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
Prostate Cancer Symptoms, PCA Test, Treatments See SlideshowSIDE EFFECTS
The following serious adverse reactions are described elsewhere in the labeling:
- Hyperglycemia [see WARNINGS AND PRECAUTIONS]
- Peripheral Neuropathy [see WARNINGS AND PRECAUTIONS]
- Ocular Disorders [see WARNINGS AND PRECAUTIONS]
- Skin Reactions [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 data in the WARNINGS AND PRECAUTIONS section reflect exposure to PADCEV as a single agent at 1.25 mg/kg in 310 patients in EV-201, EV-101 (NCT02091999), and EV-102 (NCT03219333). Among 310 patients receiving PADCEV, 30% were exposed for ≥ 6 months and 8% were exposed for ≥12 months.
The data described in this section reflect exposure to PADCEV from EV-201, a single arm study 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. 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, and sepsis (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%).
The most common adverse reactions (≥20%) were fatigue, peripheral neuropathy, decreased appetite, rash, alopecia, nausea, dysgeusia, diarrhea, dry eye, pruritus and dry skin. The most common Grade ≥3 adverse reaction (≥5%) were rash, diarrhea, and fatigue.
Table 3 summarizes the all grade and Grade ≥3 adverse reactions reported in patients in EV-201.
Table 3: Adverse Reactions Reported in ≥15% (Any Grade) or ≥5% (Grade ≥3) of Patients Treated with PADCEV in EV-201
| Adverse Reaction | PADCEV n=125 | |
| All Grades % | Grade ≥3 % | |
| Any | 100 | 73 |
| General disorders and administration site conditions | ||
| 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 |
| Eye disorders | ||
| Dry eye¶ | 40 | 0 |
| Gastrointestinal disorders | ||
| Nausea | 45 | 3 |
| Diarrhea# | 42 | 6 |
| Vomiting | 18 | 2 |
| *Includes: asthenia and fatigue †Includes: hypoesthesia, gait disturbance, muscular weakness, neuralgia, paresthesia, peripheral motor neuropathy, peripheral sensory neuropathy and peripheral sensorimotor neuropathy. ‡Includes: 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. §Includes: pruritus and pruritus generalized ¶Includes: 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 #Includes: colitis, diarrhea and enterocolitis | ||
Other clinically significant adverse reactions (≤15%) include: herpes zoster (3%) and infusion site extravasation (2%).
Table 4: Selected Laboratory Abnormalities Reported in ≥ 10% (Grades 2-4) or ≥ 5% (Grade 3-4) of Patients Treated with PADCEV in EV-201
| Adverse Reaction | PADCEV | |
| Grades 2-4* % | Grade 3-4* % | |
| Hematology | ||
| Hemoglobin decreased | 34 | 10 |
| Lymphocytes decreased | 32 | 10 |
| Neutrophils decreased | 14 | 5 |
| Leukocytes decreased | 14 | 4 |
| Chemistry | ||
| Phosphate decreased | 34 | 10 |
| Creatinine increased | 20 | 2 |
| Potassium decreased | 19† | 1 |
| Lipase increased | 14 | 9 |
| Glucose increased | -‡ | 8 |
| Sodium decreased | 8 | 8 |
| Urate increased | 7 | 7 |
| *Denominator for each laboratory parameter is based on the number of patients with a baseline and posttreatment laboratory value available for 121 or 122 patients. †Includes Grade 1 (potassium 3.0-3.5 mmol/L) - Grade 4. ‡CTCAE Grade 2 is defined as fasting glucose >160-250 mg/dL. Fasting glucose levels were not measured in EV-201. However, 23 (19%) patients had non-fasting glucose >160-250 mg/dL. | ||
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 studies described below with the incidence of antibodies in other studies or other enfortumab vedotin products may be misleading.
A total of 365 patients were tested for immunogenicity to PADCEV; 4 patients (1%) were confirmed to be transiently positive for anti-therapeutic antibody (ATA), and 1 patient (0.3%) was confirmed to be persistently positive for ATA at any post-baseline time point. No impact of ATA on efficacy, safety and pharmacokinetics was observed.
Read the entire FDA prescribing information for Padcev (Enfortumab Vedotin-ejfv for Injection)