Padcev (Enfortumab Vedotin): Uses, Dosage & Side Effects
Antibody-drug conjugate for advanced urothelial carcinoma (bladder cancer)
Quick facts about Padcev
Key takeaways about Padcev
- Targeted cancer therapy: Padcev is an antibody-drug conjugate that delivers chemotherapy directly to Nectin-4 expressing cancer cells, reducing damage to healthy tissue
- Used for bladder cancer: Approved for locally advanced or metastatic urothelial carcinoma, either as monotherapy or in combination with pembrolizumab
- Hospital treatment only: Administered as a 30-minute intravenous infusion under medical supervision – it cannot be self-administered at home
- Watch for skin reactions: Severe skin reactions including Stevens-Johnson syndrome can occur, especially in the first weeks – report any rash or blistering immediately
- Not safe in pregnancy: Padcev can harm an unborn baby – effective contraception is required during treatment and for months afterward
What Is Padcev and What Is It Used For?
Padcev (enfortumab vedotin) is an antibody-drug conjugate used to treat adults with advanced or metastatic urothelial carcinoma (bladder cancer) that has spread or cannot be surgically removed. It can be used alone after prior treatments or in combination with pembrolizumab as a first-line therapy.
Padcev contains the active substance enfortumab vedotin, which consists of a monoclonal antibody linked to a cell-killing (cytotoxic) agent called monomethyl auristatin E (MMAE). The monoclonal antibody component is designed to recognize and bind to a protein called Nectin-4, which is expressed at high levels on the surface of urothelial cancer cells. Once the antibody binds to Nectin-4, it is taken up (internalized) by the cancer cell, where the cytotoxic agent is released. MMAE then disrupts the cell's internal scaffolding (microtubule network), causing the cancer cell to stop dividing and ultimately die.
This targeted delivery mechanism means that Padcev can deliver potent chemotherapy directly to cancer cells while relatively sparing healthy tissues. This is a key advantage of antibody-drug conjugates over traditional chemotherapy, which affects both cancerous and normal rapidly dividing cells throughout the body. Clinical trials have demonstrated that Padcev significantly improves survival outcomes in patients with advanced urothelial carcinoma.
Padcev is approved for two main treatment settings. As monotherapy, it is used in adults whose cancer has progressed after treatment with an immune checkpoint inhibitor (such as pembrolizumab or atezolizumab) and platinum-based chemotherapy (such as cisplatin or carboplatin). In combination with pembrolizumab, it can be used as a first-line treatment for patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy, or more broadly as initial treatment based on the landmark EV-302 trial results.
Urothelial carcinoma (also called transitional cell carcinoma) is the most common type of bladder cancer, accounting for approximately 90% of bladder cancer cases worldwide. It arises from the urothelial cells that line the bladder, ureters, and renal pelvis. When the cancer is locally advanced or metastatic, it means it has grown into surrounding tissues or spread to distant organs, making surgical cure unlikely. Globally, bladder cancer is the 10th most common cancer, with approximately 600,000 new cases diagnosed each year according to WHO data.
How Padcev works (mechanism of action)
Padcev works through a three-step mechanism. First, the monoclonal antibody portion of the drug binds specifically to Nectin-4, a cell adhesion molecule that is overexpressed on the surface of most urothelial carcinoma cells. Second, the entire antibody-drug conjugate is internalized into the cancer cell via receptor-mediated endocytosis. Third, once inside the cell, the linker connecting the antibody to the cytotoxic payload is cleaved by lysosomal enzymes, releasing MMAE within the cancer cell.
MMAE is a potent microtubule-disrupting agent that inhibits cell division by preventing the formation of the mitotic spindle. This leads to cell cycle arrest at the G2/M phase and ultimately triggers apoptosis (programmed cell death). Additionally, released MMAE can penetrate into neighboring cancer cells through a process known as the “bystander effect,” potentially killing Nectin-4-negative tumor cells in the vicinity as well.
What Should You Know Before Taking Padcev?
