7 Keytruda Side Effects and How to Manage Them

Keytruda (pembrolizumab) is a common immunotherapy medication that treats many types of cancer. Originally FDA approved in 2014 as a melanoma (skin cancer) drug, it’s now an approved treatment option for more than 15 types of cancer. This includes certain types of lung cancer, breast cancer, head and neck cancer, and more.

As an immunotherapy treatment, Keytruda works differently than chemotherapy. It helps your immune system fight cancer more strategically. But this means it also comes with its own distinct side effects, many of which are different from side effects typically seen with traditional chemotherapy.

Below, we’ll discuss seven Keytruda side effects and how to manage them.

1. Fatigue

Fatigue, or feeling tired or burnt out, is a common side effect of almost all immunotherapy treatments. Keytruda is no exception. Around 30% of people receiving Keytruda in initial studies reported some level of fatigue.

Other contributing factors to fatigue can include the cancer itself and other treatments you may be receiving, such as chemotherapy or radiation.

Managing fatigue

The best way to manage fatigue depends on how severe it is.

If it’s an annoyance, but not necessarily severe, your cancer specialist may want you to keep taking Keytruda so you can keep receiving its benefits. They may prescribe a short course of corticosteroids (steroids), such as prednisone, to see if that helps improve your energy levels. They may also want to check your lab work to see if anemia or an underactive thyroid could be contributing to fatigue.

If your fatigue feels bothersome or excessive, be honest with your provider. Symptoms of severe fatigue may include tiredness that doesn't get better with rest and limits your ability to care for yourself. In this case, your healthcare provider may suggest temporarily pausing Keytruda to see if it improves.

2. Muscle and joint pain

Another common side effect of Keytruda is muscle and joint pain. This can include achy bones, joint stiffness, and muscle soreness. About 18% of people taking Keytruda in initial studies reported some degree of muscle and joint pain.

These symptoms are usually mild and manageable, but they can become more severe — even leading to inflammatory arthritis.

Managing muscle and joint pain

Over-the-counter (OTC) medications, such as nonsteroidal anti-inflammatory drugs (NSAIDs), can help relieve joint and muscle pain from Keytruda. This includes medications such as ibuprofen (Advil, Motrin) and naproxen (Aleve, Naprosyn). Prescription-strength NSAIDs are another option.

If your muscle and joint pain isn’t relieved by NSAIDs, your healthcare provider may recommend a short course of steroids to calm the immune system. This may lead to better pain improvement.

In the case muscle or joint pain becomes too much to handle, your provider may recommend you stop taking Keytruda altogether. They may also refer you to a rheumatologist for additional evaluation.

3. Upset stomach, including changes in bowel habits

Upset stomach — including diarrhea, constipation, and stomach pain — are also common Keytruda side effects. Of these, diarrhea is the most notable. Over 20% of people who received Keytruda in clinical trials reported experiencing diarrhea.

Diarrhea can range from mild — one to two additional bowel movements a day — to severe, including colitis (inflammation of the colon).

Managing diarrhea and upset stomach

If your diarrhea is mild, OTC antidiarrheal medications, such as loperamide (Imodium A-D), can offer some relief. You can also try temporarily adjusting your diet to avoid foods that may make diarrhea worse, such as spicy or acidic foods. Limiting yourself to plain, starchy foods can also help.

If diarrhea becomes more severe, let your healthcare provider know. They may recommend pausing Keytruda and trying other medications, such as budesonide (Entocort), to help relieve inflammation in the digestive tract. They might resume the medication when the inflammation calms down.

If you develop symptoms of colitis — such as severe diarrhea, severe stomach pain or cramping, or blood or mucus in your stool — contact your healthcare provider right away. After the situation at hand is treated and under control, they’ll likely remove Keytruda from your treatment plan.

4. Skin rashes and itchiness

Keytruda can irritate the skin, leading to itchiness and rashes. More than 20% of people in initial studies reported itchiness or rashes at some point.

Skin symptoms like these are typically mild. But they can sometimes become serious. There have been some reports of severe allergic skin conditions, including Stevens-Johnson syndrome (SJS). Symptoms of SJS can include fever, blistering or peeling of the skin, and body aches.

Managing skin rashes

For mild-to-moderate skin rashes, moisturizing creams, such as CeraVe, may be all you need. Your healthcare provider may also recommend a topical steroid, such as hydrocortisone, for rash relief in certain cases. Oral steroids are another option. OTC antihistamines, such as diphenhydramine (Benadryl) or cetirizine (Zyrtec), often do the trick for itchiness.

For more severe skin symptoms, your provider may recommend stopping Keytruda. They may want you to apply topical steroids to the rash and take oral steroids to calm the immune system.

If your skin symptoms don’t improve with these measures, they may refer you to a dermatologist.

5. Nerve problems

Although rare, Keytruda has been linked to certain nerve problems. This includes health conditions such as myasthenia gravis, Guillain-Barré syndrome, and peripheral neuropathy. These conditions can cause symptoms such as numbness, tingling, or pain in your hands and feet. Weakness and changes in muscle function are also possible.

Managing nerve problems

If you develop mild to moderate nerve pain, your healthcare provider may temporarily pause your Keytruda infusions to see if symptoms improve. During this waiting period, they may prescribe oral steroids or other medications that can help with nerve pain, including gabapentin (Neurontin) or duloxetine (Cymbalta).

If you experience signs of myasthenia gravis, Guillain-Barré syndrome, or other serious nerve problems while you’re receiving Keytruda, your healthcare provider will want you to stop taking it altogether. Keep an eye out for symptoms such as weakness in the arms and legs, trouble speaking, and double vision.

6. Underactive thyroid

Thyroid problems are another possible side effect of Keytruda. Hypothyroidism, or an underactive thyroid, develops when your thyroid doesn’t produce enough thyroid hormones. This can cause symptoms such as tiredness, weight gain, and feeling cold.

Managing thyroid changes

Your healthcare provider will likely monitor your thyroid function while taking Keytruda. This is a common preventative measure.

In many cases, hypothyroidism is mild and treatment with Keytruda can be continued. Your healthcare provider may recommend a medication like levothyroxine (Synthroid) to help replace missing thyroid hormones — especially if you’re actively experiencing symptoms of hypothyroidism. Fatigue, brain fog, and frequently feeling chilly are all common symptoms.

If hypothyroidism becomes more severe, you may be referred to an endocrinologist.

7. Lung problems

Keytruda may also cause lung inflammation. This happens as a result of overactivation of the immune system in the lungs (immune-related pneumonitis). This can lead to symptoms such as trouble breathing, cough, and low oxygen levels in the body.

This isn’t typical though. Only about 3% of people who received Keytruda in clinical trials experienced pneumonitis. Of this percentage, about two-thirds ended up needing corticosteroids to relieve immune-related pneumonitis.

Managing lung problems

Let your healthcare provider know right away if you experience shortness of breath, chest pain, or develop a new or worsening cough. These may be signs of pneumonitis.

If your symptoms are mild, your provider may recommend you pause treatment and restart it again in a few weeks. If they’re more severe, you may have to permanently stop treatment with Keytruda. They’ll likely also recommend a course of steroids and/or antibiotics.

What happens if I stop taking Keytruda?

It’s common for people who develop unmanageable side effects to stop taking Keytruda. If you stop Keytruda because of a side effect that developed, you may see the side effect improve after some time. But some side effects can continue to persist even after stopping Keytruda.

There is some debate over the right time to stop taking Keytruda if you’re also seeing a positive response in your cancer treatment. For example, one study suggests that it may be safe to stop taking Keytruda for melanoma treatment after 2 years without changing chances of survival.

Talk with a cancer specialist to determine whether or not it’s safe for you to stop Keytruda.

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Written by:

Sonja Jacobsen, PharmD, BCPS, BCOP

Sonja Jacobsen, PharmD, BCPS, BCOP,  is a clinical oncology pharmacy specialist currently practicing in Seattle. She has been practicing as a pharmacist since 2015 and is licensed to practice in Washington state and North Carolina.

Edited by:

Joshua Murdock, PharmD, BCBBS

Joshua Murdock, PharmD, BCBBS, is a licensed pharmacist in Arizona, Colorado, and Rhode Island. He has worked in the pharmacy industry for more than 10 years and currently serves as a pharmacy editor for GoodRx.

Reviewed by:

Patricia Pinto-Garcia, MD, MPH

Patricia Pinto-Garcia, MD, MPH, is a medical editor at GoodRx. She is a licensed, board-certified pediatrician with more than a decade of experience in academic medicine.

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