What should I know about side effects?

Learn How You May Feel During Treatment With KEYTRUDA® (pembrolizumab) and LENVIMA® (lenvatinib)

Learn how you may feel during treatment

Throughout treatment, side effects may happen. That’s why you should know what the possible side effects of KEYTRUDA and LENVIMA are and talk to your health care provider immediately about what you can do to help manage them.

Why Is It Important to Know About Potential Side Effects of KEYTRUDA® (pembrolizumab) and LENVIMA® (lenvatinib)?

Why is it important to know about potential side effects?

You may experience side effects at any time during your treatments or even after they have ended. That’s why it’s important to get to know what the side effects are. This can help you more easily recognize them if you start to feel any of the symptoms.

Side effects may occur while taking KEYTRUDA

During treatment with KEYTRUDA, side effects can occur and should be treated as early as possible. In clinical trials with KEYTRUDA, some patients stopped treatment due to side effects. Tell your health care provider if you have any side effect that bothers you or that does not go away.

Serious side effects

KEYTRUDA is a medicine that may treat certain cancers by working with your immune system. KEYTRUDA can cause your immune system to attack normal organs and tissues in any area of your body and can affect the way they work. These problems can sometimes become severe or life-threatening and can lead to death. You can have more than one of these problems at the same time. These problems may happen anytime during treatment or even after your treatment has ended.

Call or see your health care provider right away if you develop any signs or symptoms of the following problems or if they get worse. These are not all of the signs and symptoms of immune system problems that can happen with KEYTRUDA:

Lung problems
  • Cough
  • Shortness of breath
  • Chest pain
Intestinal problems
  • Diarrhea (loose stools) or more frequent bowel movements than usual
  • Stools that are black, tarry, sticky, or have blood or mucus
  • Severe stomach-area (abdomen) pain or tenderness
Liver problems
  • Yellowing of your skin or the whites of your eyes
  • Severe nausea or vomiting
  • Pain on the right side of your stomach area (abdomen)
  • Dark urine (tea colored)
  • Bleeding or bruising more easily than normal
Hormone gland problems
  • Headaches that will not go away or unusual headaches
  • Eye sensitivity to light
  • Eye problems
  • Rapid heartbeat
  • Increased sweating
  • Extreme tiredness
  • Weight gain or weight loss
  • Feeling more hungry or thirsty than usual
  • Urinating more often than usual
  • Hair loss
  • Feeling cold
  • Constipation
  • Your voice gets deeper
  • Dizziness or fainting
  • Changes in mood or behavior, such as decreased sex drive, irritability, or forgetfulness
Kidney problems
  • Decrease in your amount of urine
  • Blood in your urine
  • Swelling of your ankles
  • Loss of appetite
Skin problems
  • Rash
  • Itching
  • Skin blistering or peeling
  • Painful sores or ulcers in your mouth or in your nose, throat, or genital area
  • Fever or flu-like symptoms
  • Swollen lymph nodes
Problems can also happen in other organs and tissues. These are not all of the signs and symptoms of immune system problems that can happen with KEYTRUDA. Call or see your health care provider right away for any new or worsening signs or symptoms, which may include:
  • Chest pain, irregular heartbeat, shortness of breath, swelling of ankles
  • Confusion, sleepiness, memory problems, changes in mood or behavior, stiff neck, balance problems, tingling or numbness of the arms or legs
  • Double vision, blurry vision, sensitivity to light, eye pain, changes in eyesight
  • Persistent or severe muscle pain or weakness, muscle cramps
  • Low red blood cells, bruising
Infusion reactions that can sometimes be severe or life-threatening. Signs and symptoms of infusion reactions may include:
  • Chills or shaking
  • Itching or rash
  • Flushing
  • Shortness of breath or wheezing
  • Dizziness
  • Feeling like passing out
  • Fever
  • Back pain

Rejection of a transplanted organ. Your health care provider should tell you what signs and symptoms you should report and they will monitor you, depending on the type of organ transplant that you have had.

Complications, including graft-versus-host-disease (GVHD), in people who have received a bone marrow (stem cell) transplant that uses donor stem cells (allogeneic). These complications can be serious and can lead to death. These complications may happen if you underwent transplantation either before or after being treated with KEYTRUDA. Your health care provider will monitor you for these complications.

