Fentanyl; A Rose by Any Other Name Would Smell As Sweet

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A rose by any other name would smell as sweet, a phrase popularized by Shakespeare’s play Romeo and Juliet, where Juliet argues that it shouldn’t matter if her lover is from the rival Montague family; and that Romeo should be judged on his own merits.  Then in 1961, a modern-day film educed a similar theme but this time tensions were between a white American gang (the Jets) and a Puerto Rican gang (the Sharks, from the Upper West Side of Manhattan),  fueled this time by love between Riff and Maria. Fast forward to today, where we have a love affair between opioid abusers and heroin, laced with unanticipated potent illicit fentanyl derivatives – except this time, while the chemical families share similarities, the result is imminent death by unsuspecting heroin abusers. Unlike Romeo and Juliet or West Side Story, politicians, lawmakers, and journalist watching this film unwind are not grasping the message. 

It’s mind boggling to me that people are dying all around us from imported illicitly manufactured FenTanYl DERIVATIVES. I type in this fashion to sensitize readers to the fact that illegally imported DERIVATIVES are NOT synonymous with legitimate prescription fentanyl, and in fact, prescription fentanyl is on the bottom of the list as causing opioids deaths, as seen HERE.1 This week there were countless anti-opioid zealots spewing rhetoric on various mainstream media platforms (just Google it) regarding newly FDA approved Dsuvia (sufentanil sublingual), intended for medical emergencies, where oral administration is not a viable option, and IV access is not immediately feasible or medically desirable. See New Opioid 10 Times Stronger Than Fentanyl Approved Despite Abuse Concerns.

Our Albany Pain Team has recently published two articles on illicit fentanyls. A very detailed overview of the problem and the actual derivatives was published by Bettinger et al HERE in Practical Pain Management (PDF on request), and just this week by Persico and yours truly in Pharmacy Times HERE.2,3 These were preempts to today’s blog, written by a star Pharmacy Resident together with a Student Pharmacist from Western New England University College of Pharmacy.  Their bios and photos appear below.  This is what they had to say…

Opioid medications have been under heavy scrutiny over the past several years due to their associated risks of dependence, addiction, abuse, and death. The intense media coverage surrounding the ongoing opioid epidemic as well as the 2016 CDC Guideline for Prescribing Opioids for Chronic Pain continue fuel this scrutiny and cast opioids in a negative light. Irrespective, opioid prescribing has been on a steady decline as providers move to alternative analgesic options.4 While the number of prescribed opioids continues to drop, opioid-related deaths continue to rise.5 This divergence suggests that opioids largely responsible for overdose and death may not be coming from legitimate medical sources.

Significant contributors to the stunning number of opioid-related fatalities are the illicit products being used recreationally.5 Illicit fentanyl and its derivatives are used either alone or in combination with other agents, such as heroin and cocaine seen this week in the Mac Miller incident. CDC opioid overdose reports continue to highlight the detrimental impact of opioids yet fail to clearly distinguish the agents driving the alarming number of fatalities. These reports have morphed the word “fentanyl” into an umbrella term used to encompass not only the FDA-approved medication fentanyl, but its pharmaceutical and illicit derivatives, as well.6 Fentanyl derivatives drastically differ in their potency, duration of action, metabolism, and intended use more aptly described as misuse.

Fentanyl, a synthetic opioid which is about 50-100 times more potent than morphine, has been used since 1968 for the treatment of moderate to severe chronic pain in several different settings.6 Fentanyl’s unique chemical properties allow it to be formulated into a variety of dosage forms, such as transdermal patches, injections, dissolvable tablets, and nasal sprays. Each of these formulations possess different indications, attributes, and dosages. For example, the nasal spray formulation (Lazanda®) and dissolvable tablet/film formulations (Actiq, Abstral, Onsolis, and Fentora) are indicated for breakthrough cancer pain, with a rapid onset and short duration of action.3 Comparatively, the transdermal patch (Duragesic) provides around-the-clock analgesia for patients with chronic moderate-to-severe pain.6

