Zenbexus (iberdomide) is a CELMoD medicine used with daratumumab/hyaluronidase-fihj and dexamethasone to treat multiple myeloma that has relapsed or become refractory. Like all medicines, Zenbexus can cause side effects, and it may interact with other medicines. This article covers the side effects and interactions that matter most, along with practical tips for managing them.
This isn’t a complete list of every possible side effect or interaction. Always tell your health care provider about any new or worsening symptoms, even if they aren’t mentioned here.
Common Zenbexus Side Effects
- Upper respiratory tract infection
- Fatigue
- Muscle, bone, or joint pain
- Pneumonia
- Diarrhea
- Balance problems, muscle weakness, or other movement symptoms
- Rash
- Sleep problems, including insomnia or restless legs syndrome
- Low levels of antibodies (hypogammaglobulinemia)
- COVID-19
- Constipation
Serious Zenbexus Side Effects
- Severe drops in white blood cell counts (neutropenia)
- Serious or life-threatening infections
- Blood clots, including in the legs, lungs, heart, or brain
- Birth defects or pregnancy loss if taken during pregnancy
- New cancers
If you have symptoms that feel serious or life-threatening, get medical care right away.
How to Manage Zenbexus Side Effects
Low white blood cell counts (neutropenia)
Neutropenia, which is a drop in a type of white blood cell that helps fight infection, is the most common side effect of Zenbexus. In the clinical study, some degree of neutropenia occurred in about 90% of people taking Zenbexus, and a severe drop occurred in about 8 in 10 people. It most often showed up around three weeks into a cycle and typically lasted about a week.
Because neutropenia usually doesn’t cause symptoms on its own, your health care provider will check your blood counts regularly throughout treatment. Contact them right away if you get a fever because fever combined with a low white blood cell count (febrile neutropenia) needs prompt evaluation.
Depending on how low your counts get, your health care provider may:
- Pause Zenbexus temporarily until your counts recover
- Prescribe a growth factor medicine (G-CSF) to help your body make more white blood cells
- Lower your Zenbexus dose when you restart
Don’t adjust your Zenbexus dose or schedule on your own; any changes should come from your health care provider based on your lab results.
Infections
Because Zenbexus affects your immune system and can lower white blood cell counts, it can also raise your risk of infections, some of which can be serious or life-threatening. In the clinical study, infections of some kind affected about 8 in 10 people taking Zenbexus, and roughly 4 in 10 had an infection that was considered serious.
Watch for:
- Fever or chills
- Cough, sore throat, or shortness of breath
- Flu-like symptoms, such as body aches
- Pain, redness, or swelling anywhere on your body
Contact your health care provider promptly if you notice any of these. They may prescribe an antibiotic or antiviral medicine, recommend preventive medicines, or pause or lower your dose of Zenbexus until the infection clears. You shouldn’t start Zenbexus if you already have an active infection that isn’t controlled, so let your health care provider know about any illness before starting or restarting treatment.
Blood clots
Zenbexus can increase the risk of blood clots forming in your veins (deep vein thrombosis, pulmonary embolism) or affecting blood flow to your heart or brain (heart attack, stroke). In the clinical study, this happened despite most people also receiving preventive blood-thinning medicine, so your health care provider will likely prescribe one for you too.
Stay alert for the following symptoms, and make sure the people close to you know these symptoms as well:
- Swelling, pain, tenderness, or discoloration in your leg
- Sudden shortness of breath
- Chest pain that may spread to your arm, neck, jaw, back, or stomach
- Sudden numbness or weakness in your face, arm, or leg, especially on one side
- Sudden severe headache, confusion, dizziness, or trouble with vision, speech, or balance
If you notice any of these symptoms, seek medical care right away or call 911.
Your health care provider will also try to help you manage other things that raise clotting risk, such as high cholesterol, high blood pressure, and smoking, while you’re on Zenbexus.
Risk of birth defects and the Zenbexus REMS Program
Zenbexus can cause severe birth defects or pregnancy loss if taken during pregnancy, and it should not be used in pregnancy. Because of this risk, Zenbexus is only available through a restricted program called the Zenbexus Risk Evaluation and Mitigation Strategy (REMS). If you can become pregnant or can get someone else pregnant:
- You’ll need two negative pregnancy tests before starting. Then, repeat testing weekly for the first four weeks and every two to four weeks after that.