Padcev should not be used if you are allergic to enfortumab vedotin or any of its ingredients. Before starting treatment, your doctor should be informed about any existing conditions, particularly skin problems, diabetes, lung disease, nerve problems, or eye disorders. Pregnancy must be avoided during treatment.
Before receiving Padcev, it is essential that your healthcare team has a comprehensive understanding of your medical history. This allows them to assess whether Padcev is appropriate for you and to plan monitoring strategies that will help catch potential side effects early. Open communication with your oncology team is crucial throughout your treatment journey.
Contraindications
Padcev must not be given to you if you are allergic (hypersensitive) to enfortumab vedotin or any of the other ingredients in this medicine. The other ingredients include histidine, histidine hydrochloride monohydrate, trehalose dihydrate, and polysorbate 20. If you have experienced a severe allergic reaction to any antibody-drug conjugate in the past, be sure to discuss this with your doctor before starting Padcev.
Warnings and Precautions
Talk to your doctor or nurse immediately if you experience any of the following during your treatment with Padcev:
- Skin reactions: Rash or itching that continues to worsen or recurs after treatment, blisters or peeling skin, painful sores in the mouth, nose, throat or genital area, fever or flu-like symptoms, or swollen lymph nodes. These may be signs of a serious skin reaction such as Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN), which can be life-threatening. Skin reactions may be more common when Padcev is given in combination with pembrolizumab.
- High blood sugar (hyperglycemia): Symptoms include frequent urination, increased thirst, blurred vision, confusion, drowsiness, decreased appetite, fruity-smelling breath, nausea, vomiting, or stomach pain. Padcev can cause elevated blood glucose levels even in patients without a prior history of diabetes.
- Lung problems (pneumonitis/interstitial lung disease): New or worsening symptoms including difficulty breathing, shortness of breath, or cough. These lung problems may occur more frequently when Padcev is used in combination with pembrolizumab.
- Infections: If you have or suspect you have an infection. Some infections can be serious and life-threatening, including sepsis.
- Nerve problems (peripheral neuropathy): Decreased sensation, tingling, or a prickling feeling in hands or feet, or muscle weakness. Your doctor may pause treatment, reduce the dose, or discontinue Padcev if neuropathy develops.
- Eye problems: Dry eyes or other ocular symptoms during treatment. Dry eyes are a common side effect of Padcev therapy, and your doctor may recommend artificial tears or refer you to an ophthalmologist.
Padcev can cause serious and potentially life-threatening skin reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). These reactions can occur at any time during treatment but are most common during the first treatment cycles. You will receive a patient card with information about these risks – carry it with you and show it to all healthcare professionals you visit.
Seek immediate medical attention if you develop widespread rash with blisters, peeling skin, or painful mucosal sores.
Pregnancy and Breastfeeding
Padcev can cause serious harm to an unborn baby and must not be used during pregnancy. If you are pregnant, think you may be pregnant, or are planning to become pregnant, consult your doctor before starting this treatment.
Women of childbearing potential must use effective contraception during treatment and for at least 6 months after the last dose of Padcev. Your oncology team can help you select an appropriate contraceptive method.
It is not known whether Padcev passes into breast milk. Because of the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended during treatment and for at least 6 months after the last dose.
Male patients are advised to have sperm samples frozen and stored before starting treatment, as Padcev may affect fertility. Men receiving Padcev should not father a child during treatment and for at least 4 months after the last dose. Effective contraception should be used during this period.
Children and adolescents
Padcev is not intended for use in children and adolescents under 18 years of age. The safety and efficacy of this medicine have not been established in the pediatric population.
Driving and operating machinery
Padcev may indirectly affect your ability to drive or operate machinery due to side effects such as fatigue, peripheral neuropathy, or blurred vision. Do not drive or use machines if you feel unwell during treatment. Discuss with your healthcare provider if you have any concerns about your ability to perform these activities safely.
How Does Padcev Interact with Other Drugs?
