Okay, I’m back and better than ever…been side-tracked with other important dealings! Don’t worry, not a day went by where I didn’t think about GPA.com. I did a lot of daydreaming about the blog: Me, sitting in a quirky office or in the comfort of my own home or on some tropical island…you get the point (ahhh, the beauty of the internet!) working on GetPharmacyAdvice.com. Pure joy and contentment filling my life because I’m finally able to better help people with drug-related questions or issues. I’m here, there and everywhere and still able to provide this service (on my own accord and time schedule, I must add)!
Back to reality.
Here’s a pressing matter, not really, but let’s make believe for a second here! I had to do a little investigation earlier today because the increasing number of phone calls from patients seeking the “OC” oxycontin as compared to the “OP” oxycontin was really starting to peak some serious interest.
It didn’t take me too long to figure out what all the fuss is about!
Here’s the deal, oxycontin (we’re talking brandname) has been reformulated…the old form was imprinted with “OC”, the new tablets are stamped with the letters “OP.” The two tablets are said to be bioequivalent (meaning they have the same active ingredient and should absorb into your body at the same rate and extent).
When you have two bioequivalent tablets, it would be unlikely that they would differ significantly in their therapeutic or adverse effects. However, there are a couple of differences between the two oxycontin tablets, not counting the difference in what’s imprinted on the pills.
Difference #1: The new tablets take a little longer to get to peak levels in the body, which may make it seem less effective.
Difference #2: The new tablets reach a slightly higher peak level in the body, which can cause more side effects.
Difference #3: The new tablets are harder to crush or chew . It’s not easy to turn them into a powder to snort or to dissolve them to be drawn up into a syringe for injection. Bottom line, they’re harder to abuse so they’ve lost their street value!
For those who find the new oxycontin tablets are really not working for you, ask your doctor if you can titrate the dose or even switch to a different opioid of a long-acting nature.
Need more info or have some questions? E-mail me at Cate@getpharmacyadvice.com or leave a comment below.
Will be back soon!
It’s actually a bit more complicated than just those three differences.
First, I should say that in my opinion, Purdue has done a good job of creating a tamper resistant drug. For most routes of administration, addicts are finding the new drug to be too hard to tamper with. Even if they cut the pill into tiny pieces and then swallow those pieces, the fact that mechanism of release takes place at a molecular level (involving the ability of collections of extremely long polymer chains to “capture” oxycodone micro-particles) assures that the total API (Active Pharmaceutical Ingredient) delivery rate is no higher than it would be from an intact tablet. They are finding that the only route of delivery that both delivers the API and is worth the effort put into doing so is the normal route of swallowing the tablet intact.
Because these addicts are unable to get their “rush” from OxyContin, they are leaving oxyContin behind and turning to illicitly manufactured heroin. Many chronic pain patients, who have always taken oxycontin as intended, say that they are hoping the public will eventually forget the name oxycontin along with the social stigma associated with taking it.
It’s not all roses, however. Reports are coming in from physicians saying that they have had to raise patient dosages since the reformulation, that some patients have gone into withdrawal, and that some known compliant patients have been found to have plasma levels of the API that are significantly lower than expected. In some offices, the majority of patients being seen are experiencing adverse events, and many of them are being moved to other long acting opioid analgesics such as opana and methadone.
In an effort to try to make sense of these reports, this author has been studying available literature such as the proceedings of the FDA panel that approved the new formula and the clinical trial protocols and outcomes.
It has been my impression so far that, Purdue has made claims for the new drug that they have not supported and that the studies performed for it, at least those which I have examined, would have trouble standing up to close scrutiny.
Please examine the reformulated Oxycontin trial results at clinicalaltrials.gov, particularly:
http://clinicaltrials.gov/ct2/show/NCT01101308?term=reformulated+oxycontin&rank=8
and
http://clinicaltrials.gov/ct2/show/NCT01101321?term=reformulated+oxycontin&rank=7
These were two studies (one for 10 mg pills, and one for 80 mg pills) performed to determine whether pills manufactured at two different plants were bioequivalent to *each other*.
(six other studies, comparing the old and new formulas can be found by visiting clinicaltrials.gov and entering “reformulated oxycontin” in the displayed search box)
The basis of these studies is problematical, as the drug is specifically not intended to be taken on a PRN basis, and patient literature warns of this, yet the study patients were given no more than one tablet each per week. One wonders why the FDA ignored this.
The drug used in the 10mg study was reformulated Oxycontin/10 mg. Over a twelve hour period this is roughly equivalent to the amount of Oxycodone in one percocet tablet, plus the amount of oxycodone in a second percocet tablet taken 6 hours later, for a total amount of oxycodone equivalent to that found in two percocet tablets.
