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. 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
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
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.
Posted by Dr. Jim Joyner
Hospice Medication Management: Xopenex & Albuterol for Asthma and COPD
Xopenex (levalbuterol) is a beta-agonist type bronchodilator. Xopenex is very similar to, and is in fact an isomer of the earlier beta-agonist bronchodilator albuterol. Albuterol and Xopenex are both beta-2 selective agonist bronchodilators indicated for asthma and COPD.
Xopenex is more potent than Albuterol on a milligram per milligram basis, so theoretically Xopenex may have an advantage by having less risk of side effects since less drug is required for therapeutic effects. This theoretical advantage is not proven out by the clinical studies which have demonstrated comparable efficacy and safety between Albuterol and Xopenex in both short-term and long-term studies. The safety and efficacy of levalbuterol inhalation solution was evaluated in a 4-week, multi-center, randomized, doubleblind, placebo-controlled study in 362 adult and adolescent patients 12 years of age and older, with mild-to-moderate asthma. Efficacy was measured by the mean percent change from baseline in FEV1. A dose of 0.63 mg of levalbuterol and 2.5 mg of albuterol sulfate produced a clinically comparable mean percent change from baseline in FEV1 on both day 1 and day 29. No significant difference in side effects was demonstrated as measured by heart rate, blood pressure, and tremor. (Xopenex [package insert]. Marlborough, MA: Sepracor Inc.; 2003)
Albuterol is a more cost-effective alternative to Xopenex which appears to have very similar efficacy and a similar safety profile.
Xopenex should be reserved only for those hospice patients which exhibit intolerable adverse effects to albuterol, specifically: increased heart rate, elevated blood pressure, and/or tremor.
Posted by Dr. Jim Joyner
Continued from Part 1 of Discontinuing Drugs in Hospice
There is no hard and fast rule regarding drug discontinuation. The plan for each hospice patient will depend upon their individual condition, prognosis, and goals of care. In many cases, the doses being used will not be great enough to result in any significant withdrawal or rebound effects upon abrupt discontinuation of the drug. It is important for the clinician to be aware of the potential for these types of drugs to cause adverse effects if withdrawn abruptly. Decisions regarding tapering of medications can then be addressed in light of the hospice patient's current condition, the dosage of medication, and the duration of therapy with the medication. Some strategies for gradual discontinuation have been provided here and should be considered as starting points in a patient's plan for gradual dose reduction. Once the process of gradual dose reduction is initiated, it should be individualized and modified depending upon the patient's response. In dying hospice patients who are no longer able to swallow medication, it is generally acceptable to discontinue many of these medications abruptly.
Beta-blockers (metoprolol, atenolol) are one of the more widely known examples of drugs that usually requires tapering. In general, if beta-blockers are stopped abruptly the patient will be at risk for rebound hypertension, angina, and tachycardia. Patients on higher doses will be at greater risk for those problems. Patients on the lower entry-level doses such as metoprolol 25mg bid probably will not be adversely affected by an abrupt discontinuation. Beta blockers may need to be tapered over 7 to 10 days depending upon the dosage.
Antidepressants may need to be tapered over 3 to 4 weeks (reduced by 25% a week) to avoid withdrawal symptoms. This is true of SSRI type and Tricyclic type of antidepressants. SSRI withdrawal symptoms include: flu-like symptoms (muscle aches, nausea-vomiting, diarrhea), insomnia, irritability, depression, flushing, sweating, dizziness, and "electric-shock" sensations in various parts of the body. Tricyclic withdrawal symptoms are similar to that of the SSRI drugs, but without the dizziness or the "electric shock" sensations. The withdrawal syndrome has been reported most commonly with Paxil and Effexor, but may occur with any antidepressant. Patients on lower doses may have doses reduced by 50% per week over 1 to 2 weeks.
Antipsychotic drugs may need to be tapered over 1 to 2 weeks to avoid withdrawal symptoms that may include: sweating, salivation, runny nose, flu-like symptoms, parathesia, increased urination, vertigo, agitation, anorexia, and psychosis. Antipsychotics may be stopped abruptly if severe adverse effects are present (dystonia, agranulocytosis). If abrupt discontinuation is necessary, withdrawal symptoms may be managed with benzodiazepines or valproic acid.
Anticonvulsants may need to be tapered by 25% a week to reduce the risk of seizures. More rapid tapering may be initiated if there are serious adverse effects present, however, smaller dose reductions may be necessary if seizure control has been poor. Ideally, taper should start after a new agent has been titrated to an effective dose. Gabapentin & Pregabalin withdrawal symptoms may include anxiety, insomnia, nausea, pain, & sweating in addition to seizure activity.
