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The Omnicare HealthLineFebruary 2017

Focus on the 2017 ADA Diabetes Guidelines for Older Persons - by Allen Lefkovitz

Type 2 diabetes mellitus (DM2) is estimated to affect 29.1 million Americans and is currently the seventh leading cause of death. It is estimated that 25.9% of older adults (65 years and older), representing 11.8 million individuals, have DM2, which means that 40.5% of all cases of DM2 involve older adults. Each year, the American Diabetes Association (ADA) releases guidance to patients and healthcare professionals “with the components of diabetes care, general treatment goals, and tools to evaluate the quality of care.” Entitled “The Standards of Medical Care in Diabetes”, hereafter referred to as “the 2017 Standards”, this annual report is available free at: http://care.diabetesjournals.org/content/40/Supplement_1.

The number of recommendations specific to older adults increased from 12 to 14 in 2017. Also, the strength of supportive evidence improved from “expert consensus or clinical experience” (Grade E) to “supportive evidence from poorly controlled or uncontrolled studies” (Grade C) for 5 of these recommendations (where grade A evidence is the strongest and grade E evidence is the weakest). This article provides an overview of selected recommendations (new and ongoing) from the 2017 Standards that impact the care of older adults with DM2.

Glycemic Targets and Hypoglycemia

Hypoglycemia should be avoided in older adults with diabetes. It should be assessed and managed by adjusting glycemic targets and pharmacologic interventions. (Grade B)

Antidiabetics are the 3rd most common drug class and insulin is the 2nd most likely drug to result in an emergency department visit due to an adverse drug event. The most recent estimate is that approximately 282,000 emergency room visits occur each year due to hypoglycemia. A noteworthy change in the 2017 Standards involves the revised definition and classification of hypoglycemia as outlined in the table below.

Classification Glycemic Criteria Description

Glucose Alert Level ≤ 70 mg/dL Sufficiently low for treatment with fast-acting carbohydrate and dose adjustment of glucose-lowering therapy

Clinically Significant Hypoglycemia

< 54 mg/dL Sufficiently low to indicate serious, clinically important hypoglycemia

Severe Hypoglycemia No specific value Hypoglycemia associated with severe cognitive impairment requiring external assistance for recovery

Within their “Choosing Wisely” document, the American Geriatrics Society’s (AGS) recommendation is to “Avoid using medications other than metformin to achieve hemoglobin A1c < 7.5% in most older adults.” In their explanation of this recommendation, the AGS goes on to say “Reasonable glycemic targets would be 7.0 – 7.5% in healthy older

Inside This Issue1-3 Focus on the 2017

ADA Diabetes Guidelines

4 Dosing Considerations for Newer Oral Anticoagulants

5 Clinical Capsule: Adverse Effects of Select Antidiabetic Medications in Older Persons

5 Regulatory Recap

6 New Drug Eucrisa

6 New Generic Medications

7 HealthLine Quiz

“Management of diabetes in the long-

term care (LTC) setting (i.e., nursing homes and skilled nursing

facilities) is unique.”- American Diabetes Association (2017)

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adults with long life expectancy, 7.5 – 8.0% in those with moderate comorbidity and a life expectancy < 10 years, and 8.0 – 9.0% in those with multiple morbidities and shorter life expectancy.”

Glycemic goals for some older adults might reasonably be relaxed using individual criteria, but hyperglycemia leading to symptoms or risk of acute hyperglycemic complications should be avoided in all patients. (Grade C)

Patients with diabetes residing in long-term care facilities need careful assessment to establish glycemic goals and to make appropriate choices of glucose lowering agents based on their clinical and functional status. (Grade E)

Overall, relaxed goals are suitable for many elderly patients. The graphic below is intended to assist in individualizing glycemic goals for elderly diabetics. An awareness of factors such as an individual’s risk of hypoglycemia, life expectancy, and how long they have been diabetic, can impact dramatically the establishment of glycemic goals, such as the A1c. However, as recommended by the ADA, if an older adult is cognitively and functionally intact and if they have a significant life expectancy, they “may receive diabetes care with goals similar to those developed for younger adults.”

