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Statin Discontinuation in Hospice Patients
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Medication Discontinuation in Dementia Patients
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Recent Generic Drug Approvals
4
Opioids and Allergies
5
Increasing Awareness of Melatonin
6
Make Sure the Pharmacist Knows…
7
Safe Medication Practices
8
Options for Switching Antipsychotics
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Medication Discontinuation in Dementia Patients By Corina Reyna, PharmD, BCGP
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When Discontinuing Medications is Continuing Compassionate Care

Statin Discontinuation in Hospice Patients

Hospice prescribers and pharmacists have long approached statins as appropriate for discontinuation in their patients who have no active cardiovascular disease since preventative or prophylaxis medications, as well as medications with long-term therapeutic outcomes, are not considered part of palliative care.  With the benefits of statin discontinuation ranging from decreasing pill burden to preventing myopathy, from cost-savings to fewer drug-drug interactions, it has become a common practice.  However, many hospice prescribers still overlook the potential benefits of statin discontinuation such that they do not always consider it in a timely manner after admission to hospice.

When the hospice team admits a patient with no known cardiovascular disease who is on a statin, it is helpful to remind new hospice prescribers of research demonstrating that the discontinuation of statins in this population does not alter mortality rates within 60 days of discontinuation or alter the median time to death.  Similarly, discontinuation does not appear to affect rates of cardiovascular events but may actually provide improvements in quality of life.  Research findings also imply that it is possible that statin deprescribing may lead to a reduction in the number of non-statin prescriptions required, perhaps due to fewer adverse effects requiring treatment for patient comfort.  It is prudent to consider the risks of continuation of any medication that no longer provides benefit, especially when dysphagia is present.

Of course, discussions about discontinuing any therapy should occur in the context of shared decision making, especially in the case of statins as research indicates that neither continuation nor discontinuation is clearly superior.  Furthermore, the data surrounding the topic of stopping statins in late-stage terminal patients serves as a reminder of the importance of utilizing patient-centered ongoing medication therapy reviews as an opportunity to continually assess the risk versus benefit of all components of a hospice patient’s medication regimen.

 

References:

Kutner, et al. Safety and benefit of discontinuing statin therapy in the setting of advanced, life-limiting illness: a randomized clinical trial. JAMA. 2015 May;175(5):691-700  https://www.ncbi.nlm.nih.gov/pubmed/25798575

Holmes H. & Todd A. Evidence-based deprescribing of statins in patients with advanced illness. JAMA. 2015 May;175(5):701-702  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4420700/

Voelker R. Statin use may stop when illness is terminal, study says. JAMA. 2014 Jul 16;312(3):221

Medication Discontinuation in Dementia Patients

Understanding the progressive nature of dementia can help in the decision to continue or discontinue dementia medications in patients on hospice care for end-stage dementia.  Goals change as patients progress from mild to severe dementia.  In mild to moderate dementia, the primary goal is to slow the progression of the disease.  As dementia nears its end stages, the goal of care generally shifts to the control of dementia symptoms, especially when patients qualify for hospice care.

Neither the cholinesterase inhibitors nor the NMDA receptor antagonists have been proven beneficial in end-stage dementia.  Both classes of medications have the potential to cause significant adverse effects in declining patients whose bodies are less able to efficiently metabolize these medications.  Diarrhea, loss of appetite, nausea, symptomatic slow heart rate, and fainting are all potential side effects of cholinesterase inhibitors; memantine puts patients at greater risk for dizziness, headache, confusion and constipation.  When such medications are added to others commonly prescribed for patients admitted to hospice for dementia, the rates of these and other adverse effects often increase.  Though some patients gain a small benefit from the continuation of dementia medications, the potential dangers of continuing dementia medications must be considered.

The decision to continue or discontinue dementia medications can at first appear difficult, but a simple discontinuation plan can guide therapy options and ease caregiver concerns.  A prudent plan often includes a gradual discontinuation of dementia medications, monitoring patients for any new or worsening symptoms.  Some symptoms are better managed with other medications commonly used to manage dementia symptoms at end of life.  More often than not, patients do well with the discontinuation, have less risk of adverse effects from their remaining medications, and are well managed with conventional symptom management.

References:

Buckley JS, Salpeter SR. A risk-benefit assessment of dementia medications: systematic review of the evidence. Drugs Aging. 2015; 32(6):453-467.

Yang Z, Zhou X, Shand Q. Effectiveness and safety of memantine treatment for Alzheimer’s disease. J Alzheimers Dis. 2013; 36(3):445-458.

Minett TS, Thomas A, Wilkinson LM, Daniel SL, Sanders J. Richardson J, Littlewood E, Myint P, Newby J, McKeith IG. What happens when donepezil is suddenly withdrawn? An open label trial in dementia with Lewy bodies and Parkinson’s disease with dementia. Int J Geriatr Psychiatry. 2003; 18(11):988-93.

