PADCEV EJFV- enfortumab vedotin injection, powder, lyophilized, for solution
Seattle Genetics, Inc.
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HIGHLIGHTS OF PRESCRIBING INFORMATIONThese 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 REACTIONSSee full prescribing information for complete boxed warning.
RECENT MAJOR CHANGESINDICATIONS AND USAGEPADCEV is a Nectin-4-directed antibody and microtubule inhibitor conjugate indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer who:
DOSAGE AND ADMINISTRATION
DOSAGE FORMS AND STRENGTHSFor Injection: 20 mg and 30 mg of enfortumab vedotin-ejfv as a lyophilized powder in a single-dose vial for reconstitution. (3) CONTRAINDICATIONSNone. (4) WARNINGS AND PRECAUTIONS
ADVERSE REACTIONSThe most common adverse reactions, including laboratory abnormalities, (≥20%) included rash, aspartate aminotransferase increased, glucose increased, creatinine increased, fatigue, peripheral neuropathy, lymphocytes decreased, alopecia, decreased appetite, hemoglobin decreased, diarrhea, sodium decreased, nausea, pruritus, phosphate decreased, dysgeusia, alanine aminotransferase increased, anemia, albumin decreased, neutrophils decreased, urate increased, lipase increased, platelets decreased, weight decreased 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. DRUG INTERACTIONSConcomitant use of dual P-gp and strong CYP3A4 inhibitors with PADCEV may increase the exposure to monomethyl auristatin E (MMAE). (7.1) USE IN SPECIFIC POPULATIONS
See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling. Revised: 7/2021 |
• 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)].
PADCEV® is indicated for the treatment of adult patients with locally advanced or metastatic urothelial cancer (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.
The recommended dose of PADCEV is 1.25 mg/kg (up to a maximum of 125 mg for patients ≥100 kg) administered as an intravenous infusion over 30 minutes on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity.
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Adverse Reaction |
Severity* |
Dose Modification* |
Skin Reactions [see Boxed Warning, Warnings and Precautions (5.1)] |
Suspected SJS or TEN |
Immediately withhold, consult a specialist to confirm the diagnosis. If not SJS/TEN, see Grade 3 skin reactions. |
Confirmed SJS or TEN; Grade 4 or recurrent Grade 3 skin reactions |
Permanently discontinue. |
|
Grade 3 (severe) skin reactions |
Withhold until Grade ≤1, then resume treatment at the same dose level or consider dose reduction by one dose level. |
|
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 [see Warnings and Precautions (5.3)] |
Grade 2 |
Withhold until Grade ≤ 1 for persistent or recurrent Grade 2 pneumonitis, 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. |
|
Hematologic toxicity [see Adverse Reactions (6)] |
Grade 3, or Grade 2 thrombocytopenia |
Withhold until Grade ≤ 1, then resume treatment at the same dose level or consider dose reduction by one dose level. |
Grade 4 |
Withhold until Grade ≤ 1, then reduce dose by one dose level or discontinue treatment. |
|
Dose Level |
|
Starting dose |
1.25 mg/kg up to 125 mg |
First dose reduction |
1.0 mg/kg up to 100 mg |
Second dose reduction |
0.75 mg/kg up to 75 mg |
Third dose reduction |
0.5 mg/kg up to 50 mg |
Prior to administration, the PADCEV vial is reconstituted with Sterile Water for Injection (SWFI). The reconstituted solution is subsequently diluted in an intravenous infusion bag containing either 5% Dextrose Injection, USP, 0.9% Sodium Chloride Injection, USP, or Lactated Ringer’s Injection, USP.
Reconstitution in single-dose vial
Dilution in infusion bag
Administration
DO NOT administer PADCEV as an intravenous push or bolus.
DO NOT mix PADCEV with, or administer as an infusion with, other medicinal products.
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.
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 55% of the 680 patients treated with PADCEV in clinical trials. Twenty-three percent (23%) of patients had maculopapular rash and 33% had pruritus. Grade 3-4 skin reactions occurred in 13% of patients, including maculo-papular rash, rash erythematous, rash or drug eruption, symmetrical drug-related intertriginous and flexural exanthema (SDRIFE), dermatitis bullous, dermatitis exfoliative, and palmar-plantar erythrodysesthesia. In clinical trials, the median time to onset of severe skin reactions was 0.6 months (range: 0.1 to 6.4 months). Among patients experiencing a skin reaction leading to dose interruption who then restarted PADCEV (n=59), 24% of patients restarting at the same dose and 16% of patients restarting at a reduced dose experienced recurrent severe skin reactions. Skin reactions led to discontinuation of PADCEV in 2.6% of patients [see Adverse Reactions (6.1)].
Monitor patients closely throughout treatment for skin reactions. Consider topical corticosteroids and antihistamines, as clinically indicated.
Withhold PADCEV and refer for specialized care for suspected SJS, TEN or for severe (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)].
Hyperglycemia and diabetic ketoacidosis (DKA), including fatal events, occurred in patients with and without pre-existing diabetes mellitus, treated with PADCEV.
