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Emergency Medicine News:
doi: 10.1097/01.EEM.0000433392.84903.57
InFocus

InFocus: Oxymorphone: Opioid Abuse Flying Under the Radar

Roberts, James R. MD

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Dr. Roberts is the chairman of emergency medicine and the director of the division of toxicology at Mercy Catholic Medical Center, and a professor of emergency medicine and toxicology at the Drexel University College of Medicine, both in Philadelphia.

It only takes one shift in the ED to realize that the use and abuse of opioid pain medications play an integral role in emergency medicine practice. The pain relief and sedation provided by a number of opioids are a godsend, but dealing with opioid-dependent patients is simply god-awful.

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Many conditions that produce chronic pain are unsolvable, but all are at least temporarily treatable. Naturally, the ED is often the final pathway for unfortunate and hapless patients who require acute and chronic opioid use. No one argues with providing opioids for sickle cell or cancer pain, painful procedures, or acute trauma. Trying to figure out who has legitimate pain versus a bogus complaint from an opioid addict who is gaming a sympathetic clinician can be daunting — a near-impossible conundrum.

EPs and other providers are challenged daily when attempting to ferret out opioid cravings and addiction from true pain. How to deal with the individual who has become addicted because of his unsolvable but real chronic painful condition is even more of a quandary. The patient with a bona fide chronic pain diagnosis also can have pecuniary interests, nicely supplementing his income by selling opioids harvested from a naïve clinician.

It doesn't take long to get a good handle on the various methods of subterfuge commandeered to score sought-after opioids, such as oxycodone, hydrocodone, or hydromorphone. The artful tactics and clever shenanigans of individuals seeking to flummox, baffle, or otherwise bewilder the nascent opioid-prescribing ED doc are quickly evident, albeit fascinating, to anyone paying attention.

Scoring a prescription for the relatively new but very potent opioid oxymorphone is a burgeoning cottage industry, but this medication may be under the drug-abuse radar of many physicians. The brand name, Opana, may even be totally unknown. Oxymorphone, however, has surfaced as a valuable analgesic and yet another challenge for clinicians.

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An Overdose Death Involving the Insufflation of Extended-Release Oxymorphone Tablets

SP Vorce, Levine B, et al

J Anal Toxicol

2010;34(8):521

This report involves one on-scene death and one patient with severe opioid toxicity who survived after nasally inhaling (snorting) of oxymorphone extended-release tablets (Opana ER) in conjunction with alprazolam (Xanax). Opana ER tablets were crushed and snorted by two young women, resulting in the death of one and classic opioid toxicity in the other. These cases, as is common with many drug-related catastrophes, were polypharmacy overdoses that included oxymorphone, dextromethorphan, alprazolam, and other benzodiazepines. The exact clinical role of each substance was a bit vague, but oxymorphone was thought to be the major lethal culprit.

Few details are available on the clinical nuances of the specific cases, but this report is a reminder that oxymorphone tablets are highly abusable, and this opioid has gargantuan potential potency. (See Black Box Warning.) Of note, oxymorphone was not identified by standard toxicologic tests available to clinicians; specific confirmatory analysis requires the expertise of a reference laboratory. It is a common scenario in drug-related cases, that specialized testing equipment (gas chromatography and mass spectrometry) is required to confirm all of the clinically relevant substances.

Comment: Many clinicians are not familiar with oxymorphone, and a review in Pharmacy & Therapeutics is worth reading. (2010;35[6]:324.) Our hospital pharmacy does not carry it, and I had to call five drug stores (CVS, RiteAid, and Walgreens, among them) before I could find one that stocked a few versions of this opioid so I could include a picture.

Oxymorphone, which came to market in 2007, is six to eight times more powerful than morphine. It is an active metabolite of oxycodone (Percocet/Oxycontin). Getting high from oxymorphone by the standard methods — crushing an extended-release tablet followed by either IV or inhalation administration — appears to be quite popular and well known to the abusing aficionado. (J Anal Toxicol 2009;33[9]:615.)

