Opioids Complicated dosing question for when changing meds. (Not an abuse thread)

[GeisterxFahrer]

I apologize in advance if I was repetitive.

I know of a few Long Acting opiates such as: Oxycontin, Opana ER, Exalgo, Fentanyl, and MS-Contin. I have a questions about the calculations used to convert from one long acting opioid to another. The example I will use here will be as if your doctor wanted to switch you from Oxycontin to Opana ER (Oxymorphone). The question that I will raise is about "incomplete cross tolerance".

Note: All estimates are in terms of Oral Bioavailability (according to Wikipedia)

1. Oxycontin (Oxycodone) = "up to ~87%"
2. Opana ER (Oxymorphone) = "~10%"
3. MS-Contin (Morphine Sulfate) = "~25%"

First, we will start with the actual calculations and differences in dosing and potency between Oral Oxycodone vs. oral Oxymorphone. For instance, say you are currently prescribed 40mg of Oxycontin every 12 hours (oral BA of "up to ~87%"), and you are going switch to Opana ER (oral BA of ~10%); based on Opana's website, converting from a total daily dose of 80mg Oxycodone to Opana ER, you use the conversion ratio given on the Opana site of 2:1 (Implying that oral Oxymorphone is two times as potent as oral Oxycodone) and do the math: (80mg)(.5). This equation would yield a total dose of 40mg. Then we factor in the average 50% incomplete cross tolerance; which is the estimate doctors' generally use, and we end up with a resulting in a total daily dose of 20mg Opana ER (10mg every 12 hours)

Next, a little bit about the metabolism of Oxycodone. Based on this medical journal... In humans, Oxycodone's structure allows it to avoid serious first-pass metabolism. It was found that cytochrome P450(CYP)3A mediated the N-demethylation of Oxycodone into (noroxycodone, noroxymorphone, and α-/β-noroxycodol) which accounted for ~45% and ~21% of the dose of Oxycodone: whereas it was shown that CYP2D6 mediated the O-demethylation of Oxycodone into (Oxymorphone, α-/β-Oxymorphol), and 6-keto-reduction (α-/β-Oxycodol) which were shown to account for ~11%, ~6% and ~8%, ~6% of the dose respectively. It was found that the Major metabolites were Noroxycodone and Noroxymorphone both of which have half-lives longer than Oxycodone itself.

Now, we do some conversions. Assuming that ~11% of an oral dose of Oxycodone is metabolized into Oxymorphone is correct, we can calculate that for each oral dose of 40mg of Oxycodone released over a period of 12 hours (at the assumed maximum oral BA of ~87%); ~38.4mg of Oxycodone is actually absorbed by the body to be used meaning that of that, ~4.22mg of the Oxycodone is demethylated into Oxymorphone and of that ~4.22mg of Oxymorphone, (based on a the 10% oral BA of Oxymorphone) only ~.42mg of this metabolized Oxymorphone is used by the body per 40mg of Oxycontin over 12 hours.

Although exact numbers vary from article to article, It has been determined that Oxycodone is ~1.5-2 times more potent than oral Morphine and that Oxymorphone is ~3 times more potent than morphine. Using a well known converter, it shows us that 10mg of orally administered Morphine (without adjusting for incomplete cross tolerance)= ~6.67mg of orally administered Oxycodone (~1.5 x more potent) and ~3.33mg of orally administered Oxymorphone (~3 x more potent). Based on this, it can be assumed that orally administered Oxymorphone is ~2 x more potent than orally administered Oxycodone (Not taking the BA of each into account). Note: we demonstrated the 2:1 ratio between Oral Oxymorphone and Oral Oxycodone above.

