ANDEMBRY: Uses, Dosage & Side Effects

What Is ANDEMBRY and What Is It Used For?

ANDEMBRY contains the active substance garadacimab, a fully human immunoglobulin G4 (IgG4) monoclonal antibody. As a monoclonal antibody, garadacimab is a highly specialized protein engineered to recognize and bind to one specific molecular target in the body. In the case of ANDEMBRY, that target is coagulation factor XII (FXII), specifically preventing its conversion to the activated form, factor XIIa (FXIIa). By blocking this critical activation step at the very beginning of the kallikrein-kinin cascade, garadacimab addresses the root cause of excessive bradykinin production that drives HAE attacks.

Hereditary angioedema (HAE) is a rare genetic disorder characterized by recurrent episodes of severe, often debilitating swelling (angioedema) in various parts of the body. These episodes, known as HAE attacks, can affect the hands and feet, the face, eyelids, lips and tongue, the larynx and throat (which can cause life-threatening airway obstruction), the genitals, and the abdomen and intestines (causing severe abdominal pain often mistaken for surgical emergencies). HAE attacks are unpredictable, can last for several days, and significantly impair quality of life. Attacks affecting the upper airway represent a medical emergency, as progressive laryngeal swelling can lead to asphyxiation and death if not treated promptly.

HAE is typically inherited in an autosomal dominant pattern, meaning that a single copy of the defective gene from either parent is sufficient to cause the condition. However, some individuals develop HAE without a family history due to spontaneous (de novo) genetic mutations. Three types of HAE have been identified based on the underlying genetic defect and its effect on a plasma protein called C1-esterase inhibitor (C1-INH):

• Type I HAE: The most common form, accounting for approximately 85% of cases. Patients have quantitatively reduced levels of functional C1-INH protein due to mutations in the SERPING1 gene. The low levels of C1-INH result in inadequate regulation of the kallikrein-kinin system, leading to excessive bradykinin production.
• Type II HAE: Accounts for approximately 15% of cases. Patients produce normal or elevated quantities of C1-INH protein, but the protein is dysfunctional and cannot adequately regulate the kallikrein-kinin system. The clinical presentation is identical to Type I.
• Type III HAE (HAE with normal C1-INH): An extremely rare form in which C1-INH levels and function are normal. This type has been associated with mutations in the F12 gene (encoding factor XII), the PLG gene (encoding plasminogen), the ANGPT1 gene, the KNG1 gene, the MYOF gene, and the HS3ST6 gene. Because some subtypes of Type III HAE involve factor XII gain-of-function mutations, these patients may respond particularly well to factor XIIa inhibition with garadacimab, though not all Type III subtypes may benefit equally.

In all three types of HAE, the common pathological endpoint is the overproduction of bradykinin, a potent vasoactive peptide that increases vascular permeability and causes plasma to leak from blood vessels into surrounding tissues, resulting in the characteristic localized swelling. Under normal physiological conditions, the production of bradykinin is tightly regulated by the kallikrein-kinin system. Factor XII circulates in the blood as an inactive zymogen. When activated to factor XIIa – triggered by contact with negatively charged surfaces, tissue injury, or other stimuli – it initiates a cascade that converts prekallikrein to plasma kallikrein, which in turn cleaves high-molecular-weight kininogen (HMWK) to release bradykinin. C1-INH normally keeps this cascade in check by inhibiting both factor XIIa and plasma kallikrein. In patients with HAE Types I and II, the deficiency or dysfunction of C1-INH removes this regulatory brake, resulting in uncontrolled bradykinin generation.

Garadacimab represents a novel therapeutic approach by intervening at the very top of this cascade. Rather than targeting downstream mediators (as do other HAE therapies that inhibit plasma kallikrein or block bradykinin receptors), garadacimab prevents the activation of factor XII to factor XIIa in the first place. By blocking FXIIa activity, garadacimab reduces the entire downstream cascade, lowering bradykinin levels and thereby preventing the vascular permeability that causes HAE attacks. This upstream mechanism of action is what makes ANDEMBRY a first-in-class therapy.

The clinical efficacy of garadacimab was established in the VANGUARD study (NCT04656418), a pivotal phase III, randomized, double-blind, placebo-controlled trial that enrolled 63 patients aged 12 years and older with HAE Types I or II who experienced at least 2 investigator-confirmed HAE attacks per month during a run-in period. Patients were randomized to receive garadacimab 200 mg (after a 400 mg loading dose) or placebo by subcutaneous injection once monthly for 6 months. The primary endpoint was the rate of investigator-confirmed HAE attacks during the treatment period.