Fentanyl has three FDA-approved chemical derivatives for human use: alfentanil, remifentanil, and sufentanil. These medications are limited to inpatient use due to their intravenous routes of administration.6 Alfentanil is roughly one quarter as potent as fentanyl and is used for induction and maintenance of anesthesia.6 Remifentanil also serves a role in anesthesia but has a drastically different pharmacodynamic profile. It is about twice as potent as morphine and is rapidly inactivated in the body making it a suitable agent for procedures requiring rapid induction and recovery from anesthesia.6 The last derivative, sufentanil, serves an anesthetic role in patients who are intubated and ventilated and is notably 5 to 10 times more potent than fentanyl.3 One additional FDA-approved derivate, carfentanil, is not approved for use in humans. This dangerously potent medication (approximately 100 times more potent than fentanyl) is used as a tranquilizer in elephants and other large mammals.6

 While the pharmaceutical agents described above can undoubtedly be lethal when misused, they are not the primary contributors to the rise in opioid-related deaths. Illicit fentanyl and derivatives continue to be synthesized and distributed for recreational use. The United States Drug Enforcement Administration (DEA) reported a 117% increase in the identification of illicit fentanyl and its derivatives from seized drug evidence between 2016 and 2017.7 And without a doubt, some deaths that have previously been attributed to fentanyl in general, likely were from these derivatives; since they share the same chemical nucleus, forensic labs may not look for the specific illicit unless they knew what to look for. It has been challenging to study these fentanyl derivatives since they are continually being developed and produced through illegal means.

The role and reputation of pharmaceutical fentanyl and the FDA-approved derivatives in pain management, including recently approved sublingual sufentanil, have been damaged and stigmatized partly due to the current chaotic approach by which opioid-related deaths are reported. By grouping pharmaceutical fentanyl products with illicit chemical derivatives in overdose reports, the medical community is being driven away from pharmaceutical fentanyl products that have a legitimate place in therapy.  With the rise in opioid-related deaths caused by illicit fentanyl derivatives it is imperative to remind providers, journalists, politicians, and the public that not all fentanyl derivatives are created equal. 

Illicit fentanyl may smell the same to detection (aka sniffer) dogs, but we assure you, imminent death is far from sweet.

As usual, comments are welcome!


Mark E. Baker, PharmD Candidate

 

Mr. Baker is in his last year of studies at Western New England University in Springfield, MA. He has recently completed an Advanced Pharmacy Practice Experience (APPE) in chronic pain management at the Stratton Veterans Administration Medical Center in Albany, New York under the direction of Dr. Erica Wegrzyn.

 

 

 

 


Amelia L. Persico, PharmD, MBA

 

Dr. Persico is a graduate of Albany College of Pharmacy & Health Sciences and Union Graduate College. She has practiced as a community pharmacy manager and is currently a PGY1 Pharmacy Resident at the Stratton Veterans Administration Medical Center in Albany, New York.

 

 


Information provided is the sole work of the authors, and the stated opinions or assertions do not reflect the opinions of employers, employee affiliates, or any pharmaceutical companies listed. It was not prepared as part of the authors’ duties as federal employees.


References

  1. Butler SF, Black RA, Cassidy TA, Dailey TM, Budman SH. Abuse risks and routes of administration of different prescription opioid compounds and formulations. Harm reduction journal. 2011 Dec;8(1):29.
  2. Bettinger JJ, Trotta ND, Fudin J. Wegrzyn EL, Schatman ME. Understanding the differences between pharmaceutical and illicit fentanyl and their analogues could save the opioid crisis. Practical Pain Management. 2018. July/August 8(5):59-67.
  3. Persico A, Fudin J. Separating Prescription From Illicit Fentanyl. Pharmacy Times Online. Posted October 29, 2018. Available at https://www.pharmacytimes.com/contributor/jeffrey-fudin/2018/10/separating-prescription-from-illicit-fentanyl
  4. Guy GP Jr, Zhang K, Bohm Mk, et al. Vital Signs: Changes in Opioid Prescribing in the United States, 2006-2015. MMWR Morb Mortal Wkly Rep. 2017;66(26):697-704.
  5. Schatman ME, Ziegler SJ. Pain management, prescription opioid mortality, and the CDC: is the devil in the data? J Pain Res. 2017; 10:2489-2595.
  6. Bettinger JJ, Trotta ND, Fudin J, et al. Fentanyl: Separating Fact from Fiction. Pract Pain Manag. 2018;18(5):59-67
  7. Emerging Threat Report. DEA; 2017. Available at: https://ndews.umd.edu/sites/ndews.umd.edu/files/dea-emerging-threat-report-2017-annual.pdf

 

