Patient Information: Product Information

LIBTAYO 350 mg Concentrate for Solution for Infusion

cemiplimab

This medicine is subject to additional monitoring, which will expedite the detection of new information about its safety. You can contribute by reporting any adverse effects you may experience. The final part of section 4 includes information on how to report these adverse effects.

Read this entire product information carefully before you receive this medicine, as it contains important information for you.

• Keep this product information, as you may need to refer to it again.
• It is essential that you carry the patient information card with you during treatment.
• If you have any questions, consult your doctor.
• • If you experience any adverse effects, consult your doctor, even if they are not listed in this product information. See section 4.

LIBTAYO is a cancer medication that contains the active ingredient cemiplimab, which is a monoclonal antibody.

LIBTAYO is used in adults to treat:

• an advanced type of skin cancer called cutaneous squamous cell carcinoma (CSCC).
• an advanced type of skin cancer called basal cell carcinoma (BCC) that has received treatment with a Hedgehog signaling pathway inhibitor and this treatment did not work well or was not well tolerated.
• an advanced type of lung cancer called non-small cell lung cancer (NSCLC).
• an advanced type of cancer called cervical cancer that has worsened during or after chemotherapy.

LIBTAYO can be administered in combination with chemotherapy for NSCLC. It is essential that you also read the prospectuses for the specific chemotherapy you may be receiving. If you have any doubts about these medications, consult your doctor.

LIBTAYO works by helping your immune system fight cancer.

You should not receive LIBTAYO if:

• You are allergic to cemiplimab or any of the other components of this medication (listed in section 6).

If you think you may be allergic or are unsure, talk to your doctor before receiving LIBTAYO.

Warnings and precautions

Consult your doctor or nurse before receiving LIBTAYO if:

• You have an autoimmune disease (a condition in which your body attacks its own cells).
• You have undergone an organ transplant, or have received or plan to receive a bone marrow transplant using someone else's marrow (allogeneic hematopoietic cell transplant).
• You have lung or respiratory problems.
• You have liver problems.
• You have kidney problems.
• You have diabetes.
• You have any other disease.

If any of the above situations apply to you, or if you are unsure, consult your doctor or nurse before receiving LIBTAYO.

Be aware of adverse effects

LIBTAYO may cause some severe adverse effects that you should report immediately to your doctor. These problems can occur at any time during treatment or even after treatment has ended. You may experience more than one adverse effect at the same time.

These severe adverse effects include:

• Skin problems.
• Lung problems (pneumonitis).
• Intestinal problems (colitis).
• Liver problems (hepatitis).
• Problems with hormone glands - especially the thyroid, pituitary, adrenal glands, and pancreas.

• Type 1 diabetes, including diabetic ketoacidosis (acid in the blood produced by diabetes).

• Kidney problems (nephritis and renal insufficiency).
• Central nervous system problems (such as meningitis).
• Reactions related to perfusion.
• Muscle problems (inflammation of muscles called myositis).
• Inflammation of the heart muscle (myocarditis).
• A condition in which the immune system produces too many normal cells that fight infections, called histiocytes and lymphocytes, which can cause various symptoms (hemophagocytic lymphohistiocytosis) (see the list of signs and symptoms in "Possible adverse effects").
• Problems in other parts of the body (see “Possible adverse effects”).

Be aware of these adverse effects while receiving LIBTAYO. See section 4 "Possible adverse effects". If you experience any of these effects, consult your doctor immediately.

Your doctor may administer other medications to stop the most severe reactions and reduce your symptoms. Your doctor may also delay your next dose of LIBTAYO or suspend your treatment.

Children and adolescents

LIBTAYO should not be used in children and adolescents under 18 years old.

Other medications and LIBTAYO

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

Particularly, inform your doctor if you are taking or have taken any of the following medications:

• A cancer medication called idelalisib.
• Medications that weaken your immune system; for example, corticosteroids, such as prednisone. These medications may interfere with the effect of LIBTAYO. However, once you receive treatment with LIBTAYO, your doctor may administer corticosteroids to reduce the adverse effects you may experience with LIBTAYO.

