Keytruda 25 mg/ml concentrado para solucion para perfusion

Patient Information: Product Information

KEYTRUDA 25mg/ml Concentrate for Solution for Infusion

pembrolizumab

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 read it again.
• It is essential to carry the patient information leaflet 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 section4.

1.What isKEYTRUDAand how is it used

2.What you need to know before you receiveKEYTRUDA

3.How you will receiveKEYTRUDA

4.Possible adverse effects

5.Storage of KEYTRUDA

6.Contents of the pack and additional information

KEYTRUDA contains the active ingredient pembrolizumab, which is a monoclonal antibody.

KEYTRUDA works by helping your immune system fight your cancer.

KEYTRUDA is used in adults to treat:

• one type of skin cancer called melanoma
• one type of lung cancer called non-small cell lung cancer
• one type of cancer called classical Hodgkin lymphoma
• one type of cancer called bladder cancer (urothelial carcinoma)
• one type of head and neck cancer called squamous cell carcinoma of the head and neck
• one type of kidney cancer called renal cell carcinoma
• one type of cancer characterized by high microsatellite instability (MSI-H, by its English acronym) or by deficiency of the DNA mismatch repair system (dMMR, by its English acronym) in the colon or rectum (called colorectal cancer), in the uterus (called endometrial cancer), in the stomach (called gastric cancer), in the small intestine (called small intestine cancer) or in the biliary tract or gallbladder (called biliary tract cancer)
• one type of cancer called esophageal carcinoma
• one type of breast cancer called triple-negative breast cancer
• one type of uterine cancer called endometrial cancer
• one type of cancer called cervical cancer
• one type of stomach cancer called adenocarcinoma of the stomach or gastroesophageal junction
• one type of biliary tract or gallbladder cancer called biliary tract carcinoma.

KEYTRUDA is used in children and adolescents:

• from 3 years of age to treat one type of cancer called classical Hodgkin lymphoma
• from 12 years of age to treat one type of cancer called melanoma.

People receive KEYTRUDA when their cancer has spread or cannot be removed with surgery.

People receive KEYTRUDA after surgery to remove melanoma, non-small cell lung cancer, or renal cell carcinoma to help prevent their cancer from coming back (adjuvant treatment).

People receive KEYTRUDA before surgery (neoadjuvant treatment) to treat non-small cell lung cancer or triple-negative breast cancer and then continue receiving KEYTRUDA after surgery (adjuvant treatment) to help prevent their cancer from coming back.

KEYTRUDA can be administered in combination with other cancer medications. It is essential that you read the prospectuses of these other medications as well. If you have any questions about these medications, consult your doctor.

You should not receive KEYTRUDA

• if you are allergic to pembrolizumab or any of the other ingredients in this medication (listed in section 6 “Contents of the pack and additional information”). If you are unsure, consult your doctor.

Warnings and precautions

Consult your doctor or nurse before receiving KEYTRUDA.

Before receiving KEYTRUDA, tell your doctor if:

• you have an autoimmune disease (a disease in which your body attacks its own cells)
• you have pneumonia or inflammation of the lungs (called pneumonitis)
• you have been previously treated with ipilimumab, another medication for treating melanoma, and have had severe side effects due to this medication
• you have had an allergic reaction to other treatments with monoclonal antibodies
• you have chronic liver infection by a virus, such as hepatitis B or hepatitis C
• you have human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS)
• you have damaged liver
• you have damaged kidneys
• you have had a transplant of a solid organ or a bone marrow transplant (stem cell transplant) that uses donor stem cells (allogenic).

When you receive KEYTRUDA, you may experience some severe side effects. These side effects can sometimes be potentially fatal and may cause death. These side effects can occur at any time during treatment or even after treatment has ended. You may have more than one side effect at the same time.

If you experience any of the following conditions, call or visit your doctor immediately.Your doctor may give you other medications to prevent more severe complications and reduce your symptoms. Your doctor may delay the next dose of KEYTRUDA or interrupt treatment with KEYTRUDA.

