Telzepelumab- (TELSPIRE)- (Dec 2021)- To treat Asthma
Drug Name:Telzepelumab- (TELSPIRE)- (Dec 2021)- To treat Asthma
List Of Brands:
Indication Type Description:
Drug Interaction
Indication
Adverse Reaction
Contra-Indications
Dosages/ Overdosage Etc
Patient Information
Pharmacology/ Pharmacokinetics
Pregnancy and lactation
Drug Interaction:
DRUG INTERACTIONS
No formal drug interaction studies have been performed with TEZSPIRE.
Indication:
U.S. FDA APPROVED DRUGS SURING 2021
Serial No 47
Name of the Drug- TEZPIRE
Active Ingredient - Tezepelumab
Pharmacological Classification- To treat Severe Asthma Date of Approval- 12/17/21
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use
TEZSPIRE safely and effectively. See full prescribing information for
TEZSPIRE.
TEZSPIRE™ (tezepelumab-ekko) injection, for subcutaneous use
Initial U.S. Approval: 2021
INDICATIONS AND USAGE--
TEZSPIRE is a thymic stromal lymphopoietin (TSLP) blocker, human
monoclonal antibody (IgG2?), indicated for the add-on maintenance treatment
of adult and pediatric patients aged 12 years and older with severe asthma.
Limitations of Use:
Not for relief of acute bronchospasm or status asthmaticus.
Adverse Reaction:
ADVERSE REACTIONS-
Most common adverse reactions (incidence = 3%) are pharyngitis, arthralgia,
and back pain.
Contra-Indications:
CONTRAINDICATIONS-
Known hypersensitivity to tezepelumab-ekko or excipients.
WARNINGS AND PRECAUTIONS-
Hypersensitivity Reactions: Hypersensitivity reactions (e.g., rash,
allergic conjunctivitis) can occur after administration of TEZSPIRE.
Initiate appropriate treatment as clinically indicated in the event of a
hypersensitivity reaction.
Risk Associated with Abrupt Reduction in Corticosteroid Dosage: Do not discontinue systemic or inhaled corticosteroids abruptly upon
initiation of therapy with TEZSPIRE. Decrease corticosteroids
gradually, if appropriate.
Parasitic (Helminth) Infection: Treat patients with pre-existing
helminth infections before therapy with TEZSPIRE. If patients become
infected while receiving TEZSPIRE and do not respond to antihelminth
treatment, discontinue TEZSPIRE until the parasitic infection
resolves.
Vaccination: Avoid use of live attenuated vaccines. (5.5)
ADVERSE REACTIONS-
Most common adverse reactions (incidence = 3%) are pharyngitis, arthralgia,
and back pain.
Dosages/ Overdosage Etc:
DOSAGE AND ADMINISTRATION-
Administer by subcutaneous injection.
Recommended dosage is 210 mg administered once every 4 weeks.
DOSAGE FORMS AND STRENGTHS-
Injection:
210 mg/1.91 mL (110 mg/mL) solution in a single-dose glass vial.
210 mg/1.91 mL (110 mg/mL) solution in a single-dose pre-filled
syringe.
Patient Information:
PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Patient Information).
Hypersensitivity Reactions-
Inform patients that hypersensitivity reactions (e.g., rash and allergic conjunctivitis) can occur following administration of TEZSPIRE .
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.
Not for Acute Symptoms or Deteriorating Disease-
Inform patients that TEZSPIRE does not treat acute asthma symptoms or acute exacerbations.
Inform patients to seek medical advice if their asthma remains uncontrolled or worsens after initiation of treatment with TEZSPIRE
Warnings and Precautions -
Risk Associated with Abrupt Reduction of Corticosteroid Dosage-
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
Administration of Vaccines
Instruct patients to inform the healthcare provider that they are taking TEZSPIRE prior to a potential vaccination
Manufactured by: AstraZeneca AB, Sodertalje, Sweden SE-15185
US License No. 2059
At: Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320-1799
Marketed by: Amgen Inc. and AstraZeneca AB
©AstraZeneca and Amgen 2021
TEZSPIRE is a trademark of Amgen Inc.
Reference ID: 4907025
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
1. Mechanism of Action
Tezepelumab-ekko is a thymic stromal lymphopoietin (TSLP) blocker, human monoclonal antibody IgG2? that binds to human TSLP with a dissociation constant of 15.8 pM and blocks its interaction with the heterodimeric TSLP receptor.
