Padcev

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 a programmed death receptor-1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitor or platinum-based chemotherapy.

Usage and Dosage

For intravenous infusion only. Do not give PADCEV as an intravenous push or bolus dose. Do not mix with other medicines or take as an infusion.

The recommended dose of PADCEV is 1.25 mg/kg (maximum dose 125 mg) as a 30-minute intravenous infusion on days 1, 8, and 15 of a 28-day cycle until disease progression or unacceptable toxicity.

Avoid use in patients with moderate or severe hepatic impairment.

Recommended dose reduction schedule

Starting dose: 1.25 mg/kg to 125 mg

First dose reduction: 1.0 mg/kg to 100 mg

Second dose reduction: 0.75 mg/kg to 75 mg

Third dose reduction: 0.5 mg/kg to 50 mg

PADCEV is a dangerous drug. Follow applicable special handling and disposal procedures.

Prior to administration, reconstitute PADCEV vials with sterile water for injection (SWFI). Subsequently dilute the reconstituted solution in an IV bag containing 5% Dextrose Injection, USP, 0.9% Sodium Chloride Injection, or Lactated Ringer's Injection.

Proper aseptic technique is required to reconstitute and prepare dosing solutions.

Calculate recommended dosage based on patient weight to determine number of vials and strength (20 mg or 30 mg) required.

Reassemble each vial as follows, if possible directing the SWFI flow along the vial walls rather than directly onto the lyophilized powder:

a. 20 mg vial: add 2.3 mL SWFI to give 10 mg/mL PADCEV. b. 30 mg vial: Add 3.3 mL SWFI to obtain 10 mg/mL PADCEV.

Slowly swirl each vial until the contents are completely dissolved. Let the reconstituted vial sit for at least 1 minute until bubbles disappear. Do not shake the bottle. Do not expose to direct sunlight.

Prior to administration, parenteral drug products should be visually inspected for particulate matter and discoloration, whenever the solution and container permit. The reconstituted solution should be clear to slightly milky white, colorless to light yellow, with no visible particles. Discard any vial with visible particles or discoloration.

According to the calculated dose, the reconstitution solution in the vial should be added to the infusion bag immediately. This product does not contain preservatives. If not used immediately, reconstituted bottles can be stored refrigerated at 2°C to 8°C (36°F to 46°F) for 24 hours. Don't freeze. After recommended storage time, discard unused vials with reconstituted solution.

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

Dilute PADCEV with 5% glucose injection, 0.9% sodium chloride injection or lactated Ringer's injection. Infusion bag dimensions should allow sufficient dilution to achieve a final concentration of 0.3 mg/mL to 4 mg/mL PADCEV.

Mix the dilute solution by gently inverting it. Do not shake the bag. Do not expose to direct sunlight.

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

Discard any unused portion remaining in the single-dose vial.

Administer immediately through the IV line within 30 minutes.

If administration is not to be administered immediately, prepared infusion bags should not be stored for more than 8 hours at a temperature of 2°C to 8°C (36°F to 46°F). Don't freeze. Do not give PADCEV as an intravenous push or bolus dose. PADCEV should not be mixed with other medications or taken as an infusion.

Adverse reactions

The most common adverse reactions (≥20%) include rash, increased aspartate aminotransferase, increased glucose, increased creatinine, fatigue, peripheral neuropathy, lymphopenia, alopecia, decreased appetite, decreased hemoglobin, diarrhea, decreased sodium, nausea, pruritus, decreased phosphate, halitosis, increased alanine aminotransferase, anemia, decreased albumin, neutropenia, increased uric acid, increased lipase, decreased platelets, decreased body weight, and dry skin.

The most common serious adverse reactions (≥2%) were urinary tract infection, acute kidney injury (7% each), and pneumonia (5%).

Fatal adverse reactions included acute respiratory failure, aspiration pneumonia, heart disease, sepsis and pneumonia (0.8% each).