Patients with baseline hemoglobin A1C ≥8% were excluded from clinical trials. In clinical trials, 14% of the 680 patients treated with PADCEV developed hyperglycemia; 7% of patients developed Grade 3-4 hyperglycemia. The incidence of Grade 3-4 hyperglycemia increased consistently in patients with higher body mass index and in patients with higher baseline A1C. Five percent (5%) of patients required initiation of insulin therapy for treatment of hyperglycemia. The median time to onset of hyperglycemia was 0.6 months (range: 0.1 to 20.3 months). Hyperglycemia led to discontinuation of PADCEV in 0.6% of patients. [see Adverse Reactions (6.1)].
Closely monitor blood glucose levels in patients with, or at risk for, diabetes mellitus or hyperglycemia.
If blood glucose is elevated (>250 mg/dL), withhold PADCEV [see Dosage and Administration (2.2)].
Severe, life-threatening or fatal pneumonitis occurred in patients treated with PADCEV. In clinical trials, 3.1% of the 680 patients treated with PADCEV had pneumonitis of any grade and 0.7% had Grade 3-4. In clinical trials, the median time to onset of pneumonitis was 2.9 months (range: 0.6 to 6 months).
Monitor patients for signs and symptoms indicative of pneumonitis such as hypoxia, cough, dyspnea or interstitial infiltrates on radiologic exams. Evaluate and exclude infectious, neoplastic and other causes for such signs and symptoms through appropriate investigations.
Withhold PADCEV for patients who develop persistent or recurrent Grade 2 pneumonitis and consider dose reduction. Permanently discontinue PADCEV in all patients with Grade 3 or 4 pneumonitis [see Dosage and Administration (2.2)].
Peripheral neuropathy occurred in 52% of the 680 patients treated with PADCEV in clinical trials including 39% with sensory neuropathy, 7% with muscular weakness and 6% with motor neuropathy; 4% experienced Grade 3-4 reactions. Peripheral neuropathy occurred in patients treated with PADCEV with or without preexisting peripheral neuropathy. The median time to onset of Grade ≥2 peripheral neuropathy was 4.6 months (range: 0.1 to 15.8 months). Neuropathy led to treatment discontinuation in 5% of patients. [see Adverse Reactions (6.1)].
Monitor patients for symptoms of new or worsening peripheral neuropathy and consider dose interruption or dose reduction of PADCEV when peripheral neuropathy occurs.
Permanently discontinue PADCEV in patients who develop Grade >3 peripheral neuropathy [see Dosage and Administration (2.2)].
Ocular disorders were reported in 40% of the 384 patients treated with PADCEV in clinical trials in which ophthalmologic exams were scheduled. The majority of these events involved the cornea and included events associated with dry eye such as keratitis, blurred vision, increased lacrimation, conjunctivitis, limbal stem cell deficiency, and keratopathy.
Dry eye symptoms occurred in 34% of patients, and blurred vision occurred in 13% of patients, during treatment with PADCEV. The median time to onset to symptomatic ocular disorder was 1.6 months (range: 0 to 19.1 months). Monitor patients for ocular disorders. Consider artificial tears for prophylaxis of dry eyes and ophthalmologic evaluation if ocular symptoms occur or do not resolve. Consider treatment with ophthalmic topical steroids, if indicated after an ophthalmic exam. Consider dose interruption or dose reduction of PADCEV for symptomatic ocular disorders.
Skin and soft tissue reactions secondary to extravasation have been observed after administration of PADCEV. Of the 680 patients, 1.6% of patients experienced skin and soft tissue reactions, including 0.3% who experienced Grade 3-4 reactions. Reactions may be delayed. Erythema, swelling, increased temperature, and pain worsened until 2-7 days after extravasation and resolved within 1-4 weeks of peak. Two patients (0.3%) developed extravasation reactions with secondary cellulitis, bullae, or exfoliation. Ensure adequate venous access prior to starting PADCEV and monitor for possible extravasation during administration. If extravasation occurs, stop the infusion and monitor for adverse reactions.
Based on the mechanism of action and findings in animals, PADCEV can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, administration of enfortumab vedotin-ejfv to pregnant rats during the period of organogenesis caused maternal toxicity, embryo-fetal lethality, structural malformations and skeletal anomalies at maternal exposures approximately similar to the clinical exposures at the recommended human dose of 1.25 mg/kg.
Advise patients of the potential risk to the fetus. 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 (8.1, 8.3) and Clinical Pharmacology (12.1)].
The following serious adverse reactions are described elsewhere in the labeling:
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 pooled safety population described in the WARNINGS AND PRECAUTIONS reflect exposure to PADCEV as a single agent at 1.25 mg/kg in 680 patients in EV-301, EV-201, EV-101 (NCT02091999), and EV-102 (NCT03070990). Ocular disorders reflect 384 patients in EV-201, EV-101, and EV-102. Among 680 patients receiving PADCEV, 36% were exposed for >6 months, and 9% were exposed for ≥12 months. In this pooled population, the most common (>20%) adverse reactions, including laboratory abnormalities, were rash, aspartate aminotransferase increased, glucose increased, creatinine increased, fatigue, peripheral neuropathy, lymphocytes decreased, alopecia, decreased appetite, hemoglobin decreased, diarrhea, sodium decreased, nausea, pruritus, phosphate decreased, dysgeusia, alanine aminotransferase increased, anemia, albumin decreased, neutrophils decreased, urate increased, lipase increased, platelets decreased, weight decreased and dry skin.
