Padcev

Enfortumab Vedotin · Injection, Powder, Lyophilized, For Solution · Intravenous

Prescription (Rx)

Boxed warning. WARNING: SERIOUS SKIN REACTIONS
• PADCEV can cause severe and fatal cutaneous adverse reactions including Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), which occurred predominantly during the first cycle of treatment, but may occur later.
• Closely monitor patients for skin reactions.
• 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 [see Dosage and Administration ( 2.2 ), Warnings and Precautions ( 5.1 ), and Adverse Reactions ( 6.1 )]. WARNING: SERIOUS SKIN REACTIONS See full prescribing information for complete boxed warning.
• PADCEV can cause severe and fatal cutaneous adverse reactions, including Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN).
• …

Uses

1 INDICATIONS AND USAGE PADCEV ® , in combination with pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph, as neoadjuvant treatment and then continued after cystectomy as adjuvant treatment, is indicated for the treatment of adult patients with muscle invasive bladder cancer (MIBC). PADCEV ® , in combination with pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph, is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer (la/mUC). PADCEV, as a single agent, is indicated for the treatment of adult patients with la/mUC who:
• 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. PADCEV is a Nectin-4-directed antibody and microtubule inhibitor conjugate indicated:
• in combination with pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph, as neoadjuvant treatment and then continued after cystectomy as adjuvant treatment, for the treatment of adult patients with muscle invasive bladder cancer (MIBC). ( 1 )
• in combination with pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph, for the treatment of adult patients with locally advanced or metastatic urothelial cancer (la/mUC). ( 1 )
• as a single agent for the treatment of adult patients with la/mUC who: ○ 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 )

