(enfortumab vedotin-ejfv)
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)].
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 of PADCEV as a single agent, 17% of the 720 patients treated with PADCEV developed hyperglycemia of any grade; 7% of patients developed Grade 3-4 hyperglycemia (Grade 3: 6.5%, Grade 4: 0.6%). Fatal events of hyperglycemia and diabetic ketoacidosis occurred in one patient each (0.1%). The incidence of Grade 3-4 hyperglycemia increased consistently in patients with higher body mass index and in patients with higher baseline A1C. The median time to onset of hyperglycemia was 0.5 months (range: 0 to 20 months). Hyperglycemia led to discontinuation of PADCEV in 0.7% of patients [see Adverse Reactions (6.1)]. Five percent (5%) of patients required initiation of insulin therapy for treatment of hyperglycemia. Of the patients who initiated insulin therapy for treatment of hyperglycemia, 66% (23/35) discontinued insulin by the time of last evaluation.
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/ILD occurred in patients treated with PADCEV.
When PADCEV was given in combination with intravenous pembrolizumab for the treatment of MIBC, 7% of the 570 patients treated with combination therapy had pneumonitis/ILD of any grade and 1.8% had Grade 3-4. The median time to onset of any grade pneumonitis/ILD was 3.2 months (range: 0.7 to 13 months).
When PADCEV was given in combination with intravenous pembrolizumab for the treatment of la/mUC, 10% of the 564 patients treated with combination therapy had pneumonitis/ILD of any grade and 4% had Grade 3‑4. A fatal event of pneumonitis/ILD occurred in two patients (0.4%). The incidence of pneumonitis/ILD, including severe events, occurred at a higher rate when PADCEV was given in combination with intravenous pembrolizumab compared to PADCEV as a single agent. The median time to onset of any grade pneumonitis/ILD was 4 months (range: 0.3 to 26 months).
In clinical trials of PADCEV as a single agent, 3% of the 720 patients treated with PADCEV had pneumonitis/ILD of any grade and 0.8% had Grade 3-4. The median time to onset of any grade pneumonitis/ILD was 2.9 months (range: 0.6 to 6 months).
Monitor patients for signs and symptoms indicative of pneumonitis/ILD 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 Grade 2 pneumonitis/ILD and consider dose reduction. Permanently discontinue PADCEV in all patients with Grade 3 or 4 pneumonitis/ILD [see Dosage and Administration (2.2)].
When PADCEV was given in combination with intravenous pembrolizumab for the treatment of MIBC, 42% of the 570 patients treated with combination therapy had peripheral neuropathy of any grade, 14% had Grade 2 neuropathy, and 3% had Grade 3 neuropathy. The median time to onset of Grade ≥2 peripheral neuropathy was 4.9 months (range: 0.2 to 23 months) [see Adverse Reactions (6.1)]. Of the patients who experienced neuropathy and had data regarding resolution (n=239), 41% had complete resolution, and 59% of patients had residual neuropathy at last evaluation. Of the patients with residual neuropathy at last evaluation, 30% (42/142) had Grade ≥2 neuropathy.
When PADCEV was given in combination with intravenous pembrolizumab for the treatment of la/mUC, 67% of the 564 patients treated with combination therapy had peripheral neuropathy of any grade, 36% had Grade 2 neuropathy, and 7% had Grade 3 neuropathy. The incidence of peripheral neuropathy occurred at a higher rate when PADCEV was given in combination with intravenous pembrolizumab compared to PADCEV as a single agent. The median time to onset of Grade ≥2 peripheral neuropathy was 6 months (range: 0.3 to 25 months) [see Adverse Reactions (6.1)]. Of the patients who experienced neuropathy and had data regarding resolution (n=373), 13% had complete resolution, and 87% of patients had residual neuropathy at last evaluation. Of the patients with residual neuropathy at last evaluation, 45% (146/326) had Grade ≥2 neuropathy.
Peripheral neuropathy occurred in 53% of the 720 patients treated with PADCEV as a single agent in clinical trials including 38% with sensory neuropathy, 8% with muscular weakness, and 7% with motor neuropathy. Thirty percent of patients experienced Grade 2 reactions and 5% 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 4.9 months (range: 0.1 to 20 months). Neuropathy led to treatment discontinuation in 6% of patients [see Adverse Reactions (6.1)]. Of the patients who experienced neuropathy who had data regarding resolution (n=296), 11% had complete resolution, and 89% had residual neuropathy at the time of their last evaluation. Of the patients with residual neuropathy at last evaluation, 50% (132/262) had Grade ≥2 neuropathy.
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 as a single agent 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 30% of patients, and blurred vision occurred in 10% of patients, during treatment with PADCEV. The median time to onset to symptomatic ocular disorder was 1.7 months (range: 0 to 30.6 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 720 patients treated with PADCEV as a single agent in clinical trials, 1% 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 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)].
PATIENT INFORMATION PADCEV® (PAD-sev) (enfortumab vedotin-ejfv) for injection | ||||
If your healthcare provider prescribes PADCEV in combination with the medicines pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph, also read the Medication Guide that comes with these medicines for additional important information. | ||||
What is the most important information I should know about PADCEV? PADCEV may cause serious side effects, including: Skin reactions. Skin reactions including severe skin reactions have happened in people treated with PADCEV and may be more common when PADCEV is given with pembrolizumab. In some cases, these severe skin reactions have caused death. Most severe skin reactions occurred during the first cycle of treatment but may happen later. Your healthcare provider will monitor you, may stop your treatment with PADCEV completely or for a period of time (temporarily), may change your dose, 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. | ||||
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).
It is not known if PADCEV is safe and effective in children. | ||||
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. | ||||
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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Your healthcare provider may decrease your dose of PADCEV, or temporarily or completely stop your treatment with PADCEV if you get severe side effects. The most common side effects of PADCEV when used in combination with pembrolizumab include: | ||||
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The most common side effects of PADCEV when used alone include: | ||||
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PADCEV may cause fertility problems in females and males, which may affect the ability to have 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. | ||||
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. You can ask your pharmacist or healthcare provider for information about PADCEV that is written for healthcare professionals. | ||||
What are the ingredients in PADCEV? Active ingredient: enfortumab vedotin-ejfv Inactive ingredients: histidine, histidine hydrochloride monohydrate, polysorbate 20, and trehalose dihydrate. 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. ©2026 Agensys, Inc. and Seagen Inc. For more information, go to www.padcev.com or call 1-888-472-3238 10194-EV-US | ||||
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