All about dexamethasone and other corticosteroids. When we think of myeloma therapy, corticosteroids are one of the cornerstones of multiple myeloma therapy. And dexamethasone is an example of a corticosteroid. You know, admittedly, when we talk about myeloma drugs with our patients, we don't usually give the corticosteroids as much time as they ought to receive because we spend a lot of time talking about drugs like lenalidomide, also known as Revlimid, or Velcade, also known as Fortezumib. But the dexamethasone is really a fundamental drug that we use in multiple myeloma. And oftentimes when, as patients are on their journey with therapy, that's a drug where patients tend to have the most questions about, or that's a drug where we tend to make dose reductions or adjustments of the drugs that we use. It's actually the dexamethasone. And it belongs to the same family of drugs that we think about like prednisone, methylprednisolone. So it's a hormone that's created by the adrenal gland called cortisol. So this is a drug that has been around for decades. And in fact, I think a Nobel Prize was awarded for discovery of these glucocorticoids back in 1950. So it's been around for decades. Are corticosteroids related to anabolic steroids? When I think about glucocorticoids or drugs like dexamethasone, the first question that comes up, it's a steroid and people think this is like anabolic steroids. It's not an anabolic steroid at all. It's considered a glucocorticoid. Anabolic steroids is what you think of as performance enhancing drugs that athletes use to build up muscle. Glucocorticoids, on the other hand, have a different effect. When we think about drugs like dexamethasone or prednisone, we first think about it's used as an anti-inflammatory. Because it's an anti-inflammatory, we think of inflammation, we think of it as being related to the immune system. And because it's related to the immune system, drugs like dexamethasone calm down the immune system. And it also turns out that drugs like dexamethasone actually can kill myeloma cells directly. And that's how it also exerts some of its anti-inflammatory effects. Now myeloma patients, we use the dexamethasone because it actually kills myeloma cells as a single agent, just by itself. What are the side effects of dexamethasone? Just think about the drug that, where it starts from. Which is a hormone that's made by your adrenal gland. Now again, your adrenal gland makes several hormones, including cortisol. And this is a hormone that your body makes, and it has a multitude of effects across your whole body because it's a hormone and it kind of targets all the different organs in different ways. In your body, there's sort of a yin and yang. And it sort of acts as a counterbalance to the effects of other hormones in your body. When I think about what do drugs like dexamethasone do, it's sort of taking cortisol, but it's an even more potent form of cortisol. It has the effects that we want in terms of killing myeloma cells, but it can also have other unintended effects as well. Patients can have like a love-hate relationship with this drug. And it's really hard to know ahead of time when I meet a patient, are they going to love the drug, or are they going to hate it, or are they going to have a love-hate? So some patients, they love dexamethasone because, you know, it's an anti-inflammatory. And for some patients, if you have a lot of aches, they're going to have a lot of pain or a lot of aches or other pains that are related to myeloma or from inflammation in general, like a lot of it just melts away for some patients. Like they feel really achy or they have a lot of bony aches. And when they take the dexamethasone, a lot of those aches can disappear. And some patients, they also feel they have a lot of energy. It really revs up their energy. And a lot of patients tell me that they have chores or tasks that they don't want to do. For some reason, when they take it, they just love doing these tasks and chores all day. Some patients actually would like to be on more dexamethasone than is recommended because of how well it makes them feel. They feel like they can get through the day. It's almost like having a cup of coffee and then some. But then there's also, like it's a double-edged sword in the sense that some patients, when they take dexamethasone, the insomnia, trouble sleeping is like a number one complaint. Like patients, many patients have a lot of trouble sleeping at night because of it. There's so many different ways of approaching that. Timing of the deck is one factor. But beyond that, infrequently, we do use medications to help manage the insomnia. Sometimes some patients, they like over-the-counter diphenhydramine or Benadryl can be used to treat insomnia. And other patients, we do use stronger medications and they can run the gamut. Some patients, they prefer drugs like Ambien. Other patients, they might prefer drugs like Lorazepam. It's really individualized and some patients really prefer one versus the other. They prefer melatonin, for example. I should have mentioned melatonin in terms of over-the-counter things. There's like diaphenhydramine, there's melatonin. And this is probably going off topic a little bit, but some patients might use marijuana or something. There are different ways and I think at the end of the day for me, whatever works best for the patient is fine with me. It can also cause mood changes. So a lot of times, their partner or significant other, family member will say, oh, their mood is awful on the medication. It also can lead to fatigue when you're not on the medication. Some patients, they feel great on the day or two of the treatment. Some patients are expecting that to not