Risk of hypogycemia and other drugadverse events

How long have they been diabetic?

Life expectancy

Relevant comobidities

Established vascular complications

Low

MoreStringent

LessStringentA1c 7%

High

Newly diagnosed Long-standing

Long Short

Absent Few/mild Severe

Absent Few/mild Severe

Adapted from ADA Standards of medical care in diabetes-2017. Diabetes Care 2017; 40(1):S53

For more information on the risk of hypoglycemia with common drugs for DM2, please refer to the Clinical Capsule on page 5.

Considerations in Treatment of DM2Although the focus of this article is not the pharmacological treatment of diabetes, two new recommendations in the 2017 Standards are worth mentioning. The first new recommendation is actually included twice in the 2017 Standards: within the Prevention or Delay of DM2 section and the Pharmacologic Approaches to Glycemic Treatment section. This duplication may be understood by remembering that metformin “is the preferred initial pharmacologic agent” for DM2.

Long-term use of metformin may be associated with biochemical vitamin B12 deficiency, and periodic measurement of vitamin B12 levels should be considered in metformin-treated patients, especially in those with anemia or peripheral neuropathy. (Grade B)

The second new recommendation was based upon two larger clinical trials involving oral Jardiance (empagliflozin) or injectable Victoza (liraglutide). As indicated in the 2017 Standards “Ongoing studies are investigating the cardiovascular benefits of other agents in these drug classes.”

In patients with long-standing suboptimally controlled type 2 diabetes and established atherosclerotic cardiovascular disease, empagliflozin or liraglutide should be considered as they have been shown to reduce cardiovascular and all-cause mortality when added to standard care. (Grade B)

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Although not a new recommendation, the 2017 Standards emphasize education for long-term care facility staff.

Consider diabetes education for the staff of long-term care facilities to improve the management of older adults with diabetes. (Grade E)

Areas of management that should be included in this recommended education are not clearly delineated in the 2017 Standards, but should likely include:

• How to detect symptoms of DM2• Policies and procedures for preventing hypoglycemia• Policies and procedures for managing hypoglycemia• Timely reporting of “out of range” blood glucose values detected during routine monitoring or symptoms that may

indicate a hyperglycemic crisis• Nutritional considerations (e.g., individual diets, how to report decreased intake)• How to provide preventive and routine eye, foot, and oral care

Comorbid Conditions Associated with DM2In addition to recommending an overall “assessment of medical, mental, functional, and social geriatric domains”, since 2015 the Standards have specifically recommended depression screening, and in the 2017 Standards the ADA newly recommends a routine assessment for cognitive impairment.

Annual screening for early detection of mild cognitive impairment or dementia is indicated for adults 65 years of age or older. (Grade B)

Older adults (≥ 65 years of age) with diabetes should be considered a high priority population for depression screening and treatment. (Grade B)

In addition to mental health-related recommendations, the 2017 Standards continue to address cardiovascular health by including 2 recommendation that focus on enhancing cardiovascular health.

Treatment of hypertension to individualized target levels is indicated in most older adults. (Grade C)

Treatment of other cardiovascular risk factors should be individualized in older adults considering the time frame of benefit. Lipid-lowering therapy and aspirin therapy may benefit those with life expectancies at least equal to the time frame of primary prevention or secondary intervention trials. (Grade E)

The reason for individually addressing hypertension at a higher grade of evidence is because “There is strong evidence from clinical trials of the value of treating hypertension in older adults.” However, blood pressure targets, like glycemic control targets, have been relaxed to minimize the risk of hypotension, which can result in orthostasis and falls.

End of Life Considerations for Individuals with DM2Palliative care and end of life recommendations, which are particularly pertinent in the long-term care environment, remain the same.