• inflammation of the lungs, which may include difficulty breathing, chest pain, or cough
• inflammation of the intestines, which may include diarrhea or more frequent bowel movements, black, tarry, or sticky stools, stools with blood or mucus, severe stomach pain or tenderness, nausea, vomiting
• inflammation of the liver, which may include nausea or vomiting, loss of appetite, right upper quadrant abdominal pain, yellowing of the skin or white part of the eyes, dark urine, or easy bruising or bleeding
• inflammation of the kidneys, which may include changes in the amount or color of urine
• inflammation of the endocrine glands (especially the thyroid, pituitary, and adrenal glands), which may include rapid heartbeat, weight loss, increased sweating, weight gain, hair loss, feeling cold, constipation, deeper voice, muscle pain, dizziness, or fainting, unusual or severe headaches, or unusual headache
• type 1 diabetes, including diabetic ketoacidosis (acids in the blood produced by diabetes), symptoms may include increased hunger or thirst, frequent urination, or weight loss, feeling tired or unwell, stomach pain, rapid and deep breathing, confusion, unusual sleepiness, sweet odor on your breath, sweet or metallic taste in your mouth, or unusual odor in your urine or sweat
• inflammation of the eyes, which may include changes in vision
• inflammation of the muscles, which may include muscle pain or weakness
• inflammation of the heart muscle, which may include shortness of breath, irregular heartbeat, feeling tired or chest pain
• inflammation of the pancreas, which may include abdominal pain, nausea, and vomiting
• inflammation of the skin, which may include rash, itching, blisters, peeling, or ulcers on the skin and/or ulcers in the mouth, nose, throat, or genital area
• a condition that affects the immune system and may affect the lungs, skin, eyes, and/or lymph nodes (sarcoidosis)
• inflammation of the brain, which may include confusion, fever, memory problems, or seizures (encephalitis)
• numbness, tingling, or weakness in the arms or legs; urinary or intestinal problems, such as frequent urination, urinary incontinence, difficulty urinating, or constipation (myelitis)
• inflammation and fibrosis of the bile ducts, which may include right upper quadrant abdominal pain, liver or spleen enlargement, fatigue, itching, or yellowing of the skin or white part of the eyes (primary biliary cirrhosis)
• inflammation of the stomach (gastritis)
• decreased function of the parathyroid gland, which may include muscle cramps or spasms, fatigue, and weakness (hypoparathyroidism)
• reactions to infusion, which may include difficulty breathing, itching, rash, dizziness, or fever

Complications, including graft-versus-host disease (GVHD), in people with bone marrow transplant (stem cell transplant) that uses donor stem cells (allogenic).These complications can be severe and may be fatal. They may occur if you have had this type of transplant in the past or if you are going to have it in the future. Your doctor will monitor signs and symptoms, which may include rash on the skin, liver inflammation, abdominal pain, or diarrhea.

Children and adolescents

Do not administer KEYTRUDA to children under 18 years of age, except for children:

• 3 years of age or older with classical Hodgkin lymphoma
• 12 years of age or older with melanoma.

Other medications and KEYTRUDA

Consult your doctor

• If you are taking other medications that weaken your immune system. Some examples of these may include corticosteroids, such as prednisone. These medications may affect the effect of KEYTRUDA. However, once you are in treatment with KEYTRUDA, your doctor may give you corticosteroids to reduce the side effects you may have with KEYTRUDA. You may also be given corticosteroids before receiving KEYTRUDA in combination with chemotherapy to prevent and/or treat nausea, vomiting, and other side effects caused by chemotherapy.
• If you are taking, have taken recently, or may need to take any other medication.

Pregnancy

• You should not use KEYTRUDA if you are pregnant, unless your doctor specifically recommends it.
• If you are pregnant, think you may be pregnant, or plan to become pregnant, consult your doctor.
• KEYTRUDA may cause harm or death to your unborn baby.
• If you are a woman who may become pregnant, you must use an appropriate contraceptive method while receiving treatment with KEYTRUDA and for at least 4 months after your last dose.

Breastfeeding

• If you are breastfeeding, consult your doctor.
• Do not breastfeed while taking KEYTRUDA.
• The safety of KEYTRUDA for use during breastfeeding has not been established.

