Precedex May Provide Relief at End of Life When Other Drugs Fail

VANCOUVER, B.C. – Precedex (dexmedetomidine), a drug used for years by intensivists and anesthesiologists for sedation, is increasingly being recognized as a valuable palliative care tool, according to Dr. Ellen M. Flanagan.

The alpha-2 agonist is an opioid-sparing analgesic that does not depress respiratory function; an anxiolytic with benzodiazepine-like activity but less risk of delirium and disinhibition; and a sedative from which patients can be aroused, among other properties, said Dr. Flanagan, an anesthesiologist at Duke University, Durham, N.C., with a special interest in palliative and end-of-life care.

Precedex "is incredible. It has really got some pretty profound implications for those patients who are having horrible deaths [with] intractable pain, agitation, and delirium." When standard drugs are "not sufficient to control symptoms, Precedex could do the trick," she said at the annual meeting of the American Academy of Hospice and Palliative Care Medicine.

Intensive-care doctors and anesthesiologists use the drug routinely. More than 4.5 million vials have been administered since the Food and Drug Administration approved it in 1999 to sedate intubated and mechanically ventilated ICU patients. The drug received a second indication in 2008 for sedation of nonintubated patients before or during surgical and other procedures.

But "it’s a new drug to most palliative care physicians," Dr. Flanagan said.

Part of the reason is that Precedex has not been studied in palliative care patients. To date, case reports offer the strongest evidence of palliative efficacy, she said.

Dr. Flanagan and her colleagues hope to change the situation. Their investigational new drug application was approved by the FDA for a study in nine advanced cancer patients in the final week of life.

The team will assess the drug’s impact as an add-on to standard therapy for pain, agitation, delirium, communication capacity, dyspnea, vomiting, and oral secretions. The team is currently negotiating funding with Hospira, the drug’s maker, and other possible sources.

For now, the best dose, duration, and symptom targets for palliative care remain uncertain, she said.

Still, nurse practitioner Jennifer Gentry, palliative care services clinical coordinator at Duke and copresenter with Dr. Flanagan, said she has seen Precedex ease end-of-life suffering when other drugs failed to do so adequately, and enable reductions in opioid use so patients could be extubated and allowed to die in hospice or other comfortable settings, instead of the ICU.

Meanwhile, studies in other populations have shown good effect, Dr. Flanagan said.

In a study of postoperative pain control in 100 women following hysterectomy, women given Precedex required 29% less morphine and reported less pain and nausea on the first postoperative day. Sedation was similar between the morphine alone and morphine-plus-Precedex groups (Br. J. Anaesth. 2009;102:117-22).

In another trial of mechanically ventilated ICU patients, 54% of 244 patients given Precedex 0.2-1.4 mcg/kg per hour experienced delirium, but 76.6% of 122 given midazolam 0.02-0.1 mg/kg per hour became delirious. Precedex patients were able to be extubated a median of 1.9 days sooner, as well (JAMA 2009;301:489-99).

In general, the drug provides arousable sedation, which "I think is one of the most incredible things about it. Instead of just titrating morphine until the patient is unconscious, the patient can be sedated so they look like they’re sleeping, and you shake their shoulder and all of a sudden they are awake. When the family comes in and wants to talk, you may be able to arouse that patient" for meaningful communication, Dr. Flanagan said.

Precedex is expensive, however, at about $58/100 mcg, or about $600 per day. It’s coming off patent in 2013, so less-expensive generic formulations may soon be available, she said.

The drug’s side effects include dry mouth, hypotension, and bradycardia. For the study, "we did a lot of work with the FDA to try to set up parameters trying to figure out what [bradycardia and hypotension] might be due to drug and what might be due to the natural trajectory of death," Dr. Flanagan said.

Dr. Flanagan said she has no financial interests in Precedex.

VANCOUVER, B.C. – Precedex (dexmedetomidine), a drug used for years by intensivists and anesthesiologists for sedation, is increasingly being recognized as a valuable palliative care tool, according to Dr. Ellen M. Flanagan.

The alpha-2 agonist is an opioid-sparing analgesic that does not depress respiratory function; an anxiolytic with benzodiazepine-like activity but less risk of delirium and disinhibition; and a sedative from which patients can be aroused, among other properties, said Dr. Flanagan, an anesthesiologist at Duke University, Durham, N.C., with a special interest in palliative and end-of-life care.

Precedex "is incredible. It has really got some pretty profound implications for those patients who are having horrible deaths [with] intractable pain, agitation, and delirium." When standard drugs are "not sufficient to control symptoms, Precedex could do the trick," she said at the annual meeting of the American Academy of Hospice and Palliative Care Medicine.

Intensive-care doctors and anesthesiologists use the drug routinely. More than 4.5 million vials have been administered since the Food and Drug Administration approved it in 1999 to sedate intubated and mechanically ventilated ICU patients. The drug received a second indication in 2008 for sedation of nonintubated patients before or during surgical and other procedures.

But "it’s a new drug to most palliative care physicians," Dr. Flanagan said.

Part of the reason is that Precedex has not been studied in palliative care patients. To date, case reports offer the strongest evidence of palliative efficacy, she said.

Dr. Flanagan and her colleagues hope to change the situation. Their investigational new drug application was approved by the FDA for a study in nine advanced cancer patients in the final week of life.

The team will assess the drug’s impact as an add-on to standard therapy for pain, agitation, delirium, communication capacity, dyspnea, vomiting, and oral secretions. The team is currently negotiating funding with Hospira, the drug’s maker, and other possible sources.

For now, the best dose, duration, and symptom targets for palliative care remain uncertain, she said.