Recent Generic Drug Approvals

Recent Generic Drug Approvals

In the bustle of daily patient care, it is difficult to stay up-to-date on newly released generic medications, but doing so can prove beneficial.  In 2017, several medications potentially helpful in the hospice population became generic, including Seroquel XR®, Coreg CR®, and Pristiq®.  Though most generics available for these products are still quite expensive compared to previously available products, as time passes prices will continue to drop.  In the meantime, consider them as options when first-line, more cost-effective medications or medication forms are not viable options.

Brand Name Generic Name Benefit
Seroquel XR® Quetiapine extended release tablet Once daily administration
Coreg CR® Carvedilol extended release capsule Once daily administration
Pristiq® Desvenlafaxine extended release tablet Provides another antidepressant option

Opioids and Allergies

Hospice patients often communicate allergies to medications.  When the medication is an opioid, hospice staff often have to determine whether the reaction that the patient believed to be an allergy is truly an allergy and whether the reaction necessitates the avoidance of certain opioids.  True allergies involve an immune response; other reactions can fall into the category of either side effects or pseudoallergy, which is generally the result of histamine release but no actual immune response.  Given a patient’s reaction history, sometimes it can be difficult to determine which medications are safe and which are not, but some simple collection of reaction information can provide some guidance.

 

Pseudoallergy: If the following symptoms occur with respect to opioid administration, they are likely related to a pseudoallergy rather than a true drug allergy:

  • Generalized flushing, itching, and/or sweating
  • Mild hypotension
  • Itching, flushing, or hives at injection/application site

Such reactions can be managed with the following:

  • Try nonopioid analgesics for mild pain
  • Avoid codeine, morphine, and meperidine
  • Use a more potent opioid at appropriate doses (drugs listed below from least to most potent):
    • Meperidine < codeine < morphine < hydrocodone < oxycodone < hydromorphone  < fentanyl
  • If opioid in question is effective against pain and symptoms are mild, consider administering it with an antihistamine
  • Consider a reduction in dose, if tolerated
  • Avoid parenteral administration and/or slow down the rate of administration

 

Allergy: A true allergy to an opioid often displays one or more of the following:

  • Bronchospasm
  • Breathing, speaking, and/or swallowing difficulties
  • Angioedema
  • Severe hypotension
  • Urticaria

When there is a history of such symptoms related to a certain opioid:

  • Do not administer the offending agent
  • Try a nonopioid analgesic if pain is mild
  • Try an opioid from a different chemical class and monitor closely (see below for general opioid drug classes)

 

Drug Class Specific Agent Brand Names
Phenylpiperidines  

Meperidine

Fentanyl

 

Demerol®Duragesic®, Sublimaze®
Diphenylheptane Methadone Dolophine®
Phenanthrines MorphineCodeine

Hydrocodone

Oxycodone

Oxymorphone Hydromorphone

MS Contin®, Roxanol®Tylenol #3®

Vicodin®, Lortab®, Norco®

Percocet®, OxyContin®, Oxyfast®

Numorphan®, Opana®

Dilaudid®

Increasing Awareness of Melatonin

The ever-increasing awareness of the dangers of hypnotic use in the elderly leaves many patients, prescribers, and caregivers hesitant to initiate prescription medications to treat insomnia.  Combined with the increased awareness and use of natural vitamins and supplements amongst hospice patients, many hospices are finding it desirable to utilize melatonin in certain patients having difficulty sleeping.

Melatonin is a hormone naturally produced by the pineal gland as part of the sleep-wake cycle, with its blood level being highest at night. Many proponents of its use believe that it provides benefit in sleep disorder or, more specifically, sleep disorder involving circadian rhythm.  Melatonin is a body clock regulator and not a sleep initiator.  It does not increase the body’s drive for sleep but, rather, tells the brain when it is time to sleep.

Though its adverse effects are typically mild, the most common side effects include daytime sleepiness, dizziness, and headaches, with abdominal discomfort, mild anxiety, irritability, confusion, and short-lasting feelings of depression possibly occurring.  Mobile patients who take melatonin should be advised to not engage in activities requiring alertness for four to five hours after taking melatonin.

Melatonin can potentially interact with various medications.  For instance, since it slows clotting, it should be used with caution with blood thinners.  Melatonin stimulates the immune system, so its use should be avoided in patients on immunosuppressants.  Due to its effect of increasing blood sugar levels, diabetic patients may need closer monitoring while on melatonin.  Taking melatonin along with sedative medications can cause excessive sleepiness.

Though research is mostly inconclusive regarding the efficacy of melatonin, there also is no conclusive evidence of dangers of its use at reasonable doses for short periods of time.

