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Step 2: Select Agent

Step 2: Select Agent

Universal Precautions, Step 2: Select Agent

If your clinical and risk assessment of the patient with chronic pain indicates that prescription opioid therapy is appropriate, the next step is to select a specific opioid agent. Numerous treatment guidelines exist to help guide the selection of appropriate opioid therapy for patients with chronic pain.1-5

Factors to consider when selecting an opioid agent and dosage include, but are not limited to, the patient’s general condition, medical status, and prior experience with opioids, including whether he or she is opioid tolerant.1,6 Patients who are opioid tolerant are those receiving, for 1 week or longer, at least 60 mg/day oral morphine, 25 mcg/hour transdermal fentanyl, 30 mg/day oral oxycodone, 8 mg/day oral hydromorphone, 25 mg/day oral oxymorphone, or an equianalgesic dose of another opioid.6,7

Another emerging consideration is opioid pharmacogenetics.

 

Pharmacogenetics

The rapidly progressing field of pharmacogenetics promises to contribute to our understanding of the variation in patient response to mu-opioid analgesics. For example, patients who have low or high expression of enzymes that are essential to the metabolism of specific opioid agents may experience poor efficacy or exaggerated medication effects, respectively.1,2 Pharmacogenetics soon may be applied in clinical practice to better predict which opioid agent may be best for an individual patient. For now, careful titration of treatment to patient response is key.1

References

  1. Argoff CE. Clinical implications of opioid pharmacogenetics [review]. Clin J Pain. 2010;26(suppl 10):S16-S20. PMID: 20026961
  2. Vuilleumier PH, Stamer UM, Landau R. Pharmacogenomic considerations in opioid analgesia [review]. Pharmgenomics Pers Med. 2012;5:73-87. PMID: 23226064
Consider an Abuse-Deterrent Opioid to Help Address the Potential for Opioid Manipulation and Abuse

After deciding on an opioid agent, you may wish to consider prescribing an abuse-deterrent formulation of that agent, if one is available.8,9 Abuse-deterrent formulations are designed with technology intended to help protect against intentional abuse of the agent. They generally are designed to make product manipulation more difficult or make abuse of the manipulated product less attractive or rewarding. Abuse-deterrent opioids do not address all types of abuse, including oral overconsumption; however, the risk is lower than it would be for opioids without such properties.10 Therefore, abuse-deterrent opioids are an important therapeutic option for you to consider as a provider to help reduce the potential for manipulation and the risk for abuse. Select a tab below for more information about methods and routes of prescription opioid abuse, the role of abuse-deterrent opioids in mitigating the risk of opioid abuse, and the types of abuse-deterrent opioids.

Providers may also want to consider switching appropriate patients with chronic pain on immediate-release therapy to extended-release abuse-deterrent opioids. Clinical trial data suggest that about 80% of patients taking opioids for chronic pain are on immediate-release therapy;12 however, prescribing extended-release abuse-deterrent opioids may provide additional opportunities to reduce abuse and diversion for the following reasons:12

  • The majority of abusers prefer immediate-release opioids to extended-release opioids 13
  • Daily pill volume for immediate-release opioids is 2-3x greater than for extended-release opioids14-16

When appropriate, consider prescribing an extended-release abuse-deterrent opioid to address chronic pain while simultaneously reducing opportunities for abuse and diversion.

Note that careful consideration should be given to the initial quantity of opioid medication prescribed. Patients receiving opioid therapy for the first time or being switched to a different opioid agent might require dose titration within the first 2 to 4 weeks. The follow-up interval should be considered when deciding on the initial quantity of medication. Be sure you are familiar with any state regulations concerning maximum quantities for opioid prescriptions; numerous states restrict these prescriptions to a 30-day supply.17

Although abuse-deterrent opioids do not address all types of abuse, including oral overconsumption, the risk for abuse is lower than it would be for opioids without such properties. Prescribing abuse-deterrent opioids is one step prescribers can take toward addressing the problem of abuse. However, there is still a risk of addiction, abuse, misuse, and diversion with these medications.10,17

As you do with any medication, consult the product labeling for the prescription opioid agent you have selected.

Select a tab below for more information about agent selection.