Still, nurse practitioner Jennifer Gentry, palliative care services clinical coordinator at Duke and copresenter with Dr. Flanagan, said she has seen Precedex ease end-of-life suffering when other drugs failed to do so adequately, and enable reductions in opioid use so patients could be extubated and allowed to die in hospice or other comfortable settings, instead of the ICU.

Meanwhile, studies in other populations have shown good effect, Dr. Flanagan said.

In a study of postoperative pain control in 100 women following hysterectomy, women given Precedex required 29% less morphine and reported less pain and nausea on the first postoperative day. Sedation was similar between the morphine alone and morphine-plus-Precedex groups (Br. J. Anaesth. 2009;102:117-22).

In another trial of mechanically ventilated ICU patients, 54% of 244 patients given Precedex 0.2-1.4 mcg/kg per hour experienced delirium, but 76.6% of 122 given midazolam 0.02-0.1 mg/kg per hour became delirious. Precedex patients were able to be extubated a median of 1.9 days sooner, as well (JAMA 2009;301:489-99).

In general, the drug provides arousable sedation, which "I think is one of the most incredible things about it. Instead of just titrating morphine until the patient is unconscious, the patient can be sedated so they look like they’re sleeping, and you shake their shoulder and all of a sudden they are awake. When the family comes in and wants to talk, you may be able to arouse that patient" for meaningful communication, Dr. Flanagan said.

Precedex is expensive, however, at about $58/100 mcg, or about $600 per day. It’s coming off patent in 2013, so less-expensive generic formulations may soon be available, she said.

The drug’s side effects include dry mouth, hypotension, and bradycardia. For the study, "we did a lot of work with the FDA to try to set up parameters trying to figure out what [bradycardia and hypotension] might be due to drug and what might be due to the natural trajectory of death," Dr. Flanagan said.

Dr. Flanagan said she has no financial interests in Precedex.

VANCOUVER, B.C. – Precedex (dexmedetomidine), a drug used for years by intensivists and anesthesiologists for sedation, is increasingly being recognized as a valuable palliative care tool, according to Dr. Ellen M. Flanagan.

The alpha-2 agonist is an opioid-sparing analgesic that does not depress respiratory function; an anxiolytic with benzodiazepine-like activity but less risk of delirium and disinhibition; and a sedative from which patients can be aroused, among other properties, said Dr. Flanagan, an anesthesiologist at Duke University, Durham, N.C., with a special interest in palliative and end-of-life care.

Precedex "is incredible. It has really got some pretty profound implications for those patients who are having horrible deaths [with] intractable pain, agitation, and delirium." When standard drugs are "not sufficient to control symptoms, Precedex could do the trick," she said at the annual meeting of the American Academy of Hospice and Palliative Care Medicine.

Intensive-care doctors and anesthesiologists use the drug routinely. More than 4.5 million vials have been administered since the Food and Drug Administration approved it in 1999 to sedate intubated and mechanically ventilated ICU patients. The drug received a second indication in 2008 for sedation of nonintubated patients before or during surgical and other procedures.

But "it’s a new drug to most palliative care physicians," Dr. Flanagan said.

Part of the reason is that Precedex has not been studied in palliative care patients. To date, case reports offer the strongest evidence of palliative efficacy, she said.

Dr. Flanagan and her colleagues hope to change the situation. Their investigational new drug application was approved by the FDA for a study in nine advanced cancer patients in the final week of life.

The team will assess the drug’s impact as an add-on to standard therapy for pain, agitation, delirium, communication capacity, dyspnea, vomiting, and oral secretions. The team is currently negotiating funding with Hospira, the drug’s maker, and other possible sources.

For now, the best dose, duration, and symptom targets for palliative care remain uncertain, she said.

Still, nurse practitioner Jennifer Gentry, palliative care services clinical coordinator at Duke and copresenter with Dr. Flanagan, said she has seen Precedex ease end-of-life suffering when other drugs failed to do so adequately, and enable reductions in opioid use so patients could be extubated and allowed to die in hospice or other comfortable settings, instead of the ICU.

Meanwhile, studies in other populations have shown good effect, Dr. Flanagan said.

In a study of postoperative pain control in 100 women following hysterectomy, women given Precedex required 29% less morphine and reported less pain and nausea on the first postoperative day. Sedation was similar between the morphine alone and morphine-plus-Precedex groups (Br. J. Anaesth. 2009;102:117-22).

In another trial of mechanically ventilated ICU patients, 54% of 244 patients given Precedex 0.2-1.4 mcg/kg per hour experienced delirium, but 76.6% of 122 given midazolam 0.02-0.1 mg/kg per hour became delirious. Precedex patients were able to be extubated a median of 1.9 days sooner, as well (JAMA 2009;301:489-99).

In general, the drug provides arousable sedation, which "I think is one of the most incredible things about it. Instead of just titrating morphine until the patient is unconscious, the patient can be sedated so they look like they’re sleeping, and you shake their shoulder and all of a sudden they are awake. When the family comes in and wants to talk, you may be able to arouse that patient" for meaningful communication, Dr. Flanagan said.

Precedex is expensive, however, at about $58/100 mcg, or about $600 per day. It’s coming off patent in 2013, so less-expensive generic formulations may soon be available, she said.

The drug’s side effects include dry mouth, hypotension, and bradycardia. For the study, "we did a lot of work with the FDA to try to set up parameters trying to figure out what [bradycardia and hypotension] might be due to drug and what might be due to the natural trajectory of death," Dr. Flanagan said.

Dr. Flanagan said she has no financial interests in Precedex.