Overall comfort, prevention of distressing symptoms, and preservation of quality of life and dignity are primary goals for diabetes management at the end of life. (Grade E)

When palliative care is needed in older adults with diabetes, strict blood pressure control may not be necessary, and withdrawal of therapy may be appropriate. Similarly, the intensity of lipid management can be relaxed, and withdrawal of lipid-lowering therapy may be appropriate. (Grade E)

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Medication Safety by Yamini Shah

Dosing Considerations for Newer Oral Anticoagulants

A number of new or “novel” oral anticoagulants have been approved by the Food and Drug Administration (FDA) since 2010. These include: Pradaxa (dabigatran), Xarelto (rivaroxaban), Eliquis (apixaban), and most recently, Savaysa (edoxaban). In December 2016, Steinberg et al. published results of an analysis that included more than 5,000 adults treated with one of the three newer oral anticoagulants for stroke prevention in nonvalvular atrial fibrillation. Almost 1 of 8 patients treated with Pradaxa (dabigatran), Xarelto (rivaroxaban), or Eliquis (apixaban) received doses other than those recommended in the FDA-approved labels (or off-label doses). Approximately, 9% of patients received a dose lower than that recommended by the FDA-approved labeling (e.g., underdosed) and 3% received a dose higher than the FDA-approved labeling (e.g., overdosed). Relative to those patients whose doses were consistent with the FDA-approved label, patients who received off-label doses were significantly older in age (median 79 and 80 years of age vs. 70 years of age, respectively; p < 0.0001).

In the study by Steinberg et al., underdosing was associated with an increased risk of cardiovascular hospitalization. Receiving doses higher than those recommended in the FDA-approved labeling was associated with nearly double the rate of increased all-cause mortality.

Among patients taking:• Pradaxa (dabigatran), those with an estimated creatinine clearance (CrCl) of 30 mL/minute to 50 mL/minute had the

highest rates of off-label dosages: 23% were underdosed (recommended dosage is 150 mg twice a day*). • Xarelto (rivaroxaban), those with a CrCl of 15 mL/minute to 50 mL/minute had the highest rates of off-label dosages:

34% were overdosed (recommended dosage is 15 mg once daily*). • Eliquis (apixaban) with ≥ 2 or more of the following (age ≥ 80 years, body weight ≤ 60 kg, or serum creatinine ≥ 1.5

mg/dL): 21% were overdosed (recommended dosage is 2.5 mg twice daily*) *FDA recommended dosing is for stroke prevention in nonvalvular atrial fibrillation. Dosing for other indications and CrCl may vary.

The reasons for prescribing of lower than recommended doses may be related to concerns about adverse events, particularly bleeding. Prescribing doses higher than those recommended by the FDA may represent lack of awareness of approved dosing recommendations, lack of awareness of dosing variation based on indication and renal function (and in some cases, age and weight), unnoticed drug interactions, or variability in calculating creatinine clearance.

The American Geriatrics Society’s Beers Criteria provides additional recommendations for the reduction in dose or avoidance of anticoagulants due to an increased risk of bleeding in patients ≥ 65 years of age with renal impairment and/or clinical trial exclusion criteria.

• Avoid Pradaxa (dabigatran), Xarelto (rivaroxaban), or Savaysa (edoxaban) if CrCl < 30 mL/minute. • Avoid Eliquis (apixaban) if CrCl < 25 mL/minute. • Reduce dose of Xarelto (rivaroxaban) and Savaysa (edoxaban) if CrCl is 30 mL/minute to 50 mL/minute.

The Beers Criteria also suggest using Pradaxa (dabigatran) with caution in patients ≥ 75 years of age due to an increased risk of gastrointestinal bleeding compared with certain other oral anticoagulants.

Other renal, age, and weight dosing considerations for Savaysa (edoxaban) based on the FDA-approved labeling are:• Avoid Savaysa (edoxaban) if CrCl > 95 mL/minute for nonvalvular atrial fibrillation because of decreased efficacy

(e.g., increased risk of ischemic stroke compared to warfarin at the highest dose studied); use another anticoagulant. • Reduce Savaysa (edoxaban) dose if body weight ≤ 60 kg for treatment of deep vein thrombosis and pulmonary

embolism.

