Padcev 20 mg powder for concentrate for solution for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Padcev 20 mg powder for concentrate for solution for infusion

Padcev 30 mg powder for concentrate for solution for infusion

enfortumab vedotin

This medicinal product is subject to additional monitoring, which will allow quicker identification of new safety information. You can help by reporting any adverse reactions you may experience. Section 4 at the end of this leaflet contains information on how to report adverse reactions.

Read the entire leaflet carefully before you are given this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor.
• If you experience any adverse reactions, consult your doctor, even if they are possible adverse reactions not listed in this leaflet. See section 4.

Leaflet contents

1. What Padcev is and what it is used for
2. What you need to know before being given Padcev
3. How to use Padcev
4. Possible adverse reactions
5. How to store Padcev
6. Contents of the pack and other information

1. What Padcev is and what it is used for

Padcev contains the active substance enfortumab vedotin, which consists of a monoclonal antibody linked to a drug designed to kill cancer cells. The monoclonal antibody recognizes certain cancer cells and releases the drug into them.

This medicine is used alone or in combination with pembrolizumab in adults to treat a type of cancer called bladder cancer (urothelial carcinoma). Padcev is given to people whose cancer has spread or cannot be removed by surgery.

When used alone, Padcev is administered to individuals who have previously received an immunotherapy medicine and also a platinum-based chemotherapy medicine.

This medicine may be given in combination with pembrolizumab. It is important that you also read the package leaflet for this other medicine. If you have any questions, consult your doctor.

2. What you need to know before Padcev is administered to you

Do not use Padcev

• if you are allergic to enfortumab vedotin or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Contact your doctor immediately if:

• you experience any of the following symptoms of a skin reaction:

• rash or itching that worsens or returns after treatment,

• blisters or peeling of the skin,

• painful sores or ulcers in the mouth, nose, throat, or genital area,

• fever or flu-like symptoms,

• swollen lymph nodes.

• these may be signs of a serious skin reaction that can occur when receiving this medicine, particularly during the first weeks of treatment. Skin reactions may occur more frequently when this medicine is given with pembrolizumab. If this happens, your doctor will monitor you and may give you medication to treat your skin condition. Your doctor may pause your treatment until symptoms improve. If the skin reaction worsens, your doctor may stop your treatment. You can also find this information in the Patient Information Card included in the package. It is important that you carry this Patient Information Card with you and show it to any healthcare professional who treats you.

• you have symptoms of high blood sugar levels, including frequent urination, increased thirst, blurred vision, confusion, numbness, loss of appetite, fruity-smelling breath, nausea, vomiting, or stomach pain. You may experience high blood sugar levels during treatment.

• you have lung problems (pneumonitis/interstitial lung disease) or develop new symptoms or worsening symptoms, including difficulty breathing, shortness of breath, or cough. These lung problems may occur more frequently when this medicine is administered with pembrolizumab. If this occurs, your doctor may pause treatment until symptoms improve or reduce the dose. If symptoms worsen, your doctor may stop your treatment.

• you have, or think you may have, an infection. Some infections can be serious and potentially life-threatening.

• you have symptoms of a nerve problem (neuropathy), such as numbness, tingling, or a prickling sensation in the hands or feet, or muscle weakness. If this occurs, your doctor may pause treatment until symptoms improve or reduce the dose. If symptoms worsen, your doctor may stop your treatment.

• you have eye problems, such as dry eyes, during treatment. You may develop dry eye problems while receiving Padcev.

Children and adolescents

This medicine must not be used in children and adolescents under 18 years of age.

Other medicines and Padcev

Inform your doctor if you are taking, have recently taken, or might need to take any other medicines.

Tell your doctor if you are taking antifungal medications (e.g. ketoconazole), as they may increase the amount of Padcev in your blood. If you regularly take these medications, your doctor may switch you to another medicine to take during your treatment period.

Pregnancy, breastfeeding, and fertility

If you are pregnant, think you may be pregnant, or plan to become pregnant, consult your doctor before starting this medicine.

You must not use this medicine if you are pregnant. Padcev may harm the unborn baby.

If you are a woman of childbearing potential, you must use effective contraception during treatment and for at least 6 months after stopping Padcev.

