Padcev Special Precautions

Traceability: In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.
Skin reactions: Skin reactions are associated with enfortumab vedotin as a result of enfortumab vedotin binding to Nectin-4 expressed in the skin. Fever or flu-like symptoms may be the first sign of a severe skin reaction, and patients should be observed, if this occurs.
Mild to moderate skin reactions, predominantly maculo-papular rash, have been reported (see Adverse Reactions). Severe cutaneous adverse reactions, including SJS and TEN, with fatal outcome have also occurred in patients treated with enfortumab vedotin, predominantly during the first cycle of treatment. In clinical trials, the median time to onset of severe skin reactions was 0.6 months (range: 0.1 to 6.4).
Patients should be monitored starting with the first cycle and throughout treatment for skin reactions. Appropriate treatment such as topical corticosteroids and antihistamines can be considered for mild to moderate skin reactions. For suspected SJS or TEN, or in case of bullous lesions onset, withhold treatment immediately and refer to specialised care; histologic confirmation, including consideration of multiple biopsies, is critical to early recognition, as diagnosis and intervention can improve prognosis. Permanently discontinue PADCEV for confirmed SJS or TEN, Grade 4 or recurrent severe skin reactions. For Grade 2 worsening, Grade 2 with fever or Grade 3 skin reactions, treatment should be withheld until Grade ≤1 and referral for specialised care should be considered. Treatment should be resumed at the same dose level or consider dose reduction by one dose level (see Dosage & Administration).
Pneumonitis/ILD: Severe, life-threatening or fatal pneumonitis/ILD have occurred in patients treated with enfortumab vedotin (see Adverse Reactions). Monitor patients for signs and symptoms indicative of pneumonitis/ILD such as hypoxia, cough, dyspnoea or interstitial infiltrates on radiologic exams. Corticosteroids should be administered for Grade ≥2 events (e.g., initial dose of 1-2 mg/kg/day prednisone or equivalent followed by a taper). Withhold PADCEV for Grade 2 pneumonitis/ILD and consider dose reduction. Permanently discontinue PADCEV for Grade ≥3 pneumonitis/ILD (see Dosage & Administration).
Hyperglycaemia: Hyperglycaemia and diabetic ketoacidosis (DKA), including fatal events, occurred in patients with and without pre-existing diabetes mellitus, treated with enfortumab vedotin (see Adverse Reactions). Hyperglycaemia occurred more frequently in patients with pre-existing hyperglycaemia or a high body mass index (≥30 kg/m²). Patients with baseline HbA1c ≥8% were excluded from clinical trials. Blood glucose levels should be monitored prior to dosing and periodically throughout the course of treatment as clinically indicated in patients with or at risk for diabetes mellitus or hyperglycaemia. If blood glucose is elevated >13.9 mmol/L (>250 mg/dL), PADCEV should be withheld until blood glucose is ≤13.9 mmol/L (≤250 mg/dL) and treat as appropriate (see Dosage & Administration).
Peripheral neuropathy: Peripheral neuropathy, predominantly peripheral sensory neuropathy, has occurred with enfortumab vedotin, including Grade ≥3 reactions (see Adverse Reactions). Patients with pre-existing peripheral neuropathy Grade ≥2 were excluded from clinical trials. Patients should be monitored for symptoms of new or worsening peripheral neuropathy as these patients may require a delay, dose reduction or discontinuation of enfortumab vedotin (see Table 2). PADCEV should be permanently discontinued for Grade ≥3 peripheral neuropathy (see Dosage & Administration).
Ocular disorders: Ocular disorders, predominantly dry eye, have occurred in patients treated with enfortumab vedotin (see Adverse Reactions). Patients should be monitored for ocular disorders. Consider artificial tears for prophylaxis of dry eye and referral for ophthalmologic evaluation if ocular symptoms do not resolve or worsen.
Infusion site extravasation: Skin and soft tissue injury following enfortumab vedotin administration has been observed when extravasation occurred (see Adverse Reactions). Ensure good venous access prior to starting PADCEV and monitor for possible infusion site extravasation during administration. If extravasation occurs, stop the infusion and monitor for adverse reactions.
Embryo-foetal toxicity and contraception: Pregnant women should be informed of the potential risk to a foetus (see Use in Pregnancy & Lactation and Pharmacology: Toxicology: Preclinical safety data under Actions). Females of reproductive potential should be advised to have a pregnancy test within 7 days prior to starting treatment with enfortumab vedotin, to use effective contraception during treatment and for at least 12 months after stopping treatment. Men being treated with enfortumab vedotin are advised not to father a child during treatment and for up to 9 months following the last dose of PADCEV.
Effects on ability to drive and use machines: PADCEV has no or negligible influence on the ability to drive and use machines.