Getting medical treatment right away may help keep these problems from becoming more serious. Your health care provider will check you for these problems during treatment with KEYTRUDA. Your health care provider may treat you with corticosteroid or hormone replacement medicines. Your health care provider may also need to delay or completely stop treatment with KEYTRUDA if you have severe side effects.

Common side effects

Common side effects of KEYTRUDA when given with LENVIMA include: low levels of thyroid hormone, high blood pressure, feeling tired, diarrhea, joint and muscle pain, nausea, decreased appetite, vomiting, mouth sores, weight loss, stomach-area (abdominal) pain, urinary tract infection, protein in your urine, constipation, headache, bleeding, blisters or rash on the palms of your hands and soles of your feet, hoarseness, rash, liver problems, and kidney problems.

These are not all the possible side effects of KEYTRUDA. Talk to your health care provider for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Side effects may occur while taking LENVIMA

Every medication has side effects and impacts each person differently. Below is information about certain side effects for LENVIMA. If you have any side effects, tell your doctor about them right away.

LENVIMA may cause serious side effects, including:

High blood pressure (hypertension)
  • High blood pressure is a common side effect of LENVIMA and can be serious. Your blood pressure should be well controlled before you start taking LENVIMA. Your health care provider should check your blood pressure regularly during treatment with LENVIMA. If you develop blood pressure problems, your health care provider may prescribe medicine to treat your high blood pressure.
Heart problems
  • LENVIMA can cause serious heart problems that may lead to death. Call your health care provider right away if you get symptoms of heart problems, such as shortness of breath or swelling of your ankles.
Problem with blood clots in your blood vessels (arteries)
  • Get emergency medical help right away if you get any of the following symptoms:
    • severe chest pain or pressure
    • pain in your arms, back, neck or jaw
    • shortness of breath
    • numbness or weakness on one side of your body
    • trouble talking
    • sudden severe headache
    • sudden vision changes
Liver problems
  • LENVIMA may cause liver problems that may lead to liver failure and death. Your health care provider will check your liver function before and during treatment with LENVIMA. Tell your health care provider right away if you have any of the following symptoms:
    • your skin or the white part of your eyes turns yellow (jaundice)
    • dark “tea colored” urine
    • light-colored bowel movements (stools)
    • feeling drowsy, confused or loss of consciousness
Kidney problems
  • Kidney failure, which can lead to death, has happened with LENVIMA treatment. Your health care provider should do regular blood tests to check your kidneys.
Increased protein in your urine (proteinuria)
  • Proteinuria is a common side effect of LENVIMA and can be serious. Your health care provider should check your urine for protein before and during your treatment with LENVIMA.
Diarrhea
  • Diarrhea is a common side effect of LENVIMA and can be serious. If you get diarrhea, ask your health care provider about what medicines you can take to treat your diarrhea. It is important to drink more water when you get diarrhea. Tell your health care provider or go to the emergency room, if you are unable to drink enough liquids and your diarrhea is not able to be controlled.
An opening in the wall of your stomach or intestines (perforation) or an abnormal connection between two or more body parts (fistula)
  • Get emergency medical help right away if you have severe stomach (abdomen) pain.
Changes in the electrical activity of your heart called QT prolongation
  • QT prolongation can cause irregular heartbeats that can be life threatening. Your health care provider will do blood tests before and during your treatment with LENVIMA to check the levels of potassium, magnesium, and calcium in your blood, and may check the electrical activity of your heart with an ECG.
Low levels of blood calcium (hypocalcemia)
  • Your health care provider will check your blood calcium levels during treatment with LENVIMA and may tell you to take a calcium supplement if your calcium levels are low.
A condition called Reversible Posterior Leukoencephalopathy Syndrome (RPLS):
  • Call your health care provider right away if you get severe headache, seizures, weakness, confusion, or blindness or change in vision.
Bleeding
  • LENVIMA may cause serious bleeding problems that may lead to death. Tell your health care provider if you have any signs or symptoms of bleeding during treatment with LENVIMA, including:
    • severe and persistent nose bleeds
    • vomiting blood
    • red or black (looks like tar) stools
    • blood in your urine
    • coughing up blood or blood clots
    • heavy or new onset vaginal bleeding
Change in thyroid hormone levels
  • Your health care provider should check your thyroid hormone levels before starting and every month during treatment with LENVIMA.
Wound healing problems
  • Wound healing problems have happened in some people who take LENVIMA. Tell your health care provider if you plan to have any surgery before or during treatment with LENVIMA.
    • You should stop taking LENVIMA at least 1 week before planned surgery.
    • Your health care provider should tell you when you may start taking LENVIMA again after surgery.
Severe jaw bone problems (osteonecrosis)

Severe jaw bone problems have happened in some people who take LENVIMA. Certain risk factors such as taking a bisphosphonate medicine or the medicine denosumab, having dental disease, or an invasive dental procedure may increase your risk of getting jaw bone problems. Your health care provider should examine your mouth before you start and during treatment with LENVIMA. Tell your dentist that you are taking LENVIMA. It is important for you to practice good mouth care during treatment with LENVIMA. Tell your health care provider right away if you get signs or symptoms of jaw bone problems during treatment with LENVIMA, including jaw pain, toothache, or sores on your gums. Tell your health care provider if you plan to have any dental procedures before or during treatment with LENVIMA. You should avoid having invasive dental procedures if possible, during treatment with LENVIMA. Stopping your bisphosphonate medicine before an invasive dental procedure may help decrease your risk of getting these jaw problems.

  • You should stop taking LENVIMA at least 1 week before planned dental surgery or invasive dental procedures.
  • Your health care provider should tell you when you may start taking LENVIMA again after dental procedures.

The most common side effects of LENVIMA when given with KEYTRUDA include: decrease in thyroid hormone levels, increased blood pressure, tiredness, diarrhea, joint and muscle pain, nausea, decreased appetite, vomiting, mouth sores, weight loss, stomach-area (abdomen) pain, urinary tract infection, protein in your urine, constipation, headache, bleeding, rash, redness, itching, or peeling of your skin on your hands and feet, hoarseness, and rash.

LENVIMA may cause fertility problems in males and females. Talk to your health care provider if this is a concern for you.

Your health care provider may need to reduce your dose of LENVIMA, or delay or completely stop treatment if you have certain side effects.

These are not all the possible side effects of LENVIMA. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088 or visit www.fda.gov/medwatch.

Write Down All Physical and Emotional Changes That You Recognize During Treatment

Write down all physical and emotional changes

Even before you start treatment, write down how you feel physically and emotionally. This will help you recognize if you start to feel anything out of the ordinary. Keep these key things in mind:

  • Consider downloading and printing the Symptom Tracker (PDF) to make tracking easy
  • Talk to your health care provider about what you can expect from treatment
  • Write down how you are feeling early and often (before, during, after, and even in between treatment visits)
What Are Some Examples of Physical or Emotional Changes That I Should Write Down?

What are some examples of what I should write down?

Use these suggestions as a starting point to writing down how you are feeling:

  • The date you’re feeling a symptom
  • What your symptom is and/or how you feel overall
  • What your energy level and/or mood is like
Tell Your Cancer Care Team Right Away if You Feel Something New or Different

When should I speak up if I feel something new or different?

You should speak up immediately if you feel something new or different.

Calling or talking to a member of your cancer care team may keep your side effects from getting more serious. It may also enable your health care provider to help you manage any side effects.

Don't Make Changes to Your LENVIMA® (lenvatinib) Dose or Medications Without Talking to Your Health Care Provider

Should I adjust my medication if I feel something new or different?

Do not make any changes to your dose or medication without talking to your health care provider first.

Your health care provider will tell you how much LENVIMA to take and when to take it. They may also:

  • Adjust your dose during treatment
  • Stop treatment for some time
  • Completely stop treatment with LENVIMA if you have certain side effects

In addition, your health care provider will decide how many treatments of KEYTRUDA you need. If you have any side effects, they may also:

  • Treat you with corticosteroid or hormone replacement medicines
  • Delay treatment for some time
  • Completely stop treatment
Managing Some Common Side Effects of KEYTRUDA® (pembrolizumab) and LENVIMA® (lenvatinib) on Your Own

How can I potentially manage some common side effects myself?

It’s important to tell your health care provider about all side effects you have, even those you can manage at home. Use these quick tips after consulting with your health care provider.

This is not the full list of side effects you may experience while taking KEYTRUDA + LENVIMA. Please read the Patient Information for LENVIMA the Medication Guide for KEYTRUDA for additional information about potential side effects.

High blood pressure:

  • Check your blood pressure regularly with a monitor at home
  • Exercise lightly

Feeling tired (fatigue):

  • Take quick naps of 30 minutes or less for an energy boost
  • Ask others for help with difficult tasks

Mild diarrhea:

  • Drink plenty of water to keep yourself hydrated
  • Avoid dairy products, alcohol, caffeine, and spicy foods

Nausea:

  • Eat smaller meals more frequently
  • Drink clear liquids and ice-cold beverages
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Hopefully you have a better understanding of what you should know about the side effects of KEYTRUDA and LENVIMA. Now that you learned to write down how you are feeling, when you should speak up, and what to tell your doctor before and during treatment, you’re ready to move onto the next section.

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FDA-Approved Indications

  • KEYTRUDA and LENVIMA are prescription medicines used together to treat:
  • a kind of kidney cancer called advanced renal cell carcinoma (RCC) as your first treatment when your kidney cancer has spread or cannot be removed by surgery.
  • a kind of uterine cancer called endometrial carcinoma:
    • when your tumor is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), and
    • you have received anti-cancer treatment, and it is no longer working, and
    • your cancer cannot be cured by surgery or radiation (advanced endometrial carcinoma).
  • It is not known if LENVIMA is safe and effective in children.
Important Safety Information for KEYTRUDA® (pembrolizumab)

KEYTRUDA is a medicine that may treat certain cancers by working with your immune system. KEYTRUDA can cause your immune system to attack normal organs and tissues in any area of your body and can affect the way they work. These problems can sometimes become severe or life-threatening and can lead to death. You can have more than one of these problems at the same time. These problems may happen any time during treatment or even after your treatment has ended.

Call or see your health care provider right away if you develop any signs or symptoms of the following problems or if they get worse. These are not all of the signs and symptoms of immune system problems that can happen with KEYTRUDA:

Lung problems: cough, shortness of breath, or chest pain.

Intestinal problems: diarrhea (loose stools) or more frequent bowel movements than usual; stools that are black, tarry, sticky, or have blood or mucus; or severe stomach-area (abdomen) pain or tenderness.

Liver problems: yellowing of your skin or the whites of your eyes; severe nausea or vomiting; pain on the right side of your stomach area (abdomen); dark urine (tea colored); or bleeding or bruising more easily than normal.

Hormone gland problems: headaches that will not go away or unusual headaches; eye sensitivity to light; eye problems; rapid heartbeat; increased sweating; extreme tiredness; weight gain or weight loss; feeling more hungry or thirsty than usual; urinating more often than usual; hair loss; feeling cold; constipation; your voice gets deeper; dizziness or fainting; changes in mood or behavior, such as decreased sex drive, irritability, or forgetfulness.

Kidney problems: decrease in the amount of your urine; blood in your urine; swelling of your ankles; loss of appetite.

Skin problems: rash; itching; skin blistering or peeling; painful sores or ulcers in your mouth or in your nose, throat, or genital area; fever or flu-like symptoms; swollen lymph nodes.

Problems can also happen in other organs and tissues. Signs and symptoms of these problems may include: chest pain; irregular heartbeat; shortness of breath; swelling of ankles; confusion; sleepiness; memory problems; changes in mood or behavior; stiff neck; balance problems; tingling or numbness of the arms or legs; double vision; blurry vision; sensitivity to light; eye pain; changes in eyesight; persistent or severe muscle pain or weakness; muscle cramps; low red blood cells; bruising.

Infusion reactions that can sometimes be severe or life-threatening. Signs and symptoms of infusion reactions may include chills or shaking, itching or rash, flushing, shortness of breath or wheezing, dizziness, feeling like passing out, fever, and back pain.

