Tezepelumab (Monograph)

Brand name: Tezspire
Drug class: Respiratory Tract Agents, Miscellaneous
Chemical name: Immunoglobulin G2, anti-(human thymic stromal lymphopoietin) (human monoclonal MEDI9929 heavy chain), disulfide with human monoclonal MEDI9929 λ-chain, dimer
Molecular formula: C₆₄₀₀H₉₈₄₄N₁₇₃₂O₁₉₉₂S₅₂ (peptide)
CAS number: 1572943-04-4

Medically reviewed by Drugs.com on Oct 26, 2022. Written by ASHP.

Introduction

Human monoclonal antibody and a thymic stromal lymphopoietin (TSLP) blocker; an IgG2 lambda immunoglobulin antiasthmatic agent.

Uses for Tezepelumab

Asthma

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

Not indicated for treatment of acute bronchospasm or status asthmaticus. Patients should seek medical advise if their asthma remains uncontrolled or worsens after treatment with tezepelumab.

Biologics such as tezepelumab are generally recommended as add-on maintenance therapy in patients who have difficult-to-treat or severe asthma after evaluation by a specialist.

Tezepelumab Dosage and Administration

General

Pretreatment Screening

Treat underlying helminth infections prior to initiating therapy.

Patient Monitoring

Monitor patients for signs and symptoms of hypersensitivity reactions.

Other General Considerations

Concomitant oral or inhaled corticosteroids should not be discontinued abruptly. If appropriate, reduction in corticosteroid dosage should be done gradually and under the direct supervision of a physician.

Administration

Sub-Q Administration

Allow product to reach room temperature before administration. This takes about 60 minutes once removed from refrigeration. Do not shake or expose to heat.

Intended for administration by a clinician.

Inject entire contents of vial or prefilled syringe subcutaneously into the upper arm, thigh, or abdomen, except for the 2 inches around the navel. Rotate injection sites. Do not inject into tender, bruised, erythematous, or hardened skin areas.

If a dose is missed, administer the dose as soon as possible. Resume regular dosing on the usual day of administration. If the next dose is already due, administer as planned.

Administration of the Prefilled Syringe

Pinch the skin gently and administer the prefilled syringe subcutaneously at an approximately 45° angle into recommended injection site.

Inject all of the drug by pushing plunger until it is completely between the needle guard activation clips. This is necessary to activate the needle guard.

After injection, maintain pressure on plunger head and remove needle from the skin. Release pressure on plunger head to allow needle guard to cover needle.

Dosage

Pediatric Patients

Asthma

Sub-Q

Pediatric patients ≥12 years of age: 210 mg once every 4 weeks.

Adults

Asthma

Sub-Q

210 mg once every 4 weeks.

Special Populations

Hepatic Impairment

Manufacturer makes no specific dosage recommendations.

Renal Impairment

Manufacturer makes no specific dosage recommendations.

Geriatric Patients

Manufacturer makes no specific dosage recommendations.

Cautions for Tezepelumab

Contraindications

Known history of hypersensitivity to the drug or any ingredient in the formulation.

Warnings/Precautions

Hypersensitivity Reactions

Hypersensitivity reactions (e.g., rash and allergic conjunctivitis) can occur following administration of tezepelumab within hours of administration, but in some instances have a delayed onset (i.e., days).

Consider benefits and risks for the individual patient to determine whether to continue or discontinue treatment.

Acute Asthma Symptoms or Deteriorating Disease

Not indicated to treat exacerbations. Do not use tezepelumab to treat acute bronchospasm or status asthmaticus. Advise patients to seek medical advice if their asthma remains uncontrolled or worsens after initiation of treatment with tezepelumab.

Risk Associated with Abrupt Reduction of Corticosteroid Dosage

Do not discontinue systemic or inhaled corticosteroids abruptly upon initiation of therapy with tezepelumab. Reductions in corticosteroid dosage, if appropriate, should be gradual and performed under the direct supervision of a physician. Reduction in corticosteroid dosage may be associated with systemic withdrawal symptoms and/or unmask conditions previously suppressed by systemic corticosteroid therapy.

Parasitic (Helminth) Infection

Unknown response to treatments for helminth infections. Treat patients with pre-existing helminth infections before initiating therapy with tezepelumab. If patients become infected while receiving treatment with tezepelumab and do not respond to anthelmintic treatment, discontinue treatment with tezepelumab until infection resolves.

Live Attenuated Vaccines

Avoid use of live attenuated vaccines in patients receiving tezepelumab.

Specific Populations

Pregnancy

No available data on tezepelumab-ekko use in pregnant women to evaluate for any drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes.

Placental transfer of monoclonal antibodies such as tezepelumab is greater during the third trimester of pregnancy; therefore, potential effects on a fetus are likely to be greater during the third trimester of pregnancy. No fetal harm observed in animal reproduction studies.