10 thoughts on “Fentanyl; A Rose by Any Other Name Would Smell As Sweet

  1. I was injured in a fall from a balcony in 1994 and initially paralyzed from the waist down. Diagnosed ” Incomplete Parapalegic ” due to the fact that my spinal cord was compressed and punctured by many bone fragments yet, not completely severed in any one area. I lived in chronic and agonizing pain for over 5 years due to not only the injury, but the fact that in spite of my diagnosis and the insistance of any and all doctors and medical staff I talked to, even sometimes begged, for physical therapy to learn to walk again. I was constantly denied due to my insurance not wanting to cover what they called, “A waste of time.” I have a fusion of T11, T12, and L1, and had Harrington Rods placed from T8 to L5. Ignorant to the fact that these Rods held my spine in a very rigid, yet natural in a sitting position “state”. After months of coma, then rest and healing with the very welcome and badly needed “Mepergan Forte” to the layman, Demerol and Phenergan. I began trying to move my legs again, since they twitched and spasmed enough already on their own anyway. I was lucky that I was as stubborn as I am because although it was bittersweet, I did eventually teach myself to walk, with the unfortunate side effect of the hooks from the rods in my spine breaking off bone fragments from most every vertebrate from T8 down, and eventually detatching from all the hooks but two. One top, one bottom. That 5 year journey of agony, would never have been remotely possible without the aide of many different opioid pain killers over that 5 year span, from Dilaudid, Morphine, and Fentanyl, to Demerol, and many variations of Oxycodone and Hydrocodone, and also Darvon and Darvocet which I only recently learned is very similar to Methadone in many respects. Even with all of the opioid pain medications I was prescribed during that time, the pain was indescribably excruciating most of the time, exacerbated by the fact that I was unintentionally, slowly, breaking vertebrate on a daily basis while trying to walk again. I have no doubt that in the most painful years of my life, without those medications. Firstly, I would never have survived the injury to begin with. Even with all of the pain management, it was touch and go for weeks before they would even attempt surgery, which was a three surgeon tag team that took 18 1/2 hours from what I’m told. They would never have had the chance to perform the miracle that they did, if the pain management measures hadn’t kept me alive in the first place. Then most definitely kept me from taking my life due to the constant chronic pain that I endured, sometimes minute by minute, even with the pain medication. Then they continued to help me through miracle two, Walking Again. After a second surgery to remove the rods and bone fragments that I had created with my worthwhile yet foolish actions. I am happy to say that I am still walking under my own power, with the use of a cane, and the careful utilization of the opioid pain medications that I still take today, under my doctors care and communication, and also the same caring and understanding Pharmacists that have been filling my prescriptions for many years, and know me on a first name basis. There is nothing I can’t ask them, and never a time that at least one of them can’t take a few minutes to talk to me if I have a question or concern. Yes, I agree that abuse happens on both fronts, and for someone like myself, who will probably be on these much needed medications for the rest of my life, dependency is just a fact of life. That is the trade I make everyday for QUALITY of LIFE. I spent a few years with what I considered no other option, but to buy illicit drugs off the street, because as the drug addiction, overdoses, and deaths, hit the media. Doctors everywhere I turned, were afraid to keep prescribing any opiates, to anyone. Myself, and many other people, sadly, most of the people I had met were senior citizens, were forced to either go through withdrawal, and then try to deal with the pain, since most of us had already tried most of the alternative methods for pain management. I couldn’t live with the pain, and sitting in a wheelchair or being bed ridden, wasn’t an option. Not an option that I was willing to live with. What is the government going to do when the death toll rises even higher. The one fact that people are missing, is that the people that really need pain management that have to use opioid medicine to live any semblance of a normal life, will make a conscious decision to use illicit substances if they have no other avenue, because even with the chance of an overdose due to something like the Illicit Fentanyl derivatives that are so deadly compared to the pharmaceutical drug. Many will take the chance because the threat of death pales in comparison to a long existence, not even really a life, that will only be filled with pain.

  2. Greetings,

    Could someone provide some insight as to the following statement in the article: “prescription fentanyl is on the bottom of the list as causing opioids deaths, as seen HERE.1”

    The article referenced is by Butler SF et al. When I read this paper my understanding is that the graph they display is related to risk of abuse and not to deaths. Therefore, fentanyl would be at the bottom of the list causing abuse, not deaths.

    Am I reading this wrong?

    1. Prescription fentanyl is on the bottom of the list in terms of diversion, abuse, and therefore death. Illicit fentanyl derivatives are all diverted and sold on black market, are not the same as prescription fentanyl, potency and doses are variable with no controls, and yes, death from these illicit derivatives are very high and exceed that of any and all prescription opioids.

