COMMON DRUG RELATED PROBLEMS SEEN IN PACE AND MECHANISMS TO MITIGATE RISK Robert L Alesiani, PharmD, CGP Chief Pharmacotherapy Officer CareKinesis, Inc. (a Tabula Rasa Healthcare Company)
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Pharmacogenomics (PGx) PGx testing for high-risk individuals (Pharmacogenomic Insight) Pharmacokinetics (PK) Precision Dosing Matrix to detect competitive inhibition within the current drug regimen Pharmacodynamics (PD) Risk/Safety measures to assess aggregate contribution of active medications Pharmacoevidence (PEv) Standard evidenced-based criteria, such as Beers List, STOPP criteria, etc. Pharmacoeconomics (PE) ROI calculation of Medication Risk Mitigation services and cost-benefit analysis regarding pertinent outcomes. 6
ANTICHOLINERGICS First Generation Antihistamines: Highly anti-cholinergic, causes greater risk of confusion, dry mouth, constipation and other anticholinergic effects and toxicity. Clearance may be reduced with advanced age; tolerance develops when used as sedative hypnotics. Avoid use except for diphenhydramine in special situations where it may be appropriate (e.g., severe allergic reaction). 2 nd Generation Antihistamines Anti-Parkinson s Drugs: (Benztropine, Trihexyphenidyl) Not recommended for prevention of extrapyramidal symptoms with antipsychotics; more effective agents available for treatment of Parkinson disease. Carbi/Levo, Dopamine Agonists, COMT inhibitors Gastric Antispasmodics: Highly anticholinergic, with poorly documented effectiveness. Avoid except short-term use or utilize lowest effective dose. May be useful in palliative care to decrease oral secretions (disregard risks of long-term ADR s) Tricyclic Antidepressants: Avoid use. Highly anticholinergic, sedating and may cause orthostatic hypotension, syncope and falls. SSRI s (citalopram, escitalopram, sertraline) http://www.bcmj.org/articles/geriatric-depression-use-antidepressants-elderly
DIGOXIN (> 0.125MG / DAY) In patients with heart failure and/or low creatinine clearance, higher dosages associated with no additional benefit and increased risk of toxicity. While use of low dose Digoxin may reduce the risk of hospitalization in patients with left ventricular dysfunction, it shows no ( neutral ) benefit for mortality. (Follow CCF/AHA guideline for managing Heart Failure) http://my.americanheart.org/professional/sciencenews/2013-accfaha-guideline-for-the-management-of-heart-failure_ucm_452902_article.jsp
SPIRONOLACTONE (> 25MG / DAY) In patients with heart failure, risk of hyperkalemia especially if also taking an NSAID, ACE inhibitor, angiotensin receptor blocker, or K supplement; avoid in heart failure or if creatinine clearance < 30 ml/min http://my.americanheart.org/professional/sciencenews/2013-accfaha-guideline-for-the-management-of-heart-failure_ucm_452902_article.jsp
ANTI-PSYCHOTICS (1 ST & 2 ND GENERATION) Increased risk of stroke and mortality in patients with dementia. Avoid in patients with dementia-related behavior problems unless nonpharmacologic options have failed and patients are a threat to themselves or others. Some antipsychotics may also increase the risks of QT prolongation alone, in susceptible patients with bradycardia and in combination with other drugs that may prolong repolarization (i.e.: Thioridazine, Quetiapine). Antipsychotics should only be used for psychosis. Besides the safety issues listed above, when used for symptom management (agitation, restlessness, yelling out, etc), these agents are only marginally better than placebo. BMJ 2014;349:g6420 http://www.merckmanuals.com/professional/geriatrics/drug-therapy-in-the-elderly/drug-categories-of-concern-in-the-elderly
BENZODIAZEPINES & SIMILAR Short and intermediate-acting: Increased risk of cognitive impairment, delirium, falls, motor vehicle accidents, fractures as well as physical & psychological dependence. Long acting: May be appropriate for seizure disorders, rapid eye movement sleep disorders, benzodiazepine withdrawal, ethanol withdrawal, severe generalized anxiety disorder, peri-procedural anesthesia, end-of-life care. Avoid use for insomnia, agitation, or delirium. Non-Benzodiazepine Sedatives: Similar to benzodiazepines (e.g., delirium, falls, fractures); minimal improvement in sleep latency and duration. Not to be used for > 90 days Behavior Modification (Sleep hygiene, relaxation techniques, sleep restriction, light therapy, etc). For pharmacotherapy, use lowest possible dose for shortest amount of time while instituting the techniques above. An agreement with the participant should be established as to the expected duration of therapy (NOTE: Other than alcohol, benzodiazepines are the most abused class of drugs in the elderly). http://www.merckmanuals.com/professional/geriatrics/drug-therapy-in-the-elderly/drug-categories-of-concern-in-the-elderly
NSAIDS NSAIDs are used by > 30% of people aged 65 to 89, and half of all NSAID prescriptions are for people > 60. Many NSAIDs are available without prescription. The elderly may be prone to adverse effects of these drugs, and adverse effects may be more severe because of the following: NSAIDs are highly lipid-soluble, and because adipose tissue increases with age, distribution of the drugs is extensive. Plasma protein is often decreased, resulting in higher levels of unbound drug and exaggerated pharmacologic effects. Renal function is reduced in many of the elderly, resulting in decreased renal clearance and higher drug levels. Risks of abnormal bleeding increases when NSAIDs are given with warfarin, aspirin, or other antiplatelet drugs (e.g., clopidogrel). NSAIDs may increase risk of cardiovascular events and fluid retention. First Line: Acetaminophen - Prescribing Cascade Alert: PPIs, Diuretics, Antihypertensives, etc. http://www.merckmanuals.com/professional/geriatrics/drug-therapy-in-the-elderly/drug-categories-of-concern-in-the-elderly
DIURETICS All diuretics should be used with caution and elderly patients should be monitored frequently as the population is pre-disposed to dehydration. Low doses of thiazide diuretics can effectively control hypertension in many elderly patients and have less risk of hypokalemia and hyperglycemia than other diuretics. Potassium sparing diuretics should be used with caution in the elderly as they may often be used in conjunction with ACE-Is, ARBs or with when a participant is prone to impaired kidney function. If required, utilized the lowest effective dose and monitor potassium levels routinely.
OTHERS Antibiotics Nitrofurantoin Risk pulmonary toxicity, poor urinary concentration in patients with renal insufficiency Antithrombotics Dipyridamole Risk orthostatic hypotension, other safer, more effective agents available. Cardiovascular α blockers Risk orthostatic hypotension, other safer, more effective agents available. If necessary, use lower effective dose taken at bedtime. α (central) agonists Risk CNS ADRs, bradycardia, orthostatic hypoternsion Nifedipine (IR) Antiarrhythmics classes Ia, Ic & III Risk of hypotension, myocardial ischemia Rate control preferred over rhythm control, avoid as first-line treatment of Atrial Fibrillation (for Amiodarone, increased risk of thyroid and pulmonary disease as well as QT interval prolongation.
OTHERS Barbiturates Insulin Sliding Scale Risk of overdose at low dosages. High rate of physical dependence and tolerance. Regardless of care setting, risk hypoglycemia without improvement in glucose control Pain Management Meperidine Risk neurotoxicity, not an effective agent at common oral dosages; safer alternatives available. Skeletal Muscle Relaxants Questionable efficacy at doses that are tolerable to older adults. Highly sedative and anticholinergic. Risk falls and fractures Journal of the American Geriatrics Society 60: 616 631, 2012.
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