The Hospice Clinician Blog

The Journal of The American Society of Consultant Pharmacist has recently described a comparison between two criteria commonly use to identify potential inappropriate prescribing in elderly, the Beers Criteria and the relatively new, validated criteria, START (Screening Tool to Alert doctors to the Right Treatment) /STOPP (Screening Tool of Older Person’s Prescriptions). These newer tools are evidence-based and were validated since 2006 by a panel of 18 professionals from Ireland and the United Kingdom with Expertise in geriatrics or pharmacology. Many geriatric clinicians utilize them to identify inappropriate use of medications in elderly because they found them more user-friendly than the Beers Criteria.

For the last 20 years, the Beers Criteria has been the most commonly used tool and it is the basis of a Health care Effectiveness Data and Information Set (HEDIS) performance measure outlined by the National Committee for Quality Assurance. It contains 68 criteria, 48 of which describe medications to avoid in all elderly patients, while the rest are medications to avoid in the presence of 20 diseases or conditions. For more details on the Beers Criteria, please visit our previous blog posts on “Updated Beers Criteria and Implications for Hospice Care”.

In the new criteria, START/STOPP accounts for 22 scenarios that can be used to detect potential omissions in therapy of elderly patients and 65 commonly encountered instances of potentially inappropriate prescribing including drug-drug and drug-disease interactions, drugs which increased risk of falls and drugs which duplicate therapy.  The detailed criteria are summarized in the table available for download below. In comparison to the Beers Criteria, START and STOPP seem to be more user-friendly because they are organized by physiological system where specific medications are recommended and it provided more specificity on rational of inappropriateness. In addition to the Beers Criteria, START and STOPP also presented the potential omissions in therapy and the common drugs with duplicate therapy.

The additional categories and specificity provided in START/STOPP presented another valuable tool to alert clinicians on the potential medication errors seen in elderly (including elderly hospice patients) and it is easy to use.  Similar to the Beers Criteria, it is a list of explicit criteria for the general population of elderly above 65 years of age and it can sometimes incorrectly identify appropriate medication use as inappropriate in different settings, such as palliative care in hospice.   Precautions should be taken when using both Beers Criteria and START/STOPP criteria.  They are only tools, not rules, to provide guidance to aid clinicians to identify potential medication problem areas efficiently. The final judgment of the appropriateness of medication should be determined in light of a patient’s overall clinical picture and goals of care.

References:
1. Potentially Inappropriate Medications Defined by STOPP Criteria and the Risk of Adverse Drug Events in Older Hospitalized Patients. H. Hamilton, P. Gallagher, C Ryan, S Byrne, and Denis O’Mahony. Arch Intern Med. 2011;171(11):1013-1019 . Assessed <http://ageing.oxfordjournals.org/content/37/6/673.full.pdf+html>
2. START (screening tool to alert doctors to the right treatment)—an evidence-based screening tool to detect prescribing omissions in elderly patients. P. J. BARRY, P. GALLAGHER, C. RYAN, D. O’MAHONY. Age and Ageing 2007; 36: 632–638. Assessed <http://ageing.oxfordjournals.org/content/36/6/632.full.pdf+html>
3. STOPP (Screening Tool of Older Persons’ potentially inappropriate Prescriptions): application to acutely ill elderly patients and comparison with Beers’ criteria PAUL GALLAGHER, DENIS O’MAHONY Age and Ageing 2008; 37: 673–679
4. Inappropriate Medication Use in the Elderly. A. M. Petrarca, A.J. Lengel, and M.N. Mangan. The Journal of the American Society of Consultant Pharmacists. August 2012: 27: 583-586. 

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Hospice patients are, by definition, at high risk of delirium due to advanged age and terminal illness. Patients with dementia or cognitive impairment or who have a history of delirium are at even higher risk. In these patients, Histamine-2 Receptor Antagonists (H2RAs) such as ranitidine (Zantac), famotidine (Pepcid) and cimetidine (Tagamet) may cause delirium or other mental status changes, or may worsen cognitive impairment. Cimetidine, in particular, has been on the Beers List for years due, in part, to its potential for causing adverse CNS effects in the elderly. As of the 2012 update, the Beers List now contains the entire class of H2RAs. (See our Updated Beers List Blog Series)

How do H2RAs cause delirium?

It is well understood that drugs with anticholinergic activity can cause delirium and cognitive decline in elderly patients, especially those with Alzheimer’s disease or dementia. The H2RAs have varying degrees of anticholinergic activity (ranitidine and cimetidine – medium to high;  famotidine and nizatidine – low). There is inconsistent evidence linking H2RAs to delirium in clinical trials, but numerous case reports (particularly with cimetidine) indicate a possible relationship. When a patient suffers from delirium or an acute decline in cognitive status, always review their medication list. The obvious culprits, such as benzodiazepines and first-generation antihistamines, will stand out, but don’t overlook H2RAs as possible contributors.

Should H2RAs be avoided in hospice patients?

Sometimes. For patients at especially high risk of delirium, including those with cognitive impairment, consider another agent for acid suppression, such as an antacid or proton-pump inhibitor (PPI). For best cost-effectiveness, we recommend Prilosec OTC as the PPI of choice. When using an H2RA, keep the patient’s renal function in mind. All H2RAs are eliminated by the kidneys and have to be dose-adjusted for renal impairment; failure to do so will increase the risk of all side effects, including delirium. As a rule of thumb, cut the dose in half if the patient’s creatinine clearance is less than 50 mL/min, and consider further reductions in either dose or dosing frequency as renal function declines further.

Please post your comments/questions below. Outcome Resources strives to provide the very best hospice medication information to ensure not only cost efficiencies but best patient care. Contact Us to learn more about the resources available to help your hospice succeed.

So far, we have discussed some of the medications commonly used in hospice that appear on the Beers list and should be used with caution in all of our elderly patients. In this blog article, I’ll look at some disease-specific recommendations made by the Beers Criteria authors. These medications should be used with caution in particular patient populations, depending on their current disease states and symptomatology.

Heart Disease

For patients with heart disease, avoid the following:

Nifedipine, immediate-release: Extended-release nifedipine is fine, but the immediate-release form can cause severe hypotension and may precipitate myocardial ischemia due to the rebound tachycardia that occurs when blood pressure drops rapidly.

Alpha-1 blockers doxazosin, prazosin, terazosin: These medications pose a high risk of orthostatic hypotension, making them especially risky in patients with a history of falls or syncope. Because alternative antihypertensives have a superior risk/benefit profile, these medications are not recommended as routine treatment for hypertension.

Digoxin > 0.125 mg/day: At higher doses, the risk/benefit profile is unfavorable – the benefits of doses > 0.125 mg/day are negligible and the risk of digoxin toxicity is higher, especially in patients with any degree of renal impairment.

Spironolactone > 25 mg/day: In older adults, the risk of hyperkalemia is higher, especially if creatinine clearance is less than 30 mL/min or if combined with an ACE inhibitor, ARB, potassium supplement, or NSAID. In some cases, higher doses of spironolactone may be needed, but use this Beers list recommendation as a reminder to keep an eye on potassium levels.

In your heart failure patients, avoid the following medications; they all have the potential to cause fluid retention and exacerbate heart failure:

• NSAIDs and COX-2 inhibitors (if an NSAID must be used, choose naproxen as your first-line – see “How to Choose an NSAID for Hospice Patients, Part 1”)
• Nondihydropyridine calcium-channel blockers diltiazem and verapamil (in systolic heart failure only)
• Cilostazol (Pletal)
• Dronedarone (Multaq)
• Pioglitazone and rosiglitazone

Dementia and Cognitive Impairment

The following medications have adverse CNS effects in dementia patients. They should be avoided, when possible, and monitored closely if they must be used.