      1. Hi Jeff,

        Thanks for the prompt reply. I agree with your position and your concerns about illicit fentanyl and the article as a whole. I just disagree with the use of the Butler et al study to demonstrate prescription fentanyl is at the bottom of the list in terms of deaths. The exposure variable in their study involved the 7 opioid compounds and their outcome measure was abuse based on patient self-report. In the end, they report a relative risk of abuse (For which I agree, fentanyl is at the bottom) but this is much different from an outcome of/risk of death.

        As always, I appreciate what you do and the issues you bring to light.

        -Ryan

  3. I am a severe rheumatoid arthiritis sufferer for ten years now . I aquired the the disease when I turned forty . I’ve been prescribed many different treatments . The last six years I’ve been prescribed 75 microgram 3 day patches which have been very effective on taking away 95 percent if my pain . With low to no side effects. I’ve found them to be the most effective and safest treat mentioned to date. However because of the illicit fentanal overdose deaths in the news my pain management doctor is changing my treatment to hemp oil and an opioid drug called nucynta. I’m petrified this treatment wont be effective. I know my pain is so bad without an effective treatment I will be suicidal . The pain is that bad. Can these two drugs treat severe rheumatoid arthiritis pain effectively or is it my doctors reacting to pressures from dea? I’m willing to change if it will work. Any advice should I find a new pain management doctor or try this new treatment. I feel like the deal is stealing my life saving treatment because of the illicit drug users overdosing along with inaccurate reporting on real Dr prescribed fentanal patch treatment . For me it has been safe and effective. Any advice on what I should do . I am scared to death of returning to a life of pain and having to go on disability and possible suicidal

  4. It’s seems as though people are continuously being fed a completely incorrect narrative about prescription fentanyl. Fentanyl Analogues and Carfentanil (elephant tranquilizer) being sent through Mexico and Canada from China, are being added to street drugs in amounts that are amazingly deadly to the unknowing users. Reported as “Opioid Overdoses”, while accurate, the pictures of prescription medication bottles in the background immediately paint a different story in the head of the recipient of the report.

    The media has a hand in increasing the misleading reports about prescription fentanyl. I’ve seen written and televised reports of fentanyl and its dangers to police officers, first responders, even police K-9s, as well as those inadvertently overdosing on heroin and many other street drugs laced with non-prescription analogues of fentanyl.

    These reports inevitably depict prescription boxes of fentanyl patches while reporting on a completely different substance. I have written comments on many of these erroneously depicted stories. I also wrote an article for Pain News Network about the “REAL Opioid Epidemic” and its causes attempting to point out the use of “OPIOIDS” in general, when the true culprit cannot be obtained via prescription:

    https://www.painnewsnetwork.org/stories/2017/8/2/stop-torturing-chronic-pain-patients#.WYIDMkWeBbI.facebook=

    Kim Miller

  5. Thank you for this excellent delineation between pharmaceutical grade fentanyl and illicit fentanyl. I have survived severe, chronic, intractable pain for the last 17 years only because of pharmaceutical fentanyl. I had reached the point of hopelessness after 11 years of experience with every pain treatment imaginable, from acupuncture to pain pills, when a Pain Management Specialist tried fentanyl patches and lozenges. The last 17 years have been tolerable, but I fear that the actions of the CMS and its granting of power to the insurance companies that will decide whether I can or, most likely, cannot continue this treatment will be the end of my tolerable life.

  6. i have multiply documented conditions that cause me chronic pain. vascular ehlers danlos syndrome, crcps, degenerative disc disease, multi disc spinal fusion, pinched nerves, bulging discs, bone spurs and i have 2 inoperable aneurysms due to my veds.. my pain dr just up and eft with no warning so after 16 years on the same dose of meds, i was without any for over a week. i drank kratom tea to help with the withdrawals till i could find a new pain dr. so when i came to my first appointment i was drug tested and the kratom showed up as buprenorphine on the test. i informed them i have never taken it and it has to be the kratom. they refused my meds and dropped me as a patient. now i am living with horrible untreated pain and it is not fair. i followed the rules, never took more than prescribed, never asked for more or stronger meds. and this happens..the rate of suicide is rising in chronic pain patients ..and will continue because we are made to pay for jumkies getting high. we are forgotten people, expendable..these deaths will be on the governments hands. our meds are just as necessary to chronic pain patients as insulin is to a diabetic..but no one takes their meds away

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