Driving and operating machinery

KEYTRUDA has a mild effect onyour ability to drive or operate machinery. Feeling dizzy, tired, or weak are possible side effects of KEYTRUDA. Do not drive or operate machinery after receiving KEYTRUDA unless you are sure you are feeling well.

KEYTRUDA will be administered in a hospital or clinic under the supervision of an experienced oncologist.

• The recommended dose of KEYTRUDA in adults is 200mg every 3weeks or 400mg every 6weeks.
• The recommended dose of KEYTRUDA in children and adolescents 3years of age or older with classical Hodgkin lymphoma and adolescents 12years of age or older with melanoma is 2mg/kg of body weight (up to a maximum of 200mg) every 3weeks.
• Your doctor will administer KEYTRUDA through an intravenous infusion over a period of approximately 30minutes.
• Your doctor will decide how many treatments you need.

If you miss an appointment to receive KEYTRUDA

• Call your doctor immediately to reschedule your appointment.
• It is very important that you do not miss any doses of this medication.

If you interrupt treatment with KEYTRUDA

Interrupting your treatment may stop the medication's effect. Do not interrupt treatment with KEYTRUDA unless you have discussed it with your doctor.

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

You will also find this information on the patient information leaflet that your doctor has given you. It is important that you keep this leaflet and show it to your partner or caregivers.

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

When you receive KEYTRUDA, you may experience serious side effects. See section2.

The following side effects have been reported with pembrolizumab monotherapy:

Very common (may affect more than1 in 10people)

• Decreased red blood cell count
• Reduced thyroid gland activity
• Loss of appetite
• Headache
• Shortness of breath; cough
• Diarrhea; stomach pain; nausea; vomiting; constipation
• Itching; skin rash
• Muscle and bone pain; joint pain
• Feeling tired; unusual fatigue; swelling; fever

Common (may affect up to 1 in 10people)

• Pulmonary infection
• Decreased platelet count (bruising or bleeding more easily); decreased white blood cell count (neutrophils, lymphocytes)
• Medication infusion-related reactions
• Hyperactive thyroid gland; hot flashes
• Decreased sodium, potassium, or calcium levels in the blood
• Difficulty sleeping
• Dizziness; inflammation of the nerves causing numbness, weakness, tingling, or burning in the arms and legs; lack of energy; change in sense of taste
• Dry eyes
• Abnormal heart rhythm
• High blood pressure
• Pulmonary inflammation
• Intestinal inflammation; dry mouth
• Liver inflammation
• Erythematous, sometimes blistering, rash; skin inflammation; skin color loss; skin dryness and itching; hair loss; acne-like skin problem
• Muscle pain, continuous or hypersensitivity pain; joint pain with swelling
• Flu-like illness; chills
• Abnormal liver enzyme levels in the blood; increased calcium levels in the blood; abnormal renal function tests

Uncommon (may affect up to1 in 100people)

• Decreased white blood cell count (leukocytes); immune response against platelets; increased eosinophil count
• A condition that can affect the lungs, skin, eyes, and/or lymph nodes (sarcoidosis)
• Decreased secretion of hormones produced by the adrenal glands; pituitary gland inflammation located at the base of the brain; thyroid inflammation
• Type 1 diabetes, including diabetic ketoacidosis
• A condition in which muscles weaken and tire easily; seizures
• Eye inflammation; eye pain, irritation, itching, or redness; discomfort to light; seeing spots
• Heart muscle inflammation, which may include shortness of breath, irregular heartbeat, feeling tired or chest pain; fluid accumulation around the heart; heart covering layer inflammation
• Pancreas inflammation; stomach inflammation; stomach lining ulcer or small intestine lining ulcer
• Skin thickening or peeling; small skin bumps, blisters, or papules; hair color changes
• Tendon surrounding tissue inflammation
• Kidney inflammation
• Increased amylase levels, an enzyme that breaks down starch

Rare (may affect up to1 in 100,000people)