The results were striking: patients treated with garadacimab experienced an approximately 87% reduction in the rate of HAE attacks compared with placebo (0.27 attacks per month with garadacimab versus 2.01 attacks per month with placebo). Furthermore, 53% of patients in the garadacimab group were attack-free during the entire 6-month treatment period, compared with only 3% in the placebo group. Garadacimab also demonstrated significant improvements in secondary endpoints, including reduced use of on-demand rescue medication, fewer days of swelling, and improvement in HAE-specific quality of life measures. The benefits were sustained in an open-label extension study, with continued reductions in attack frequency over 12 months and beyond.

ANDEMBRY was first approved by the European Medicines Agency (EMA) in 2024 and has subsequently received approval in additional countries. It is manufactured by CSL Behring GmbH, a global biopharmaceutical company with extensive expertise in plasma-derived and recombinant therapies for rare diseases. ANDEMBRY represents a significant addition to the growing armamentarium of targeted prophylactic therapies for HAE, offering patients an option with a novel mechanism of action, monthly dosing convenience, and a favorable safety profile.

What Should You Know Before Taking ANDEMBRY?

Contraindications

The primary contraindication to ANDEMBRY use is hypersensitivity (allergy) to garadacimab or to any of the other ingredients in the formulation. The excipients in ANDEMBRY include histidine, arginine monohydrochloride, proline, polysorbate 80, and water for injections. If you have a known allergy to any of these substances, you must not use ANDEMBRY. If you experience signs of a serious allergic reaction after using ANDEMBRY – such as hives, tightness in the chest, difficulty breathing, wheezing, low blood pressure, or anaphylaxis – seek immediate medical attention and do not administer further doses until you have consulted your healthcare provider.

It is important to distinguish between an HAE attack and an allergic reaction to ANDEMBRY, as both can cause swelling. An HAE attack typically presents with gradually progressive, non-pruritic (non-itchy) swelling, whereas an allergic reaction is more likely to involve hives (urticaria), itching, and respiratory symptoms. If you are uncertain whether you are experiencing an HAE attack or an allergic reaction, seek medical advice promptly.

Warnings and Precautions

Before starting ANDEMBRY, discuss the following with your healthcare provider:

• Batch number record-keeping: It is strongly recommended that you record the name of the medicine and the batch number each time you receive a dose of ANDEMBRY. This creates a clear overview of which manufacturing batches you have used, which is important for traceability and pharmacovigilance purposes.
• Laboratory test interference: Because ANDEMBRY targets factor XIIa, it may affect certain coagulation laboratory tests, including activated partial thromboplastin time (aPTT) and other tests that rely on the contact activation pathway. This can lead to falsely prolonged results that do not reflect an actual increased risk of bleeding. Always inform your doctor and laboratory that you are using ANDEMBRY before undergoing any blood coagulation tests to ensure accurate interpretation of results.
• Hyperprolinemia: ANDEMBRY contains 19.3 mg of proline per pre-filled pen (equivalent to 16.1 mg/mL). Proline may be harmful to patients with hyperprolinemia, a rare genetic disorder in which proline accumulates in the body. Do not use ANDEMBRY if you or your child has hyperprolinemia unless your doctor has specifically recommended it.
• Polysorbate 80 sensitivity: ANDEMBRY contains 0.24 mg of polysorbate 80 per pre-filled pen (equivalent to 0.2 mg/mL). Polysorbates can cause allergic reactions in susceptible individuals. Inform your doctor if you have any known allergies to polysorbates.

Children and Adolescents

ANDEMBRY is indicated for use in patients aged 12 years and older. The safety and efficacy of garadacimab in children younger than 12 years have not been established, and the medication is not recommended for this age group. Adolescents aged 12 to 17 years were included in clinical trials and received the same dosing regimen as adults (400 mg loading dose followed by 200 mg monthly). The safety and efficacy profile in adolescents was consistent with that observed in the adult population. When ANDEMBRY is administered to adolescents, it should be given under the supervision of an adult.

Pregnancy and Breastfeeding

If you are pregnant, think you may be pregnant, or are planning to become pregnant, consult your doctor before using ANDEMBRY. There is limited data on the use of garadacimab in pregnant women. As a monoclonal antibody (IgG4), garadacimab is expected to cross the placenta, particularly during the second and third trimesters. While animal studies may not always predict human outcomes, the potential effects of factor XIIa inhibition on the developing fetus have not been fully characterized. As a precautionary measure, ANDEMBRY should be avoided during pregnancy unless the potential benefit to the mother clearly outweighs the potential risk to the fetus. Your doctor will discuss the individual risks and benefits with you.