Pregnancy

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

• LIBTAYO may harm the fetus.
• Inform your doctor immediately if you become pregnant while receiving treatment with LIBTAYO.
• If you can become pregnant, you must use an effective contraceptive method to avoid becoming pregnant:

• While you are being treated with LIBTAYO and
• For at least 4 months after the last dose.

• Consult your doctor about the contraceptive methods you should use during this time.

Breastfeeding

• If you are breastfeeding or plan to do so, consult your doctor before receiving this medication.
• Do not breastfeed while receiving LIBTAYO and for at least 4 months after the last dose.
• The passage of LIBTAYO into breast milk is unknown.

Driving and operating machinery

The influence of LIBTAYO on your ability to drive and operate machinery is negligible or insignificant. If you feel tired, do not drive or operate machinery until you feel better.

• You will receive LIBTAYO in a hospital or clinic - supervised by a doctor with experience in cancer treatment.
• LIBTAYO is administered intravenously by infusion.
• The infusion will last about 30 minutes.
• LIBTAYO is generally administered every 3 weeks.

How much you will receive

The recommended dose of LIBTAYO is 350 mg.

Your doctor will decide how much LIBTAYO you will receive and how many treatments you will need.

Your doctor will make blood tests to detect certain adverse effects during your treatment.

If you have forgotten your appointment

Call your doctor as soon as possible to schedule another appointment. It is very important that you do not miss a dose of this medication.

If you interrupt treatment with LIBTAYO

Do not interrupt treatment with LIBTAYO unless you have spoken with your doctor. This is because interrupting your treatment may stop the effect of the medication.

Patient information leaflet

The information in this leaflet can be found in the patient information leaflet that your doctor gave you. It is important that you keep this patient information leaflet and show it to your partner or caregivers.

If you have any questions about your treatment, consult your doctor.

Like all medicines, this medicine can cause side effects, although not everyone will experience them. Your doctor will talk to you and explain the risks and benefits of your treatment.

LIBTAYO acts on your immune system and can cause inflammation in some parts of your body (see the conditions listed in section 2, "Be aware of side effects"). Inflammation can cause serious damage and you may need treatment or have to stop taking LIBTAYO. Some inflammatory conditions could also cause death.

Seek medical attention urgentlyif you have any of the following signs or symptoms, or if they worsen:

• Skin problemssuch as rash or itching, blisters on the skin or ulcers in the mouth or other mucous membranes.
• Lung problems (pneumonitis)such as new or worsening cough, shortness of breath or chest pain.
• Intestinal problems (colitis)such as frequent diarrhea, often with blood or mucus, more frequent bowel movements, black or tarry stools and severe stomach pain or tenderness.
• Liver problems (hepatitis)such as yellowing of the skin or the white part of the eyes, intense nausea or vomiting, right upper stomach pain, feeling drowsy, dark urine (tea-colored), easy bruising or bleeding, and decreased appetite.
• Problems with hormone glandssuch as headache that does not go away or unusual headaches, rapid heartbeat, increased sweating, feeling too hot or cold, intense fatigue, dizziness or fainting, weight gain or loss, increased or decreased hunger or thirst, hair loss, constipation, deepening voice, low blood pressure, frequent urination, nausea or vomiting, stomach pain, changes in mood or behavior (such as decreased sex drive, irritability or frequent forgetfulness).
• Symptoms of type 1 diabetes or diabetic ketoacidosissuch as feeling hungrier or thirstier than usual, needing to urinate more frequently, losing weight, feeling tired or nauseous, rapid breathing and deep breathing, confusion, unusual drowsiness, sweet-smelling breath, sweet or metallic taste in the mouth, or a different odor of urine or sweat.
• Kidney problems (nephritis and renal insufficiency)such as urinating less frequently than usual, blood in urine, swelling of the ankles and feeling less hungry than usual.
• Reactions related to infusion (which can be severe or fatal)such as chills, tremors or fever, itching or rash, redness or swelling of the face, shortness of breath or wheezing, feeling dizzy or faint, and back or neck pain, nausea, vomiting or abdominal pain.

