Nectin-4 Antibody-Drug Conjugate Pregnancy: Contraindicated — cytotoxic MMAE payload; effective contraception required during and for 6 months (male) or 2 months (female) after treatment

Enfortumab Vedotin

Brand names: Padcev

Adult dose

Dose: 1.25 mg/kg IV on days 1, 8, 15 of each 28-day cycle

Route: Intravenous infusion over 30 minutes

Frequency: Days 1, 8, 15 of 28-day cycle

Max: 1.25 mg/kg per dose (max 125 mg for patients ≥100 kg)

Locally advanced or metastatic urothelial carcinoma (la/mUC) — post-platinum and post-PD-1/L1 inhibitor; first-line combination with pembrolizumab (EV-302 NEJM 2024) now MHRA licensed

Paediatric dose

Dose: Not established N/A/kg

Route: N/A

Frequency: N/A

Max: N/A

Not licensed in paediatrics

Dose adjustments

Renal

No dose adjustment for CrCl ≥15 mL/min; avoid in end-stage renal disease on dialysis (limited data)

Hepatic

Moderate-severe impairment: avoid — MMAE clearance impaired

Paediatric weight-based calculator

Patient weight (kg)

Not licensed in paediatrics

Clinical pearls

EV-301 trial (Powles et al. NEJM 2021): enfortumab vedotin significantly improved OS vs chemotherapy in previously treated la/mUC (12.9 vs 8.9 months) — MHRA 2022 approved; NICE TA812; EV-302 (NEJM 2024) established EV+pembrolizumab as new first-line standard (OS 31.5 vs 16.1 months vs gemcitabine-platinum)
Nectin-4 targeting: nectin-4 is a cell adhesion molecule overexpressed in >95% of urothelial carcinomas — MMAE (monomethyl auristatin E) cytotoxic payload disrupts microtubule polymerisation after internalisation; bystander killing effect also kills Nectin-4-low adjacent cells
MHRA hyperglycaemia warning: significant hyperglycaemia/new-onset diabetes reported (including diabetic ketoacidosis) — monitor blood glucose before each dose; hold if >250 mg/dL; ensure insulin/anti-diabetic medication adjusted; risk particularly high in pre-diabetic patients
Ocular toxicity: keratitis and corneal disease reported — baseline ophthalmological assessment recommended; prophylactic lubricating eye drops throughout treatment; refer urgently if visual changes, photophobia, or eye pain; this ADC has unique ocular toxicity not seen with other ADCs
Skin toxicity: severe cutaneous reactions (SJS/TEN) reported rarely — monitor rash carefully; any blistering, mucous membrane involvement, or widespread desquamation requires immediate drug discontinuation and urgent dermatology referral

Contraindications

Moderate-severe hepatic impairment
Known hypersensitivity
Active corneal disease (see clinicalPearls)

Side effects

Peripheral neuropathy (dose-limiting, cumulative)
Skin reactions (rash, palmar-plantar erythrodysaesthesia, SJS/TEN — rare but severe)
Ocular toxicity (keratitis, corneal disease)
Hyperglycaemia/diabetes (MHRA warning)
Fatigue
Alopecia
Neutropenia

Interactions

Strong CYP3A4 inhibitors — increase MMAE (cytotoxic payload) exposure; avoid or monitor
P-gp inhibitors — increased MMAE levels

Monitoring

FBC (before each dose)
Blood glucose (before each dose — MHRA requirement)
LFTs
Peripheral neuropathy grading (each visit)
Ophthalmological symptoms (each visit)
Skin assessment

Reference: BNFc; BNF 90; EV-301 trial (Powles et al. NEJM 2021); EV-302 trial (NEJM 2024); NICE TA812; MHRA SPC Padcev; EAU Bladder Cancer Guidelines 2024. Verify against your local formulary and the latest BNF before prescribing.

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways