ongoing regulatory oversight to ensure manufacturing standards and safety profiles are maintained. Healthcare providers are encouraged to report any serious adverse events to the FDA MedWatch program.

Insurance Coverage

Most insurance plans, including Medicare and Medicaid, provide coverage for Hizentra. However, because it is a specialty medication, insurance companies often require prior authorization. This process involves your healthcare provider submitting documentation to prove the medical necessity of the treatment before the insurer agrees to cover the cost.

Financial Assistance Programs

There are several options available to help manage the expenses associated with Hizentra:

• Co-pay Relief: Eligible patients with private or commercial insurance may qualify for a co-pay assistance program provided by the manufacturer to reduce out-of-pocket costs.
• Patient Assistance: For those without insurance or with limited coverage, patient assistance programs may provide the medication at a lower cost or for free, depending on financial eligibility.
• Support Programs: Specialized support services can assist patients in understanding their benefits and finding financial resources.

The final cost is also determined by the specific dosage and frequency of administration, which are tailored to the individual's weight and medical condition.