Dosage and administration

• For intravenous infusion only. Do not administer PADCEV as an intravenous push or bolus. Do not mix with, or administer as an infusion with, other medicinal products. ( 2.3 )
• MIBC: The recommended dose of PADCEV in combination with pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph is 1.25 mg/kg (up to a maximum dose of 125 mg) given as an intravenous infusion over 30 minutes. For patients who: ○ are eligible for cisplatin-containing chemotherapy, PADCEV is administered as neoadjuvant treatment on Days 1 and 8 of each 21‑day cycle for 4 cycles or until disease progression that precludes curative intent cystectomy or unacceptable toxicity, followed by adjuvant treatment on Days 1 and 8 of each 21-day cycle for 5 cycles or until disease recurrence or unacceptable toxicity, or ○ are ineligible for cisplatin-containing chemotherapy, PADCEV is administered as neoadjuvant treatment on Days 1 and 8 of each 21‑day cycle for 3 cycles or until disease progression that precludes curative intent cystectomy or unacceptable toxicity, followed by adjuvant treatment on Days 1 and 8 of each 21‑day cycle for 6 cycles or until disease recurrence or unacceptable toxicity. ( 2.1 )
• La/mUC: The recommended dose of PADCEV in combination with pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph is 1.25 mg/kg (up to a maximum dose of 125 mg) given as an intravenous infusion over 30 minutes on Days 1 and 8 of a 21-day cycle until disease progression or unacceptable toxicity. ( 2.1 )
• La/mUC: The recommended dose of PADCEV as a single agent is 1.25 mg/kg (up to a maximum dose of 125 mg) given as an intravenous infusion over 30 minutes on Days 1, 8, and 15 of a 28‑day cycle until disease progression or unacceptable toxicity. ( 2.1 )
• Avoid use in patients with moderate or severe hepatic impairment. ( 8.6 ) 2.1 Recommended Dosage The recommended dosages for PADCEV in combination with pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph, and PADCEV as a single agent are presented in Table 1 and Table 2 . Administer PADCEV as an intravenous infusion over 30 minutes as recommended [ see Instructions for Preparation and Administration ( 2.3 ) ]. Administer PADCEV prior to pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph if administering on the same day. Table 1. Recommended Dosages for PADCEV in combination with pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph Administer PADCEV prior to pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph if administering on the same day. For the recommended dosage of pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph, refer to the respective Prescribing Information . Indication Recommended PADCEV Dosage Duration of Therapy Neoadjuvant and Adjuvant Muscle Invasive Bladder Cancer (MIBC) PADCEV 1.25 mg/kg (up to a maximum of 125 mg for patients ≥100 kg) on Days 1 and 8 of a 21-day cycle . Patients who are cisplatin-eligible Cisplatin ineligibility is defined as meeting at least one of the following criteria: Creatinine clearance of less than 60 mL/min, ECOG PS 2 or higher, Grade 2 or higher hearing loss, NYHA Class III or higher heart failure, or Grade 2 or higher peripheral neuropathy. :
• Neoadjuvant: 4 cycles or until disease progression that precludes curative intent cystectomy or unacceptable toxicity.
• Adjuvant: 5 cycles or until disease recurrence or unacceptable toxicity . Patients who are cisplatin-ineligible :
• Neoadjuvant: 3 cycles or until disease progression that precludes curative intent cystectomy or unacceptable toxicity.
• Adjuvant: 6 cycles or until disease recurrence or unacceptable toxicity . Locally advanced or metastatic Urothelial Cancer (la/mUC) PADCEV 1.25 mg/kg (up to a maximum of 125 mg for patients ≥100 kg) on Days 1 and 8 of a 21-day cycle . Until disease progression or unacceptable toxicity. Table 2. Recommended Dosages for PADCEV as a single agent Indication Recommended PADCEV Dosage Duration of Therapy Locally advanced or metastatic Urothelial Cancer (la/mUC) PADCEV 1.25 mg/kg (up to a maximum of 125 mg for patients ≥100 kg) on Days 1, 8, and 15 of a 28-day cycle. Until disease progression or unacceptable toxicity. 2.2 Dose Modifications Table 3. Dose Modifications Adverse Reaction Severity Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, Grade 4 is life-threatening. Dose Modification Skin Reactions [see Boxed Warning , Warnings and Precautions ( 5.1 )] For persistent or recurrent Grade 2 skin reactions Consider withholding until Grade ≤1, then resume treatment at the same dose level or dose reduce by one dose level. Grade 3 skin reactions Withhold until Grade ≤1, then resume treatment at the same dose level or dose reduce by one dose level. Suspected SJS or TEN Immediately withhold, consult a specialist to confirm the diagnosis. If not SJS/TEN, see Grade 2-4 skin reactions. Confirmed SJS or TEN; Grade 4 or recurrent Grade 3 skin reactions Permanently discontinue. Hyperglycemia [see Warnings and Precautions ( 5.2 )] Blood glucose >250 mg/dL Withhold until elevated blood glucose has improved to ≤250 mg/dL, then resume treatment at the same dose level. Pneumonitis/Interstitial Lung Disease (ILD) [see Warnings and Precautions ( 5.3 )] Grade 2 Withhold until Grade ≤1, then resume treatment at the same dose level or consider dose reduction by one dose level. Grade ≥3 Permanently discontinue. Peripheral Neuropathy [see Warnings and Precautions ( 5.4 )] Grade 2 Withhold until Grade ≤1, then resume treatment at the same dose level (if first occurrence). For a recurrence, withhold until Grade ≤1, then resume treatment reduced by one dose level. Grade ≥3 Permanently discontinue. Other Nonhematologic Toxicity [see Adverse Reactions ( 6 )] Grade 3 Withhold until Grade ≤1, then resume treatment at the same dose level or consider dose reduction by one dose level. Grade 4 Permanently discontinue.