Padcev can interact with certain medications, particularly strong CYP3A4 inhibitors such as ketoconazole, which may increase the levels of the cytotoxic component (MMAE) in the blood. Tell your doctor about all medicines you are taking, including prescription drugs, over-the-counter medications, and herbal supplements.
Drug interactions with Padcev primarily relate to the cytotoxic payload MMAE, which is metabolized by the cytochrome P450 enzyme CYP3A4. Medications that inhibit or induce this enzyme can alter the blood levels of MMAE, potentially affecting both the efficacy and safety of the treatment. Your oncologist will review your current medications before starting Padcev and may make adjustments if necessary.
Major Interactions
Strong CYP3A4 inhibitors are the most clinically significant interaction concern. These medications can increase the blood concentration of MMAE, potentially leading to a higher risk of side effects such as peripheral neuropathy and myelosuppression. If you regularly take any of these medications, your doctor may prescribe an alternative during Padcev treatment.
| Drug / Class | Interaction Type | Effect | Clinical Action |
|---|---|---|---|
| Ketoconazole | Strong CYP3A4 inhibitor | Increases MMAE levels in blood | Avoid or substitute during treatment |
| Itraconazole | Strong CYP3A4 inhibitor | Increases MMAE levels in blood | Avoid or substitute during treatment |
| Ritonavir, Cobicistat | Strong CYP3A4 inhibitor | Increases MMAE exposure | Monitor closely; consider alternatives |
| Pembrolizumab | Approved combination | Synergistic antitumor activity; increased skin/lung toxicity risk | Use per approved regimen with enhanced monitoring |
| Rifampicin | Strong CYP3A4 inducer | May decrease MMAE levels | Avoid if possible; may reduce efficacy |
Minor Interactions
Moderate CYP3A4 inhibitors (such as fluconazole, erythromycin, and diltiazem) may have a lesser effect on MMAE levels but should still be discussed with your healthcare team. Grapefruit and Seville oranges are also CYP3A4 inhibitors and should be consumed with caution during Padcev treatment, though the clinical significance of dietary interactions is less well established.
No formal drug-drug interaction studies have shown clinically significant pharmacokinetic interactions between the antibody component of Padcev and other medications. The antibody portion is expected to be metabolized through catabolic pathways rather than by cytochrome P450 enzymes.
What Is the Correct Dosage of Padcev?
Padcev is given as a 30-minute intravenous infusion at a dose of 1.25 mg/kg. When used alone, it is administered on days 1, 8, and 15 of a 28-day cycle. In combination with pembrolizumab, it is given on days 1 and 8 of a 21-day cycle. The dose is calculated based on your body weight.
Padcev is always administered in a hospital or specialized clinic under the supervision of a physician experienced in the use of anticancer therapies. You will never need to prepare or administer this medicine yourself. Before each infusion, your healthcare team will check your blood counts and overall condition to ensure you are fit to receive treatment.
Adults
The recommended dose of Padcev is 1.25 mg per kilogram of body weight, given as an intravenous infusion over approximately 30 minutes. The dosing schedule depends on whether Padcev is used as monotherapy or in combination:
Padcev Monotherapy (28-day cycle)
1.25 mg/kg on days 1, 8, and 15 of each 28-day treatment cycle. Your doctor will determine how many cycles you need based on your response to treatment and tolerability.
Padcev + Pembrolizumab Combination (21-day cycle)
1.25 mg/kg on days 1 and 8 of each 21-day treatment cycle. Pembrolizumab (200 mg) is administered on day 1 of each cycle. Please also read the package leaflet for pembrolizumab.
| Regimen | Dose | Schedule | Cycle Length |
|---|---|---|---|
| Monotherapy | 1.25 mg/kg IV | Days 1, 8, 15 | 28 days |
| + Pembrolizumab | 1.25 mg/kg IV | Days 1, 8 | 21 days |
Children
Padcev is not approved for use in children or adolescents under 18 years of age. Urothelial carcinoma is exceedingly rare in the pediatric population, and no clinical studies have been conducted in this age group.
