KEYTRUDA® 25 mg/mL concentrate for solution for infusion

pembrolizumab

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

KEYTRUDA works by helping your immune system fight your cancer.

KEYTRUDA is used in adults to treat:

• a kind of skin cancer called melanoma
• a kind of lung cancer called non-small cell lung cancer
• a kind of cancer called classical Hodgkin lymphoma
• a kind of cancer called bladder cancer (urothelial carcinoma)
• a kind of head and neck cancer called head and neck squamous cell carcinoma.
• a kind of kidney cancer called renal cell carcinoma
• a kind of cancer that is determined to be microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) in the colon or rectum (called colorectal cancer), uterus (called endometrial cancer), stomach (called gastric cancer), small bowel (called small intestine cancer), or bile duct or gallbladder (called biliary tract cancer)
• a kind of cancer called oesophageal carcinoma
• a kind of breast cancer called triple-negative breast cancer
• a kind of uterine cancer called endometrial carcinoma
• a kind of cancer called cervical cancer
• a kind of stomach cancer called gastric or gastro-oesophageal junction adenocarcinoma
• a kind of bile duct or gallbladder cancer called biliary tract carcinoma

KEYTRUDA is used in children and adolescents:

• aged 3 years and older to treat a kind of cancer called classical Hodgkin lymphoma
• aged 12 years and older to treat a kind of cancer called melanoma.

People get KEYTRUDA when their cancer has spread or cannot be taken out by surgery.

People get KEYTRUDA after they have had surgery to remove melanoma, non-small cell lung cancer or renal cell carcinoma to help prevent their cancer from coming back (adjuvant therapy).

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

KEYTRUDA may be given in combination with other anti-cancer medicines. It is important that you also read the package leaflets for these other medicines. If you have any questions about these medicines, ask your doctor.

You should not be given KEYTRUDA

• if you are allergic to pembrolizumab or any of the other ingredients of this medicine (listed in section 6 “Contents of the pack and other information”). Talk to your doctor if you are not sure.

KEYTRUDA will be given to you in a hospital or clinic under the supervision of a doctor experienced in cancer treatment.

• The recommended dose of KEYTRUDA in adults is either 200 mg every 3 weeks or 400 mg every 6 weeks.
• The recommended dose of KEYTRUDA in children and adolescents aged 3 years and older with classical Hodgkin lymphoma and adolescents aged 12 years and older with melanoma, is 2 mg/kg bodyweight (up to a maximum of 200 mg) every 3 weeks.
• Your doctor will give you KEYTRUDA through an infusion into your vein (intravenous) for about 30 minutes.
• Your doctor will decide how many treatments you need.

Like all medicines, this medicine can cause side effects, although not everybody gets them.

When you get KEYTRUDA, you can have some serious side effects. See section 2.

The following side effects have been reported with pembrolizumab alone:

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

• decrease in the number of red blood cells
• reduced thyroid gland activity
• feeling less hungry
• headache
• shortness of breath; cough
• diarrhoea; stomach pain; nausea; vomiting; constipation
• itching; skin rash
• pain in muscle and bones; joint pain
• feeling tired; unusual tiredness or weakness; swelling; fever

Common (may affect up to 1 in 10 people)

• lung infection
• decrease in the number of platelets (bruising or bleeding more easily); decrease in the number of white blood cell (neutrophils; lymphocytes)
• reactions related to the infusion of the medicine
• overactive thyroid gland; hot flush
• decreased sodium, potassium, or calcium in the blood
• trouble sleeping
• dizziness; inflammation of the nerves causing numbness, weakness, tingling or burning pain of the arms and legs; lack of energy; change in your sense of taste
• dry eye
• abnormal heart rhythm
• high blood pressure
• inflammation of the lungs
• inflammation of the intestines; dry mouth
• inflammation of the liver
• red raised rash sometimes with blisters; inflammation of the skin; patches of skin which have lost colour; dry, itchy skin; hair loss; acne-like skin problem
• muscle pain, aches or tenderness; pain in arms or legs; joint pain with swelling
• flu-like illness; chills
• increased liver enzyme levels in the blood; increased calcium in the blood; abnormal kidney function test

Uncommon (may affect up to 1 in 100 people)

• a decreased number of white blood cells (leukocytes); inflammation response against platelets; an increased number of white blood cells (eosinophils)
• an immune disorder that can affect the lungs, skin, eyes and/or lymph nodes (sarcoidosis)
• decreased secretion of hormones produced by the adrenal glands; inflammation of the pituitary gland situated at the base of the brain; inflammation of the thyroid
• type 1 diabetes, including diabetic ketoacidosis
• a condition in which the muscles become weak and tire easily; seizure
• inflammation of the eyes; eye pain, irritation, itchiness or redness; uncomfortable sensitivity to light; seeing spots
• inflammation of the heart muscle, which may present as shortness of breath, irregular heartbeat, feeling tired, or chest pain; accumulation of fluid around the heart; inflammation of the covering of the heart
• inflammation of the pancreas; inflammation of the stomach; a sore that develops on the inside lining of your stomach or upper part of your small intestine
• thickened, sometimes scaly, skin growth; small skin bumps, lumps or sores; hair colour changes
• inflammation of the sheath that surrounds tendons
• inflammation of the kidneys
• increased level of amylase, an enzyme that breaks down starch

Rare (may affect up to 1 in 1000 people)

• a condition called haemophagocytic lymphohistiocytosis, where the immune system makes too many infection fighting cells called histiocytes and lymphocytes that may cause various symptoms; inflammation response against red blood cells; feeling weak, lightheaded, short of breath or if your skin looks pale (signs of low level of red blood cells, possibly due to a type of anaemia called pure red cell aplasia)
• decreased function of the parathyroid gland, which may present as muscle cramps or spasms, fatigue and weakness
• a temporary inflammation of the nerves that causes pain, weakness, and paralysis in the extremities (Guillain-Barré syndrome); inflammation of the brain, which may present as confusion, fever, memory problems or seizures (encephalitis); pain, numbness, tingling, or weakness in the arms or legs; bladder or bowel problems including needing to urinate more frequently, urinary incontinence, difficulty urinating and constipation (myelitis); swelling of the optic nerve that may result in vision loss in one or both eyes, pain with eye movement, and/or loss of colour vision (optic neuritis); inflammation of the membrane around the spinal cord and brain, which may present as neck stiffness, headache, fever, eye sensitivity to light, nausea or vomiting (meningitis)
• inflammation of the blood vessels
• lack or reduction of digestive enzymes made by the pancreas (pancreatic exocrine insufficiency); a hole in the small intestines; coeliac disease (characterised by symptoms such as stomach pain, diarrhoea, and bloating after consuming gluten-containing foods)
• inflammation of the bile ducts
• itching, skin blistering, peeling or sores, and/or ulcers in mouth or in lining of nose, throat, or genital area (Stevens-Johnson syndrome or toxic epidermal necrolysis); tender red bumps under the skin
• disease in which the immune system attacks the glands that make moisture for the body, such as tears and saliva (Sjogren’s syndrome)
• inflammation of the bladder, which may present as frequent and/or painful urination, urge to pass urine, blood in urine, pain or pressure in lower abdomen

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

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

• decrease in the number of red blood cells; decreased number of white blood cells (neutrophils); decrease in the number of platelets (bruising or bleeding more easily)
• reduced thyroid gland activity
• decreased potassium in the blood; feeling less hungry
• trouble sleeping
• inflammation of the nerves causing numbness, weakness, tingling or burning pain of the arms and legs; headache
• shortness of breath; cough
• diarrhoea; vomiting; nausea; stomach pain; constipation
• hair loss; itching; skin rash
• pain in the muscles and bones; joint pain
• feeling tired; unusual tiredness or weakness; fever
• increased blood level of the liver enzyme alanine aminotransferase; increased blood level of the liver enzyme aspartate aminotransferase

Common (may affect up to 1 in 10 people)

• lung infection
• decreased number of white blood cells (neutrophils) with a fever; decreased number of white blood cells (leukocytes, lymphocytes)
• reaction related to the infusion of the medicine
• decreased secretion of hormones produced by the adrenal glands; inflammation of the thyroid; overactive thyroid gland
• decreased sodium or calcium in the blood
• dizziness; change in your sense of taste; lack of energy
• dry eye
• abnormal heart rhythm
• high blood pressure
• inflammation of the lungs
• inflammation of the intestines; inflammation of the stomach; dry mouth
• inflammation of the liver
• red raised rash, sometimes with blisters; inflammation of the skin; acne-like skin problem; dry, itchy skin
• muscle pain, aches or tenderness; pain in arms or legs; joint pain with swelling
• sudden kidney damage
• swelling; flu-like illness; chills
• increased bilirubin in the blood; increased blood level of the liver enzyme alkaline phosphatase; abnormal kidney function test; increased calcium in the blood

Uncommon (may affect up to 1 in 100 people)

• an increased number of white blood cells (eosinophils)
• inflammation of the pituitary gland situated at the base of the brain
• type 1 diabetes, including diabetic ketoacidosis
• inflammation of the brain, which may present as confusion, fever, memory problems or seizures (encephalitis); seizure
• inflammation of the heart muscle, which may present as shortness of breath, irregular heartbeat, feeling tired, or chest pain; accumulation of fluid around the heart; inflammation of the covering of the heart
• inflammation of the blood vessels
• inflammation of the pancreas; a sore that develops on the inside lining of your stomach or upper part of your small intestine
• thickened, sometimes scaly, skin growth; patches of skin which have lost colour; small skin bumps, lumps or sores
• inflammation of the sheath that surrounds tendons
• inflammation of the kidneys; inflammation of the bladder, which may present as frequent and/or painful urination, urge to pass urine, blood in urine, pain or pressure in lower abdomen
• increased level of amylase, an enzyme that breaks down starch

Rare (may affect up to 1 in 1000 people)

• inflammation response against red blood cells or platelets
• an immune disorder that can affect the lungs, skin, eyes and/or lymph nodes (sarcoidosis)
• decreased function of the parathyroid gland, which may present as muscle cramps or spasms, fatigue and weakness
• a condition in which the muscles become weak and tire easily; a temporary inflammation of the nerves that causes pain, weakness, and paralysis in the extremities (Guillain-Barré syndrome); swelling of the optic nerve that may result in vision loss in one or both eyes, pain with eye movement, and/or loss of colour vision (optic neuritis)
• inflammation of the eyes; eye pain, irritation, itchiness or redness; uncomfortable sensitivity to light; seeing spots
• lack or reduction of digestive enzymes made by the pancreas (pancreatic exocrine insufficiency); a hole in the small intestines; coeliac disease (characterised by symptoms such as stomach pain, diarrhoea, and bloating after consuming gluten-containing foods)
• inflammation of the bile ducts
• itching, skin blistering, peeling or sores, and/or ulcers in mouth or in lining of nose, throat, or genital area (Stevens-Johnson syndrome); tender red bumps under the skin; hair colour changes
• disease in which the immune system attacks the glands that make moisture for the body, such as tears and saliva (Sjogren’s syndrome)

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

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

• urinary infections (increased frequency in urination and pain in passing urine)
• decrease in the number of red blood cells
• reduced thyroid gland activity
• feeling less hungry
• headache; change in your sense of taste
• high blood pressure
• shortness of breath; cough
• diarrhoea; stomach pain; nausea; vomiting; constipation
• skin rash; itching
• joint pain; pain in the muscles and bones; muscle pain, aches or tenderness; pain in arms or legs
• feeling tired; unusual tiredness or weakness; swelling; fever
• increased levels of lipase, an enzyme that breaks down fats; increased liver enzyme levels in the blood; abnormal kidney function test

