LIBTAYO 350 mg concentrate for infusion solution

Introduction

Package Leaflet: Information for the Patient

LIBTAYO 350 mg concentrate for solution for infusion

cemiplimab

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 the package leaflet contains information on how to report side effects.

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

• Keep this leaflet, you may need to read it again.
• It is important that you carry the patient information card with you during treatment.
• If you have any further questions, ask your doctor.
• • If you experience side effects, consult your doctor, even if they are not listed in this leaflet. See section 4.

Contents of the pack

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

1. What is LIBTAYO and what is it used for

LIBTAYO is a cancer medicine that contains the active substance cemiplimab, which is a monoclonal antibody.

LIBTAYO is used in adults to treat:

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

LIBTAYO may be given in combination with chemotherapy for NSCLC. It is important that you also read the package leaflets of the specific chemotherapy you may be receiving. If you have any questions about these medicines, ask your doctor.

LIBTAYO works by helping your immune system fight cancer.

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

You should not be given LIBTAYO if:

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

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

Warnings and precautions

Talk to your doctor or nurse before you are given LIBTAYO if:

• you have an autoimmune disease (a condition where the body attacks its own cells)
• you have had an organ transplant, or have received or plan to receive a bone marrow transplant using bone marrow from another person (allogeneic hematopoietic stem cell transplant)
• you have lung or breathing problems
• you have liver problems
• you have kidney problems
• you have diabetes
• you have any other illness

If any of the above applies to you, or if you are unsure, talk to your doctor or nurse before receiving LIBTAYO.

Pay attention to side effects

LIBTAYO may cause some serious side effects that you need to tell your doctor about immediately. These problems can occur at any time during treatment or even after your treatment has finished. You may have more than one side effect at the same time.

These serious side effects include:

• skin problems
• lung problems (pneumonitis)
• intestinal problems (colitis)
• liver problems (hepatitis)
• problems with hormone glands - especially the thyroid, pituitary, adrenal, and pancreas

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

• kidney problems (nephritis and renal failure)
• problems with the central nervous system (such as meningitis)
• infusion-related reactions
• muscle problems (inflammation of the muscles called myositis)
• inflammation of the heart muscle (myocarditis)
• a disease in which the immune system produces too many normal cells that fight infection, called histiocytes and lymphocytes, which can cause various symptoms (hemophagocytic lymphohistiocytosis) (see the list of signs and symptoms in "Possible side effects")
• problems in other parts of the body (see "Possible side effects")

Pay attention to these side effects while you are receiving LIBTAYO. See section 4 "Possible side effects". If you get any of these, tell your doctor immediately.

Your doctor may give you other medicines to stop the more serious reactions and reduce your symptoms. Your doctor may also delay your next dose of LIBTAYO or stop your treatment.

Children and adolescents

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

Other medicines and LIBTAYO

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

In particular, tell your doctor if you are taking or have taken any of the following medicines:

• a cancer medicine called idelalisib
• medicines that weaken your immune system; for example, corticosteroids, such as prednisone. These medicines may interfere with the effect of LIBTAYO. However, once you receive treatment with LIBTAYO, your doctor may give you corticosteroids to reduce the side effects you may have with LIBTAYO.

Pregnancy

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

• LIBTAYO may harm your unborn baby.
• Tell your doctor immediately if you become pregnant while being treated with LIBTAYO.
• If you can become pregnant, you must use an effective method of birth control to avoid becoming pregnant:

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

• Talk to your doctor about the birth control methods you should use during this time.

Breast-feeding

• If you are breast-feeding or plan to breast-feed, talk to your doctor before you are given this medicine.
• Do not breast-feed when you are being treated with LIBTAYO and for at least 4 months after the last dose.
• It is not known whether LIBTAYO passes into breast milk.

Driving and using machines

LIBTAYO has no or negligible influence on the ability to drive and use machines. If you feel tired, do not drive or use machines until you feel better.

3. How LIBTAYO is given

• You will be given LIBTAYO in a hospital or clinic - supervised by a doctor with experience in treating cancer.
• LIBTAYO is given into a vein by drip (intravenous infusion).
• The infusion will take about 30 minutes.
• LIBTAYO is usually given every 3 weeks.