The extended-release formulation contains a whole lot of potent drug. Oxymorphone excess produces a classic opioid overdose, manifested as somnolence, coma, miosis, diaphoresis, decreased bowel sounds, decreased respirations, cyanosis, hypotension, and bradycardia, and it's readily reversed by naloxone. The clinical toxidrome is readily appreciated, but the cause cannot be confirmed by the dearth of information gleaned by the immunoassay available to mere emergency clinicians. Similar problems exist with fentanyl, meperidine, propoxyphene, tramadol, and methadone, and even the frequently prescribed oxycodone; all can escape detection with many routine assays.

Oxymorphone has a unique relationship to ethanol, unlike other opioids, and this pharmacologic quirk is not well known to clinicians. Taken with alcohol, the extended-release formulation will exhibit up to an amazing 100 percent increase in blood levels. It would not take much for a user to nearly double the oxymorphone level if the ER formation were taken with a few drinks. This observation has forensic importance when seemingly nontoxic doses are taken with ethanol. This characteristic of oxymorphone is emphasized in the drug's black box warning.

Opana abuse in the United States has overtaken Oxycontin abuse, according to USA Today. (July 10, 2012; http://usat.ly/1234NOP.) This popular newspaper describes frenzied attempts by drug addicts to obtain oxymorphone (Opana), often eschewing the previous favorite, Oxycontin. Overdose deaths from opioid pain relievers have surpassed deaths from heroin and cocaine since 2008 despite pharmaceutical company attempts to concoct tamper-resistant tablets or to add narcotic antagonists, such as naloxone, to their products. Interventions designed to limit inhalation and pill injection use by blocking the talents of the abuser to crush, break, or dissolve pills have met with varying success. Efforts have been attempted with oxymorphone, but it is problematic that a generic, non-manipulated product still exists. The extended-release pills, with their coatings formulated to provide slow release, are favorite prey of the abuser because each pill contains large amounts of medication. Pharmaceutical alterations may limit the ability to crush, dissolve, inject, or snort medications, but it does nothing to curb abuse by simply swallowing it.

A Philadelphia division of the Drug Enforcement Administration highlighted the potential for abuse of Opana in May 2011. It's becoming a new favorite. The DEA emphasized that oxymorphone is a powerful semi-synthetic opioid analgesic that may provide euphoria perceived to be better than heroin or morphine. Oxymorphone is quite effective for relief of moderate to severe pain, and is often used as a postoperative medication. Oxymorphone is available as immediate-release and extended-release tablets, with the brand names Opana and Opana ER, respectively. Opana ER is available in 5, 7.5, 15, 10, 20, 30, and 40 mg tablets, available on the street for up to $75, making it a very popular and seemingly profitable drug of abuse in Philadelphia. The Philadelphia Medical Examiner reported four deaths from oxymorphone in the first six months of 2011. Many contend that Opana threatens to become the next Oxycontin.

The medical use of oxymorphone is well supported. (J Opioid Manag 2008;4[3]:131.) The extended-release formulation is quite effective for chronic cancer and chronic non-cancer pain, with analgesic efficacy and tolerability comparable with or better than morphine and oxycodone. The makers of Opana and Oxycontin have included tamper-resistant formulations, but easily crushed, injected, and snorted generic brands of oxymorphone are still marketed. There appears to be some controversy between the FDA and the manufacturers about whether their reformulated versions actually inhibit abuse.

Oxymorphone may frequently be requested by name in the ED by legitimate patients and by those seeking to dupe physicians charged with relieving pain. Add it to your list of medications that can cause an opioid overdose and respond to naloxone but otherwise remain clandestine. It appears that oxymorphone is becoming a favorite of drug-abusing mavens because it produces an effective and pleasant narcotic high and great euphoria.

Attempts at strict regulation, decreased prescriptions for opioid pain medications, and efforts to deter abuse have led to the increased popularity of heroin, a drug that can be snorted and injected. It's probably easier now to get heroin on the street in the Philadelphia area than it is to obtain Oxycontin. Many physicians still prescribe opioid pain medications with reckless abandon. New York City hospitals and the American Academy of Emergency Medicine have taken a stab at attempting to limit prescriptions for opioids emanating from the ED. Whether this will have any real effect remains to be seen. Of course, such a broad brush will limit appropriate use of oral opioids, and many ED clinicians oppose such efforts.

