Icatibant Injection - Approved Drug for Hereditary Angioedema

Overview:

Hereditary angioedema (HAE) abrupt attacks are treated with Icatibant injection. Icatibant prevents a chemical in the body that HAE patients' bodies employ to produce edema, inflammation, and pain. This medication does not treat HAE. Icatibant is given as an injectable, and it functions by preventing specific bodily processes that can cause these swelling episodes. It assists in symptom relief during a HAE attack. The US Food and Drug Administration (FDA) approved Icatibant injection on August 25, 2011. Icatibant Injection is an approved medication for adults with hereditary angioedema experiencing acute attacks.

Drug Group:

Icatibant is a drug that belongs to the bradykinin B2 receptor antagonist class. It is a member of the class of medications known as "Kinin receptor antagonists." Hereditary angioedema (HAE), a rare genetic ailment characterized by recurrent episodes of swelling in numerous body areas, including the skin and mucous membranes, is this medicine's main condition. Icatibant functions by inhibiting the actions of bradykinin, a chemical in the body that contributes to swelling and other HAE symptoms. Icatibant helps to treat acute HAE attack symptoms like swelling, pain, and discomfort by preventing bradykinin's action at the B2 receptors, giving patients with this condition much-needed respite.

Dosages:

The most common form of Icatibant is a pre-filled syringe that contains a single dose of 30 milligrams (mg) of the medication.

Adults - intravenously 3 milliliters (mL) or 30 milligrams (mg). If the symptoms persist or return after six hours, the doctor could prescribe another prescription or instruct the patient to take one. Use no more than three doses in 24 hours.

Children - A doctor should determine the use and dosage.

For Patients:

What Is Hereditary Angioedema?

An uncommon genetic condition known as hereditary angioedema (HAE) is characterized by repeated bouts of severe swelling under the skin and in the mucous membranes. Angioedema, the medical term for this swelling, often impacts the face, limbs, digestive system, and airway. A C1 esterase inhibitor protein shortage or malfunction, which results in the uncontrolled activation of specific complement system enzymes, is the root cause of HAE. These assaults can be excruciatingly painful and, if they affect the airway, even fatal. HAE is hereditary, meaning families may pass it down through the generations.

What Is the Management of Hereditary Angioedema?

Hereditary Angioedema (HAE) is often treated with acute attack therapies and long-term prevention measures.

Long-term Preventive Measures:

• Medication: To stop HAE attacks, patients frequently use drugs called Kallikrein inhibitors or C1 inhibitor replacement treatment.

• Trigger Identification: The frequency of attacks can be decreased by recognizing and avoiding triggers, such as specific drugs or stress.

• Regular Monitoring: Visiting a professional regularly to monitor the condition and modify treatment as necessary.

Acute Attack Treatments:

• C1 Inhibitor Replacement: To treat symptoms of an acute attack, doctors may prescribe C1 Inhibitor Replacement Therapy or other drugs like Icatibant or Ecallantide.

• Supportive Care: Giving comfort measures during severe episodes, such as managing discomfort, keeping hydrated, and keeping an eye on breathing and the airway.

Patient Education: Educate the patient on how to spot the early symptoms of an attack and how to utilize medication properly.

Psychological Support: Providing counseling, as having HAE, can be emotionally taxing due to the episodes' unpredictable nature.

Emergency Plan: Establishing an emergency plan with medical professionals and ensuring patients have access to the required medications and medical care in case of a serious attack.

Genetic Counseling: Individuals with HAE can benefit from genetic counseling to better understand their hereditary risk and make educated decisions regarding family planning.

How Does Icatibant Injection Work?

The body overproduces bradykinin during an attack in a person with HAE. Swelling and inflammation are brought on by bradykinin's expansion and leakiness of blood vessels. Icatibant is a bradykinin receptor antagonist, a class of drugs. It targets and turns off the body's bradykinin receptors selectively. It functions by preventing the action of the hormone bradykinin, which produces swelling by causing blood vessels to enlarge and become leaky.

Icatibant blocks the actions of bradykinin, which include vasodilation (widening of blood vessels) and enhanced vascular permeability (leakiness), by binding to these bradykinin receptors. Icatibant thus assists those suffering from HAE attacks by reducing edema and accompanying symptoms. It is vital to remember that Icatibant is commonly injected under the skin.

