Omalizumab

Omalizumab belongs to the Anti-Immunologlobulin E Antibody Pharmacological class.

Omalizumab is approved for the treatment of severe asthma and chronic idiopathic urticaria.

The bioavailability after absorption is found to be 62%, with its peak plasma time of 7-8 days. The volume of distribution of Omalizumab was found to be 78 +/- 32 mL/kg. The excretion occurs mainly through Bile and the total body clearance was found to be 2.4 +/- 1.1 mL/kg/day.

The common side effects associated with Omalizumab are headache, dizziness, nausea, pain, itching, swelling at the site of Injection, ear pain, etc.

Omalizumab is available in the form of subcutaneous injection in the form of prefilled syringes and powder to be reconstituted.

Omalizumab is available in India, U.K., U.S., Canada, India, E.U., China, Japan, and Australia.

Omalizumab binds to IgE and hence prevents binding of IgE to FcRI i.e. high-affinity IgE receptor, on the basophils and mast cells, thereby reducing the amount of free IgE that is available to trigger the cascade of allergic reactions.

Treatment with Omalizumab inhibits IgE-mediated inflammation, which has been evidenced by the presence of reduced blood and tissue eosinophils and inflammatory mediators, including IL4, IL-5, and IL-13 by innate cells, adaptive cells, and non-immune cells.

Omalizumab hence leads to relief from severe asthma and chronic idiopathic urticaria.

Omalizumab onset of action is found to be 90 minutes, and the duration of action is around 7-8 days.

Omalizumab is available in Subcutaneous Injection.

Subcutaneous Preparation

Lyophilized powder (vials)

• Vials are reconstituted with 1.4 mL sterile water for injection into a 3-mL syringe equipped with a 1-inch, 18-gauge needle which results in the solution of 150 mg/1.2 mL
• The vial is placed upright on a flat surface and using a standard aseptic technique, the needle is inserted and sterile water for injection is injected directly onto the product
• The vial is kept upright and gently swirled for ~1 minute to evenly wet powder. Shaking should be avoided
• The vial is gently swirled for 5-10 seconds at ~5 minutes intervals until there are no visible gel-like particles in the solution. The lyophilized product takes about 15-20 minutes to completely dissolve. If the case contents of the vial do not dissolve completely in 40 minutes, discard the product.
• The reconstituted solution will appear clear or slightly opalescent and somewhat viscous. It may have a few small bubbles or foam around the edge of the vial
• To obtain the full 1.2-mL dose is withdrawn with a new needle and 3-mL syringe all of the product from the vial before any air or excess solution from the syringe is expelled.

Prefilled syringes

• Each carton consists of 1 syringe
• If the cartoon says it is expired, discard the product
• The carton is removed from the refrigerator and set aside for at least 15-30 minutes to calibrate to room temperature.
• The syringe should not be allowed to become hot or speed up the warming process in any way, and the syringe should not be kept in a microwave or in warm water
• The syringe is visually inspected so as to ensure that the solution should be clear to slightly opalescent and colorless to pale brownish-yellow. If the liquid is cloudy it is discolored or contains foreign particles

Omalizumab can be used in the treatment of:

• Severe Asthma
• Chronic Idiopathic Urticaria

Omalizumab can help to relieve symptoms of Severe Asthma and Chronic Idiopathic Urticaria.

Omalizumab is approved for use in the following clinical indications:

• Severe Asthma
• Chronic Idiopathic Urticaria (CIU)
• Nasal Polyps

Asthma

Moderate-to-severe persistent -150-375 mg SC q2-4Weeks

Chronic Idiopathic Urticaria

Chronic Idiopathic Urticaria (CIU) -150-300 mg SC q2-4Weeks

Nasal Polyps

Add-on maintenance treatment of nasal polyps in adults aged ≥18 years who have an inadequate response to nasal corticosteroids-75-600 mg SC q2-4weeks

Single-dose prefilled syringe

• 75mg/0.5mL
• 150mg/mL

Lyophilized powder for reconstitution

• 150mg/vial
• 125mg/mL after reconstitution

Subcutaneous Injection: Pre-Filled Syringe, Lyophilized Powder for Reconstitution.

Maintaining health and smoking cessation is a must.

Avoid or restrict or limit the usage of caffeine as it might lead to the risk of nausea, palpitations, nervousness, rapid heartbeat, etc.

Diet containing refined and high energy-dense foods, low fiber, food with a high glycemic index, saturated and trans fat food, red and processed meat, added sugar, salt, preservatives, low antioxidants, and vitamins needs to be restricted.

The dietary restrictions should be individualized as per the patient's requirements.

Omalizumab may be contraindicated in the condition of Hypersensitivity to Omalizumab or to the ingredients of the medication.

The treating physician should closely monitor the patient and keep pharmacovigilance as follows:

• Anaphylaxis: Administration should be done only in a healthcare setting prepared to manage anaphylaxis that can be life-threatening and patients should be observed for an appropriate period of time after administration.

• Malignancy: Malignancies had been reported to be observed in clinical studies.

• Acute Asthma Symptoms: Not to be used for the treatment of acute bronchospasm or status asthmaticus.

• Corticosteroid Reduction: Corticoids should not be abruptly discontinued upon initiation of Omalizumab therapy.

• Fever, Arthralgia, and Rash: Use of Omalizumab should be stopped if patients develop signs and symptoms similar to serum sickness.

• Eosinophilic Conditions: During the eosinophilic condition one should be watchful for the conditions such as vasculitic rash, and worsening pulmonary symptoms, especially upon reduction of oral corticosteroids

Avoid alcohol usage while on Omalizumab Medication as alcohol can worsen the effects of any underlying disease condition.

It is not known whether Omalizumab is excreted in human milk. Therefore, Omalizumab should be used during nursing only if the potential benefits outweigh the potential risks associated with newborn growth. Immunoglobulins G is present in human milk and therefore it is expected that Omalizumab might be present in human milk. Available data from the studies in non-human primates have shown excretion of Omalizumab into milk The study with 154 infants who had been exposed to Omalizumab during pregnancy and breastfeeding did not indicate any adverse effects on the breastfed infant. As Omalizumab is immunoglobulin and can undergo proteolysis in the liver therefore no adverse effect can be anticipated to occur.

Pregnancy Category C.

There is no well-documented experience of clinical studies in pregnant women. Omalizumab should only be used during pregnancy if the potential benefits outweigh the risks associated with the fetus’s growth. Omalizumab is transported across the placenta in a linear fashion as pregnancy progresses; therefore, potential risks to a fetus are likely to be greater during the second and third trimesters of pregnancy. In the US population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies was found to be 2 to 4% and 15 to 20%, respectively.

No sufficient scientific evidence is traceable regarding the use and safety of Omalizumab in concurrent use with any particular food.

The adverse reactions related to Omalizumab can be categorized as:

Common

• Bruise or pain at the site of injection
• Vomiting
• Headache
• Hoarseness
• Leg pain

Less common

• Muscle pain or stiffness
• Pain in the joints
• Stomach pain
• Blistering, or reddening of the skin
• Difficulty in moving

Rare

• Malignant tumor
• Puffiness or swelling of the eyelids face and tongue
• Tightness in the chest
• Unusual tiredness or weakness
• Cough
• Difficulty with swallowing
• Dizziness
• Fast heartbeat
• Hives, itching, or skin rash

The clinically relevant drug interactions of Omalizumab are briefly summarized here:

No drug interaction studies have been done with Omalizumab. In patients suffering with asthma, the concomitant use of Omalizumab and allergen immunotherapy has not been evaluated. In patients with Chronic Idiopathic Urticaria, the use of Omalizumab in combination with immunosuppressive therapies has not been studied.

The common side of Omalizumab includes the following:

• Stomach pain
• Nose bleeds
• Tiredness
• Ear pain
• Headache
• Nausea
• Pain, redness, swelling, in the place Omalizumab was injected
• Pain, especially in the joints, arms, or legs
• Swelling inside of the nose, and throat.

Pregnancy

There is no well-documented experience of clinical studies in pregnant women. Omalizumab should only be used during pregnancy if the potential benefits outweigh the risks associated with the fetus’s growth. Omalizumab is transported across the placenta in a linear fashion as pregnancy progresses hence potential effects on a fetus are expected likely to be greater during the second and third trimesters of pregnancy. In the US population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Labor and Delivery

There is no well-documented experience of clinical studies in women undergoing labor and delivery. Omalizumab should only be used during pregnancy if the potential benefits outweigh the risks associated with the fetus’s growth.

Nursing Mothers

It is not known whether Omalizumab is excreted in human milk. Therefore, Omalizumab should be used during nursing only if the potential outweighs the potential benefits and risks associated with newborn growth. Immunoglobulins G (IgGs) are present in human milk and therefore it is expected that Omalizumab will be present in human milk. Available data from the studies in non-human primates have shown excretion of Omalizumab into milk The EXPECT study, with 154 infants who had been exposed to Omalizumab during pregnancy and breast-feeding did not indicate any adverse effects on the breastfed infant. As Omalizumab is immunoglobulin and can undergo proteolysis in the liver therefore no adverse effect can be anticipated to occur.

