How dexamethasone works
A steroid is a type of hormone. Steroidal hormones are produced by the body, and the synthetic analogues (equivalents) of some steroids can be manufactured in a laboratory. Dexamethasone is a synthetic steroid that has multiple effects and is used for many conditions, including myeloma. Dexamethasone is a synthetic adrenocortical steroid. In the body, adrenocortical steroids are produced naturally by the adrenal glands and are also known as glucocorticosteroids or corticosteroids. These compounds will be referred to as “steroids” throughout this booklet.
Adrenal glands produce both hormones and steroids. These steroids influence many actions of the body’s systems. They are involved in regulation of carbohydrates, proteins, and fats. They also inhibit inflammatory, allergic, and normal immune responses. Synthetic versions of steroids can imitate the actions of the naturally occurring compounds, or replace them in conditions that are associated with insufficient production of much-needed steroids that are normally produced by the adrenal glands.
Dexamethasone is used to treat a wide variety of medical conditions in addition to myeloma and other hematologic malignancies. Steroids are generally additive or synergistic with other treatments. Steroids as a component of treatment for myeloma may also help improve other conditions, such as the following:
¡ Endocrine disorders,
¡ Rheumatic or collagen disorders,
¡ Dermatologic diseases,
¡ Allergic states,
¡ Ophthalmic (eye) diseases,
¡ Gastrointestinal (GI) diseases,
¡ Respiratory diseases,
¡ Hematologic disorders.
Dexamethasone and other steroids suppress certain actions of the immune system and also inhibit cytokines, which control inflammation. Dexamethasone decreases inflammation by stopping white blood cells (WBC), which normally fight infection, from traveling to areas of the body where there is swelling. Dexamethasone’s anti-inflammatory actions can stop the swelling around tumors and the pain caused by tumors pressing on nerve endings. Dexamethasone can also alter normal immune system responses and is therefore useful in the treatment of conditions that affect the immune system.
Dexamethasone has demonstrated activity in myeloma as a single agent but it is typically given in combination with one or more other agents as it appears to increase the ability of other drugs to destroy myeloma cells.
How dexamethasone is given
Dexamethasone is available in many forms. To treat myeloma, dexamethasone can be given as either an oral tablet or as an intravenous (IV) infusion, alone or in combination with other agents. Dexamethasone can irritate the stomach; taking it with food can reduce the chances of this happening.
Steroid therapy cannot be stopped abruptly as such discontinuation can lead to withdrawal symptoms. If steroid therapy must be discontinued, it must be done gradually and under the supervision of your myeloma doctor.
Dosages and scheduling of dexamethasone
Many factors are taken into consideration by your myeloma doctor when determining your overall treatment strategy. Ideally, the dose of your medication and how it is administered is not only appropriate for the treatment of your individual myeloma but also well tolerated by you.
Steroids are associated with many short-term and long-term side effects. In an effort to reduce the side effects experienced by patients, there have been many clinical trials investigating the use of low-dose dexamethasone, establishing this approach as the standard of care in myeloma.
Currently, depending upon the age and fitness or frailty of the myeloma patient, dexamethasone is usually prescribed at a dose of 20 mg to 40 mg once-weekly. For patients who cannot tolerate these doses, dexamethasone has proven to be effective at doses as low as 4 mg once-weekly.
Clinical trial experience with dexamethasone
A clinical trial is a medical research study with people who volunteer to test scientific approaches to a new treatment or a new combination therapy. Each clinical trial is designed to find better ways to prevent, detect, diagnose, or treat cancer and to answer scientific questions.
Historically, dexamethasone doses used to be as high as 40 mg for 4 days per week. Then the ECOG E4A03 clinical trial demonstrated increased mortality at this dexamethasone dosing when compared with 40 mg once-weekly dexamethasone dosing. In addition, the recent increase in the number of effective anti-myeloma therapies and the growing use of effective quadruplet (4-drug) induction therapy regimens raised the question to what extent dexamethasone is necessary to treat myeloma.