Antipsychotics: the use of antipsychotics in patients with dementia has been all over the literature lately, due to findings of increased risk of CVA and mortality in persons with dementia. Avoid use for behavioral problems of dementia unless nonpharmacological options have failed and the patient is a threat to self or others.

Benzodiazepines: Benzodiazepines can worsen confusion and agitation in patients with dementia, especially when used routinely for extended periods of time. Use cautiously and consider discontinuing if cognitive symptoms worsen.

Medications with strong anticholinergic properties: Anticholinergic medications can also worsen cognitive symptoms in patients with dementia, and should therefore be avoided or used with close monitoring. Common culprits include first-generation antihistamines, tricyclic antidepressants, antipsychotics, muscle relaxants, and medications used for management of secretions, such as scopolamine and atropine.

Zolpidem (and, by extension, zaleplon and eszopiclone): These medications are similar to the benzodiazepines in their adverse effects in dementia patients.

Parkinson’s Disease

Benztropine and trihexyphenidyl: More effective agents are available for the treatment of Parkinson’s disease, and the Beers Criteria authors do not recommend that these agents be used for the prevention of extrapyramidal symptoms in patients taking antipsychotics.

Dopamine receptor antagonists: because Parkinson’s disease is related to low levels of dopamine in the brain, any medication that antagonizes dopamine’s effects has the potential to worsen parkinsonian symptoms:

• All antipsychotics except for quetiapine and clozapine, which appear to be less likely to precipitate worsening of Parkinson’s disease
• Antiemetics: metoclopramide, prochlorperazine, promethazine

Seizures

All of the following lower the seizure threshold and may increase the frequency and/or severity of seizures. Use of these medications may be acceptable in patients with well-controlled seizures in whom alternative agents have not been effective.

• Bupropion
• Chlorpromazine
• Olanzapine
• Tramadol
• Metoclopramide (this is my personal addition to the list)

Delirium

All of the following may induce or worsen delirium in older adults. If you have a hospice patient experiencing delirium, review their med list for any of these potential causes.

• All TCAs
• Medications with strong anticholinergic properties
• Benzodiazepines
• Chlorpromazine
• Corticosteroids
• H2-receptor antagonists
• Meperidine
• Sedative hypnotics

Constipation

While opioids are the most common cause of constipation in the hospice population, the following medications can also cause or worsen constipation:

• Non-dihydropyridine calcium channel blockers diltiazem and verapamil
• First-generation antihistamines
• Anticholinergics and antispasmodics
• Oral antimuscarinics for urinary incontinence: These agents differ in incidence of constipation, and response is variable. Consider an alternative agent if constipation develops.

A couple of days ago, we reviewed some key medications that have been newly added to the Beers List with the new 2012 update: megestrol (Megace), sliding scale insulin, glyburide, metoclopramide (Reglan), and the non-benzodiazepine hypnotics. Today, I’d like to look at some of the medications used in hospice that were previously on the Beers list and have remained there. These are medications that have been consistently demonstrated to be problematic in older adults, for a variety of reasons. As I emphasized in the previous post, the fact that these medications appear on the Beers list does not make them absolutely contraindicated in the elderly – in fact, as you will see, many of them are quite commonly (and, for the most part, appropriately) used in the hospice setting. However, despite the fact that we use some of these medications every day, we should still exercise caution, remembering that there can be serious adverse effects to watch out for. Others we should avoid altogether.

Meperidine (Demerol): Meperidine is not an effective oral analgesic in dosages commonly used, and it may cause neurotoxicity in older adults. Because a wide variety of safer and more effective opioids are available, there is virtually no role for meperidine in pain management.

NSAIDs (non-COX2-selective): NSAIDs have a slew of detrimental effects that are more likely to occur in the elderly, including cardiovascular, gastrointestinal and renal toxicities. Of course, there are situations in hospice when an NSAID must be used for effective pain management. But it is important to keep these toxicities in mind and to choose an NSAID that is most appropriate for your patient (see our three-part blog series on NSAIDs for more information), and use a gastroprotective agent for your patients at especially high GI risk. The Beers Criteria authors note that indomethacin has the most toxicities of all the NSAIDs. So, for your patients with gout pain, use a different NSAID. Even though indomethacin is the NSAID we usually associate with gout, there’s no real mechanistic reason for this – any NSAID will work.

