Padcev Side Effects: What to Expect and When to Call Your Doctor

Padcev (enfortumab vedotin-ejfv) is a powerful cancer treatment, and like most oncology medications, it comes with a range of potential side effects. Some are mild and manageable; others are serious — and in rare cases, life-threatening. Knowing what to watch for and when to contact your care team can help you stay safe during treatment.

This guide covers the most important Padcev side effects based on FDA prescribing information and clinical trial data. Always consult your oncologist or call your care team immediately if you experience anything concerning.

Boxed Warning: Severe Skin Reactions (SJS and TEN)

Padcev carries the FDA's strongest warning — a boxed warning — for severe and potentially fatal cutaneous (skin) adverse reactions, specifically Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN). These conditions predominantly occur during the first cycle of treatment, but can happen at any time.

Call 911 or go to the emergency room immediately if you experience:

Severe blistering or peeling of the skin

Painful or widespread rash with target lesions (bull's-eye pattern)

Rash involving the mouth, eyes, or genitals

Skin that looks burned or red with extensive areas separating from the body

Skin reactions of any kind occur in approximately 55–65% of patients on Padcev. Grade 3–4 (serious) skin reactions occur in 10–13% of patients. Any rash should be reported to your doctor promptly — do not wait for your next scheduled appointment.

Common Side Effects of Padcev

Based on clinical trial data (EV-302/KEYNOTE-A39 and EV-201), the most common side effects seen in patients receiving Padcev with pembrolizumab include:

Skin rash and pruritus (itching): Affects up to 33% of patients. Report any rash to your oncology team promptly.

Fatigue: One of the most commonly reported side effects. Rest when needed and inform your team if it significantly affects your daily function.

Peripheral neuropathy: Tingling, numbness, or pain in hands and feet. Often cumulative and may worsen with each cycle. Report to your doctor immediately — dose modifications may be needed.

Alopecia (hair loss): Hair thinning or loss is common. Hair typically regrows after treatment ends.

Decreased appetite and weight loss: Work with a registered dietitian if maintaining nutrition is a challenge.

Nausea, diarrhea, and constipation: GI symptoms can be managed with supportive medications — ask your team for anti-nausea or stool-softener prescriptions.

Dysgeusia (taste changes): Foods may taste metallic or different than usual. This often improves between cycles.

Elevated liver enzymes (AST/ALT) and blood glucose: Routine blood work monitors these lab values before each dose.

Serious Side Effects That Require Prompt Medical Attention

Hyperglycemia (high blood sugar) and DKA: Padcev can cause significantly elevated blood sugar, even in patients without pre-existing diabetes. Symptoms: excessive thirst, frequent urination, blurred vision, fruity-smelling breath. If blood glucose exceeds 250 mg/dL, Padcev is withheld. This can progress to diabetic ketoacidosis (DKA), which requires emergency care.

Pneumonitis (lung inflammation): Interstitial lung disease or pneumonitis can be serious or life-threatening. Symptoms: new or worsening cough, shortness of breath, chest pain. Seek emergency help if you have severe breathing difficulty.

Eye problems: Dry eye, conjunctivitis (pink eye), and keratitis (corneal inflammation) can occur. Padcev may also attract immune cells that affect eye tissue. Report any vision changes, eye pain, or red eyes to your doctor promptly.

Infusion site extravasation: If Padcev leaks from the vein during infusion, it can damage surrounding tissue. Tell your nurse immediately if you feel pain, swelling, or see redness at the IV site during infusion.

Embryo-fetal toxicity: Padcev can cause fetal harm. Women of reproductive potential must use effective contraception during treatment and for 2 months after the last dose. Men should use contraception for 4 months after their last dose.

Managing Padcev Side Effects: Tips That Help

Use gentle, fragrance-free moisturizers and mild soaps to protect skin during treatment

Monitor blood sugar regularly — especially if you have diabetes or high BMI

Use lubricating eye drops for dry eye symptoms — ask your doctor for a recommendation

Keep a symptom diary to track patterns and bring it to each appointment

Never stop Padcev on your own — contact your oncology team first if side effects are affecting your quality of life

Also read: Padcev Drug Interactions: What to Avoid and What to Tell Your Doctor.

If you're having trouble finding a Padcev infusion center near you, medfinder can help locate facilities in your area.