The data described in the following sections reflect exposure to PADCEV from an open-label, randomized, study (EV-301); and Cohort 1 and Cohort 2 of an open-label, single arm, two cohort study (EV-201). Patients received PADCEV 1.25 mg/kg on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity.
Previously Treated Locally Advanced or Metastatic Urothelial Cancer
EV-301
The safety of PADCEV was evaluated in EV-301 in patients with locally advanced or metastatic urothelial cancer (n=296) who received at least one dose of PADCEV 1.25 mg/kg and who were previously treated with a PD-1 or PD-L1 inhibitor and a platinum-based chemotherapy [see Clinical Studies (14)]. Routine ophthalmologic exams were not conducted in EV-301. The median duration of exposure to PADCEV was 5 months (range: 0.5 to 19.4 months).
Serious adverse reactions occurred in 47% of patients treated with PADCEV. The most common serious adverse reactions (≥2%) were urinary tract infection, acute kidney injury (7% each) and pneumonia (5%). Fatal adverse reactions occurred in 3% of patients, including multiorgan dysfunction (1.0%), hepatic dysfunction, septic shock, hyperglycemia, pneumonitis and pelvic abscess (0.3% each).
Adverse reactions leading to discontinuation occurred in 17% of patients; the most common adverse reactions (≥2%) leading to discontinuation were peripheral neuropathy (5%) and rash (4%).
Adverse reactions leading to dose interruption occurred in 61% of patients; the most common adverse reactions (≥4%) leading to dose interruption were peripheral neuropathy (23%), rash (11%) and fatigue (9%).
Adverse reactions leading to dose reduction occurred in 34% of patients; the most common adverse reactions (≥2%) leading to dose reduction were peripheral neuropathy (10%), rash (8%), decreased appetite (3%) and fatigue (3%).
Table 3 summarizes the most common (≥15%) adverse reactions in EV-301.
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Adverse Reaction |
PADCEV n=296 |
Chemotherapy n=291 |
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All Grades % |
Grade 3-4 % |
All Grades % |
Grade 3-4 % |
|
Skin and subcutaneous tissue disorders | ||||
Rash* |
54 |
14 |
20 |
0.3 |
Alopecia |
47 |
0 |
38 |
0 |
Pruritus |
34 |
2 |
7 |
0 |
Dry skin |
17 |
0 |
4 |
0 |
General disorders and administration site conditions |
||||
Fatigue† |
50 |
9 |
40 |
7 |
Pyrexia‡ |
22 |
2 |
14 |
0 |
Nervous system disorders | ||||
Peripheral neuropathy§ |
50 |
5 |
34 |
3 |
Dysgeusia¶ |
26 |
0 |
8 |
0 |
Metabolism and nutrition disorders | ||||
Decreased appetite |
41 |
5 |
27 |
2 |
Gastrointestinal disorders | ||||
Diarrhea# |
35 |
4 |
23 |
2 |
Nausea |
30 |
1 |
25 |
2 |
Constipation |
28 |
1 |
25 |
2 |
Abdominal PainÞ |
20 |
1 |
14 |
3 |
Musculoskeletal and connective tissue disorders |
||||
Musculoskeletal Painß |
25 |
2 |
35 |
5 |
Eye Disorders |
||||
Dry eyeà |
24 |
0.7 |
6 |
0.3 |
Blood and lymphatic system disorders |
||||
Anemia |
20 |
6 |
30 |
12 |
Infections and infestations |
||||
Urinary Tract Infectionè |
17 |
6 |
13 |
3 |
Vascular disorders |
||||
Hemorrhageð |
17 |
3 |
13 |
2 |
Investigations |
||||
Weight decreased |
16 |
0.3 |
7 |
0 |
Clinically relevant adverse reactions (<15%) include vomiting (14%), aspartate aminotransferase increased (12%), hyperglycemia (10%), alanine aminotransferase increased (9%), pneumonitis (3%) and infusion site extravasation (0.7%).
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Laboratory Abnormality |
PADCEV* |
Chemotherapy* |
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Grades 2-4 % |
Grade 3-4 % |
Grades 2-4 % |
Grade 3-4 % |
|
Hematology |
||||
Lymphocytes decreased |
41 |
14 |
34 |
18 |
Hemoglobin decreased |
28 |
4 |
42 |
14 |
Neutrophils decreased |
27 |
12 |
25 |
17 |
Chemistry |
||||
Phosphate decreased |
39 |
8 |
24 |
6 |
Glucose increased (non-fasting) |
33 |
9 |
27 |
6 |
Creatinine increased |
18 |
2 |
13 |
0 |
Potassium decreased |
16 |
2 |
7 |
3 |
Lipase increased |
13 |
8 |
7 |
4 |
Sodium decreased |
8 |
8 |
5 |
5 |
EV-201, Cohort 1
The safety of PADCEV was evaluated in EV-201, Cohort 1 in patients (n=125) with locally advanced or metastatic urothelial cancer who had received prior treatment with a PD-1 or PD-L1 inhibitor and platinum-based chemotherapy [see Clinical Studies (14)]. Patients received PADCEV 1.25 mg/kg on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity. The median duration of exposure to PADCEV was 4.6 months (range: 0.5-15.6).
