Posted by Dr. Julia Harder
A study published in this month’s issue of the New England Journal of Medicine demonstrated the value of early palliative care services in the treatment of patients with advanced lung cancer. A total of 151 patients recently diagnosed with metastatic non-small-cell lung cancer were randomized to either routine cancer care or routine cancer care plus palliative care. Patients assigned to early palliative care met with a member of the palliative care team, which consisted of board-certified palliative care physicians and advanced-practice nurses, within 3 weeks after enrollment and at least monthly thereafter until death. Additional visits with the palliative care service were scheduled at the discretion of the patient, oncologist, or palliative care provider.
General guidelines for the palliative care visits were adapted from the National Consensus Project for Quality Palliative Care and were included in the study protocol. Specific attention was paid to assessing physical and psychosocial symptoms, establishing goals of care, assisting with decision making regarding treatment, and coordinating care on the basis of the individual needs of the patient.
More than half (54%) of patients in the standard care group received aggressive end-of-life care (defined as chemotherapy within 14 days before death, no hospice care, or admission to hospice 3 days or less before death), compared to 33% in the palliative care group (p = 0.05). Despite receiving less aggressive end-of-life care, patients in the palliative care group had significantly longer survival than those in the standard care group (median survival: 11.6 vs. 8.9 months; p = 0.02). Furthermore, patients assigned to early palliative care had significantly higher scores on quality-of-life measures than did those assigned to standard care, and depression was less than half as common in the palliative care group.
While costs of care were not specifically addressed, the study did show that early palliative care for patients with advanced cancer can alter the use of health care services, including care at the end of life. In addition to receiving less aggressive end-of-life care, significantly more patients in the early palliative care had resuscitation preferences documented in their medical record.
These results indicate that timely introduction of palliative care may serve to mitigate unnecessary and burdensome personal and societal costs. Future research will be needed to investigate whether palliative care can indeed reduce healthcare expenditures, and whether the early introduction of palliative care can extend survival in other types of cancer and life-limiting illnesses.
Temel JS, Greer JA, Muzikansky A, Gallagher ER, Admane S, Jackson VA, et al. Early palliative care for patients with metastatic non-small-cell lung cancer. N Engl J Med 2010;363:733-742. The full text is available online at http://www.nejm.org/doi/full/10.1056/NEJMoa1000678.
Photo Credit: erika_herzog
Posted by Dr. Julia Harder
The FDA has approved donepezil (Aricept) 23 mg once daily for the treatment of patients with moderate to severe Alzheimer’s disease who have been using 10 mg daily for at least 3 months. This approval comes at an opportune moment for the manufacturers of Aricept (Eisai Inc. and Pfizer Inc.), as the 5 mg and 10 mg strengths of Aricept go off patent in November of this year. The new 23 mg strength is expected to be available this month and the manufacturers will have 3 years of market exclusivity.
The FDA’s approval was based on the results of a clinical trial (Ref.1) comparing the 23 mg and 10 mg strengths. The randomized, double-blind, multicenter study enrolled 1467 patients age 45-90 with probable AD and a Mini Mental Status Exam score of 0 – 20 (indicating moderate to severe cognitive impairment) who had been receiving donepezil 10 mg daily for at least 12 weeks. Patients were randomized to 24 weeks of treatment with either high-dose donepezil (23 mg daily) or continued treatment with standard-dose donepezil (10 mg daily).
The two primary effectiveness measures were cognition and global functioning. Cognition was measured using the Severe Impairment Battery (SIB), a validated clinical instrument used to rate 9 aspects of cognition, including social interaction skills, memory, orientation, language, attention, praxis, visuospatial ability, construction and orientation to name. Scores on the SIB range from 0 to 100, where lower scores indicate greater impairment. There was a statistically significant difference between the two groups in the change from baseline SIB score: +2.6 in the 23 mg group vs. +0.4 in the 10 mg group (P = 0.0001). However, the study did not address the clinical significance of these changes.
Global functioning, the second primary outcome measure, was assessed using the Clinician’s Interview-Based Impression of Change Plus Caregiver Input (the CIBIC-Plus). The CIBIC-Plus examines four major areas of patient function: general, cognitive, behavioral and activities of daily living. It combines the assessment of a skilled clinician based upon his/her observations of the patient with information supplied by a caregiver familiar with the patient’s behavior. The CIBIC-plus is scored as a seven-point categorical rating, ranging from a score of 1, indicating “markedly improved,” to a score of 4, indicating “no change,” to a score of 7, indicating “markedly worse.” The between-treatment difference in CIBIC-Plus score was not statistically significant (4.23 vs. 4.29, P = 0.1789).