Fall risk, psychiatric conditions, and concurrent drug therapy can make the use of traditional hypnotics undesirable.  In such patients, it may be reasonable to consider a conservative dose of melatonin.  Doses of 3 to 5 mg are commonly used, but research indicates that lower doses in the range of 0.3 to 1 mg are more effective and possibly safer.  Regardless of the dose used, it is typically advised to administer melatonin about 90 minutes prior to the desired bedtime.

Make Sure the Pharmacist Knows…

Meeting the Conditions of Participations (CoPs) medication review requirements is important.  However, even more important is ensuring that the pharmacist performing the reviews is aware of all pertinent patient co-morbidities.  A complete list of co-morbidities is valuable in order to ensure that all potential disease-state/medication interactions are detected and the appropriate interventions are made.  Nursing staff can greatly assist in this transmission of information.  If staff is conscientious to double check patient charts for several of the most common disease states that interact with medications, patient care can be significantly improved.  Some of the most important disease states to communicate to the individual performing the medication review(s) are:

  • Renal disease (include disease stage or renal lab values)
  • Hepatic disease (type and severity)
  • Congestive heart failure (include stage, if available)
  • Heart block (include degree of heart block)
  • Benign prostate hyperplasia (BPH)
  • Asthma
  • Parkinson’s disease
  • Arrhythmias
  • Hypertension

Safe Medication Practices

The Institute for Safe Medication Practices (ISMP) has long recognized the frequency of mix-ups resulting from the non-standardization of units utilized in measuring volume of oral liquid medications.  Since 2009, ISMP has strongly encouraged all practitioners to solely utilize the metric system for measuring oral liquid doses.

The National Council for Prescription Drug Programs (NCPDP) supports the use of the milliliter (mL) as the standard unit of liquid measure for prescription oral liquid medications.  In addition to encouraging the use of the milliliter unit alone for such products, NCPDP stresses that dose amounts should always include leading zeros before the decimal point when the amount is less than one milliliter and should not include trailing zeros after a decimal point.  For instance, directions for eight tenths of a milliliter should be written as 0.8 mL and never .8 mL where the decimal point can be overlooked and the dose misinterpreted as 8 mL.  Similarly, utilize 2 mL rather than 2.0 mL which can be confused as 20 mL.  Altogether avoid the use of the teaspoon or other non-metric measurements for all patient instructions.

Always ensure that patients have a measuring device marked clearly in milliliters only to prevent errors.  For further patient safety, ISMP recommends that patients and/or caregivers be coached on use and cleaning of oral liquid measuring devices, utilizing the “teach back” approach to ascertain whether or not training is understood.

References:

  1. NCPDP recommendations and guidance for standardizing the dosing designations on prescription container labels of oral liquid medications. http://www.ncpdp.org/Education/Whitepaper. March 2014
  2. ISMP 2014-15 targeted medication safety best practices for hospitals, best practice 5. ismp.org/tools/bestpractices/TMSBP-for-Hospitals.pdf.

Options for Switching Antipsychotics

Medication cost, adverse effects, and poor therapeutic response often necessitate switching a hospice patient from one antipsychotic to another.  Prescribers can choose among several options when a switch is necessary.

Abrupt switch:

Often preferred by hospice prescribers, one antipsychotic can be abruptly discontinued with the immediate start of a new antipsychotic at a therapeutic dose.

Gradual tapering:

The initial antipsychotic dosage can be decreased by 25 to 50% of the total daily dose every 4 or 5 half-lives with concurrent up-titration of the new antipsychotic.  Refer to the chart of half-lives of common antipsychotics.

Overlap:

When overlapping products, the initial antipsychotic is continued at full dose while titrating the patient’s new antipsychotic.  When the new antipsychotic is at a therapeutic dose, the initial antipsychotic is tapered for discontinuation.

Since no one option is universally superior to another, prescribers must select the best switch method on a patient-by-patient basis.  Patient prognosis, patient stability, clinical status, efficacy of current medication(s), type of side effect(s) present, potential side effects of the new antipsychotic, and caregiver limitations are important factors that must be considered.

Problems occurring early after a switch can include psychotic symptoms, insomnia, anxiety, agitation, and extrapyramidal effects.  Since these effects can be either a response to the new medication or a result of withdrawal of the previous medication, they can be managed in various ways.  Watchful waiting is often preferred when symptoms are mild.  A slow restart of the initial antipsychotic may be necessary if severe rebound effects or withdrawal symptoms are present.  When the switch results in anxiety and restlessness, the addition of a benzodiazepine can provide temporary benefit of withdrawal effects, allowing clinicians to wait to see how the patient tolerates the switch once withdrawal dissipates.