It is unknown whether this medicine passes into breast milk; if it does, it could harm your baby. Do not breastfeed during treatment and for at least 6 months after stopping Padcev.

Men treated with this medicine are advised to freeze and store semen samples before treatment. Men should avoid fathering a child during treatment with this medicine and for at least 4 months after the last dose.

Driving and using machines

Do not drive or operate machinery if you feel unwell during treatment.

3. How to use Padcev

You will receive Padcev at a hospital or clinic, under the supervision of a doctor experienced in administering these treatments.

How much Padcev you will receive

When used alone, the recommended dose of this medicine is 1.25 mg/kg on days 1, 8, and 15 of every 28-day cycle. When used in combination with pembrolizumab, the recommended dose of this medicine is 1.25 mg/kg on days 1 and 8 of every 21-day cycle. Your doctor will decide how many treatment cycles you will need.

How you will receive Padcev

You will receive Padcev as an intravenous infusion into a vein over 30 minutes. Before administration, Padcev will be added to an infusion bag containing glucose solution, sodium chloride solution, or Ringer's lactate solution.

If you miss a dose of Padcev

It is very important that you attend all your appointments to receive Padcev. If you miss an appointment, ask your doctor when to schedule your next dose.

If you stop receiving Padcev

Do not discontinue treatment with Padcev unless discussed with your doctor. Stopping treatment may interrupt the medicine's effect.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them.

Some possible adverse effects may be serious:

• Skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, and other severe rashes, such as drug-related symmetric intertriginous and flexural exanthema). Inform your doctor immediately if you experience any of the following signs of a severe skin reaction: rash or itching that worsens or returns after treatment, blistering or peeling of the skin, painful sores or ulcers in the mouth, nose, throat, or genital area, fever or flu-like symptoms, or swollen lymph nodes (frequency not known).

• High blood sugar levels (hyperglycaemia). Inform your doctor immediately if you experience any symptoms of high blood sugar levels, including: frequent urination, increased thirst, blurred vision, confusion, numbness, loss of appetite, fruity-smelling breath, nausea, vomiting, or stomach pain (may affect more than 1 in 10 people).

• A serious complication of diabetes with high levels of ketones in the blood that may make the blood more acidic (diabetic ketoacidosis) (frequency not known).

• Lung problems (pneumonitis/interstitial lung disease). Inform your doctor immediately if you develop new symptoms or existing symptoms worsen, including difficulty breathing, shortness of breath, or cough (may affect up to 1 in 10 people).

• Nerve problems (peripheral neuropathy, such as motor neuropathy, sensorimotor neuropathy, paresthesia, hypoesthesia, and muscle weakness). Inform your doctor immediately if you experience numbness, tingling, or a pins-and-needles sensation in your hands or feet, or muscle weakness (may affect more than 1 in 10 people).

• Leakage of Padcev from the vein into surrounding tissues at the infusion site (extravasation). Inform your doctor or seek immediate medical help if you notice redness, swelling, itching, or discomfort at the infusion site. If Padcev leaks from the injection site or vein into the surrounding skin and tissues, it may cause a reaction at the infusion site. These reactions may occur immediately after receiving an infusion, but sometimes may occur days after the infusion (may affect up to 1 in 10 people).

• Severe infection (sepsis) when bacteria and their toxins circulate in the blood, causing organ damage (may affect up to 1 in 10 people).

• Lung infection (pneumonia) (may affect up to 1 in 10 people).

• Infusion-related reaction

Medicines of this type (monoclonal antibodies) may cause infusion-related reactions such as:

• low blood pressure
• swelling of the tongue
• difficulty breathing (dyspnoea)
• fever
• chills
• skin redness (rubor)
• itching
• rash
• vomiting
• general malaise

Generally, these types of reactions occur from minutes to several hours after completing the infusion. However, they may develop up to several hours after the infusion is complete, although this is uncommon. Infusion-related reactions may affect up to 1 in 10 people.