How Should the Drug Be Taken?

• Healthcare providers or patients themselves should adhere to particular instructions when administering Icatibant. For subcutaneous injection, the drug is normally given in pre-filled syringes. Establishing a clean, sterile atmosphere and properly washing their hands before administering is important.

• Choose an injection site, typically in the abdomen, and clean it with an alcohol swab before starting. When removing the Icatibant syringe from its packaging, look for any indications of contamination or damage. Remove the needle cap, hold the syringe like a pen or dart, and insert the needle at a 90-degree angle into the skin. Then, gently and steadily push the plunger down to inject the drug.

• After injection, apply mild pressure with a cotton ball or piece of sterile gauze to the injection site to reduce bleeding. Use a sharp container and dispose of the discarded syringe according to safety regulations. It is essential to record the injection time and location for future use.

• Patients should receive sufficient self-administration instruction and seek medical attention immediately after taking Icatibant to monitor their condition and guarantee the necessary follow-up care.

• For a safe and efficient course of therapy, Icatibant injection for HAE requires prepping the injection site, administering the medication subcutaneously, and adhering to proper disposal protocols while following physician advice.

What Are the Benefits of Using Icatibant Injection for Hereditary Angioedema?

• Self-Administration: It is designed for self-administration, allowing patients to treat themselves at home reducing the need for frequent hospital visits.

• Rapid Relief: Icatibant can provide quick relief from acute HAE attacks by blocking the action of bradykinin, a substance responsible for the swelling.

• Reduced Symptoms: Icatibant can help reduce the severity and duration of HAE attacks, improving a patient's overall quality of life.

• Prevention of Airway Obstruction: By promptly treating swelling in the throat and other airway-related symptoms, Icatibant can prevent life-threatening situations.

• Convenience: Its easy-to-use pre-filled syringe format makes it accessible for patients to administer when needed.

• Minimal Side Effects: Icatibant generally has few side effects, making it a well-tolerated option for managing HAE.

What Must the Patient Inform the Doctor Before Taking Icatibant Injection?

Before taking an Icatibant injection, patients should inform their doctor about the following:

• Allergies: Let the doctor know if they have allergies to Icatibant or any other drugs, chemicals, or foods.

• Medical History: Be sure to provide all relevant medical information, particularly if the patient has a history of angioedema, liver, renal, or cardiac illness.

• Medication Interactions: Icatibant may be affected by any medications they are already taking, including supplements, herbal remedies, and dietary fiber.

• Breastfeeding: If breastfeeding or planning a pregnancy, talk to their doctor about the risks and advantages of Icatibant.

• Recent Surgery: Mention any recent surgeries they have had or plan to have because Icatibant may influence bleeding.

• Medical Conditions: If they have additional medical conditions, such as diabetes or high blood pressure, let the doctor know.

• Prior angioedema: Describe any prior angioedema events they may have had, including the medications they took to treat them.

• Any New Symptoms: Contact the doctor immediately if they notice any new symptoms or changes in their health.

The doctor will use this information to determine whether Icatibant is the right course of therapy and whether any modifications or safety measures are required.

What Are the Side Effects of Using Icatibant Injection?

• Injection site reactions.

• Headache.

• Nausea.

• Abdominal pain.

• Diarrhea.

• Fatigue.

• Dizziness

• Rash.

• Bleeding.

• Blistering.

• Burning.

• Coldness.

• Discoloration of the skin.

• The feeling of pressure.

• Hives.

• Infection.

• Numbness.

• Scarring.

• Soreness.

• Stinging.

• Swelling.

• Tenderness.

• Tingling.

• Ulceration.

For Doctors:

Description:

Hereditary angioedema (HAE) abrupt attacks are treated with Icatibant injection. Icatibant prevents a chemical in the body that HAE patients' bodies employ to produce edema, inflammation, and pain. This medication does not treat HAE. A prescription from a doctor is required to purchase this medication.

Icatibant is a bradykinin type 2 (B2) receptor-selective competitive antagonist. It is a synthetic decapeptide with five non-proteinogenic amino acids and a structure resembling bradykinin.