Rejection of a transplanted organ. Your health care provider should tell you what signs and symptoms you should report and they will monitor you, depending on the type of organ transplant that you have had.

Complications, including graft-versus-host disease (GVHD), in people who have received a bone marrow (stem cell) transplant that uses donor stem cells (allogeneic). These complications can be serious and can lead to death. These complications may happen if you underwent transplantation either before or after being treated with KEYTRUDA. Your health care provider will monitor you for these complications.

Getting medical treatment right away may help keep these problems from becoming more serious. Your health care provider will check you for these problems during treatment with KEYTRUDA. They may treat you with corticosteroid or hormone replacement medicines. They may also need to delay or completely stop treatment with KEYTRUDA if you have severe side effects.

Before you receive KEYTRUDA, tell your health care provider if you have immune system problems such as Crohn’s disease, ulcerative colitis, or lupus; have had an organ transplant or have had or plan to have a bone marrow (stem cell) transplant that uses donor stem cells (allogeneic); have had radiation treatment in your chest area; have a condition that affects your nervous system, such as myasthenia gravis or Guillain-Barré syndrome.

If you are pregnant or plan to become pregnant, tell your health care provider. KEYTRUDA can harm your unborn baby. If you are able to become pregnant, you will be given a pregnancy test before you start treatment. Use effective birth control during treatment and for at least 4 months after your final dose of KEYTRUDA. Tell them right away if you think you may be pregnant or you become pregnant during treatment with KEYTRUDA.

Tell your health care provider if you are breastfeeding or plan to breastfeed. It is not known if KEYTRUDA passes into your breast milk. Do not breastfeed during treatment with KEYTRUDA and for 4 months after your final dose of KEYTRUDA.

Tell your health care provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Common side effects of KEYTRUDA when given with LENVIMA include low levels of thyroid hormone; high blood pressure; feeling tired; diarrhea; joint and muscle pain; nausea; decreased appetite; vomiting; mouth sores; weight loss; stomach-area (abdominal) pain; urinary tract infection; protein in your urine; constipation; headache; bleeding; blisters or rash on the palms of your hands and soles of your feet; hoarseness; rash; liver problems; and kidney problems.

These are not all the possible side effects of KEYTRUDA. Talk to your health care provider for medical advice about side effects.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

Please read the accompanying Medication Guide for KEYTRUDA and discuss it with your doctor. The physician Prescribing Information also is available.

Important Safety Information for LENVIMA® (lenvatinib)

LENVIMA may cause serious side effects, including:

High blood pressure (hypertension): High blood pressure is a common side effect of LENVIMA and can be serious. Your blood pressure should be well controlled before you start taking LENVIMA. Your healthcare provider should check your blood pressure regularly during treatment with LENVIMA. If you develop blood pressure problems, your healthcare provider may prescribe medicine to treat your high blood pressure.

Heart problems: LENVIMA can cause serious heart problems that may lead to death. Call your healthcare provider right away if you get symptoms of heart problems, such as shortness of breath or swelling of your ankles.

Problem with blood clots in your blood vessels (arteries): Get emergency medical help right away if you get any of the following symptoms: severe chest pain or pressure; pain in your arms, back, neck, or jaw; shortness of breath; numbness or weakness on one side of your body; trouble talking; sudden severe headache; sudden vision changes.

Liver problems: LENVIMA may cause liver problems that may lead to liver failure and death. Your healthcare provider will check your liver function before and during treatment with LENVIMA. Tell your healthcare provider right away if you have any of the following symptoms: your skin or the white part of your eyes turn yellow (jaundice); dark “tea-colored” urine; light-colored bowel movements (stools); feeling drowsy, confused or loss of consciousness.

Kidney problems: Kidney failure, which can lead to death, has happened with LENVIMA treatment. Your healthcare provider should do regular blood tests to check your kidneys.

Increased protein in your urine (proteinuria): Proteinuria is a common side effect of LENVIMA and can be serious. Your healthcare provider should check your urine for protein before and during your treatment with LENVIMA.