Drug-addicted patients gain information on how to obtain and manipulate prescription medications in numerous ways. One of the more popular and most toxicologically fascinating websites is Erowid. (www.erowid.org.) This website is described by Wikipedia as: “ …a 501(c)(3) non-profit educational organization that provides information about psychoactive plants and chemicals as well as activities that can produce altered states of consciousness such as meditation and lucid dreaming.” Some rather interesting Erowid-gleaned comments concerning the use of oxymorphone appear in the box.

A rather interesting side note: Opana ER when crushed, dissolved, or injected has been associated with the development of a thrombotic thrombocytopenic purpura-like illness. The Centers for Disease Control and Prevention reported 14 patients with a microangiopathic hemolytic anemia and thrombocytopenia who had injected the reformulated Opana ER. (MMWR Morb Mortal Wkly Rep 2013;62[1]:1.) The specifics of this possible association are unknown, but patients with a clinical scenario similar to TTP should be asked about Opana ER abuse. Cocaine is also associated with TTP.

Reader Feedback: Readers are invited to ask specific questions and offer personal experiences, comments, or observations on InFocus topics. Literature references are appreciated. Pertinent responses will be published in a future issue. Please send comments to emn@lww.com.

Dr. Roberts: I noted that you and Dr. Larry Mellick advocate using needles to fill the balloon when using a Word catheter. (“Avoid I&D for Bartholin Gland Abscess, and Try a Word Catheter Instead,” Roberts JR, EMN 2013;35[6]:16 and “A Word about Word Catheters,” Mellick LB, M2E Too! Mellick's Multimedia EduBlog; EM-News.com; http://bit.ly/12pBoC8.

But you can fill the balloon without a needle and decrease the risk of needlestick. Just take a slip tip, push up into the depression where the needle would go, make a seal, and fill the balloon with water or saline. — Thomas R. Jones, MD, Temple, TX

Dr. Roberts: I have been using Word catheters for years, and one tip that I didn't see in the article or the video is that after insertion and inflation, rotate the catheter so that the stem is directed into the patient's vagina, not hanging externally. It's more comfortable and less likely to be pulled out inadvertently. — Vivian Kane, MD, Allentown, PA

Dr. Roberts: In an ideal world, all Bartholin gland abscesses would be packed with a Word catheter. I have had the fortune of working in a quite a few locations, however, that have refused to stock or release from the OR the famed Word catheter. The residency where I trained under the tutelage of Dr. Paul Gennis came up with the novel Jacobi ring as a substitute. Proper placement is described in his article: “Jacobi Ring Catheter Treatment of Bartholin's Abscesses,” Am J Emerg Med 2005;23(3):414. — Harry Kopolovich, MD, Bronx, NY

Dr. Roberts responds: These are helpful and nifty suggestions from ED docs who obviously have adopted this technique. Let us know if any of you are motivated to try the loop drainage technique rather than the Word catheter.

Dr. Kopolovich has experience with the Jacobi technique, which is quite similar to loop drainage, and he offers the following insights:

“The loop technique is actually quite simple to use. It requires a simple stab incision to treat the abscess followed by an additional stab incision to create a tract through which to pass the loop of rubber. An additional item that can be used instead of OR rubber tubing is simple butterfly tubing. One merely cuts the plastic from the butterfly needle and passes a 1-0 silk suture through the tubing.

“The technique may be somewhat more complicated than placing a Word catheter, but the loop ring will not fall out as compared with the catheter. Incidentally, the few patients that I have seen for follow-up have preferred the loop technique because there is less protrusion from the wound compared with the catheter.”

Click and Connect! Access the links in EMN by reading this issue on our website or in our iPad app, both available on www.EM-News.com.

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Experiences Abusing Opana ER

The Champagne of Opioids1

“I was lucky enough to be able to purchase a 40 mg Opana ER, and had never used this specific chemical. I got it for a mere 60 bucks, and shared a bump with my friend, who had a small amount of alcohol prior to the experience.