Benzodiazepines when stopped abruptly from moderate to high doses may result in a true physiological withdrawal and may also cause a relapse in the original anxiety symptoms that the patient was being treated for. Symptoms of benzodiazepine withdrawal include: sweating, tremor, agitation, nausea, and tachycardia. At very high doses, abrupt stoppage of the drug may result in seizures. Patients on high doses may need to be tapered over 4 weeks. Those at the low end of the dosage range may not require a taper.
Muscle relaxants, including Baclofen, Carisoprodal, and Tizanidine may need to be tapered over 1 week to avoid symptoms ranging from mild reactions of body aches, anxiety, sweating, and insomnia to severe reactions including hallucinations, hypertension, tachycardia, and seizures. Doses in the lower range are generally associated with only mild reactions upon abrupt discontinuation.
Corticosteroids may need to be tapered to avoid a rebound of symptoms of the underlying condition being treated (flares of rheumatoid arthritis, lupus, dermatitis) as well as to avoid steroid withdrawal symptoms. Steroid withdrawal symptoms include: flu-like symptoms (muscle aches, nausea/vomiting, diarrhea), hypotension, abdominal pain, weakness, and weight loss. Steroid withdrawal symptoms are due to the unmasking of adrenocortical suppression seen with the abrupt stoppage of corticosteroids in patients on long-term therapy. Generally significant adrenocortical suppression is not a concern in patients who have received corticosteroids for 3 weeks or less and have not received a dosage of > 20mg/day of Prednisone or Prednisone equivalent (dexamethasone > 3mg/day). Abrupt cessation in these patients is unlikely to trigger significant steroid withdrawal symptoms. For patients who have been on higher dose steroids or receive courses of therapy longer than 3 weeks, a gradual taper is recommended. Steroid doses may initially be reduced rapidly (by halving the dose every 2 days) until physiological doses are reached (prednisone 7.5mg daily or equivalent), then more slowly (1-2 mg/week) to allow the adrenals to recover.
Clonidine, the antihypertensive medication, may need to be tapered over 2 to 4 days to reduce the risk of a discontinuation syndrome. The discontinuation syndrome with Clonidine consists of rebound hypertension, headache, anxiety, insomnia, sweating, tachycardia, tremor, muscle cramps, hiccups,nausea, and salivation. Rarely, in extreme cases of abrupt withdrawal off of very high doses, encephalopathy, stroke, and death have been reported. The risk of the discontinuation syndrome is greater with oral Clonidine than with the Transdermal patch, however, it is recommended that the patch be tapered or the patient switched to oral and then tapered.
Opioid withdrawal symptoms consist of runny nose, tearing, chills, muscle aches, vomiting, diarrhea, cramps, anxiety, insomnia, and agitation. Rebound pain from the underlying condition being treated may also present. Initial dosage reduction should be at an increments of 25% every 3 days.
Posted by Dr. Jim Joyner
The Food and Drug Administration Amendments Act (FDAA) passed by congress in September of 2007 provides the FDA with new expanded authority to require Risk Evaluation and Mitigation Strategies (REMS) for drugs and biologicals.
Essentially the FDA can now require the manufacturer of any drug to develop and submit a REMS if the FDA determines that it is necessary to ensure that the benefits of the drug outweigh the risks of drug.
This applies not only to applications for new drugs, but also to drugs that have previously been approved by the FDA and are currently in use by patients. The decision to require REMS for an existing preapproved drug may be triggered at any time if the FDA becomes aware of new safety information that makes the determination necessary in the opinion of the agency.
The REMS are required to contain one or more of the following elements; a patient medication guide, communication plan to healthcare providers, and more complex components to assure safe use (such as a restrictive distribution plan, special training for prescribers and pharmacists, and patient, pharmacy, and prescriber registries). The law states that a REMS should not have "unduly burdensome" effects on patient access to medication, however there are no guidelines or examples offered as to what would constitute an undue burden.
Letters were sent to all of the opioid drug manufacturers on February 6th 2009 to inform them that the FDA has determined that they would be required to develop a comprehensive REMS plan. The purpose of the REMS, according to the FDA, is to ensure that the benefits of the opioids continue to outweigh the risks of misuse, abuse, and accidental overdose and to manage any known or potential serious risk associated with an opioid. The FDA's rationale for this approach is that despite numerous efforts taken by the agency, drug manufacturers, and others in the past, the rates of misuse, abuse, and accidental overdose of opioids has continued to rise over the past decade. The FDA believes that establishing REMS for opioids will reduce these risks, while still ensuring that patients with legitimate need will continue to have appropriate access. All of us in the hospice industry are aware of the need for the use of opioids for pain management in end of life care.
