Medical Editor: John P. Cunha, DO, FACOEP
What Is Padcev?
Padcev (enfortumab vedotin-ejfv) is a Nectin-4-directed antibody and microtubule inhibitor conjugate used to treat adult patients with locally advanced or metastatic urothelial cancer who have previously received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor, and a platinum-containing chemotherapy in the neoadjuvant/adjuvant, locally advanced or metastatic setting.
What Are Side Effects of Padcev?
Side effects of Padcev include:
- fatigue,
- numbness and tingling in extremities,
- decreased appetite,
- rash,
- hair loss,
- nausea,
- changes in taste,
- diarrhea,
- dry eye,
- itching,
- dry skin,
- dry eye, and
- vomiting
Dosage for Padcev
The recommended dose of Padcev 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.
Padcev In Children
Safety and effectiveness of Padcev in pediatric patients have not been established.
What Drugs, Substances, or Supplements Interact with Padcev?
Padcev may interact with other medicines such as:
- strong CYP3A4 inhibitors
Tell your doctor all medications and supplements your child uses.
Padcev During Pregnancy and Breastfeeding
Tell your doctor if you are pregnant or plan to become pregnant before using Padcev; it may harm a fetus. Females of reproductive potential are advised to use effective contraception during treatment with Padcev and for 2 months after the last dose. Males with female partners of reproductive potential are advised to use effective contraception during treatment with Padcev and for 4 months after the last dose. It is unknown if Padcev passes into breast milk. Breastfeeding is not recommended while using Padcev and for at least 3 weeks after the last dose.
Additional Information
Our Padcev (enfortumab vedotin-ejfv) for Injection, for Intravenous Use Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
SLIDESHOW
Signs of Prostate Cancer: Symptoms, PSA Test, Treatments See SlideshowGet emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.
Call your doctor at once if you have symptoms of high blood sugar:
- increased thirst, dry mouth, fruity breath odor;
- increased urination,
- confusion, drowsiness; or
- nausea, vomiting, stomach pain, loss of appetite.
Also call your doctor at once if you have:
- numbness, tingling, or burning pain in your hands or feet;
- pain, redness, and peeling skin on your hands or feet;
- a severe skin rash with itching, scaling, or blisters;
- severely dry eyes, vision problems; or
- redness, itching, swelling, or discomfort where the medicine was injected.
Your cancer treatments may be delayed or permanently discontinued if you have certain side effects.
Common side effects may include:
- numbness or tingling;
- muscle weakness;
- feeling tired;
- nausea, loss of appetite, diarrhea;
- rash, dry skin;
- hair loss; or
- changes in your sense of taste.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Read the entire detailed patient monograph for Padcev (Enfortumab Vedotin-ejfv for Injection)
SIDE EFFECTS
The following serious adverse reactions are described elsewhere in the labeling:
- Skin Reactions [see BOXED WARNING, WARNINGS AND PRECAUTIONS]
- Hyperglycemia [see WARNINGS AND PRECAUTIONS]
- Pneumonitis [see WARNINGS AND PRECAUTIONS]
- Peripheral Neuropathy [see WARNINGS AND PRECAUTIONS]
- Ocular Disorders [see WARNINGS AND PRECAUTIONS]
- Infusion Site Extravasation [see WARNINGS AND PRECAUTIONS]
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 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]. 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.