Therapeutic Uses of Icatibant Injection:

Hereditary angioedema (HAE), a rare genetic condition characterized by repeated, severe swelling of numerous body areas, is largely treated with Icatibant injection, a bradykinin B2 receptor antagonist. Icatibant reduces the symptoms of HAE by inhibiting the bradykinin receptor, especially in acute bouts of edema in the skin, gastrointestinal tract, or respiratory system. It quickly relieves pain and swelling when administered subcutaneously, enhancing the patient's quality of life. Although HAE is the main treatment target, ongoing research examines possible applications in additional ailments linked to bradykinin dysregulation, such as cardiovascular and inflammatory disorders. This broadens the therapeutic potential of the drug.

Dosage Forms and Strengths:

Icatibant is normally sold as an injection in syringes that have already been filled. Icatibant injection typically has a strength of 30 mg per 3.2 mL in a pre-filled syringe for subcutaneous delivery. 30 mg subcutaneously administered once in the abdomen region; if the response is insufficient or symptoms return, repeat every 6 hours

Maximum daily dose: 90 mg

Dosage and Administration:

The Icatibant dose and administration may change depending on the specific disease and personal patient characteristics. However, a 30 mg subcutaneous injection is typical for people with HAE. It is crucial to adhere to the healthcare provider's recommendations and any dosing schedule that may be given. Icatibant injections should be given at most three times in 24 hours. Only one usage is permitted for each prefilled syringe. Even if there is medication inside, discard it after one use.

Indications:

Hereditary angioedema (HAE), a rare genetic illness that causes swelling of numerous body areas, including the face, mouth, and limbs, is treated with the Icatibant.

The following are some uses for Icatibant injection:

• Icatibant is recommended for treating acute attacks in individuals with hereditary angioedema (HAE). During a HAE episode, it aids in the relief of symptoms like swelling, pain, and discomfort.

• It is designed to treat acute episodes when they happen rather than prevent or prophylactic routine HAE attacks.

Contradictions:

Contraindications are conditions or situations where a particular treatment should not be used due to potential risks. While Icatibant is generally safe and effective for many people, it may be contraindicated in the following situations:

• Hypersensitivity: Individuals with a known hypersensitivity or allergic reaction to Icatibant or its components should not use this medication.

• Pregnancy and Breastfeeding: The safety of Icatibant during pregnancy and breastfeeding has not been well studied. Therefore, it is generally avoided unless the potential benefits outweigh the risks and a healthcare provider determines it's necessary.

• Severe Cardiovascular Disease: Icatibant can cause a transient increase in blood pressure. Individuals with severe cardiovascular disease or uncontrolled hypertension may need to avoid this medication.

• Pediatric Use: Icatibant's safety and efficacy in children under 18 may not be established, so its use in this age group is generally avoided.

• Renal Impairment: Patients with severe renal impairment may require dosage adjustments or should be closely monitored when using Icatibant.

• Hepatic Impairment: People with severe hepatic (liver) impairment may also need dosage adjustments or close monitoring when using Icatibant.

Precautions:

• Do not inject Icatibant into a painful, swollen, or bruised area.

• Use only the needle that is supplied with this medicine.

• If they still have symptoms of angioedema after the first injection, they may use another injection after at least 6 hours.

What Are the Adverse Reactions of Icatibant Injection?

• Injection site reactions (pain, redness, swelling).

• Gastrointestinal symptoms (nausea, diarrhea, vomiting).

• Headache.

• Fever.

• Dizziness.

• Rash.

What Are the Pharmacological Aspects of Icatibant Injection?

Mechanism of action:

Icatibant is a competitive antagonist with a similar affinity to bradykinin that targets the bradykinin B2 receptor. C1-esterase-inhibitor, a crucial regulator of the Factor XII or kallikrein proteolytic cascade that results in bradykinin production, is either absent or dysfunctional in hereditary angioedema. The vasodilator bradykinin causes the localized swelling, inflammation, and discomfort that characterize HAE. Icatibant cures the clinical signs of an acute, episodic incident of HAE by preventing bradykinin from binding to the B2 receptor.

Pharmacodynamics:

After a bradykinin challenge, intravenous injection of Icatibant caused the development of bradykinin-induced hypotension, vasodilation, and reflex tachycardia to be dose- and time-dependently inhibited in healthy volunteers.

