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AstraZeneca

Keytruda
pembrolizumab

Package leaflet: Information for the patient


KEYTRUDA 25 mg/mL concentrate for solution for infusion

pembrolizumab


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


Warnings and precautions

Talk to your doctor or nurse before receiving KEYTRUDA.


Before you get KEYTRUDA, tell your doctor if you:


Complications, including graft-versus-host-disease (GVHD), in people with bone marrow (stem cell) transplant that uses donor stem cells (allogeneic). These complications can be severe and can lead to death. They may occur if you had this kind of transplant in the past or if you get it in the future. Your doctor will monitor you for signs and symptoms, which may include skin rash, liver inflammation, abdominal pain, or diarrhoea.


Children and adolescents

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


If you stop receiving KEYTRUDA

Stopping your treatment may stop the effect of the medicine. Do not stop treatment with KEYTRUDA unless you have discussed this with your doctor.


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


You will also find this information in the patient alert card you have been given by your doctor. It is important that you keep this alert card and show it to your partner or caregivers.


  1. Possible side effects


    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 activity; 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; patches of skin which have lost colour; inflammation of the skin; dry, itchy skin; hair loss; acne-like skin problem

    • muscle pain, aches or tenderness; pain in arms or legs; joint pain with swelling

    • chills; flu-like illness

    • 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 and eosinophils)

    • inflammation response against platelets

    • 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

    • inflammation of the covering of the heart; accumulation of fluid around 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; hair colour changes; small skin bumps, lumps or sores

    • 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 1,000 people)

    • 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); a condition called haemophagocytic lymphohistiocytosis, where the immune system makes too many infection fighting cells called histiocytes and lymphocytes that may cause various symptoms

    • a temporary inflammation of the nerves that causes pain, weakness, and paralysis in the extremities

    • 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)

    • 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

    • a hole in the small intestines

    • inflammation of the bile ducts

    • tender red bumps under the skin

    • 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)

    • 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. Signs and symptoms may include 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)

    • decreased number of white blood cells (neutrophils, leukocytes); decrease in the number of red blood cells; 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; dizziness; change in your sense of taste

    • shortness of breath; cough

    • nausea; diarrhoea; vomiting; stomach pain; constipation

    • hair loss; skin rash; itching

    • joint pain; pain in the muscles and bones; muscle pain, aches or tenderness

    • unusual tiredness or weakness; fever; swelling

    • 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 (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 activity

    • decreased sodium or calcium in the blood

    • 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; acne-like skin problem; inflammation of the skin; dry, itchy skin

    • pain in arms or legs; joint pain with swelling

    • sudden kidney damage

    • flu-like illness; chills

    • abnormal kidney function test; increased blood level of the liver enzyme alkaline phosphatase; increased calcium in the blood; increased bilirubin in the blood


      Uncommon (may affect up to 1 in 100 people)

    • a decreased 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 that 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 1,000 people)

    • inflammation response against red blood cells or platelets

    • an immune disorder that can affect the lungs, skin, eyes and/or lymph nodes (sarcoidosis)

    • condition known as Guillain- Barré syndrome, which causes muscle weakness on both sides of the body, and can be severe; a condition in which the muscles become weak and tire easily

    • inflammation of the eyes; eye pain, irritation, itchiness or redness; uncomfortable sensitivity to light; seeing spots

    • a hole in the small intestines

    • 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 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, leukocytes, lymphocytes); 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; increased thyroid gland activity; inflammation of the thyroid

    • decreased sodium, potassium, or calcium in the blood

    • trouble sleeping

    • dizziness, lack of energy, inflammation of the nerves causing numbness, weakness, tingling or burning pain of the arms and legs

    • 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, itchy 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 liver enzyme levels 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)

    • decreased 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

    • inflammation of the 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 1,000 people)

    • 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


    Reporting of side effects

    image

    If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.


  2. How to store KEYTRUDA


    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.


    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, chemical and physical in-use stability of KEYTRUDA has been demonstrated for 96 hours at 2ºC to 8ºC. This 96-hour hold may include up to 6 hours at room temperature (at or below 25°C). 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.


  3. Contents of the pack and other information What KEYTRUDA contains

    The active substance is pembrolizumab.


    One vial of 4 mL contains 100 mg of pembrolizumab. Each mL of concentrate contains 25 mg of pembrolizumab.


    The other ingredients are L-histidine, L-histidine hydrochloride monohydrate, sucrose, polysorbate 80 and water for injections.


    What KEYTRUDA looks like and contents of the pack

    KEYTRUDA is a clear to slightly opalescent, colourless to slightly yellow solution, pH 5.2 5.8. It is available in cartons containing one glass vial.