By replacing the single 40mg dose of Oxycontin with the adjusted 10mg Opana ER; (based on a 10% oral bioavailability) only ~1mg of Oxymorphone is actually used by the body over this 12 hour period meaning that two 10mg Opana ER tablets taken orally every 12 hours would produce ~2mg of active Oxymorphone over 24 hours. Whereas before the switch to Opana ER; based on our calculations, we were already essentially absorbing ~.84mg of Oxymorphone over a period of 24 hours already. This means that by switching from 80mg of Oxycontin a day to 20mg of Opana ER a day; over a period of 24 hours, the body's dose of absorbed Oxymorphone has gone up from ~.84mg to ~2mg. However, Oxycodone itself IS active on its own, and produces a little less than half of the new dose of Oxymorphone already; Why would anyone want to go from Oxycontin to Opana ER? Using the reverse 2:1 ratio again (and going by our converter again), 20mg of Opana ER over 24 hours would be approximately equal to 40mg of Oxycodone (again, not taking BA into account).

So my questions is essentially, WHY do doctors' use this "incomplete cross tolerance"? When I was switched in December from MS Contin to Opana ER, I went through terrible withdrawals.

On a side note:
It has been demonstrated that "Oxymorphone['s oral bioavailability can] increase [by] ~50% when taken with food and erratically with alcohol use."

 

[NeighborhoodThreat]

A D D - O D

This is more appropriate for Other Drugs, so I'll move it there for ya. Feel free to PM me if you have any questions.

-NT

 

[ActiqAnnie]

I know of a few Long Acting opiates such as: Oxycontin, Opana ER, Exalgo, Fentanyl, and MS-Contin. I have a questions about the calculations used to convert from one long acting opioid to another. The example I will use here will be as if your doctor wanted to switch you from Oxycontin to Opana ER (Oxymorphone). The question that I will raise is about "incomplete cross tolerance".

So my questions is essentially, WHY do doctors' use this "incomplete cross tolerance"? When I was switched in December from MS Contin to Opana ER, I went through terrible withdrawals.

On a side note:
It has been demonstrated that "Oxymorphone['s oral bioavailability can] increase [by] ~50% when taken with food and erratically with alcohol use."

I want to think more about some of this, but I have a couple of quick little responses just to avoid some misunderstanding:
Fentanyl, oxycodone and oxymorphone are not long-acting narcotics. I completely understand why it would seem this way, however, when talking about the actual life of an opioid, an example of one that is long-acting (has a long half-life) is methadone. Fentanyl has one of the shortest durations of action. What has happened is that through time-release, Opana ER and some preparations of fentanyl, etc can be administered for a long period of time.

Unfortunately, my answer to your question about your Dr and the issue of cross-tolerance and your unpleasant experience with withdrawals is that most often, doctors err on the side of caution. Cross tolerance (or lack there-of) is a real thing, and can be unpredictable. Another part of the unpredictability is that everyone metabolizes their drugs slightly more or less efficiently than another person. It is possible that while you did not actually abuse your oxycodone prior to the Opana switch, you had been getting a greater yield of bioavailable drug, which made it difficult to calculate the switch correctly. Further, many doctors intentionally under-prescribe when switching - in part to try to get patients stabilized on lower doses of pain medication and, of course, for safety concerns. Also, there is always ignorance and misunderstanding. The only way I can think of to prevent this in the future is that when switching, make sure you follow-up with the doctor closely so that individual adjustments can be made.

Finally, you mention the changes made to the bioavailability of oxymorphone from food and alcohol. This is indeed true, but I just wanted to mention, for the kids at home, that taking alcohol with Opana will cause a massive "blast" of the drug to suddenly become available and is the leading cause of oxymorphone-related deaths. I had a personal experience with this. The very first time I took an Opana 40mg ER I took the pill in the morning. That evening, about 12 hours after the pill, I had dinner with a friend and I had half a glass of white wine (I'm not usually a drinker). That half a glass caused me to throw up and fall soundly asleep on her couch. It was not a pleasant experience, but it revealed dramatically how alcohol can affect Opana and also how incredibly long the Timerx systen on the ER works for (artificially making it a very long-acting drug indeed).

 

[HaZeX]

Very interesting...Waiting to hear what the experienced people have to say about the oral ROA for Opana ER...

 

[amapola]

^Unless you are invested enough to try and break the ER preparation then oral is your only real option.

