A Drug Topics reader has asked: “What are your thoughts on making hydrocodone/APAP combinations CII?” At present, there is not much compelling, valid evidence upon which to base an answer.
No doubt FDA has based its move to make the schedule change on the many opioid deaths seen nationwide, which CDC has labeled an “epidemic.”1 There is more to the picture, however.
A murky subject
Many have said that the United States uses more hydrocodone than any other nation, but that is quite misleading.2,3 Most other countries do not report prescription opioid use, so to say that more opioids are prescribed by the United States than by the rest of the world is unsubstantiated.
Prescribed indications are also a consideration. European countries use dihydrocodeine more commonly than they do codeine, hydrocodone, or morphine.
In Canada, hydrocodone is generally used only in cough syrups or elixirs, not for pain treatment.
In Australia hydrocodone has largely been replaced by morphine.
Ignoring these factors skews the argument that the United States consumes the most hydrocodone worldwide and the claim that hydrocodone has been prescribed more than any other prescription drug in the United States. Unfortunately, many journalists have chosen to disregard these points in order to sell stories.
Mainstream media also are not shy about skewing the data, and politicians are not far behind, often avoiding objective evidence.
Practically in my own backyard, speaking on an extended-release formulation of hydrocodone, Senator Chuck Schumer said, “It’s tremendously concerning that at the same time policymakers and law enforcement professionals are waging a war on the growing prescription drug crisis, new superdrugs could well be on their way, flooding the market …The FDA needs to grab the reins and slow down the stampede to introduce these powerful narcotics.”
This is an example of media-driven political hyperbole. Hydrocodone is not a new drug; it has been on the market for over 40 years; and it certainly is not a “superdrug.” Compared to hydrocodone, hydromorphone (Dilaudid) is 10 times more potent and fentanyl is 100 times more potent; and remifentanil and sufentanil supersede both of these in potency.5
The therapeutic reasons for including hydrocodone (and other opioids) in the standard formulary are to expand the armamentarium from which to choose for patients in legitimate need of opioid analgesic therapy.
While there are five different chemical classes of opioids6, among the phenanthrenes alone there are very significant pharmacological and therapeutic differences. Examples of phenanthrene opioids include morphine, opium, diacetylmorphine (heroin), hydroco-done, naloxone, hydromorphone, oxycodone, oxymorphone, buprenorphine, nalbuphine, levorphanol, codeine, dextromethorphan, and others.
Each has its drawbacks and advantages. Codeine is very constipating and less potent than most. Oxycodone often causes agitation and inability to sleep. Morphine has a higher incidence of neurotoxicity and histamine reactions, etc.
Some of these drugs are pure mu agonists, others are partial agonists/antagonists, some are kappa, some cause NMDA receptor blockade, and others are uptaken variously by certain mu-receptor subtypes.
These differences all have a bearing on therapy choices, which is why several options are needed for specific pain types and select patients — and we have not yet even considered the metabolic differences resulting from polymorphism, specific opioid selection to avoid drug interactions, and several other therapeutic factors. For politicians to simplify these issues is naïve at best.
While these considerations are not a direct response to the original query of whether or not hydrocodone should be included under Schedule II or Schedule III, in my mind there are other, more pressing questions, such as:
How difficult should we make it to get these drugs?
- Should they be nonrefillable, regardless of schedule?
- Should all scheduled drugs be treated the same, since all have potential for abuse?
- If two drugs are mg-for-mg equipotent (e.g., hydrocodone and morphine), do they have the same abuse potential?
- How can we best monitor for diversion?
- Whose responsibility is it to monitor these drugs along the supply chain?
- How can we encourage and engage contiguous states and federal facilities to share PMP (prescription monitoring program) data?
- What does it take to educate healthcare providers about important therapeutic distinctions among opioids and adjuvant analgesic options?
- How can we hold politicians accountable for promulgating fear among constituents, instead of supporting prescription take-back programs and calling for education for consumers and the prescribers/pharmacists who care for them?
- The poorest patients have the least medical coverage, the greatest access to abusable immediate-release formulations, and the least access to brand-name extended-release products and abuse-deterrent formulations. How can we convince third-party payers to cover such options as nutritional counseling, exercise (yoga, fitness centers, etc.), psychotherapy, and other alternatives to drugs?
- Most important, how do we ensure that our legitimate patients have access to the drugs they really need?
âNew York State changed hydrocodone over to a Schedule II drug as of April 2013. Since that time, hydrocodone prescriptions for pain have diminished, codeine prescriptions for pain and cough products has remained the same, and prescriptions for oxycodone IR use have increased. I’m not sure whether these consequences are good, bad, or irrelevent; nor do I know whether trends will change or whether the example of New York’s outcomes is an isolated one, compared to those of the rest of the country.
I have often been asked whether or not hydrocodone should be rescheduled. To my mind, at least for now, we won’t know whether there’s a negative impact on legitimate pain patients or a positive impact on mitigating overdose risk until we have more data — after it is rescheduled. Perhaps the New York State PMP data will shed some light on possible outcomes.
1. CDC Grand Rounds: Prescription drug overdoses — a U.S. epidemic. Morbidity and Mortality Weekly Report. January 13, 2012. 61(01);10-13. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6101a3.htm
2. Drummond G, Vowler S. Type I: Families, planning, and errors. Editorial. Exp Physiol. 2013; 98.1:3-6.
3. Manchikanti L, Fellows B, Ailinani H et al. Therapeutic use, abuse, and nonmedical use of opioids: A ten-year perspective. Pain Physician. 2010;13:401-435.
4. Gormley M. Chuck Schumer warns FDA on danger of “super painkillers.” Huffington Post. November 6, 2013. http://www.huffingtonpost.com/2012/01/09/chuck-schumer-painkillers_n_119....
5. Fudin J. Hydrocodone: Potency, popularity, politics, and practicality. August 1, 2012.
6. Fudin J. Chemical classes of opioids. http://paindr.com/wp-content/uploads/2012/05/Opioid-Chemistry-09-2011.pdf.
Dr. Fudin is adjunct associate professor, pharmacy practice and pain management, Albany College of Pharmacy and Health Sciences; adjunct assistant professor, pharmacy practice, University of Connecticut School of Pharmacy; and founder and chair, PROMPT (Professionals for Rational Opioid Monitoring & Pharmacotherapy). Contact him through his blog, PainDr.com.