• Problems in other parts of the bodysuch as:

• Problems in the nervous systemsuch asheadache or stiffness in the neck, fever, fatigue or weakness, cold, vomiting, confusion, memory problems or drowsiness, convulsions (seizures), seeing or hearing things that are not there (hallucinations), severe muscle weakness, tingling, numbness, weakness or burning pain in arms or legs, paralysis in limbs
• Problems with muscles and jointssuch as joint pain or swelling, muscle pain, weakness or stiffness
• Problems with the eyessuch as changes in vision, eye pain or redness, sensitivity to light
• Problems with the heart and circulatory systemsuch as changes in heart rate, rapid heartbeat, feeling like skipping beats or palpitations, chest pain, difficulty breathing
• Others:dryness in many parts of the body from the mouth to the eyes, nose, throat and upper layers of the skin, bruises on the skin or bleeding, enlarged liver and/or spleen, enlargement of lymph nodes.

The following side effects have been reported in clinical trials of patients treated only with cemiplimab:

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

• feeling tired
• muscle or bone pain
• rash
• diarrhea (soft stools)
• decreased red blood cell count
• nausea
• less hunger
• itching
• constipation
• cough
• abdominal pain
• upper respiratory tract infection

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

• vomiting
• difficulty breathing
• fever
• urinary tract infection
• headache
• swelling (edema)
• thyroid problems (hyperthyroidism and hypothyroidism)
• high blood pressure
• increased liver enzymes in the blood
• rough, scaly or crusted skin patches (actinic keratosis)
• cough, lung inflammation
• infusion-related reactions
• liver inflammation
• intestinal inflammation (diarrhea, more frequent bowel movements, black or tarry stools, severe abdominal pain or tenderness)
• mouth inflammation
• abnormal kidney function tests
• nerve inflammation causing tingling, numbness, weakness or burning pain in arms or legs
• kidney inflammation.

Rare(may affect up to 1 in 1000 people):

• inflammation of the membranes of the brain and spinal cord, which may be caused by an infection
• type 1 diabetes, which may include feeling hungrier or thirstier than usual, needing to urinate more frequently, losing weight and feeling tired or nauseous, or diabetic ketoacidosis
• eye pain, irritation, itching or redness; inflammation, blurred vision, discomfort due to light sensitivity (uveitis and keratitis)
• a temporary inflammation of the nerves causing pain, weakness and paralysis in the limbs
• a condition in which muscles become weakened and easily fatigued, muscle pain

Other side effects reported(frequency unknown):

• organ transplant rejection
• bladder inflammation. Symptoms may include frequent or painful urination, urgent need to urinate, blood in urine, abdominal pain or pressure in the lower abdomen
• hemophagocytic lymphohistiocytosis. A condition in which your immune system produces too many normal cells that fight infections, called histiocytes and lymphocytes. Symptoms may include enlarged liver and/or spleen, skin rash, enlarged lymph nodes, respiratory problems, easy bruising, kidney and heart problems
• celiac disease (characterized by symptoms such as stomach pain, diarrhea and bloating after consuming foods containing gluten)
• pancreatic exocrine insufficiency (absence or reduction of digestive enzymes produced by the pancreas).

The following side effects have been reported in clinical trials of patients treated with cemiplimab in combination with chemotherapy:

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

• decreased red blood cell count
• hair loss
• muscle or bone pain
• nausea
• feeling tired
• nerve inflammation causing tingling, numbness, weakness or burning pain in arms or legs
• high blood sugar
• less hunger
• increased liver enzymes in the blood
• decreased white blood cell count (neutrophils)
• constipation
• decreased platelet count
• difficulty breathing
• rash
• vomiting
• weight loss
• sleep problems
• diarrhea (soft stools)
• low albumin levels in the blood

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

• abnormal kidney function tests
• thyroid problems (hyperthyroidism and hypothyroidism)
• cough, lung inflammation
• itching
• kidney inflammation
• intestinal inflammation (diarrhea, more frequent bowel movements, black or tarry stools, severe abdominal pain or tenderness)
• joint pain, swelling, polyarthritis and joint effusion

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

• thyroid inflammation
• infusion-related reactions
• type 1 diabetes, which may include feeling hungrier or thirstier than usual, needing to urinate more frequently, losing weight and feeling tired or nauseous

Other side effects that have been reported(frequency unknown):

• celiac disease (characterized by symptoms such as stomach pain, diarrhea and bloating after consuming foods containing gluten)
• pancreatic exocrine insufficiency (absence or reduction of digestive enzymes produced by the pancreas).

