PADCEV EJFV- enfortumab vedotin injection, powder, lyophilized, for solution

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

ENFORTUMAB VEDOTIN (UNII: DLE8519RWM) (ENFORTUMAB VEDOTIN - UNII:DLE8519RWM)

Available from:

SEAGEN INC.

Administration route:

INTRAVENOUS

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

PADCEV® , in combination with pembrolizumab, is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer (mUC). PADCEV, as a single agent, is indicated for the treatment of adult patients with locally advanced or mUC who: None. Risk Summary Based on the mechanism of action and findings in animals, PADCEV can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1)] . There are no available human data on PADCEV use in pregnant women to inform a drug-associated risk. In an animal reproduction study, administration of enfortumab vedotin-ejfv to pregnant rats during organogenesis caused maternal toxicity, embryo-fetal lethality, structural malformations and skeletal anomalies at maternal exposures similar to the exposures at the recommended human dose of 1.25 mg/kg (see Data) . Advise patients of the potential risk to the fetus. The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%-4% and 15%-20%, respectively. Data Animal Data In a rat pilot embryo-fetal development study, administration of enfortumab vedotin-ejfv on gestation day 6 and 13 during the period of organogenesis resulted in a complete litter loss in all pregnant rats at the maternally toxic dose of 5 mg/kg (approximately 3 times the exposure at the recommended human dose). A dose of 2 mg/kg (similar to the exposure at the recommended human dose) resulted in maternal toxicity, embryo-fetal lethality and structural malformations that included gastroschisis, malrotated hindlimb, absent forepaw, malpositioned internal organs and fused cervical arch. Additionally, skeletal anomalies (asymmetric, fused, incompletely ossified, and misshapen sternebrae, misshapen cervical arch, and unilateral ossification of the thoracic centra) and decreased fetal weight were observed. Risk Summary There are no data on the presence of enfortumab vedotin-ejfv in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in a breastfed child, advise lactating women not to breastfeed during treatment with PADCEV and for 3 weeks after the last dose. Pregnancy Testing Verify pregnancy status in females of reproductive potential prior to initiating PADCEV treatment [see Use in Specific Populations (8.1)] . Contraception Females PADCEV can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)] . Advise females of reproductive potential to use effective contraception during treatment with PADCEV and for 2 months after the last dose. Males Advise male patients with female partners of reproductive potential to use effective contraception during treatment with PADCEV and for 4 months after the last dose. Infertility Females Based on findings in animal studies with MMAE-containing antibody-drug conjugates (ADCs), PADCEV may impair female fertility. The effect on fertility is reversible [see Nonclinical Toxicology (13.1)] . Males Based on findings from animal studies, PADCEV may impair male fertility [see Nonclinical Toxicology (13.1)] . Safety and effectiveness of PADCEV in pediatric patients have not been established. Of the 564 patients treated with PADCEV in combination with pembrolizumab, 44% (n=247) were 65-74 years and 26% (n=144) were 75 years or older. Of the 720 patients treated with PADCEV as a single agent in clinical trials, 39% (n=282) were 65-74 years and 24% (n=170) were 75 years or older. No overall differences in effectiveness were observed between patients 65 years of age or older and younger patients. Patients 75 years of age or older treated with PADCEV in combination with pembrolizumab experienced a higher incidence of fatal adverse reactions than younger patients. The incidence of fatal adverse reactions was 4% in patients younger than 75 and 7% in patients 75 years or older. Patients 75 years of age or older treated with PADCEV as a single agent experienced a higher incidence of fatal adverse reactions than younger patients. The incidence of fatal adverse reactions was 6% in patients younger than 75 years, and 11% in patients 75 years or older. No significant difference was observed in the pharmacokinetics of PADCEV between patients 65 years and older and younger patients [see Clinical Pharmacology (12.3 )]. Avoid the use of PADCEV in patients with moderate or severe hepatic impairment (total bilirubin >1.5 x ULN and AST any). PADCEV has only been studied in a limited number of patients with moderate hepatic impairment (n=3) and has not been evaluated in patients with severe hepatic impairment [see Clinical Pharmacology (12.3)] . In another ADC that contains MMAE, the frequency of ≥ Grade 3 adverse reactions and deaths was greater in patients with moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment compared to patients with normal hepatic function.

Product summary:

How Supplied PADCEV (enfortumab vedotin-ejfv) 20 mg and 30 mg are supplied as a sterile, preservative-free, white to off-white lyophilized powder in single-dose vials. PADCEV vials are available in the following packages: Storage Store PADCEV vials refrigerated at 2ºC to 8ºC (36ºF to 46ºF) in the original carton. Do not freeze. Do not shake. Special Handling PADCEV is a hazardous drug. Follow applicable special handling and disposal procedures.1

Authorization status:

Biologic Licensing Application

Summary of Product characteristics

PADCEV EJFV- ENFORTUMAB VEDOTIN INJECTION, POWDER, LYOPHILIZED, FOR
SOLUTION
SEAGEN INC.
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
PADCEV SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR PADCEV.
PADCEV (ENFORTUMAB VEDOTIN-EJFV) FOR INJECTION, FOR INTRAVENOUS USE
INITIAL U.S. APPROVAL: 2019
WARNING: SERIOUS SKIN REACTIONS
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING. _
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RECENT MAJOR CHANGES
Indications and Usage (1)
12/2023
Warnings and Precautions
(5.1), (5.2), (5.3), (5.4), (5.5), (5.6)
12/2023
INDICATIONS AND USAGE
PADCEV is a Nectin-4-directed antibody and microtubule inhibitor
conjugate indicated:
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DOSAGE AND ADMINISTRATION
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DOSAGE FORMS AND STRENGTHS
For Injection: 20 mg and 30 mg of enfortumab vedotin-ejfv as a
lyophilized powder in a single-dose vial for
reconstitution. (3)
CONTRAINDICATIONS
None. (4)
WARNINGS AND PRECAUTIONS
•
®
PADCEV CAN CAUSE SEVERE AND FATAL CUTANEOUS ADVERSE REACTIONS,
INCLUDING
STEVENS-JOHNSON SYNDROME (SJS) AND TOXIC EPIDERMAL NECROLYSIS (TEN).
IMMEDIATELY WITHHOLD PADCEV AND CONSIDER REFERRAL FOR SPECIALIZED CARE
FOR
SUSPECTED SJS OR TEN OR SEVERE SKIN REACTIONS.
PERMANENTLY DISCONTINUE PADCEV IN PATIENTS WITH CONFIRMED SJS OR TEN;
OR GRADE 4
OR RECURRENT GRADE 3 SKIN REACTIONS. (2.2), (5.1) (6.1)
in combination with pembrolizumab for the treatment of adult patients
with locally advanced or
metastatic urothelial cancer. (1)
as a single agent for the treatment of adult patients with locally
advanced or metastatic urothelial
cancer who:
o
o
have previously received a programmed death receptor-1 (PD-1) or
programmed death-ligand 1
(PD-L1) inhibitor and platinum-containing chemotherapy, or
are ineligible for cisplatin-containing chemotherapy and have
previously received one or more
prior lines of therapy. (1)
_For intravenous infusion only._ Do not administer PADCEV as an
intravenous push or bolus. Do not mix
with, or administer as an infusion with,