    Marketing Authorisation Holder Merck Sharp & Dohme B.V. Waarderweg 39

    2031 BN Haarlem The Netherlands


    Manufacturer

    Schering-Plough Labo NV

    Industriepark 30

    B-2220 Heist-op-den-Berg

    Belgium


    image

    Merck Sharp & Dohme B.V. Waarderweg 39

    2031 BN Haarlem The Netherlands


    For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:


    België/Belgique/Belgien

    MSD Belgium

    Tél/Tel: +32(0)27766211

    dpoc_belux@merck.com

    Lietuva

    UAB Merck Sharp & Dohme Tel. + 370 5 278 02 47

    msd_lietuva@merck.com


    България

    Мерк Шарп и Доум България ЕООД Тел.: +359 2 819 3737

    info-msdbg@merck.com

    Luxembourg/Luxemburg

    MSD Belgium

    Tél/Tel: +32(0)27766211

    dpoc_belux@merck.com


    Česká republika

    Merck Sharp & Dohme s.r.o. Tel: +420 233 010 111

    dpoc_czechslovak@merck.com

    Magyarország

    MSD Pharma Hungary Kft. Tel.: +36 1 888 5300

    hungary_msd@merck.com

    Danmark

    MSD Danmark ApS Tlf: + 45 4482 4000

    dkmail@merck.com

    Malta

    Merck Sharp & Dohme Cyprus Limited Tel: 8007 4433 (+356 99917558)

    malta_info@merck.com


    Deutschland

    MSD Sharp & Dohme GmbH

    Tel: 0800 673 673 673 (+49 (0) 89 4561 0)

    e-mail@msd.de

    Nederland

    Merck Sharp & Dohme B.V.

    Tel: 0800 9999000

    (+31 23 5153153)

    medicalinfo.nl@merck.com


    Eesti

    Merck Sharp & Dohme OÜ Tel.: +372 6144 200

    msdeesti@merck.com

    Norge

    MSD (Norge) AS Tlf: +47 32 20 73 00

    msdnorge@msd.no


    Ελλάδα

    MSD Α.Φ.Β.Ε.Ε.

    Τηλ: +30 210 98 97 300

    dpoc_greece@merck.com

    Österreich

    Merck Sharp & Dohme Ges.m.b.H. Tel: +43 (0) 1 26 044

    dpoc_austria@merck.com


    España

    Merck Sharp & Dohme de España, S.A. Tel: +34 91 321 06 00

    msd_info@merck.com

    Polska

    MSD Polska Sp. z o.o. Tel: +48 22 549 51 00

    msdpolska@merck.com


    France

    MSD France

    Tél: + 33 (0) 1 80 46 40 40

    Portugal

    Merck Sharp & Dohme, Lda Tel: +351 21 4465700

    inform_pt@merck.com


    Hrvatska

    Merck Sharp & Dohme d.o.o. Tel: + 385 1 6611 333

    croatia_info@merck.com

    România

    Merck Sharp & Dohme Romania S.R.L. Tel: +40 21 529 29 00

    msdromania@merck.com


    Ireland

    Merck Sharp & Dohme Ireland (Human Health) Limited

    Tel: +353 (0)1 2998700

    medinfo_ireland@merck.com

    Slovenija

    Merck Sharp & Dohme, inovativna zdravila d.o.o.

    Tel: +386 1 5204 201

    msd.slovenia@merck.com


    Ísland

    Vistor hf.

    Sími: + 354 535 7000

    Slovenská republika

    Merck Sharp & Dohme, s. r. o. Tel: +421 2 58282010

    dpoc_czechslovak@merck.com


    Italia

    MSD Italia S.r.l.

    Tel: 800 23 99 89 (+39 06 361911)

    medicalinformation.it@msd.com

    Suomi/Finland

    MSD Finland Oy

    Puh/Tel: +358 (0)9 804 650

    info@msd.fi


    Κύπρος

    Merck Sharp & Dohme Cyprus Limited

    Τηλ.: 800 00 673 (+357 22866700)

    cyprus_info@merck.com

    Sverige

    Merck Sharp & Dohme (Sweden) AB Tel: +46 77 5700488

    medicinskinfo@merck.com

    Latvija

    SIA Merck Sharp & Dohme Latvija Tel: + 371 67364224

    msd_lv@merck.com

    United Kingdom (Northern Ireland)

    Merck Sharp & Dohme Ireland (Human Health) Limited

    Tel: +353 (0)1 2998700

    medinfoNI@msd.com


    This leaflet was last revised in

    .


    image

    The following information is intended for healthcare professionals only:


    Preparation and administration of the infusion

    • Do not shake the vial.

    • Equilibrate the vial to room temperature (at or below 25°C).

    • Prior to dilution, the vial of liquid can be out of refrigeration (temperatures at or below 25°C) for up to 24 hours.

    • Parenteral medicinal products should be inspected visually for particulate matter and

      discolouration prior to administration. The concentrate is a clear to slightly opalescent, colourless to slightly yellow solution. Discard the vial if visible particles are observed.

    • Withdraw the required volume up to 4 mL (100 mg) of concentrate and transfer into an

      intravenous bag containing sodium chloride 9 mg/mL (0.9%) or glucose 50 mg/mL (5%) to prepare a diluted solution with a final concentration ranging from 1 to 10 mg/mL. Each vial contains an excess fill of 0.25 mL (total content per vial 4.25 mL) to ensure the recovery of 4 mL of concentrate. Mix diluted solution by gentle inversion.

    • 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, chemical and physical in-use stability of KEYTRUDA has been demonstrated for 96 hours at 2ºC to 8ºC. This 96-hour hold may include up to 6 hours at room temperature (at or below 25°C). If refrigerated, the vials and/or intravenous bags must be allowed to come to room temperature prior to use. Translucent to white proteinaceous particles may be seen in diluted solution. Administer the infusion solution intravenously over 30 minutes using a sterile, non-pyrogenic, low-protein binding 0.2 to 5 µm in-line or add-on filter.

    • Do not co-administer other medicinal products through the same infusion line.

    • KEYTRUDA is for single use only. Discard any unused portion left in the vial.


Any unused medicinal product or waste material should be disposed of in accordance with local requirements.