Pediatric Use

Asthma

Safety and efficacy of Omalizumab for asthma were evaluated in 2 trials in 926 consisting of Omalizumab 624 and placebo 302, pediatric patients 6 to <12 years of age. Omalizumab-treated patients were found to have a statistically significant reduction in the rate of exacerbations (exacerbation was defined as worsening of asthma that required treatment ) . Safety and efficacy in pediatric patients suffering from asthma aged below 6 years have not been established.

Chronic Idiopathic Urticaria (CIU)

The safety and effectiveness of Omalizumab for adolescent patients with CIU were evaluated in 39 patients 12 to 17 years of age (Omalizumab 29, placebo 10) . This was included in three randomized and placebo-controlled CIU trials. A numerical decrease in weekly itching was observed, and adverse reactions were similar to those reported in patients aged 18 years and older. Safety and efficacy in pediatric patients with Chronic Idiopathic Urticaria below 12 years of age have not been established.

Geriatric Use

In clinical studies, 134 asthma patients and 37 Chronic Idiopathic Urticaria, phase three study patients aged 65 yrs or older were treated with Omalizumab. No significant changes have been observed

The number of patients who were aged 65 and over is not sufficient to determine whether they respond differently from younger patients.

The physician should be vigilant about the knowledge and treatment pertaining to the identification and treatment of overdosage of molecule Omalizumab.

The maximum tolerated dose of Omalizumab in patients has not been determined. Single intravenous doses of up to 4,000 mg have been administered to patients which showed no evidence of dose-limiting toxicities. The highest cumulative dose of about 44,000 mg was administered to patients over a 20-week period, and this dose did not result in any acute effects.

Pharmacodynamics

Omalizumab is said to be a recombinant, humanized, a monoclonal antibody against human immunoglobulin E commonly called IgE. Omalizumab is used in the treatment of asthma and chronic idiopathic urticaria. It acts by limiting the allergic response.

Mast cell activation and release of mediators, in response to exposure to the allergen and IgE, results in a cascade of events. such as the activation of B-lymphocytes, T-lymphocytes, eosinophils, fibroblasts, smooth muscle cells, and the endothelium.

Omalizumab inhibits the binding of IgE to receptors on mast cells and basophils, blocking the IgE-mediated secretion of inflammatory mediators from these cells.

Pharmacokinetics

• Absorption

After subcutaneous administration, Omalizumab was found to be absorbed with an average absolute bioavailability of about 62%. After a single subcutaneous dose in adult and adolescent patients who were suffering from asthma, Omalizumab was found to be absorbed slowly. The peak serum concentrations were observed after an average of 7-8 days. The pharmacokinetics of Omalizumab was found to be linear at doses greater than 0.5 mg/kg. After multiple doses of Omalizumab, areas under the serum concentration-time curve from Day 0 to Day 14 at a steady state were found to be up to 6-fold of those after the first dose.

• Volume of distribution

The apparent volume of distribution in the patients suffering from Severe Asthma after subcutaneous administration was found to be 78 ± 32 mL/kg. In patients with Chronic Idiopathic Urticaria, the distribution of Omalizumab was similar to that in asthmatic patients.

• Protein binding

There are no protein binding studies for monoclonal antibodies.

• Metabolism

The elimination of Omalizumab is dose-dependent. The Omalizumab and IgE complexes are thought to be cleared via interactions with Fc- gamma-Rs at rates that are found to be more rapid than that of IgG clearance. The relative clearances of free Omalizumab, free IgE, and complexes is summarized as follows free IgE clearance > > omalizumab:IgE clearance > omalizumab clearance .

• Elimination

Elimination of IgG mainly occurs in the liver which includes degradation in the liver reticuloendothelial system (RES) and endothelial cells. Intact IgG was also found to be excreted in bile, in pharmacokinetic studies.

1. https://medlineplus.gov/druginfo/meds/a603031.html
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4533538/
3. https://reference.medscape.com/drug/xolair-omalizumab-343444#10
4. https://www.xolair.com/
5. https://www.mayoclinic.org/drugs-supplements/omalizumab-subcutaneous-route/description/drg-20065207
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7. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/103976s5225lbl.pdf
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11. 261991017_Bioequivalence_of_a_Novel_Omalizumab_Solution_for_Injection_Compared_with_the_Standard_Lyophilized_Powder_Formulation