Elderly
No dose adjustment is required based on age alone. In clinical trials, patients aged 65 years and older received the same dose as younger adults. However, elderly patients may be at increased risk of certain side effects, particularly peripheral neuropathy, fatigue, and hyperglycemia. Your doctor will monitor you closely and may adjust the dose if needed based on tolerability rather than age.
Dose adjustments
Your doctor may need to reduce the dose, delay treatment, or discontinue Padcev depending on the severity of side effects you experience. Common reasons for dose modification include:
- Peripheral neuropathy: Treatment may be paused for grade 2 neuropathy and resumed at a reduced dose once symptoms improve; discontinued for grade 3 or higher
- Skin reactions: Treatment paused or discontinued based on severity; grade 3 reactions require dose reduction upon rechallenge
- Hyperglycemia: Blood sugar must be adequately controlled before resuming treatment; dose reduction may be necessary
Missed Dose
It is very important to keep all scheduled appointments for your Padcev infusions. If you miss a scheduled appointment, contact your oncology team as soon as possible to reschedule. Do not try to “make up” a missed dose on your own. Your doctor will determine the appropriate timing for your next infusion based on your treatment schedule and clinical status.
Overdose
Since Padcev is prepared and administered by healthcare professionals in a controlled clinical setting, overdose is unlikely. However, in the event of an overdose, you would be monitored closely for any adverse effects, and supportive care would be provided as needed. There is no specific antidote for Padcev overdose. Side effects of an overdose would likely be amplified versions of the known side effects, particularly myelosuppression, neuropathy, and skin reactions.
What Are the Side Effects of Padcev?
Like all medicines, Padcev can cause side effects, although not everyone gets them. The most common side effects include fatigue, nausea, hair loss, decreased appetite, peripheral neuropathy, skin rash, diarrhea, and dry eyes. Serious side effects include severe skin reactions, high blood sugar, lung inflammation, and infections.
Padcev, like all effective anticancer therapies, is associated with a range of side effects. The nature and severity of these effects vary between individuals and may also differ depending on whether Padcev is used as monotherapy or in combination with pembrolizumab. Your medical team will monitor you closely throughout treatment, and most side effects can be managed through dose adjustments, supportive medications, or temporary treatment pauses.
It is critically important to report any new or worsening symptoms to your healthcare team promptly. Early detection and management of side effects can prevent them from becoming severe and can help you stay on treatment longer, which may improve your overall outcomes.
Padcev Monotherapy – Side Effect Frequency
Very Common
- Anemia (low red blood cells)
- Nausea, diarrhea, and vomiting
- Fatigue
- Decreased appetite
- Taste changes (dysgeusia)
- Dry eyes
- Hair loss (alopecia)
- Weight loss
- Dry or itchy skin
- Rash
- Flat or raised red bumps on skin (maculopapular rash)
- Elevated liver enzymes (AST or ALT)
- Peripheral neuropathy (nerve damage in hands/feet)
- Hyperglycemia (high blood sugar)
Common
- Abnormal gait (walking difficulties)
- Red eyes (conjunctival hyperemia)
- Hives (urticaria)
- Skin redness (erythema)
- Inflamed, itchy, cracked and uneven patches of skin
- Redness and stinging in palms or soles (palmar-plantar erythrodysesthesia)
- Skin peeling (exfoliation)
- Mouth sores (stomatitis)
- Low platelet count (thrombocytopenia)
- Pneumonitis / interstitial lung disease
- Pneumonia
- Sepsis
- Infusion-related reactions
Uncommon
- Skin irritation
- Burning sensation of the skin
- Nerve function problems causing unusual sensations or movement issues
- Muscle wasting (muscle atrophy)
- Blood blisters
- Allergic skin reaction
- Target lesion-like rash
- Skin peeling over entire body
- Inflammation in skin folds (intertrigo)
- Blisters or blister-like sores on skin
Rare / Frequency Not Known
- Stevens-Johnson syndrome (SJS)
- Toxic epidermal necrolysis (TEN)
- Low white blood cell count with or without fever
- Skin discoloration or abnormal dark pigmentation (hyperpigmentation)
- Diabetic ketoacidosis
- Extravasation (leakage at infusion site)
Padcev + Pembrolizumab Combination – Additional Side Effects
When Padcev is used in combination with pembrolizumab, the side effect profile is broadly similar but with some notable additions and differences. The combination may cause increased immune-related side effects due to the mechanism of pembrolizumab, which activates the immune system against cancer cells.
- Very common (additional): Hypothyroidism (decreased thyroid function)
- Common (additional): Elevated lipase (a pancreatic enzyme), myositis (muscle inflammation)
- Skin reactions may be more frequent and severe when the two drugs are combined
- Pneumonitis may also occur more frequently with combination therapy
If you are receiving the combination treatment, please also read the package leaflet for pembrolizumab for a complete list of its potential side effects. Your oncology team will monitor for side effects specific to each medication.
It is important to report suspected side effects after the medicine has been approved. This allows ongoing monitoring of the benefit-risk balance of the medicine. Healthcare professionals and patients can report suspected side effects to their national medicines regulatory authority (e.g., FDA MedWatch in the United States, Yellow Card Scheme in the United Kingdom, or the EMA in the European Union).
How Should You Store Padcev?
Padcev must be stored in a refrigerator (2°C – 8°C) and must not be frozen. As a hospital-administered medicine, storage is handled by the pharmacy and clinical staff. The prepared infusion solution should be used promptly and not saved for later use.
Keep this medicine out of the sight and reach of children. Do not use this medicine after the expiry date stated on the carton and vial label after “EXP.” The expiry date refers to the last day of that month.
As a patient, you will not typically need to store Padcev yourself, as it is prepared and administered in a hospital or clinic setting. However, it is useful to know the storage requirements:
- Unopened vials: Store in a refrigerator (2°C – 8°C / 36°F – 46°F)
- Do not freeze
- Reconstituted solution: Should be used promptly after preparation; unused solution should be discarded
- Prepared infusion bag: May be stored at room temperature for a limited period as defined by institutional guidelines, but should ideally be administered as soon as possible
Any unused medicine or waste material should be disposed of in accordance with local requirements. Padcev is a cytotoxic agent and requires special handling and disposal procedures to protect healthcare workers and the environment.
What Does Padcev Contain?
Each vial of Padcev contains either 20 mg or 30 mg of enfortumab vedotin as a white to off-white lyophilized (freeze-dried) powder. After reconstitution with sterile water, each ml contains 10 mg of enfortumab vedotin. The other ingredients include histidine, histidine hydrochloride monohydrate, trehalose dihydrate, and polysorbate 20.
Active ingredient
The active substance is enfortumab vedotin, an antibody-drug conjugate consisting of a human monoclonal antibody (enfortumab) conjugated to a microtubule-disrupting agent (MMAE) via a protease-cleavable linker. The antibody is produced using Chinese hamster ovary (CHO) cell technology.
- 20 mg vial: Contains 20 mg enfortumab vedotin; reconstituted with 2.3 mL of sterile water to give 10 mg/mL
- 30 mg vial: Contains 30 mg enfortumab vedotin; reconstituted with 3.3 mL of sterile water to give 10 mg/mL
Inactive ingredients (excipients)
The other ingredients help maintain the stability and integrity of the active substance during storage and administration:
- Histidine and histidine hydrochloride monohydrate – buffer agents to maintain pH
- Trehalose dihydrate – a stabilizer that protects the protein during freeze-drying
- Polysorbate 20 – a surfactant that prevents protein aggregation
Appearance and packaging
Padcev powder for concentrate for solution for infusion is a white to off-white lyophilized (freeze-dried) powder supplied in a single-dose glass vial. Each carton contains 1 vial. After reconstitution, the solution should appear clear to slightly opalescent, colorless to light yellow, and free from visible particles. Vials showing particles or discoloration should not be used.