- If you can become pregnant, you must use two effective forms of birth control, starting at least four weeks before your first dose, continuing through any breaks in treatment, and for at least four weeks after your last dose. This applies even if you have a history of infertility, unless you’ve had a hysterectomy.
- If you can get someone pregnant, you must always use a latex or synthetic condom during sex while you are taking Zenbexus and for at least four weeks after your last dose. This applies even if you have had a vasectomy because Zenbexus may pass into semen.
- You shouldn’t donate blood, eggs, or sperm while taking Zenbexus or for four weeks afterward.
- Stop taking Zenbexus and call your health care provider right away if you become pregnant, miss a period, have unusual bleeding, or think of any reason you might be pregnant. If your provider isn’t reachable, call the REMS call center at 888-423-5436.
Don’t breastfeed during Zenbexus treatment because it’s not known whether the medicine passes into breast milk.
New cancers
A small number of people in the clinical study developed a new, unrelated cancer while on Zenbexus (about 7 in 100, compared with about 5 in 100 on the comparison treatment). Your health care provider will monitor you for this over time, including with routine exams and any screening tests appropriate for your age and health history. Tell them about any new lumps, unusual bleeding, unexplained weight loss, or other symptoms that concern you.
Low antibody levels (hypogammaglobulinemia)
About 1 in 4 people taking Zenbexus may have lower-than-normal levels of antibodies, proteins your immune system uses to fight infection. This is one reason Zenbexus carries an added infection risk beyond what neutropenia alone would explain. There often aren’t obvious symptoms, so your health care provider may check your antibody levels periodically, especially if you’re getting frequent infections. If your levels drop significantly, they may recommend preventive antibiotics or, in some cases, antibody replacement therapy.
Fatigue
Fatigue, including feeling tired or weak, is common with Zenbexus and may improve somewhat as your body adjusts. To help support your energy:
- Get plenty of sleep, and try to keep a consistent sleep schedule.
- Include protein- and nutrient-rich foods at meals.
- Stay lightly active if your health care provider says it’s safe. Long periods of inactivity can actually make fatigue worse.
- Plan demanding activities for times of day when your energy tends to be highest.
- Talk to your health care provider if fatigue is severe or doesn’t improve. Since fatigue can also be a sign of anemia or low blood counts, they may want to check your labs.
Diarrhea and constipation
Both diarrhea and constipation are common with Zenbexus, and it’s possible to have either one.
For diarrhea:
- Choose bland foods, such as rice, bananas, or toast.
- Avoid greasy, spicy, or high-fiber foods and caffeine and alcohol, until diarrhea improves.
- Drink fluids often (water, broth, or an electrolyte drink) to avoid dehydration.
- Ask your health care provider whether an over-the-counter (OTC) antidiarrheal medicine is appropriate for you.
For constipation:
- Drink plenty of fluids, and stay as active as you can.
- Gradually add fiber-rich foods, such as fruits, vegetables, and whole grains.
- Ask your health care provider about an OTC stool softener, laxative, or fiber supplement that you can use.
Contact your health care provider if either symptom is severe, doesn’t improve, or comes with a fever, blood in your stool, or significant stomach pain.
Nerve and muscle symptoms
Zenbexus can cause muscle-related symptoms (weakness, muscle spasms,or gait or balance problems) as well as nerve-related sensory changes (numbness, tingling, or pain in the hands or feet). Nerve-related changes are reported less often with Zenbexus than with some other multiple myeloma regimens that include bortezomib.
- Tell your health care provider about any new numbness, tingling, weakness, or balance changes because these may need dose adjustments to prevent them from getting worse.
- Use handrails, and take precautions to prevent falls if you notice balance or gait changes.
- Wear supportive, well-fitting shoes if you have numbness or tingling in your feet.
Sleep problems
Insomnia, restless legs syndrome, and other sleep disturbances can happen with Zenbexus. To support better sleep:
- Keep a consistent sleep and wake schedule.