How much you will be given

The recommended dose of LIBTAYO is 350 mg.

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

Your doctor will do blood tests to check for certain side effects during your treatment.

If you miss an appointment

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

If you stop treatment with LIBTAYO

Do not stop treatment with LIBTAYO unless you have talked to your doctor. This is because stopping your treatment may stop the effect of the medicine.

Patient information card

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

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

4. Possible Adverse Effects

Like all medicines, this medicine may cause adverse effects, although not all people suffer from them. Your doctor will talk to you and explain the risks and benefits of your treatment.

LIBTAYO acts on your immune system and may cause inflammation in some parts of your body (see the conditions detailed in section 2, "Pay attention to adverse effects"). Inflammation can cause you serious damage and may require treatment or discontinuation of treatment with LIBTAYO. Some inflammatory conditions could also lead to death.

Seek urgent medical attentionif 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 bowel movements than usual, black or tarry stools, and severe abdominal pain or tenderness.
• Liver problems (hepatitis)such as yellowing of the skin or the white part of the eyes, severe nausea or vomiting, pain in the right side of the abdomen, feeling of sleepiness, dark urine (tea-colored), bleeding or bruising that appears more easily than usual, and decreased appetite.
• Problems with hormonal glandssuch as persistent or unusual headaches, rapid heartbeats, increased sweating, feeling of more cold or heat than usual, intense fatigue, dizziness or fainting, weight gain or loss, increased or decreased appetite, hair loss, constipation, deepening of the voice, very low blood pressure, need to urinate more frequently than usual, nausea or vomiting, abdominal pain, mood or behavior changes (such as decreased sexual desire, irritability, or frequent forgetfulness).
• Type 1 diabetes symptoms or diabetic ketoacidosissuch as feeling more hungry or thirsty than usual, needing to urinate more frequently, weight loss, feeling tired or nauseous, abdominal pain, rapid and deep breathing, confusion, unusual sleepiness, sweet breath odor, sweet or metallic taste in the mouth, or a different odor of urine or sweat.
• Kidney problems (nephritis and renal failure)such as urinating less frequently than usual, blood in urine, swelling of ankles, and feeling less hungry than usual.
• Infusion-related reactions (sometimes can be severe or fatal)such as chills, shaking or fever, itching or rash, redness or swelling of the face, shortness of breath or wheezing, feeling of dizziness or fainting, and back or neck pain, nausea, vomiting, or abdominal pain.

• Problems in other parts of the bodysuch as:

• Nervous system problemssuch as headache or neck stiffness, fever, fatigue or weakness, cold, vomiting, confusion, memory problems or sleepiness, seizures (attacks), seeing or hearing things that really do not exist (hallucinations), severe muscle weakness, tingling, numbness, weakness, or burning pain in arms or legs, paralysis in the limbs.
• Muscle and joint problemssuch as joint pain or swelling, muscle pain, weakness, or stiffness.
• Eye problemssuch as changes in vision, eye pain or redness, sensitivity to light.
• Heart and circulatory problemssuch as changes in heartbeats, rapid heartbeats, feeling of skipped 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, bruising or bleeding, enlarged liver and/or spleen, enlarged lymph nodes.

The following adverse effects have been reported in clinical trials of patients treated with cemiplimab alone:

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

• feeling of fatigue.
• muscle or bone pain.
• rash.
• diarrhea (soft stools).
• decrease in the number of red blood cells.
• nausea.
• decreased appetite.
• 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 gland problems (hyperthyroidism and hypothyroidism).
• high blood pressure.
• increase in liver enzymes in the blood.
• rough, scaly, or crusty areas on the skin (actinic keratosis).
• cough, lung inflammation.
• infusion-related reactions.
• liver inflammation.
• intestinal inflammation (diarrhea, more bowel movements than usual, black or tarry stools, severe abdominal pain or tenderness).
• mouth inflammation.
• abnormal kidney function tests.
• nervous system inflammation causing tingling, numbness, weakness, or burning pain in arms or legs.
• kidney inflammation.

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

• joint pain, swelling, polyarthritis, and joint effusion.
• bruising or bleeding.
• thyroid inflammation.