Study discontinuation due to medication adverse effects were far more common in the high-dose donepezil group (18.6% vs. 7.9%). The most common adverse effects leading to study discontinuation, in order of prevalence, were vomiting, diarrhea, nausea and dizziness. The following table compares the percentage of patients in each group experiencing adverse effects:
| ADVERSE EFFECT |
23 mg/day
(% of patients)
|
10 mg/day
(% of patients)
|
| Nausea |
12 |
3 |
| Vomiting |
9 |
3 |
| Diarrhea |
8 |
5 |
| Weight Loss |
5 |
3 |
| Anorexia |
5 |
2 |
| Dizziness |
5 |
3 |
The Aricept package insert (Ref. 2) claims that, in most cases, side effects were mild and transient, tending to resolve during the first month of continued donepezil use.
In the past, the FDA has warned that cholinesterase inhibitors such as donepezil may have vagotonic effects on the sinoatrial and atrioventricular nodes, leading to bradycardia or heart block in patients with and without underlying cardiac conduction abnormalities. Syncopal episodes have been reported. The percentage of patients experiencing syncope was not reported in this trial, but it may be expected that the higher donepezil dose would increase the risk of cardiovascular side effects. Caution is warranted when prescribing high-dose donepezil to patients with a history of bradycardia, heart block or syncope, or who are taking other medications that slow transmission through the sinoatrial or atrioventricular nodes (such as beta blockers, calcium channel blockers, or digoxin).
The role of high-dose donepezil in the management of advanced Alzheimer’s disease will remain to be seen. Given the questionable clinical benefit and the increased side effects, the use of high-dose donepezil should, for now, be reserved for select patients in whom the benefit outweighs the risk. Further research is needed to demonstrate the efficacy of high-dose donepezil in this patient population before its use can be routinely recommended.
(Ref. 1) Farlow MR, Salloway S, Tariot PN, Yardley J, Moline ML, Wang Q, et al. Effectiveness and tolerability of high-dose (23 mg/d) versus standard-dose (10 mg/d) donepezil in moderate to severe Alzheimer's disease: A 24-week, randomized, double-blind study. Clin Ther 2010;32:1234-1251.
(Ref. 2) Aricept® (donepezil hydrochloride) tablets. Package insert, revised July 2010. Eisai, Inc and Pfizer, Inc. Available online at http://www.aricept.com.
Photo Credit
Posted by Dr. Julia Harder
This final article in our pediatric series will focus on the management of some of the most common non-pain symptoms encountered in pediatric palliative care. Research is notoriously lacking in this area, so much of what is done in pediatric palliative care is derived from the general pediatric population, from adult palliative care, or simply from clinical experience.
Specific symptom complexes that are addressed include: anxiety & depression, agitation, insomnia, anorexia-cachexia, nausea-vomiting, constipation, and dyspnea. Specific medication strategies will be presented for managing each of these troubling symptoms in pediatric hospice patients.
Posted by Dr. Jim Joyner
The July issue of The Clinician, our quarterly clinical newsletter, will feature the final article in our three-part series on pediatric palliative care. In the upcoming article, Julia Harder, PharmD, will discuss the management of some of the most common non-pain symptoms encountered in pediatric palliative care. Specific symptom complexes that will be addressed include: anxiety & depression, agitation, insomnia, anorexia-cachexia, nausea-vomiting, constipation, and dyspnea. Specific medication strategies will be presented for managing each of these troubling symptoms in pediatric hospice patients. All clients of Outcome Resources receive complimentary copies of The Clinician each quarter. Previous issues of The Clinician can be obtained by contacting Jim Joyner, PharmD, at jjoyner@outcomeresources.com Be sure to check the Blog for the upcoming Part 3 in the series.
Dowload Part 1 of Pediatric Palliative Care Series: Current Concepts in Drug Therapy
Dowload Part 2 of Pediatric Palliative Care Series: Pain Management
Posted by Dr. Julia Harder
In pediatric palliative care, the first rule of pain management is to always tailor assessment and treatment to the unique needs of the child and his or her family. Many factors will shape a child's pain, including developmental level, emotional and cognitive state, personality traits, physical condition, and past experiences. The meaning of the pain for the child; the child's fears and concerns about illness and death; issues, attitudes, and reactions of the family; cultural background; and the environment are all elements in a child's perception of pain. Getting to know the child and having knowledge of developmental norms and behavioral competencies are important in the assessment and management of pain.
Open communication about pain among the child, the family, and the health care team is critical to successful pain assessment and management. To encourage open communication, determine the language the child uses for pain (e.g., hurt, owie, booboo) and how and to whom the child communicates pain. Often, parents/caregivers are the primary source of information about how the child exhibits and responds to pain and should be encouraged to be active participants in both assessment and management. Parents/caregivers can also contribute important information including prior painful events, previously used methods for pain control and preferences for assessing and treating pain.