It is not known whether garadacimab is excreted in human breast milk. Human IgG antibodies are known to be present in breast milk, particularly in the early postnatal period. A risk to the breastfed infant cannot be excluded. The decision to breastfeed while using ANDEMBRY should be made in consultation with your doctor, weighing the benefits of breastfeeding for the infant against the benefits of continued ANDEMBRY treatment for the mother.

Driving and Operating Machinery

ANDEMBRY has no or negligible effect on the ability to drive or use machines. Based on its pharmacological properties and the known side effect profile from clinical trials, garadacimab is not expected to impair cognitive function or psychomotor performance. However, if you experience any unusual symptoms after injection that could affect your ability to drive or operate machinery, refrain from these activities until you feel well again.

Other Medicines and ANDEMBRY

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. ANDEMBRY is not known to affect other medicines or to be affected by other medicines. As a monoclonal antibody, garadacimab is not metabolized by cytochrome P450 (CYP) enzymes and is therefore not expected to interact with other medications through traditional pharmacokinetic drug-drug interaction mechanisms. No formal drug interaction studies have been conducted. Patients should continue their on-demand rescue medication for breakthrough HAE attacks as prescribed.

How Does ANDEMBRY Interact with Other Drugs?

One of the significant practical advantages of ANDEMBRY in the management of hereditary angioedema is its favorable drug interaction profile. Unlike small-molecule drugs that are metabolized by hepatic cytochrome P450 (CYP) enzymes and can interact with a wide range of co-administered medications, garadacimab is a large monoclonal antibody protein that is degraded through general protein catabolic pathways rather than through enzyme-mediated hepatic metabolism. This means that ANDEMBRY is not expected to affect or be affected by other drugs through pharmacokinetic interactions.

No formal drug-drug interaction studies have been conducted with garadacimab. However, population pharmacokinetic analyses from the clinical development program did not identify any meaningful effects of concomitant medications on garadacimab pharmacokinetics. In clinical trials, patients were permitted to continue their existing medications, and no clinically relevant interactions were observed.

Patients with HAE typically use several concomitant medications, including on-demand rescue treatments for breakthrough attacks and medications for comorbid conditions. The table below summarizes the expected interaction status of common medications used alongside ANDEMBRY:

While ANDEMBRY does not have pharmacokinetic drug interactions, there is an important pharmacodynamic consideration regarding coagulation laboratory testing. Because garadacimab inhibits factor XIIa, it affects the contact activation pathway of the coagulation cascade. This can lead to prolongation of the activated partial thromboplastin time (aPTT) in laboratory tests. Critically, this prolongation reflects the pharmacological activity of garadacimab and does not indicate an increased risk of clinical bleeding. Healthcare providers must be aware that aPTT results in patients receiving ANDEMBRY may be unreliable and should not be used as the sole basis for clinical decisions regarding anticoagulation or surgical readiness.

Although no formal interaction with anticoagulants has been identified, patients taking concurrent anticoagulant therapy (such as warfarin or direct oral anticoagulants) should inform all treating physicians that they are receiving ANDEMBRY, particularly before any surgical procedures or if coagulation testing is required. Alternative coagulation assays that do not depend on the contact activation pathway (such as the prothrombin time/INR for monitoring warfarin therapy) are not affected by garadacimab.

What Is the Correct Dosage of ANDEMBRY?

ANDEMBRY is supplied as a solution for injection in single-use pre-filled pens, each containing 200 mg of garadacimab in 1.2 mL of solution. Treatment should be initiated and supervised by a healthcare professional experienced in the management of hereditary angioedema. After appropriate training, patients or their caregivers may self-administer ANDEMBRY at home.

Adults and Adolescents (12 Years and Older)

The recommended dosing regimen for ANDEMBRY is as follows:

The loading dose of 400 mg on the first day of treatment is designed to rapidly achieve therapeutic drug levels in the body, providing earlier onset of protection against HAE attacks. After the loading dose, the 200 mg monthly maintenance dose sustains these therapeutic levels over time. The same dosing regimen is used for both adults and adolescents aged 12 years and older; no dose adjustment based on body weight is required.

ANDEMBRY is injected subcutaneously (under the skin) into one of the following body areas:

• Abdomen (belly): Maintain a distance of at least 2 cm from the navel. Avoid areas that are tender, bruised, red, or hardened.
• Front of the thigh: Select the middle portion of the front of the thigh.
• Back of the upper arm: This site may be used if another person (caregiver) is giving the injection. Do not attempt to self-inject into the upper arm.