Dosage forms and strengths

For Injection: 20 mg and 30 mg of enfortumab vedotin-ejfv as a white to off-white lyophilized powder in a single-dose vial for reconstitution. 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. None. ( 4 )

Warnings and precautions

• Hyperglycemia: Diabetic ketoacidosis may occur in patients with and without preexisting diabetes mellitus, which may be fatal. Closely monitor blood glucose levels in patients with, or at risk for, diabetes mellitus or hyperglycemia. Withhold PADCEV if blood glucose is >250 mg/dL. ( 2.2 , 5.2 )
• Pneumonitis/Interstitial Lung Disease (ILD): Severe, life-threatening or fatal pneumonitis/ILD may occur. Withhold PADCEV for Grade 2 pneumonitis/ILD and consider dose reduction. Permanently discontinue PADCEV for Grade 3 or 4 pneumonitis/ILD. ( 2.2 , 5.3 )
• Peripheral Neuropathy: Monitor patients for new or worsening peripheral neuropathy and consider dose interruption, dose reduction, or discontinuation of PADCEV. ( 2.2 , 5.4 )
• Ocular Disorders: Ocular disorders, including vision changes, may occur. Monitor patients for signs or symptoms of ocular disorders. Consider prophylactic artificial tears for dry eyes and treatment with ophthalmic topical steroids after an ophthalmic exam. Consider dose interruption or dose reduction of PADCEV when symptomatic ocular disorders occur. ( 5.5 )
• Infusion Site Extravasation: Ensure adequate venous access prior to administration. Monitor the infusion site during PADCEV administration and stop the infusion immediately for suspected extravasation. ( 5.6 )
• Embryo-Fetal Toxicity: PADCEV can cause fetal harm. Advise of the potential risk to a fetus and to use effective contraception. ( 5.7 , 8.1 , 8.3 ) 5.1 Skin Reactions Severe cutaneous adverse reactions, including fatal cases of SJS or TEN occurred in patients treated with PADCEV. SJS and TEN occurred predominantly during the first cycle of treatment but may occur later. Skin reactions occurred in 65% (all grades) of the 570 patients treated with PADCEV in combination with intravenous pembrolizumab for the treatment of MIBC in clinical trials. The majority of the skin reactions that occurred with combination therapy included rash and maculo-papular rash. Grade 3-4 skin reactions occurred in 13% of patients (Grade 3: 12%, Grade 4: 1.1%), including maculo-papular rash, rash, Stevens-Johnson syndrome, dermatitis, exfoliative generalized dermatitis, toxic skin eruption, acute generalized exanthematous pustulosis, bullous dermatitis, erythema, macular rash, and pruritic rash. A fatal reaction of TEN occurred in one patient (0.2%). The median time to onset of severe skin reactions was 0.6 months (range: 0.1 to 24 months). Skin reactions led to discontinuation of PADCEV in 8% of patients [see Adverse Reactions ( 6.1 )] . Of the patients who experienced a skin reaction and had data regarding resolution (n=367), 87% had complete resolution and 13% had residual skin reactions at their last evaluation. Of the patients with residual skin reactions at last evaluation, 31% (15/49) had Grade ≥2 skin reactions. Skin reactions occurred in 70% (all grades) of the 564 patients treated with PADCEV in combination with intravenous pembrolizumab for the treatment of la/mUC in clinical trials. When PADCEV was given in combination with intravenous pembrolizumab, the incidence of skin reactions, including severe events, occurred at a higher rate compared to PADCEV as a single agent. The majority of the skin reactions that occurred with combination therapy included maculo-papular rash, macular rash, and papular rash. Grade 3-4 skin reactions occurred in 17% of patients (Grade 3: 16%, Grade 4: 1%), including maculo-papular rash, bullous dermatitis, dermatitis, exfoliative dermatitis, pemphigoid, rash, erythematous rash, macular rash, and papular rash. A fatal reaction of bullous dermatitis occurred in one patient (0.2%). The median time to onset of severe skin reactions was 1.7 months (range: 0.1 to 17.2 months). Skin reactions led to discontinuation of PADCEV in 6% of patients [see Adverse Reactions ( 6.1 )] . Of the patients who experienced a skin reaction and had data regarding resolution (n=391), 59% had complete resolution and 41% had residual skin reactions at their last evaluation. Of the patients with residual skin reactions at last evaluation, 27% (43/159) had Grade ≥2 skin reactions. Skin reactions occurred in 58% (all grades) of the 720 patients treated with PADCEV as a single agent in clinical trials. Twenty-three percent (23%) of patients had maculo-papular rash and 34% had pruritus. Grade 3-4 skin reactions occurred in 14% of patients, including maculo-papular rash, erythematous rash, rash or drug eruption, symmetrical drug-related intertriginous and flexural exanthema (SDRIFE), bullous dermatitis, exfoliative dermatitis, and palmar-plantar erythrodysesthesia. The median time to onset of severe skin reactions was 0.6 months (range: 0.1 to 8 months). Among patients experiencing a skin reaction leading to dose interruption who then restarted PADCEV (n=75), 24% of patients restarting at the same dose and 24% of patients restarting at a reduced dose experienced recurrent severe skin reactions. Skin reactions led to discontinuation of PADCEV in 3.1% of patients [see Adverse Reactions ( 6.1 )] . Of the patients who experienced a skin reaction and had data regarding resolution (n=328), 58% had complete resolution and 42% had residual skin reactions at their last evaluation. Of the patients with residual skin reactions at last evaluation, 39% (53/137) had Grade ≥2 skin reactions. Monitor patients closely throughout treatment for skin reactions. Consider topical corticosteroids and antihistamines, as clinically indicated. For persistent or recurrent Grade 2 skin reactions, consider withholding PADCEV until Grade ≤1. Withhold PADCEV and refer for specialized care for suspected SJS, TEN or for Grade 3 skin reactions. Permanently discontinue PADCEV in patients with confirmed SJS or TEN; or Grade 4 or recurrent Grade 3 skin reactions [see Dosage and Administration ( 2.2 )] .

