Padcev

Instructions for Padcev for injection

[Manufacturer]: Seattle Genetics, Inc/Astellas Pharma Inc

[Specification]: 30mg/bottle or 20mg/bottle

[Trademark]: Padcev

[Common name]: enfortumab vedotin-ejfv

[English name]: enfortumab vedotin-ejfv for injection

【Storage】: Keep refrigerated in the original carton at 2ºC to 8ºC (36ºF to 46ºF). Do not freeze.

[Padcev for injection (enfortumab vedotin-ejfv) Indications]

PADCEV is a nectin-4-directed antibody and microtubule inhibitor conjugate indicated for the treatment of adult patients with locally advanced metastatic urothelial carcinoma who have previously received adjuvant therapy with programmed death receptor-1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitors or platinum-based chemotherapy.

[Padcev for injection (enfortumab vedotin-ejfv) dosage and administration]

1. For intravenous infusion only. Do not give PADCEV as an intravenous push or bolus injection. Do not mix with other medicines or use as infusion.

2. The recommended dose of PADCEV is 1.25 mg/kg (maximum dose is 125 mg), intravenously infused over 30 minutes on days 1, 8, and 15 of a 28-day cycle until disease progression or unacceptable toxicity occurs.

3. Avoid use in patients with moderate or severe hepatic insufficiency.

[Padcev for injection (enfortumab vedotin-ejfv) dosing configuration]

Before dosing, reconstitute the PADCEV vial with sterile water for injection (SWFI). The reconstituted solution is then diluted in an IV bag containing 5% Dextrose Injection, 0.9% Sodium Chloride Injection, or Lactated Ringer's Injection.

Configuration Steps:

1. Follow procedures for proper handling and disposal of anticancer medications.

2. Use appropriate aseptic technique to reconstitute and prepare solutions.

3. Calculate the recommended dose based on the patient’s weight to determine the required dose.

4. Reconfigure as follows, directing SWFI flow along the walls of the vial if possible:

a. 20 mg vial: add 2.3 mL of SWFI to yield 10 mg/mL PADCEV.

b. 30 mg vial: Add 3.3 ml SWFI to yield 10 mg/ml PADCEV.

5. Slowly swirl each vial until the contents are completely dissolved. Let sit for 1 minute until bubbles disappear.

6. Visually inspect drug products for particulate matter and discoloration before administration. The reconstituted solution should be clear to slightly milky, colorless to light yellow, and have no visible particles. If the solution is cloudy, discolored, or contains visible particles, discard immediately.

7. According to the calculated dose, the solution in the vial should be added to the infusion bag immediately. This product does not contain preservatives. If not using immediately, store refrigerated at 2℃ to 8℃ (36℉ to 46℉) for up to 4 hours. Do not freeze.

8. Remove the calculated dose of solution from the vial and transfer to the infusion bag.

9. Dilute PADCEV with 5% glucose injection, 0.9% sodium chloride injection or lactated Ringer's injection. The size of the infusion bag should allow sufficient diluent to achieve a final concentration of 0.3 mg/ml to 4 mg/ml.

10. Gently invert to mix the diluted solution.

11. Visually inspect the infusion bag for any particulate matter or discoloration before use. The reconstituted solution should be clear to slightly milky, colorless to light yellow, and have no visible particles. Do not use the infusion bag if particulate matter or discoloration is observed.

12. Discard unused portion of single-dose vial.

13. Administer the infusion immediately through the intravenous line within 30 minutes.

14. If the infusion is not performed immediately, the prepared infusion bag should not be stored for more than 8 hours at a temperature of 2℃ to 8℃ (36℉ to 46℉). Do not freeze.

Do not give this product as an intravenous push or bolus injection.

Do not mix this product with other medicines or use it as an infusion.

[Warnings and Precautions for Padcev (enfortumab vedotin-ejfv) for injection]

1. Hyperglycemia: Diabetic ketoacidosis may occur in patients with or without diabetes and can be fatal. Closely monitor blood glucose levels in patients who have or are at risk for diabetes or hyperglycemia. Discontinue PADCEV if blood glucose is >250 mg/dL.

2. Peripheral neuropathy: Monitor patients for new or worsening peripheral neuropathy and consider dose interruption, dose reduction, or discontinuation of PADCEV.

3. Eye diseases: Eye diseases, including changes in vision, may occur. Monitor patients for signs or symptoms of eye disease. Consider prophylactic artificial tears for dry eyes and treatment with ophthalmic steroids after an eye examination. Consider dose interruption or dose reduction of PADCEV when symptomatic ocular disease occurs.

4. Skin reaction: If severe, keep PADCEV until improvement or resolution.

5. Infusion site spillage: Ensure adequate intravenous access before administration. Monitor the infusion site during PADCEV administration and stop the infusion immediately in case of suspected extravasation.

6. Embryo-fetal toxicity: PADCEV may cause fetal harm. Advise on potential risks to the fetus and use of effective contraception.

[Padcev for injection (enfortumab vedotin-ejfv) overdose]

No relevant information

[Padcev for injection (enfortumab vedotin-ejfv) vedotin-ejfv) Contraindications]

None

[Adverse reactions of Padcev for injection (enfortumab vedotin-ejfv)]

The most common adverse reactions (≥20%) include fatigue, peripheral neuropathy, decreased appetite, rash, alopecia, nausea, indigestion, diarrhea, dry eye, pruritus and dry skin.

[Padcev for injection (enfortumab vedotin-ejfv) is used in special groups]

Lactation period: It is recommended not to breastfeed.

Children: Safety and effectiveness have not been established in pediatric patients.

Avoid the use of PADCEV in patients with moderate or severe hepatic impairment.

[General description of Padcev for injection (enfortumab vedotin-ejfv)]

enfortumab vedotin-ejfv is an antibody-drug complex (ADC) directed to Nectin-4. The antibody is human IgG1 directed against Nectin-4, an adhesion protein located on the cell surface. The small molecule MMAE is a microtubule-disrupting agent that is linked to antibodies via a protease-cleavable linker. The molecular weight is approximately 152kDa.

[Mechanism of action of Padcev for injection (enfortumab vedotin-ejfv)]

Non-clinical data suggest that the anti-cancer activity of enfortumab vedotin-ejfv is due to ADC binding to Nectin-4-expressing cells, subsequent internalization of the ADC-Nectin-4 complex, and release of MMAE through proteolytic cleavage. The release of MMAE disrupts the intracellular microtubule network, subsequently inducing cell cycle arrest and apoptotic cell death.

[Padcev for injection (enfortumab vedotin-ejfv) patient information]

1. Advise patients to contact their medical staff immediately if they experience any of the above adverse reactions (warnings and precautions).

2. Inform pregnant women and women of reproductive potential that PADCEV may cause fetal harm and to use effective contraceptive measures during treatment with PADCEV and within 2 months after the last dose of PADCEV.

3. Inform nursing mothers not to breastfeed during treatment with PADCEV and for at least 3 weeks after the last dose of PADCEV

4. Advise male patients with female partners to use effective contraception during treatment with PADCEV and for 4 months after the last dose of PADCEV.

5. The use of PADCEV may damage male fertility.