____________________________________________ Assessment and Management of Pain at the End of Life
Fentanyl is the strongest opioid (approximately 80 times the potency of morphine) and is available as a transdermal drug- delivery system (Duragesic; Ionsys); a buccal film (Onsolis) and tablet (Fentora); a nasal spray (Lazanda); a sublingual spray (Subsys); a sublingual tablet (Abstral); and a lozenge (Actiq) [37; 42]. Fentanyl preparations have a more rapid onset than other opioids given nonparenterally [8]. Because of its potency, fentanyl must be used with extreme care, as deaths have been associated with its use. Physicians must emphasize to patients and their families the importance of following prescribing information closely, and members of the healthcare team should monitor the use of the drug. Fentanyl, administered subcutaneously, is the recommended choice for patients with advanced chronic kidney disease [28]. The use of methadone to relieve pain has increased substan- tially over the past few years, moving from a second-line or third-line drug to a first-line medication for severe pain in peo- ple with life-limiting diseases [43]. A systematic review showed that methadone had efficacy similar to that of morphine [44]. However, the authors’ conclusions were based on low-quality evidence. Other opioids (e.g., morphine, fentanyl) are easier to manage but may be more expensive than methadone in many economies [44]. Physicians must be well educated about the pharmacologic properties of methadone, as the risk for serious adverse events, including death, is high when the drug is not administered appropriately [44; 45]. If the dose of methadone is increased too rapidly or administered too frequently, toxic accumulation of the drug can cause respiratory depression and death. Because of the unique nature of methadone, and its long and variable half-life, extreme care must be taken when titrating the drug, and frequent and careful evaluation of the patient is required. Practitioners are advised to consult with a pain or palliative care specialist if they are unfamiliar with methadone prescribing or if individual patient considerations necessitate rapid switching to or from methadone [4]. Meperidine (Demerol) should not be used in the palliative care setting because of limited efficacy and potential for severe toxicity [12; 33]. Agonist-antagonist opioids (nalbuphine [Nubain], butorphanol [Stadol], and pentazocine [Talwin]) are not recommended for use with pure opioids, as they compete with them, leading to possible withdrawal symptoms. Tapentadol (Nucynta) is a short-acting opioid approved for moderate to severe pain in adults; an extended release formula- tion (Nucynta ER) was approved in 2011 for moderate-to-severe chronic pain when an around-the-clock opioid is needed [46].
The drug is associated with a lower incidence of adverse effects than other opioids, and it has been shown to be highly effec- tive for chronic pain conditions but has not been extensively studied in cancer-related pain or the palliative care setting [47]. A 2014 study of 123 patients that had previously received long- term analgesia for cancer-related pain showed tapentadol sig- nificantly reduced pain scores and was generally well tolerated; concomitant use of pain medications was also reduced [48]. The most appropriate option for breakthrough pain is an immediate-release opioid taken in addition to the around-the- clock regimen [8]. The fentanyl buccal tablet has been shown to be effective and safe for relieving breakthrough pain in people who are opioid tolerant [4; 49; 50]. Between January 2011 and January 2012, three forms of fentanyl were approved for breakthrough pain in people with cancer: fentanyl sublingual tablet (Abstral), fentanyl nasal spray (Lazanda), and fentanyl sublingual spray (Subsys) [37]. Abstral and Lazanda have since been discontinued [37; 41]. As of 2021, the fentanyl lozenge (Actiq) and buccal tablet (Fentora) are also approved for break- through cancer pain [41]. For each formula, the initial dose may be repeated once if pain is not relieved adequately after 30 minutes. Patients must wait at least two hours before using the sublingual tablet, buccal film, or the nasal spray for another breakthrough pain episode; the interval is four hours for the sublingual spray, lozenge, or buccal tablet [37; 41]. When pain responds poorly to escalated doses of an opioid, other approaches should be considered, including alternative routes of administration, use of alternate opioids (termed opioid rotation or opioid switching), use of adjuvant analge- sics, and nonpharmacologic approaches. A process for opioid switching has been established; the first step is to calculate the equianalgesic dose of the new drug [4; 8; 34]. Additional care is needed when switching to methadone, and conversion ratios have been established [4]. Evidence suggests that the traditionally recommended equianalgesic doses for the fentanyl transdermal patch are subtherapeutic for patients with chronic cancer-related pain, and more aggressive approaches may be warranted [4; 8; 51]. Another approach that has been used for pain management in the cancer setting is combination opioid therapy, or the concurrent use of two strong opioids. The effectiveness of this approach has been evaluated in only two studies, and the combination was morphine and oxycodone or morphine with fentanyl or methadone [52]. The evidence to support a recommendation of combination opioid therapy is weak, and the side effects most likely outweigh the benefit [52]. Opioids are associated with many side effects, the most notable of which is constipation, occurring in nearly 100% of patients. The universality of this side effect mandates that once extended treatment with an opioid begins, prophylactic treatment with laxatives must also be initiated.
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MDNJ1525
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