In the other study, the drug being evaluated was reformulated Oxycontin/80 mg. Over a twelve hour period this is roughly equivalent to the oxycodone in eight (8) percocet tablets, plus the amount of oxycodone in an additional eight (8) percocet tablets taken 6 hours later, for a total amount of oxycodone equivalent to that found in sixteen percocet tablets.
In the 80mg tablet study, there were 22 females and 36 males among which the number of participants affected by adverse events from taking 80 mg pills made in Purdue’s Totowa plant was 58 and the number of participants affected by adverse events from taking 80 mg pills made in Purdue’s Wilson (North Carolina) plant was 48.
I think it would be highly unlikely for an opioid naive patient who was actually administered an 80 mg tablet to not experience any adverse effects whatsoever. Remember, this is the equivalent of sixteen percocet tablets!
For 10 patients taking 80 mg tablets made in one plant to experience no adverse events whatsoever, either (A) most or all of these 10 misrepresented themselves as being opioid naive when they were not, or (B) the tablets did not truly contain 80 mg, or (C) something was interfering with the absorption of API from tablets made at that plant. Unless the patients had been untruthful, it is likely that there was some kind of problem in the manufacturing process at that plant.
Either the study was tainted, or it had caught a manufacturing defect to which no attention had been paid. An investigation would have been the appropriate response for either situation.
In the 10mg tablet study, there were 26 females and 29 males among which the number of participants affected by adverse events from taking 10 mg pills made in Totowa was 25 while the number of participants affected by adverse events from taking 10 mg pills made in Wilson (NC) was 17.
The 10mg study was interesting in that it was both the case that a sizable portion of participants did not have adverse events, and also the case that the number of patients reporting adverse events for pills made in Totowa was 50% higher than for pills made in Wilson.
Given that two studies were performed at dosage extremes, some comparative analysis can be done.
At high opioid levels (a single 80 mg dose containing the oxycodone content of sixteen percocets) where all patients would be expected to experience adverse events, a statistically significant number of patients receiving tablets made at the Wilson plant did not experience any adverse events.
Second, at the relatively low level of 10 mg for a 12 hour dose, 50% more patients experienced adverse effects with pills made in Totowa than in Wilson. Statistically speaking, this is huge. Taken together, the results of both studies would tend to indicate that the Wilson plant is not producing tablets that function as they would be expected to function when administered to opioid naive patients.
An implication here is that in both studies, less of the API was being delivered by tablets made at Wilson than at Totowa. Likely enough less so as to cause withdrawal symptoms in some patients receiving putative 80 mg tablets from the Wilson plant. This may account for conflicting reports from the field, where some patients achieve adequate pain control, while many do not and some patients even experience adverse events that imply withdrawal.
I suspect, simply, that real world experience may be mirroring the discrepancies that were seen betweeen plants in the studies.
In other words, some patients may be receiving tablets made in the Wilson plant, and it may be that it is these patients who are the ones reporting that the new formula has been providing adequate pain relief, while others who are receiving tablets made in the Totowa plant, are more satisfied with their pain relief.
A separate issue that I’ve only glossed over is that while the drugs are intended for continuous, non-stop use, the studies used methodology more appropriate to PRN pain medication. The study designs contained no provisions for evaluating the possibility of the drug failing to be biocompatible with the original formula in long-term usage. This, despite complete replacement of the previous release mechanism with a new mechanism in which the API and release mechanism are very tightly coupled.
Patients receiving the newly formulated drugs from their local pharmacy may have effectively become unknowing participants in a hugely multi-central clinical trial of the drug’s effectiveness and safety when used as intended. I’m wondering what protocols may (or should) be in place to handle compensation of unknowing participants.
While writing all of the above, I had the opportunity to more fully review the remaining six (of the eight open label phase one) clinical trials than I had previously been able to. Here is a summary:
The clinical trials that were performed are available for all to see. Please go to clinicaltrials.gov and enter “reformulated oxycontin” in the search box.
The clinical trials were all phase 1. They were all open label meaning that no blinding was done.
All study subjects were healthy volunteers with no medical problems, and all were opiate naive. Pain relief was not assessed (The subjects did not have pain that needed to be relieved).
In all studies the methodology was the same. Except when comparing manufacturing plants (studies 7 and 8), “test” referred to the new formula, and “reference” referred to the old formula.
In each study the subjects were divided into two groups. In group A, subjects were given one tablet of the reference drug, and then a week later they were given one tablet of the test drug. In group B, the order was reversed: subjects were given one tablet of the test drug, and then a week later they were given one tablet of the reference drug.