Lactation

Not known whether tezepelumab is distributed into human milk, or if the drug has any effects on the breastfed infant or on milk production. The drug has been detected in animal milk. Tezepelumab is a human monoclonal antibody IgG₂ lambda, and IgG is present in human milk in small amounts.

Consider developmental and health benefits of breast-feeding along with the mother's clinical need for tezepelumab and any potential adverse effects on the breast-fed infant from the drug or underlying maternal condition.

Pediatric Use

Safety and efficacy of tezepelumab-ekko for add-on maintenance treatment of severe asthma have been established in pediatric patients 12–17 years of age. The safety profile and pharmacodynamic responses in pediatric patients were generally similar to the overall study population.

Safety and effectiveness in patients <12 years of age not established.

Geriatric Use

No overall differences in safety or effectiveness observed between patients ≥65 years of age and younger patients.

Hepatic Impairment

Since tezepelumab is not metabolized by hepatic-specific enzymes, changes in hepatic function are not expected to influence the drug's clearance.

Renal Impairment

Clearance does not appear to be affected by mild or moderate renal function. No information available in patients with severe renal impairment.

Common Adverse Effects

Adverse effects (≥3%): pharyngitis, arthralgia, back pain.

Drug Interactions

No formal drug interaction studies performed.

Not metabolized by hepatic enzymes.

Leukotriene Receptor Antagonists

Based on population pharmacokinetic analysis, co-administered asthma medications, including leukotriene receptor antagonists, did not have a clinically meaningful effect on tezepelumab clearance.

Theophylline/Aminophylline

Based on population pharmacokinetic analysis, co-administered asthma medications, including theophylline/aminophylline, did not have a clinically meaningful effect on tezepelumab clearance.

Oral and Inhaled Corticosteroids

Based on population pharmacokinetic analysis, co-administered asthma medications, including oral and inhaled corticosteroids, did not have a clinically meaningful effect on tezepelumab clearance.

Live Attenuated Vaccines

The concomitant use of tezepelumab and live attenuated vaccines has not been evaluated. The use of live attenuated vaccines should be avoided in patients receiving tezepelumab.

Tezepelumab Pharmacokinetics

Absorption

Time to peak plasma concentrations achieved in approximately 3 to 10 days.

Steady state: 12 weeks when administered every 4 weeks.

Bioavailability

77%.

Onset

Administration every 4 weeks reduced blood eosinophil counts, FeNO, and concentrations of IL-5 and IL-13 from baseline with an onset 2 weeks after initiation.

Elimination

Half-life

Approximately 26 days.

Elimination Route

Eliminated by intracellular catabolism. Also degraded by proteolytic enzymes that are widely distributed in the body.

Special Populations

Pharmacokinetics not formally studied in patients with hepatic impairment or severe renal impairment (Cl_cr <30 mL/minute). Drug clearance was similar in patients with normal renal function and mild to moderate renal impairment (Cl_cr >30 mL/minute).

Age, sex, and race did not have a clinically meaningful effect on pharmacokinetics.

Higher body weight was associated with lower drug exposure; however, no impact on efficacy or safety was observed.

Stability

Storage

Parenteral

Single-use vial or prefilled syringe for sub-Q administration

Store refrigerated (2–8°C). Keep in original package to protect from light. Do not shake or expose to heat; do not freeze.

Excursion permitted to room temperature 20–25°C for a maximum of 30 days. Do not return to refrigerator once the drug has been stored at room temperature.

Actions

Binds to human thymic stromal lymphopoietin (TSLP) and blocks its interaction with the heterodimeric TSLP receptor. TSLP is a cytokine mainly derived from epithelial cells and occupies an upstream position in the asthma inflammatory cascade.
Reduces biomarkers and cytokines associated with inflammation including blood eosinophils, airway submucosal eosinophils, IgE, FeNO, IL-5, and IL-13.
Mechanism of tezepelumab action in asthma has not been definitively established.

Advice to Patients

Advise the patient to read the FDA-approved patient labeling (patient information).
Inform patients that hypersensitivity reactions (e.g., rash, allergic conjunctivitis) can occur following administration of tezepelumab. These reactions can occur within hours of administration, but in some instances have a delayed onset (i.e., days). Instruct patients to contact their healthcare provider if they experience symptoms of an allergic reaction.
Inform patients that tezepelumab does not treat acute asthma symptoms or acute exacerbations. Instruct patients to seek medical advice if their asthma remains uncontrolled or worsens after initiation of treatment with tezepelumab.
Inform patients to not discontinue systemic or inhaled corticosteroids except under the direct supervision of a healthcare provider. Inform patients that reduction in corticosteroid dose may be associated with systemic withdrawal symptoms and/or unmask conditions previously suppressed by systemic corticosteroid therapy.
Instruct patients to inform the healthcare provider that they are taking tezepelumab prior to a potential vaccination.
Advise women to inform their clinician if they are or plan to become pregnant or plan to breast-feed.
Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.
Advise patients of other important precautionary information.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Tezepelumab-ekko can only be obtained through designated specialty pharmacies. Contact the manufacturer for specific availability information.