• heart muscle inflammation, which may present as difficulty breathing, irregular heartbeat, fatigue, or chest pain.
• decrease in the secretion of hormones produced by the adrenal glands.
• muscle weakness.
• inflammation of the pituitary gland located at the base of the brain.
• inflammation of the heart lining.
• dryness in many parts of the body, from the mouth to the eyes, nose, throat, and upper layers of the skin.

• muscle inflammation that may include muscle pain or weakness (myositis) and may be associated with a rash (dermatomyositis).
• inflammation of the stomach lining.
• muscle pain or stiffness (polymyalgia rheumatica).

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 increased hunger or thirst, frequent urination, weight loss, and feeling of fatigue 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 that causes pain, weakness, and paralysis in the limbs.
• a condition in which the muscles weaken and tire easily, muscle pain.

Other reported adverse effects(frequency not known):

• organ transplant rejection.
• bladder inflammation. The signs and symptoms may include frequent and/or painful urination, urgent need to urinate, blood in the urine, pain or pressure in the lower abdomen.
• hemophagocytic lymphohistiocytosis. A disease in which your immune system produces too many normal cells that fight infections, called histiocytes and lymphocytes. The 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 abdominal pain, diarrhea, and bloating after consuming foods that contain gluten).
• absence or reduction of digestive enzymes produced by the pancreas (exocrine pancreatic insufficiency).

The following adverse 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):

• decrease in the number of red blood cells.
• hair loss.
• muscle or bone pain.
• nausea.
• feeling of fatigue.
• nervous system inflammation causing tingling, numbness, weakness, or burning pain in arms or legs.
• high blood sugar levels.
• decreased appetite.
• increase in liver enzymes in the blood.
• decrease in the number of white blood cells (neutrophils).
• constipation.
• decrease in the number of platelets.
• difficulty breathing.
• rash.
• vomiting.
• weight loss.
• sleep problems.
• diarrhea (soft stools).
• low levels of a protein called "albumin" in the blood.

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

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

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

• thyroid inflammation.
• infusion-related reactions.
• type 1 diabetes, which may include increased hunger or thirst, frequent urination, weight loss, and feeling of fatigue.

Other reported adverse effects(frequency not known):

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

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor, even if it is a possible adverse effect that is not listed in this prospectus. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: www.notificaRAM.es.

By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of LIBTAYO

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

Do not use this medicine 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.

Keep in the original package to protect it from light.

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

Chemical and physical stability in use has been demonstrated:

• at room temperature up to 25 °C for no more than 8 hours from the time of preparation of the infusion to 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 to 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 discarded in accordance with local requirements.

6. Container contents and additional information

LIBTAYO composition

The active ingredient is cemiplimab:

• one 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, L-Histidine monohydrochloride monohydrate, L-proline, sucrose, polysorbate 80, and water for injectable preparations.

Product appearance and container contents

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

Each container 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

Manufacturer

Regeneron Ireland DAC

Raheen Business Park

Limerick

Ireland

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Date oflast revision of this leaflet:

Detailed information on this medicine is available on the European Medicines Agency website: 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 for particles and discoloration. LIBTAYO is a solution from transparent to slightly opalescent, from colorless to pale yellow that may contain traces of translucent to white particles.
• Discard the vial if the solution is cloudy, discolored, or contains foreign particles that are not traces of translucent to white particles.
• Do not shake the vial.
• Extract 7 ml (350 mg) from the LIBTAYO vial and transfer it to an intravenous infusion bag containing a 9 mg/ml (0.9%) sodium chloride injectable solution or a 50 mg/ml (5%) glucose injectable solution. Mix the diluted solution by gentle inversion. Do not shake the solution. The final concentration of the diluted solution should be between 1 mg/ml and 20 mg/ml.
• LIBTAYO is for single use. Discard any unused medicine or waste material in accordance with local regulations.

Storage of the diluted solution

LIBTAYO does not contain preservatives.

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

Chemical and physical stability in use has been demonstrated:

• at room temperature up to 25 °C for no more than 8 hours from the time of preparation of the infusion to 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 to the end of the infusion. Allow the diluted solution to reach room temperature before administration.

Do not freeze.

Administration

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