Omalizumab - Indication, Dosage, Precautions, Side Effects, and Pharmacological Aspects

Drug Overview:

If you are suffering from allergic asthma, you can take an Omalizumab injection. Allergic asthma is asthma. It happens when you are allergic to pollen, dust mites, and animal dander. If your asthma is not controlled even after taking other asthma medicines, you can take Omalizumab. This drug will help you get free from asthma symptoms. The FDA (Food and Drug Administration) approved Omalizumab for moderate-to-severe asthma on June 20, 2003.

Dose Form and Strength:

Subcutaneous Injection: 150 mg per site.

For asthma patients, the dose is 75 to 375 mg every two or four weeks.

For chronic idiopathic urticaria, the dose is 150 to 300 mg every four weeks.

For Patients:

How Is Omalizumab Used for Allergic Asthma?

You can understand allergic asthma from its name. You may suffer from asthma when you have allergies. When you take in the allergens, your immune system will start shouting. Imagine you are suffering from allergic asthma and are exposed to these allergens (such as pollen, pet dander, dust mites, or mold). This can change your immune system, waking up the inflammatory cells and ultimately causing airway narrowing. You may have symptoms like wheezing, coughing, shortness of breath, and chest tightness.

The monoclonal antibody class is for Omalizumab. The Omalizumab injection is available as a prefilled syringe and as a powder that requires mixing with water for subcutaneous administration (under the skin). You can take this injection once every two or four weeks to treat allergic asthma or nasal polyps. The injection dose is based on your body mass index.

How Should Omalizumab Be Used?

If you have chronic hives (raised, itchy welts on the skin), take this injection once every four weeks. You should not take this injection by yourself. Your doctor will give it to you. The treatment will be planned based on your body's response to the medicine and your health.

If you want to take this injection yourself or have someone else inject it, you must follow your doctor's instructions. Your doctor will tell you how to inject the medication properly. Reading the provided written instructions for use is also recommended.

When you remove the drug from the refrigerator, you should keep it outside so that it can set at room temperature. The injection should be given within four hours of removing it from the refrigerator. You should also keep this drug away from sunlight for 15 to 30 minutes. Microwave, use hot water, or other methods should not be used to warm the medication.

Before injecting, just check the expiration date on the prefilled syringe packaging. When holding the syringe with the covered needle downward, the liquid should be clear or slightly pale in color, without cloudiness, discoloration, lumps, or particles. Any issues with the package or syringe should be addressed with the pharmacist before injection.

Some points to remember: The cap on the prefilled syringe should only be removed right before injection and should not be replaced afterward. If the syringe falls on the floor, you should not use it. Injection sites can be the front of the thighs, various areas on the stomach (excluding the navel and its 2-inch vicinity), and, if given by another person, the outer part of the upper arms. You should not inject it when you have damaged skin, moles, or bruises. You should shift the injection spot at least 1 inch away from previous sites to prevent discomfort.

What Are the Things to Inform the Doctor About Before Taking the Drug?

Before using Omalizumab, you should tell your doctor about the following points:

• Before taking the Omalizumab injection, you should tell your doctor about any allergies, other medications, or any components present in the Omalizumab injection. If opting for the prefilled syringe, you should inform your doctor if you are allergic to rubber or latex.

• You should inform your doctor about the medications and supplements you are taking. The drug may interact and cause complications.

• If you have a history of cancer, you should tell your doctor about it.

• If you are pregnant, planning for conception, or breastfeeding, it is important to discuss this with your doctor. If you get pregnant while taking the Omalizumab injection, you should immediately go to your doctor and tell them about it.

• If you have any parasitic infections, like hookworm and roundworm, you should tell your doctor. Your infection will increase if you take this drug with an Omalizumab injection.

What Are the Side Effects of Omalizumab?

The side effects of Omalizumab are as follows:

Pain, redness, swelling, warmth, burning, bruising, hardness, or itching at the injection site of Omalizumab.

• Pain, particularly in joints, arms, or legs.

• Tiredness.

• Ear pain.

• Headache.

• Nausea.

• Swelling within the nose, throat, or sinuses.

• Stomach pain.

• Nosebleeds.

If you are having severe side effects, you should see your doctor.

• Fever, muscle aches, rash, and swollen glands occur within one to five days of an Omalizumab injection.

• Shortness of breath.

• Coughing up blood.

• Skin sores.

• Intense pain, numbness, and tingling are experienced in the hands and feet.

You may experience severe side effects like chest pain, heart attacks, blood clots in the lungs or legs, temporary instances of one-sided body weakness, slurred speech, and alterations in vision. You might have cancer after taking this injection. But, no proven studies show the link between Omalizumab and cancer.

Drug Dosage and Administration

Missed Dose:

If you miss your dose, you should take it at that time. Then, take the next dose. But, if you remember at the time of your next dose, then you should not take the missed dose. For this, you have to go to your doctor.

Overdose:

In the case of overdose, you should immediately call your doctor. You should also check for abnormal signs and symptoms.

Storage and Disposal:

The medication should be stored in a safe place, protected from light, and kept tightly closed. It also should be kept away from your children. Omalizumab injection should be stored in a refrigerator; however, it should not be frozen. You should see the expiry date; if it has expired or is no longer required, it should be properly discarded. You should dispose of the needle in the container.

For Doctors:

Indication:

Omalizumab injection is indicated for:

• If your kid is six years and above with moderate to severe persistent asthma and shows a positive skin test along with symptoms, which are not treated with medicines, then your doctor will inject you with Omalizumab

• If you are an adult or adolescent aged 12 and above with chronic idiopathic urticaria, you can go for Omalizumab. If your condition is not treated even after taking antihistamine drugs, you can go for this drug.

Dose:

The recommended daily dose is a subcutaneous injection of 75 to 375 mg (milligrams) every two or four weeks.

What Are the Pharmacological Aspects of Omalizumab?

Mechanism of Action:

Asthma:

Omalizumab acts by impeding the interaction between immunoglobulin E (IgE) and the high-affinity IgE receptor found on mast cells and basophils. The allergic response mediators will activate if you suffer from an allergy. The drug will reduce the presence of IgE and the release of allergic response mediators. The drug lowers basophil cells and allergic receptors if you suffer from atopy.

Pharmacokinetics:

The bioavailability of Omalizumab is 62 percent. In adult asthmatic folks and even those who take a single dose of this drug, the drug will be gradually absorbed. Similar peak serum concentrations were observed for patients with chronic idiopathic urticaria (CIU) after a single SC dose. The pharmacokinetics of Omalizumab were linear at doses greater than 0.5 mg/kg (milligrams per kilogram).

In asthma patients, following multiple doses of Omalizumab. In CIU patients, Omalizumab's pharmacokinetics remained linear, ranging from 75 mg to 600 mg when administered as a single subcutaneous dose. With repeat dosing from 75 to 300 mg every four weeks, the trough serum concentrations of Omalizumab increased proportionally with the dose levels.

In vitro studies showed that Omalizumab formed complexes with IgE of limited size, and no precipitating or excessively large complexes were observed either in vitro or in vivo. Distribution studies in Cynomolgus monkeys indicated no specific uptake of 125I-labeled Omalizumab by any organ or tissue. The apparent volume of distribution of Omalizumab after SC administration in asthma patients was 78 ± 32 mL/kg (milliliters per kilogram), and the distribution profile in CIU patients resembled that of asthma patients based on population pharmacokinetics.

Omalizumab clearance involves IgG clearance mechanisms facilitated by specific binding and complex formation with its target ligand, IgE. Liver elimination of IgG involves degradation within the liver's reticuloendothelial system (RES) and endothelial cells, with intact IgG also excreted in bile.

Omalizumab: IgE complexes were eliminated through interactions with Fcγ receptors within the RES at rates generally faster than IgG clearance. In asthma patients, Omalizumab's serum elimination half-life averaged 26 days, with an apparent clearance averaging 2.4 ± 1.1 mL/kg/day. Doubling body weight roughly doubled the apparent clearance. In CIU patients at steady state, Omalizumab's serum elimination half-life averaged 24 days, and the apparent clearance averaged 240 mL/day (equivalent to 3.0 mL/kg/day for an 80 kg patient).

What Are the Clinical Studies of Omalizumab?

Adult and Adolescent Patients 12 Years of Age and Older:

The safety and effectiveness of Omalizumab were assessed through three randomized, double-blind, placebo-controlled, multicenter trials. These trials included individuals aged 12 to 76 years with moderate to severe persistent asthma, according to NHLBI (National Heart, Lung, and Blood Institute) criteria, lasting at least one year. For a perennial aeroallergen, the skin test is positive. Omalizumab dosage was determined in all trials based on the individual's body weight and baseline serum total IgE concentration. Patients needed a baseline IgE level between 30 and 700 IU/mL (international units per milliliter) and a body weight not exceeding 330 pounds (150 kg).