The FDA has specifically targeted all of the long-acting opioids, with heavy utilization in hospice care, including the following: morphine extended release tablets and capsules, oxycodone extended release tablets, oxymorphone extended release tablets, methadone, and the fentanyl transdermal patch.
A meeting between the FDA and the opioid drug manufacturers was held on March 3, 2009 as a follow-up to the FDA letter regarding REMS development. At this meeting Dr. Bob Rappaport, Division of Analgesics, Anesthetics, and Rheumatology Products Director (FDA) stated, "We expect all companies marketing these products to work with us to get this done expeditiously . If not, we cannot guarantee that these products will remain on the market." (The Pain Practitioner vol 1, no 2).
In subsequent meetings with the various stakeholders (including professional societies, consumer groups, industry representatives, providers, patients, and pharmacists), the FDA again indicated that long-acting opioids could be removed from the market if the benefits of the medications are not demonstrated to outweigh the risks.
Dr. John Jenkins, Director of the Office of New Drugs (FDA) stated: "We recognize this is going to be a relatively massive new program... the 21 million prescriptions is orders of magnitude greater than any other program now in place. It's likely that legitimate patients will see new procedures that will be in place for obtaining these drugs, but we hope to make those procedures not so intrusive that it impacts their ability to receive the products while still meeting the second goal of having an impact on safe use."
The recent actions and public comments from FDA regarding opioid medications should give all of us who serve hospice patients great concern. There is a real possibility of serious unintended consequences if the FDA doesn't get this right. If opioid REMS is not developed carefully, so as not to interfere with the appropriate medical care of legitimate patients, another layer of barriers will emerge resulting in even greater problems with under-treatment of pain than we already have today. Some of these unintended consequences may include:
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More pharmacies refusing to stock opioid medications
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Less physicians who are willing to prescribe opioids
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Increased cost of opioid prescriptions for hospice patients
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Increased use of short-acting opioids in cases where the long-acting opioid is more appropriate
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Delayed response in prescribing and dispensing of opioids to hospice patients due to bureaucratic barriers
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Increased pain in our hospice patients
A variety of groups and professional organizations are providing input to the FDA regarding REMS. One among many that has taken an aggressive approach is the American Academy of Pain Management. They have provided some concrete recommendations to help ensure an effective REMS plan that does not lead to unintended adverse consequences.
Continue to support the efforts of your local, state and national organizations to ensure that your hospice patients will continue to have appropriate access to these critical medications without formidable bureaucratic barriers.
If your hospice is in need of hospice pharmacy services, Sign up for a Free Hospice Pharmacy Consultation or Contact Us today!
Photo Credit: Erix!
Posted by Dr. Jim Joyner
Hospice patients may report allergies to opioids, but often these are pseudoallergies consisting of symptoms of itching, flushing and sweating. Pseudoallergy type reactions are relatively common.
True allergy to opioids is rare. (1) Pseudoallergy is caused by release of histamine from the mast cells in the skin, a non-immunologic event. (2) True allergy is believed to be IgE mediated or T-cell mediated. (3) If the reaction is only flushing, itching, or sweating the opioid can often be continued with the addition of an antihistamine or dose reduction. (4) If the true nature of the reaction to an opioid is not clarified, the hospice patient may be incorrectly "labeled" as allergic to opioids and opioid drugs may be withheld unnecessarily.
If the reaction consists of hives, increased heart rate, severe hypotension, or bronchospasm the patient should be assumed to be exhibiting a true allergic reaction and the clinician will need to decide which, if any, opioid is safe for the hospice patient.
Codeine, Morphine, and Meperidine are associated with the most allergictype reactions. (1) It has been suggested that hospice patients allergic to one opioid are less likely to react to an opioid in a different structural class.
It is reasonable to consider rotating from an opioid from one class to one from another distinct class in some situations. The 3 main structural classes are as follows:
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Morphine group: morphine, codeine hydrocodone, oxycodone, oxymorphone, hydromorphone, levorphanol
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Diphenylheptanes: methadone, propoxyphene
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Phenylpiperidines: fentanyl, meperidine
Some patients may experience localized itching and redness underneath the Fentanyl patch. Patch site rotation is very important to reduce this risk. This reaction can be managed by topical application of a steroid, such as triamcinolone spray prior to application of the patch.
Although many hospice patients may report a history of allergy to opioids, most have only experienced a side effect . Proper selection of an opioid medication based upon past history can result in significantly improved outcomes in pain management for the hospice patient.
(1) J Oncol Pharm Practice 2004;10: 177-82 (2) Immunol Allergy Clin North Am 1991;111: 635-44 (3) Anesthesiology 1989; 71: 489-94 (4) Applied Therapeutics: The Clinical Use of Drugs 8th ed. 2005