Half-Lives of Common Antipsychotic Medications

Haloperidol 15-37 hours
Olanzapine 21-54 hours
Quetiapine 6 hours
Risperidone 3 hours in extensive metabolizers;20 hours in poor metabolizers
Ziprasidone 7 hours

 

References:

Martin, C. Reducing antipsychotic medications: developing a systematic process. Consult Pharm 2015;30:378-84.

Bobo, W. (2013, Mar 13). Switching anitpsychotics: why, when, and how? Psychiatric Times. Retrieved from http://www.psychiatrictimes.com

Medication Discontinuation in Dementia Patients By Corina Reyna, PharmD, BCGP

Understanding the progressive nature of dementia can help in the decision to continue or discontinue dementia medications in patients on hospice care for end-stage dementia.  Goals change as patient’s progress from mild to severe dementia.  In mild to moderate dementia, the primary goal is to slow the progression of the disease.  As dementia nears its end stages, the goal of care generally shifts to the control of dementia symptoms.

Neither the cholinesterase inhibitors nor the NMDA receptor antagonists have been proven helpful in end-stage dementia.  Both classes of dementia medications have the potential to cause significant adverse effects in declining patients whose bodies are less able to efficiently metabolize these medications.  Diarrhea, loss of appetite, nausea, symptomatic slow heart rate, and fainting are all potential side effects of cholinesterase inhibitors.  Interactions with other medications increase the risk for symptoms such as worsening of mental status, urinary retention, constipation, and dry mouth.  Though some patients gain a small benefit from the continuation of dementia medications, the potential dangers of continuing dementia medications must be considered.

The decision to continue or discontinue dementia medications can seem difficult until it is realized that a simple discontinuation plan can guide therapy options and ease caregiver concerns.  A prudent plan is to gradually discontinue dementia medications, monitoring patients for any new or worsening symptoms.  Some symptoms are better managed with other medications commonly used to manage dementia symptoms at end of life.  More often than not, patients do well with the discontinuation of medications, have less risk of adverse effects from their remaining medications, and are well managed with conventional symptom management.

When Discontinuing Medications is Continuing Compassionate Care

If ever there is a time for compassionate medicine, it is when a patient is nearing the end of life.  Unfortunately, when hospice becomes involved in patient care and recommendations are made for the discontinuation of medications, patients and caregivers alike can feel abandoned.  They may feel as though the discontinuations will hasten death, worsen symptoms, or imply the patient is not worth treating any longer.

The difficulty of appropriately communicating rationale for drug discontinuation often results in continuation of unnecessary polypharmacy in order to avoid those difficult discussions.  However, if approached appropriately, these discontinuations can be made while assuring patients and caregivers of a desire to improve quality of life.

Careful consideration must be made when determining what medications to discontinue in hospice patients.  Helpful questions to ask include:

–Does a medication’s risks outweigh its benefits?

–Is the therapeutic benefit diminished to the extent that the medication no longer provides benefit?

–Is there a lack of evidence to support the continuation of therapy?

–Does this medication help meet goals of care for this patient?

–If the medication was recently added, is the time to benefit longer than life expectancy?

–Is there a clear indication for the medication?

–Has the medication been effective?

–Does the medication interact with other products or disease states?

–Are there therapeutic duplications in the patient’s drug regimen?

–Could the medication be treating a side effect of another medication?

–Is the patient and/or caregiver over-burdened with current drug regimen?

When there is no time to taper medications, ensure staff and caregivers are aware to monitor patients for withdrawal symptoms, such as rebound hypertension when blood pressure medications are discontinued or agitation when antipsychotics are stopped.

Discussions regarding discontinuation of medications can be intimidating for case managers to initiate, but educating staff on the benefits of appropriate discontinuation can give them more confidence in their presentation of such recommendations.  As hospice staff knowledge increases regarding issues surrounding the continuation versus discontinuation of risky medications, case managers are more likely to seize the opportunity to discuss the benefits of timely discontinuation.  Are family members recognizing the patient’s decline?  Consider discontinuing unnecessary medications.  Is the patient experiencing troublesome side effects that decrease quality of life?  Consider discontinuation of offending medications.  Are medications becoming ineffective?  Consider stopping those drugs that are no longer providing benefit.

Additional education regarding optimal discontinuation methods can prevent undesirable withdrawal symptoms.  Tapering may be necessary, especially in discontinuation of:

Paroxetine and venlafaxine

Beta-blockers

Clonidine

Anti-seizure medications

Antipsychotics

Baclofen and tizanidine

Corticosteroids

Benzodiazepines

 

Ultimately, goals of care should always center around providing the most excellent care for the hospice patient.  As medication decisions are made, ensure that both the patient’s and physician’s goals of care are met.  Honest, open communication with the patient, family, and caregivers as well as among participants of IDG will help guide decision-making and result in the  medication regimen most appropriate for the compassionate care of each patient.

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