Side effects

The following serious adverse reactions are described elsewhere in the labeling:
• Skin Reactions [see Boxed Warning , Warnings and Precautions ( 5.1 )]
• Hyperglycemia [see Warnings and Precautions ( 5.2 )]
• Pneumonitis/Interstitial Lung Disease (ILD) [see Warnings and Precautions ( 5.3 )]
• Peripheral Neuropathy [see Warnings and Precautions ( 5.4 )]
• Ocular Disorders [see Warnings and Precautions ( 5.5 )]
• Infusion Site Extravasation [see Warnings and Precautions ( 5.6 )] The most common adverse reactions, including laboratory abnormalities, (≥20%) were:
• PADCEV in combination with intravenous pembrolizumab for the treatment of MIBC: decreased hemoglobin, increased aspartate aminotransferase, increased alanine aminotransferase, rash, increased creatinine, decreased lymphocytes, fatigue, pruritus, decreased sodium, peripheral neuropathy, increased potassium, diarrhea, alopecia, dysgeusia, decreased appetite, nausea, constipation, urinary tract infection, dry eye, increased glucose, decreased weight, decreased potassium, hyperglycemia, decreased phosphate, and decreased neutrophils. ( 6.1 )
• PADCEV in combination with intravenous pembrolizumab for the treatment of la/mUC: increased aspartate aminotransferase, increased creatinine, rash, increased glucose, peripheral neuropathy, increased lipase, decreased lymphocytes, increased alanine aminotransferase, decreased hemoglobin, fatigue, decreased sodium, decreased phosphate, decreased albumin, pruritus, diarrhea, alopecia, decreased weight, decreased appetite, increased urate, decreased neutrophils, decreased potassium, dry eye, nausea, constipation, increased potassium, dysgeusia, urinary tract infection, and decreased platelets. ( 6.1 )
• PADCEV as a single agent: increased glucose, increased aspartate aminotransferase, decreased lymphocytes, increased creatinine, rash, fatigue, peripheral neuropathy, decreased albumin, decreased hemoglobin, alopecia, decreased appetite, decreased neutrophils, decreased sodium, increased alanine aminotransferase, decreased phosphate, diarrhea, nausea, pruritus, increased urate, dry eye, dysgeusia, constipation, increased lipase, decreased weight, decreased platelets, abdominal pain, and dry skin. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Astellas Pharma US, Inc. at 1-800-727-7003 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety population described in the WARNINGS AND PRECAUTIONS reflect exposure to PADCEV 1.25 mg/kg in combination with intravenous pembrolizumab for the treatment of MIBC in 570 patients in EV-303 (NCT03924895) and EV-304 (NCT04700124) and for the treatment of la/mUC in 564 patients in EV-302 (NCT04223856) and EV-103 (NCT03288545); PADCEV as a single agent at 1.25 mg/kg in 720 patients in EV-301 (NCT03474107), EV‑201 (NCT03219333), EV-203 (NCT04995419), EV-101 (NCT02091999), and EV-102 (NCT03070990). Ocular disorders reflect 384 patients in EV‑201, EV-101, and EV-102. Among 570 patients receiving PADCEV in combination with intravenous pembrolizumab for the treatment of MIBC, the most common (≥20%) adverse reactions, including