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The Omnicare HealthLineOctober 2016

Focus on COPD Exacerbation – Part I: Identification and Risk Factors - by Allen Lefkovitz

Chronic Obstructive Pulmonary Disease (COPD) is the 3rd leading cause of death in the United States and affects an estimated 21.5% of long-term care (LTC) residents. Within their last year of life, an estimated 40% of COPD patients will be admitted to a LTC facility. Exacerbations of COPD account for the greatest proportion of the total COPD burden on the health care system due to hospitalizations and emergency department visits. As 30-day readmissions for COPD ranged from 17-25% at baseline, in October 2014, CMS added acute exacerbation of COPD to their Hospital Readmissions Reduction Program. With the prevalence of COPD in LTC, this article will focus on defining and identifying a COPD exacerbation as well as discussing risk factors associated with COPD exacerbations. Next month’s focus article, will examine both treatment and prevention of COPD exacerbations.

What is a COPD exacerbation?Within their 2015 “Prevention of Acute Exacerbations of COPD” guideline, the American College of Chest Physicians (ACCP) and the Canadian Thoracic Society (CTS) stated “Exacerbations are to COPD what myocardial infarctions are to coronary artery disease: They are acute, trajectory-changing, and often deadly manifestations of a chronic disease.” The 2016 Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines define a COPD exacerbation as “an acute event characterized by a worsening of the patient’s respiratory symptoms that is beyond normal day-to-day variations and leads to a change in medication.”

The large impact of COPD exacerbations can be seen when it is recognized that they:

Negatively affect quality of life;

Have effects on symptoms and lung function that take several weeks to recover from;

Accelerate the rate of decline of lung function; and

Are associated with significant mortality, especially if hospitalization is required.

Identifying a COPD Exacerbation Diagnosis of a COPD exacerbation relies exclusively on the individual’s clinical presentation and involves a change from baseline in:

Dyspnea Cough; and/or Sputum production

“Exacerbations are to COPD what myocardial infarctions are to coronary artery disease”~ ACCP and CTS ~

Inside This Issue1-3 Focus on COPD

Exacerbation: Part 1

4 Boxed Warning for Opioids and Benzodiazepines

5 Clinical Capsule: COPD Beyond Bronchodilators

5 Regulatory Recap

6 New Drug Erelzi

6 New Generic Medications

7 HealthLine Quiz

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The ACCP and CTS further describe categories of severity for an exacerbation, which are frequently used in clinical trials and are based upon actual outcomes.

Mild Moderate Severe

Clinical symptoms are present but no

change in treatment or outcome is documented

Clinical symptoms result in a change

in medication (e.g., use of systemic corticosteroids)

Clinical symptoms result in a change in

medication and lead to a hospitalization

Early detection of a COPD exacerbation, particularly in an older person with cognitive impairment can be challenging as symptoms of an exacerbation can be non-specific. Specific and non-specific symptoms that should be monitored closely for are shown below.

SPECIFIC NON-SPECIFIC

• Increased breathlessness with use of routine medicine **most common**

• Wheezing

• Chest tightness

• Increased cough

• Increased sputum

• Change of the color and/or tenacity of sputum

• Fever [>100˚F (>37.8˚C)]

• New radiological abnormalities

• Tachycardia

• Tachypnea

• Malaise

• Insomnia

• Sleepiness

• Fatigue

• Depression

• Mental status change

Interdisciplinary monitoring for each of these symptoms is imperative and if any of the above are noted, nursing assistants or other trained staff should obtain a full set of vital signs and a process should be implemented to communicate significant changes in the resident’s status to the prescriber immediately.