Table 3: Adverse Reactions (≥15%) in Patients Treated with PADCEV in EV-301
| Adverse Reaction | PADCEV n=296 |
Chemotherapy n=291 |
||
| All Grades % | Grade 3-4 % | All Grades % | Grade 3-4 % | |
| Skin and subcutaneous tissue disorders | ||||
| Rash1 | 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 | ||||
| Fatigue2 | 50 | 9 | 40 | 7 |
| Pyrexia3 | 22 | 2 | 14 | 0 |
| Nervous system disorders | ||||
| Peripheral neuropathy4 | 50 | 5 | 34 | 3 |
| Dysgeusia5 | 26 | 0 | 8 | 0 |
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 41 | 5 | 27 | 2 |
| Gastrointestinal disorders | ||||
| Diarrhea6 | 35 | 4 | 23 | 2 |
| Nausea | 30 | 1 | 25 | 2 |
| Constipation | 28 | 1 | 25 | 2 |
| Abdominal Pain7 | 20 | 1 | 14 | 3 |
| Musculoskeletal and connective tissue disorders | ||||
| Musculoskeletal Pain8 | 25 | 2 | 35 | 5 |
| Eye Disorders | ||||
| Dry eye9 | 24 | 0.7 | 6 | 0.3 |
| Blood and lymphatic system disorders | ||||
| Anemia | 20 | 6 | 30 | 12 |
| Infections and infestations | ||||
| Urinary Tract Infection10 | 17 | 6 | 13 | 3 |
| Vascular disorders | ||||
| Hemorrhage11 | 17 | 3 | 13 | 2 |
| Investigations | ||||
| Weight decreased | 16 | 0.3 | 7 | 0 |
| 1Includes: blister, blood blister, conjunctivitis, dermatitis, dermatitis bullous, drug eruption, eczema, erythema, erythema multiforme, exfoliative rash, intertrigo, palmar-plantar erythrodysesthesia syndrome, rash, rash erythematous, rash macular, rash maculo-papular, rash papular, rash pruritic, rash vesicular, skin irritation, skin exfoliation, stomatitis. 2Includes: fatigue, asthenia 3Includes: pyrexia, hyperthermia, hyperpyrexia, body temperature increased 4Includes: burning sensation, demyelinating polyneuropathy, dysesthesia, hypoesthesia, muscular weakness, neuralgia, neuropathy peripheral, neurotoxicity, paresthesia, peripheral motor neuropathy, peripheral sensorimotor neuropathy, peroneal nerve palsy, peripheral sensory neuropathy, gait disturbance, polyneuropathy, sensory loss 5Includes: dysgeusia, ageusia, hypogeusia 6Includes: diarrhea, colitis, enterocolitis 7Includes: abdominal pain, abdominal pain upper, abdominal pain lower, abdominal discomfort, hepatic pain, abdominal tenderness, gastrointestinal pain 8Includes: myalgia, arthralgia, back pain, bone pain, pain in extremity, musculoskeletal pain, arthritis, neck pain, non-cardiac chest pain, musculoskeletal chest pain, spinal pain, musculoskeletal stiffness, musculoskeletal discomfort 9Includes: blepharitis, conjunctivitis, dry eye, eye irritation, keratitis, keratopathy, lacrimation increased, Meibomian gland dysfunction, ocular discomfort, punctate keratitis 10Includes: urinary tract infection, urinary tract infection bacterial, urinary tract infection enterococcal, streptococcal urinary tract infection, escherichia urinary tract infection, pyelonephritis acute, escherichia pyelonephritis, urinary tract infection fungal, cystitis, urinary tract infection staphylococcal, urinary tract infection pseudomonal 11Includes: hematuria, rectal hemorrhage, gastrointestinal hemorrhage, epistaxis, upper gastrointestinal hemorrhage, tumor hemorrhage, hemoptysis, vaginal hemorrhage, anal hemorrhage, hemorrhagic stroke, urethral hemorrhage, infusion site hemorrhage, conjunctival hemorrhage, hemorrhagic ascites, hemorrhoidal hemorrhage |
||||
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%).
Table 4: Selected Laboratory Abnormalities Reported in ≥15% (Grades 2-4) or ≥5% (Grade 3-4) of Patients Treated with PADCEV in EV-301
| Laboratory Abnormality | PADCEV1 | Chemotherapy1 | ||
| 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 |
| 1The denominator used to calculate the rate varied from 262 to 287 based on the number of patients with a baseline value and at least one post-treatment value. | ||||
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]. 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.
Table 5: Adverse Reactions Reported in ≥15% (All Grades) or ≥5% (Grade 3-4) of Patients Treated with PADCEV in EV-201 Cohort 1
| Adverse Reaction | PADCEV n=125 |
|
| All Grades % | Grade 3-4 % | |
| Any | 100 | 73 |
| General disorders and administration site conditions | ||
| Fatigue1 | 56 | 6 |
| Nervous system disorders | ||
| Peripheral neuropathy2 | 56 | 4 |
| Dysgeusia | 42 | 0 |
| Metabolism and nutrition disorders | ||
| Decreased appetite | 52 | 2 |
| Skin and subcutaneous tissue disorders | ||
| Rash3 | 52 | 13 |
| Alopecia | 50 | 0 |
| Dry skin | 26 | 0 |
| Pruritus4 | 26 | 2 |
| Gastrointestinal disorders | ||
| Nausea | 45 | 3 |
| Diarrhea5 | 42 | 6 |
| Vomiting | 18 | 2 |
| Eye disorders | ||
| Dry eye6 | 40 | 0 |
| 1Includes: asthenia and fatigue 2Includes: hypoesthesia, gait disturbance, muscular weakness, neuralgia, paresthesia, peripheral motor neuropathy, peripheral sensory neuropathy and peripheral sensorimotor neuropathy. 3Includes: dermatitis acneiform, dermatitis bullous, dermatitis contact, dermatitis exfoliative, drug eruption, erythema, erythema multiforme, exfoliative rash, palmar-plantar erythrodysesthesia syndrome, photosensitivity reaction, rash, rash erythematous, rash generalized, rash macular, rash maculo-papular, rash papular, rash pustular, rash pruritic, rash vesicular, skin exfoliation, stasis dermatitis, and symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) and urticaria. 4Includes: pruritus and pruritus generalized 5Includes: colitis, diarrhea and enterocolitis 6Includes: blepharitis, conjunctivitis, dry eye, eye irritation, keratitis, keratopathy, lacrimation increased, limbal stem cell deficiency, Meibomian gland dysfunction, ocular discomfort, punctate keratitis, tear break up time decreased |
||
Clinically relevant adverse reactions (<15%) include herpes zoster (3%), pneumonitis (2%) and infusion site extravasation (2%).
