Let’s take a look. to see if the LA Times is in fact an oxymoron.
Merriam-Webster’s online dictionary defines moron as “a very stupid or foolish person”, but since this country treats corporate entities as people, I’d say LA Times qualifies. Their legal definition is “a person with a mild or moderate intellectual disability —used formerly — see also idiot.”
Other OXY-morons include anti-opioid zealots in the lay press, some propagandists, and politicians who persistently call OxyContin “synthetic heroin”. One who is skilled in the art and science of pharmaceutics knows this to be untrue. In fact, oxycodone is a precursor to oxymorphone, a CYP2D6 metabolite of the former. Oxymorphone is one substituent on the tertiary amine (nitrogen) different in chemical structure to naloxone as pointed out in a previous post Breaking Bad 2.0: Is it possible to synthesize Oxycodone from Naloxone?. That said, OxyContin, oxycodone, and oxymorphone are synthetic congeners of naloxone, an opioid receptor blocker with virtually no medical dangers and an antidote to what anti-opioid zealots otherwise describe as “synthetic heroin”: morphine, fentanyl, and heroin itself. Naloxone actually saves people from respiratory depression from opioid overdose. In fact, OxyContin is more similar in chemistry to over-the-counter dextromethorphan (the ‘DM’ in Robitussin DM) than it is to heroin. Truth be told, heroin is semi-“synthetic morphine” because heroin is essentially two morphine molecules synthetically sandwiched together by an acetyl group, more commonly known as vinegar. But alas, I suppose not knowing this science doesn’t make someone a moron; professing to know something you know nothing about is certainly short-sided, idiotic, and without a doubt approaches moronism.
On May 5, 2016 LA Times printed an OxyContin dosing article, “You want a description of hell?’ OxyContin’s 12-hour dosing problem” by Rion and Girion (two potential OXY-morons).1 In rebuttal, I wrote an editorial with Drs. Mena Raouf and Erica Wegrzyn in a highly regarded refereed periodical, the Journal of Pain Research, entitled “OxyContin was submitted and justifiably approved by the Agency as a twelve-hour dosage form”, to clarify the idiocy of LA Times authors Rion and Girion and the editorial staff that allows such nonsense to be published.2
I encourage anybody that is interested to look at the JPR article mentioned above by clicking HERE. But, as an educational exercise, I thought it would be nice to engage an up and coming Student Pharmacist Lindsay Worthmann to summarize our JPR editorial and the various issues by posting a guest blog. Overseeing Lindsay’s writing was Dr. Erica Wegrzyn, my current PGY2 Pain and Palliative Care Resident. Here for your information and entertainment is what both of these young professionals had to say…
Ms. Lindsay Worthman and Dr. Erica Wegrzyn:
As we all know, just about every aspect of life is governed in some way, shape, or form by Big Brother and/or the letter of the law. Fortunately, there is some degree of leeway in medicine. Behold, the off-label use function.
When OxyContin came to market, it was intended for every 12-hour dosing (Q12H). This is how the product was approved by the FDA and what the manufacturer (Purdue Pharma) marketed and subsequently endorses. The recent article in the LA Times, mentioned above, called Purdue out for “knowing” that some patients experience an end-of-dose effect as the12-hour mark approaches.1 Now, if this is true (which it sometimes is), patients would be experiencing pain or perhaps mild opioid withdrawal before the next scheduled dose. This can result in additional immediate release medications (like oxycodone) prescribed to cover that time-span, i.e. breakthrough pain. More medications may affect other risks such as overdose, opioid craving, and the like. So what exactly is all the fuss about? It appears that the LA Times is upset that Purdue is not formally addressing this presumed “lack of efficacy”, or what is commonly known as “end-of dose failure” of a 12-hour dosing interval and isn’t promoting its use at 8-hour intervals. This is because Purdue is a pharmaceutical company and is LEGALLY prohibited from promoting off-label uses.