Although unnecessary for establishing the diagnosis of a COPD exacerbation, additional laboratory and diagnostic monitoring that may help in assessing the severity of an exacerbation (beyond the presence of purulent sputum), include:

Pulse oximetry

Chest x-ray

Electrocardiogram

White blood cell count

Electrolyte disturbances

(including hyperglycemia)

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What are Risk Factors for a COPD Exacerbation?Risk factors for an acute exacerbation include:

• Active or passive smoking

• Interruption of, or non-compliance with maintenance COPD therapy

• Delayed diagnosis of COPD

• Advanced age

• Severity of COPD and exacerbation history

• Other comorbidities (e.g., gastroesophageal reflux disease, heart failure)

• Exposure to air pollution

• Viral or bacterial respiratory tract infections

Among these risk factors, viral or bacterial respiratory tract infections are the most common cause of COPD exacerbations, but in up to one-third of severe exacerbation cases, a precipitating cause cannot be identified, which further underscores the need for vigilance in monitoring and early detection. Likewise, according to GOLD guidelines, the best predictor of having frequent exacerbations (defined as “2 or more exacerbations per year”) is having a history of previous treated exacerbations. Although based on spirometric findings, which often cannot be obtained in LTC elderly residents, GOLD guidelines provide further insight into the risk of exacerbation as shown in the table below.

GOLD ClassificationExacerbations

per yearHospitalizations

per year3-Year

mortality

GOLD 1: Mild Unknown Unknown Unknown

GOLD 2: Moderate 0.7–0.9 0.11–0.2 11%

GOLD 3: Severe 1.1–1.3 0.25–0.3 15%

GOLD 4: Very Severe 1.2–2.0 0.4–0.54 24%

In addition to ruling out other conditions that may mimic or aggravate a COPD exacerbation (e.g., pneumonia, pulmonary embolism, heart failure), it also is important to evaluate risks associated with medications that might predispose them to, or precipitate, an exacerbation. Some commonly used medications that may be associated with risk of a COPD exacerbation are shown in the figure below.

Antipsychotics and Anticholinergics

(e.g., olanzapine, diphenhydramine)

Histamine-2 Receptor Blocker and/or Proton Pump Inhibitor

(e.g., rantidine, omeprazole)

Short-Acting Agents Instead of Long-Acting (e.g., albuterol or

ipratropium vs. salmeterol or tiotropium

Dry mouth and central side effects may interfere with the swallowing

reflex

Increased gastric pH may increase the risk of aspiration of colonized enteric Gram-negative organisms

(e.g., Klebsiella pneumoniae)

Long-acting agents better improve lung function and quality of life, as well as reducing the risk of COPD exacerbations and hospitalizations

Minimizing and/or evaluating the use of antipsychotics, anticholinergics, histamine-2 receptor blockers, and proton pump inhibitors for discontinuation may provide an important strategy in helping to prevent future COPD exacerbations.

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Medication Safety by Yamini Shah

FDA Requiring a Boxed Warning for Combined Use of Opioids and Benzodiazepines

In August 2016, the Food and Drug Administration (FDA) announced that combined use of opioids with benzodiazepines (e.g., alprazolam, lorazepam) or other drugs that depress the central nervous system (CNS) resulted in serious side effects, including slowed or difficult breathing and deaths. These findings were based on a review of studies involving use of opioid analgesics; however, because of similar pharmacologic properties, it is reasonable to expect similar risks with concomitant use of opioid cough medications and benzodiazepines, other CNS depressants, or alcohol.

In an effort to decrease the use of opioids with CNS depressants, the FDA is adding Boxed Warnings, the strongest warning, to the drug labeling of opioids and benzodiazepines. The FDA will also require updates to other sections of the opioid and benzodiazepine labeling. These changes will affect nearly 400 prescription products. The FDA is continuing to evaluate the evidence regarding combined use of benzodiazepines or other CNS depressants with medication-assisted therapy drugs used to treat opioid addiction and dependence. FDA is also evaluating whether labeling changes are needed for other CNS depressants, and will provide an update when more information is available.

Opioidsb

(e.g., fentanyl, hydromorphone, morphine, oxycodone, tramadol)

Muscle Relaxants (e.g., baclofen, methocarbamol, tizanidine)

Benzodiazepinesc (e.g., alprazolam, lorazepam, oxazepam, temazepam)

Other Sleep Drugs and Tranquilizers (e.g., eszopiclone, ramelteon, zaleplon, zolpidem)

Antipsychotics (e.g., aripiprazole, haloperidol,

quetiapine, risperidone)

a This is not a comprehensive list. b Opioids are used to treat pain severe enough to warrant use of an opioid when other pain medications cannot be taken or are not able to provide

enough pain relief. Opioids are also approved in combination with other medications to reduce coughing.c Benzodiazepines are medications used to treat conditions including anxiety, insomnia, and seizures.