A dosing table guided the administration to deliver at least 0.016 mg/kg/IU (IgE/mL) of Omalizumab or an equivalent volume of placebo during each 4 weeks. The highest permissible Omalizumab dose within 4 weeks was 750 mg.

Across the three trials, an exacerbation was defined as a deterioration of asthma necessitating systemic corticosteroid treatment or doubling the baseline inhaled corticosteroid (ICS) dose. Most exacerbations were managed in an outpatient setting, with the majority being addressed using systemic steroids. Hospitalization rates did not differ significantly between patients treated with Omalizumab and those receiving a placebo. Notably, the overall hospitalization rate remained low. Among individuals encountering exacerbations, the severity distribution of these events was comparable between the treatment groups.

What Are the Warnings and Precautions of Using Omalizumab?

The following precautions should be taken:

• Anaphylaxis: Instances of anaphylaxis have been documented following the administration of Omalizumab, both during premarketing clinical trials and through post-marketing spontaneous reports. These occurrences have presented with symptoms such as bronchospasm, hypotension, urticaria, syncope, and angioedema of the throat or tongue, some of which have posed life-threatening risks.

• Malignancy: Malignant neoplasms were identified in 20 out of 4127 Omalizumab-treated patients (0.5 percent) as opposed to 5 out of 2236 control patients (0.2 percent) during clinical studies involving adults and adolescents aged 12 years and above with asthma and other allergic disorders. The potential impact of extended exposure to Omalizumab or its usage in patients at a higher risk for malignancy (such as the elderly or current smokers) remains unknown.

• Acute Asthma Symptoms: There is no evidence that Omalizumab helps in acute asthmatic flare-ups. Omalizumab should not be used to treat status asthmaticus or acute bronchospasm.

• Corticosteroid Reduction: If you are taking Omalizumab treatment with systemic or inhaled corticosteroids, you should not take that steroid.

• Eosinophilic Conditions: Rarely, asthma patients on Omalizumab may develop significant systemic eosinophilia, which may occasionally accompany clinical signs of vasculitis associated with Churg-Strauss syndrome, a disease that is frequently managed with systemic corticosteroid treatment. These occurrences have typically, but not always, been linked to the cessation of oral corticosteroid medication.

• Rash, Fever, and Arthralgia: Following the initial or subsequent injections of Omalizumab, some patients have reported a constellation of signs and symptoms, including arthritis or arthralgia, rash, fever, and lymphadenopathy, which usually appear one to five days later. Some individuals' indications and symptoms returned after subsequent dosages. These signs and symptoms are comparable to those experienced by individuals with serum sickness, despite the absence of circulating immune complexes or a skin biopsy consistent with a Type III response in these situations. If a patient exhibits this combination of symptoms, doctors should discontinue the patient's use of Omalizumab.

• Parasitic Infection: While using Omalizumab, monitor individuals who are very susceptible to helminth infection. The period of monitoring for helminth infections after ceasing Omalizumab medication cannot be determined due to a lack of evidence.

Use in Specific Population:

• Pregnancy: The available data concerning the use of Omalizumab in pregnant women are inadequate to provide conclusive information regarding associated drug risks. Monoclonal antibodies, such as Omalizumab, exhibit a linear transport pattern across the placenta as pregnancy advances. Consequently, the potential impact on a developing fetus will likely be more pronounced during the second and third trimesters. It is classified as a pregnancy category C drug, which means it should only be used when it is necessary.

  • Reproductive studies conducted in Cynomolgus monkeys did not uncover any evidence of harm to the fetus when subjected to subcutaneous doses of Omalizumab that were approximately ten times the maximum recommended human dose (MRHD), as indicated in animal data.

• Lactation: There is no information on Omalizumab's presence in human milk. IgG1 kappa is a human monoclonal antibody found in Omalizumab, and human milk contains immunoglobulin G (IgG). Before starting the medication, the developmental and health advantages of nursing should be taken into account, as well as the mother's clinical requirement for Omalizumab and any potential negative effects of Omalizumab or the underlying maternal disease on the breastfed infant.

• Pediatric Population: The safety and effectiveness of Omalizumab in children with asthma under the age of six have not yet been studied. However, clinical trial results show that patients on Omalizumab saw a statistically significant decrease in the risk of exacerbations for children aged six to 12.

• Geriatric Population: There is insufficient data to support that patients 65 and older respond differently from younger patients while receiving treatment from Omalizumab.

Key Takeaway/ Note from Icliniq

Omalizumab is a drug that can be given to help you with allergic asthma. The doctor will inject this drug to calm down your allergic asthma symptoms. You should take this drug under the supervision of your doctor.