OP all those values you quote have a good deal of uncertainty and combining them necessitates a very "better safe than sorry" stance. From a purely chemical point of view instant release pure opioids administered as needed for pain every hour or so would solve all our problems. Of course most people aren't willing to take a pill every hour and there is the whole liability for abuse aspect which can't be ignored. It is unfortunate that you ended up on the side of the spectrum that experienced some painful withdrawal and didn't have a smooth transition. Just count yourself lucky that you weren't overmedicated to the point where narcotics do nothing/you stop breathing nor were you tempted into the depths of opioid addiction by an overly generous supply

 

[GeisterxFahrer]

ActiqAnnie, Again thank you for your insight. I should have been more specific when discussing "long acting opiates" because you are right, those preparations do indeed have a short half life. I should have worded things differently because of how I was just talking about the long acting versions of these short acting opiates.
As for the other responses, I definitely understand a doctor's approach to being better safe than sorry, but I had some test, I dont remember what it was called, but it showed that I metabloize opiates rather rapidly and that the effects of a particular medication (say prescribed every 6 hours PRN) After about a half hour, I feel the relief, but the way I metabolize, the effects are pretty much gone (for most IR preparations) within 2-3 hours of the effects beginning. I have always had this problem with most medications and anasthesia. I need more than the average person of my size. I need even need more novacaine for dental procedures. Its just the way my body works. I am pretty sure that for this reason, I have issues with extended release versions of opiates (ie Oxycontin, Opana ER, Duragesic, etc) And because of my metabolism, the amount of the drug released gets metabolized too quickly, resulting in my needing a higher dose of the extended release versions of meds. So when I doctor account for ICT for me, and they use the average 50% when switching meds, I will go trough withdrawals. As far as addiction and abuse goes, I was tempted, and did give in to temptation a few times (during the withdrawals after my switch to Opana ER) and i did abuse both my Roxys and the Opana ER to try to lessen the withdrawals. But now, I have effectively lowered my tolerance, probably due in part to the withdrawals I experienced. also since then, I have been gradually reducing my doses; until recently, now I am back on 15mg oxy ir every 6 hours, and when I see my doc next wednesday, we will discuss going back on a long acting opiod. He knows that fentanyl patches do not work well for me (trans dermal anything doesnt work for me), I cant take MS Contin for long periods of time and morphine is oddly ineffective in me, and he was also the one who prescribed me the Opana ER. because of my age, he is VERY VERY reluctant to put me on Oxycontin (even though after I left his care, my next pain doctor switched me to Oxycontin with massive success (in terms of pain relief as well as the goal of reducing my intake of break through medications.) Now That I am back at this pain doctor again, I am hoping that he will finally prescribe me Oxycontin despite my age because 1) I was on it before and it was VERY effective, 2) his typical prescriptions for ER pain meds are for Mscontin, Duragesic, and Opana; which he knows are relatively ineffective in me. so next wednesday at my appointment, we will be discussing these long acting opiates because of my worsening pain and spinal conditions. And he would rather prescribe an extended release opiate, and a BT med for every 6 to 8 hours, rather than prescribing something like 30mg oxy IR every 4 to 6 hours as needed. And the oxy IR 15mg that I am on now, sadly does not provide the necessary relief for the length of time I need. I guess he knows this, and that is why my appointment is only one week apart right now, so that he can monitor the effects and adjust then much faster if needed. I am just worried that he will insist i take Mscontin, duragesic, or opana er. I know oxycontin has a HUGE stigma, and is WIDELY abused by a lot of people everyone, but it IS effective for me, moreso than his normal three. But now have gone way off topic. Sorry about that.
Anyway, How are doctors supposed to know (aside from whatever that test was that I got) how to calculate and titrate doses? My doctor doesnt seem the type to be worried about the DEA breathing down his neck, but he is definitely NOT a pill mill. I saw him reject a patient before because he suspected abuse. (I know for a fact that that patient WAS indeed abusing). So my particular doctor seems to be pretty balanced and generally is good about not overprescribing or underprescribing.
How do docs know how to do that? And how does the DEA play into this?