tezepelumab (Rx)

1-10%

Pharyngitis (4%)

Arthralgia (4%)

Back pain (4%)

Injection-site reactions (3.3%)

Contraindications

Hypersensitivity to tezepelumab or its excipients

Cautions

Hypersensitivity reactions (eg, rash and allergic conjunctivitis) can occur after administration; typically occur within hours of administration, but some instances have a delayed onset (ie, days); in event of a hypersensitivity reaction, consider benefits and risks to determine whether to continue or discontinue treatment

Do not use to treat acute asthma symptoms, acute exacerbations, acute bronchospasm, or status asthmaticus; instruct patient to seek medical attention if asthma remains uncontrolled or worsens after treatment initiation

Do not discontinue systemic or inhaled corticosteroids abruptly upon initiating therapy; reduce corticosteroid dose gradually, if appropriate, under direct supervision of a physician

Treat preexisting helminth infection before initiating; if patients become infected while taking tezepelumab and do not respond to antihelminth treatment, discontinue tezepelumab until infection resolves

Concomitant use with live, attenuated vaccines has not been evaluated; avoid administering live vaccines while taking tezepelumab

Pregnancy

Data are not available regarding use in pregnant females to evaluate for any drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes

Placental transfer of monoclonal antibodies is greater during third trimester; therefore, potential effects on fetus are likely to be greater during that time

Animal studies

• In an enhanced prenatal and postnatal development study conducted in cynomolgus monkeys, placental transport of tezepelumab observed
• There was no evidence of fetal harm following IV administration throughout pregnancy at doses that produced maternal exposures up to 168 times the exposure at the maximum recommended human dose (MRHD) of 210 mg administered SC

Clinical considerations

• Females with poorly or moderately controlled asthma have increased risk of preeclampsia in the mother and prematurity, low birth weight, and small for gestational age, in the neonate
• Closely monitor asthma control in pregnant females and adjust treatment to maintain optimal control

Lactation

Data are not available regarding the presence of tezepelumab in human milk, effects on breastfed infants, or effects on milk production

IgG is present in human milk in small amounts; tezepelumab was present in the milk of cynomolgus monkeys postpartum following dosing during pregnancy

Consider the developmental and health benefits of breastfeeding along with the mother's clinical need for tezepelumab and any potential adverse effects on the breastfed infant or from the underlying maternal condition

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Human monoclonal antibody immunoglobulin G2 (IgG2)-lambda that inhibits thymic stromal lymphopoietin (TSLP)

TSLP is a key epithelial cytokine involved in multiple inflammatory cascades and initiates an overreactive immune response to allergic, eosinophilic, and other types of airway inflammation associated with severe asthma

TSLP released in response to multiple triggers associated with asthma exacerbations, including allergens, viruses, and other airborne particles; increased expression of TSLP in the airways of patients with asthma has been correlated with disease severity

Blocking TSLP may prevent release of proinflammatory cytokines by immune cells, resulting in prevention of asthma exacerbations and improved asthma control

Absorption

Peak plasma concentration: 3-10 days

Bioavailability: ~77%

Distribution

Vd: 3.9 L (central); 2.2 L (peripheral)

Metabolism

Degraded by proteolytic enzymes and widely distributed in the body and not metabolized by hepatic enzymes

Elimination

Half-life: ~26 days

Clearance: 0.17 L/day

SC Preparation

Before administration, remove from refrigerator and allow vial/syringe to reach room temperature (~60 minutes)

Do not expose to heat and do not shake

Do not use if security seal on carton has been broken

Do not put back in the refrigerator once drug has reached room temperature; after removal from the refrigerator, must be used within 30 days or discarded

Prefilled syringe may contain small air bubbles (this is normal); do not expel the air bubbles before administering

Visually inspect for particulate matter and discoloration; solution should appear clear to opalescent, colorless to light yellow; discard if liquid is cloudy, discolored, or contains large particles or foreign particulate matter

SC Administration

Inject SC into upper arm, thigh, or abdomen, except for the 2 inches (5 cm) around navel

Avoid injecting into areas where skin is tender, bruised, erythematous, or hardened

Rotate injection site with each administration

See prescribing information for diagrams on SC prefilled syringe

Missed dose

• Administer dose as soon as possible
• Thereafter, resume dosing on the usual day of administration
• If the next dose is already due, then administer as planned

Storage

Refrigerate at 36-46ºF (2-8ºC)

If necessary, may be kept at room temperature, between 68-77ºF (20-25ºC), for up to 30 days

Do not put back in the refrigerator once drug has reached room temperature; discard after 30 days

Store in original carton to protect from light

Do not freeze, do not shake, do not expose to heat