Oxycodone to Morphine Rotation
There is clear evidence that—with appropriate patient selection and opioid selection—outcomes, including improved function, are better when opioid therapy is considered in certain chronic non-terminal pain.1-3 With opioid therapy that may last a lifetime, opioid rotation will have to be periodically used to improve analgesia, minimize tolerance, and reduce side effects of opioid therapy in both malignant and non-malignant pain syndromes.3,4
Opioid rotation can be done by changing the drug or the route of administration.2,4 Long acting opioids have been associated with better analgesia, less side effects, better patient compliance and reduced risk of tolerance and aberrant drug behavior/addiction and abuse.4 Opioids, like methadone, have been a common rotation for one long acting opioid to another.4 However, in view of methadone’s association with drug addiction and its complex pharmacokinetics, many patients and doctors elect not to use it in chronic non-terminal pain conditions. This is further complicated by the fact that there may be incomplete cross-tolerance between opioids.3,4 This could be due to differences in opioid receptors, occupancy, or efficacy. Though opioid rotation has been associated with improved analgesia, there have been significant side effects during rotation.2,4 These include dose escalation, symptoms of overdose and, most annoyingly, withdrawal symptoms.2,4 The withdrawal symptoms vary in severity and include cold sweats, headaches, feeling cold, and insomnia.2,4 These symptoms can be quite distressing and can occur in up to 32% of cases of long acting opioid rotation.4
We attempted both rapid and gradual opioid rotation with the aim of finding a better rotation approach having less side effects and/or withdrawal symptoms.
We attempted to covert a regimen of sustained release oxycodone (OSR) to sustained release morphine (MSR). Initially, we attempted to convert oxycodone to Morphine using a standard 1:1.5 ratio. This was done in single step over 7 to 10 days. This, however, resulted in poor compliance by the patient, mostly due to withdrawal symptoms. As a result, most patients abandoned the process.
To avoid these symptoms, we elected to do a gradual conversion from oxycodone SR to morphine SR. In this study, we converted only 50% of the initial oxycodone dose to long acting morphine, while the remaining 50% was left as sustained release oxycodone. For breakthrough pain, immediate release morphine (MSIR) was used. Every two weeks, a further 50% of the remaining dose of oxycodone was converted to morphine. Once the total daily dose of oxycodone was less than 30 mg, we discontinued all oxycodone and used only morphine along with MSIR, for breakthrough pain. Clonidine 0.1mg weekly patches were also used to reduce withdrawal symptoms.
A total of 15 male patients (ages 34-52) taking 140-180mg of Oxycodone daily (in the form of both sustained release and immediate release for break through pain) for mechanical low back pain were included. Their pain syndromes did not respond to physical therapy nor interventional pain management. All of those selected had already failed the initial short period (7-10 days) conversion from oxycodone to morphine (1:1.5 ratio) due to withdrawal symptoms. All selected patients were free of any litigations (including worker compensation) to avoid potential symptoms magnification for secondary gain. Random urine testing confirmed the absence of illegal and/or non-prescribed opioid/drugs.
History and complete physical examination was performed. This included Waddell testing, McGill questionnaire, and pain drawings. All candidates signed opioid agreements and random urine testing was performed. None of the urine test came back positive for illicit drugs before the trial. Using the gradual tapering/ conversion (50% reduction from oxycodone to morphine sustained release), we were able to successfully convert all patients to morphine (both single dose and MSIR 15mg BID). The final ratio of morphine to oxycodone was 1:1-1.2. Three patients (20%) developed mild withdrawal symptoms. Pain relief was comparable to the analgesia provided by oxycodone derivatives. Two patients had mild itching (defined as not requiring any intervention). Three patients experienced nausea in the first week of the trial but, again, no treatment was needed.
The use of opioid therapy in chronic non-malignant pain syndrome has been shown to improve the quality of life issues.1 There should be appropriate patient and opioid selection and co-morbid conditions such as depression and anxiety should be addressed to optimize the outcomes.1,9 The controversy of opioid use in chronic non-terminal pain comes from confusing addiction for tolerance that may result from chronic opioid therapy.1,2,4,9 While opioid therapy for both terminal and non-terminal pain syndrome is effective, side effects of opioid therapy have an important role in the success and/or failure of the treatment plan.1-4
Furthermore, treating physicians sometimes meet a required dose escalation due to tolerance with resistance. This is due to the fear of aberrant drug behavior including addiction or drug trafficking.1,3,5 Opioid rotation is a well-recognized method used to address rapid tolerance and other side effects of opioid therapy (sedation, altered mental status and aberrant drug behaviors).1,4,9
Opioid rotation is commonly used for malignant (terminal) pain syndromes.1,4 Opioid rotation can be accomplished by converting from short acting to long acting opioid, short acting to another short acting opioid, or long acting to another long acting opioid.4 Opioid rotation can also be done by altering the route of administration.2,4 Opioid rotation, while effective in treating tolerance and opioid side effects during therapy, can be associated with some difficulties. Part of the difficulty is due to the withdrawal symptoms that are associated with opioid rotation.4 This also includes dose escalation (over-dosage and sedation) or under-dosing (leading to increased pain).2,4 This may occur due to incomplete opioid cross tolerance, genetic polymorphism, difference in opioid receptor affinities, and/or different pharmacokinitics of the opioid or the delivery system.2,4,6
A good example of this phenomena is demonstrated in the use of codeine products. There is 7-10% of the population with lower CYP2D6 enzyme activity,6,8 which is needed to convert codeine to morphine and also is utilized in the metabolism of the R Isomer of methadone.6,7,8 This means that such patients would not have good analgesia with codeine and would instead express a preference for another opioid. This situation could be mistakenly interpreted as drug seeking behavior if the treating physician was unfamiliar with codeine metabolization deficiencies in some patients. This enzymatic difference is probably more prevalent in black Americans.6,8