Case Vignette
Bill H. McCarberg, MD

Slide 1. Our first patient is Linda M. She’s a 49-year-old female; she is on oxycodone/acetaminophen 3 qid for failed back syndrome. She has a contract or an agreement with you to take 360 tablets every 30 days; however, her husband’s calling you on the phone because he’s worried about her because she’s spending excessive time in bed. She’s also called in early for refills and you’ve discovered that she’s borrowing some medication from a sibling. When confronted, and you have confronted her, she tells you that her pain is worsening and she just needs more medication. So this is the case and this is a common scenario for you that someone would give you some more information. And my question is: What are the issues involved?

Slide 2. So I ask: Is she taking too much oxycodone/acetaminophen or is this an issue of the husband just being overprotective of this patient and it’s really between you and the patient, not the husband? Is the patient getting adequate or inadequate pain relief? Is it just a matter of pushing up the dose of the medication? Or, is this really addiction? And this is a common case again; it’s something that you will be struggling with because I struggle with it all the time in my practice. So is she getting too much oxycodone/acetaminophen and the typical Percocet tablet has 325 mg of acetaminophen and 5 mg of oxycodone and 12 pills, which is 3 pills four times a day, is the maximum dose of Tylenol that she can take. So she’s not taking too much of the oxycodone/acetaminophen based upon the criteria of too much acetaminophen. Is this husband overprotective? Well, he could be; this may be the case of the husband just paying too much attention to his wife, but you have to pay attention to other information, collateral information when a patient comes in.

I find collateral information from a spouse, from a sibling, from a child, from somebody, for example, a boss or somebody at work telling you something because a patient has a reason to give you a history; it’s not just that they’re reporting how they feel, but there is an ulterior motive, especially when an opioid’s involved. So there’s a reason for her to tell you something such as: Oh, I’ve returned to work; I’m doing fine, I’m working around the house as well and I’m putting dinner on the table. And when the spouse says: She spends more time in bed; she really isn’t functional at all, that’s important information for you to know. But the question is: Can you talk to the spouse? Because remember, this is HIPAA [Health Insurance Portability and Accountability Act] protected; you just can’t talk to anybody. This is a patient confidentiality issue.

Now that opioid agreement that I told you about in the first slide very likely would have covered the ability to talk to other people about the patient’s care because that’s certainly in my agreement; it’s common in medication agreements. However, you want to make sure that you have that authorization to talk to spouses and you want to talk to the spouse about that so you can confront the patient because the patient’s done three things here. She borrowed from a sibling, calls in early for refills, and even though your point of prescribing is to make the patient comfortable—not just comfortable but functional—what she’s done is she’s spending more time in bed. So the information isn’t coming in correctly.

Now you could be undertreating her; that could be a correct answer, inadequate pain treatment. She could be addicted; she may be taking more medication to get high and also to feel groggy and sleep. You don’t quite know that from what I’m describing, but the HIPAA criteria that you can’t talk to the husband without authorization is very important. And the husband’s information is important to you; you can listen to him talk —that is not protected by HIPAA, just him telling you—but talking to him, giving information back is and his information is very important because it’s collateral, it’s other observed information. And #2, spouses and family members are commonly the ones that tell medical boards about our prescribing. When they are not informed or on the same page with you in prescribing for this patient, that is a risk and you need to get that spouse in and talk to him about why you’re using medication in this patient because if he’s unhappy, even with adequate function and pain control, if the spouse is unhappy, this is a risk for you and you need to identify that risk and pay attention to it.

Slide 3. Our next patient is Julie K. She’s a 38-year-old female with low back pain. Now she comes to you from the orthopedic surgeon because the orthopedic surgeon has done the procedure and has done everything that can be done and has started the patient on hydrocodone/acetaminophen 5/500 at 2 pills four times a day; that’s 8 pills and that is Vicodin. That’s the standard dose for Vicodin. Now her pain levels are at 7 out of 10; it’s interfering with her ability to sleep and function, and the orthopedic doctor has done further evaluation as described by this MRI and it doesn’t demonstrate anything more he can do to her. So he started her on medication and sends her back to you and asks for you to take care of her. So of course, her pain isn’t under control; it’s interfering with her life and now it’s your problem.