laboratory abnormalities, were decreased hemoglobin, increased aspartate aminotransferase, increased alanine aminotransferase, rash, increased creatinine, decreased lymphocytes, fatigue, pruritus, decreased sodium, peripheral neuropathy, increased potassium, diarrhea, alopecia, dysgeusia, decreased appetite, nausea, constipation, urinary tract infection, dry eye, increased glucose, decreased weight, decreased potassium, hyperglycemia, decreased phosphate, and decreased neutrophils. Among 564 patients receiving PADCEV in combination with intravenous pembrolizumab for the treatment of la/mUC, 59% were exposed to PADCEV for ≥6 months, and 24% were exposed for ≥12 months. In this pooled population, the most common (≥20%) adverse reactions, including laboratory abnormalities, were increased aspartate aminotransferase, increased creatinine, rash, increased glucose, peripheral neuropathy, increased lipase, decreased lymphocytes, increased alanine aminotransferase, decreased hemoglobin, fatigue, decreased sodium, decreased phosphate, decreased albumin, pruritus, diarrhea, alopecia, decreased weight, decreased appetite, increased urate, decreased neutrophils, decreased potassium, dry eye, nausea, constipation, increased potassium, dysgeusia, urinary tract infection, and decreased platelets. Among 720 patients receiving PADCEV as a single agent, 37% were exposed for ≥6 months, and 14% were exposed for ≥12 months. In this pooled population, the most common (≥20%) adverse reactions, including laboratory abnormalities, were increased glucose, increased aspartate aminotransferase, decreased lymphocytes, increased creatinine, rash, fatigue, peripheral neuropathy, decreased albumin, decreased hemoglobin, alopecia, decreased appetite, decreased neutrophils, decreased sodium, increased alanine aminotransferase, decreased phosphate, diarrhea, nausea, pruritus, increased urate, dry eye, dysgeusia, constipation, increased lipase, decreased weight, decreased platelets, abdominal pain, and dry skin. The data described in the following section reflects exposure to PADCEV in combination with intravenous pembrolizumab from EV‑302, the dose escalation cohort, Cohort A and Cohort K of EV-103, EV-303, and EV-304. Patients from EV-302 and EV-103 received PADCEV 1.25 mg/kg in combination with intravenous pembrolizumab until disease progression or unacceptable toxicity. Patients from EV-303 and EV-304 received PADCEV 1.25 mg/kg in combination with intravenous pembrolizumab for 9 cycles or until disease progression or unacceptable toxicity.

Drug interactions

Concomitant use of dual P-gp and strong CYP3A4 inhibitors with PADCEV may increase the exposure to monomethyl auristatin E (MMAE). ( 7.1 ) 7.1 Effects of Other Drugs on PADCEV Dual P-gp and Strong CYP3A4 Inhibitors Concomitant use with dual P-gp and strong CYP3A4 inhibitors may increase unconjugated MMAE exposure [see Clinical Pharmacology ( 12.3 )] , which may increase the incidence or severity of PADCEV toxicities. Closely monitor patients for signs of toxicity when PADCEV is given concomitantly with dual P-gp and strong CYP3A4 inhibitors.