The FDA recommends that health care professionals:

• Limit prescribing opioid pain medications with benzodiazepines or other CNS depressants to patients for whom alternative treatment options are inadequate.

• Limit the dosages and duration of opioids and CNS depressants, if prescribed together, to the minimum possible while achieving the desired clinical effect. Monitor patients closely for respiratory depression (e.g., shallow breathing, fewer breaths per minute) and sedation.

• Inform patients and caregivers about the risks of slowed or difficult breathing and/or sedation, and the associated signs and symptoms, if opioids are used with CNS depressants. Patients should be attended to immediately if they experience unusual dizziness or lightheadedness, extreme sleepiness, slowed or difficult breathing, or unresponsiveness.

• Avoid prescribing opioid cough medications for patients taking benzodiazepines or other CNS depressants, including alcohol.

Additional information on this Drug Safety Communication, along with a list of CNS depressants, is available through this link: http://www.fda.gov/Drugs/DrugSafety/ucm518473.htm.

Concomitant use of opioid pain or cough medications and benzodiazepines, other central nervous system (CNS) depressants, or alcohol may result in profound sedation, respiratory depression, coma, and/or death.

Examples of Medications that are CNS Depressantsa

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The Clinical Capsule by Kori Hauersperger

Treatment of Chronic Obstructive Pulmonary Disease (COPD): Beyond BronchodilatorsIn addition to bronchodilators (e.g., beta-agonists and anticholinergics) The 2016 GOLD guidelines provide recommendations on the use of other pharmacologic interventions.

Medication Adverse Effects and Monitoring

Rec

om

men

ded

Roflumilast (Daliresp)Decreases inflammation by inhibiting PDE4

Not for acute symptoms; must be used with a long-acting bronchodilator Adverse effects were noted early in therapy and lessened as therapy was continued. Nausea, abdominal pain, diarrhea, sleep problems, and headache were the most common. Appetite was affected and slight weight loss occurred; monitor weight. Monitor for psychiatric changes and development or worsening of insomnia, depression and anxiety.

Oral Steroids(e.g., Prednisone)Not for chronic use

Steroid myopathy leads to muscle weakness with decreases in ADLs and possible respiratory failure in severe COPD. Increased glucose, increased risk for agitation, confusion and delusions. May be used for short-term for acute exacerbations.

Montelukast(Singulair)

No evidence of efficacy. Adverse effects include: gastrointestinal symptoms (abdominal pain, diarrhea) and dizziness. Mood changes with depression and suicidal thoughts can occur, but are rare.

Antitussives Cough is protective. The regular use of antitussives is not recommended in stable COPD

GOLD = Global Initiative for Chronic Obstructive Lung Disease ; PDE4 = phosphodiesterase-4; ADL = Activities of daily living

Regulatory Recap: CMS Adverse Event Trigger Tool: Change in mental status/delirium related to psychotropic medications- by Carrie Allen

Psychotropic medications (antipsychotics, antidepressants, anxiolytics, and hypnotics) are frequently implicated in causing changes in mental status/delirium. The CMS Adverse Event Trigger Tool includes PRN and routine use of psychotropic medications as risk factors for changes in mental status/delirium, as well as using more than one psychotropic medication (from the same class or different classes), advanced age, and polypharmacy. In addition, the tool directs surveyors to look for specific documentation such as:

• Is there evidence in the medical record that the resident or representative were involved in decisions related to medication use?

• Does the medical record include consistent documentation of clinical indication, e.g., do physician notes, care plan, and tracking sheets all address the same indication?

• If receiving psychotropics PRN and routinely, is there consideration for the timing of administration of the PRN? Facilities should ensure PRN medication timing of administration is being considered in the context of when routinely scheduled medications are given, so that adverse reactions are not precipitated due to psychotropic medications being administered too closely together.