Slide 4. So what do you do with her? What’s your best options here? So the answers are: Increase the current medication to 3 pills four times a day, the way you did with that last patient; or switch her to oxycodone/acetaminophen, instead of hydrocodone to oxycodone 5/325 3 pills four times a day. Switch her to propoxyphene N-100, which is the Darvocet compound 2 pills three times a day; or switch her to an extended-release morphine product, which is 20 mg bid. So these are four different options and I’ve seen all of these options used in the primary-care setting, so let’s go through these one by one. 

Now how about increasing the dose of her Vicodin to 3 four times a day, just pushing the dose up? And even though that will give her more hydrocodone, it also gives her more acetaminophen and that pushes her beyond the limit of 4 grams a day that she can take, so that is not a good option. You could switch her to oxycodone/acetaminophen at a higher dose; this will be a lot more equivalent dose because it’ll push her—she’s on 40 mg of hydrocodone, that’s 8 pills of the Vicodin a day. Now you’re pushing her to 12 pills of the oxycodone. Now oxycodone is more powerful milligram per milligram and you’re also giving her more milligrams of this pill; you’re giving her 60 mg instead of 40. So you would actually be increasing her opioid and that could be an option for us. So that’s not bad. The third option is propoxyphene, the Darvocet compound, which would be much less powerful for her as far as a strict opioid. And propoxyphene/acetaminophen is not a good drug anyway because it has a high level of acetaminophen in the compound, 650 mg per tablet, and the propoxyphene has a lot of cardiac and neurocognitive effects that are higher than other opioids, to the point that many formularies are withdrawing Darvocet so that it’s not a very good option and not likely to have better pain control with that.

The fourth option is the extended-release morphine compound; now that would be 40 mg a day of morphine compared to 40 mg of hydrocodone, which is equivalent to the same dose, and that is actually the right answer. Now there are a couple of things you need to point out here. It is equivalent dose; you’re not actually changing the dose of the opioid. However, since the new opioid is morphine compared to hydromorphone, you may get more medication effect out of it because patients that are switched to a different opioid may find that the new opioid has a different effect on their system and may be a stronger effect. That’s called incomplete cross tolerance so that when you’re tolerant to one opioid, you may not be equally tolerant to another opioid. So she’s tolerant to 40 mg of hydrocodone, which is the Vicodin at 40 mg, but you switch her to morphine at the same equivalent dose; she may not be tolerant to that, so she may have a better effect. She may have more side effects, but she may have a better effect. The extended-release morphine is a better option also because she has a chronic long-term problem and it’s better to use a long-term opioid for a long-term problem and since she will likely be on this medication because of her back for a long time, it’s better to give something that will pharmacologically last throughout the day as opposed to having a drug that just peaks and valleys very quickly throughout the day.

Slide 5. Our next patient is Michael B. He’s an 85-year-old man with osteoarthritis of the hips, chronic obstructive pulmonary disease, congestive heart failure, and has a mild case of dementia. Surgery is not an option for his pain syndrome that comes largely from his osteoarthritis and he’s trying to remain as active and his spouse is trying to keep him there as well. But his pain just is not adequately controlled. The patient currently is taking oxycodone/acetaminophen 5/325 – that’s Percocet – and he’s taking 2 of those four times a day. But because of his lifestyle and his dementia, that’s a four-time-a-day pill and he just can’t remember and forgets pills.

Slide 6. So now the question is: What would you decide to switch him to and why would you do that? So how about an extended-release oxycodone at 40 mg bid; morphine, an extended-release compound, the one-a-day pill which I have in parentheses there as Avinza 60 mg; methadone, one half of a 5 mg pill twice a day; transdermal fentanyl—it now comes in a 12 ½ microgram per hour patch, so you could use that. Or the final answer is long-acting opioid formulations are contraindicated in this man because of his COPD, that if you take away his pulmonary drug, he may go into respiratory failure. So those are the questions that I ask and I have on the next slide some advantages and disadvantages of short-acting versus long-acting opioids.

Slide 7. And once again, this is another case of a problem that this 85-year-old’s going to have for quite a long time and using a short-acting agent for a long-term problem, especially in someone like him who forgets during the day, it’s better to use a long-acting agent. What would happen with him is that he may forget a dose just because he’s trying to stay active and he’s got a busy lifestyle and he’s forgetful anyway and his pain escalates to the point where he can no longer ignore the pain, so he forgot the medication that controls it, he ignores the pain as long as he can. Now the pain’s at a 7, 8, 9 level and at that point, medications don’t work nearly as well as if you take a long-acting agent, have that in the bloodstream for the entire time and therefore the pain control is much more adequate because it’s in the system; it doesn’t have to be reminded by high levels of pain.

Slide 8. Your answer to the questions that I gave you would not only relate to using a long-acting agent and I gave you several long-acting agents; I gave you four different ones and that is the right answer, to use a long-acting agent, but it also relates to how do you calculate the correct dose. Because if you look at what he’s actually taking, he’s taking 40 mg of oxycodone and he has inadequate pain control and he also forgets the medication, so you want to use a long-acting agent, but which one would you switch him to? So at 40 mg of oxycodone, you could give him extended-release oxycodone as an option because it’s an extended-release product and you could give it to him at 80 mg. So the first answer is 80 mg 40 bid, 80 mg, that’s a not bad answer because you’re increasing the dose because of his pain control. The second answer is also not a bad option because at, he’s on currently 40 mg of oxycodone, he could be pushed to 60 mg of morphine which is the equivalent dose and he actually may get better pain control out of that because of the incomplete cross tolerance. Maybe morphine will work better for him because he hasn’t been exposed to it. So even though it’s equal analgesic according to the conversion charts that you can see on that slide of conversions, it still may be more pain control for him.

Now how about methadone? Now notice I said 5 mg; he’s going to take a half a pill twice a day so that’s 5 mg. So if you look over at methadone; notice you have a fairly large dosage range – 2 ½ mg to 5 mg is equivalent to 30 mg of morphine. Now remember, he’s on 40 mg of oxycodone; that’s equivalent to 40 mg of morphine and I am giving him 5 mg of methadone. Now the conversion is anywhere from 6:1, as you can see 5 compares to 30 is 6:1, all the way up to 12:1. And that is the problem with methadone, is there can be this large dosage range, so in that dosage range, this may be the appropriate dose because it is between 6:1 and 12:1, the 5 mg. And this is the correct dose for him. And I just want to caution you: If you’re switching from a long-acting agent to methadone, underdose the drug because of the pharmacokinetics of methadone, it has—you have to go lower than you think you should go. The higher the dose of morphine that the patient is on or morphine equivalence, the lower the dose of the methadone you have to give; in other words, the conversion table is even lower because the incomplete cross tolerance, the fact that people may respond less to morphine and more to methadone, increases so you’ve got to use a lower dose. Now at the same time, since you’re calculating a lower dose, you may be undertreating the patient’s pain until they get up to the usual level of the drug, so that means you need to use an agent for breakthrough pain.

Now if you look at the fourth answer on the chart, transdermal fentanyl, and the answer was 12.5 mcg per hour. Now is that the right dose? Now remember, we’re comparing this to 40 mg of oxycodone; if you look on the chart, it’s 0.1 and that is mg so there’s a little confusion between milligrams and micrograms, but it’s 0.1, which is about 10 mcg, so that would mean therefore it’s about the right dose at 30 mg of morphine. So that’s not a bad answer – 12 ½ mcg per hour is equivalent to about 30 mg of oral morphine, so that’s not bad. But remember, we have incomplete cross tolerance so the patient’s taking 40 mg equivalent of morphine and you’re giving 12 ½ mcg of transdermal fentanyl so that’s not too bad as an option; you may be underdosing a little bit.

Now the final answer is long-acting opioids are contraindicated and I want to point out here that they are not contraindicated in COPD. When used judiciously, they can be used in people even having trouble breathing. As a matter of fact, opioids are used in end-stage COPD because it relaxes patients and they often times breathe easier. The problem is that when you overdose people on the opioid, if you incorrectly calculate their ability to tolerate something that depresses their respiratory drive can be more dramatic. However, it’s not contraindicated; you just have to use judgment with patients.

Slide 9. Our next case is Helen K. She’s an 80-year-old female with osteoporosis and has a compression fracture at the T2 level. Her pain levels are fairly high at 7 out of 10; she’s currently taking 9 tablets of a hydrocodone/acetaminophen compound 7.5/325. Now that’s equivalent to 67 ½ mg of hydrocodone. Due to her other medical problems, and she has plenty of them, she takes many, many pills during the day and just doesn’t like taking that many pills. Now the primary physician prescribed for the patient the transdermal fentanyl patch at 25 mcg per hour and the patient states that this really worked for her; the pain was under better control; she was more functional, but she became nauseated within 12 hours of putting the patch on and now it’s a week later and she’s still nauseated. She likes the pain control and even though she’s changed her diet and does all sorts of things, she’s still nauseated.

