Methadone
Guidelines
38. The decision has been made to use oral methadone to treat A.J.'s pain. What are guidelines for the safe use of methadone in treating cancer pain?
Clinical experience with the use of methadone for cancer pain is favorable.139 The patient's physical and mental condition should be monitored closely, and clinicians should be aware of the long elimination half-life of methadone. Repeated dosing with methadone requires decreasing the dose when comfort is achieved to prevent drug accumulation and overdose. Methadone is 85% bound to serum proteins, and its average plasma half-life is approximately 23 hours, with a range of 13 to 47 hours. Therefore, the drug is tightly bound and only slowly released from its binding sites. Plasma levels of methadone can continue to rise for up to 10 days after an increase in dose.
The duration of analgesia, however, does not correlate to the serum half-life, and multiple doses must be given each day. The absolute amount of methadone in plasma, although it undoubtedly affects sedation and respiratory depression, is not a factor in the magnitude of analgesic response. Nevertheless, analgesic effects are obtained only while methadone plasma levels are above a certain individualized concentration. Most patients can be maintained on doses of methadone every 6 or 8 hours after pain control is achieved, but the drug often must be given every 4 hours or administered with another short-acting opioid analgesic during the first day or two of therapy to control pain.140 Alternatively, methadone loading with larger doses for the first few doses can accomplish rapid analgesia at the onset of methadone administration. However, this carries a higher risk of rapid drug accumulation and excessive drowsiness. Thus, loading doses must be reduced after the first one to two doses.
The necessity for shorter dosing intervals during the initiation of methadone can cause clinicians who are unfamiliar with the long half-life of methadone to adjust doses too frequently or to maintain a patient at an inappropriately high dose after initial pain control is achieved. This can threaten the patient with dangerous drug accumulation. A scenario that often is repeated is one in which analgesia and patient comfort are achieved after 2 or 3 days of gradually increasing doses. On days 4 and 5, the patient becomes increasingly sedated and on day 6 alarmingly so. The drug is then discontinued, or the opioid antagonist naloxone (Narcan) is administered. Suddenly, the patient is no longer sedated, but the pain has reappeared. This sudden reversal of sedation may be short lived. Because the half-life of methadone is much longer than that of naloxone, the patient can still slip back into sedation once the naloxone is cleared from the plasma in 1 to 2 hours.141 Elderly and severely debilitated patients may require smaller doses of methadone for pain control; therefore, caution must be exercised when methadone is used in these patients.142
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