Serious adverse reactions occurred in 46% of patients treated with PADCEV. The most common serious adverse reactions (≥3%) were urinary tract infection (6%), cellulitis (5%), febrile neutropenia (4%), diarrhea (4%), sepsis (3%), acute kidney injury (3%), dyspnea (3%), and rash (3%). Fatal adverse reactions occurred in 3.2% of patients, including acute respiratory failure, aspiration pneumonia, cardiac disorder, sepsis and pneumonitis (each 0.8%).
Adverse reactions leading to discontinuation occurred in 16% of patients; the most common adverse reaction leading to discontinuation was peripheral neuropathy (6%).
Adverse reactions leading to dose interruption occurred in 64% of patients; the most common adverse reactions leading to dose interruption were peripheral neuropathy (18%), rash (9%) and fatigue (6%).
Adverse reactions leading to dose reduction occurred in 34% of patients; the most common adverse reactions leading to dose reduction were peripheral neuropathy (12%), rash (6%) and fatigue (4%).
Table 5 summarizes the All Grades and Grades 3-4 adverse reactions reported in patients in EV-201, Cohort 1.
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Adverse Reaction |
PADCEV n=125 |
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All Grades % |
Grade 3-4 % |
|
Any |
100 |
73 |
General disorders and administration site conditions |
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Fatigue* |
56 |
6 |
Nervous system disorders |
||
Peripheral neuropathy† |
56 |
4 |
Dysgeusia |
42 |
0 |
Metabolism and nutrition disorders |
||
Decreased appetite |
52 |
2 |
Skin and subcutaneous tissue disorders |
||
Rash‡ |
52 |
13 |
Alopecia |
50 |
0 |
Dry skin |
26 |
0 |
Pruritus§ |
26 |
2 |
Gastrointestinal disorders |
||
Nausea |
45 |
3 |
Diarrhea¶ |
42 |
6 |
Vomiting |
18 |
2 |
Eye disorders |
||
Dry eye# |
40 |
0 |
Clinically relevant adverse reactions (<15%) include herpes zoster (3%), pneumonitis (2%) and infusion site extravasation (2%).
Laboratory Abnormality |
PADCEV |
|
Grades 2-4* % |
Grade 3-4* % |
|
Hematology |
||
Hemoglobin decreased |
34 |
10 |
Lymphocytes decreased |
32 |
10 |
Neutrophils decreased |
14 |
5 |
Chemistry |
||
Phosphate decreased |
34 |
10 |
Glucose increased (non-fasting) |
27 |
8 |
Creatinine increased |
20 |
2 |
Potassium decreased |
19† |
1 |
Lipase increased |
14 |
9 |
Sodium decreased |
8 |
8 |
Urate increased |
7 |
7 |
EV-201, Cohort 2
The safety of PADCEV was evaluated in EV-201, Cohort 2 in patients with locally advanced or metastatic urothelial cancer (n=89) who received at least one dose of PADCEV 1.25 mg/kg and had prior treatment with a PD-1 or PD-L1 inhibitor and were not eligible for cisplatin-based chemotherapy. The median duration of exposure was 5.98 months (range: 0.3 to 24.6 months).
Serious adverse reactions occurred in 39% of patients treated with PADCEV. The most common serious adverse reactions (≥3%) were pneumonia, sepsis and diarrhea (5% each). Fatal adverse reactions occurred in 8% of patients, including acute kidney injury (2.2%), metabolic acidosis, sepsis, multiorgan dysfunction, pneumonia and pneumonitis (1.1% each).
Adverse reactions leading to discontinuation occurred in 20% of patients; the most common adverse reaction (≥2%) leading to discontinuation was peripheral neuropathy (7%).
Adverse reactions leading to dose interruption occurred in 60% of patients; the most common adverse reactions (≥3%) leading to dose interruption were peripheral neuropathy (19%), rash (9%), fatigue (8%), diarrhea (5%), aspartate aminotransferase increased (3%) and hyperglycemia (3%).
Adverse reactions leading to dose reduction occurred in 49% of patients; the most common adverse reactions (≥3%) leading to dose reduction were peripheral neuropathy (19%), rash (11%) and fatigue (7%).
Table 7 summarizes the All Grades and Grades 3-4 adverse reactions reported in patients in EV-201, Cohort 2.
