Drug therapy for cancer-related pain—evidence regarding hydromorphone, oxycodone, and methadone
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Cancer pain is unfortunately very prevalent, with opioids the mainstay of treatment. Knowledge of the types of pain caused by cancer and the effects of various opioids would be expected to improve pain therapy. This article addresses the use, side effects, formulations, and metabolism of the most commonly used opioids in cancer pain management, including morphine, codeine, hydrocodone, hydromorphone, fentanyl, and methadone. The role of opioid conversion and equipotent dosing when changing from one opioid to another is also described.
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The US is experiencing an epidemic of opioid overdoses which may be at least partially due to an over-reliance on opioid analgesics in the treatment of chronic non-cancer pain and subsequent escalation to heroin or illicit fentanyl. As Texas was reported to be among the lowest in the US for opioid use and misuse, further examination of this state is warranted.
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Abstract Study Objective The US is experiencing an epidemic of opioid overdoses which may be at least partially due to an over-reliance on opioid analgesics in the treatment of chronic non-cancer pain and subsequent escalation to heroin or illicit fentanyl. As Texas was reported to be among the lowest in the US for opioid use and misuse, further examination of this state is warranted. Study Design This study was conducted to quantify prescription opioid use in Texas. Data Source Data was obtained from the publically available US Drug Enforcement Administration’s Automation of Reports and Consolidated Orders System (ARCOS) which monitors controlled substances transactions from manufacture to commercial distribution. Measurement and Main Results Data for 2006-2017 from Texas for ten prescription opioids including eight primarily used to relieve pain (codeine, fentanyl, hydrocodone, hydromorphone, meperidine, morphine, oxycodone, oxymorphone) and two (buprenorphine and methadone) for the treatment of an Opioid Use Disorder (OUD) were examined. The change in Morphine Mg Equivalent (MME) of all opioids (+23.3%) was only slightly greater than the state’s population gains (21.1%). Opioids used to treat an OUD showed pronounced gains (+90.8%) which were four-fold faster than population growth. Analysis of individual agents revealed pronounced elevations in codeine (+387.5%), hydromorphone (+106.7%), and oxycodone (+43.6%) and a reduction in meperidine (−80.3%) in 2017 relative to 2006. Methadone in 2017 accounted for a greater portion (39.5%) of the total MME than hydrocodone, oxycodone, morphine, hydromorphone, oxymorphone, and meperidine, combined. There were differences between urban and rural areas in the changes in hydrocodone and buprenorphine. Conclusions Collectively, these findings indicate that continued vigilance is needed in Texas to appropriately treat pain and an OUD while minimizing the potential for prescription opioid diversion and misuse. Texas may lead the US in a return to pre opioid crisis prescription levels.
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Abstract A middle-aged woman with recent cervical diskectomy with spinal fusion at C3-C4 suffered a mechanical fall with bilateral upper extremity paresthesia requiring admission but no surgical intervention. Patient was seen by orthopedic service and was recommended to continue using Aspen collar and oxycodone for pain. Following discharge, a drug urine screen test was performed, and showed positive for oxycodone by immunoassay. Confirmatory urine test by liquid chromatography-tandem mass spectrometry (LC-MS/MS) showed detectable oxycodone, oxymorphone and hydromorphone. In patients treated with opioid therapy for chronic pain, urine drug monitoring is an important tool to ensure that patients are adhering to the prescribed medication. Hydrocodone and hydromorphone are not metabolites of oxycodone. However, hydrocodone can be present in oxycodone preparations with an estimated impurity of <1%. Hydrocodone can be metabolized into hydromorphone, although, there is no literature reporting detectable hydromorphone in patients’ urine with prescribed oxycodone only. This case resulted in a quality improvement project where we evaluated the detection of hydrocodone and hydromorphone in positive oxycodone urine samples using LC-MS/MS. We analyzed 322 oxycodone positive urine samples. Twenty-one samples (6%) had detectable hydrocodone and/or hydromorphone below 100 ng/mL. Twelve out of the 21 were from patients taking no opioid medication other than oxycodone in the last week, with 33.3% showing detectable hydromorphone and 75% for hydrocodone below 100 ng/dL. The calculated hydrocodone/oxycodone (HC/OC) and hydromorphone/oxycodone (HM/OC) ratios were on average 0.26% HC/OC = 0.26% (0.05-0.69% SD 0.002; HM/OC = 0.26% (0.18-0.37% SD 0.001)] each (<1%). Patients taking oxycodone and other opioids had ratios >1% [HC/OC = 168% (3-563% SD 2.53; HM/OC = 699% (1.09-6585% SD 15.96)] and had higher detected levels (>100 ng/mL). Pain management can be very challenging; therefore, laboratory testing provides an objective assessment of drug exposure and adherence to treatment. Cut-off values for considering positive the detection of hydrocodone and hydromorphone may change the interpretation of the drug urine tests in patients with prescribed oxycodone. Using higher cutoff (100 ng/mL) and the ratios HC/OC and HM/OC (<1%) may be useful to determine that the detection of these components is due to impurity of oxycodone formulation.
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