PADCEV 20 mg POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION

Introduction

Package Leaflet: Information for the Patient

Padcev 20mg powder for concentrate for solution for infusion

Padcev 30mg powder for concentrate for solution for infusion

enfortumab vedotin

This medicinal product is subject to additional monitoring, which will allow for quick identification of new safety information. You can help by reporting any side effects you may get. The last section of this leaflet includes information on how to report side effects.

Read all of this leaflet carefully before this medicine is given to you because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor.
• If you get any side effects, talk to your doctor, even if you think they might be unrelated to the medicine. See section 4.

Contents of the pack

1. What is Padcev and what is it used for
2. What you need to know before you are given Padcev
3. How to use Padcev
4. Possible side effects
5. Storage of Padcev
6. Contents of the pack and other information

1. What is Padcev and what is it used for

Padcev contains the active substance enfortumab vedotin, which consists of a monoclonal antibody attached 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 given to people who have received an immunotherapy medicine and have also received 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, ask your doctor.

2. What you need to know before you are given Padcev

You should not be given Padcev

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

Warnings and precautions

Tell your doctor immediately if:

• you have any of the following symptoms of skin reaction:

• rash or itching that gets worse or comes back after treatment,
• blisters or peeling of the skin,
• sores or painful ulcers in the mouth or nose, throat or genital area,
• fever or flu-like symptoms,
• or swollen lymph nodes.

• these may be signs of a severe skin reaction that can occur when receiving this medicine, particularly during the first few weeks of treatment. Skin reactions may occur more often when this medicine is given with pembrolizumab. If this happens, your doctor will monitor you and may give you a medicine to treat your skin condition. You may need to take a break from your treatment until your symptoms improve. If the skin reaction gets worse, your doctor may stop your treatment. You can also find this information in the Patient Information Card that comes with the pack. It is important that you carry this Patient Information Card with you and show it to any healthcare professional who treats you.

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

• you have lung problems (pneumonitis/interstitial lung disease) or if you have new or worsening symptoms, including difficulty breathing, shortness of breath, or cough. These lung problems may occur more often when this medicine is given with pembrolizumab. If this happens, your doctor may take a break from your treatment until your symptoms improve or reduce the dose. If your symptoms get worse, your doctor may stop your treatment.

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

• you have any symptoms of a nerve problem (neuropathy) such as numbness, tingling, or a tingling sensation in your hands or feet or muscle weakness. If this happens, your doctor may take a break from your treatment until your symptoms improve or reduce the dose. If your symptoms get worse, your doctor may stop your treatment.

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

Children and adolescents

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

Other medicines and Padcev

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

Tell your doctor if you are taking medicines for fungal infections (e.g., ketoconazole), as they may increase the amount of Padcev in your blood. If you normally take these medicines, your doctor may switch you to another medicine that you should take during treatment.

Pregnancy, breastfeeding, and fertility

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

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

If you are a woman who starts using this medicine and can become pregnant, you must use an effective contraceptive during treatment and for at least 6 months after stopping Padcev.

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

In men treated with this medicine, it is recommended to freeze and store semen samples before treatment. Men are advised not to father a child during treatment with this medicine and for at least 4 months after the last dose of this medicine.

Driving and using machines

Do not drive or use machines if you feel unwell during treatment.

3. How to use Padcev

You will receive Padcev in a hospital or clinic, under the supervision of a doctor with experience 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 every 28 days. When used with pembrolizumab, the recommended dose of this medicine is 1.25 mg/kg on days 1 and 8 every 21 days. Your doctor will decide how many treatments you need.

How you will receive Padcev

You will receive Padcev through a vein in your arm over 30 minutes. Before use, Padcev will be added to an infusion bag with a glucose, sodium chloride, or Ringer's lactate solution.

If you miss a dose of Padcev

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

If you stop receiving Padcev

Do notstop treatment with Padcev unless you have discussed it with your doctor. Stopping treatment may stop the effect of the medicine.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Some possible side effects may be serious:

• Skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, and other severe rashes, such as intertriginous and flexural symmetrical drug-related exanthema).Tell your doctor immediately if you have any of these signs of severe skin reaction: rash or itching that gets worse or comes back after treatment, blisters or peeling of the skin, sores or painful ulcers in the mouth or nose, throat or genital area, fever or flu-like symptoms, or swollen lymph nodes (frequency not known).

• High blood sugar (hyperglycemia).Tell your doctor immediately if you have any symptoms of high blood sugar, including: frequent urination, increased thirst, blurred vision, confusion, numbness, loss of appetite, fruity breath odor, 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 can make the blood more acidic (diabetic ketoacidosis)(frequency not known).

• Lung problems (pneumonitis/interstitial lung disease).Tell your doctor immediately if you have new or worsening symptoms, 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).Tell your doctor immediately if you have numbness, tingling, or a tingling sensation in your hands or feet or muscle weakness (may affect more than 1 in 10 people).