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 Spanish System for Pharmacovigilance of Medicines for Human Use: www.notificaRAM.es.

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 packaging and on the vial after CAD. The expiration date is the last day of the month indicated.

Store in the refrigerator (between 2 °C and 8 °C).

Do not freeze.

Store in the original packaging to protect it from light.

From a microbiological standpoint, the prepared infusion solution must be used immediately. If the diluted solution is not administered immediately, the storage times in use and the conditions before use are the responsibility of the user.

Chemical and physical stability has been demonstrated in use:

• At room temperature up to 25 °C for no more than 8 hours from the time of preparation of the infusion until the end of the infusion.

Or

• Refrigerated between 2 °C and 8 °C for no more than 10 days from the time of preparation of the infusion until the end of the infusion. Allow the diluted solution to reach room temperature before administration.

Do not store any unused portion of the infusion solution for reuse.

Any unused portion of the infusion solution should not be reused and should be disposed of in accordance with local requirements.

Composition of LIBTAYO

The active ingredient is cemiplimab:

• 1 ml of concentrate contains 50 mg of cemiplimab.
• Each vial contains 350 mg of cemiplimab in 7 ml of concentrate.

The other components are L-Histidine, monohydrochloride of L-Histidine monohydrate, L-proline, sucrose, polisorbate 80, and water for injection.

Appearance of the product and contents of the pack

LIBTAYO concentrate for solution for infusion (sterile concentrate) is supplied as a sterile, transparent to slightly opalescent, colorless to pale yellow solution that may contain traces of translucent to white particles.

Each pack contains 1 glass vial with 7 ml of concentrate.

Marketing Authorization Holder

Regeneron Ireland Designated Activity Company (DAC)

One Warrington Place,

Dublin 2, D02 HH27

Ireland

Responsible for manufacturing

Regeneron IrelandDAC

Raheen Business Park

Limerick

Ireland

For more information about this medicine, please contact the local representative of the marketing authorization holder:

Last update of this leaflet:

The detailed information on this medicine is available on the website of the European Medicines Agency:http://www.ema.europa.eu

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This information is intended only for healthcare professionals:

Instructions for use

Preparation

• Before administration, visually inspect the medicine to detect particles and discoloration. LIBTAYO is a solution that is transparent to slightly opalescent, colorless to pale yellow that may contain traces of translucent to white particles.
• Discard the vial if the solution is turbid, discolored, or contains foreign particles that are not traces of translucent to white particles.
• Do not shake the vial.
• Withdraw 7 ml (350 mg) from the LIBTAYO vial and transfer it to an intravenous infusion bag that contains a sterile, non-pyrogenic, low-protein-binding filter in line or in parallel (pore size of 0.2 microns to 5 microns).
• LIBTAYO is for single use only. Discard any unused medicine or waste according to local regulations.

Storage of the diluted solution

LIBTAYO does not contain preservatives.

From a microbiological point of view, the infusion solution prepared must be used immediately. If the diluted solution is not administered immediately, the storage times in use and the conditions before use are the responsibility of the user.

The chemical and physical stability has been demonstrated in use:

• at room temperature up to 25 °C for no more than 8 hours from the time of preparation of the infusionuntil completion of the infusion.

Or

• refrigerated between 2 °C and 8 °C for no more than 10 days from the time of preparation of the infusionuntil completion of the infusion. Allow the diluted solution to reach room temperature before administration.

Do not freeze.

Administration

• LIBTAYO is administered by intravenous infusion. It is administered by infusion over 30 minutes through an intravenous line that contains a sterile, non-pyrogenic, low-protein-binding filter in line or in parallel (pore size of 0.2 microns to 5 microns).
• Do not administer concomitantly with other medicines through the same infusion line.