10 Lenalidomide Side Effects You Should Know About

In the 1950s and 1960s, doctors often turned to thalidomide as the answer for expecting mothers experiencing morning sickness. They prescribed the medication in hopes of relieving their patients’ nausea and vomiting — but instead the results were unexpectedly grim. Thalidomide was found to cause birth defects — the most infamous being phocomelia, or shortened arms or legs.

This unfortunate phenomenon is now known as the thalidomide tragedy. And since then, medication safety standards have grown much more strict. Prescription medications are required to go through rigorous testing, including looking for potentially harmful effects on developing babies prior to being given to the public. Today, many effective medications are out there, but some of them come with heavy disclaimers on their use.

Lenalidomide (Revlimid) is one of these medications. It’s used for blood cancers like multiple myeloma, myelodysplastic syndrome, and certain B-cell lymphomas. But since it’s in the same medication class as thalidomide, it still has the potential to cause birth defects. And just like any other medication, it has other side effects to be aware of. 

Below, we’ll detail 10 possible lenalidomide side effects and how to manage them.

1. Diarrhea

Diarrhea is a common lenalidomide side effect, but it’s often manageable. It’s usually mild and can be treated with anti-diarrheal medications. Lenalidomide dose changes can also help. 

There’s a number of lifestyle changes you might also try to help treat diarrhea and minimize dehydration, including:

• Drinking plenty of fluids throughout the day

• Avoiding foods that could worsen your symptoms, like those that are spicy, acidic, or high in fiber

• If you’re lactose-intolerant, check with your pharmacist to determine if your specific lenalidomide capsule contains lactose

However, if your diarrhea is severe or doesn’t go away, make sure to let your healthcare provider know.

2. Fatigue

Fatigue is a common side effect of many cancer treatments, including lenalidomide. You may feel tired, weak, or slow. Fortunately, there are a few things you can do at home to help combat fatigue. These include:

• Avoiding caffeine

• Participating in moderate exercise throughout the week

• Taking lenalidomide at night

• Prioritizing adequate sleep — aim for 7 to 8 hours per night

3. Insomnia

Insomnia is a common side effect that occurs in nearly 30% of people taking lenalidomide. In turn, this can carry over and contribute to fatigue the next day. 

Lifestyle changes can make a small difference for treating insomnia. Many recommendations for treating insomnia prioritize a sense of calm at night:

• Avoid alcohol and caffeine close to bedtime

• Only exercise during the day

• Try relaxation methods like breathing exercises, music, or meditation 

• Enjoy a warm, caffeine-free beverage before bed

You can also reach out to your healthcare provider to see if any other medications might be contributing to insomnia. For instance, dexamethasone, which is commonly prescribed with lenalidomide, can cause insomnia. You can minimize insomnia from dexamethasone by taking it in the morning. 

4. Back, stomach, or joint pain

Pain in your back, stomach, or joints can appear while taking lenalidomide. It’s also possible to experience muscle cramps. 

It’s helpful to keep track of when your pain is occurring, how long it lasts, and what it feels like. This is because pain, especially cancer-related pain, is a very personal experience. Keeping track of your pain helps give your healthcare provider a better idea of what’s happening over time. They can offer tips and tricks to help make your symptoms more manageable.

5. Appetite changes

Your appetite may be smaller than normal while taking lenalidomide. This is because it can change the way that food tastes or smells. It can also cause nausea, which may lessen appetite.

Regardless of cause, a decreased appetite can lead to weight loss and weakness. This can make it harder to tolerate your treatments. Here are a few things you can do to help boost your appetite and maintain your weight:

• Eat five to six small, nutrient-rich meals throughout the day (rather than two to three large meals).

• Increase your physical activity, if possible.

• Meet with a dietitian. There are many who specialize in cancer-related nutrition.

However, compared to other cancer medications, lenalidomide has a low to minimal potential for causing nausea. 

6. Birth defects

As mentioned, lenalidomide can cause severe birth defects if taken during pregnancy. In fact, it has a boxed warning about birth defects — the most serious type of FDA medication warning. 

Because of this, lenalidomide is only available through an FDA-required Risk Evaluation and Mitigation Strategies (REMS) medication safety program. This helps make sure that pregnant women aren’t exposed to lenalidomide.

It’s important to follow all the requirements of the lenalidomide REMS program. The requirements of the program are a little different depending on your “risk category,” which is all detailed in the graph below.

7. Low blood counts

Medications like lenalidomide make different types of blood cells less abundant in your body. 

White blood cells are one example. With fewer of these infection-fighting cells, there’s a greater risk of getting an infection. What’s more, lenalidomide can lower your platelet counts. Platelets normally help clot your blood, so if you don’t have enough of them, your risk for bleeding goes up. Lenalidomide has a boxed warning for both of these side effects. 

As a precaution, your healthcare provider will monitor your blood counts through regular blood draws. If you have low blood counts, your healthcare provider may decrease your dose or have you stop lenalidomide for a period of time. It’s also a good idea to minimize your risk of infection by avoiding sick people whenever possible.

8. Cough

Lenalidomide can cause a cough in around 20% of people who take it. Even though a cough may seem minor, it’s important to tell your healthcare provider about any symptoms of a cough or cold you have while taking lenalidomide. It could be a sign of an infection. 

Since lenalidomide can weaken your immune system, infections are more likely to become severe. It’s important to treat infections right away to avoid possible complications down the line.

9. Blood clots

Lenalidomide has a boxed warning about a potential risk for blood clots. As a preventative measure, you’ll likely need to take medication to prevent blood clots while taking lenalidomide. This includes medications like aspirin, warfarin (Coumadin, Jantoven), or apixaban (Eliquis).

Your healthcare provider can tell you which medication would be best for your situation.

10. Skin reactions

Mild-to-moderate skin rashes are common with lenalidomide. These can usually be treated by briefly stopping lenalidomide. Antihistamines like diphenhydramine (Benadryl) or topical steroids like hydrocortisone can also help. Once they go away, lenalidomide can usually be safely restarted at a lower dose. 

Still, it’s important to reach out to your care team if a rash occurs at any point while you’re taking the medication. In rare cases, lenalidomide can cause more serious skin conditions, including Stevens-Johnson syndrome or toxic epidermal necrolysis (SJS/TEN). These are medical emergencies that can cause problems if they’re not caught early.

When should I contact my healthcare provider about lenalidomide side effects?

Some lenalidomide side effects are expected and can be managed at home. However, some are more severe and need treatment from your care team. Contact your healthcare provider if you experience any of the following:

• Sudden abdominal pain

• Cough

• Dark or brown urine

• Fever

• Rash or blistering skin

• Shortness of breath

• Swelling of your lips, mouth, tongue or throat

• Uncontrolled or bloody diarrhea

• Unusual bruising or bleeding

• Yellowing of the skin or eyes

• You think you or your partner could be pregnant

Why trust our experts?

Written by:

Rachel Feaster, PharmD, BCOP, BCPS

Rachel Feaster has over 10 years of professional experience in ambulatory, inpatient, pharmacogenomics, and oncology care. She is board certified in oncology and pharmacotherapy.

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:

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.

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