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Adverse Reaction |
PADCEV n=89 |
|
All Grades (%) |
Grades 3-4 (%) |
|
Skin and subcutaneous tissue disorders |
||
Rash* |
66 |
17 |
Alopecia |
53 |
0 |
Pruritus |
35 |
3 |
Dry skin |
19 |
1 |
Nervous system disorders |
||
Peripheral neuropathy† |
58 |
8 |
Dysgeusia‡ |
29 |
0 |
General disorders and administration site conditions |
||
Fatigue§ |
48 |
11 |
Metabolism and nutrition disorders |
||
Decreased appetite |
40 |
6 |
Hyperglycemia |
16 |
9 |
Blood and lymphatic disorders |
||
Anemia |
38 |
11 |
Gastrointestinal disorders |
||
Diarrhea¶ |
36 |
8 |
Nausea |
30 |
1 |
Investigations |
||
Weight decreased |
35 |
1 |
Eye disorders |
||
Dry eye# |
30 |
0 |
Clinically relevant adverse reactions (<15%) include vomiting (13%), aspartate aminotransferase increased (12%), lipase increased (11%), alanine aminotransferase increased (10%), pneumonitis (4%) and infusion site extravasation (1%).
|
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Laboratory Abnormality |
PADCEV N=88* |
|
Grades 2-4* % |
Grade 3-4* % |
|
Hematology |
||
Lymphocytes decreased |
43 |
15 |
Hemoglobin decreased |
34 |
5 |
Neutrophils decreased |
20 |
9 |
Chemistry |
||
Glucose increased (non-fasting) |
36 |
13 |
Phosphate decreased |
25 |
7 |
Creatinine increased |
23 |
3 |
Lipase increased |
18 |
11 |
Urate increased |
9 |
9 |
Potassium increased |
8 |
6 |
Sodium decreased |
7 |
7 |
The following adverse reactions have been identified during post-approval use of PADCEV. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Skin and subcutaneous tissue disorders: Epidermal necrosis, Stevens-Johnson syndrome, toxic epidermal necrolysis [see Warnings and Precautions (5.1)].
As with all therapeutic proteins, there is a potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies in the trials described below with the incidence of antibodies in other trials or other enfortumab vedotin-ejfv products may be misleading.
Following administration of PADCEV 1.25 mg/kg; 16/590 (2.7%) patients tested positive for anti-therapeutic antibody (ATA) against enfortumab vedotin-ejfv at one or more post-baseline time points. Due to the limited number of patients with ATA against enfortumab vedotin-ejfv, no conclusions can be drawn concerning a potential effect of immunogenicity on efficacy, safety or pharmacokinetics.
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.
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 approximately 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 (approximately 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 at least 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
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 680 patients treated with PADCEV in clinical trials, 440 (65%) were 65 years or older and 168 (25%) were 75 years or older. No overall differences in safety or effectiveness were observed between these patients 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. No adjustment in the starting dose is required when administering PADCEV to patients with mild hepatic impairment (total bilirubin 1 to 1.5 × ULN and AST any, or total bilirubin ≤ULN and AST >ULN).
No dose adjustment is required in patients with mild (CrCL >60-90 mL/min), moderate (CrCL 30-60 mL/min) or severe (CrCL <30 mL/min) renal impairment [see Clinical Pharmacology (12.3)].
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.
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.
Enfortumab vedotin-ejfv is an ADC. The antibody is a human IgG1 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 apoptotic cell death.
In an exposure-response analysis, higher enfortumab vedotin-ejfv exposure was associated with higher incidence of some adverse reactions (e.g., Grade ≥2 peripheral neuropathy, Grade ≥3 hyperglycemia). The exposure-response relationship for efficacy has not been fully characterized.
Cardiac Electrophysiology
At the recommended dose, PADCEV had no large QTc prolongation (>20 msec).
Population pharmacokinetic analysis included data from 748 patients based on five studies. Enfortumab vedotin-ejfv pharmacokinetics were characterized after single and multiple doses in patients with locally advanced or metastatic urothelial carcinoma and other solid tumors.
The exposure parameters of ADC and unconjugated MMAE (the cytotoxic component of enfortumab vedotin-ejfv) are summarized in Table 9 below. Peak ADC concentrations were observed near the end of intravenous infusion while peak MMAE concentrations were observed approximately 2 days after enfortumab vedotin-ejfv dosing. Minimal accumulation of the ADC and MMAE was observed following repeat administration of enfortumab vedotin-ejfv in patients. Steady-state concentrations of ADC and MMAE were reached after 1 treatment cycle.
Cmax = maximum concentration, AUC0-28d = area under the concentration-time curve from time zero to 28 days, Ctrough,0-28d = pre-dose concentration on day 28 | ||
ADC Mean (± SD) |
Unconjugated MMAE Mean (± SD) |
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Cmax |
28 (6.1) µg/mL |
5.5 (3.0) ng/mL |
AUC0-28d |
110 (26) µg∙d/mL |
85 (50) ng∙d/mL |
Ctrough,0-28d |
0.31 (0.18) µg/mL |
0.81 (0.88) ng/mL |
Distribution
The estimated mean steady-state volume of distribution of ADC was 12.8 liters following administration of enfortumab vedotin-ejfv. Plasma protein binding of MMAE ranged from 68% to 82%, in vitro.