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The Clinical Capsule by Kori Hauersperger

Adverse Effects of Select Antidiabetic Medications in Older Persons Medication Risk of hypoglycemia, other adverse effects

Sulfonylureas(e.g., glyburide)

Moderate to high risk of hypoglycemia; Not recommended in older adultsDecreased renal/hepatic function, inconsistent food intake and insulin use increase risk for hypoglycemia

Biguanides(i.e., metformin)

Low risk of hypoglycemia; Recommended as first line therapy in older adultsFrail patients at risk for GI distress/weight loss; titrate slowly and monitor weight. Avoid in CrCl < 30 mL/min

DPP-4 Inhibitors (e.g., Tradjenta, Januvia)

Low risk of hypoglycemia; Recommended as second line or add-on therapyFrail patients may be at risk for GI distress but less than metformin. No renal dose adjustment required for linagliptin

SGLT2 Inhibitors(e.g., Invokana)

Low risk of hypoglycemia; Not recommended in older adultsRisk of dehydration, weight loss, and genitourinary tract infections. Monitor for hypotension and dizziness

Insulin High risk of hypoglycemiaBegin with basal, avoiding prandial coverage if possible due to increased complexity and hypoglycemia risk

GI = gastrointestinal; CrCl = creatinine clearance; DPP = dipeptidyl peptidase; SGLT2 = sodium-glucose contransporter 2

Standards of Medical Care in Diabetes 2017 available at care.diabetesjournals.org. Drug information available at https://dailymed.nlm.nih.gov/

Regulatory Recap: CMS Adverse Event Trigger Tool: Toxicity Related to Angiotensin-Converting Enzyme Inhibitors- by Carrie Allen

Angiotensin-converting enzyme inhibitors (ACEI) are used frequently in the long-term care setting (e.g., lisinopril). The CMS Adverse Event Trigger Tool focuses on 3 ACEI associated adverse drug events (ADE): hyperkalemia, angioedema, and acute kidney failure. The table* below lists selected risk factors, signs and symptoms, and specific documentation related to this issue.

Risk Factors for ADE with ACEI¥ Signs and Symptoms Documentation

• Congestive heart failure• Impaired renal function • Dehydration • Hypersensitivity to ACEI • Concurrent use with:

– Diuretics – NSAIDs – Anticoagulants – Cyclosporine – Potassium supplements

Elevated potassium levels • Fatigue, weakness, or nausea• Dizziness, syncope • Headaches • Slow, weak, or irregular pulse• Abnormal heart rhythmAngioedema • Swelling of soft tissues• Shortness of breath, wheezing• Persistent non-productive cough Acute Kidney Failure • Elevated BUN/creatinine and/or

reduced/absent urine output • Swelling of feet/legs • Nausea/vomiting, anorexia• Flank pain

Is there evidence of a system to ensure: • changes in condition are identified

and assessed promptly, including an assessment of medications?

• serum potassium, BUN, and creatinine levels are drawn routinely?

• lab results are appropriately communicated to the physician including when panic values are obtained?

For residents with risk factors for drug toxicity, does the care plan reflect interdisciplinary monitoring for signs/symptoms of adverse drug reactions?

* This table is not all-inclusive; refer to the CMS Adverse Event Trigger Tool and relevant clinical references for more information. ¥ Multiple risk factors increase the risk of an ADE occurring.

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NEW Drug by Dave Pregizer

Eucrisa™ Ointment

Brand Name (Generic Name)

Eucrisa [you-KRIS-a] (crisaborole) [kris-a-BOR-ole]

How Supplied 2% crisaborole in 60 gm and 100 gm laminate tubes

Therapeutic Class Phosphodiesterase-4 inhibitor

Approved Indication Topical treatment of mild to moderate atopic dermatitis in patients 2 years of age & older

Usual Dosing Apply a thin layer twice daily to affected areas

Select Drug Interactions None expected

Most Common Side Effects

Application site pain

Miscellaneous For external use only and not for ophthalmic, oral, or intravaginal use

Website http://labeling.pfizer.com/ShowLabeling.aspx?id=5331

NEW Generic Medications

Generic Name Brand Name Date Generic Available

Dexmethylphenidate 25 mg and 35 mg Extended-Release Capsule

Focalin XR® Capsule ER 1/5/17

Rasagiline 0.5 mg and 1 mg Tablet Azilect® Tablet 1/4/17

Aprepitant 40 mg, 80 mg and 125 mg Capsule Emend® Capsule 12/27/16

Ergotamine / Caffeine 1 mg / 100 mg Tablet Cafergot® Tablet 12/27/16

Oseltamivir 30 mg, 45 mg, 75 mg Capsule Tamiflu® Capsule 12/12/16

Ezetimibe 10 mg Tablet Zetia® Tablet 12/12/16

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HealthLine Quiz- by Steve Law

1. Which statement about diabetes in Older Persons is FALSE?a. Diabetes Type 2 (DM2) is the 7th leading cause of

deathb. Clinically significant hypoglycemia is defined as a

glucose level less than 54 mg/dLc. Insulin is the second most likely drug to result in

an emergency department visit due to an adverse drug event

d. Victoza should not be used in diabetics with established atherosclerotic cardiovascular disease

2. Long-term use of metformin may be associated with a biochemical vitamin B-6 deficiency:a. True b. False

3. Which statement is FALSE concerning comorbid conditions associated with DM2 in older adults (age 65 years or older)?a. Annual screening for early detection of mild

cognitive impairment or dementia is indicated b. Older adults should be screened for depressionc. The blood pressure goal for most older adults is to

be below 120/80 mmHgd. All older adults should be assessed to determine

their need to be on a statin and asprin

4. Xarelto (rivaroxaban) generally should be avoided in older adults with a CrCl less than 30 mL/minute:a. True b. False

5. Which medication has the highest risk of hypoglycemia in the elderly?a. Metforminb. Glyburidec. Januviad. Invokana

6. An adverse effect to monitor for with an ACE Inhibitor is hypokalemia?a. True b. False

7. Which is TRUE about the new medication Eucrisa™ (crisaborole)?a. It is a cream indicated for the topical treatment of

mild to moderate atopic dermatitisb. It is a phosphodiesterase-2 inhibitorc. Application site pain is the most common side

effectd. Usual dosing is to apply a thin layer three times a

day to affected areas

*Please note, the HealthLine Quiz is designed to help readers retain information that is relevant to their care setting. It is not an approved source of continuing education credits for healthcare professionals.

Editorial BoardAllen L. Lefkovitz, PharmD, BCGP, FASCP – Senior Editor

Carrie Allen, PharmD, BCGP, BCPS, BCPP, CCHP – Assistant Editor

Kori Hauersperger, PharmD, BCGP

Steve Law, PharmD, BCGP

Terry O’Shea, PharmD, BCGP

David Pregizer, RPh

Yamini Shah, PharmD

Barbara J. Zarowitz, PharmD, FCCP, BCPS, FCCM, BCGP, FASCP

Contributing Authors for This IssueAllen L. Lefkovitz, PharmD, BCGP, FASCP Director - Clinical Pharmacy Education and Drug Data, CVS Health

Yamini Shah, PharmD Clinical Pharmacist, Clinical Development, CVS/caremark

Kori Hauersperger, PharmD, BCGP OSC2OR Clinical and Drug Information Analyst, CVS Health

Carrie Allen, PharmD, BCGP, BCPS, BCPP, CCHP Clinical Pharmacist, CVS Health

David Pregizer, RPh Consultant Pharmacist, HCR-Manorcare

Steve Law, PharmD, BCGP Clinical Services Manager for Indiana; Omnicare Pharmacies in Indiana

Answers to the HealthLine Quiz: 1) D 2) B 3) C 4) A 5) B 6) B 7) C