Patients with myeloma are now living longer than ever, and it is important to minimize treatment toxicities. Possible steroid toxicities include insomnia, heartburn, edema, psychiatric disturbances, muscle weakness,
hyperglycemia, and diabetic complications. There is a need to better identify which myeloma patients may benefit from dexamethasone dose reduction. National Comprehensive Cancer Network (NCCN) guidelines recommend limiting steroid use to the lowest possible effective dose in older adults but do not provide specific recommendations on how to determine that dose.
Secondary SWOG analysis
In January 2025, the journal Blood published a secondary analysis by Dr. Banerjee et al. of pooled data from two completed clinical trials by the SWOG Cancer Research Network, known as SO777 and S1211. Data from both studies showed that dexamethasone dose reductions did not have a negative impact on outcomes in patients with newly diagnosed multiple myeloma (NDMM). There was no significant change to progression-free survival (PFS) and overall survival (OS) after induction therapy.
The same edition of Blood included a commentary on the secondary analysis, concluding that dexamethasone-sparing strategies can reduce steroid-induced toxicity and help patients to continue their long-term myeloma treatment with improved quality of life. Although the exact dosing and role of dexamethasone in the treatment of myeloma still needs to be clearly defined, the secondary analysis suggests that further reduction of dexamethasone toxicity is possible.
This secondary analysis adds to the growing evidence that limiting dexamethasone exposure may be possible without adversely affecting treatment outcomes. Less than a third of patients on stringently controlled clinical trials could tolerate full-dose dexamethasone, while also showing that dexamethasone dose reductions were not associated with decreased PFS or OS.
Rd regimen vs. DR regimen
In December 2022, at the annual meeting of the American Society of Hematology (ASH), the efficacy and safety analysis of the IFM2017-03 phase III clinical trial became a point of interest for its limited use of dexamethasone in frail or elderly patients with newly diagnosed myeloma. The Rd regimen was compared to a combination of Darzalex® (daratumumab) + Revlimid [DR], in which patients received only 2 months of dexamethasone. The DR regimen had deeper responses, with an overall response rate (ORR) of 96% and a complete response (CR) rate of 37%. The Rd regimen had an ORR of 85% and a CR of 10%.
Rd-R regimen vs. continuous Rd
In 2021, the journal Blood published the results of a clinical trial designed specifically for treatment of older and less fit patients with myeloma, a group usually excluded from clinical trials. Newly diagnosed patients who
were 65–80 years old and who were “intermediate-fit” on the International Myeloma Working Group (IMWG) frailty score were randomized to receive 9 months of Rd followed by maintenance therapy of Revlimid (without dexamethasone) at 10 mg per day [Rd-R] or to a study arm that received continuous Rd.
Side effects were mainly related to dexamethasone and were more frequent with continuous Rd. After 9 cycles of Rd, switching to reduced-dose Revlimid maintenance therapy without dexamethasone was feasible, with similar outcomes to standard continuous Rd.
Possible side effects of dexamethasone
Dexamethasone can cause side effects. Few patients experience all of the possible side effects described in this section. Some patients do not experience any side effects at all while taking dexamethasone.
You and your doctor can take precautionary measures in order to reduce or avoid side effects. The most important precautions are described in this booklet, and your doctor can provide greater detail about these and other possible side effects and make recommendations about their management.
The longer you take a steroid, and the higher the dose, the greater your chances of experiencing side effects, but most side effects will go away when treatment is completed. Alert your doctor if you are experiencing side effects or if you notice changes in your health.
Do not stop taking any of your medications or reduce your doses on your own. Discuss your concerns with the doctor who is treating your myeloma.
Infections
Dexamethasone is a component of nearly all combination therapies used in myeloma. Any drug that suppresses normal immune responses can make you susceptible to infections, and patients who are taking dexamethasone or other steroids have an increased risk of all types of infections (bacterial, viral, or fungal).
Steroids block white blood cells from reaching sites of infection, and may cause existing infections to get worse or allow new infections to begin. Steroids can mask signs that an infection is present and may also decrease your immune system’s ability to fight the start of a new infection.
Prevention and treatment of infections
Generally, steroids should not be administered to a patient who has a known infection. Nevertheless, there are some situations in which steroids may be important or necessary during the time that an active infection is
being treated appropriately. For example, steroids are useful in the treatment of septic shock, an infection that involves the whole body, and in treating any serious infection that causes a major inflammatory response and/or tissue destruction.
You must tell your doctor as soon as possible if you have been exposed to any infectious illnesses, or if you have any signs or symptoms of an infection. In addition, your doctor must know your entire vaccination history to date. Also, make sure to wash your hands frequently, especially after being in public places.
Cardiac conditions and fluid retention
Use of dexamethasone and other steroids can cause increases in blood pressure, salt and water retention, and potassium and calcium excretion. These changes are more likely to occur when steroids are taken in large doses. Salt retention may lead to edema or swelling. You may notice that your ankles and feet are swollen. Fluid retention and loss of potassium can be a problem for patients who have cardiac conditions, especially congestive heart failure and hypertension.
Prevention and treatment of cardiac conditions and fluid retention
Discuss with your doctor if changes to your diet may be needed, such as restricting your salt intake or replacing the potassium and calcium that you may be losing. Consult with your healthcare team to make sure that you are eating the right foods.
Dermatologic effects
Patients taking dexamethasone or other steroids may notice that it takes longer than usual for wounds to heal. Patients may develop acne and rashes while taking dexamethasone. Increased sweating is seen in some patients during steroid therapy.
Prevention and treatment of dermatologic conditions
Proper hygiene is important. If your dermis (skin) is injured, administer first aid and contact your healthcare team.
Endocrine effects
Steroids, including dexamethasone, may interfere with the way patients metabolize carbohydrates and can cause blood glucose levels to rise. This is especially important in patients who have diabetes. Patients with diabetes can take steroids, but additional treatment, including insulin therapy, may be needed to control blood sugar levels. Steroids can also cause menstrual irregularities.
Prevention and treatment of endocrine effects
Patients with diabetes may need to monitor their blood glucose levels more frequently. These patients may need to adjust the doses of their insulin or diabetes medications. This decision needs to be made by healthcare professionals and not by patients themselves. If you have diabetes, tell the doctor who is treating your diabetes that you have been prescribed dexamethasone.
Females of childbearing potential, especially those experiencing menstrual irregularities, should take added precautions not to become pregnant while taking dexamethasone, and should speak with their doctor about the potential effects of steroids on the developing child.
Gastrointestinal (GI) effects
Steroids can have various effects on your GI tract, such as increasing the risk of GI perforations (holes). Therefore, patients who have peptic ulcers, diverticulitis, and ulcerative colitis should use corticosteroids cautiously to minimize the risk of perforation. For these reasons, many physicians automatically recommend antacid therapy of some type for patients taking steroids. Other possible GI side effects seen with dexamethasone therapy are increased or decreased appetite, stomach bloating, nausea, vomiting, hiccups, and heartburn.
Prevention and treatment of gastrointestinal effects
Tell your doctor if you experience any GI side effects while taking dexamethasone and ask for advice on how to manage or avoid these events. To avoid or minimize GI irritation, dexamethasone should be taken with food or after meals. Alcoholic beverages, which may also irritate the stomach, should be avoided while taking dexamethasone. Limiting intake of caffeine-containing foods and drinks (e.g., colas, coffee, tea, and chocolate) may also help. Eating small, frequent meals may decrease nausea. Antacids taken between meals may also be helpful, but should not be taken unless approved by your healthcare team. Treatment for persistent hiccups may require such prescription drugs as baclofen, chlorpromazine, or promethazine.
Musculoskeletal effects
Because steroids decrease calcium absorption and increase its excretion, they affect bones. These effects can lead to pain and osteoporosis in adults. Patients with myeloma who are already subject to severe bone loss and bone pain must be watched carefully and given appropriate supportive care to prevent further bone damage. Patients taking steroids may also experience muscle pains because they may be losing potassium.
Prevention and treatment of musculoskeletal effects
Consult with your doctor before taking any supplements or changing your diet. Do not take any supplements or make changes to your diet on your own. Your doctor may recommend supplements or that you increase your intake of calcium and potassium. The best dietary sources of calcium are dairy products, dark-green leafy vegetables, peas and beans, canned fish such as sardines and salmon, and calcium-fortified juices and cereals. Potassium is available in many fruits and vegetables, leafy greens, beans, nuts, dairy foods, and starchy vegetables.
Many patients with myeloma receive bisphosphonate therapy as treatment for myeloma-related bone disease. Bisphosphonate therapy also combats the negative effects of steroids on bone strength and density. For more information, read the IMF’s publication Understanding Treatment of Myeloma Bone Disease.
Ophthalmologic effects
Prolonged steroid treatment may produce elevated intraocular pressure that could lead to glaucoma, optic nerve damage, eye infections, and cataracts. Cataracts occur commonly in older age and usually take years to develop to the point where surgery is indicated. Steroids can speed up this process. With ongoing steroid treatment, it is not uncommon for myeloma patients to develop mature cataracts requiring surgery. This involves removal of the cataract and implantation of a new lens in the eye, which usually allows for enhanced vision.
Prevention and treatment of ophthalmologic effects
Have your eyes checked regularly. Any change in vision should be reported immediately to your healthcare team.
Psychiatric and neurologic effects
Steroids can also cause irritability, mood swings, personality changes, insomnia, and severe depression. Emotional instability or psychotic tendencies are aggravated and may become worse during steroid therapy. Patients also have reported experiencing headaches and dizziness.
Prevention and treatment of psychiatric and neurologic effects
If you are having problems sleeping, ask your healthcare team if you can adjust the time you take dexamethasone so it doesn’t interfere with your sleep during the night. Taking steroids before going to bed can be very effective in allowing sleep during the night, with increased activity delayed until morning. However, regular sleep medications can be helpful or necessary for some patients.
Do not hesitate to contact your doctor if you are experiencing any mood or personality effects. Your doctor may need to reduce or stop your steroid therapy temporarily or permanently. Do not stop steroid therapy on your own without consulting your doctor.
Care partners should be advised that the patient may be more irritable while receiving steroid therapy. The stresses and pressures of a myeloma diagnosis added to life’s other challenges may lead to psychological overload for the patient as well as for the care partners and family members. A consultation with a counselor can be most helpful. Care partners are encouraged to visit carepartners.myeloma.org for available resources.
Allergic reactions
Allergic and hypersensitivity reactions to steroids are possible in patients who are susceptible or have had allergic reactions to other drugs. Allergic reactions can include difficulty breathing, closing of the throat, swelling of the lips and tongue, and hives. Such allergic reactions to steroids are exceedingly rare.
Prevention and treatment of allergic reactions
Special precaution should be used before administering dexamethasone or any other corticosteroid to patients who have histories of any type of allergic reactions to medications. Be sure to alert your healthcare team if you have a history of allergic responses when given any medication.
General effects
Some patients may experience coughing or hoarseness. Resting the voice can help with this condition.
Use of steroids, including dexamethasone, can cause weight gain.
Prevention and treatment of weight gain
Some weight gain is to be expected during steroid therapy. Dexamethasone has a tendency to increase patients’ appetites. Patients may need to control their caloric intake. Reduced carbohydrate intake is especially helpful during steroid therapy. Let your healthcare team know immediately if there is a sudden, large weight gain (more than 5 pounds over a day or two).
Other corticosteroids used to treat myeloma
In addition to dexamethasone, other corticosteroids are used to treat patients with myeloma. Because these drugs all belong to the glucocorticosteroids class of drugs, they act very similarly and can be used to treat many of the same medical conditions. They behave the same way chemically in the body to treat diseases. Because they are so similar in their mechanisms of action, many of the side effects and associated precautions are the same.
Some of the steroids may be better tolerated than others, depending on the patient and the drug.
The uses, side effects, precautions, and considerations described previously for dexamethasone are relevant for the entire class of corticosteroids and thus pertain to prednisone, prednisolone, and methylprednisolone. Prednisolone is a metabolite of prednisone. Methylprednisolone, although structurally similar, may be less toxic and appears to be associated with less sodium and fluid retention than prednisolone.
Ask your doctor if any steroid other than dexamethasone might be more effective or more appropriate in your particular case.
