Clinical Geriatrics

Part I of this two-part article, published in the March issue of the Journal, provided information on selected general concepts in opioid therapeutics, including the role of opioids in pain management, treatment of concurrent acute pain, toxicity, and drug-drug interactions. Part II will discuss dosing of opioid analgesics, pharmacogenomics, and the individual agents.

Dosing of Opioid Analgesics
Due to space limitations, this dosing section will focus only on opioid-to-opioid switch therapy (also called “opioid rotation”), breakthrough pain (BTP) management, and methadone dosing.

Switching Opioid Analgesics
Opioid-to-opioid switch therapy should be reserved for four clinical reasons: (1) lack of efficacy (for worsening of existing pain, development of analgesic tolerance, or a dose for analgesia in combination products that causes acetaminophen daily-dose ingestion to exceed 4 g); (2) development of intolerable adverse events (AEs; gastrointestinal, central nervous system, cardiovascular); (3) change in patient status (inability to swallow, poor peripheral vascular access, poor or variable dermatologic absorption from transdermal [TD] formulations, requirement for high-dose opioids that cannot be practically administered); and (4) practical considerations (not available in local pharmacies, high cost, large amount needed, route of administration, and opiophobia [fear of  1 opioid “associated” with death or addiction]).¹

In this process, the clinician must first calculate the morphine equianalgesic daily dose for the current opioid analgesic(s) using a dose equivalence table similar to the one illustrated in Table I. Then, the daily dose of the new opioid regimen can be calculated using the same table. Remember that equivalence values are route-specific (oral/rectal vs intramuscular [IM]/intravenous [IV]/subcutaneous [SC]). Since cross-tolerance between opioids is incomplete, the actual daily dose of the new opioid that should be prescribed should be lowered by 25-50%. Once the formulation is selected, the appropriate dosing interval (from 4-24 hr or even 72 hr) can be selected.¹

When rotating from (an) other opioid(s) to TD fentanyl, two sets of recommendations are available. The very conservative set of recommendations from the initial manufacturer of the TD product (Ortho-McNeil-Janssen Pharmaceuticals, Inc) is illustrated in Table II. However, use of this set of recommendations produces suboptimal initial analgesia in over 50% of patients.² A somewhat more “aggressive” set of recommendations derived from the results of clinical trials serves to minimize the initial suboptimal analgesia produced by the manufacturer’s set. Table III illustrates this more “aggressive” set of recommendations.³ Regardless of the recommendations used, patients need additional opioid during the initial 18-24 hours after application of the first TD patch to compensate for the lag time until the skin depot is saturated with drug and the delivery to the systemic circulation is at a steady state. Generally, the recommended supplemental opioid dose needed over this period is 25% of the equianalgesic daily dose of the previously-used regimen. Supplemental dosing will not only assist with analgesia during the transition period, but also prevent the emergence of opioid withdrawal signs/symptoms.³

Due to the complex mechanism of action of tramadol/tapentadol, these agents cannot be represented in a dose equivalence table such as Table I. Thus, they cannot enter into the process of opioid-to-opioid switch therapy, as discussed previously.

Breakthrough Pain Management
Along with the scheduled opioid dosage regimen, an “as-needed” opioid regimen is necessary to manage BTP.