• Is there evidence that the facility implements non-pharmacological approaches and interdisciplinary management of the condition that the medication targets?

• Is there evidence of a system for ensuring that the resident is routinely assessed for effectiveness of the medication and signs/symptoms of adverse drug reactions/events?

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NEW Drug by Dave Pregizer

Erelzi™ Subcutaneous Injection

Brand Name (Generic Name) Erelzi [eh rel’ zee]; (etanercept-szzs) [et a NER sept]

How Supplied 25 mg/0.5 mL & 50 mg/mL single-dose prefilled syringe and 50 mg/mL prefilled Pen

Therapeutic Class Tumor necrosis factor (TNF) blocker

Approved Indication Rheumatoid Arthritis (RA), Polyarticular Juvenile Idiopathic Arthritis (JIA), Psoriatic Arthritis (PsA), Ankylosing Spondylitis (AS), Plaque Psoriasis (PsO)

Usual Dosing RA/PsA: 50 mg weekly (with or without methotrexate), AS: 50 mg weekly, Adult PsO: 50 mg twice weekly for 3 months then 50 mg weekly, JIA patients who weigh >63 kg: 0.8 mg/kg weekly (max 50 mg per week)

Select Drug Interactions Live vaccines, Anakinra, Abatacept, Cyclophosphamide, Antidiabetic agents

Most Common Side Effects Infections and injection site reactions

Miscellaneous Biosimilar to Enbrel; boxed warning for risk of serious infections, and lymphoma and other malignancies

Website www.Erelzi.com

NEW Generic Medications

Generic Name Brand Name Date Generic Available

Nilutamide 150 mg Tablet Nilandron® Tablet 8/29/16

Nitroglycerin 0.3 mg, 0.4 mg, and 0.6 mg Sublingual Tablets

Nitrostat® Sublingual Tablet 8/26/16

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HealthLine Quiz- by Steve Law

1. Which is a FALSE statement about Chronic Obstructive Pulmonary Disease (COPD)?a. It is the third leading cause of death in the United

Statesb. COPD exacerbations are associated with

significant mortality, especially if hospitalization is required

c. Within their last year of life, an estimated 40% of COPD patients will be admitted to a LTC facility

d. A specific symptom of a COPD exacerbation is tachypnea

2. A chest x-ray is necessary for establishing the diagnosis of a COPD exacerbation:a. True b. False

3. Which is a risk factor for a COPD exacerbation?a. Advanced ageb. Active or passive smokingc. Viral or bacterial respiratory tract infectionsd. Severity of COPD and exacerbation historye. All of the above

4. Diphenhydramine (Benadryl) would be an appropriate medication to use for insomnia in someone prone to COPD exacerbations:a. True b. False

5. A new Boxed Warning from the FDA states concomitant use of opioid pain or cough medications and benzodiazepines, other CNS depressants, or alcohol may result in profound sedation, respiratory depression, coma, and/or death:a. True b. False

6. The new medication, Erelzi™ injection is approved for Osteoarthritis:a. True b. False

7. Which statement concerning the treatment of COPD is TRUE?a. Daliresp is indicated for acute symptoms of COPDb. The use of cough suppressants are recommended

in COPD patientsc. Oral steroids should be used in patients with

chronic COPDd. Singular is not a recommended medication for the

treatment of COPD

*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, CGP, FASCP – Senior Editor

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

Kori Hauersperger, PharmD

Steve Law, PharmD, CGP

Terry O’Shea, PharmD, CGP, FASCP

David Pregizer, RPh

Yamini D. Shah, PharmD

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

Contributing Authors for This IssueAllen L. Lefkovitz, PharmD, CGP, FASCPDirector - Clinical Pharmacy Education and Drug Data, CVS Health

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

Kori Hauersperger, PharmDOSC2OR Clinical and Drug Information Analyst, CVS Health

Carrie Allen, PharmD, CGP, BCPS, BCPP, CCHPClinical Pharmacist, CVS Health

David Pregizer, RPh, Consultant Pharmacist, HCR-Manorcare

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

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