• Leakage of Padcev from the vein into the tissues surrounding the infusion site (extravasation). Tell your doctor or get medical help immediately if you notice any redness, swelling, itching, or discomfort at the infusion site. If Padcev leaks from the injection site or vein into the skin and surrounding tissues, it could cause a reaction at the infusion site. These reactions can occur immediately after receiving an infusion, but sometimes they can 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).

• Infusion-related reaction

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

• low blood pressure
• swelling of the tongue
• difficulty breathing (dyspnea)
• fever
• chills
• redness of the skin (flushing)
• itching
• rash
• vomiting
• general discomfort

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

Other possible side effects

The following side effects have been reported with Padcev alone:

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

• low red blood cell count (anemia)
• nausea, diarrhea, and vomiting
• fatigue
• decreased appetite
• change in sense of taste
• dry eyes
• hair loss
• weight loss
• dryness or itching of the skin
• rash
• flat or raised red patches 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
• urticaria on the skin
• redness of the skin
• inflamed skin patches, with itching, cracking, and roughness
• redness and tingling sensation in the palms of the hands or soles of the feet
• skin peeling
• mouth ulcers
• rash accompanied by symptoms: patches that resemble erythema multiforme, itching, redness, red or flat patches on the skin, fluid-filled blisters, large blisters, skin lesions

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

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

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

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

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

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

• low red blood cell count (anemia)
• nausea, diarrhea, and vomiting
• fatigue
• decreased appetite
• change in sense of taste
• dry eyes
• hair loss
• weight loss
• dryness or itching of the skin
• flat or raised red patches 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
• urticaria on the skin
• redness of the skin
• rash
• inflamed skin patches, with itching, cracking, and roughness
• redness and tingling sensation in the palms of the hands or soles of the feet
• skin peeling
• mouth ulcers
• rash accompanied by symptoms: patches that resemble erythema multiforme, itching, redness, red or flat patches on the skin, fluid-filled blisters, large blisters, skin lesions
• increased lipase (blood test to check your pancreas)
• inflammation of the muscles (myositis)

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

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

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

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

Reporting of side effects

If you experience any side effects, talk to your doctor, even if you think they might be unrelated to the medicine. You can also report side effects directly through the national reporting system listed in Appendix V. By reporting side 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 which is stated on the carton and vial label after EXP. The expiry date is the last day of the month shown.

Store in a refrigerator (2°C to 8°C). Do not freeze.

Do not store the infusion solution that is left over for reuse. Disposal of the unused medicine and all materials that have come into contact with it should be done in accordance with local regulations.

6. Container contents and additional 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, histidine monohydrochloride, trehalose dihydrate, and polysorbate 20.

Appearance and container contents of the product

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 authorisation holder and manufacturer

Marketing authorisation holder:

Astellas Pharma Europe B.V.

Sylviusweg 62

2333 BE Leiden

Netherlands

Manufacturer:

Astellas Ireland Co. Ltd

Killorglin

Co Kerry

V93 FC86

Ireland

For further information on this medicinal product, please contact the local representative of the marketing authorisation holder:

Date of last revision of this leaflet:MM/YYYY.

Other sources of information

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

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This information is intended for healthcare professionals only:

Traceability

In order to improve the traceability of biological medicinal products, the name and batch number of the administered product should be clearly recorded.

Instructions for preparation and administration

Reconstitution in a single-dose vial

1. Follow the procedures for the proper handling and disposal of cancer medicines.
2. Use the appropriate aseptic technique for reconstitution and preparation of solutions for administration.
3. Calculate the recommended dose based on the patient's weight to determine the number and strength (20 mg or 30 mg) of vials needed.
4. Reconstitute each vial as follows and, if possible, direct the jet of sterile water for injection towards the vial walls and not directly towards 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. Slowly rotate each vial until the contents are completely dissolved. Allow the reconstituted vials to stand for at least 1 minute, until the bubbles have disappeared. Do not shake the vial. Do not expose to direct sunlight.
6. Visually inspect the solution for particulate matter or color change. The reconstituted solution should be clear to slightly opalescent, colorless to pale yellow, and free of visible particles. Discard any vial with visible particles or color change.

Dilution in an infusion bag

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

The diluted infusion solution of enfortumab vedotin is compatible with intravenous infusion bags made of polyvinyl chloride (PVC), ethylene-vinyl acetate, polyolefin, such as polypropylene (PP), or intravenous bags made of polyethylene (PE), modified polyethylene terephthalate, and PVC infusion equipment with plasticizer (bis(2-ethylhexyl) phthalate (DEHP) or tri(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 gently inverting. Do not shake the bag. Do not expose to direct sunlight.
2. Visually inspect the infusion bag for particulate matter or color change before use. The reconstituted solution should be clear to slightly opalescent, colorless to pale yellow, and free of visible particles. Do not use the infusion bag if particulate matter or color change is observed.
3. Discard any unused contents of 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 reconstituted solution.

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

Disposal

Padcev is for single use only.

Disposal of unused medicinal product and all materials that have come into contact with it should be carried out in accordance with local regulations.