If a patient is experiencing this lack of benefit at Q12H dosing intervals, a Q8H dosing interval sounds like a plausible option. Logically, it makes sense: prevent return of pain, prevent withdrawal, avoid adding additional medications, and maybe even diminish the risk for diversion. The concern expressed by some, with dosing OxyContin Q8H, is that the patient could potentially experience a higher oxycodone plasma level, therefore increasing the risk for side effects such as a loss of consciousness or a decrease in respirations. There is no evidence to support this.
Off-label use is not an uncommon scenario. For example, fentanyl patches are marketed as Q72H, but may be used for Q48H as indicated in the label3. Tricyclic antidepressants (TCAs) such as amitriptyline for neuropathic pain are commonly used off-label4,5.
Can the pharmaceutical companies that make these drugs legally and openly support off-label uses? No.
Is fentanyl often dosed Q48H? Yes.
Is amitriptyline used for neuropathic pain? Yes.
Can oxycodone ER be usedQ8H? Yes.
Obviously, there are always risks associated with off-label use. There are also risks associated with any medication even when taken as prescribed. It is the responsibility of the medical provider to discuss risks vs. benefits of any treatment plan. The further a medical provider deviates from the intended use, the higher the liability. Many antidepressants and anticonvulsants without a pain indication are routinely used to treat neuropathic pain syndromes. Cancer drugs are frequently used for malignancies for which there is poor evidence. In the grand scheme of things, whether or not Purdue Pharma openly supports or endorses OxyContin Q8H is irrelevant, other than their obligation to follow the law and not promote for off-label use.
In closing, it is noteworthy that newspapers should provide accurate information by honest journalists who do their homework and provide each side of a controversial story. Perhaps the term Newspaper here is an oxymoron too, since the definition of oxymoron is “a combination of words that have opposite or very different meanings”.
Lindsay Worthmann will be graduating with her PharmD from Western New England University in May 2017. She is currently on rotation at the VA in Albany with Dr. Jeffrey Fudin and has a full year of rotations ahead of her. While not working, she enjoys spending time with her family and friends, she looks for adventure in everything, and has a desire to travel and see the world. Most recently she traveled to Utah to attend the APhA Institute on Alcoholism and Drug Dependencies. That conference and this time spent with Dr. Fudin has only fueled her interest in addiction and pain management that much more. Lindsay is looking forward to the upcoming year and finding her place in the field of pharmacy. She is pictured here receiving her certificate for induction into the Epsilon Iota chapter of the Rho Chi Honor Society.
Erica Wegrzyn, B.A., B.S., PharmD is currently completing a PGY-2 Pain and Palliative Care residency at the Stratton VA Medical Center, Albany NY. Dr. Wegrzyn received her PharmD from Western New England University College of Pharmacy, Springfield MA and completed a PGY-1 residency at Maine General Medical Center, Augusta ME. Prior to completing her PharmD, Dr. Wegrzyn also received her bachelors’ degrees in Biochemistry and Music (trombone) from Ithaca College. Dr. Wegrzyn recently had the honor of presenting her ongoing research at the #PAINWeek2016 national conference in Las Vegas, NV.
- Ryan H, Girion L, Glover S. ‘You want a description of hell?’ OxyContin’s 12-hour dosing problem. LA Times. May 5, 2016. Available from: http://www.latimes.com/projects/oxycontin-part1/. Accessed July 22, 2-16.
- Fudin J, Raouf M, Wegrzyn EL. OxyContin was submitted and justifiably approved by the agency as a 12-hour dosage form. J Pain Res. 2016 Sep; 9:613-624.
- Fudin J. Can Fentanyl Patches Be Replaced Sooner to Improve Pain Control? Medscape. 11 Jan 2008. Available online at: http://www.medscape.com/viewarticle/566115
- Sansone RA, Sansone LA. Pain, Pain, Go Away: Antidepressants and Pain Management. Psychiatry (Edgmont). 2008 Dec; 5(12): 16-19.
- Moore RA, Derry S, Aldington D, Cole P, Wiffen PJ. Amitriptyline for neuropathic pain and fibromyalgia in adults. The Cochrane Collaboration. John Wiley & Sons, Ltd. 2012 (12).