___________________________________________ Palliative Care and Pain Management at the End of Life
OPIOIDS FOR THE MANAGEMENT OF PAIN IN ADULTS a
Typical Starting Dose b
Drug
Onset of Action 30 to 60 minutes 10 to 20 minutes
Duration of Action
Codeine
15–60 mg 2.5–10 mg 15–30 mg
4 to 6 hours 4 to 8 hours 3 to 6 hours 3 to 4 hours 8 to 12 hours 4 to 5 hours 4 to 6 hours 4 to 6 hours
Hydrocodone
Morphine, immediate release
15 to 30 minutes or 5 to 10 minutes
Oxycodone, immediate release Oxymorphone, sustained release
5–10 mg
10 to 30 minutes 5 to 10 minutes 15 to 30 minutes 30 to 60 minutes
10 mg
Hydromorphone
2–4 mg 5–10 mg
Methadone Tapentadol
50–100 mg 50–100 mg 100–200 mcg
<60 minutes
Tapentadol, extended release
—
—
Fentanyl (buccal tablet)
5 to 15 minutes 12 to 18 hours
2 to 4 hours
Fentanyl (transdermal patch)
25 mcg/hour (worn for 3 days) 5–10 mcg/hour (worn for 7 days)
48 to 72 hours
Buprenorphine (transdermal patch)
—
—
a All information is given for oral formulations unless otherwise specified. b Doses given are guidelines for opioid-naïve patients; actual doses should be determined on an individual basis. Source: [187; 223; 247; 248; 249]
Table 8
people with life-limiting diseases [254]. A systematic review showed that methadone had efficacy similar to that of mor- phine. 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 [255]. 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 [255; 256]. If the dose of methadone is increased too rapidly or administered too frequently, toxic accumulation of the drug can cause respira- tory 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 [187]. Meperidine (Demerol) should not be used in the palliative care setting because of limited efficacy and potential for severe toxicity. Agonist-antagonist opioids (nalbuphine [Nubain], butorphanol [Stadol], and pentazocine [Talwin]) are not rec- ommended 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 for- mulation (Nucynta ER) was approved in 2011 for moderate- to-severe chronic pain when an around-the-clock opioid is needed [257]. The drug is associated with a lower incidence
of adverse effects than other opioids, and it has been shown to be highly effective for chronic pain conditions but has not been extensively studied in cancer-related pain or the pallia- tive care setting [258]. A 2014 study of 123 patients that had previously received long-term analgesia for cancer-related pain showed tapentadol significantly reduced pain scores and was generally well tolerated; concomitant use of pain medications was also reduced [259]. The most appropriate option for breakthrough pain is an immediate-release opioid taken in addition to the around- the-clock regimen [223]. The fentanyl buccal tablet has been shown to be effective and safe for relieving breakthrough pain in people who are opioid tolerant [187; 260; 261]. 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). Abstral and Lazanda have since been discontinued [247; 252]. As of 2021, the fentanyl lozenge (Actiq) and buccal tablet (Fentora) are also approved for breakthrough cancer pain [252]. For each formula, the initial dose may be repeated once if pain is not relieved adequately after 30 minutes. Patients should 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 [247; 252]. 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
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MDCA1525
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