Posted by Dr. Julia Harder
Sublingual nitroglycerin (Nitrostat) is indicated for the relief of an acute angina attack. One sublingual tablet should be used at the first sign of an acute attack. Up to two additional doses can be taken at 5 minute intervals if relief is not seen.
In the past, patients have been counseled to contact EMS if angina is still not relieved after 3 doses. However, the American College of Cardiology and the American Heart Association revised these recommendations in 2004, recognizing that delay in seeking medical attention (as may occur during this 15 minute span) may adversely affect patient survival. The updated recommendations state that patients should contact EMS if there is no relief after just one dose of sublingual nitroglycerin. Patients should continue to use the second and third doses, if needed, while waiting for EMS to arrive. Patients are also encouraged to wait for an ambulance rather than having family or friends provide transportation to the hospital, so that they may be treated en route if necessary.
Further counseling points regarding sublingual nitroglycerin include:
- Patients should take nitroglycerin while sitting, in case they become dizzy or lightheaded.
- The tablets do not need to be replaced every 6 months, as was previously recommended. If tablets are properly stored and handled, they should be stable until the expiration date indicated by the manufacturer.
The same recommendations also apply to nitroglycerin lingual spray (e.g. Nitrolingual, NitroMist). An important note about the spray is that it must be "primed" with one spray before being used for the first time, and must be reprimed if not used for 6 weeks.
Posted by Dr. Julia Harder
Generic Memantine Approved
The FDA has approved Sun Pharmaceuticals' Abbreviated New Drug Application for memantine hydrochloride 5 and 10 mg tablets, indicated for the treatment of moderate to severe Alzheimer's disease. The medication is the generic equivalent of Namenda by Forest Laboratories.
Briefing Document on Memantine from the FDA
Posted by Dr. Julia Harder
While the elderly constitute the vast majority of patients requiring hospice and palliative care, approximately 50,000 infants, children and adolescents die annually in the United States. Of these, epidemiologic studies estimate that 15,000 might benefit from palliative care. In addition, the
National Hospice and Palliative Care Organization has estimated that palliative care would be an appropriate model of care for approximately 1.5 to 2 million children in the United States living with serious medical conditions. As the medical community has become more aware of this need, pediatric palliative care has received increasing attention as an emerging sub-specialty of palliative care focusing on achieving the best possible quality of life for children with life-threatening conditions and their families.
This article is the first in a series of three articles focusing on pediatric palliative care, and will introduce the topic by comparing palliative care of children to that of adults, reviewing pediatric pharmacokinetics, and giving general guidelines for pediatric medication administration. Subsequent articles will focus in more detail on pain management and the management of other symptoms commonly experienced by children at the end of life.
Photo Credit http://www.flickr.com/photos/spigoo/ / CC BY 2.0
Posted by Dr. Jim Joyner
A group of investigators from a Japanese palliative care unit published an article describing the benefits of Baclofen (Lioresal) for managing cancer pain.
(1) This is significant since Baclofen, an effective muscle relaxant, has not previously been studied for its effect as an adjuvant medication specifically for managing cancer pain. Baclofen has potent antispasmodic activity making it a logical choice for numerous conditions associated with muscle spasm and pain related to muscle spasm. There are also reports in the medical literature that describe the effectiveness of Baclofen for certain neuropathic pain syndromes such as trigeminal neuralgia as well as post herpetic neuralgia.
(2) Baclofen's mechanism for pain relief is thought to be mediated via the GABA receptors in the central nervous system, a mechanism distinctly separate from that of the opioids which are the primary category of drugs used to manage cancer pain in hospice patients.
(3) Adding Baclofen to opioid therapy may make sense from the perspective of attacking the pain from two separate mechanisms of action.
This study was limited to 25 cancer patients who had pain resulting from the following conditions: spinal metastasis, pelvic plexus invasion, thoracic wall invasion, neck invasion, bone metastasis, brachial plexus invasion, celiac plexus invasion, and thalamic pain. The maintenance dosage range was 10mg-40mg per day in 2 to 4 divided doses. Pain was rated by the patient on a numerical rating scale (NRS) of 0 to 10. A 50% or greater reduction in pain according to the NRS was reported by 21 of the 25 patients after the addition of Baclofen. Side effects of sleepiness and GI symptoms were minimized by initiating therapy at a low initial dose of 10mg/day and titrating up to 40mg/day with gradual increases every 2 days depending upon response. Weakness is also a common side effect related to the muscle relaxant properties of Baclofen, however, in this study weakness was only noted in 1 patient. Baclofen was continued for a median duration of 114 days in the 21 patients who reported positive effectiveness.