Slide 10. So what do you tell this patient? Do you tell her the nausea will improve with time? I’ve already told you—most side effects do improve with time. Do you give her some phenergan, something to treat the side effect, the nausea? Do you switch her to another opioid, which is oxycodone continuous release at 20 mg twice a day, or do you switch her to another opioid, oxymorphone? And I’ve given you two different doses of this; 5 mg twice a day or 10 mg twice a day. So the answer to this is that after a week, it’s not likely this nausea will improve. The transdermal patch actually is better for most patients with constipation and nausea, but some people just have this side effect. And if they are not accommodated to it by a week, they probably will not accommodate to it. And that’s not true for everybody; some people if they put up with it longer, they’ll get better, but most people will continue to be nauseated. Now you could give her something to treat the nausea but the specific example I gave you was phenergan 25 mg three times a day. That’s actually relatively contraindicated in this age group; as a matter of fact, the American Geriatric Society says it’s a pill that we should not be using in this age group, so that would not be the right answer, although treating her side effect is a potential treatment for her, but remember, you’d have to treat her side effect for a long time, assuming she doesn’t accommodate.

So I gave you a variety of treatments here; one was oxycodone continuous release. And again, I like the long-acting drugs because this is going to be a longstanding problem for her. So it’s 40 mg of oxycodone and that compared to 67 ½ mg of hydrocodone. Now that’s not bad; that’s actually equal equivalent 3 mg of hydrocodone compared to 2 mg of oxycodone, that’s just about equally equivalent, so that may be something she could take. But remember, you have incomplete cross tolerance so that may be a little high for her. The oxymorphone, two different doses; now oxymorphone is 3 times the strength of morphine, so you would have to look at her morphine dose—and, remember, she’s on 67.5 mg of hydrocodone, which is equivalent to 67.5 mg of morphine, so that would be equivalent to 22 ½ mg of oxymorphone. So what dose would you pick? Would you pick the 5 mg twice a day, which is 10, or would you pick the 10 mg twice a day which is 20? Well, equal equivalence would be the fifth answer, 10 mg twice a day, and it’s actually just a little bit less. That may be the right dose, but if she has incomplete cross tolerance again, you may want to pick even the lower dose than that because she may be more sensitive to the oxymorphone.

Slide 11. I'm going to go on to the next case, which is John S, a 50-year-old male. He’s on high doses of opioids for pain from cancer with metastatic disease to his bones. But now he has a history of chemical dependency; he was in a lot of trouble with heroin in the past and he had history of alcohol abuse and you’re not quite sure whether he’s doing that now. And what’s happening is he’s requiring more and more doses of his opioids; he’s running out early, so he’s showing some behavior that worries you somewhat about it.

Slide 12. What would you do with this man with cancer with metastatic disease? Answer 1 is his disease is serious, so just renew his drugs. I mean he’s got cancer; just give him his drugs. Answer 2: Reexamine him to see if the cancer has changed in any way; maybe there’s something else just going on. Send him to a substance abuse counselor is the third answer, and the last answer is to talk to him about his unilateral dose escalation, reestablish the dose, and then add a nonsteroidal.

So the reason this case is important is because there are different standards that we have compared to the fibromyalgia patient, the patient that comes in with myofascial pain, the chronic back pain patient, or cancer patient, an HIV/AIDS patient. I think it’s appropriate that we have a different standard because a patient who is at end stage of life, they’re struggling just maintaining their dignity and their pain control. Even with a heroin addiction in the past or alcohol dependence wouldn’t preclude me trying to be maximally analgesic; give him the most medicine I possibly can. However, you see a man over here who’s wearing a suit; he looks functional, he’s got this background and just because he’s got cancer doesn’t mean that he can’t get into trouble with his alcohol again. So for example, if he were still continuing his alcohol—now he’s got cancer; he’s got a good reason for it, yet he was using alcohol to treat his pain and his wife says, you know, he’s drunk, he falls asleep, he’s staggering around and he’s falling, he’s doing bad behavior at home, he gets really angry and he hits me. You wouldn’t tolerate that. So the opioid could be filling into that, so because it’s also an addictive drug at the same time. So just because he has cancer doesn’t mean that he can’t get into trouble with his painkillers, so even though it’s appropriate to have two standards, you still need the individualized treatment; you need to look at his longevity, what’s his behavior around this drug, and he may need to go to counseling. You may need to tell him about having some other expert get involved in this case, admonishing him about the unilateral dose escalation. Even though he’s got cancer, you still need to talk to him about what the agreement is between the two of you. You certainly want to investigate his cancer stage, so that’s not a bad answer, but I wanted to point out just because the “cancer” word is there, it doesn’t mean that patients just get automatic doses of their medication without reevaluating and deciding what to do.