2. Pharmacokinetics-
The pharmacokinetics of tezepelumab-ekko were dose-proportional following administration of a single subcutaneous dose over a dose range from 2.1 mg to 420 mg (0.01 to 2 times the recommended dose). With an every 4 weeks dosing regimen, tezepelumab-ekko achieves steady-state after 12 weeks and the accumulation ratio for Ctrough is 1.86-fold.
Absorption
Following subcutaneous administration, the maximum serum concentration was reached in approximately 3 to 10 days. Based on population pharmacokinetic analysis, the estimated absolute bioavailability was approximately 77%.
There was no clinically relevant difference in bioavailability when administered to different injection sites (abdomen, thigh, or upper arm).
Distribution
Based on population pharmacokinetic analysis, central and peripheral volume of distribution of tezepelumab-ekko were 3.9 L and 2.2 L, respectively, for a 70 kg individual.
Elimination
Based on population pharmacokinetic analysis, the estimated clearance for tezepelumab-ekko was 0.17 L/d for a 70 kg individual. The elimination half-life was approximately 26 days.
Metabolism
Tezepelumab-ekko is a human monoclonal antibody (IgG2?) that is degraded by proteolytic enzymes widely distributed in the body and not metabolized by hepatic enzymes.
Specific Populations
Age, Sex, Race Based on population pharmacokinetic analysis, age (12 to 80 years), sex and race (White, Black, Asian, Other) had no clinically meaningful effects on the pharmacokinetics of tezepelumab-ekko.
Body Weight- Based on population pharmacokinetic analysis, higher body weight was associated with lower exposure. However, the effect of body weight on exposure had no meaningful impact on efficacy or safety and does not require dose adjustment.
Patients with Renal impairment
No formal clinical studies have been conducted to investigate the effect of renal impairment on tezepelumab-ekko. The population pharmacokinetic analysis included 320 (23%) subjects with mild renal impairment and 38 (3%) subjects with
moderate renal impairment.
Tezepelumab-ekko clearance was similar in patients with mild renal impairment (estimated creatinine clearance 60 to 89 mL/min), moderate renal impairment (estimated creatinine clearance 30 to 59 mL/min) and those with normal renal function (estimated creatinine clearance = 90 mL/min).
Tezepelumab-ekko has not been studied in patients with severe renal impairment (estimated creatinine clearance < 30 mL/min).
Patients with Hepatic impairment
No formal clinical studies have been conducted to investigate the effect of hepatic impairment on tezepelumab-ekko.
Since tezepelumab-ekko is degraded by proteolytic enzymes widely distributed in the body and not metabolized byhepatic-specific enzymes, change in hepatic function is not expected to influence tezepelumab-ekko clearance.
Drug Interaction Studies-
No formal drug interaction studies have been conducted with tezepelumab-ekko.
Based on the population pharmacokinetic analysis, commonly co-administered asthma medications (leukotriene receptor antagonist, theophylline/aminophylline, oral and inhaled corticosteroid) had no clinically meaningful effect on tezepelumab-ekko
clearance.
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1. Pregnancy
Risk Summary
There are no available data on TEZSPIRE use in pregnant women to evaluate for any drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes.
The estimated background risk of major birth defects and miscarriages for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
2. Lactation
Risk Summary
There is no information regarding the presence of tezepelumab-ekko in human milk, its effects on the breastfed infant, or its effects on milk production.
The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for TEZSPIRE and any potential adverse effects on the breastfed infant from TEZSPIRE or from the underlying maternal condition.
3.Pediatric Use
The safety and effectiveness of TEZSPIRE for the add-on maintenance treatment of severe asthma have been established in pediatric patients aged 12 years and older .
Use of TEZSPIRE for this indication is supported by evidence from a total of 82 pediatric patients aged 12 to 17 years enrolled in
NAVIGATOR and received treatment with TEZSPIRE 210 mg subcutaneously every 4 weeks (n=41) or placebo (n=41).
The safety profile and pharmacodynamic responses in pediatric patients were generally similar to the overall study population.
The safety and effectiveness in patients younger than 12 years of age have not been established.
4. Geriatric Use
Of the 665 patients with asthma treated with TEZSPIRE in clinical trials (PATHWAY and NAVIGATOR) for severe asthma, 119 patients (18%) were 65 years or older.
No overall differences in safety or effectiveness of TEZSPIRE have
been observed between patients 65 years of age and older and younger patients.