Muscle relaxants: The efficacy of muscle relaxants is questionable at best, especially since they have so many side effects that most older adults can only tolerate low doses. They are highly anticholinergic, increase the risk of fracture, and cause sedation. If a patient is experiencing pain thought to be due to muscle spasm, you may consider a trial of a muscle relaxant, but monitor closely for both efficacy and side effects, and discontinue the muscle relaxant if there is not a clear improvement in pain.

Benzodiazepines: We use benzodiazepines so often in hospice that it’s hard to believe that, in general geriatric practice, benzodiazepines aren’t recommended at all. All benzodiazepines increase the risk of cognitive impairment, delirium, falls and fractures in older adults. Use extra caution if using a benzo in a patient with dementia – in many cases, benzodiazepines worsen agitation and restlessness for these patients. Also, avoid the longer-acting benzos like diazepam and clorazepate whenever possible – older adults metabolize these agents more slowly, making them susceptible to prolonged adverse reactions.

First-generation antihistamines (e.g., diphenhydramine, hydroxyzine, doxylamine): All of the first-generation antihistamines are highly anticholinergic, which means they can cause confusion, dry mouth, constipation, urinary retention, and other toxicities. In older adults, clearance is reduced, increasing the risk of side effects even further. When possible, try to use alternatives before moving to a first-generation antihistamine, especially in your dementia patients. For itching or other histamine-related symptoms, try a second-generation antihistamine such as loratadine (Claritin), fexofenadine (Allegra) or cetirizine (Zyrtec), or topical agents if treating a localized rash. For insomnia, some patients may be able to tolerate the occasional low dose of a first-generation antihistamine at bedtime. But if used routinely, tolerance will develop, and the risk of side effects will be higher, so an alternative agent may be more appropriate – and always try non-pharmacologic measures first.

Tertiary tricyclic antidepressants (e.g., amitriptyline, imipramine, doxepin > 6 mg/day): The tertiary TCAs are highly anticholinergic, cause orthostatic hypotension, and are able to cross the blood brain barrier to a greater extent than the secondary TCAs (like nortriptyline), making them more likely to cause weakness and sedation (in fact, they are sometimes used for insomnia). If you’re considering a TCA for neuropathic pain, stick with nortriptyline. For insomnia, nortriptyline won’t work as well, so consider other sedating antidepressants, like trazodone or mirtazapine. Especially avoid TCAs in patients with any form of heart disease because of their cardiovascular side effects.

Barbiturates: Barbiturates pose a risk of overdose, even at low doses. Tolerance to their effects develops and they carry a high risk of physical dependence. Reserve barbiturates as a “last resort” in patients experiencing refractory agitation, restlessness or insomnia.

Nitrofurantoin (Macrobid, Macrodantin): Nitrofurantoin can cause severe, potentially fatal pulmonary toxicity, in both acute and chronic form. Plus, nitrofurantoin is ineffective at treating UTI due to inadequate drug concentration in the urine when creatinine clearance is less than 60 mL/min – which applies to the majority of hospice patients (on average, a healthy 70-year old man of average height and weight will have a CrCl of about 68 mL/min; a woman’s would be only 58 mL/min). Because many other safer and more effective antimicrobials are available, avoid nitrofurantoin for both treatment of active infection AND for long-term UTI suppression.

Our final blog post on the Beers List 2012 Update will include some disease-specific recommendations, so be sure to check the blog next week for Part 3!

As mentioned on the blog a couple of months ago, the Beers Criteria, last updated in 2003, has been newly updated. Using a comprehensive, systematic review of the literature, the American Geriatrics Society (AGS) and an interdisciplinary panel of experts have reached consensus on the updated 2012 AGS Beers Criteria, and presented the updated list in the Journal of the American Geriatrics Society.