Rotate injection sites regularly to minimize the risk of injection site reactions. Do not inject into the same location repeatedly, and avoid injecting into areas with moles, scars, bruises, or skin damage.

Children Under 12 Years

ANDEMBRY is not recommended for use in children under 12 years of age. The safety and efficacy of garadacimab have not been studied in this age group. Healthcare providers should consider alternative therapies for the prophylactic management of HAE in children younger than 12 years.

Missed Dose

If you forget a dose of ANDEMBRY, inject the missed dose as soon as possible. If you are unsure about when to administer your next scheduled dose after a missed dose, consult your doctor, pharmacist, or nurse for guidance. Do not take a double dose to make up for a forgotten injection. Using a calendar, diary, or mobile phone reminder can help you stay on schedule with your monthly injections.

Overdose

If you have used more ANDEMBRY than prescribed, inform your doctor, pharmacist, or nurse immediately. There is limited data on overdose with garadacimab. Treatment of overdose should be supportive, with monitoring of vital signs and clinical status. Given the long half-life of monoclonal antibodies, monitoring may need to continue for an extended period. There is no specific antidote for garadacimab overdose.

How to Use the Pre-Filled Pen

Before using ANDEMBRY for the first time, your doctor or nurse must train you or your caregiver on the proper injection technique. The pre-filled pen is designed for single use only and should not be reused. The following is a general overview of the injection process:

1. Preparation: Remove the pre-filled pen from the refrigerator 30 minutes before use to allow it to reach room temperature. Do not heat the pen using a microwave, hot water, or direct sunlight. Do not attempt to speed up the warming process.
2. Inspection: Check the expiration date on the label. Inspect the solution through the viewing window – it should be slightly opalescent to clear, and brownish-yellow to yellow in color. Small air bubbles are normal. Do not use the pen if the solution is discolored, contains particles, appears damaged, has cracks, or is leaking.
3. Site preparation: Wash your hands thoroughly with soap and water or use hand sanitizer. Clean the chosen injection site with an alcohol swab and allow it to air dry. Do not blow on or fan the cleaned area.
4. Remove the clear cap: Pull the transparent cap straight off (do not twist). Do not replace the cap once removed, as this may trigger the injection mechanism and cause injury. Do not touch the grey needle shield.
5. Injection: Gently pinch the skin around the injection site. Place the pen at a 90-degree angle to the skin and press firmly. Wait until the yellow plunger has stopped moving and filled the entire viewing window, and at least 5 seconds have passed after the second click sound.
6. Removal and disposal: Release the skin and remove the pen at a 90-degree angle. The grey needle shield will automatically lock into place. If there is slight bleeding, gently press a cotton ball or gauze over the injection site – do not rub. Place the used pen immediately into an approved sharps disposal container.

If you believe the pen did not function correctly or that you did not receive the full dose, contact your healthcare provider immediately. Each pre-filled pen contains a single dose and must not be reused.

If You Stop Using ANDEMBRY

It is important to continue your ANDEMBRY injections as prescribed by your doctor, even if you are feeling well and not experiencing HAE attacks. Discontinuation of prophylactic therapy may result in a return of HAE attacks. If you are considering stopping treatment, discuss this decision with your doctor first, who can help you understand the potential risks and develop an appropriate management plan.

What Are the Side Effects of ANDEMBRY?

Like all medicines, ANDEMBRY can cause side effects, although not everyone who receives it will experience them. The safety profile of garadacimab has been established through the VANGUARD phase III trial and its open-label extension study. Overall, ANDEMBRY has demonstrated a favorable tolerability profile, with the majority of adverse events being mild to moderate in severity and consistent with the known effects of subcutaneous monoclonal antibody therapies.

The following side effects have been observed during clinical trials with ANDEMBRY, categorized by their frequency of occurrence according to the standard medical convention:

Injection site reactions are the most frequently reported side effects with ANDEMBRY. In the VANGUARD trial, injection site reactions occurred in a higher proportion of patients receiving garadacimab compared with placebo. These reactions are generally mild to moderate in intensity and typically resolve within a few days without requiring specific treatment. Rotating injection sites between administrations can help minimize these reactions. Injecting the medication at room temperature (after allowing the pen to warm for 30 minutes) can also reduce discomfort at the injection site.

Headache was reported as a common side effect, occurring at a rate that was modestly higher in the garadacimab group compared with placebo. The headaches were generally mild, self-limiting, and did not require discontinuation of treatment. Abdominal pain was similarly mild to moderate and self-resolving in most cases. It is worth noting that abdominal pain can also be a symptom of an HAE attack, so patients should be aware of the distinction between a side effect and a possible breakthrough attack.