References

  1. Dowell D, et al. CDC Guideline for Prescribing Opioids for Chronic Pain — United States, 2016. MMWR Recomm Rep. 2016;65(No. RR-1):1-49. DOI: http://dx.doi.org/10.15585/mmwr.rr6501e1.
  2. Chou R, Fanciullo GJ, Fine PG, et al; American Pain Society–American Academy of Pain Medicine Opioids Guidelines Panel. Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain. J Pain. 2009;10(2):113-130. PMID: 19187889
  3. US Department of Veterans Affairs, US Department of Defense. VA/DoD Clinical Practice Guideline for Management of Opioid Therapy for Chronic Pain. Version 2.0. Washington, DC: US Dept of Veterans Affairs, US Dept of Defense; 2010. http://www.va.gov/PAINMANAGEMENT/docs/CPG_opioidtherapy_summary.pdf. Accessed November 6, 2017.
  4. Washington State Agency Medical Directors’ Group (AMDG). Interagency Guideline on Opioid Dosing for Chronic Noncancer Pain: An Educational Aid to Improve Care and Safety With Opioid Therapy. 2010 Update. Olympia, WA: Washington State Agency Medical Directors Group; 2010. http://www.agencymeddirectors.wa.gov/Files/OpioidGdline.pdf. Accessed November 6, 2017.
  5. Manchikanti L, Abdi S, Atluri S, et al; American Society of Interventional Pain Physicians. American Society of Interventional Pain Physicians (ASIPP) guidelines for responsible opioid prescribing in chronic non-cancer pain: part 2—guidance. Pain Physician. 2012;15(3 suppl):S67-S116. PMID: 22786449
  6. Utah Department of Health. Utah Clinical Guidelines on Prescribing Opioids for Treatment of Pain. Salt Lake City, UT: Utah Dept of Health; 2009. http://www.dopl.utah.gov/licensing/forms/OpioidGuidlines.pdf. Accessed November 6, 2017.
  7. US Food and Drug Administration. ER/LA Opioid Analgesic Class Labeling Changes and Postmarket Requirements. Letter to ER/LA opioid application holders. http://www.fda.gov/downloads/Drugs/DrugSafety/InformationbyDrugClass/UCM367697.pdf. Accessed November 6, 2017.
  8. Passik SD. Issues in long-term opioid therapy: unmet needs, risks, and solutions. Mayo Clin Proc. 2009;84(7):593-601. PMID: 19567713
  9. Webster LR, Fine PG. Approaches to improve pain relief while minimizing opioid abuse liability. J Pain. 2010;11(7):602-611. PMID: 20444651
  10. US Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER). Abuse-deterrent opioids; evaluation and labeling. https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM334743.pdf. Published April 2015. Accessed November 6, 2017.
  11. Roland CL, Setnik B, Cleveland JM, Brown DA. Clinical outcomes during opioid titration following initiation with or conversion to Remoxy®, an extended-release formulation of oxycodone. Postgrad Med. 2011;123(4):148-159. PMID: 21680999
  12. Cicero TJ, Ellis MS, Kasper ZA. Relative preferences in the abuse of immediate-release versus extended-release opioids in a sample of treatment-seeking opioid abusers. Pharmacoepidemiol Drug Saf. 2017;26(1):56-63. PMID: 27594167
  13. Morphine Sulfate Tablets [prescribing information]. Columbus, OH; Roxanne Laboratories, Inc.; October 2014.
  14. MS CONTIN (morphine sulfated extended-release tablets [prescribing information]. Stamford, CT; Purdue Pharma LP; December 2016. http://app.purduepharma.com/xmlpublishing/pi.aspx?id=ms. Accessed November 6, 2017.
  15. AVINZA (morphine sulfated extended-release capsules) [prescribing information]. Bristol, TN; King Pharmaceuticals, Inc.; November 2012. https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021260s017lbl.pdf. Accessed November 6, 2017.
  16. Centers for Disease Control and Prevention. Public Health Law Program Prescription Drugs. Menu of Prescription Drug Time and Dosage Limit Laws. https://www.cdc.gov/phlp/docs/menu_prescriptionlimits.pdf. Accessed November 29, 2017.
  17. Stanos S. Continuing evolution of opioid use in primary care practice: implications of emerging technologies. Curr Med Res Opin. 2012;28(9):1505-1516. PMID: 22937723

Pharmacogenetics

The rapidly progressing field of pharmacogenetics promises to contribute to our understanding of the variation in patient response to mu-opioid analgesics. For example, patients who have low or high expression of enzymes that are essential to the metabolism of specific opioid agents may experience poor efficacy or exaggerated medication effects, respectively.1,2 Pharmacogenetics soon may be applied in clinical practice to better predict which opioid agent may be best for an individual patient. For now, careful titration of treatment to patient response is key.1

References

  1. Argoff CE. Clinical implications of opioid pharmacogenetics [review]. Clin J Pain. 2010;26(suppl 10):S16-S20. PMID: 20026961
  2. Vuilleumier PH, Stamer UM, Landau R. Pharmacogenomic considerations in opioid analgesia [review]. Pharmgenomics Pers Med. 2012;5:73-87. PMID: 23226064

Methods and Routes of Prescription Opioid Abuse

Universal Precautions, Step 2: Select Agent

Opioids can also be abused without tampering.
Adapted from Katz N, Dart RC, Bailey E, Trudeau J, Osgood E, Paillard F. Tampering with prescription opioids: nature and extent of the problem, health consequences, and solutions. Am J Drug Alcohol Abuse. 2011;37(4):205-217. PMID: 21517709