Common (may affect up to 1 in 10 people)

• lung infection
• decreased number of white blood cells (neutrophils, lymphocytes, leukocytes); decrease in the number of platelets (bruising or bleeding more easily)
• reaction related to the infusion of the medicine
• decreased secretion of hormones produced by the adrenal glands; overactive thyroid gland; inflammation of the thyroid
• decreased sodium, potassium, or calcium in the blood
• trouble sleeping
• dizziness; inflammation of the nerves causing numbness, weakness, tingling or burning pain of the arms and legs; lack of energy
• dry eye
• abnormal heart rhythm
• inflammation of the lungs
• inflammation of the intestines; inflammation of the pancreas; inflammation of the stomach; dry mouth
• inflammation of the liver
• red raised rash, sometimes with blisters; inflammation of the skin; dry skin; acne-like skin problem; hair loss
• joint pain with swelling
• inflammation of the kidneys
• flu-like illness; chills
• increased levels of amylase, an enzyme that breaks down starch; increased bilirubin in the blood; increased blood levels of a liver enzyme known as alkaline phosphatase; increased calcium in the blood

Uncommon (may affect up to 1 in 100 people)

• an increased number of white blood cells (eosinophils)
• inflammation of the pituitary gland situated at the base of the brain
• type 1 diabetes, including diabetic ketoacidosis
• a condition in which the muscles become weak and tire easily; inflammation of the brain, which may present as confusion, fever, memory problems or seizures (encephalitis)
• inflammation of the eyes; eye pain, irritation, itchiness or redness; uncomfortable sensitivity to light; seeing spots
• inflammation of the heart muscle, which may present as shortness of breath, irregular heartbeat, feeling tired, or chest pain; accumulation of fluid around the heart
• inflammation of the blood vessels
• a sore that develops on the inside lining of your stomach or upper part of your small intestine
• dry, itchy skin; thickened, sometimes scaly, skin growth; patches of skin which have lost colour; small skin bumps, lumps or sores; hair colour changes
• inflammation of the sheath that surrounds tendons

Rare (may affect up to 1 in 1000 people)

• decreased function of the parathyroid gland, which may present as muscle cramps or spasms, fatigue and weakness
• swelling of the optic nerve that may result in vision loss in one or both eyes, pain with eye movement, and/or loss of colour vision (optic neuritis)
• a hole in the small intestines
• itching, skin blistering, peeling or sores, and/or ulcers in mouth or in lining of nose, throat, or genital area (toxic epidermal necrolysis or Stevens-Johnson syndrome)
• disease in which the immune system attacks the glands that make moisture for the body, such as tears and saliva (Sjogren’s syndrome)
• inflammation of the bladder, which may present as frequent and/or painful urination, urge to pass urine, blood in urine, pain or pressure in lower abdomen

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

• lack or reduction of digestive enzymes made by the pancreas (pancreatic exocrine insufficiency); coeliac disease (characterised by symptoms such as stomach pain, diarrhoea, and bloating after consuming gluten-containing foods)

Rash is more common when KEYTRUDA is given in combination with enfortumab vedotin than when KEYTRUDA is given alone.

Unopened vial

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

Do not use this medicine after the expiry date which is stated on the carton and vial label 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 carton in order to protect from light.

After preparation of infusion

Chemical and physical in-use stability has been demonstrated for up to 42 days at 2 °C to 8 °C or at 23 °C to 27 °C. From a microbiological point of view, the product, once diluted, should be used immediately. The diluted solution must not be frozen. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 7 days at 2 °C to 8 °C, or 12 hours at room temperature, unless dilution has taken place in controlled and validated aseptic conditions. If refrigerated, the vials and/or intravenous bags must be allowed to come to room temperature prior to use.

Do not store any unused portion of the infusion solution for reuse. Any unused medicine or waste material should be disposed of in accordance with local requirements.

For any information about this medicine, please contact: