Label: information for the patient

Padcev 20mg powder for concentrate for solution for infusion

Padcev 30mg powder for concentrate for solution for infusion

enfortumab vedotina

This medication is subject to additional monitoring, which will expedite the detection of new information about its safety. You may contribute by reporting any adverse effects you experience. The final part of section4 includes information on how to report these adverse effects.

Read this label carefully before this medication is administered to you, because it contains important information for you.

• Keep this label, as you may need to read it again.
• If you have any questions, consult your doctor.
• If you experience adverse effects, consult your doctor, even if they are possible adverse effects not listed in this label. See section4.

Padcev contains the active ingredient enfortumab vedotina, which is composed of a monoclonal antibody linked to a drug intended to kill cancer cells. The monoclonal antibody recognizes certain cancer cells and releases the drug in them.

This medication is usedalone or in combination with pembrolizumabin adults to treat a type of cancer called bladder cancer (urothelial carcinoma). Padcev is administered to people whose cancer has spread or cannot be removed by surgery.

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

This medication may be administered in combination with pembrolizumab. It is essential that you also read the prospect for this other medication. If you have any doubts, consult your doctor.

Do not administer Padcev

• if you are allergic to enfortumab vedotina or any of the other components of this medication (listed in section6).

Warnings and precautions

Consult your doctor immediately if:

• you have any of the following skin reaction symptoms:

• eruption 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.

• These may be signs of a severe skin reaction that can occur when receiving this medication, particularly during the first weeks of treatment. Skin reactions may occur more frequently in patients when this medication is administered with pembrolizumab. If this occurs, your doctor will monitor you and may prescribe a medication to treat your skin condition. Your doctor may also pause your treatment until symptoms improve. If the skin reaction worsens, your doctor may stop your treatment.Also, you may find this information in the Patient Information Leaflet included in the packaging. It is essential to carry this Patient Information Leaflet 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-smelling breath, nausea, vomiting, or stomach pain. You may experience high blood sugar during treatment.

• you have lung problems (neumonitis/interstitial lung disease) or if you experience new or worsening symptoms, including difficulty breathing, shortness of breath, or coughing.These lung problems may occur more frequently when this medication is administered with pembrolizumab.If this occurs, your doctor may pause your 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 severe and life-threatening.

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

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

Children and adolescents

This medication should not be used in children and adolescents under 18years.

Other medications and Padcev

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

Inform your doctor if you are taking medications for fungal infections (e.g., ketoconazole), as they may increase the amount of Padcev in your blood. If you normally take these medications, your doctor may change them and prescribe another medication for you to take during treatment.

Pregnancy and breastfeeding and fertility

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

You should not use this medication if you are pregnant. Padcev may harm your baby.

If you are a woman starting treatment with this medication and may become pregnant, you should use effective contraception during treatment and for at least 6months after stopping Padcev.

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

Men treated with this medication are advised to freeze and store semen samples before treatment. It is recommended that men not conceive a child during treatment with this medication and for at least 4months after the last dose of this medication.

Driving and operating machinery

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

You will receive Padcev in a hospital or clinic under the supervision of an experienced doctor who administers these treatments.

How Much Padcev You Will Receive

When used alone, the recommended dose of this medication is 1.25 mg/kg on days 1, 8, and 15 every 28 days.When used with pembrolizumab, the recommended dose of this medication 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 intravenous infusion in a vein for 30 minutes.Before use, Padcev will be added to a perfusion bag with a glucose solution, sodium chloride, or lactate Ringer 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.The suspension of treatment may stop the effect of the medication.

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

Some possible side effects can be serious:

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

• High blood sugar (hyperglycemia).Inform 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-smelling breath, nausea, vomiting, or stomach pain (may affect more than 1 in 10 people).

• A severe 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).Inform your doctor immediately if you experience new or worsening symptoms, including difficulty breathing, shortness of breath, or coughing (may affect up to 1 in 10 people).

• Nervous system problems (peripheral neuropathy, such as motor neuropathy, sensory-motor neuropathy, paresthesia, hypoesthesia, and muscle weakness).Inform your doctor immediately if you have numbness, tingling, or prickling sensations in your hands or feet or muscle weakness (may affect more than 1 in 10 people).

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

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

• Perfusion-related reaction

Medicines of this type (monoclonal antibodies) can cause perfusion-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 malaise

These types of reactions can occur from minutes to several hours after completing the perfusion. However, they can develop up to several hours after completing the perfusion, although this is rare. Perfusion-related reactions can affect up to 1 in 10 people.

Other possible side effects

The following side effects have been reported with Padcev only:

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

• Low red blood cell count (anemia)
• Nausea, diarrhea, and vomiting
• Fatigue
• Loss of appetite
• Change in taste
• Dry eyes
• Hair loss
• Weight loss
• Dry or itchy skin
• Rash
• Flat or red raised bumps 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)
• Redness of the eyes
• Urticarial hives on the skin
• Redness of the skin
• Inflamed skin plaques, itchy, cracked, and rough
• 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 plaques on the skin, blisters filled with liquid, 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 unusual sensations or movement problems
• Decreased muscle size
• Blisters with blood
• Allergic reaction on the skin
• Rash accompanied by symptoms: scaly patches, skin peeling, flat blisters filled with liquid
• Widespread skin peeling
• Inflammation of skin folds, including the groin
• Blisters or lesions similar to blisters on the skin
• Inflammation or itching that appears only on the legs and feet

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

• Low white blood cell count with or without fever
• Abnormal skin discoloration (hypopigmentation of the skin, skin color change, pigment 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
• Loss of appetite
• Change in taste
• Dry eyes
• Hair loss
• Weight loss
• Dry or itchy skin
• Flat or red raised bumps 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)
• Redness of the eyes
• Urticarial hives on the skin
• Redness of the skin
• Rash
• Inflamed skin plaques, itchy, cracked, and rough
• 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, itching, redness, red bumps or plaques on the skin, blisters filled with liquid, large blisters, skin lesions
• Increased lipase (blood test to check the pancreas)
• Muscle inflammation (myositis)

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

• Skin irritation
• Burning sensation on the skin
• Problems affecting nerve function and causing unusual sensations or movement problems
• Reactions on the skin
• Rash accompanied by symptoms: skin peeling, flat blisters filled with liquid
• Widespread skin peeling
• Inflammation of skin folds, including the groin
• Blisters or lesions similar to blisters on the skin
• Inflammation or itching that appears only on the legs and feet

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

• Low white blood cell count with or without fever

• Abnormal skin discoloration (hypopigmentation of the skin, skin color change, pigment disorder)

Reporting of side effects

If you experience any type of side effect, consult your doctor, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the national notification system included in theAppendix V. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the box and vial label after CAD. The expiration date is the last day of the month indicated.

Store in refrigerator (between 2°C and 8°C). Do not freeze.

Do not store unused perfusion solution for re-use. The disposal of unused medication and all materials that have been in contact with it will be carried out in accordance with local regulations.

Composition of Padcev

• The active ingredient is enfortumab vedotina
• A vial of 20 mg of powder for concentrate for solution for infusion contains 20 mg of enfortumab vedotina
• A vial of 30 mg of powder for concentrate for solution for infusion contains 30 mg of enfortumab vedotina
• After reconstitution, each ml of solution contains 10 mg of enfortumab vedotina

The other components are histidine, monohydrate chlorhidrate of histidine, dihydrate of trehalose and polisorbate 20.

Appearance of the product and contents of the pack

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

Padcev is supplied in a pack containing 1 vial of glass.

Holder of the marketing authorisation and responsible for manufacturing

Holder of the marketing authorisation:

Astellas Pharma Europe B.V.

Sylviusweg 62

2333 BE Leiden

Netherlands

Responsible for manufacturing:

Astellas Ireland Co. Ltd

Killorglin

Co Kerry

V93 FC86

Ireland

For further information about this medicinal product, please consult the representative of the marketing authorisation holder in your country.

Last update of the summary of product characteristics:MM/AAAA.

Other sources of information

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

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This information is intended for healthcare professionals only:

Traceability

To improve the traceability of biological medicinal products, the name and batch number of the medicinal product administered must be clearly recorded.

Instructions for preparation and administration

Reconstitution in single-dose vial

1. Follow the procedures for the correct 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 required.
4. Reconstitute each vial as follows, and if possible, direct the sterile water for injection stream towards the vial walls and not directly at the lyophilized powder:
   1. Vial of 20 mg: Add 2.3 ml of sterile water for injection to obtain enfortumab vedotina 10 mg/ml.
   2. Vial of 30 mg: Add 3.3 ml of sterile water for injection to obtain enfortumab vedotina 10 mg/ml.
5. Gently rotate each vial until the contents are fully dissolved. Allow the reconstituted vials to settle for at least 1 minute, until the bubbles disappear. Do not agitate the vial. Do not expose to direct sunlight.
6. Visually inspect the solution to detect particles in suspension or colour change. The reconstituted solution must be between transparent and slightly opalescent, colourless to light yellow and without visible particles. Discard any vial with visible particles or colour change.

Dilution in infusion bag

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

The solution for administration of enfortumab vedotina diluted is compatible with PVC infusion bags, ethylene-vinyl acetate, polyolefin, such as polypropylene (PP), or PE infusion bags, terephthalate of modified polyethylene glycol and PVC infusion equipment with plasticizer (bis(2-ethylhexyl) phthalate (DEHP) or tris(2-ethylhexyl) trimellitate (TOTM)), PE and with filters (pore size: 0.2-1.2 μm) of polyethersulfone, fluorinated polyvinylidene or mixed cellulose esters.

1. Mix the solution by gently inverting it. Do not agitate the bag. Do not expose to direct sunlight.
2. Visually inspect the infusion bag to detect particles in suspension or colour change before use. The reconstituted solution must be between transparent and slightly opalescent, colourless to light yellow and without visible particles. Do not use the infusion bag if particles in suspension or colour change are observed.
3. Discard any unused solution in the single-dose vials.

Administration

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

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

1. Do not administer other medicinal products 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, fluorinated polyvinylidene or mixed cellulose esters).

Disposal

Padcev is for single use only.

The disposal of unused medicinal product and all materials that have been in contact with it will be in accordance with local regulations.