- Avoid caffeine and heavy meals close to bedtime.
- Create a calming bedtime routine and a dark, cool sleeping environment.
- Talk to your health care provider if sleep problems persist. They can check whether another cause (such as anxiety or a medicine interaction) is contributing, and discuss options that may help.
Rash
Skin rash is a common Zenbexus side effect. Mild rashes often improve with basic skin care:
- Use fragrance-free, gentle moisturizers.
- Avoid hot showers and harsh soaps because they can worsen skin irritation.
- Wear loose, breathable clothing over affected areas.
Contact your health care provider right away if a rash spreads quickly, blisters, involves your mouth or eyes, or comes with fever, as these can be signs of a more serious reaction that needs prompt evaluation.
Tell your health care provider about any side effect (whether or not it’s listed here), especially if it is severe or doesn’t go away.
Zenbexus Drug Interactions
A drug interaction happens when another medicine, supplement, or substance changes how well Zenbexus works or raises the risk of side effects. Zenbexus is broken down in your body mainly by a liver enzyme called CYP3A. Other medicines that affect this enzyme can change how much Zenbexus stays in your bloodstream. You can also check your specific medicines using WebMD’s interaction checker.
This isn’t a full list of every possible interaction. Always give your health care provider and pharmacist a complete list of everything you take, including prescription medicines, over-the-counter products, vitamins, and herbal supplements.
Medicines that can raise Zenbexus levels
Some medicines, known as strong or moderate CYP3A inhibitors, can slow down how your body breaks down Zenbexus. This can raise the amount of Zenbexus in your body and increase the risk of side effects.
Examples include:
- Itraconazole, an antifungal medicine (a strong CYP3A inhibitor; in a study, it roughly doubled the amount of Zenbexus in the body)
- Fluconazole, another antifungal medicine (a moderate CYP3A inhibitor)
- Diltiazem, a blood pressure and heart medicine (a moderate CYP3A inhibitor)
Your health care provider will generally try to avoid combining Zenbexus with these medicines. If the combination can’t be avoided, they may lower your Zenbexus dose or change how often you take it, to help offset the interaction. Don’t change your Zenbexus dose or schedule on your own; let your health care provider make that call and guide any switch.
Medicines that can lower Zenbexus levels
Other medicines, known as strong or moderate CYP3A inducers, can speed up how your body clears Zenbexus. This can lower the amount of Zenbexus in your body and make it not work as well against your cancer.
Examples include:
- Rifampin, an antibiotic used for infections such as tuberculosis (a strong CYP3A inducer)
- Efavirenz, a medicine used to treat HIV (a moderate CYP3A inducer)
The herbal supplement St. John’s wort is also a well-known CYP3A inducer, so it could reduce how well Zenbexus works. Tell your health care provider before starting St. John’s wort or any other herbal supplement while taking Zenbexus.
Your health care provider will generally recommend avoiding these medicines while you’re on Zenbexus. If a combination truly can’t be avoided, don’t adjust your Zenbexus dose yourself; work with your health care provider on the safest plan.
FAQs: Zenbexus interactions
Does Zenbexus interact with alcohol?
The Zenbexus prescribing information doesn’t list a specific interaction with alcohol. Still, ask your health care provider whether drinking alcohol is a good idea for you during treatment. Alcohol can add to fatigue, dehydration risk from diarrhea, and general strain on your body while you’re being treated for cancer.
Does Zenbexus interact with food?
No. Studies found no meaningful difference in how Zenbexus is absorbed whether it’s taken with or without food, so you can take it either way.
Reducing Your Risk
- Tell your pharmacist and other health care providers about every medicine, supplement, and vitamin you take before you start Zenbexus and any time something changes.
- Ask before starting or stopping any medicine, including over-the-counter products, while on Zenbexus.
- Keep every scheduled blood test and monitoring appointment; many Zenbexus side effects are caught early through lab tests rather than symptoms.
- Report new or worsening symptoms promptly instead of waiting for your next visit.
Your health care provider can adjust your treatment plan (including your Zenbexus dose or schedule), as needed, based on how you respond. Never change or stop Zenbexus on your own without talking to your health care provider first.