Diarrhea: Diarrhea is a common side effect of LENVIMA and can be serious. If you get diarrhea, ask your healthcare provider about what medicines you can take to treat your diarrhea. It is important to drink more water when you get diarrhea. Tell your healthcare provider or go to the emergency room, if you are unable to drink enough liquids and your diarrhea is not able to be controlled.

An opening in the wall of your stomach or intestines (perforation) or an abnormal connection between two or more body parts (fistula): Get emergency medical help right away if you have severe stomach (abdomen) pain.

Changes in the electrical activity of your heart called QT prolongation: QT prolongation can cause irregular heartbeats that can be life threatening. Your healthcare provider will do blood tests before and during your treatment with LENVIMA to check the levels of potassium, magnesium, and calcium in your blood, and may check the electrical activity of your heart with an ECG.

Low levels of blood calcium (hypocalcemia): Your healthcare provider will check your blood calcium levels during treatment with LENVIMA and may tell you to take a calcium supplement if your calcium levels are low.

A condition called Reversible Posterior Leukoencephalopathy Syndrome (RPLS): Call your healthcare provider right away if you get severe headache, seizures, weakness, confusion, or blindness or change in vision.

Bleeding: LENVIMA may cause serious bleeding problems that may lead to death. Tell your healthcare provider if you have any signs or symptoms of bleeding during treatment with LENVIMA, including severe and persistent nose bleeds; vomiting blood; red or black (looks like tar) stools; blood in your urine; coughing up blood or blood clots; heavy or new onset vaginal bleeding.

Change in thyroid hormone levels: Your healthcare provider should check your thyroid hormone levels before starting and every month during treatment with LENVIMA.

Wound healing problems: Wound healing problems have happened in some people who take LENVIMA. Tell your healthcare provider if you plan to have any surgery before or during treatment with LENVIMA.

  • You should stop taking LENVIMA at least 1 week before planned surgery.
  • Your healthcare provider should tell you when you may start taking LENVIMA again after surgery.

Severe jaw bone problems (osteonecrosis): Severe jaw bone problems have happened in some people who take LENVIMA. Certain risk factors such as taking a bisphosphonate medicine or the medicine denosumab, having dental disease, or an invasive dental procedure may increase your risk of getting jaw bone problems. Your healthcare provider should examine your mouth before you start and during treatment with LENVIMA. Tell your dentist that you are taking LENVIMA. It is important for you to practice good mouth care during treatment with LENVIMA. Tell your healthcare provider right away if you have any signs or symptoms of jaw bone problems during treatment with LENVIMA, including jaw pain, toothache, or sores on your gums, and if you plan to have any dental procedures before or during treatment with LENVIMA.

  • You should stop taking LENVIMA at least 1 week before planned dental surgery or invasive dental procedures.
  • Your healthcare provider should tell you when you may start taking LENVIMA again after dental procedures.

The most common side effects of LENVIMA when given with KEYTRUDA include decrease in thyroid hormone levels, increased blood pressure, tiredness, diarrhea, joint and muscle pain, nausea, decreased appetite, vomiting, mouth sores, weight loss, stomach-area (abdomen) pain, urinary tract infection, protein in your urine, constipation, headache, bleeding, rash, redness, itching, or peeling of your skin on your hands and feet, hoarseness, and rash.

LENVIMA may cause fertility problems in males and females and can harm your unborn baby. Tell your healthcare provider if you are:

  • pregnant or plan to become pregnant. For females who are able to become pregnant, your healthcare provider should do a pregnancy test before you start treatment with LENVIMA. Use an effective method of birth control during treatment with LENVIMA and for at least 30 days after the last dose of LENVIMA
  • breastfeeding or plan to breastfeed. It is not known if LENVIMA passes into your breast milk. Do not breastfeed during treatment with LENVIMA and for at least 1 week after the last dose

Your healthcare provider may need to reduce your dose of LENVIMA, or delay or completely stop treatment if you have certain side effects.

These are not all the possible side effects of LENVIMA. Call your doctor for medical advice about side effects.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

Please read the accompanying Patient Information for LENVIMA and discuss it with your doctor. The physician Prescribing Information also is available.