Elimination
ADC and MMAE exhibited multi-exponential declines with an elimination half-life of 3.6 days and 2.6 days, respectively. The mean clearance (CL) of enfortumab vedotin-ejfv and unconjugated MMAE in patients was 0.11 L/h and 2.11 L/h, respectively, in patients. Elimination of MMAE appeared to be limited by its rate of release from enfortumab vedotin-ejfv.
Metabolism
Enfortumab vedotin-ejfv catabolism has not been studied in humans; however, it is expected to undergo catabolism to small peptides, amino acids, unconjugated MMAE, and unconjugated MMAE-related catabolites. Enfortumab vedotin-ejfv releases MMAE via proteolytic cleavage, and MMAE is primarily metabolized by CYP3A4 in vitro.
Excretion
The excretion of enfortumab vedotin-ejfv is not fully characterized. Following a single-dose of another ADC that contains MMAE, 17% of the total MMAE administered was recovered in feces and 6% in urine over a 1-week period, primarily as unchanged drug. A similar excretion profile of MMAE is expected after enfortumab vedotin-ejfv administration.
Specific Populations
Based on population pharmacokinetic analysis, no clinically significant differences in the pharmacokinetics of enfortumab vedotin-ejfv were observed based on age (24 to 90 years), sex, or race/ethnicity (Caucasian, Asian, Black, or others).
Hepatic Impairment
Based on population pharmacokinetics analysis, there was a 37% AUC0-28d increase in unconjugated MMAE exposure observed in patients with mild hepatic impairment (total bilirubin of 1 to 1.5 × ULN and AST any, or total bilirubin ≤ULN and AST >ULN, n=65) compared to normal hepatic function. Enfortumab vedotin-ejfv has only been studied in limited number of patients with moderate hepatic impairment and has not been evaluated in patients with severe hepatic impairment. The effect of moderate or severe hepatic impairment (total bilirubin >1.5 x ULN and AST any) or liver transplantation on the pharmacokinetics of ADC or unconjugated MMAE is unknown.
Renal Impairment
The pharmacokinetics of enfortumab vedotin-ejfv and unconjugated MMAE were evaluated after the administration of 1.25 mg/kg of enfortumab vedotin-ejfv to patients with mild (creatinine clearance; CrCL >60–90 mL/min; n=272), moderate (CrCL 30–60 mL/min; n=315) and severe (CrCL <30 mL/min; n=25) renal impairment. No significant differences in exposure (AUC) of ADC and MMAE were observed in patients with mild, moderate or severe renal impairment compared to patients with normal renal function. The effect of end stage renal disease with or without dialysis on the pharmacokinetics of ADC or unconjugated MMAE is unknown.
Drug Interaction Trials
No clinical trials evaluating the drug-drug interaction potential of enfortumab vedotin-ejfv have been conducted.
Physiologically Based Pharmacokinetic (PBPK) Modeling Predictions:
Dual P-gp and Strong CYP3A4 Inhibitor: Concomitant use of enfortumab vedotin-ejfv with ketoconazole (a dual P-gp and strong CYP3A4 inhibitor) is predicted to increase unconjugated MMAE Cmax by 15% and AUC by 38%.
Dual P-gp and Strong CYP3A4 Inducer: Concomitant use of enfortumab vedotin-ejfv with rifampin (a dual P-gp and strong CYP3A4 inducer) is predicted to decrease unconjugated MMAE Cmax by 28% and AUC by 53%.
Sensitive CYP3A substrates: Concomitant use of enfortumab vedotin-ejfv is predicted not to affect exposure to midazolam (a sensitive CYP3A substrate).
In Vitro Studies
Transporter Systems: MMAE is a substrate of P-glycoprotein (P-gp), but not an inhibitor of P-gp.
Carcinogenicity studies with enfortumab vedotin-ejfv or the small molecule cytotoxic agent (MMAE) have not been conducted.
MMAE was genotoxic in the rat bone marrow micronucleus study through an aneugenic mechanism. This effect is consistent with the pharmacological effect of MMAE as a microtubule-disrupting agent. MMAE was not mutagenic in the bacterial reverse mutation assay (Ames test) or the L5178Y mouse lymphoma forward mutation assay.
Fertility studies with enfortumab vedotin-ejfv or MMAE have not been conducted. However, results of repeat-dose toxicity studies in rats indicate the potential for enfortumab vedotin-ejfv to impair male reproductive function and fertility.
In repeat-dose toxicology studies conducted in rats for up to 13 weeks, doses ≥2 mg/kg enfortumab vedotin-ejfv (at exposures similar to the exposures at the recommended human dose) resulted in decreases in testes and epididymis weights, seminiferous tubule degeneration, spermatid/spermatocyte depletion in the testes and cell debris, sperm granuloma and hypospermia/abnormal spermatids in the epididymis. Findings in the testes and epididymis did not reverse by the end of the recovery period.