In tests 7 and 8, tablets made in the Wilson Plant were labeled “reference”, and tablets made int the Totowa plant were labeled “test”.
Study 7 compared 80 mg tablets made in two plants, designated “Wilson” and “Totowa”.
At high opioid levels (a single 80 mg dose contains the oxycodone content of sixteen percocet tablets) where all of the (opiate naive) subjects would be expected to experience adverse events, a statistically significant number of subjects receiving tablets made at the Wilson plant did not experience any adverse events, while all subjects receiving tablets made at the Totowa plant experienced adverse events, as would be expected. [editorial comment: Reviewing the other studies, subsequently, perhaps my original thoughts on what should be expected were premature, but I still question the methodology of dispensing such dangerously high dosages to opioid naive patients to whom they would never be prescribed.]
Study 8 was similar to study 7, except that subjects were given 10 mg tablets instead of 80 mg tablets. In this study 50% more subjects experienced adverse effects with pills made in Totowa than in Wilson. Statistically speaking, this is huge.
Taken together, the results of both studies would tend to indicate that the Wilson plant was not producing tablets that functioned as they would be expected to function when administered to opioid naive patients.
The remainder of the studies compared old and new versions of 80, 40, and 10 mg tablets. It is unknown which plants manufactured the tablets used in any of these studies. In some studies the tablets were given to fasting subjects, and in in others, to fed subjects, In most of the studies, there were more adverse events with the new formula than with the old.
Here are the adverse event numbers. “Subjects” are the total number of subjects in the trial / “new” are the number of subjects experiencing one or more adverse events with the new formula / “old” are the number of subjects experiencing one or more adverse events with the old formula.
(study # / dose / fed or fasting: (subjects / new / old))
1. 40 mg Fed: 88 / 35 / 22 (subjects/new / old )
2. 40 mg Fast: 92 / 30 / 32 (subjects/new / old )
3. 80 mg Fed: 79 / 53 / 43 (subjects/new / old )
4. 10 mg Fast: 84 / 23 / 14 (subjects/new / old )
5. 10 mg Fed: 85 / 41 / 29 (subjects/new / old )
6. 80 mg Fast: 84 / 47 / 69 (subjects/new / old )
In 4 of the 6 studies, subjects given the new formulation tablets had more adverse events than those given the old formulation. This included all studies where the subjects had been fed and the 10 mg fasting study. While this tends to show a trend, the studies are uncontrolled, and we don’t even know how the results may have been influenced by which plant the test tablets were manufactured in (see discussion of tests 7 and 8).
As far as calling the FDA, I did so months ago, at the urging of my physician, who informed me that the majority of those patients he had been prescribing oxycontin to were also experiencing problems of one sort or another. He said that I was one of the lucky ones who haven’t been experiencing worse problems, but should call anyway.
I think that they should still make the “OC” verson for the people who are haveing bad reactions to the new verson “OP”.
i think they just need to be more selective about perscribing oxy cottin rather than changing the formula and messing with people who seek legit medical pain releaf.
These pills need to be checked by a chemist to see what is really in the op oxycontin i just don’t beleive purdue or the fda there is something in these pills other then what they are saying to be makingall these people sick
Hello, I have been taking oxy oc 10 for about a year now. I started taking the new oxy op 10 a while ago and there is a huge differnce!!!! First with my old oxy I got my pain relief and it last. With this new oxy it took for ever for me to get any kind if relief but even that was not effective at all I was still in pain. Then I broke out in hives, I was super itchy, I was sweating, my head started hurting so bad, I was crying. Then my body started to hurt all over, and I could not sleep at all!!!! Then I relized that I was going threw withdrawl!!! omg Really!! Then I did some research and found this oc vs op. I think its carzy!!! How can you do a test study for a different formation on a drug with people who have never used them! That makes no sense because We dont know how this new formation of the oxy effect people who have already been using it. So I dont yndetstand why the FDA would ever approve this new formation because what I have taking from the study that there is no evidence that it is effecttive and the possible side effects of long term oxy user is not there!!! Which makes no sense to have a test study on people who have never used the drug!!! I Have stop taking the the oxy op 10 because the side effects are just to much for me.
I have been taking oxicontin oc for afew years now. It has been a life saver ,it works it does exactly what it is supposed to do take pain away. the new op does nothing except make my knees swell and give me more pain. people in real pain need a good drug that works please go back and fix this I’ve cryed all week end w/my pain!
i have had gastric bypass in 2003 and still find medicine doesn’t work normal, no kind of meds. are there any studies out there. do you know of any medicine for chronic pain for gastric patients. as a result of my gastric i was sick and had to have thoracic surgery. my pain gets worse every year. thanks
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