Use in specific populations

Lactation: Advise women not to breastfeed. ( 8.2 ) 8.1 Pregnancy 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. 8.2 Lactation 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. 8.3 Females and Males of Reproductive Potential 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 )] . 8.4 Pediatric Use Safety and effectiveness of PADCEV in pediatric patients have not been established. 8.5 Geriatric Use Of the 570 patients treated with PADCEV in combination with intravenous pembrolizumab for the treatment of MIBC, 45% (n=259) were 65-74 years and 22% (n=125) were 75 years or older. Of the 564 patients treated with PADCEV in combination with intravenous pembrolizumab for the treatment of la/mUC, 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 intravenous pembrolizumab for the treatment of MIBC experienced a higher incidence of fatal adverse reactions than younger patients. The incidence of fatal adverse reactions was 3.6% in patients younger than 75 and 11% in patients 75 years or older. Patients 75 years of age or older treated with PADCEV in combination with intravenous pembrolizumab for the treatment of la/mUC 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 )]. 8.6 Hepatic Impairment Avoid the use of PADCEV in patients with moderate or severe hepatic impairment (total bilirubin >1.5 × ULN and any AST). PADCEV has only been studied in a limited number of patients with moderate or 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.

Pregnancy

8.1 Pregnancy 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.

Pediatric use

8.4 Pediatric Use Safety and effectiveness of PADCEV in pediatric patients have not been established.

Geriatric use

8.5 Geriatric Use Of the 570 patients treated with PADCEV in combination with intravenous pembrolizumab for the treatment of MIBC, 45% (n=259) were 65-74 years and 22% (n=125) were 75 years or older. Of the 564 patients treated with PADCEV in combination with intravenous pembrolizumab for the treatment of la/mUC, 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 intravenous pembrolizumab for the treatment of MIBC experienced a higher incidence of fatal adverse reactions than younger patients. The incidence of fatal adverse reactions was 3.6% in patients younger than 75 and 11% in patients 75 years or older. Patients 75 years of age or older treated with PADCEV in combination with intravenous pembrolizumab for the treatment of la/mUC 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 )].

Description

Enfortumab vedotin-ejfv is a Nectin-4 directed antibody-drug conjugate (ADC) comprised of a fully human anti-Nectin-4 IgG1 kappa monoclonal antibody (AGS-22C3) conjugated to the small molecule microtubule disrupting agent, monomethyl auristatin E (MMAE) via a protease-cleavable maleimidocaproyl valine-citrulline (vc) linker (SGD-1006). Conjugation takes place on cysteine residues that comprise the interchain disulfide bonds of the antibody to yield a product with a drug-to-antibody ratio of approximately 3.8:1. The molecular weight is approximately 152 kDa. Figure 1. Structural Formula Approximately 4 molecules of MMAE are attached to each antibody molecule. Enfortumab vedotin-ejfv is produced by chemical conjugation of the antibody and small molecule components. The antibody is produced by mammalian (Chinese hamster ovary) cells and the small molecule components are produced by chemical synthesis. PADCEV (enfortumab vedotin-ejfv) for injection is provided as a sterile, preservative-free, white to off-white lyophilized powder in single-dose vials for intravenous use. PADCEV is supplied as a 20 mg per vial and a 30 mg per vial and requires reconstitution with Sterile Water for Injection, USP, (2.3 mL and 3.3 mL, respectively) resulting in a clear to slightly opalescent, colorless to slightly yellow solution with a final concentration of 10 mg/mL [see Dosage and Administration ( 2.3 )]. After reconstitution, each vial allows the withdrawal of 2 mL (20 mg) and 3 mL (30 mg). Each mL of reconstituted solution contains 10 mg of enfortumab vedotin-ejfv, histidine (1.4 mg), histidine hydrochloride monohydrate (2.31 mg), polysorbate 20 (0.2 mg), and trehalose dihydrate (55 mg) with a pH of 6.0. Figure 1