• A condition called hemophagocytic lymphohistiocytosis, in which the immune system produces too many cells that fight infections, called histiocytes and lymphocytes, which can cause different symptoms; immune response against red blood cells; feeling weak, dizzy, short of breath, or pale skin (signs of low red blood cell count, possibly due to a type of anemia called pure red cell aplasia)
• Decreased parathyroid gland function, which may include muscle cramps or spasms, fatigue, and weakness
• Temporary nerve inflammation causing pain, weakness, and paralysis in the limbs (Guillain-Barré syndrome); brain inflammation, which may include confusion, fever, memory problems, or seizures (encephalitis);pain, numbness, tingling, or weakness in the arms or legs; urinary or intestinal problems, such as frequent urination, urinary incontinence, difficulty urinating, and constipation (myelitis); eye nerve inflammation that can cause vision loss in one or both eyes, eye movement pain, and/or color vision loss (neuritis optic)
• Eye inflammation; eye pain, irritation, itching, or redness; discomfort to light; seeing spots
• Heart muscle inflammation, which may include shortness of breath, irregular heartbeat, feeling tired or chest pain; fluid accumulation around the heart; heart covering layer inflammation
• Artery inflammation
• Pancreas inflammation; stomach lining ulcer or small intestine lining ulcer
• Skin thickening or peeling; small skin bumps, blisters, or papules; hair color changes
• Tendon surrounding tissue inflammation
• Kidney inflammation
• Increased amylase levels, an enzyme that breaks down starch

Rare (may affect up to1 in 100,000people)

• Immune response against red blood cells or platelets
• A condition that can affect the lungs, skin, eyes, and/or lymph nodes (sarcoidosis)
• Decreased parathyroid gland function, which may include muscle cramps or spasms, fatigue, and weakness

• A condition in which muscles weaken and tire easily; heart muscle inflammation, which may include shortness of breath, irregular heartbeat, feeling tired or chest pain; temporary nerve inflammation causing pain, weakness, and paralysis in the limbs (Guillain-Barré syndrome); eye nerve inflammation that can cause vision loss in one or both eyes, eye movement pain, and/or color vision loss (neuritis optic)

• Eye inflammation; eye pain, irritation, itching, or redness; discomfort to light; seeing spots
• Pancreas inflammation; stomach lining ulcer or small intestine lining ulcer; celiac disease (characterized by symptoms such as stomach pain, diarrhea, and bloating after consuming gluten-containing foods)
• Bile duct inflammation
• Itching, blistering, peeling, or ulcerative skin and/or mouth, nose, throat, or genital area ulcers (Stevens-Johnson syndrome or toxic epidermal necrolysis); red, soft lumps under the skin
• A condition in which the immune system attacks the glands that produce moisture in the body, such as tears and saliva (Sjögren's syndrome)

The following side effects have been reported in clinical trials with pembrolizumab in combination with chemotherapy:

Very common (may affect more than1 in 10people)

• Decreased red blood cell count; decreased white blood cell count (neutrophils); decreased platelet count (bruising or bleeding more easily)
• Reduced thyroid gland activity
• Decreased potassium levels in the blood; loss of appetite
• Difficulty sleeping
• Nerve inflammation causing numbness, weakness, tingling, or burning in the arms and legs; headache
• Shortness of breath; cough
• Diarrhea; vomiting; nausea; stomach pain; constipation
• Skin rash; itching
• Joint pain; muscle and bone pain; muscle pain, continuous or hypersensitivity pain; pain in the arms or legs
• Feeling tired; unusual fatigue; inflammation; fever
• Increased liver enzyme levels in the blood; increased liver enzyme levels in the blood

Common (may affect up to 1 in 10people)