Previously Treated Locally Advanced or Metastatic Urothelial Carcinoma
EV-301
The efficacy of PADCEV was evaluated in EV-301 (NCT03474107), an open-label, randomized, multicenter trial that enrolled 608 patients with locally advanced or metastatic urothelial cancer who received prior treatment with a PD-1 or PD-L1 inhibitor and platinum-based chemotherapy. Patients were randomized 1:1 to receive either PADCEV 1.25 mg/kg on Days 1, 8 and 15 of a 28-day cycle or investigator’s choice of chemotherapy. Randomization was stratified by ECOG PS (0 vs 1), region of world (Western Europe vs US vs Rest of World), and presence of liver metastasis.
Patients were excluded if they had active central nervous system (CNS) metastases, ongoing sensory or motor neuropathy ≥Grade 2, or uncontrolled diabetes defined as hemoglobin A1C (HbA1c) ≥8% or HbA1c ≥7% with associated diabetes symptoms.
The median age was 68 years (range: 30 to 88 years) and 77% were male. Racial demographics were reported as White (52%), Asian (33%), Black (0.7%), Native Hawaiian or Other Pacific Islander (0.2%) or not reported (15%). Nine percent of patients were Hispanic or Latino. All patients had a baseline Eastern Cooperative Oncology Group (ECOG) performance status of 0 (40%) or 1 (60%). Thirty-four percent of patients had tumors located in the upper tract that included the renal pelvis and ureter. Eighty percent of patients had visceral metastases including 31% with liver metastases. Seventy-six percent of patients had pure transitional cell carcinoma (TCC) histology; 14% had TCC with other histologic variants; and 10% had other tumor histologies including adenocarcinoma and squamous cell carcinoma. The median number of prior therapies was 2 (range 1 to ≥3). Sixty-three percent of patients received prior cisplatin-based regimens, 26% received prior carboplatin-based regimens, and an additional 11% received both cisplatin and carboplatin-based regimens. Patients on the control arm received docetaxel (38%), paclitaxel (36%) or vinflunine (25%).
The major efficacy outcome measures were overall survival (OS), progression free survival (PFS), and overall response rate (ORR) assessed by investigator using RECIST v1.1. Efficacy results were consistent across all stratified patient subgroups.
Table 10 and Figures 2-3 summarize the efficacy results for EV-301.
Endpoint |
PADCEV N=301 |
Chemotherapy N=307 |
Overall Survival* |
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Number (%) of patients with events |
134 (44.5) |
167 (54.4) |
Median in months (95% CI) |
12.9 (10.6, 15.2) |
9.0 (8.1, 10.7) |
Hazard ratio (95% CI) |
0.70 (0.56, 0.89) |
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p-value |
0.0014 |
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Progression Free Survival* |
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Number (%) of patients with events |
201 (66.8) |
231 (75.2) |
Median in months (95% CI) |
5.6 (5.3, 5.8) |
3.7 (3.5, 3.9) |
Hazard ratio (95% CI) |
0.62 (0.51, 0.75) |
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p-value |
<0.0001 |
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Overall Response Rate (CR + PR)† |
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ORR (%) (95% CI) |
40.6 (34.9, 46.5) |
17.9 (13.7, 22.8) |
p-value |
<0.0001 |
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Complete response rate (%) |
4.9 |
2.7 |
Partial response rate (%) |
35.8 |
15.2 |
EV-201, Cohort 1
The efficacy of PADCEV was also investigated in Cohort 1 of EV-201, a single-arm, multi-cohort, multicenter trial that enrolled 125 patients with locally advanced or metastatic urothelial cancer who received prior treatment with a PD-1 or PD-L1 inhibitor and a platinum-based chemotherapy. Patients were excluded if they had active central nervous system (CNS) metastases, ongoing sensory or motor neuropathy ≥Grade 2, heart failure, or uncontrolled diabetes defined as hemoglobin A1C (HbA1c) ≥8% or HbA1c ≥7% with associated diabetes symptoms.
PADCEV was administered at a dose of 1.25 mg/kg, as an intravenous (IV) infusion on days 1, 8, and 15 of each 28-day cycle.
The median age was 69 years (range: 40 to 84 years) and 70% were male. Racial demographics were reported as White (85%), Asian (9%), Black (2%), Other (0.8%) or not reported (4%). Four percent of patients were Hispanic or Latino. All patients had a baseline Eastern Cooperative Oncology Group (ECOG) performance status of 0 (32%) or 1 (68%). Ninety percent of patients had visceral metastases including 40% with liver metastases. Approximately two-thirds (67%) of patients had pure transitional cell carcinoma (TCC) histology; 33% had TCC with other histologic variants. The median number of prior systemic therapies was 3 (range: 1 to 6). Sixty-six percent of patients received prior cisplatin-based regimens, 26% received prior carboplatin-based regimens, and an additional 8% received both cisplatin and carboplatin-based regimens.
The major efficacy outcome measures were confirmed objective response rate (ORR) and duration of response (DOR) assessed by blinded independent central review (BICR) using RECIST v1.1.
Efficacy results are presented in Table 11.