The Beers Criteria has been the most consulted source of information about the safety of prescribing medications to the elderly for more than 20 years. Beyond being an invaluable reference for clinicians, the Beers Criteria is used in research and in training healthcare professionals, it informs quality measures, and it has been incorporated into Medicare Part D policy used to evaluate medication use in nursing homes.

This does not mean that medications listed in the Beers Criteria are absolutely contraindicated in elderly patients. The authors of the updated Beers Criteria are careful to emphasize that the Beers List should not serve as a substitute for clinical judgment or replace the careful consideration of each individual patient’s unique needs. There will be situations when a clinician decides that a medication listed on the Beers Criteria is the only reasonable choice for a particular patient, and this type of clinical reasoning is not to be discouraged or punished. Furthermore, the panel points out that the Criteria are not necessarily applicable in all circumstances, including palliative and hospice care.

However, even in situations where the list may not apply, it can serve as an important reminder of the potential dangers of using certain medications in older adults. According to the Beers Criteria authors, “If a provider is not able to find an alternative and chooses to continue to use a drug on this list in an individual patient, designation of the medication as potentially inappropriate can serve as a reminder for close monitoring so that ADEs [adverse drug events] can be incorporated into the electronic health record and prevented or detected early.”

With this in mind, let’s review some of the important ways in which we can apply the Beers Criteria to hospice and palliative care.

Notable Medications Added Since 2003

Megestrol (Megace): Other than in patients with AIDS-wasting syndrome, megestrol has minimal effect on weight, and increases the risk of thrombotic events and possibly death in older adults. For a review of the literature, see Dr. Jim Joyner’s excellent blog post entitled “The Use of Megestrol Acetate (Megace) in Elderly Hospice Patients” (To find it, scroll down to the sub-heading “Megace” on the left side of the screen.)

Sliding-scale insulin: The use of sliding-scale insulin (SSI) protocols is still common in inpatient settings and long-term care facilities, despite a large body of evidence demonstrating that SSI increases the risk of hypoglycemia without improving hyperglycemia management. The use of SSI is routinely discouraged, regardless of care setting.

Glyburide (DiaBeta, Micronase): Glyburide is a long-acting sulfonylurea that poses a greater risk of severe prolonged hypoglycemia in elderly patients (chlorpropamide is also on the list, though this medication is rarely used). Sulfonylureas in general should be used with caution in the elderly because they are all renally eliminated and pose a greater risk of hypoglycemia in older adults. All sulfonylureas should be discontinued if the patient is no longer eating full meals.

Metoclopramide (Reglan): Metoclopramide has dopamine-antagonist properties and can cause extrapyramidal side effects (EPS), including tardive dyskinesia. The risk may be greater in frail older adults. In the palliative care setting, this medication is commonly used and there is clearly a role for the use of metoclopramide in the management of nausea/vomiting. However, the addition of this medication to the Beers List may serve as a reminder of the risks associated with use of metoclopramide. Close monitoring for extrapyramidal side effects should accompany use of this medication, especially if it is being used in combination with an SSRI antidepressant. Metoclopramide should generally not be prescribed to patients with Parkinson’s disease, a history of EPS, or a seizure disorder (it lowers the seizure threshold).

Non-benzodiazepine hypnotics: The non-benzodiazepine hypnotics include zolpidem (Ambien), zaleplon (Sonata) and eszopiclone (Lunesta). These medications have been added to the Beers List because of an increasing body of literature demonstrating that they have adverse events similar to benzodiazepines in older adults, including delirium, falls and fractures, while demonstrating minimal improvement in sleep latency and duration. The authors of the updated Beers Criteria recommend avoiding chronic use > 90 days.

The next blog post will address some of the medications commonly used in hospice that were previously on the Beers List and remain on the list in the 2012 update. Stay tuned!

The complete text of the AGS Beers Criteria 2012 Update can be

viewed and downloaded here.

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