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Patients Who Require Ultra-high Opioid Doses

The goal of ultra-high dosage therapy is to relieve pain and improve function in those chronic pain patients that are profoundly ill, impaired, and/or bed- or house-bound, without producing sedation.
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Family Involvement

A patient who requires over 1000mg of morphine equivalents a day should involve the family in the management process, if at all possible. To help document the need and insure compliance with taking ultra-high doses, the closest family members (preferably spouse and/or children) of the patient should meet the prescribing physician. Family members need to know the cause of pain and reason for the high dosage. Oftentimes the family is the agent that demands the patient take an ultra-high dose because they recognize the suffering and impairment of the patient and want “something done.” Families may also question the necessity of an ultra-high dose and need to be educated on the need for it. Further, family reporting is essential to help assess and evaluate the treatment process.

Dosage Regimen

Patients whose pain requires ultra-high opioid doses generally require more than one opioid. A sustained-release (SR) opioid (such as sustained-release mor-phine, oxycodone, or oxymorphone or a fentanyl patch) or an opioid with a long-half life (methadone) is required for baseline, constant or persistent pain, while short-acting or immediate-release opioids are required for flares or episodes of breakthrough pain. The long-acting or SR opioid is given on a fixed, around-the-clock schedule in order to attain a smooth and consistent blood level of the drug. For breakthrough pain, a second, rapidly acting opioid is given, to be taken on an as-needed basis. If the patient has breakthrough pain episodes that reach maximal intensity within minutes, he/she additionally require a prescription for an ultra-rapid-acting opioid (e.g., fentanyl in the form of lollipops [Actiq®] or lozenges [Fentora®], sublingual liquid oxycodone, or morphine suppository). If a patient requires more than one long-acting and/or more than one short-acting opioid, it’s essential to document the reason for this in the patient’s chart.

Table 2. Calculation of Morphine Equivalents
Opioid Mg Dosage Per Day r Calculation Multiplie   Total Morphine Each Day (mg)
Morphine   X 1 =  
Hydromorphone   X 4 =  
Oxymorphone   X 10 =  
Levorphanol   X 5 =  
Methadone   X mcg/hr fentanyl x 2.5 = mg morphine/day =  
Fentanyl patch   X .08 =  
Codeine   X 2 =  
Hydrocodone   X 1.5 =  
Oxycodone   X 1.5 =  
Meperidine   X .13 =  
Total daily morphine equivalents ___________mgs
Caution: This is not a conversion table. Conversion must be extremely conservative and not assume full cross-tolerance between opioids.
Also, morphine and methadone are equivalent only at very low doses.

Body Fluid Testing

Urine drug testing (UDT) is currently recommended for most patients being treated with opioids for chronic pain. Urine testing is used to detect drugs of abuse including cocaine, methamphetamine and cannabinoids. It may also give a clue as to whether the patient is complying with prescription instructions. The absence or very low concentrations of opioids in urine may suggest diversion of prescribed drugs. It is crucial, however, for the physician to understand (1) the limitations of urine drug testing and (2) the metabolic pathways of prescribed opioids. Urine drug screens typically screen only for natural opioids (e.g., morphine, codeine and hydrocodone) but will fail to detect synthetic and semi-synthetic opioids (e.g., oxycodone and fentanyl). The outcome for a patient who is taking oxycodone or fentanyl as prescribed will be a false-negative urine drug screen which, unfortunately, has resulted in patients being unjustly discharged. To avoid this possibility, it is important to ask the laboratory to specifically test for every opioid that the patient has been prescribed. Another situation that often leads to undeserved problems for the patient is when the patient is being prescribed a short-acting opioid to be taken as needed for breakthrough pain. The serum half-life of oxycodone (e.g., Percocet®) or hydrocodone (e.g., Vico-din®) is about four hours so, if several half-lives have elapsed since the patient last took the pill, the amount remaining in the urine may be below the limit of detection. It is crucial, therefore, at the time that the patient provides the urine specimen, to ask exactly when each opioid was last taken and record this in the chart.

When comprehensive urine drug tests are ordered, it’s common to find an opioid in the urine that was not prescribed. Before concluding that the patient obtained that drug on the street or from another physician, it is crucial to find out from the clinical laboratory whether the unexpected drug could be a legitimate finding of a metabolite. For example, codeine is metabolized to morphine, hydrocodone to hydromorphone, and oxycodone to oxymorphone. Thus, a patient who is taking Percocet (oxyco-done) is very likely to have oxymorphone in the urine and the quantity might be even greater than the amount of oxycodone.”5 The bottom line is, if you order a UDT, be prepared to follow-up with the lab on any unexpected finding.

Finally, it is a mistake to draw conclusions about the patient’s prescription compliance on the basis of quantitative levels of the opioid in the urine. There is tremendous variation in the way different people metabolize different drugs—not to mention that the time between when the drug was taken and the urine collected varies. UDTs should not be used to determine how much of the prescribed drug the patient is taking.

Blood levels of opioids are not generally used in a clinical setting but they have value in two situations. One is when there is a significant discrepancy between the prescribed dose and the effect of the drug, suggesting the possibility of variation in the metabolism of the drug.6 This has proven especially helpful regarding methadone, whose metabolism varies significantly from patient to patient. The following case report illustrates this:

Last updated on: December 20, 2011