Libtayo

Package leaflet: Information for the patient

LIBTAYO 350 mg concentrate for solution for infusion

cemiplimab
Please read this leaflet carefully before this medicine is administered to you 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 Alert Card throughout your treatment.
• If you have any questions, ask your doctor.
• If you experience any side effects, including those not listed in this leaflet, inform your doctor. See section 4.

Contents of this leaflet

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

1. What LIBTAYO is and what it is used for

LIBTAYO is an anticancer medicine containing 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) that has not responded well to, or was not well tolerated by, treatment with a Hedgehog pathway inhibitor
• a type of lung cancer called advanced non-small cell lung cancer (NSCLC)
• a type of cancer called cervical cancer that has worsened during or after chemotherapy.

LIBTAYO is used after surgical removal of CSCC to help prevent the cancer from returning (adjuvant therapy).
LIBTAYO may be given in combination with chemotherapy for the treatment of NSCLC. It is important that you also read the package leaflets for the specific chemotherapy you are receiving. If you have any questions about these medicines, consult your doctor.
LIBTAYO works by helping the immune system fight the cancer.

2. What you should know before you are given LIBTAYO

Do not receive LIBTAYO if:

• you are allergic to cemiplimab or to any of the other ingredients of this medicine (listed in section 6). If you think you may be allergic or have any doubts, consult your doctor before receiving LIBTAYO.

Warnings and precautions
Talk to your doctor or nurse before receiving LIBTAYO if:

• you have an autoimmune disease (a condition in which the body attacks its own cells)
• you have had an organ transplant, have received or are on the waiting list to receive a bone marrow transplant using another person’s bone marrow (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 medical condition.

LIBTAYO acts on the immune system. It may cause inflammation in certain parts of the body.
The risk of these side effects may be higher if you already have an autoimmune disease
(a condition in which the body attacks its own cells). You may also experience frequent
flare-ups of your autoimmune disease, which in most cases are mild.
If any of the conditions described above apply to you (or if you have any doubts), talk to your doctor or
nurse before receiving LIBTAYO.
Side effects to watch for
LIBTAYO may cause serious side effects that you must report to your doctor
immediately. These problems may occur at any time during treatment or even after treatment has ended.
You may experience more than one side effect simultaneously.
These serious side effects include:

• Skin problems
• Lung problems (pneumonitis)
• Intestinal problems (colitis)
• Liver problems (hepatitis)
• Problems affecting hormone glands, especially the thyroid, pituitary gland, adrenal glands, and pancreas
• Type 1 diabetes, including diabetic ketoacidosis (acid in the blood caused by diabetes)
• Kidney problems (nephritis and impaired kidney function)
• Problems affecting 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 condition in which the immune system produces too many otherwise normal infection-fighting cells called histiocytes and lymphocytes, which can cause various symptoms (hemophagocytic lymphohistiocytosis) (see “Possible side effects” for a list of signs and symptoms)
• Problems in other parts of the body (see “Possible side effects”).

Be vigilant for these side effects while receiving LIBTAYO. Refer to section 4, “Possible side effects”.
If you experience any of these side effects, contact your doctor immediately.
Your doctor may give you other medicines to stop more severe reactions and relieve symptoms.
Your doctor may also delay your next dose of LIBTAYO or stop treatment altogether.
Children and adolescents
LIBTAYO must not be used in children and adolescents under 18 years of age.
Other medicines and LIBTAYO
Inform your doctor if you are taking, have recently taken, or might take any other
medicines.
In particular, inform your doctor if you are taking or have taken any of the following medicines:

• a cancer medicine called idelalisib
• medicines that weaken the immune system; some examples include corticosteroids such as prednisone. These medicines may interfere with the effect of LIBTAYO. However, once treatment with LIBTAYO has started, your doctor may give you corticosteroids to reduce side effects that you may experience with LIBTAYO.

Pregnancy
If you are pregnant, suspect you may be pregnant, or are planning to become pregnant, ask your doctor for advice before receiving this medicine.

• LIBTAYO may harm the unborn baby.
• Inform your doctor immediately if you become pregnant while receiving LIBTAYO.
• If you are of childbearing age, you must use an effective method of contraception to prevent pregnancy:
  • while you are receiving treatment with LIBTAYO and
  • for at least 4 months after the last dose.
• Talk to your doctor about which contraceptive methods you should use during this time period.

Breast-feeding

• If you are breast-feeding or plan to breast-feed, ask your doctor for advice before receiving this medicine.
• Avoid breast-feeding while receiving treatment 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 does not affect or has a negligible effect on the ability to drive and use machines.
However, if you experience fatigue, do not drive or operate machinery until you feel better.
LIBTAYO contains L-proline
This medicine contains 105 mg of L-proline in each 7 ml vial, equivalent to 15 mg/ml.
L-proline may be harmful in patients with hyperprolinemia, a rare genetic disorder in which L-proline accumulates in the body. If you have hyperprolinemia, do not use this medicine unless recommended by your doctor.
LIBTAYO contains polysorbate 80
This medicine contains 14 mg of polysorbate 80 per 7 ml vial, equivalent to 2 mg/ml.
Polysorbates may cause allergic reactions. Inform your doctor if you have known allergies.

3. How LIBTAYO is administered

• LIBTAYO will be administered in a hospital or clinic setting under the supervision of a doctor experienced in the treatment of cancers.
• LIBTAYO is given by intravenous infusion (infusion into a vein).
• The infusion will last approximately 30 minutes.

How much you will receive
LIBTAYO is usually administered at a dose of 350 mg every 3 weeks.
When given to help prevent the recurrence of CSCC after surgery, treatment may be administered as 350 mg every 3 weeks for 48 weeks or as 350 mg every 3 weeks for 12 weeks, followed by 700 mg every 6 weeks for a total of 48 weeks.
Your doctor will decide the dose of LIBTAYO and how many treatments you will need.
Your doctor will perform blood tests to monitor for the occurrence of certain side effects during treatment.

If you miss a scheduled administration
Contact your doctor as soon as possible to reschedule your appointment. It is very important that you do not miss any doses of this medicine.

If you stop treatment with LIBTAYO
Do not stop taking LIBTAYO without first discussing it with your doctor. Stopping treatment may interrupt the medicine’s effect.

Patient Alert Card
The information contained in this Package Leaflet is also included in the Patient Alert Card provided to you by your doctor. It is important that you carry this Patient Alert Card with you and show it to your partner or caregivers.
If you have any questions about your treatment, speak with your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Your doctor will discuss these side effects with you and explain the risks and benefits of your treatment.
LIBTAYO acts on your immune system and may cause inflammation in various parts of the body (see the conditions listed under “Side effects that need attention” in section 2). This inflammation can cause serious harm to your body and may require appropriate treatment or may necessitate discontinuation of treatment with LIBTAYO. Some inflammatory conditions may even lead to death.
Seek urgent medical care if you experience any of the following signs or symptoms, or if they worsen:

• Skin problems such as rash or itching, skin blisters, or mouth or other mucosal ulcers.
• Lung problems (pneumonitis) such as new cough or worsening of existing cough, shortness of breath, or chest pain.
• Intestinal problems (colitis) such as frequent diarrhoea, often with blood or mucus, more bowel movements than usual, black or tarry stools, or severe stomach (abdominal) pain or tenderness.
• Liver problems (hepatitis) such as yellowing of the skin or whites of the eyes, severe nausea or vomiting, pain on the right side of the stomach (abdomen), feeling unusually tired, dark-coloured urine (tea-coloured), bleeding or bruising more easily than normal, and reduced appetite.
• Problems with hormone glands such as persistent or unusual headaches, increased heart rate, increased sweating, feeling unusually cold or hot, extreme tiredness, dizziness or fainting, weight gain or weight loss, increased hunger or thirst, hair loss, constipation, deeper voice, very low blood pressure, urinating more often than usual, nausea or vomiting, stomach (abdominal) pain, or changes in mood or behaviour (such as decreased sex drive, irritability, or forgetfulness).
• Symptoms of type 1 diabetes or diabetic ketoacidosis include increased hunger or thirst, need to urinate more often, weight loss, feeling tired or unwell, stomach pain, rapid deep breathing, confusion, unusual drowsiness, sweet-smelling breath, sweet or metallic taste in the mouth, or unusual odour of urine or sweat.
• Kidney problems (nephritis and kidney failure) such as less frequent urination, blood in the urine, swollen ankles, and reduced appetite.
• Infusion-related reactions (sometimes severe or potentially life-threatening) such as chills, shaking, or fever, itching or rash, facial flushing or swelling, shortness of breath or wheezing, dizziness or feeling faint, back or neck pain, nausea, vomiting, or abdominal pain.
• Problems affecting other parts of the body such as:
  • Nervous system problems, such as headache or stiff neck, fever, feeling tired or weak, chills, vomiting, confusion, memory problems or drowsiness, seizures (convulsions), seeing or hearing things that are not real (hallucinations), severe muscle weakness, tingling, numbness, weakness, or burning (burning pain) in arms or legs, limb paralysis
  • Muscle and joint problems such as joint pain or swelling, muscle pain, weakness, or stiffness
  • Eye problems such as changes in vision, eye pain or redness, sensitivity to light
  • Heart and circulation problems such as irregular heartbeat, fast heartbeat, feeling that the heart skips a beat or pounds, chest pain, shortness of breath
  • Other: dryness in many parts of the body from mouth to eyes, nose, throat, and superficial layers of the skin, skin bruising or bleeding, enlarged liver and/or spleen, swollen lymph nodes.

The following side effects have been observed in clinical trials of patients treated with cemiplimab alone:
Very common (may affect more than 1 in 10 people):

• feeling tired
• muscle pain or bone pain
• rash
• diarrhoea (loose stools)
• reduced number of red blood cells
• nausea
• loss of appetite
• itching
• constipation
• cough
• stomach pain (abdominal pain)
• upper respiratory tract infection

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

• vomiting
• shortness of breath
• fever
• urinary tract infection
• headache
• swelling (oedema)
• thyroid problems (hyperthyroidism and hypothyroidism)
• high blood pressure
• increased liver enzymes in the blood
• thick, scaly, or crusted skin patches (actinic keratosis)
• cough, lung inflammation
• infusion-related reactions
• liver inflammation
• intestinal inflammation (diarrhoea, more frequent bowel movements than normal, black or tarry stools, severe stomach [abdominal] pain or tenderness)
• mouth inflammation
• abnormal kidney function test
• nerve inflammation causing tingling, numbness, weakness, or burning in arms or legs
• kidney inflammation

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

• joint pain, swelling, polyarthritis, and joint effusion
• skin bruising or bleeding
• thyroid inflammation
• inflammation of the heart muscle, which may present with shortness of breath, irregular heartbeat, feeling tired, or chest pain
• reduced production of hormones from the adrenal glands
• muscle weakness
• inflammation of the pituitary gland, a gland located at the base of the brain
• inflammation of the outer lining of the heart
• dryness in various parts of the body, from mouth to eyes, nose, throat, and superficial layers of the skin
• muscle inflammation which 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 1,000 people):

• inflammation of the membranes covering the brain and spinal cord, which may be caused by infection
• type 1 diabetes, which may present with increased hunger or thirst, need to urinate more often, weight loss, and feeling tired, or diabetic ketoacidosis
• eye pain, irritation, itching, or redness, inflammation, blurred vision, discomfort in sensitivity to light (uveitis and keratitis)
• temporary nerve inflammation causing pain, weakness, and paralysis in limbs
• a condition in which muscles become easily weak and tired, muscle pain