Table 6: Selected Laboratory Abnormalities Reported in ≥15% (Grades 2-4) or ≥5% (Grade 3-4) of Patients Treated with PADCEV in EV-201, Cohort 1
| Laboratory Abnormality | PADCEV | |
| Grades 2-41 % | Grade 3-41 % | |
| 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 | 192 | 1 |
| Lipase increased | 14 | 9 |
| Sodium decreased | 8 | 8 |
| Urate increased | 7 | 7 |
| 1Denominator for each laboratory parameter is based on the number of patients with a baseline and post-treatment laboratory value available for 121 or 122 patients. 2Includes Grade 1 (potassium 3.0-3.5 mmol/L) - Grade 4. |
||
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.
Table 7: Adverse Reactions ≥15% (All Grades) or ≥5% (Grades 3-4) in Patients Treated with PADCEV in EV-201, Cohort 2
| Adverse Reaction | PADCEV n=89 |
|
| All Grades (%) | Grades 3-4 (%) | |
| Skin and subcutaneous tissue disorders | ||
| Rash1 | 66 | 17 |
| Alopecia | 53 | 0 |
| Pruritus | 35 | 3 |
| Dry skin | 19 | 1 |
| Nervous system disorders | ||
| Peripheral neuropathy2 | 58 | 8 |
| Dysgeusia3 | 29 | 0 |
| General disorders and administration site conditions | ||
| Fatigue4 | 48 | 11 |
| Metabolism and nutrition disorders | ||
| Decreased appetite | 40 | 6 |
| Hyperglycemia | 16 | 9 |
| Blood and lymphatic disorders | ||
| Anemia | 38 | 11 |
| Gastrointestinal disorders | ||
| Diarrhea5 | 36 | 8 |
| Nausea | 30 | 1 |
| Investigations | ||
| Weight decreased | 35 | 1 |
| Eye disorders | ||
| Dry eye6 | 30 | 0 |
| 1Includes: blister, conjunctivitis, dermatitis bullous, dermatitis exfoliative generalized, eczema, erythema, erythema multiforme, intertrigo, palmar-plantar erythrodysesthesia syndrome, rash, rash erythematous, rash macular, rash maculo-papular, rash papular, rash vesicular, skin exfoliation, stomatitis 2Includes: demyelinating polyneuropathy, gait disturbance, hypoesthesia, motor dysfunction, muscle atrophy, muscular weakness, paresthesia, peripheral motor neuropathy, peripheral sensorimotor neuropathy, peroneal nerve palsy, peripheral sensory neuropathy 3Includes: dysgeusia, ageusia, hypogeusia 4Includes: fatigue, asthenia 5Includes: diarrhea, colitis, enterocolitis 6Includes: blepharitis, conjunctivitis, dry eye, eye irritation, keratitis, keratopathy, lacrimation increased, limbal stem cell deficiency, Meibomian gland dysfunction, ocular discomfort, punctate keratitis, tear break up time decreased |
||
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%).
Table 8: Selected Laboratory Abnormalities Reported in ≥15% (Grades 2-4) or ≥5% (Grades 3-4) of Patients Treated with PADCEV in EV-201, Cohort 2
| Laboratory Abnormality | PADCEV N=881 |
|
| Grades 2-41 % | Grade 3-41 % | |
| 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 |
| 1Based on the number of patients with a baseline value and at least one post-treatment value. | ||
Post Marketing Experience
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].
Immunogenicity
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.
DRUG INTERACTIONS
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], 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.
Read the entire FDA prescribing information for Padcev (Enfortumab Vedotin-ejfv for Injection)
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