Mechanism of action

12.1 Mechanism of Action Enfortumab vedotin-ejfv is an ADC. The antibody is a human IgG1 kappa directed against Nectin-4, an adhesion protein located on the surface of cells. The small molecule, MMAE, is a microtubule-disrupting agent, attached to the antibody via a protease-cleavable linker. Nonclinical data suggest that the anticancer activity of enfortumab vedotin-ejfv is due to the binding of the ADC to Nectin-4-expressing cells, followed by internalization of the ADC-Nectin-4 complex, and the release of MMAE via proteolytic cleavage. Release of MMAE disrupts the microtubule network within the cell, subsequently inducing cell cycle arrest and apoptosis. The combination of enfortumab vedotin-ejfv with a PD-1 blocking antibody resulted in up-regulation of immune function and increased anti-tumor activity in syngeneic mouse tumor models expressing Nectin-4.

How supplied

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:
• Carton of one 20 mg single-dose vial (NDC 51144-020-01)
• Carton of one 30 mg single-dose vial (NDC 51144-030-01) 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

Patient information

Advise the patient to read the FDA-approved patient labeling (Patient Information). Skin Reactions Inform patients that severe skin reactions including SJS and TEN with fatal outcomes have occurred after administration of PADCEV, predominantly during the first cycle of treatment but may occur later. Advise patients to contact their healthcare provider immediately if they develop new target lesions, progressively worsening skin reactions, severe blistering, or peeling of the skin [see Boxed Warning and Warnings and Precautions ( 5.1 )]. Hyperglycemia Inform patients about the risk of hyperglycemia and how to recognize associated symptoms [see Warnings and Precautions ( 5.2 )] . Pneumonitis/ILD Advise patients to immediately report new or worsening respiratory symptoms [see Warnings and Precautions ( 5.3 )]. Peripheral Neuropathy Inform patients to report to their healthcare provider any numbness and tingling of the hands or feet or muscle weakness [see Warnings and Precautions ( 5.4 )]. Ocular disorders Advise patients to contact their healthcare provider if they experience any visual changes [see Warnings and Precautions ( 5.5 )] . In order to prevent or treat dry eyes, advise patients to use artificial tear substitutes. Infusion Site Extravasation Inform patients that infusion site reactions have occurred after administration of PADCEV. These reactions generally occurred immediately after administration but, in some instances, had a delayed onset (e.g., 24 hours). Instruct patients to contact their healthcare provider immediately if they experience an infusion site reaction [see Warnings and Precautions ( 5.6 )] . Embryo-Fetal Toxicity Advise pregnant women and females of reproductive potential of the potential risk to the fetus. Advise females to inform their healthcare providers of a known or suspected pregnancy [see Warnings and Precautions ( 5.7 ) and Use in Specific Populations ( 8.1 )] . Females and Males of Reproductive Potential Advise female patients of reproductive potential to use effective contraception during treatment with PADCEV and for 2 months after the last dose. 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 [see Use in Specific Populations ( 8.3 )] . Lactation Advise women not to breastfeed during treatment with PADCEV and for 3 weeks after the last dose [see Use in Specific Populations ( 8.2 )] . Infertility Advise females and males of reproductive potential that PADCEV may impair fertility [see Use in Specific Populations ( 8.3 )]. Manufactured and Marketed by: Astellas Pharma US, Inc. Northbrook, Illinois 60062 Distributed and Marketed by: Seagen Inc. Bothell, WA 98021 1-855-4SEAGEN U.S. License 2124 PADCEV is a registered trademark jointly owned by Agensys, Inc. and Seagen Inc. ©2026 Agensys, Inc. and Seagen Inc. 11817-EV-US

Label text from the FDA structured product label by SEAGEN INC. (revised Aug 4, 2026). Long sections are shortened; the complete label is on DailyMed.

Active ingredients

Enfortumab Vedotin in 2 products

Padcev NDC products (2)

NDC	Strength & form	Labeler	Type
51144-020	Enfortumab Vedotin 20 mg/2mL Injection, Powder, Lyophilized, For Solution	SEAGEN INC.	BLA
51144-030	Enfortumab Vedotin 30 mg/3mL Injection, Powder, Lyophilized, For Solution	SEAGEN INC.	BLA