Other side effects that have been reported (frequency not known):

• organ transplant rejection
• bladder inflammation. Signs and symptoms may include frequent and/or painful urination, urgency to urinate, blood in the urine, pain or pressure in the lower abdomen
• haemophagocytic lymphohistiocytosis. A condition in which the immune system produces excessive numbers of cells called histiocytes and lymphocytes that fight infections. Symptoms may include enlarged liver and/or spleen, rash, swollen lymph nodes, breathing problems, easy bruising, kidney and heart problems
• coeliac disease (characterised by symptoms such as stomach pain, diarrhoea, and bloated stomach after consuming foods containing gluten)
• lack of or reduced digestive enzymes produced by the pancreas (pancreatic exocrine insufficiency)

The following side effects have been observed in clinical trials of patients treated with cemiplimab in combination with chemotherapy:
Very common (may affect more than 1 in 10 people):

• reduced number of red blood cells
• hair loss
• muscle pain or bone pain
• nausea
• tiredness
• nerve inflammation causing tingling, numbness, weakness, or burning pain in arms or legs
• high blood sugar levels
• loss of appetite
• increased liver enzymes in the blood
• reduced number of white blood cells (neutrophils)
• constipation
• reduced number of platelets
• shortness of breath
• rash
• vomiting
• weight loss
• difficulty sleeping
• diarrhoea (loose stools)
• low blood levels of a protein called “albumin”

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 (diarrhoea, more frequent bowel movements than normal, black or tarry stools, severe stomach [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 present with increased hunger or thirst, need to urinate more often, weight loss, and feeling tired

Other side effects that have been reported (frequency not known):

• coeliac disease (characterised by symptoms such as stomach pain, diarrhoea, and bloated stomach after consuming foods containing gluten)
• lack of or reduced digestive enzymes produced by the pancreas (pancreatic exocrine insufficiency)

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store LIBTAYO

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 vial after
Exp. The expiry date refers to the last day of that month.
Store in a refrigerator (2°C–8°C).
Do not freeze.
Store in the original container to protect the medicine from light.
From a microbiological standpoint, the prepared infusion solution should be used immediately. If the diluted solution is not administered immediately, the duration and conditions of storage prior to use are the responsibility of the user.
Chemical and physical in-use stability has been demonstrated as follows:

• at room temperature up to 25°C for no more than 8 hours from the time of infusion preparation until the end of administration. Or
• in a refrigerator at 2–8°C for no more than 10 days from the time of infusion preparation until the end of administration. Allow the diluted solution to reach room temperature before administration.

Do not store any unused portion of the infusion solution for reuse. Any unused infusion solution residue must not be reused and should be disposed of in accordance with local regulations.

