PADCEV

/ Astellas

The recommended dose of enfortumab vedotin is 1.25 mg/kg (up to a maximum of 125 mg for patients ≥ 100 kg) administered as an intravenous infusion over 30 minutes on Days 1, 8 and 15 of a 28-day cycle until disease progression or unacceptable toxicity
See prescribing information for full details.

Treatment of adult patients with locally advanced or metastatic urothelial cancer (mUC) who:
* 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
* Ineligible for cisplatin-containing chemotherapy and having previously received one or more prior lines of therapy.

Hypersensitivity to the active substance or to any of the excipients

Skin Reactions
Severe cutaneous adverse reactions, including fatal cases of SJS or TEN occurred in patients treated with enfortumab vedotin. SJS and TEN occurred predominantly during the first cycle of treatment but may occur later.
Monitor patients closely throughout treatment for skin reactions. Consider topical corticosteroids and antihistamines, as clinically indicated. Withhold enfortumab vedotin and refer for specialized care for suspected SJS, TEN or for severe (Grade 3) skin reactions. Permanently discontinue enfortumab vedotin in patients with confirmed SJS or TEN; or Grade 4 or recurrent Grade 3 skin reactions
Hyperglycemia
Hyperglycemia and diabetic ketoacidosis (DKA), including fatal events, occurred in patients with and without pre-existing diabetes mellitus, treated with enfortumab vedotin. Closely monitor blood glucose levels in patients with, or at risk for, diabetes mellitus or hyperglycemia. If blood glucose is elevated (> 250 mg/dL), withhold enfortumab vedotin.
Pneumonitis
Severe, life-threatening or fatal pneumonitis occurred in patients treated with enfortumab vedotin. In clinical trials, the median time to onset of pneumonitis was 2.9 months (range: 0.6 to 6 months). Monitor patients for signs and symptoms indicative of pneumonitis such as hypoxia, cough, dyspnea or interstitial infiltrates on radiologic exams. Evaluate and exclude infectious, neoplastic and other causes for such signs and symptoms through appropriate investigations.
Withhold enfortumab vedotin for patients who develop persistent or recurrent Grade 2 pneumonitis and consider dose reduction. Permanently discontinue enfortumab vedotin in all patients with Grade 3 or 4 pneumonitis.
Peripheral Neuropathy
Peripheral neuropathy occurred in patients treated with enfortumab vedotin with or without preexisting peripheral neuropathy. The median time to onset of Grade ≥ 2 peripheral neuropathy was 4.6 months (range: 0.1 to 15.8 months). Neuropathy led to treatment discontinuation in 5% of patients. Monitor patients for symptoms of new or worsening peripheral neuropathy and consider dose interruption or dose reduction of enfortumab vedotin when peripheral neuropathy occurs. Permanently discontinue enfortumab vedotin in patients that develop Grade > 3 peripheral neuropathy.
Ocular Disorders
Ocular disorders were reported in 40% of the 384 patients treated with enfortumab vedotin in clinical trials in which ophthalmologic exams were scheduled. The majority of these events involved the cornea and included events associated with dry eye such as keratitis, blurred vision, increased lacrimation, conjunctivitis, limbal stem cell deficiency, and keratopathy. The median time to onset to symptomatic ocular disorder was 1.6 months (range: 0 to 19.1 months). Monitor patients for ocular disorders. Consider artificial tears for prophylaxis of dry eyes and ophthalmologic evaluation if ocular symptoms occur or do not resolve. Consider treatment with ophthalmic topical steroids, if indicated after an ophthalmic exam. Consider dose interruption or dose reduction of enfortumab vedotin for symptomatic ocular disorders.
Infusion Site Extravasation
Skin and soft tissue reactions secondary to extravasation have been observed after administration of enfortumab vedotin. Of the 680 patients, 1.6% of patients experienced skin and soft tissue reactions, including 0.3% who experienced Grade 3-4 reactions. Reactions may be delayed. Erythema, swelling, increased temperature, and pain worsened until 2-7 days after extravasation and resolved within 1-4 weeks of peak. Ensure adequate venous access prior to starting enfortumab vedotin and monitor for possible extravasation during administration. If extravasation occurs, stop the infusion and monitor for adverse reactions.
Embryo-Fetal Toxicity
Advise female patients of reproductive potential to use effective contraception during treatment with enfortumab vedotin and for 2 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with enfortumab vedotin and for 4 months after the last dose
See prescribing information for full details.

The following serious adverse reactions are described elsewhere in the labeling:
• Skin Reactions
• Hyperglycemia
• Pneumonitis
• Peripheral Neuropathy
• Ocular Disorders
• Infusion Site Extravasation
See prescribing information for full details.

Effects of Other Drugs on enfortumab vedotin
Dual P-gp and Strong CYP3A4 Inhibitors
Concomitant use with dual P-gp and strong CYP3A4 inhibitors may increase unconjugated MMAE exposure, which may increase the incidence or severity of enfortumab vedotin toxicities. Closely monitor patients for signs of toxicity when enfortumab vedotin is given concomitantly with dual P-gp and strong CYP3A4 inhibitors.

Pregnancy
There are no available human data on enfortumab vedotin use in pregnant women to inform a drug-associated risk.
Lactation
There are no data on the presence of enfortumab vedotin in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in a breastfed child, advise lactating women not to breastfeed during treatment with enfortumab vedotin and for at least 3 weeks after the last dose.
Contraception
Females
Advise females of reproductive potential to use effective contraception during treatment with enfortumab vedotin and for 2 months after the last dose.
Males
Advise male patients with female partners of reproductive potential to use effective contraception during treatment with enfortumab vedotin and for 4 months after the last dose.