Speaker 1 00:00 Hi. Welcome to Rosalind Franklin University College of Pharmacy top 200 drugs podcast. Speaker 2 00:12 This podcast is produced by the pharmacy faculty members to supplement study material for students learning the top 200 drugs we're hoping that our real life clinical pearls and discussions from practicing pharmacists will help you study for your next drug quiz. Speaker 1 00:29 No participants have any conflicts of interest to disclose. This podcast is for educational purposes only and is not intended to treat a particular patient. This information should not be used in lieu of the judgment of a health care provider. Dr. Sean Kane 00:41 This podcast is copyright Rosalind Franklin University of Medicine and Science, and now on to the show. Welcome to Week 11 of Rosalind Franklin University's top 200 drugs podcast. I'm your co host, Dr Unknown Speaker 00:54 King, I'm Dr. Mitchner, Unknown Speaker 00:56 Dr. Holmes. I'm Dr. Weatherton, Dr. Sean Kane 00:58 and I'm Dr. Patel. So this week, we're talking about agents that are used to treat osteoporosis. The first agent is calcitonin. The brand name is Miacalcin, Speaker 3 01:07 Dr. Patel. I understand this product comes from an interesting source. Is that correct? Unknown Speaker 01:12 That is correct? Actually, it is derived from salmon. Dr. Sean Kane 01:15 So I've heard that actually the salmon, the salmon, calcitonin, is actually more potent than the human version. Is that correct? Yes, in fact, it is interesting. So what do we what do we use calcitonin for? Speaker 4 01:26 We use Miacalcin for Paget's disease, hypercalcemia and osteoporosis. Dr. Sean Kane 01:31 And I've never heard of Paget's disease. What is it? Speaker 4 01:35 So Paget's disease is excessive breakdown of the formation of bone. Speaker 3 01:39 All right? Dr. Mitchener, is Miacalcin or calcitonin a very good drug for osteoporosis, Speaker 5 01:45 not so much. It's has marginal efficacy, but it is very costly. I can tell you that much from a hospital Dr. Sean Kane 01:51 standpoint, how does calcitonin or Miacalcin come Speaker 6 01:54 so calcitonin is basically a protein that's derived or secreted by the thyroid gland. So it's a protein. So you can imagine we can't pack it in a pill form. So it is available as nasal spray and IM injection. So Dr, Brotherton, can you tell us a little bit about how this protein works in the body? Speaker 3 02:13 It's sort of Miacalcin, or calcitonin, is a counterbalance to parathyroid hormone. So calcitonin job is to sort of keep calcium low in the blood, and it does that by inhibiting osteoclasts. You guys know what osteoclasts are, right? Sure do lasts. Speaker 5 02:30 They'll build the bone, and clasts consume the bone. So B build, C consume and Speaker 3 02:36 so if we're inhibiting osteoclasts, we can expect less bone loss, is that correct? Unknown Speaker 02:41 Sure is so. Dr. Sean Kane 02:43 Because it's derived from salmon, I would imagine that there are certain patient populations that we probably can't use calcitonin or Miacalcin. Unknown Speaker 02:50 That is correct. Ding, ding, ding, fish allergies. Dr. Sean Kane 02:53 So any patient with a fish allergy, because of the way it's produced, can't take calcitonin or Miacalcin. Speaker 3 02:59 This is, however, the agent of choice for bears with osteoporosis. Dr. Sean Kane 03:03 So what are some adverse effects that we see from calcitonin? Well, we Speaker 3 03:07 said that calcitonin keeps calcium out of the blood, so I imagine we can see hypocalcemia that can be severe. Is that correct? Dr. Patel, Speaker 6 03:16 yes, that definitely is true. It causes a drop in calcium, which can eventually lead to tetany. Speaker 4 03:22 And remember, the product is an intranasal formulation. So we can see with the nasal spray, rhinitis or ulceration of the nasal mucosa Speaker 3 03:30 also a very rare side effect. But one that you may possibly warn your patients about is nocturia, which has been reported with this agent. And what is nocturia? Dr. Weatherton, I believe it's a technical term for wetting the bed. Oh, don't want that. So as Dr. Sean Kane 03:46 far as patient education goes, obviously it's a nasal spray. But an interesting fact about the nasal spray is that you only squirt it in one nostril, and then every other day you alternate which nostril you're using it in. This is to avoid some of the nasal ulceration problems that can occur. Speaker 3 04:02 So I see Miacalcin or calcitonin in the refrigerator at my pharmacy. Is it okay to just pop it out of the fridge and spray it right into my nose? Unknown Speaker 04:10 Sure, go ahead and see what happens. Dr. ratherton, Speaker 3 04:13 yeah, that probably won't feel very good. So the agent can be stored at room temperature for up to 35 days, and you want to encourage your patients to do that when it's time to start using the bottle. Speaker 5 04:23 And don't forget, you got to prime that pump before you use it first, which means that the device won't deliver the drug until you actually pump it first to see that the spray is coming out. Dr. Sean Kane 04:32 All right. So the next class of agents, the next three, top 200 drugs that we'll be discussing are under the drug class of bisphosphonates. Now they share a lot of commonalities, so we're going to discuss them as a group, and then we'll go into each individual agent. Speaker 3 04:45 We talked about how Miacalcin or calcitonin is not really the first agent that we would use for patients with osteoporosis. Where do the bisphosphonates fall on our list of agents to use? Dr. Sean Kane 04:56 Yeah, my impression has always been that the bisphosphonates really changed. The face of osteoporosis, they're incredibly efficacious. They have a minimal side effect profile, and we really use them a lot now for the treatment of osteoporosis, going Speaker 6 05:10 with the efficacy profile in the clinical trials is these class of agents have shown to increase bone mineral density, which is a big deal. So that Speaker 3 05:19 means they work, right? If they increase bone mineral density, is that all we care about? Speaker 6 05:23 No, we all. We are also looking at preventing or reducing the risk of fractures. And these agents also showed reduced fractures, both hip fractures and spine fractures. Dr. Sean Kane 05:33 And that's a great example of the difference between a clinical endpoint of fractures and surrogate endpoint of just increasing bone mineral density. Unknown Speaker 05:40 Dr. Holmes, how do the bisphosphonates work? Speaker 4 05:44 Well, bisphosphonates work by inhibiting osteoclast activity. Remember that class consume bone, so inhibiting their activity would allow growth of bone. Speaker 3 05:55 I once heard an ad for fossamax that said that fossamax works with your body to prevent osteoporosis, but really it doesn't work with your body and inhibits a natural process to make sure that bones are being built. Very astute, back to retherton. So what kind of things can we use? These agents Speaker 4 06:11 for prevention of osteoporosis and treatment of osteoporosis? Speaker 6 06:15 This agent is also used in treatment of Paget's disease. I've also Speaker 3 06:19 heard that it can be used in glucocorticoid induced osteoporosis in both males and females. Dr. Sean Kane 06:23 And finally, the last potential indication is bone pain from bone metastases from things like breast cancer. And it should be noted that the indications we mentioned are both labeled and off labeled indications for the bisphosphonates as a whole, and some indications are approved for some bisphosphonates, but not others. Which is important Speaker 3 06:43 to note, Wow, it sounds like these agents really work well. So what are some adverse reactions that we can expect from the bisphosphonates in general? Dr. Sean Kane 06:50 So the main thing is gi complaints, so constipation or diarrhea, upset stomach, kind of non specific gi complaints. But there are some more rare side effects that the patient should at least be aware of Speaker 4 07:01 rare side effects would be esophageal irritation, so esophagitis, just general irritation, or possibly heartburn, and very Speaker 6 07:08 rarely, osteonecrosis of the drug can happen. So if your patient is at high risk, we recommend that there is a pre evaluation by the dentist performed prior to starting bisphosphonates. Unknown Speaker 07:21 Osteonecrosis sounds bad. Speaker 6 07:23 What is that? Dr. Patel, it's basically a necrosis of your jaw bone. Speaker 5 07:28 And as long as you take the phosphonates as directed, you can avoid the esophageal irritation, the esophagitis, specifically. And there are some very important instructions that you have to follow for that. Speaker 6 07:40 So in order to avoid the esophageal irritation, the manufacturer recommends to take this medication first thing in the morning on an empty stomach with the full glass of water. Speaker 3 07:50 I like orange juice. In the morning, can I take mine with orange juice? Speaker 6 07:52 No. Dr. Weatherton, unfortunately, you won't be able to take this medication with orange juice, because these orange juice or any sort of antacids or minerals or vitamins will decrease the bisphosphonate absorption. The manufacturer even recommends not to eat drink any non water items, at least for 30 minutes after the administration. Speaker 3 08:13 So normally, we tell patients that taking their medication with food can reduce stomach upset, but I'm guessing that that's just not appropriate in this case, right? That is correct. Well, Dr. Kane, why do we have to avoid food with these agents? Dr. Sean Kane 08:25 So the problem with the bisphosphonates is that they have extremely low bioavailability, so less than 1% of the actual dose will get absorbed into the bloodstream, but when you take it with food, you reduce that by about half, so the patient effectively gets about half the dose that they would get normally if they were fasting when they took the medication. Speaker 6 08:43 So usually in the morning, if I had to take this medication, I'm not a morning person, can I take the medication and just go back to Unknown Speaker 08:49 sleep? No. Dr. Patel, that's a great point. Nah. Speaker 5 08:52 If you lie down, you could actually erode your esophagus, and that could lead to esophagitis. So you really need to sit up with for at least a half an hour. And in fact, the Boniva or the ibandranate requires an hour of you to sit up and not eat foods or drink. Dr. Sean Kane 09:10 So kind of finishing off some of the adverse effects that we see with bisphosphonates. In addition to what we've already mentioned, there can be some mild bone joint or muscle pain, hypocalcemia, which we would expect, because the agent does inhibit the classic activity of the bone, and then also the final kind of rare side effect that we're learning more about now are atypical femur fractures, Speaker 3 09:32 and I hear that those are more common in patients who've been on bisphosphonates for a long time. Is that true? That's correct. Dr. Sean Kane 09:38 So the half life of bisphosphonates overall is extremely long. We think the reason is that it binds to the bone, and it really doesn't leave the bone very quickly. So these agents stick around for a very long time. So for that reason, we really don't know how long to treat patients with bisphosphonates, because they kind of hold on to all the drug that we end up giving them. Speaker 5 09:57 So is that why you can take these agents a. Only once a month, or they take it every three months. Is that why that's correct? Dr. Sean Kane 10:04 So the half life is so long. We can do daily, weekly, in some cases, monthly or even every three month administrations, because the half life is so long. Speaker 3 10:13 Wow. What types of things do we need to monitor when patients are taking bisphosphonates? Speaker 6 10:18 So because those agents are contraindicated in patients with low calcium levels as well as patients with creatinine clearance of less than 30 we do want to monitor patients calcium going along with supplementation vitamin D, un incident creatinine, as well as other electrolytes such as magnesium and phosphates. Dr. Sean Kane 10:36 We have three specific agents that are part of our top 200 drugs list. So the first one, the generic name, is alendronate, brand name, Fosamax, and that Speaker 3 10:45 one is my favorite, personally, because it has a generic on the market. So it's probably the least expensive agent. Unknown Speaker 10:51 How is it available? Dr. Holmes, it Speaker 4 10:53 is available in 35 milligram weekly dose packages, or 70 milligrams weekly. You can also take it daily, depending on the indication. Dr. Sean Kane 11:03 Our next bisphosphonate is called risedronate. The brand name is Actonel. Speaker 6 11:07 What is so special about this agent? Dr. Kane, so of Dr. Sean Kane 11:11 the three agents we're discussing, it's actually the most potent in terms of its ability to inhibit osteoclasts. Speaker 3 11:17 If it's so potent, I imagine it probably has a lot of Gi side effects as well, right? Dr. Mitchener Speaker 5 11:23 actually it has potentially fewer gi side effects. Dr. Sean Kane 11:26 So risedronate Actonel comes as tablets that are daily, weekly or monthly. And the daily tablets come as either an immediate release or an extended release, which is under a different brand name. Some interesting counseling point about the extended release or the Atelvia is that you actually take it after breakfast, as opposed to all the other bisphosphonates that you take before breakfast. And why is that? So they actually formulated Atelvia so that it wouldn't be as affected with having food in your stomach as the other bisphosphonates are. The next Speaker 3 11:57 agent we're going to talk about is ibandronate, or Boniva. Speaker 4 12:00 Ibandronate is different because patients are required to sit up for 60 minutes instead of 30 minutes, unlike the other drugs in its class, not eating food or drinks, which makes it a little bit less convenient. Speaker 3 12:14 So I understand that ibandronate or Boniva can be taken orally. Is there any other way to take this one Speaker 5 12:20 actually it comes intravenously, so you can give this as an IV every three months. Speaker 4 12:26 Oscar award winning actress, Sally Field popularized Boniva in 2006 with her direct to consumer advertising campaign when she was seated on a couch. You might remember this campaign, which received a lot of scrutiny for its use of public figures to promote drugs. Dr. Sean Kane 12:42 So just to review, we have three bisphosphonates. We have alendronate, or Fosamax that is the least potent we have ibandronate, or Boniva that is the second most potent. And this you have to wait 60 minutes instead of 30 minutes after taking the medication before you lay down or eat or drink. Then the third agent was risedronate, or Actonel. That was the most potent of the three. So getting Speaker 3 13:05 away from bone health for a minute, the next agent that we're going to be talking about is potassium chloride, which comes as a couple brand names. One is K-Dur and one is Klor-Con. I think the dur in the brand name is due to the duration of action. This is an extended release product that works for a long time. Dr. Sean Kane 13:23 So why would anyone ever need to take a potassium chloride supplement? Speaker 4 13:26 So some patients that are on certain medications that deplete potassium, such as loop diuretics or furosemide in that family, may require potassium supplementation. Speaker 5 13:36 And then some patients with chronic diarrhea, they may actually lose potassium due to losses from the GI tract. That could actually also be a reason that they might have potassium loss. So what might a Dr. Sean Kane 13:48 patient expect when they're Speaker 3 13:50 taking potassium supplements? So the biggest thing that I think of when I think of potassium replacement is GI upset. These things can really upset the stomach, and that's one of the reasons they're formulated as extended release products, so that they're not dumping the whole dose right away, kind Dr. Sean Kane 14:04 of piggybacking on that. Because they are extended release products, we can't crush these. We can't split them. These are very hard tablets, or capsules that, because of the formulation, have to be taken whole. And to piggyback on that Unknown Speaker 14:17 these tablets are huge, Speaker 5 14:18 and to piggyback on that they might have trouble swallowing them. So you might have to consider other forms of them, such as powders for oral solution to Dr. Sean Kane 14:28 piggyback on that in the ICU we have IV piggybacks. So unlike the bisphosphonates, potassium supplements should always be taken with food to avoid some of the GI complications that we see any patient who's taking a potassium supplement. What kinds of things might we want to monitor for those patients? Speaker 4 14:43 Well, Dr. Kane, we're clearly going to monitor these patients potassium levels so to avoid hyperkalemia, or to ensure that their levels are therapeutic and not sub therapeutic with hypokalemia. Dr. Sean Kane 14:55 What's the worst that could happen with a little hypokalemia? Speaker 5 14:57 Though, arrhythmias could be very serious if you really your body has a very sensitive electrolyte balance that you achieve, and so it could actually result in arrhythmias, which may be fatal, Speaker 4 15:10 common prescribing errors. Maybe a patient is discontinued on a diuretic and they will become hyperkalemic because they continued on their potassium supplements. Dr. Sean Kane 15:21 Also some medications do increase potassium levels, like ACE inhibitors, ARBs, Spironolactone. So in patients who have low potassium, who are started on a potassium supplement, and then, in turn, are started on another agent, we could actually see hyperkalemia with those as well. Speaker 3 15:37 One other interesting fact about patients who need to monitor their potassium levels are that they should avoid salt substitutes. And the reason that salt substitutes can affect potassium is because they contain potassium chloride. Dr. Sean Kane 15:49 So to kind of wrap up our top 200 drugs for this week, the last drug is calcium citrate, or Speaker 6 15:54 citrical and this medication is available over the counter. What a clever Speaker 3 15:59 brand name. It really says exactly what it is. So why would a patient need to take citracal Well, as we talked about, patients with osteoporosis need to be sure that they keep their calcium levels high in order to maintain as much bone density as possible. Dr. Sean Kane 16:13 So is there a difference between calcium carbonate or Tums and calcium citrate or citrical? Speaker 3 16:19 There are a couple of cool differences. One of them is that calcium citrate doesn't require as an acidic of a stomach pH in order to be absorbed. So it may be an option for patients who are taking acid suppression therapy Speaker 6 16:31 or patients who are older, who can have a condition such as achlorhydria, their stomach is not producing enough acid for digestion. Speaker 3 16:38 Dr. Kane, if my patient wants to switch from calcium carbonate to calcium citrate, can I just switch them over using a one to one ratio? Dr. Sean Kane 16:46 Actually, they're not equivalent. So the way that we dose calcium is based on elemental calcium. So patients with osteoporosis need anywhere from a gram to a gram and a half of elemental calcium. The difference, though, is that calcium carbonate has about 40% elemental calcium, whereas citrate has about 20% so it's about half the amount of elemental calcium and citrate that one would have in calcium carbonate. Speaker 3 17:09 Interesting, so if my patient needs a gram or a gram and a half of elemental calcium per day, can I just take all that in the morning and be done with it? Speaker 6 17:17 No, it is actually recommended that we split this dose into three to four different doses because of the saturable absorption. So we recommend the doses are to be divided anytime the dose is over 500 milligrams. So Dr. Weatherton, if my patient doesn't want to take bisphosphonates, would supplementing them with calcium be enough? No. Speaker 3 17:42 Calcium is really good at increasing the bone mineral density, because it's what bones are made out of. However, there's not evidence to show that just giving calcium by itself actually reduces fracture rates at all. So your patient probably would need to take calcium and a bisphosphonate. Is it okay for them to take all that in the same swallow in the morning. Speaker 6 18:00 Calcium and other bivalent cations can reduce the bioavailability of bisphosphonates, so we do not recommend taking anything around 30 minutes after taking bisphosphonates. Dr. Sean Kane 18:10 Are there any other drugs that we can't take with our calcium products? Speaker 3 18:14 The big one that I think of are Fluoroquinolone antibiotics like Cipro and Levaquin. If you take Cipro or Levaquin with your calcium products, they'll stick together in your stomach and you won't absorb either one of them. I also think of tetracyclines like doxycycline or minocycline that also have the same effect. So it seems like it should be a pretty benign agent, calcium citrate or citrical. So we probably don't see a lot of side effects from it. Is that correct? Speaker 4 18:37 That's wrong. Dr. Kane, we see a lot of constipation, bloating and gas, among other GI side effects, especially elderly patients sometimes are more susceptible to this constipation and can be intolerable. Speaker 3 18:51 So to review this week's drugs, the first one that we talked about was calcitonin or Miacalcin. Speaker 6 18:57 The second on the list was alendronate brand name, Fosamax. Unknown Speaker 19:01 The third on the list is risedronate, Actonel. Dr. Sean Kane 19:04 The next one was ibandronate, or Boniva. Speaker 4 19:06 Then we talked about potassium chloride, K-Dur or Klor-Con. Speaker 3 19:10 And finally, we wrapped up with calcium citrate, which is citrical. Dr. Sean Kane 19:14 So that concludes week 11 of Rosalind Franklin University's top 200 drugs podcast. I'm your co host, Dr. Kane, I'm Dr. Mitchener, Speaker 6 19:21 I'm Dr. Holmes, I'm Dr. Weatherton And I'm Dr. Patel. Speaker 5 19:26 Dem bones, dem bones, dem beef bones. Speaker 1 19:36 This has been an educational production by the Rosalind Franklin University, College of Pharmacy. The music for this podcast is an excerpt of Metro Mix by see song released under Creative Commons. You.