Other possible adverse effects

The following adverse effects have been reported with Padcev alone:

Very common (may affect more than 1 in 10 people):

• low red blood cells (anaemia)
• nausea, diarrhoea, and vomiting
• fatigue
• decreased appetite
• change in taste sensation
• dry eyes
• hair loss
• weight loss
• dry or itchy skin
• rash
• flat or raised red spots on the skin
• increased liver enzymes (aspartate aminotransferase [AST] or alanine aminotransferase [ALT])

Common (may affect up to 1 in 10 people):

• abnormal gait (gait disturbance)
• eye redness
• hives on the skin
• skin redness
• inflamed, itchy, cracked, and rough skin patches
• redness and tingling sensation on the palms of the hands or soles of the feet
• skin peeling
• mouth ulcer
• rash accompanied by symptoms: itching, redness, red bumps or red patches on the skin, fluid-filled blisters, large blisters, skin lesions
• low platelet count in the blood, which may cause bleeding and bruising (thrombocytopenia)

Uncommon (may affect up to 1 in 100 people):

• skin irritation
• burning sensation on the skin
• nerve problems affecting nerve function, causing unusual sensations or movement problems
• reduction in muscle size
• blood-filled blister
• skin allergic reaction
• rash accompanied by symptoms: scaly patches resembling psoriasis, skin peeling, flat fluid-filled blister
• skin peeling all over the body
• inflammation of skin folds, including the groin
• blister or blister-like lesions on the skin
• swelling or itching affecting only the legs and feet

Frequency not known (frequency cannot be estimated from available data):

• low white blood cell count with or without fever
• abnormal skin discoloration or darkening (skin hyperpigmentation, skin colour change, pigment disorder)

The following adverse effects have been reported with Padcev in combination with pembrolizumab:

Very common (may affect more than 1 in 10 people):

• low red blood cells (anaemia)
• nausea, diarrhoea, and vomiting
• fatigue
• decreased appetite
• change in taste sensation
• dry eyes
• hair loss
• weight loss
• dry or itchy skin
• flat or raised red spots on the skin
• increased liver enzymes (aspartate aminotransferase [AST] or alanine aminotransferase [ALT])
• reduced thyroid gland activity (hypothyroidism)

Common (may affect up to 1 in 10 people):

• abnormal gait (gait disturbance)
• eye redness
• hives on the skin
• skin redness
• rash
• inflamed, itchy, cracked, and rough skin patches
• redness and tingling sensation on the palms of the hands or soles of the feet
• skin peeling
• mouth ulcer
• rash accompanied by symptoms: scaly patches resembling psoriasis, itching, redness, red bumps or red patches on the skin, fluid-filled blisters, large blisters, skin lesions
• elevated lipase (a blood test used to check your pancreas)
• muscle inflammation (myositis)
• low platelet count in the blood, which may cause bleeding and bruising (thrombocytopenia)

Uncommon (may affect up to 1 in 100 people):

• skin irritation
• burning sensation on the skin
• nerve problems affecting nerve function, causing unusual sensations or movement problems
• skin allergic reaction
• rash accompanied by symptoms: skin peeling, flat fluid-filled blister
• skin peeling all over the body
• inflammation of skin folds, including the groin
• blister or blister-like lesions on the skin
• swelling or itching affecting only the legs and feet

Frequency not known (frequency cannot be estimated from available data):

• low white blood cell count with or without fever
• abnormal skin discoloration or darkening (skin hyperpigmentation, skin colour change, pigment disorder)

Reporting of adverse effects

If you experience any adverse effect, consult your doctor, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly through the national reporting system listed in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Padcev

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the carton and label of the vial following EXP. The expiry date refers to the last day of the stated month.

Store in a refrigerator (between 2 ºC and 8 ºC). Do not freeze.

Do not store any unused infusion solution for later use. Disposal of unused medicine and of all materials that have been in contact with it must be carried out in accordance with local regulations.

6. Contents of the pack and other information

Composition of Padcev

• The active substance is enfortumab vedotin.
• A 20 mg vial of powder for concentrate for solution for infusion contains 20 mg of enfortumab vedotin.
• A 30 mg vial of powder for concentrate for solution for infusion contains 30 mg of enfortumab vedotin.
• After reconstitution, each mL of solution contains 10 mg of enfortumab vedotin.

The other components are histidine, monohydrate histidine hydrochloride, trehalose dihydrate, and polysorbate 20.

Nature and contents of the container

Padcev powder for concentrate for solution for infusion is a white to off-white lyophilized powder.

Padcev is supplied in a carton containing 1 glass vial.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder:

Astellas Pharma Europe B.V.

Sylviusweg 62

2333 BE Leiden

The Netherlands

Manufacturer:

Astellas Ireland Co. Ltd

Killorglin

Co Kerry

V93 FC86

Ireland

More information about this medicinal product is available upon request by contacting the local representative of the Marketing Authorization Holder:

Date of the most recent review of this leaflet: MM/YYYY.

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency website: https://www.ema.europa.eu.

This information is intended for healthcare professionals only:

Traceability

To improve the traceability of biological medicines, the name and batch number of the administered medicine should be clearly recorded.

Instructions for preparation and administration

Reconstitution in single-dose vial

1. Follow appropriate procedures for the safe handling and disposal of anticancer medicines.
2. Use appropriate aseptic techniques for reconstitution and preparation of solutions for administration.
3. Calculate the recommended dose based on the patient's body weight to determine the number and strength (20 mg or 30 mg) of vials required.
4. Reconstitute each vial as follows, directing the stream of sterile water for injection preferably onto the vial walls and not directly onto the lyophilized powder:
   1. 20 mg vial: Add 2.3 ml of sterile water for injection to obtain enfortumab vedotin 10 mg/ml.
   2. 30 mg vial: Add 3.3 ml of sterile water for injection to obtain enfortumab vedotin 10 mg/ml.
5. Gently rotate each vial until the contents are completely dissolved. Allow reconstituted vials to stand for at least 1 minute until bubbles disappear. Do not shake the vial. Do not expose to direct sunlight.
6. Visually inspect the solution for particulate matter or discoloration. The reconstituted solution should be clear to slightly opalescent, colourless to pale yellow, and free of visible particles. Discard any vial showing visible particles or discoloration.

Dilution in infusion bag

1. Withdraw the calculated dose volume of reconstituted solution from the vials and transfer it into an infusion bag.
2. Dilute enfortumab vedotin with either 50 mg/ml (5%) glucose injection solution, 9 mg/ml (0.9%) sodium chloride injection solution, or lactated Ringer's solution. The infusion bag size must provide sufficient diluent to achieve a final concentration of enfortumab vedotin between 0.3 mg/ml and 4 mg/ml.

The diluted enfortumab vedotin solution for administration is compatible with intravenous infusion bags made of polyvinyl chloride (PVC), ethylene vinyl acetate, polyolefin such as polypropylene (PP), or IV bottles made of polyethylene (PE), polyethylene glycol-modified polyethylene terephthalate, and with infusion sets made of PVC with plasticizers (bis(2-ethylhexyl) phthalate (DEHP) or tris(2-ethylhexyl) trimellitate (TOTM)), PE, and with filter membranes (pore size: 0.2–1.2 μm) made of polyethersulfone, polyvinylidene fluoride, or mixed cellulose esters.

1. Mix the solution by gentle inversion. Do not shake the bag. Do not expose to direct sunlight.
2. Visually inspect the infusion bag for particulate matter or discoloration before use. The reconstituted solution should be clear to slightly opalescent, colourless to pale yellow, and free of visible particles. Do not use the infusion bag if particulate matter or discoloration is observed.
3. Discard any unused portion remaining in the single-dose vials.

Administration

1. Administer the infusion over 30 minutes through an intravenous line. Do not administer as a rapid infusion or intravenous bolus.

No incompatibilities have been observed with closed drug transfer devices made of acrylonitrile butadiene styrene (ABS), acrylic, activated carbon, ethylene propylene diene monomer, ABS methacrylate, polycarbonate, polyisoprene, polyoxymethylene, PP, silicone, stainless steel, or thermoplastic elastomer for the reconstituted solution.

1. Do not administer other medicines simultaneously through the same infusion line.
2. During administration, in-line filters or syringe filters (pore size: 0.2–1.2 μm, recommended materials*: polyethersulfone,* polyvinylidene fluoride, mixed cellulose esters) are recommended.

Disposal

Padcev is for single use only.

Any unused medicine and all materials that have come into contact with it must be disposed of in accordance with local regulations.