Tezepelumab

Tezepelumab is an monoclonal antibodies belonging to Anti-asthmatic agents

Tezepelumabis used in the treatment of Asthma.

Tezepelumab is administered through subcutaneous injection. The absorption of the drug occurs gradually over time from the injection site. Tezepelumab is distributed throughout the body via the bloodstream. It binds specifically to an immune protein called thymic stromal lymphopoietin (TSLP) and blocks its activity.

Tezepelumab is not metabolized by the body. It is a protein drug and is broken down into small peptides and amino acids.Tezepelumab is eliminated from the body mainly via urine and feces. It has a long half-life of about 25 days, which means that it takes about 25 days for half of the drug to be eliminated from the body.

The Tmax of Tezepelumab is approximately 4 to 5 days

The Cmax values at steady state were found to be 40.6 ± 8.1 μg/mL, 80.1 ± 21.3 μg/mL, and 164 ± 44.5 μg/mL for doses of 70 mg, 140 mg, and 280 mg, respectively.

Tezepelumab shows common side effects like Injection site reactions, such as pain, redness, or swelling Headache, Fatigue Muscle pain Dizziness

Tezepelumab is available in the form of Solution for Auto-injector, (Subcutaneous), Solution for Prefilled Syringe (Subcutaneous)

Tezepelumab is available in India, Germany, Canada, Italy, USA

Tezepelumab-ekko is a human monoclonal antibody IgG2λ that binds to human thymic stromal lymphopoietin (TSLP), an epithelial cytokine, and prevents human TSLP from interacting with the heterodimeric TSLP receptor. Blocking TSLP with tezepelumab-ekko reduces biomarkers and cytokines associated with inflammation including blood eosinophils, airway submucosal eosinophils, IgE, FeNO, IL-5, and IL-13; however, the mechanism of tezepelumab-ekko action in asthma has not been definitively established.

Tezepelumab is available in the form of Solution for Auto-injector, (Subcutaneous), Solution for Prefilled Syringe (Subcutaneous).

Tezepelumab is used in the treatment of Asthma.

Tezepelumab Is approved for for following clinical indications:-

Asthma: Add-on maintenance treatment of severe asthma in adult and pediatric patients ≥12 years of age.

• Asthma, severe: Note: May consider as add-on therapy in patients with severe asthma (with or without inflammatory markers) and a history of severe exacerbations.

Tezepelumab is available in various strengths as1.91 mL.

Tezepelumab is available in the form of Solution for Auto-injector, (Subcutaneous), Solution for Prefilled Syringe (Subcutaneous).

• Dosage Adjustment for Pediatric Patients:

Asthma, severe; maintenance therapy: Children ≥12 years and Adolescents: SUBQ: 210 mg every 4 weeks.

Hypersensitivity to Tezepelumab or any component of the formulation.

Concerns related to adverse effects:

• Hypersensitivity reactions: Hypersensitivity reactions (eg, rash, allergic conjunctivitis) may occur within hours of administration. Delayed hypersensitivity reactions, occurring days after administration, have also been reported. Consider benefits and risks for discontinuing use in patients who experience a hypersensitivity reaction.

Disease-related concerns:

• Asthma: Not indicated for the treatment of acute asthma symptoms (eg, acute bronchospasm) or acute exacerbations, including status asthmaticus. Seek medical advice if asthma remains uncontrolled or worsens after initiation of tezepelumab.

• Helminth infections: It is unknown if administration of tezepelumab will influence a patient's immune response against parasitic infections. Therefore, patients with preexisting helminth infections should undergo treatment of the infection prior to initiation of tezepelumab therapy. Patients who become infected during tezepelumab treatment and do not respond to antihelminth therapy should discontinue therapy until the infection resolves.

Concurrent drug therapy issues:

• Corticosteroids: Do not discontinue systemic or inhaled corticosteroids abruptly upon initiation of tezepelumab. Reductions in corticosteroid dose should be gradual, if appropriate. Clinicians should note that a reduction in corticosteroid dose may be associated with withdrawal symptoms and/or unmask conditions previously suppressed by systemic corticosteroid therapy.

Common Adverse effects:

Injection site reactions, such as pain, redness, or swelling Headache Fatigue Muscle pain Dizziness Itching Upper respiratory tract infections, such as the common cold Nasal congestion Nausea Diarrhea

Less Common Adverse effects:

Allergic reactions, which may include hives, swelling of the face, lips, tongue, or throat, or difficulty breathing Increased risk of infection, including viral or bacterial infections Injection site reactions, such as bruising, bleeding, or infection Low blood cell counts, which may increase your risk of bleeding or infection Hypersensitivity reactions, which may include anaphylaxis or angioedema Elevated liver enzymes Insomnia Depression Anxiety

Rare Common Adverse effects:

Anaphylaxis, a severe allergic reaction that can be life-threatening Hypersensitivity reactions, including drug rash with eosinophilia and systemic symptoms (DRESS) Malignancy, such as lymphoma Thrombosis, including deep vein thrombosis (DVT) and pulmonary embolism (PE).

The common side effects of Tezepelumab include the following Injection site reactions (such as pain, redness, or swelling) Headache Fatigue Muscle pain Dizziness Itching.

Toxicity information regarding tezepelumab is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as opportunistic infections and other conditions related to immunosuppression. Symptomatic and supportive measures are recommended.

Pharmacodynamic

Tezepelumab is a human monoclonal IgG2λ antibody blocking thymic stromal lymphopoietin (TSLP). Tezepelumab treatment in asthmatic patients improves disease markers, including blood and airway submucosal eosinophils and IgE, FeNO, IL-5, and IL-13 levels. Despite an excellent safety profile, tezepelumab may be associated with hypersensitivity reactions and increased risk of infection, especially by parasitic helminths. Patients receiving tezepelumab should not discontinue systemic or inhaled corticosteroids, and any reduction in these drugs should be performed cautiously.

Pharmacokinetics

• Absorption: When administered subcutaneously, tezepelumab reaches Cmax in approximately 3-10 days with an estimated absolute bioavailability of 77%, regardless of injection site choice. Tezepelumab displays dose-proportional pharmacokinetics over a range of 2.1-420 mg (0.01-2 times the recommended dose) following a single subcutaneous dose. With a 4-week dosing schedule, tezepelumab achieves steady-state kinetics after 12 weeks with a 1.86-fold C trough accumulation ratio.

• Distribution: Tezepelumab has a central Vd of 3.9 L and a peripheral Vd of 2.2 L (for a 70 kg individual)
• Metabolism:As a human monoclonal antibody, tezepelumab is expected to be degraded by various proteolytic enzymes throughout the body.
• Excretion: As a human monoclonal antibody, tezepelumab is eliminated primarily through catabolism; there is no evidence of target-mediated clearance at the therapeutic dose.

• https://www.rxlist.com/dopram-drug.htm
• https://www.mims.com/india/drug/info/Tezepelumab ?type=full&mtype=generic
• https://go.drugbank.com/drugs/DB00561
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003846/