feel well on the days of the treatment, but because they're getting dexamethasone, they actually feel okay on the day of the treatment. But then on the days when they're not on treatment, it can be like a valley where they can have a lot of fatigue on the off period of the dexamethasone. The dexamethasone can also stimulate appetite and cause a significant amount of weight gain in some patients over time. In some patients, the dexamethasone can also really affect your blood sugars as well. As you get older, your ability to control your glucose is affected. In some patients that can evolve into, for example, type 2 diabetes, where some patients are on medications like oral medications or injectable medications or insulin to keep their glucose in better range. When patients start myeloma therapy and the regimens include dexamethasone, the dexamethasone can really affect that delicate balance with your blood glucose control. For some patients, it's just a matter of we just observe. It's sort of a very transient thing where we can see that their blood glucose has become elevated, but during the rest of the week, they're not as elevated. And it really revolves around the day of the dexamethasone. Now for some patients, if they're already on oral medications or they're on insulin, that might require some adjustment. This is where we engage the primary care doctor or the endocrinologist for assistance in managing their blood sugars. I think there's a big range in terms of some patients that weren't on insulin. Some patients occasionally end up starting the medication like insulin. And oftentimes we coordinate with the primary care doctor or their end or an endocrinologist for help in managing their blood sugars. Are there certain foods to avoid when taking dexamethasone? For blood glucose control, diet is important as a general overarching statement in terms of for blood sugars or just in terms of just day to day living. Diet is important for that. But when it comes to the dexamethasone and your blood sugars, I think the dexamethasone is such an overpowering factor that it would be really difficult to make a complete dietary modification to manage that risk. So I think there's only so much you can do. So I don't necessarily make a strong argument saying you should radically change your diet, like avoid all carbs or something like that to deal with the effects of the dexamethasone and the blood sugars. Occasionally some patients can experience blurry vision, which could be related to the dexamethasone. How that happens is somewhat complicated. In some patients where there are big changes in their glucose, that can cause shifts in the concentrations of the glucose in your eye with respect to the lens, and that could lead to blurring of the vision. But thankfully that's a transient phenomenon and it's not necessarily a long term issue. My sense is it's related to the glucose. There could be other reasons for blurry vision beyond cataracts and beyond the fluid shifts that I mentioned. So if you do have blurry vision, I think it would be advisable to see an ophthalmologist to evaluate for other possible causes of blurry vision, because it could be related to the retina, glaucoma, etc. Longer term corticosteroids can have effects on cataracts, so that's one possible, and it can also decrease muscle mass. Also longer term it can also have effects on your immune system as well. It can have some effects where it can increase your risk for certain infections as well. In multiple myeloma, the way we use glucocorticoids is a little bit different than how we use it in other settings. So for example, in some patients who see rheumatologists who have autoimmune conditions where they take a corticosteroid every day of the week, I think that's different than when in multiple myeloma we take it for a few days or one day of the week. And I think that has different effects in terms of side effects as well as perhaps risk for infection. One side effect that is also important to note is that dexamethasone can also cause fluid retention. When it causes fluid retention, some patients can experience a lot of swelling, for example in the feet and the ankles as one potential side effect of the dexamethasone. And so in some patients where that happens, that can be managed with keeping the legs elevated. Some patients use compression stockings. Some patients might use a diuretic. And in other patients we might lower the dose of the dexamethasone. The side effects with dexamethasone can be so variable. Steroids can affect your GI tract. GI side effects seen with dexamethasone therapy include heartburn, stomach bloating, nausea, vomiting, and hiccups. Dexamethasone can also cause GI perforations. Taking dexamethasone with food or after meals will help minimize these GI side effects. Also eliminating other foods and beverages, including alcohol, that irritate the stomach will help resolve some of the GI side effects associated with dexamethasone. Eating smaller, more frequent meals may also help. Also, many physicians recommend anti-acid therapy of some type for patients taking steroids. Treatment for persistent hiccups may require such prescription drugs as baclofen, chlorprosamine, or promethazine. Other side effects include bone loss, osteoporosis, glaucoma, increased hair growth, acne, and thinning of the skin. These side effects are more likely when these medications are taken in larger doses or for a long time. Patients also have reported experiencing headaches and dizziness. Serious but rare side effects include difficulty breathing, closing of the throat, swelling of the lips, tongue, or face, and rash. If any of these side effects occur, call your healthcare provider right away. How are glucocorticoids such as dexamethasone used in myeloma treatment? When we think about using corticosteroids like dexamethasone from myeloma therapy, there's several components to that. Number one is it does have anti-myeloma effect in and of itself. So one, it works by itself as a single agent, which is important in myeloma therapy. And then number two is that it actually adds to the effect of other drugs in combination. So a consistent theme that we see in myeloma therapies is that the dexamethasone can have a synergistic and or an additive effect to almost any drug that we use in multiple myelomas. So we can see added effects when you combine it with revlimid, Velcade, pomalidomide, Delisk goes on and on. Dexamethasone is also used to help prevent infusion reactions too. For some of our treatments that we give in the infusion unit, there can be risk of having a reaction to the infusion itself. And that's more typical with monoclonal antibodies. Daratumumab, elotuzumab, isotuxumab, those types of therapies, the dexamethasone can help because it's an anti-inflammatory, it can help prevent an infusion reaction. But it's almost like having an asthma type reaction where patients can get wheezy and shorter breaths. So the dexamethasone when it's given ahead of time can help minimize those reactions. And when patients can have nausea, for example, dexamethasone can be used as an anti-emetic. Most of our therapies in multiple myeloma thankfully are not associated with nausea compared to the other therapies that are used in other cancer therapies. Dexamethasone can also be really useful for treating bone-related pain complaints or just pain complaints in general. A, because it works as an anti-inflammatory as well as its anti-myeloma effects. When used to kill myeloma, is it used alone or in combination with other myeloma killing agents? What does synergy mean? So I mentioned how the dexamethasone is a sort of fundamental component in many therapies because it synergizes with the other components, the other partners in that regimen. So synergy means that the total is more than the sum of its parts. So it's more than just adding A plus B. The effect you get is over and beyond A and B. And there are so many examples in myeloma therapy where you see this over and over again. What is the mode of administration of dexamethasone? There's several ways you can give dexamethasone. It's either intravenously or you can take it on your own as a pill. And a lot of times it depends on the regimen. It's a four-medicine pill, but I'm also aware that there's a newer formulation where it can come in 10 and 20-milligram pills. But generally speaking, when I think of dexamethasone, I usually think of a medication they can pick up from the pharmacy. When should dexamethasone be taken? Patients typically take it in the morning. Now either they take it in the morning before their scheduled infusion appointment or they just take it in the morning as part of their overall therapy. And the reason for that is because of its effects on sleep. Really, there is the occasional patient who may prefer to take it in the evening, actually. I would defer to the doctor, the nurse, the nurse practitioner, who may have a particular recommendation on when to take it. Cortisol is an adrenocorticoid produced each day by the adrenal gland. It is essential to life and is a major factor in controlling our reaction to stress and significantly affects our mood, energy, digestion, immune system, and emotions. The adrenal gland, like many others in the body, is controlled by the pituitary master which constantly monitors body hormone levels, regulates glandular activity, and controls adrenal hormone production. Dexamethasone is chemically similar to cortisol. If you take a high dose of dexamethasone at bedtime, there is still a significant level of dexamethasone in your blood in the morning. When the pituitary discovers that there is plenty of steroid in the blood, it decreases ACTH production. This tells the adrenal gland to not produce any cortisol on the morning following an evening dex binge. How is dexamethasone usually dosed? The dosing of dexamethasone has evolved over the years. Now currently a lot of the contemporary regimens that we use, dexamethasone on average is given about 40 milligrams once a week. That's as a general starting point. There can be a lot of variability in how the dosing is given. So just take that with a grain of salt. Conventionally, 40 milligrams once a week is one starting point. For some regimens, we split the dose of the 40 milligrams over two days. So sometimes if their starting cycle was on a Monday, they could take 20 milligrams on Monday and then 20 milligrams on Tuesday and then repeat on a weekly basis. And there may be some modifications on that based on the actual regimen in terms of is it being used to prevent an infusion reaction. So that's sort of a starting point. Now there are other regimens, for example, like a traditional 21-day cycle of RVD, for example, the dexamethasone is like 20 milligrams a day of the Velcade and 20 milligrams a day after. So you can see there are some modifications with that. For some regimens, for patients who are 75 and older, the dosing of dexamethasone is further reduced where it's 20 milligrams once a week instead of 40 milligrams a week. Dose reductions in dexamethasone are very common. When I think about myeloma therapy, I'm thinking we're in this together for the long haul. And we want to hear about how you're feeling on therapy. Patients are treated for long periods of time. We want to make sure that they're comfortable with the treatment that they're on. So I think it's important that patients establish that communication with their team early on. And that particularly comes with the dexamethasone. So frequently we may make a dose reduction, say if they're taking 20 milligrams, that might be reduced to 12 milligrams or 8 milligrams. There are so many different ways that this can be reduced. Is dexamethasone used as part of maintenance therapy? When I think about myeloma therapy, there's usually a couple of phases of treatment. Usually there's the initial phase of treatment, which is pretty intensive and which typically includes dexamethasone. And then there's the maintenance phase of treatment, where after you've achieved a response, the goal is to maintain the response. And typically for many of the current regimens that we use for maintenance therapy, dexamethasone is not typically part of the maintenance treatment. Should a prophylactic antibiotic be taken while on dexamethasone? As a general statement, corticosteroids can have some immune-suppressive effects. And that typically applies to when you're taking corticosteroids every day at a higher dose. And there is a concern for increasing the risk for infection with a certain type of bacteria that we call pneumocystis. There are some practices where patients may take a medication like Bactrim, also known as trimethoprim sulfamethoxazole, to help prevent this infection with pneumocystis. You do being on corticosteroids for long term. But I do want to acknowledge that there is a lot of variability in practice. I don't think there's a right answer with that. Why is it important to not stop steroid use abruptly? When someone's taking dexamethasone as part of their regimen, do you have to taper off of it? And that's a common question. And I understand where that question is coming from. Because there are, in other parts of medicine, for other conditions, patients can be on corticosteroids that they take every day as part of their treatment for an inflammatory condition. And so for patients who take, say, prednisone every day at a certain dose, and they've been doing it for several weeks, the patient's body becomes used to the prednisone being around because the prednisone sort of replaces the hormone that normally the body would normally make. And for those patients where the body becomes used to the prednisone being around every day, taper is sometimes recommended because stopping altogether, your body would not be used to just having the prednisone taken away all of a sudden. Now in myeloma therapies, that is less of an issue because the way the dexamethasone is given, there's already a built-in break. So if you're taking it for two out of seven days or one out of seven days, there's already that break. So you could discontinue it without necessarily having to taper off of it. What is the difference between dexamethasone and prednisone? So in corticosteroids, there are so many different kinds of corticosteroids. Prednisone, there's metha-prednisolone, and then there's dexamethasone. And I think I've said the word dexamethasone like a hundred times already. I've said it so many times. The way they differ is that it differs in terms of potency. One milligram of dexamethasone is about equivalent to five milligrams of prednisone. So the dexamethasone is more potent than prednisone. When people think about corticosteroids, they have different glucocorticoid and different mineralocorticoid activities. So people think of dexamethasone as having pure glucocorticoid activity. And the way they are interchangeable to some extent, but so some of the reasons why we use dexamethasone has to do with clinical trials. A lot of the clinical trials use dexamethasone, so some of it's just related to historical practice. There are some trials which have compared dexamethasone to prednisone directly. In some of those trials, they showed that dexamethasone had a higher response rate than, for example, the prednisone. There are occasional patients who, for some reason, they don't tolerate the dexamethasone. Because occasionally, some patients, it really affects their mood to the point where they have trouble functioning. There's an occasional patient where instead of dexamethasone, we'll use a different corticosteroid like methaprednisolone, which is also known as sodium medrol, or prednisone. So there is an occasional patient where we would make a substitution. So the question comes, will there be a future where you don't need to have dexamethasone? I think we would all love a future where you don't need drugs like dexamethasone. Dexamethasone is kind of a… it's not like the cleanest drug in the world where it has great benefits, but there's also a lot of side effects associated with it. In the beginning, when patients are first diagnosed, the dexamethasone really does play a role in terms of when patients have a lot of symptoms where you want that response. If patients are not feeling well and do the myeloma, I think you want to put all… you want to do a full-court press. And I think the dexamethasone is important as part of the full-court press to kind of get them over the hump. Now over time, once your disease is responding well, you don't really need the dexamethasone as much. So I can see situations where once you're over the hump and where you're in the maintenance phase of treatment, you know, the dose in the dexamethasone can be peeled back. You know, there have been trials actually looking at maintenance therapy where they combined… they looked at, you know, linalytomyte versus linalytomyte plus dexamethasone in older individuals. And they found that the patients in the Revlimid alone arm did better. So I think certainly when you're on a regimen… if you're going to be on a regimen longer term, you know, the role of the dexamethasone becomes less and less.