For six to eight hours after the end of the infusion, Icatibant intravenous dosages of 0.4 and 0.8 mg/kg reduced responsiveness to the bradykinin challenge. Based on exposure-response analysis, a subcutaneous dose of 30 mg Icatibant is anticipated to be efficacious against the bradykinin challenge for at least 6 hours.

These data's clinical relevance is uncertain. In a randomized, placebo- and active-controlled, four-period comprehensive QT research including 72 healthy volunteers, the effects of Icatibant 30 and 90 mg following a single subcutaneous injection on QTc interval were assessed.

The biggest placebo-adjusted, baseline-corrected QTc based on individual correction method (QTcI) in a study with a shown capacity to detect minor effects has an upper bound of the one-sided 95 percent confidence interval below 10 ms(millisecond), which is the regulatory threshold. The dose of 90 mg is sufficient to simulate the clinical scenario with high exposure.

Pharmacokinetics:

Studies employing intravenous and subcutaneous injections to healthy volunteers and patients have investigated the pharmacokinetics of Icatibant. Patients with HAE have a pharmacokinetic Icatibant profile comparable to that of healthy persons.

Following subcutaneous injection of 30 mg of Icatibant, its absolute bioavailability is around 97 percent. Healthy volunteers received a single 30 mg dosage of Icatibant subcutaneously, and after around 0.75 hours, a mean ( standard deviation) maximum plasma concentration (Cmax) of 974 280 ng/mLng (nanograms)/mL (milliliters) was noted. After a single 30 mg dose, the mean area under the concentration-time curve (AUC0-) was 2165 568 ng/hr/mL(nanograms per milliliter per hour), and there was no sign of Icatibant accumulation after three 30 mg doses given six hours apart.

Following subcutaneous administration, the plasma clearance was 245 58 mL/min (milliliter per minute), the volume of distribution at steady state (Vss) was 29 8.7 Liters (l), and the mean elimination half-life was 1.4 0.4 hours. Less than 10] percent of the dose of Icatibant is excreted as an unmodified medication because proteolytic enzymes extensively degrade it to inactive metabolites predominantly excreted in the urine. The primary cytochrome P450 (CYP) isoenzymes (CYP 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4) are not inhibited by Icatibant, which is not destroyed via oxidative metabolic pathways.

Drug Interactions:

Icatibant has severe interactions with no drugs.

Icatibant has serious interactions with the following drugs.

• Axicabtagene Ciloleucel.

• Brexucabtagene Autoleucel.

• Ciltacabtagene Autoleucel.

• Idecabtagene Vicleucel.

• Lisocabtagene Maraleucel.

• Tisagenlecleucel.

Icatibant has moderate interactions with the following drugs.

• Benazepril.

• Captopril.

• Enalapril,

• Fosinopril.

• Isavuconazonium Sulfate.

• Moexipril.

• Ofatumumab SC.

• Ozanimod.

• Perindopril.

• Quinapril.

• Ramipril.

• Siponimod.

• Trandolapril.

• Ublituximab.

Icatibant has minor interactions with no other drugs.

Use of Icatibant Injection in specific populations:

• Pregnancy: Much research has not been done on its safety during pregnancy. It is important to review the potential risks and advantages of using Icatibant with the doctor if a patient is pregnant or intends to become pregnant and needs treatment. They can offer advice based on their particular circumstances and, if necessary, consider alternative treatments.

• Lactation: The clinical investigations that resulted in the approval of the medication did not establish the safety of Icatibant in women who are expecting or nursing. Formula milk should be utilized if a patient needs prompt treatment for a swelling attack and cannot wait six or more hours to feed her baby.

• Pediatrics: Icatibant is generally prescribed to adults to treat the uncommon genetic disorder known as hereditary angioedema (HAE). A healthcare provider with experience treating pediatric HAE situations should decide its use in children because its safety and effectiveness in pediatric patients may differ. It is preferable to seek advice from a physician or a specialist in pediatric allergology or immunology if they have particular queries or concerns regarding administering Icatibant to children.

• Geriatrics: Although it has not been examined as thoroughly in geriatric populations (older adults) as in younger persons, older people with HAE may be prescribed an Icatibant injection when a healthcare professional deems it necessary. Care should be taken while treating the elderly because they typically have a greater frequency of infections.