Slide 13. The next case is Bill R, a 56-year-old male with diabetes. He’s got peripheral neuropathy; he doesn’t check his blood sugars very often and when you do a hemoglobin A1C, it comes out 11 ½ so he doesn’t have very good blood sugar control, even though he’s not checking, and he describes his pain level as being pretty high as well. He’s currently taking 1200 mg of morphine; he’s been doing that for years but now it’s not nearly as effective.

Slide 14. So what do you do with this particular case? The first answer would be to improve his blood sugar control so that that can be maximized. Or you look for other causes for his increased pain; there must be something else going on because he’s been on this dose for years and it had been okay. You switch him to sustained-release oxycodone compound and I gave you a milligram dose there or switch him to methadone and I gave you a strength of 20 mg qid. Certainly blood sugar control is important in this man, but at this point where he’s having poor pain control, even if you control blood sugars, it’s not likely you’ll get much pain reduction with that. So it’s good medical practice to control blood sugars, but I wouldn’t use that as the primary treatment modality for his pain because it’s not going to control his pain very much. You always look for other causes. I mean, he may have a vitamin B12 deficiency; he may have cellulitis—there may be something else causing his pain.

You want to certainly not get lulled into complacency and believe because he’s got peripheral neuropathy, because he has poor control, that’s got to be it, so you always think about secondary diagnosis. But certainly you’d want to treat his pain at a higher level and certainly other drugs, the serotonin norepinephrine reuptake inhibitors, the anticonvulsants, certainly that’s not precluded, but if you’re going to use opioids as the dose, which one should you use? Now on 1200 mg of morphine, he’s highly tolerant to this drug and what I want to suggest to you is that you use a different criteria, that you describe a dose by looking at the equivalent charts that I’ve already shown you, but you have to look at a lower, lower dose than this because he’s highly tolerant to the morphine and because of that, he may be less tolerant to the other drugs. So I gave you oxycodone and that’s 240 mg; that’s 80 mg three times a day. And remember, that’s much less than the equal equivalent dose; equal equivalent would be about 800, 900 mg of oxycodone. I wouldn’t nearly give him that much. I’d cut the dose way down. Methadone is another example here; methadone, notice I’m giving him 80 mg. Now 80 mg is under a tenth of the equal equivalent dose; remember it was 12, because you have the 6:1 up to 12:1 ratio and that’s appropriate; I think 80 mg is an appropriate dose. Once again, there is  incomplete cross tolerance. And if you push the dose too high, you could get into trouble.

Slide 15. The next slides describe several ways of calculating the dose and for him, even if you calculate equal potency, notice how they say you take that equal dose and you even cut that down because when people are highly tolerant to one opioid, the tolerance to another opioid may not be there and you just need to figure out what to do.

Slide 16. The next slide describes calculating one dose, using your judgment, giving some breakthrough pain medicine if you under dose the medication.

Slide 17. And indeed, in this particular patient, as shown on the last slide, you decided to go with the methadone because the methadone may work better in nerve pain and this is a particular type of nerve pain. He did all right on his 80 mg; you eventually had to get him up to 120 mg a day and it was a success.

Slide 18. Pain control is very difficult with patients, even if you have the help of experts and even if they’re telling you how to manage a patient, you still have to do the primary management yourself. The slides that I’ve shown you today exemplify certain types of patients that you’ll see in your practice, not uncommonly, and they will present to you with difficult decisions that you have to make. You will want to just refer the patient back to a pain specialist and often times the pain specialist isn’t available, they may not be available in the timeframe that you want, the patient may not be able to afford it, and you’re going to have to make some decisions. And these slides describe for you these particular patients and how you would calculate doses, talks about converting, incomplete cross tolerance, how to understand behavior in patients, and I think these are skills that you can learn. And if you do learn these skills and you understand how to convert people and try different opioids, you will be providing a tremendous service to your patients and with this, we’re able to control pain and the suffering that’s going on that hasn’t been adequately controlled up to now.