When selecting an opioid agent, consideration should be given to the potential methods and routes of prescription opioid abuse.1 While the majority of abusers begin with oral consumption, they often progress to injection or inhalation. In one study, 83% of opioid-dependent individuals surveyed reported that they had first used the prescription opioid orally. By the time they were admitted for treatment, only 14% were still using the oral route while 62% were inhaling and 26% were injecting.2

The most common methods of abuse may also vary depending on the opioid medication.3 Extended-release (ER) formulations of prescription opioids are prone to tampering for abuse by non-oral routes because of their relatively high opioid content compared with immediate-release (IR) formulations.1,4

Manipulation for the purpose of non-oral abuse is not just highly prevalent, but also very dangerous. Non-oral abuse is associated with up to a 2-fold higher risk for several health consequences compared with oral abuse.5

While there is no current solution to oral overconsumption, manipulation is a serious issue that must be addressed. Abuse-deterrent opioids are part of a comprehensive approach to addressing opioid abuse and an important consideration for providers when prescribing opioid therapy for the treatment of chronic pain. For this reason, the FDA considers the development of abuse-deterrent opioids a high public health priority.6

References

  1. Katz N, Dart RC, Bailey E, Trudeau J, Osgood E, Paillard F. Tampering with prescription opioids: nature and extent of the problem, health consequences, and solutions. Am J Drug Alcohol Abuse. 2011;37:205-217. PMID: 21517709
  2. Hays LR. A profile of OxyContin addiction. J Addict Dis. 2004;23(4):1-9. PMID: 15339710
  3. Butler SF, Black RA, Cassidy TA, Dailey TM, Budman SH. Abuse risks and routes of administration of different prescription opioid compounds and formulations. Harm Reduct J. 2011;8:29. PMID: 22011626
  4. Butler SF, Cassidy TA, Chilcoat H, et al. Abuse rates and routes of administration of reformulated extended-release oxycodone: initial findings from a sentinel surveillance sample of individuals assessed for substance abuse treatment. J Pain. 2013;14(4):351-358. PMID: 23127293
  5. Green JL, Bucher Bartelson B, Le Lait MC. Medical outcomes associated with prescription opioid abuse via oral and non-oral routes of administration. Drug Alcohol Depend. 2017 Jun 1;175:140-145. PMID: 28414990.
  6. US Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER). Abuse-deterrent opioids; evaluation and labeling https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM334743.pdf. Published April 2015. Accessed November 6, 2017.

Categories of Abuse-Deterrent Opioids

Universal Precautions, Step 2: Select Agent

Abuse-Deterrent Formulation (ADF) Categories1

Category
 
Description
Physical/chemical barrier Deter manipulation and tampering
Agonist/antagonist combination Antagonist can interfere with, reduce, or defeat euphoria associated with abuse (eg, crushing, chewing, injecting)
Aversion Substances can be combined to produce unpleasant effect if dosage manipulated or higher-than-directed dose used
Delivery system Drug-release design or method of drug delivery (eg, depot injection) offers resistance to abuse
New molecular entities and prodrugs Lacks opioid activity until converted to active drug in GI tract
Combination Two or more of the above methods
Novel approaches Additional novel approaches or technologies not captured in previous categories
Adapted from US Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER). Abuse-deterrent opioids; evaluation and labeling. Available at: https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformat.... Published April 2015. Accessed November 6, 2017

Abuse-deterrent formulations of prescription opioids may be grouped into several distinct categories, based on the potential mechanism(s) by which they are designed to help to deter abuse.1-3 The categories shown here represent potential types of abuse-deterrent opioids.

Although abuse-deterrent opioids do not address all types of abuse, including oral overconsumption, the risk for abuse is lower than it would be for opioids without such properties. Prescribing abuse-deterrent opioids is one step prescribers can take toward addressing the problem of abuse. However, there is still a risk of addiction, abuse, misuse, and diversion with these medications.4,5

References

  1. US Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER). Abuse-deterrent opioids; evaluation and labeling. https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM334743.pdf. Published April 2015. Accessed November 6, 2017.
  2. Romach MK, Schoedel KA, Sellers EM. Update on tamper-resistant drug formulations. Drug Alcohol Depend. 2013;130(13):13-23. PMID: 23415386
  3. Stanos SP, Bruckenthal P, Barkin RL. Strategies to reduce the tampering and subsequent abuse of long-acting opioids: potential risks and benefits of formulations with physical or pharmacologic deterrents to tampering. Mayo Clin Proc. 2012;87(7):683-694. PMID: 22766088
  4. US Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER). Abuse-deterrent opioids; evaluation and labeling. Available at: https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformat.... Published April 2015. Accessed November 6, 2017.
  5. Stanos S. Continuing evolution of opioid use in primary care practice: implications of emerging technologies. Curr Med Res Opin. 2012;28(9):1505-1516. PMID: 22937723