Marketing authorization
Padcev is marketed by Astellas Pharma Europe B.V. (Sylviusweg 62, 2333 BE Leiden, Netherlands) in the European Union, and by Seagen Inc. (now part of Pfizer) in collaboration with Astellas in the United States. The medicine was first approved by the FDA in December 2019 under an accelerated approval pathway, with full approval granted based on confirmatory trial data. In Europe, it received marketing authorization from the European Medicines Agency (EMA).
Frequently Asked Questions About Padcev
Padcev (enfortumab vedotin) is used to treat adults with locally advanced or metastatic urothelial carcinoma (the most common type of bladder cancer). It can be given as monotherapy in patients who have previously received immunotherapy and platinum-based chemotherapy, or in combination with pembrolizumab as a first-line treatment. The choice of regimen depends on your prior treatment history, overall health, and your oncologist's assessment.
Padcev is given as a 30-minute intravenous (IV) infusion in a hospital or specialized clinic. It must not be given as an IV push or bolus. The drug is reconstituted from a powder form and diluted in an infusion bag before administration. The dose is based on your body weight (1.25 mg/kg). A healthcare professional will prepare and administer the infusion while monitoring you for any reactions.
The most common side effects (affecting more than 1 in 10 patients) include fatigue, nausea, diarrhea, decreased appetite, hair loss, peripheral neuropathy (tingling or numbness in hands and feet), skin rash, dry eyes, taste changes, weight loss, and elevated liver enzymes. Most of these are manageable with supportive care and dose adjustments. Serious but less common side effects include severe skin reactions (SJS/TEN), hyperglycemia, and pneumonitis – all of which require immediate medical attention.
Yes, Padcev has been associated with serious and potentially life-threatening skin reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). These can occur at any time during treatment but are most common in the early treatment cycles. Warning signs include worsening rash, blisters, skin peeling, painful mouth or genital sores, fever, and swollen lymph nodes. If you experience any of these symptoms, stop treatment and contact your healthcare provider immediately. You will be given a patient alert card to carry with you during treatment.
No. Padcev can cause harm to a developing baby and must not be used during pregnancy. Women who could become pregnant must use effective contraception during treatment and for at least 6 months after the last dose. Men receiving Padcev should not father a child during treatment and for at least 4 months after the last dose. Breastfeeding is also not recommended during treatment and for 6 months afterward. If you are planning a family, discuss fertility preservation options with your doctor before starting treatment.
Padcev has demonstrated significant clinical efficacy in clinical trials. In the EV-301 trial (monotherapy in previously treated patients), Padcev showed a significant improvement in overall survival compared to chemotherapy (median 12.9 months vs. 9.0 months). In the EV-302/KEYNOTE-A39 trial (combination with pembrolizumab as first-line treatment), the combination nearly doubled overall survival compared to platinum-based chemotherapy (median not reached vs. 16.1 months at interim analysis), establishing it as a new standard of care for first-line treatment of advanced urothelial carcinoma.
References
This article is based on the following peer-reviewed sources and official medical guidelines:
- European Medicines Agency (EMA). Padcev (enfortumab vedotin) – Summary of Product Characteristics. Last updated 2025. Available at: ema.europa.eu/padcev
- Powles T, Rosenberg JE, Sonpavde GP, et al. Enfortumab Vedotin in Previously Treated Advanced Urothelial Carcinoma (EV-301). N Engl J Med. 2021;384(12):1125-1135. doi:10.1056/NEJMoa2035807
- Powles T, Valderrama BP, Gupta S, et al. Enfortumab Vedotin and Pembrolizumab in Untreated Advanced Urothelial Cancer (EV-302/KEYNOTE-A39). N Engl J Med. 2024;390(10):875-888. doi:10.1056/NEJMoa2312117
- National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Bladder Cancer. Version 3.2025.
- Powles T, Bellmunt J, Comperat E, et al. Bladder cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2024;35(2):159-174.
- U.S. Food and Drug Administration (FDA). PADCEV (enfortumab vedotin-ejfv) Prescribing Information. Revised 2024. Available at: FDA.gov
- World Health Organization (WHO). WHO Model List of Essential Medicines – 23rd List. 2023. Geneva: World Health Organization.
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