Contraindications

Based on its mechanism of action and research results in animals, PADCEV can cause harm to the fetus when administered to pregnant women.

Because of the potential for serious adverse reactions in breastfed children, lactating women are advised not to breastfeed during treatment with PADCEV and for at least 3 weeks after the last dose.

The female contraceptive pill PADCEV can cause harm to the fetus when taken by pregnant women. Advise females of reproductive potential to use effective contraception during treatment with PADCEV and for 2 months after the last dose. Men Advise male patients with female partners of reproductive potential to use effective contraception during treatment with PADCEV and for 4 months after the last dose.

Based on animal studies, PADCEV may harm male fertility.

Pediatric Use The safety and effectiveness of PADCEV in pediatric patients have not been established.

Hepatic Impairment Avoid use in patients with moderate or severe hepatic impairment.

Storage Methods

Storage Keep PADCEV vials refrigerated in the original carton at 2ºC to 8ºC (36ºF to 46ºF). Don't freeze. Don't Shake

Indicated Population

Indicated for the treatment of adult patients with locally advanced or metastatic urothelial carcinoma

Drug Interactions

Dual P-gp and strong CYP3A4 inhibitors may increase unbound MMAE exposure when used concomitantly with dual P-gp and strong CYP3A4 inhibitors, which may increase the incidence or severity of PADCEV toxicity. Monitor patients closely for signs of toxicity when PADCEV is coadministered with dual P-gp and strong CYP3A4 inhibitors.

Validity period

24 months

Dosage form

lyophilized powder

Manufacturer

Astellas Japan

Ingredients

PADCEV is Nectin-4-directed antibody and microtubule inhibitor conjugate

Characteristics

White or off-white lyophilized powder

Precautions

1. Closely monitor the patient's skin reaction throughout the treatment process. Consider topical corticosteroids and antihistamines as clinically indicated. Do not use PADCEV and seek specialized care in patients suspected of having SJS, TEN, or severe (Grade 3) skin reactions.

2. If patients are at risk of diabetes or hyperinsulinemia, please closely monitor the blood sugar levels of patients with diabetes or hyperglycemia. If blood sugar levels rise (>250 mg/dL), stop using PADCEV.

3. Monitor patients for signs and symptoms of pneumonia, such as hypoxia, cough, dyspnea, or interstitial infiltrates during radiological examinations. With appropriate investigations, evaluate and rule out infectious, neoplastic, and other causes for these signs and symptoms. For patients with persistent or recurrent grade 2 pneumonitis, PADCEV should be withheld and a dose reduction considered. Permanently discontinue PADCEV in all patients with Grade 3 or 4 pneumonia

4. Peripheral neuropathy can occur in patients treated with PADCEV, regardless of whether peripheral neuropathy is present. Monitor patients for new or worsening symptoms of peripheral neuropathy and consider dose interruption or dose reduction of PADCEV if peripheral neuropathy occurs. Permanently discontinue PADCEV in patients who develop >Grade 3 peripheral neuropathy.

5. Monitor patients for eye disease. If ocular symptoms occur or fail to resolve, consider using artificial tears to prevent dry eye syndrome and obtain an ophthalmological evaluation. Consider topical ophthalmic steroid treatment if indicated after an eye examination. For symptomatic eye disease, consider interrupting or reducing the dose of PADCEV.

Ensure adequate intravenous access before initiating PADCEV and monitor for possible extravasation during dosing. If extravasation occurs, discontinue the infusion and monitor for adverse reactions.

6. Inform the patient of potential risks to the fetus. Advise female patients of reproductive potential to use effective contraception during treatment with PADCEV and for 2 months after the last dose. Advise patients with female partners of reproductive potential to use effective contraception during treatment with PADCEV and for 2 months after the last dose. Advise male patients with female partners of reproductive potential to use an effective method of contraception during treatment with PADCEV and for 4 months after the last dose.