6. Package contents and other information

What LIBTAYO contains
The active substance 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 injections.
Description of the appearance of LIBTAYO and contents of the pack
LIBTAYO concentrate for solution for infusion (sterile concentrate) is supplied as a sterile solution, colourless to pale yellow, from clear to slightly opalescent, which may contain traces of translucent to white particles.
Each pack contains 1 glass vial with 7 mL of concentrate.
Marketing Authorisation Holder
Regeneron Ireland Designated Activity Company (DAC)
One Warrington Place,
Dublin 2, D02 HH27
Ireland
Manufacturer
Regeneron Ireland DAC
Raheen Business Park
Limerick
Ireland
For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
België/Belgique/Belgien Lietuva
Regeneron Ireland DAC Medison Pharma Lithuania UAB
Tél/Tel: 0800 89383 Tel: 8 800 33598
България Luxembourg/Luxemburg
Medison Pharma Bulgaria Ltd. Regeneron Ireland DAC
Тел.: 008002100419 Tél/Tel: 8007-9000
Česká republika Magyarország
Medison Pharma s.r.o. Medison Pharma Hungary Kft
Tel: 800 050 148 Tel.: 06-809-93029
Danmark Malta
Regeneron Ireland DAC Genesis Pharma (Cyprus) Ltd
Tlf: 80 20 03 57 Tel: 80065169
Deutschland Nederland
Regeneron GmbH Regeneron Ireland DAC
Tel.: 0800 330 4267 Tel: 0800 020 0943
Eesti Norge
Medison Pharma Estonia OÜ Regeneron Ireland DAC
Tel: 800 004 4845 Tlf: 8003 15 33
Ελλάδα Österreich
ΓΕΝΕΣΙΣ ΦΑΡΜΑ Α.Ε. Regeneron Ireland DAC
Τηλ: 00800 44146336 Tel: 01206094094
España Polska
Regeneron Spain S.L.U. Medison Pharma Sp. z o.o.
Tel: 900031311 Tel.: 800 080 691
France Portugal
Regeneron France SAS Regeneron Ireland DAC
Tél: 080 554 3951 Tel: 800783394
Hrvatska România
Medison Pharma d.o.o. Medison Pharma SRL
Tel: 0800 787 074 Tel: 0800 400670
Ireland Slovenija
Regeneron Ireland DAC Medison Pharma d.o.o.
Tel: 1800800920 Tel: 0800 83155
Ísland Slovenská republika
Regeneron Ireland DAC Medison Pharma s.r.o.
Sími: 800 4431 Tel: 0800 123 255
Italia Suomi/Finland
Regeneron Italy S.r.l. Regeneron Ireland DAC
Tel: 800180052 Puh/Tel: 0800 772223
Κύπρος Sverige
Genesis Pharma (Cyprus) Ltd Regeneron Ireland DAC
Τηλ: 800 925 47 Tel: 0201 604786
Latvija
Medison Pharma Latvia SIA
Tel: 8000 5874
More detailed information on this medicinal product is available on the website of the European Medicines Agency, https://www.ema.europa.eu.

The following information is intended for healthcare professionals only:

Instructions for use

Preparation

• Perform a visual inspection of the medicinal product for particulate matter and discoloration prior to administration. LIBTAYO is a solution that ranges from colourless to pale yellow and from clear to slightly opalescent, which may contain traces of translucent to white particles.
• Discard the vial if the solution appears cloudy, has changed colour, or contains foreign particulate matter other than a few translucent/white particles.
• Do not shake the v游戏副本ino.
• Withdraw 7 mL (350 mg) from the LIBTAYO vial and transfer into an intravenous infusion bag containing either 9 mg/mL (0.9%) sodium chloride injection solution or 50 mg/mL (5%) glucose injection solution. Mix the diluted solution by gentle inversion. Do not shake the solution. The final concentration of the diluted solution must be between 1 mg/mL and 20 mg/mL. Use 2 vials for 700 mg doses.
• LIBTAYO is for single use only. Any unused medicinal product and waste materials derived from it must be disposed of in accordance with local regulations.

Storage of the diluted solution
LIBTAYO does not contain preservatives.
From a microbiological standpoint, the prepared infusion solution should be used immediately. If not administered immediately, the storage times and conditions prior to use are the responsibility of the user.
Chemical and physical in-use stability has been demonstrated as follows:

• at room temperature up to 25°C for no more than 8 hours from the time of infusion preparation until completion of the infusion. Or
• refrigerated at 2–8°C for no more than 10 days from the time of infusion preparation until completion of the infusion. Allow the diluted solution to reach room temperature before administration.

Do not freeze.
Administration

• LIBTAYO is for intravenous use. It is administered as an intravenous infusion over 30 minutes through an intravenous line equipped with an in-line or additional sterile, pyrogen-free, low protein-binding filter (with pore sizes between 0.2 and 5 microns).
• Avoid concomitant administration of other medicinal products through the same infusion line.