“After measuring an equal amount for both of us, we insufflated the substance. It took about one hour for the effects to truly peak, and [we had] five hours of complete bliss. It was much stronger than any white heroin I've had and much more deep. I soon became very relaxed and my body was in pure ecstasy, warm and fuzzy with a feeling I like to call ‘comfortably numb,’ meaning in a perfect state of tranquility. It had almost a roll type feel to it, except instead of hyper and full of energy and empathy, I felt the previously described states.

“All [in] all, it felt very different from Oxycontin and heroin and any other opioid really, except fentanyl and Dilaudid, of which it shared some very strong effects and similarities. I would love to have this again. One of my favorites, hands down.”

Near Death2

“After procuring the drug off a friend who had a relative prescribed to it, I decided to go over to a friend's house and snort half a pill. About three minutes after snorting the half, I started to notice the ever-so-familiar warm opioid feeling coming over my body and head. This opioid buzz, however, was different from any other buzz I have ever experienced. The buzz was so euphoric and enjoyable; I felt as if nothing mattered in the world and everything was fine. After around an hour of this feeling, a friend of mine wanted to try this pill out so I broke up the other half between us and insufflated my share. After that, we went outside for a walk or a cigarette, and that was the last thing I remembered.

“I woke up in a hospital bed shaking violently, with tubes sticking down my nose and mouth and barely being able to breath. The doctor explained to me that I had overdosed and that I had stopped breathing for a few minutes and had CPR administered to me. I was in a state of utter shock! How could I OD off of less than one pill of any kind, I asked myself? My tolerance to opioids is somewhat astronomical so this was an astonishing thing to happen. Obviously, I have learned a great deal off of this, and have limited my drug use to Ultram (tramadol) and other weak opioids.”

1. “The Champagne of Opioids: Experience with Oxymorphone (Opana).” (ID 68518) Erowid.org. Mar 29, 2008; www.erowid.org/exp/68518.

2. “Near Death: Experience with Oxymorphone (Opana ER).” (ID 69911) Erowid.org. Apr 18, 2008. www.erowid.org/exp/69911.

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Oxymorphone (Opana) Black Box Warnings

Respiratory Depression

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Life-threatening and fatal cases may occur even with recommended use; monitor for respiratory depression especially during treatment start or after dose increase. Instruct patients to swallow tabs whole; crushing, dissolving, or chewing tabs can cause rapid release and absorption of potentially fatal oxymorphone dose.

Accidental Exposure

Accidental ingestion, especially by children, can result in fatal oxymorphone overdose.

Avoid Alcohol

Do not consume alcoholic beverages; do not use alcohol-containing prescription or non-prescription medications; alcohol consumption during treatment may result in increased plasma levels and potentially fatal oxymorphone overdose.

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Endo Pharmaceutical Company Attempts to Discourage Abuse of Opana ER (oxymorphone) Tablets

Endo Pharmaceuticals received FDA approval for a reformulation of its extended-release oxymorphone tablets (Opana ER) in 2011 designed to make them crush-resistant yet be bioequivalent with the original version and not interfere with drug absorption following oral administration. The company no longer manufactured the older version of the drug by the end of 2012, but generic, non-tamper-resistant pills were still on the market.

The new formulation, termed INTACT technology, incorporated polyethylene oxide to render the pills crush-resistant, requiring up to 225 pounds to accomplish crushing. A gel-like substance forms when water is added to the pulverized pill, which is meant to discourage IV injection. Snorting the pill's contents is still possible if it can be ground to a fine powder. The crushed pills also resisted extraction with water, cooking oil, and acetone. It is debatable whether this method is effective enough to stop diversion and pill abuse.

Abuse is defined as crushing the extended-release pill and inhaling the powder or dissolving the pulverized material in water and injecting the solution intravenously, both of which are designed to produce a rapid effect.

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FastLinks

* Read the Procedural Pause, EMN's newest blog by Dr. Roberts and his daughter, Martha Roberts, ACNP, CEN, at http://bit.ly/ProceduralPause.

* Read all of Dr. Roberts' past columns at http://bit.ly/RobertsInFocus.

* Comments about this article? Write to EMN at emn@lww.com.

© 2013 by Lippincott Williams & Wilkins

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