All of the options for BTP can be used in the inpatient setting, but parenteral administration may be less applicable in the outpatient setting. Patients who might be appropriate candidates for parenteral opioid therapy in the outpatient setting include those who are highly motivated to comply with the regimen, are receiving a relatively stable dose for BTP, and are not experiencing significant adverse effects, chiefly respiratory depression or confusion. For most outpatients, however, the oral and oral transmucosal routes are generally preferred.
Subtypes of Breakthrough Pain
The subtype of BTP serves as a basis for tailoring the treatment approach (Table 2). For end-of-dose pain, the ATC dosing needs to be carefully calculated (see Part 1, Table 1, in the May 2005 issue of P&T). For predictable incident pain, such as that occurring with movement, the pre-emptive use of a hydrophilic IR opioid given 30 minutes prior to the incident is reasonable. Of course, when incident pain is predictable but occurs with little advance notice (e.g., as in coughing), oral transmucosal fentanyl citrate is a good choice because of its rapid onset of action. suhagra
Table 2 Management by Subtype of Breakthrough Pain
General Management Approach
|End-of-dose||Carefully tailored around-the-clock dosing|
|Incident, predictable||Pre-emptive use of a hydrophilic immediate-release opioid,given 30 minutes prior to activity|
|Incident, unpredictable||Trial of hydrophilic immediate-release opioid; if a poor patient response, switch to a lipophilic immediate-release opioid or a parenteral opioid in carefully selected patients|
|Idiopathic||Trial of a lipophilic immediate-release opioid|
A trial of an IR opioid should be initiated for unpredictable incident pain or idiopathic pain. An oral IR hydrophilic opioid (e.g., morphine or oxycodone) may be a reasonable choice if the onset of BTP is slower than the average three to five minutes or longer than the average duration of 15 to 30 minutes.
Case Study (continued)
T. G. returns in one week for a re-evaluation. A discussion with her and a review of her patient diary indicate that IR morphine is effective when it is given pre-emptively before she stands or walks for an extended time. However, the IR morphine has been ineffective on several occasions of the severe, sharp, shooting pain (9 on a scale of 1 to 10) in her right hip and leg—pain that seems to have no precipitating features when she is at rest.
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Although she has taken the morphine when these episodes have occurred, it has been ineffective because of the speed and intensity of the pain. As the pain lessens,T. G. is left feeling “hung over” from the effects of the morphine— which had not been a problem with her opioid therapy until now.
A trial of oral transmucosal fentanyl is discussed. T. G. is to use oral transmucosal fentanyl citrate 200 mcg over 15 minutes for each episode of BTP for the next week.This dosage is to be re-evaluated at her follow-up visit. T. G. is again reminded to use her pain diary to record her response to therapy and to document the variability of her pain daily.
Alternatively, acetaminophen or another NSAID may be considered for episodes of BTP with a slow onset or a long duration. Conversely, oral transmucosal fentanyl citrate may
be a good choice if the BTP is unpredictable and has an onset within several minutes and a short duration.
In a study by Mercadante et al., intravenous (IV) morphine was effective in reducing cancer-related BTP when administered as a dose equivalent to one-fifth of the oral daily morphine dose. Pain was reduced from a mean intensity of 7.9 on a scale of 1 to 10 to 3 out of 10 within a mean of 17.7 minutes. This is the only retrieved study that formally assessed the use of a fixed dose of an opioid as a percentage of the daily opioid dose.
Oral Transmucosal Fentanyl Citrate
Oral transmucosal fentanyl citrate has been investigated for the management of cancer-related and non-cancer-related BTP. Two dose-ranging studies that involved 127 patients with cancer-related BTP demonstrated significant efficacy in reducing BTP, with doses varying from 550 to 650 mcg (range, 200-6,400 mcg). In both cases, there was no correlation between the effective dose of oral transmucosal fentanyl citrate and the ATC dose of an opioid. Approximately 50% of the reduction in pain intensity from oral transmucosal fentanyl citrate occurs within 15 minutes. order levitra
In a direct comparison with IR oral morphine, oral transmucosal fentanyl citrate was found to be more effective in reducing the intensity of cancer-related BTP. The use of this agent over a mean of three months showed no trend toward decreased effectiveness.
Oral transmucosal fentanyl citrate is also effective in the outpatient management of sickle cell pain. A recent review of four previously conducted trials of this agent for the treatment of BTP in patients with cancer demonstrated similar efficacy in both nociceptive and neuropathic pain. Common side effects included somnolence, constipation, nausea, dizziness, and vomiting, all with an incidence of less than 15%.