Sustained release formulations should generally only be initiated in the acute setting if pain is present most of the time and it is assumed that the pain generator will last for an extended period of time (e.g., >2 weeks). If the pain is more incident related or expected to be of a brief duration, then immediate release agents should be employed. If initiating or increasing a sustained release opioid (e.g., if greater than four rescue doses are needed in 24 h while on a sustained release agent); start or go up on the sustained release agent by 50-100% of the total 24-h breakthrough dose used. When using a sustained release opioid, also provide doses of an immediate release opioid equivalent to 10-15% of the 24 h total, to be used every few hours for breakthrough pain.
Transdermal fentanyl is not appropriate for acute pain, especially in the opioid naïve. There is a black box warning against its use in the acute setting due to the risk of severe respiratory depression from the delayed peak effect of the drug as the pain level decreases. It is intended for use in patients who are already tolerant to opioids of comparable potency.
Methadone is not appropriate as the first-line agent in the acute setting, especially in the opioid naïve. Its use requires an understanding of the unique pharmacology of the drug, especially its extended duration of action and its dose-dependent potency. Also, as it takes a few days to reach a stable plasma concentration, patients will need to be followed closely to monitor for effectiveness and side effects. It must also be realized that methadone is a racemic mixture of a |x agonist and an NMDA antagonist (see the section "Adjuvant Analgesics") which causes patients to have a lesser degree of tolerance development.
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