NE = not estimable | ||||
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Endpoint |
PADCEV n=125 |
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Confirmed ORR (95% CI) |
44% (35.1, 53.2) |
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Complete Response Rate (CR) |
12% |
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Partial Response Rate (PR) |
32% |
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Median* Duration of Response, months (95% CI) |
7.6 (6.3, NE) |
Cisplatin Ineligible Patients with Locally Advanced or Metastatic Urothelial Carcinoma
The efficacy of PADCEV was also evaluated in Cohort 2 of EV-201, a single-arm, multi-cohort, multicenter trial in 89 patients with locally advanced or metastatic urothelial cancer who received prior treatment with a PD-1 or PD-L1 inhibitor, and were cisplatin ineligible and did not receive platinum in the locally advanced or metastatic setting. Patients were excluded if they had active CNS metastases, ongoing sensory or motor neuropathy ≥Grade 2, heart failure, or uncontrolled diabetes defined as hemoglobin A1C (HbA1c) ≥8% or HbA1c ≥7% with associated diabetes symptoms.
PADCEV was administered at a dose of 1.25 mg/kg, as an intravenous (IV) infusion on days 1, 8, and 15 of each 28-day cycle.
The median age was 75 years (range: 49 to 90 years), 74% were male. Racial demographics were reported as White (70%), Asian (22%) or not reported (8%). One percent of patients were Hispanic or Latino. Patients had a baseline ECOG performance status of 0 (42%), 1 (46%) and 2 (12%). Forty-three percent of patients had tumors located in the upper tract that included the renal pelvis and ureter. Seventy-nine percent of patients had visceral metastases and 24% had liver metastases.
Reasons for cisplatin ineligibility included: 66% with baseline creatinine clearance of 30 – 59 mL/min, 7% with ECOG PS of 2, 15% with Grade 2 or greater hearing loss, and 12% with more than one cisplatin-ineligibility criteria. Seventy percent of patients had TCC histology; 13% had TCC with squamous differentiation and 17% had TCC with other histologic variants.
The median number of prior systemic therapies was 1 (range: 1 to 4).
Efficacy results are presented in Table 12 below.
NE = not estimable | ||||||
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Endpoint |
PADCEV N=89 |
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Confirmed ORR (95% CI) |
51% (39.8, 61.3) |
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Complete Response Rate (CR) |
22% |
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Partial Response Rate (PR) |
28% |
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Median* Duration of Response, months (95% CI) |
13.8 (6.4, NE) |
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:
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
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 Population (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 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.
©2021 Agensys, Inc. and Seagen Inc.
301048-EV-USA
PATIENT INFORMATION PADCEV® (PAD-sev) (enfortumab vedotin-ejfv) for injection |
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What is the most important information I should know about PADCEV? PADCEV may cause serious side effects, including: Skin reactions. Severe skin reactions have happened in people treated with PADCEV, in some cases severe skin reactions have caused death. Most severe skin reactions occurred during the first cycle (28 days) of treatment but may happen later. Your healthcare provider will monitor you during treatment and may prescribe medicines if you get skin reactions. Tell your healthcare provider right away if you develop any of these signs of a new or worsening skin reaction: |
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See “What are the possible side effects of PADCEV?” for more information about side effects. |
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What is PADCEV? PADCEV is a prescription medicine used to treat adults with bladder cancer and cancers of the urinary tract (renal pelvis, ureter or urethra) that has spread or cannot be removed by surgery. PADCEV may be used if you:
It is not known if PADCEV is safe and effective in children. |
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Before receiving PADCEV, tell your healthcare provider about all of your medical conditions, including if you:
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Taking PADCEV with certain other medicines may cause side effects. |
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How will I receive PADCEV?
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What are the possible side effects of PADCEV? PADCEV may cause serious side effects, including: |
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The most common side effects of PADCEV include: |
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If you have certain side effects, your healthcare provider may decrease your dose or stop your treatment with PADCEV for a period of time (temporarily) or completely. PADCEV may cause fertility problems in males, which may affect the ability to father children. Talk to your healthcare provider if you have concerns about fertility. These are not all of the possible side effects of PADCEV. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. |
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General information about the safe and effective use of PADCEV. Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. If you would like more information about PADCEV, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about PADCEV that is written for healthcare professionals. |
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What are the ingredients in PADCEV? Active ingredient: enfortumab vedotin-ejfv Inactive ingredients: histidine, histidine hydrochloride monohydrate, polysorbate 20, and trehalose dehydrate. Manufactured and Marketed by: Astellas Pharma US, Inc., Northbrook, Illinois 60062 Distributed and Marketed by: Seagen Inc., Bothell, WA 98021 U.S. License 2124 PADCEV® is a registered trademark jointly owned by Agensys, Inc. and Seagen Inc. ©2021 Agensys, Inc. and Seagen Inc. For more information, go to www.padcev.com or call 1-888-4-PADCEV |
This Patient Information has been approved by the U.S. Food and Drug Administration. Revised: July 2021
PADCEV
EJFV
enfortumab vedotin injection, powder, lyophilized, for solution |
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PADCEV
EJFV
enfortumab vedotin injection, powder, lyophilized, for solution |
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Labeler - Seattle Genetics, Inc. (028484371) |
Registrant - Astellas Pharma US, Inc. (605764828) |