ORLANDO — In his presentation at the 2017 annual meeting of the American Academy of Pain Medicine (AAPM), Jeffrey Fudin, PharmD, DAAPM, FCCP, FASHP, adjunct associate professor at Western New England University College of Pharmacy, highlighted some of the major concerns he has regarding the guidelines established by the Centers for Disease Control and Prevention (CDC) for prescribing opioid for chronic pain.1,2
This guideline, consisting of 12 recommendations, was issued in June 2016 and provoked much controversy and anxiety within the medical community. As Dr Fudin mentioned during his talk, despite the fact that these guidelines were based on either case series or expert opinion, they were assigned a grade A recommendation, a grading which usually requires a minimum of 2 class I studies.
Dr Fudin cited a study published in January 2016, which states: “For reasons that are unclear, the notion has become entrenched that 100 or 120 mg per day of morphine equivalent is a ‘high dose’ of opioids and is associated with an inflection point of risk for overdose, despite varying definitions of how daily dose is calculated.”3 This study examined data from more than 2 million patients over a one-year period in the state of North Carolina which uses a controlled substances prescription monitoring program. Of those patients, 478 died from overdose, amounting to 0.022% of overdose-related deaths per year. In addition, 80% of those deaths occurred in patients who had been co-prescribed opioids and benzodiazepines. “That’s one CDC guideline I’ll go along with,” remarked Dr Fudin, referring to guideline #3, which points to the “increased risks for respiratory depression when opioids are taken with benzodiazepines, other sedatives, alcohol, illicit drugs such as heroin, or other opioids.”2 Patients in this group had rates of death from overdose 10 times higher than in those patients not co-dispensed benzodiazepines.
This study, according to Dr Fudin, contributed to setting the stage for the negative perception of opioids. He then went on to explain the issues he has with some of the “most egregious’ of the CDC guidelines.
Guideline #4: “When starting opioid therapy for chronic pain, clinicians should prescribe immediate-release opioids instead of extended-release/long-acting (ER/LA) opioids (recommendation category: A, evidence type: 4).”2
Dr Fudin pointed to the fact that there is a lack of evidence indicating that ER opioids are more dangerous than immediate-release (IR) opioids. In fact, he added, ER opioids are safer, as their curve is blunted, and their peaks are lower than those observed with IR opioids. ER opioids are problematic when they are misused or abused, he added. According to him, an issue with opioid prescribing is that healthcare providers often struggle to adequately convert equianalgesic doses, and the real issue with ER opioids lies in their abuse, or use inconsistent with prescriptions.
Guideline #5: “When opioids are started, clinicians should prescribe the lowest effective dosage. Clinicians should use caution when prescribing opioids at any dosage, should carefully reassess evidence of individual benefits and risks when considering increasing dosage to ≥50 morphine milligram equivalents (MME)/d, and should avoid increasing dosage to ≥90 MME/d or carefully justify a decision to titrate dosage to ≥90 MME/d (recommendation category: A, evidence type: 3).”2
The lowest effective dose should be used for any drug, remarked Dr Fudin. “While it is true that doses ≥90 to 100 morphine equivalent daily dose (MEDD) have been associated with 8 times greater chances of accidental overdose, it may be that the conversion and titration are responsible, not the MEDD.” The issues that Dr Fudin has with MEDD are the following: 1) MEDD does not account for body weight; 2) There is significant pharmacogenetic variability; 3) Drug interactions vary across different opioids; 4) A subset of opioids should never have an MEDD, and this includes methadone (because of the great variability in its half-life), buprenorphine (because of its plateau dose), and tramadol (for which there is no equivalent to morphine).
Guideline #7:”Clinicians should evaluate benefits and harms with patients within 1 to 4 weeks of starting opioid therapy for chronic pain or of dose escalation. Clinicians should evaluate benefits and harms of continued therapy with patients every 3 months or more frequently. If benefits do not outweigh harms of continued opioid therapy, clinicians should optimize other therapies and work with patients to taper opioids to lower dosages or to taper and discontinue opioids (recommendation category: A, evidence type: 4).”2
“Not all opioids are created equal, so that if one opioid does not work, there may be other options,” commented Dr Fudin. In addition, “[patients] may tolerate and/or respond to one opioid better than to the others.”
Dr Fudin has several disclosures to report, including with Astra Zeneca, Depomed, Endo, Iroko, Millenium Health, and Remitigate.
- Fudin J. Pharmacologic and medical literature considerations when prescribing opioids for continuous use in noncancer patients. Presented at: the American Academy of Pain Medicine 33rd Annual Meeting; March 16-19, 2017; Orlando, Florida.
- Centers for disease control and prevention public health service u s department of health and human services. Guideline for prescribing opioids for chronic pain. J Pain Palliat Care Pharmacother. 2016;30(2):138-140.
- Dasgupta N, Funk MJ, Proescholdbell S, Hirsch A, Ribisl KM, Marshall S. Cohort study of the impact of high-dose opioid analgesics on overdose mortality. Pain Med. 2016;17(1):85-98.