The overall discontinuation rate due to adverse events in clinical trials was low, comparable between the garadacimab and placebo groups, indicating that ANDEMBRY is generally well tolerated. No signals of hepatotoxicity (liver damage), cardiovascular events, or significant changes in standard laboratory parameters (beyond the expected effect on aPTT) were identified during clinical trials.

It is important to note that because ANDEMBRY inhibits factor XIIa, it affects the contact activation pathway of coagulation as measured by the activated partial thromboplastin time (aPTT). This prolongation of aPTT is a direct consequence of the drug’s mechanism of action and does not indicate an increased clinical risk of bleeding. In the VANGUARD trial, there was no increase in bleeding events in the garadacimab group compared with placebo.

How Should You Store ANDEMBRY?

Proper storage of ANDEMBRY is essential to maintain the quality, safety, and efficacy of the medication. As a biological product (monoclonal antibody), garadacimab is sensitive to temperature extremes, light exposure, and physical stress, all of which can compromise its structural integrity and therapeutic effectiveness. Follow these storage guidelines carefully:

• Refrigerated storage (primary): Store ANDEMBRY in the refrigerator at 2–8 °C (36–46 °F). This is the primary storage condition. Keep the pre-filled pen in the outer carton to protect it from light.
• Do not freeze: Freezing can permanently damage the monoclonal antibody protein structure and render the medication ineffective. If ANDEMBRY has been accidentally frozen, do not use it – discard it safely and use a new pen.
• Temporary room temperature storage: ANDEMBRY can be stored at room temperature (up to 25 °C / 77 °F) for a single period of up to 2 months, but not beyond the printed expiration date. This is convenient for travel or situations where refrigeration is not available. Write the date you first removed the pen from the refrigerator on the designated space on the outer carton to track the storage period.
• Do not return to refrigerator: Once ANDEMBRY has reached room temperature, do not return it to the refrigerator. If it has been stored at room temperature for more than 2 months, discard the pen safely.
• Keep out of reach of children: Store ANDEMBRY in a secure location where children cannot access it.
• Check expiration date: Do not use ANDEMBRY after the expiration date printed on the outer carton and pen label after “EXP.” The expiration date refers to the last day of the stated month.
• Inspect before use: Before each injection, visually inspect the solution through the viewing window. The solution should be slightly opalescent to clear, and brownish-yellow to yellow in color. Do not use ANDEMBRY if the solution contains particles, has changed color, or if the pen appears damaged.
• Single use only: Each pre-filled pen is intended for single use. Do not attempt to reuse a pen.
• Proper disposal: After use, place the pen immediately into an approved sharps disposal container. Do not dispose of used pens in household waste. Ask your pharmacist about the correct method of disposal in your area.

When traveling with ANDEMBRY, you may use the room temperature storage option (up to 25 °C for up to 2 months). For longer trips or warmer climates, consider using an insulated bag with a cold pack. Avoid exposing the medication to excessive heat, direct sunlight, or freezing temperatures. ANDEMBRY should be carried in hand luggage rather than checked baggage during air travel to avoid extreme temperature fluctuations in the cargo hold.

What Does ANDEMBRY Contain?

Understanding what your medication contains is important, particularly if you have known allergies or sensitivities to specific pharmaceutical ingredients. Below is a detailed breakdown of the composition of ANDEMBRY.

Active Ingredient

The active substance is garadacimab, a fully human IgG4 monoclonal antibody. Each pre-filled pen contains 200 mg of garadacimab in 1.2 mL of solution, corresponding to a concentration of approximately 167 mg/mL. Garadacimab selectively binds to coagulation factor XII and prevents its activation to factor XIIa, thereby reducing bradykinin production through the kallikrein-kinin pathway.

Inactive Ingredients (Excipients)

Appearance and Pack Sizes

ANDEMBRY is supplied as a slightly opalescent to clear, brownish-yellow to yellow solution for injection in a single-use pre-filled pen containing 1.2 mL of solution. ANDEMBRY is available as a single pack containing one pre-filled pen, or as a multipack containing three cartons with one pre-filled pen in each. Not all pack sizes may be marketed in every country.

Marketing Authorization Holder and Manufacturer

ANDEMBRY is manufactured and marketed by CSL Behring GmbH, located at Emil-von-Behring-Strasse 76, D-35041 Marburg, Germany. CSL Behring is a global biopharmaceutical company with a long history of developing and manufacturing therapies for rare and serious diseases, particularly those involving the complement and coagulation systems. ANDEMBRY is approved in the European Union and is being progressively registered in additional countries worldwide.