Possible drug interactions
Interactions are possible with dexamethasone or other steroids and other medications. Patients with myeloma typically need to take a number of medications to treat the disease as well as other medical conditions that also may be present. Chances of drug interactions increase with multiple medications. Below is a partial list of medications or classes of medications that may interact with dexamethasone or other steroids. These interactions may increase or decrease the actions of any of the drugs. It is very important to tell your doctor about all prescription and over-the-counter (OTC) medications, as well as any herbal preparations, vitamins, or minerals that you are taking.
¡ Amphotericin B and diuretics that affect potassium levels (such as amiloride, spironolactone, and triamterene).
¡ Antibiotics (such as erythromycin, clarithromycin, rifampicin, and azithromycin).
¡ Anticoagulant medications (such as warfarin and aspirin).
¡ Barbiturates (such as amobarbital, butalbital, pentobarbital, and secobarbital).
¡ Diabetes medications (e.g., insulin, glibenclamide, and metformin).
¡ Cyclosporine.
¡ Digitalis.
¡ Ephedrine, which is most commonly found in weight-loss products.
¡ Estrogen-containing medications, including oral contraceptives and hormone-replacement therapy products.
¡ Nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, ibuprofen, indomethacin, and naproxen.
¡ Phenytoin.
In closing
This booklet is not meant to replace the advice of your doctors and nurses who are best able to answer questions about your specific healthcare management plan. The IMF intends only to provide you with information that will guide you in discussions with your healthcare team.
To help ensure a good quality of life through effective treatment, you must play an active role in your own medical care. We encourage you to visit myeloma.org for more information and to join the Myeloma Knowledge Platform at myprofile.myeloma.org.
To receive the most up-to-date information about myeloma in a caring and compassionate manner, call the IMF InfoLine at 1.818.487.7455, email InfoLine@myeloma.org, or visit mmsm.link/infoline to schedule a convenient time to talk with an IMF InfoLine Coordinator.
To get answers to your questions without having to wait, ask Myelo® anytime 24/7 at myeloma.org. This generative AI assistant is designed to help you find the right resources.
Use the hyperlinks and web addresses included in this publication for quick access to resources from the IMF. Sign up at subscribe.myeloma.org for our quarterly journal Myeloma Today and weekly e-newsletter Myeloma Minute, as well as alerts about IMF news, events, and actions.
The International Myeloma Foundation (IMF) is the global leader in myeloma. Our mission is to improve the quality of life of myeloma patients while working toward prevention and a cure. Since 1990, the IMF has been serving the myeloma community through the following four pillars:
RESEARCH At the IMF, finding a cure for myeloma is our top priority. The IMF Scientific Advisory Board (SAB) of leading myeloma experts identifies key opportunities to drive research forward. The IMF Black Swan Research Initiative® (BSRI®) is pushing the boundaries with early screening for a precursor condition of myeloma as well as cure-focused myeloma clinical trials. The IMF International Myeloma Working Group (IMWG) provides trusted guidelines for diagnosing, treating, and managing myeloma. We also fund innovative research through the IMF Brian D. Novis Research Grants.
EDUCATION Myeloma is a complex and unique journey for each patient. The IMF offers hundreds of videos and free publications in multiple languages to inform and empower patients and care partners to navigate their myeloma journey. All IMF seminars, webinars, and workshops are free-of-charge and designed to directly connect the patient community with expert myeloma clinicians. The IMF Nurse Leadership Board (NLB) provides recommendations for the management of myeloma. The IMF M-Power Project works to break down barriers and ensure health equity in underserved populations.
SUPPORT Studies show that social support can greatly improve the quality of life of people with cancer. The IMF offers more than 160 myeloma support groups across North America, including specialized groups for Spanish-speakers, people with smoldering myeloma, care partners of patients with myeloma, and patients who do not have care partners. The IMF InfoLine answers myeloma-related questions. Myelo®, the IMF’s generative AI assistant, is available 24/7 to help you find the right resources.
ADVOCACY In the U.S., the IMF Advocacy team represents your interests at the federal and state levels. Internationally, the IMF Global Myeloma Action Network (GMAN) works to improve patient access to treatments.