The effectiveness of Baclofen in a few of the cancerous conditions is not too surprising since these conditions were likely to have a significant neuropathic pain component (ex; pelvic plexus invasion or spinal mets). The interesting finding is that it was also effective for other pain types such as bone metastases. This study suggests that Baclofen can be an effective adjuvant analgesic for managing cancer pain in combination with opioid therapy.
References: (1.) Yomiya, Matsuo, Tomiyasu, et al. Amer.J.Hosp&PalliatCare Med. 2009;Vol26, No2, 112-118. (2.) Fromm, et al. Arch Neurol. 1980;37:768-771 (3.) Chen, Pan . Neuroscience. 2006;142:595-606
Posted by Dr. Jim Joyner
Yesterday (March 24, 2010) The Senate held a hearing regarding this issue.
Read and view the testimonies from the Senate Hearing on DEA Actions on Pain Meds in SNFs at: http://aging.senate.gov/hearing_detail.cfm?id=323367&
Also, there have been several articles this week in the News on this issue:
NY Times Article "U.S. Drug Move Said to Deprive Elderly"
WSJ Article "Nurses' Drug Dispensing Examined"
PR Newswire Article "AHCA/NCAL Praises Senate Committee for Shining Light on Outdated Rules Causing Delays with Medication for Patients in Pain"
Our original article follows:
Recent actions by the Drug Enforcement Agency (DEA) may have an adverse impact upon availability of opioids and other controlled substance medications for hospice patients that reside in skilled nursing facilities (SNFs). The DEA has recently launched a series of enforcement actions against several pharmacies that provide service to SNFs in the state of Ohio. Citations were issued to the pharmacies for following common standards of practice that have evolved over time to meet the needs of patients in long-term care facilities. As a result of the DEA action, many pharmacies, nationwide, are initiating significant changes to their policies and procedures for dispensing prescriptions for controlled substances to patients residing in SNFs. This includes hospice patients. Specifically, pharmacies may refuse to fill any prescriptions for controlled substances (including drugs in schedules II through V) that are written on a chart order from a SNF. The DEA has indicated that it considers chart orders for controlled substances to be invalid prescriptions unless they contain the following information:
1) Full name and address of the patient
2) The drug name, strength, dosage form, quantity prescribed, and directions for use
3) The name, address and registration number of the prescriber
4) Dated and signed by the prescriber on the date it is issued
Most chart orders do not contain this information and therefore the pharmacy cannot legally fill the prescription for a controlled substance off of a chart order. In addition the DEA does not recognize the nurse in the SNF as an agent of the physician and therefore the nurse cannot legally transmit the physician's order for a controlled substance to the pharmacy. For example, it is currently a common practice in many regions for the nurse at the SNF to fax chart orders for schedule II controlled drugs to the pharmacy, or for the physicians to call the orders into the pharmacy. Both of these procedures technically violate the DEA regulations and pharmacies cannot legally dispense these drugs based on chart orders that are faxed by the facility or verbal orders over the phone. In response to requests from pharmacy professional associations, the DEA has responded that it is looking into the possibility of relaxing it's interpretation of the law to allow for the use of chart-orders as recognized legal prescriptions for controlled drugs in schedules III-V, but not schedule IIs.
The DEA has clarified it's view regarding when a pharmacist may dispense a schedule II controlled drug upon the verbal order of a physician. This is allowed only in an emergency situation. The pharmacy may dispense a quantity limited to the amount adequate to treat the patient during the emergency period. The DEA defines an emergency in the following way:
1) immediate administration of the drug is necessary for proper treatment
2) no appropriate alternative is available
3) it is not reasonably possible for the physician to provide a written prescription to be presented to the pharmacist prior to dispensing
Pharmacist and physician groups have expressed concern that many physicians will likely be resistant to complying with the changes that are necessary to meet this new strict compliance with the law. Some physicians may decide to forgo practicing in the long term care environment altogether, further exacerbating the problem.
Pharmacies are striving to comply with the DEA's new strict interpretation of their rules and regulations to avoid potential fines and penalties. As a result, standard operating procedures that have been in place for many years at pharmacies are being evaluated and revised. This may result in significant delays in availability of certain critical medications for hospice patients that reside in a SNF. DEA is apparently aware of the potentially serious negative impact that their actions will have upon the timely availability of controlled substance drugs for hospice patients in the SNF. They have indicated they are considering sending out a "Dear Physician" letter to inform physicians and other health care providers about the need for strict compliance. In the mean time, don't be surprised to see new standard operating procedures emerging from the pharmacies with regard to controlled drug prescription requirements for your SNF hospice patients. The situation is still rapidly evolving and we will keep you informed as new details become available.