• Pulmonary infection
• Decreased white blood cell count (neutrophils, lymphocytes, leukocytes); decreased platelet count (bruising or bleeding more easily)
• Medication infusion-related reactions
• Decreased secretion of hormones produced by the adrenal glands; hyperactive thyroid gland; thyroid inflammation
• Decreased sodium, potassium, or calcium levels in the blood
• Difficulty sleeping
• Dizziness; nerve inflammation causing numbness, weakness, tingling, or burning in the arms and legs; lack of energy
• Dry eyes
• Abnormal heart rhythm
• High blood pressure
• Pulmonary inflammation
• Intestinal inflammation; pancreas inflammation; stomach inflammation; dry mouth
• Liver inflammation
• Erythematous, sometimes blistering, rash; skin inflammation; skin dryness; acne-like skin problem; hair loss
• Joint pain with swelling
• Kidney inflammation
• Flu-like illness; chills
• Increased bilirubin levels in the blood; increased liver enzyme levels in the blood; abnormal renal function tests; increased calcium levels in the blood

Uncommon (may affect up to1 in 100people)

• Increased white blood cell count (eosinophils)
• Pituitary gland inflammation located at the base of the brain
• Type 1 diabetes, including diabetic ketoacidosis
• A condition in which the brain becomes inflamed, which may include confusion, fever, memory problems, or seizures (encephalitis); seizures
• Heart muscle inflammation, which may include shortness of breath, irregular heartbeat, feeling tired or chest pain; fluid accumulation around the heart
• Artery inflammation
• Pancreas inflammation; stomach lining ulcer or small intestine lining ulcer
• Skin thickening or peeling; skin color loss; small skin bumps, blisters, or papules; hair color changes
• Tendon surrounding tissue inflammation
• Kidney inflammation; urinary inflammation, which may include frequent urination, urinary incontinence, difficulty urinating, and constipation
• Increased amylase levels, an enzyme that breaks down starch

Rare (may affect up to1 in 100,000people)

• Immune response against red blood cells or platelets
• A condition that can affect the lungs, skin, eyes, and/or lymph nodes (sarcoidosis)
• Decreased parathyroid gland function, which may include muscle cramps or spasms, fatigue, and weakness

• A condition in which muscles weaken and tire easily; heart muscle inflammation, which may include shortness of breath, irregular heartbeat, feeling tired or chest pain; temporary nerve inflammation causing pain, weakness, and paralysis in the limbs (Guillain-Barré syndrome); eye nerve inflammation that can cause vision loss in one or both eyes, eye movement pain, and/or color vision loss (neuritis optic)

• Eye inflammation; eye pain, irritation, itching, or redness; discomfort to light; seeing spots
• Pancreas inflammation; stomach lining ulcer or small intestine lining ulcer; celiac disease (characterized by symptoms such as stomach pain, diarrhea, and bloating after consuming gluten-containing foods)
• Bile duct inflammation
• Itching, blistering, peeling, or ulcerative skin and/or mouth, nose, throat, or genital area ulcers (Stevens-Johnson syndrome); red, soft lumps under the skin; hair color changes
• A condition in which the immune system attacks the glands that produce moisture in the body, such as tears and saliva (Sjögren's syndrome)

The following side effects have been reported in clinical trials with pembrolizumab in combination with axitinib or lenvatinib:

Very common (may affect more than1 in 10people)

• Urinary tract infections (increased urination frequency and painful urination)
• Decreased red blood cell count
• Reduced thyroid gland activity
• Loss of appetite
• Headache; change in sense of taste
• High blood pressure
• Shortness of breath; cough
• Diarrhea; stomach pain; nausea; vomiting; constipation
• Skin rash; itching
• Joint pain; muscle and bone pain; muscle pain, continuous or hypersensitivity pain; pain in the arms or legs
• Feeling tired; unusual fatigue; inflammation; fever
• Increased lipase levels, an enzyme that breaks down fats; increased liver enzyme levels in the blood; abnormal renal function tests

Common (may affect up to 1 in 10people)

• Pulmonary infection
• Decreased white blood cell count (neutrophils, lymphocytes, leukocytes); decreased platelet count (bruising or bleeding more easily)
• Medication infusion-related reactions
• Decreased secretion of hormones produced by the adrenal glands; hyperactive thyroid gland; thyroid inflammation
• Decreased sodium, potassium, or calcium levels in the blood
• Difficulty sleeping
• Dizziness; nerve inflammation causing numbness, weakness, tingling, or burning in the arms and legs; lack of energy
• Dry eyes
• Abnormal heart rhythm
• High blood pressure
• Pulmonary inflammation
• Intestinal inflammation; pancreas inflammation; stomach inflammation; dry mouth
• Liver inflammation
• Erythematous, sometimes blistering, rash; skin inflammation; skin dryness; acne-like skin problem; hair loss
• Joint pain with swelling
• Kidney inflammation
• Flu-like illness; chills
• Increased bilirubin levels in the blood; increased liver enzyme levels in the blood; abnormal renal function tests; increased calcium levels in the blood

Uncommon (may affect up to1 in 100people)

• Increased white blood cell count (eosinophils)
• Pituitary gland inflammation located at the base of the brain
• Type 1 diabetes, including diabetic ketoacidosis
• A condition in which the brain becomes inflamed, which may include confusion, fever, memory problems, or seizures (encephalitis)
• Heart muscle inflammation, which may include shortness of breath, irregular heartbeat, feeling tired or chest pain; fluid accumulation around the heart
• Artery inflammation
• Pancreas inflammation; stomach lining ulcer or small intestine lining ulcer
• Skin thickening or peeling; skin color loss; small skin bumps, blisters, or papules; hair color changes
• Tendon surrounding tissue inflammation

Rare (may affect up to1 in 100,000people)

• Decreased parathyroid gland function, which may include muscle cramps or spasms, fatigue, and weakness
• Eye nerve inflammation that can cause vision loss in one or both eyes, eye movement pain, and/or color vision loss (neuritis optic)
• Pancreas inflammation; stomach lining ulcer or small intestine lining ulcer
• Itching, blistering, peeling, or ulcerative skin and/or mouth, nose, throat, or genital area ulcers (Stevens-Johnson syndrome); red, soft lumps under the skin; hair color changes
• A condition in which the immune system attacks the glands that produce moisture in the body, such as tears and saliva (Sjögren's syndrome)
• Urinary inflammation, which may include frequent urination, urinary incontinence, difficulty urinating, and constipation

Other side effects that have been reported with unknown frequency (cannot be estimated from available data)

• Pancreas inflammation; celiac disease (characterized by symptoms such as stomach pain, diarrhea, and bloating after consuming gluten-containing foods)

Rash is more frequent when KEYTRUDA is administered in combination with enfortumab vedotina than when KEYTRUDA is administered alone.

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 prospectus. You can also report them directly through thenational notification system included in theAppendix V. By reporting side effects, you can contribute to providing more information about the safety of this medicine.

Unopened vial

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 on the vial 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.

Store in the original packaging to protect it from light.

After preparation for infusion

Chemical and physical stability has been demonstrated for use up to 42días between 2°C and 8°C or between 23°C and 27°C.From a microbiological standpoint, the product, once diluted, should be used immediately. Do not freeze the diluted solution. If not used immediately,the storage times and conditions in use before its use are the responsibility of the user and should normally not exceed 7díasbetween 2°C and 8°C, or 12hours at room temperature, unless the dilution was performed in controlled and validated aseptic conditions. If refrigerated, the vials and/or intravenous bags should be allowed to reach room temperature before use.

Do not store any unused portion of the infusion solution for reuse. All unused medication or residual material should be disposed of in accordance with local requirements.

Composition of KEYTRUDA

The active ingredient is pembrolizumab.

One vial of 4ml contains 100mg of pembrolizumab.

Each ml of concentrate contains 25mg of pembrolizumab.

The other components are L-histidine, L-histidine hydrochloride monohydrate, sucrose, polisorbate80 and water for injection.

Appearance of the product and contents of the pack

KEYTRUDA is a clear, slightly opalescent, colourless to slightly yellow solution, with a pH between 5.2and5.8.

It is available in boxes containing a glass vial.

Marketing authorisation holder

Merck Sharp & Dohme B.V.

Waarderweg 39

2031 BN Haarlem

Netherlands

Responsible for manufacturing

Organon Heist bv

Industriepark 30

2220 Heist-op-den-Berg

Belgium

Merck Sharp & Dohme B.V.

Waarderweg 39

2031 BN Haarlem

Netherlands

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:

Other sources of information

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