As Americans age, health-care providers will be faced with new and challenging issues
related to the care of older adults. One critical issue that is unique to the aging
population is polypharmacy. Older adults are frequently prescribed multidrug therapy
to treat a plethora of chronic illnesses. On average, individuals aged 70 years and
older have 3 or more comorbidities (Extermann, 2007; Fortin, Bravo, Hudon, Vanasse,
& Lapointe, 2005). In the United States, approximately 60% of older adults take 5
medications and 20% take 10 or more medications daily (Rocchiccioli, Sanford, & Caplinger,
2007; Slone Epidemiology Center at Boston University, 2006). In addition, older adults
consume 40% to 50% of all over-the-counter medications (Budnitz et al., 2006).
Polypharmacy increases the risk of adverse drug reactions (ADRs) in the older adult
as a result of overmedication, drug interactions, medication errors, or noncompliance,
often leading to increased morbidity (Corsonello et al., 2009; Nixdorff et al., 2008).
Cancer-related medications can add to the complexity of polypharmacy related not only
to cancer therapy but also to the multitude of supportive medications used by the
cancer patient. Furthermore, other challenges in medication management are age-related
changes and pharmacotherapeutics. The advanced practitioner (AP) in oncology is in
a key position to assess and manage the older adult’s pharmaceutical agents and maximize
drug therapy. This article will define polypharmacy and discuss inappropriate agents
for older adults, drug interactions, pharmacotherapeutics, age-related changes, pharmacodynamics,
and the role of APs in oncology in ensuring drug safety and reducing adverse drug
reactions in the older adult with cancer.
Definitions of Polypharmacy
Several definitions exist for polypharmacy. Initially, polypharmacy was defined as
the use of multiple medications, also termed polymedicine (Pham & Dickman, 2007; Rocchiccioli,
Sanford, & Caplinger, 2007; Stewart, 1990), although no specific number of drugs has
been identified in the literature (Planton & Edlund, 2010). The definition of polypharmacy
has since been expanded beyond the number of medications and now also includes the
use of potentially inappropriate medications (PIMs) and drug interactions (Maggiore,
Gross, & Hurria, 2010; Planton & Edlund, 2010; Rocchiccioli, Sanford, & Caplinger,
2007) that can lead to adverse drug reactions in the older adult. Factors other than
multiple medications that can enhance polypharmacy in the older adult patient include
multiple prescribers and pharmacies, medications taken without clear clinical indications,
and duplicate medications.
Potentially Inappropriate Medications
Two tools that have been frequently used to evaluate potentially inappropriate medication
use in older adults have been the Beers criteria and the Medication Appropriateness
Index (MAI) (Maggiore, Gross, & Hurria, 2010). The Beers criteria, based upon expert
consensus, consist of a list of medications thought to be inappropriate for use in
older adults and are divided into two sections: (1) medications or medication classes
that should generally be avoided in persons 65 years or older because they are either
ineffective or they pose unnecessarily high risk for older persons and a safer alternative
is available and (2) medications that should not be used in older persons known to
have specific medical conditions (American Geriatrics Society 2012 Beers Criteria
Update Expert Panel, 2012; Fick et al., 2003).
The MAI assesses the degree of appropriateness to a medication using evaluation criteria
and a three-point Likert scale (Hanlon et al., 1992). The evaluation criteria include
indication, effectiveness, dosage, directions, drug-drug interaction, drug-disease
interaction, duplication, duration, and comparative cost.
Another list of high-risk medications available to the health-care provider has been
developed by the National Committee for Quality Assurance. The Healthcare Effectiveness
and Data Information Set (HEDIS) is a program designed to identify standards of care
for clinical measures. The HEDIS recently added a list of "Drugs to be Avoided in
the Elderly" that is similar to but not as extensive as the Beers criteria (National
Committee on Quality Assurance, 2007). Smartphone users can scan the barcode below
to access this list; other readers can visit http://www.ncqa.org/portals/0/newsroom/2007/Drugs_Avoided_Elderly.pdf
Drug Interactions
A drug-drug interaction is defined as an increase or decrease in the clinical effect
of a given drug due to interaction of another drug (Scripture & Figg, 2006). Drug
interactions can occur between drugs, and between drugs and food, herbs, or tobacco.
Older adults are at high risk for drug interactions due to the incidence of increased
comorbidities, multiple medication use, altered nutritional status, age-related physiologic
and cognitive changes, and alterations in pharmacokinetics.
Approximately one-third of ambulatory cancer patients are at risk for drug-drug interactions
because of the use of multiple medications to treat comorbidities, cancer, and treatment-related
toxicities (Riechelmann & Del Giglio, 2009). Pharmacokinetic changes may also occur
with impaired absorption due to mucositis and malnutrition and impaired distribution
and excretion due to fluid imbalances and organ dysfunction. A summary of drug-drug
interactions seen with chemotherapy agents, supportive care agents, and other drugs
is presented in Table 1.
Table 1
Table 1.Potential Interactions Between Non-Antineoplastic and Antineoplastic Drugs
Pharmacokinetics and Age-Related Changes
Pharmacokinetics of drug therapy is an important issue in the care of the older adult
because of the many age-related changes occurring in this age group (He, Clarke, &
McLachlan, 2011; Hurria & Lichtman, 2007). Pharmacokinetics is the physiologic effects
of drugs within the body. The four major processes are absorption, distribution, metabolism,
and elimination. Age-related changes can significantly impact these processes and
alter the expected outcomes of therapy (Table 2).
Table 2
Table 2. Age-Related Changes Impacting Pharmacokinetics
Absorption
Age-related changes that can occur in the gastrointestinal tract can alter the drug
absorption process for oral medications (Schwartz, 2006). A decrease in the intestinal
epithelium surface can decrease the area of drug absorption and may increase the length
of time medications remain in the tract. A decrease in gastric motility can decrease
or increase drug absorption, depending on the medication. A decrease in secretion
of digestive enzymes and gastric acid can alter drug disintegration and dissolution
and decrease drug absorption. A decrease in gastrointestinal blood flow can decrease
drug absorption through the gut wall (He, Clarke, & McLachlan, 2011; Schwartz, 2006;
Zurakowski, 2009).
Transdermal medications may also be altered due to age-related skin changes. With
age, epidermal cell growth slows, causing thinning of the skin. The skin becomes dry
with less subdermal fat (Zurakowski, 2009). Drug absorption of topical medications
can be at a different rate or amount when these changes are present in the older adult.
Decreases in muscle mass occur during aging and can alter intramuscular drug absorption.
Intramuscular injections may be absorbed faster; however, decreases in absorption
may also be seen because of the decreased peripheral blood flow (Zurakowski, 2009).
Distribution
Drug distribution is dependent upon fat, protein, and water content in the body. Age-related
changes result in an increase in body fat and a decrease in muscle mass and protein,
and total body water composition (He, Clarke, & McLachlan, 2011; Schwartz, 2006; Zurakowski,
2009). Drugs that are fat-soluble may remain longer in the body and increase the risk
of overdose. Lower levels of protein can cause higher serum concentrations of protein-binding
drugs such as warfarin. Water-soluble drugs can also be more active as a result of
lower body water composition.
Metabolism
With aging, liver mass, hepatic enzyme activity, and hepatic blood flow are decreased,
resulting in alterations in drug metabolism in the liver. These changes may result
in alterations in drug metabolism to an inactive form, and therefore there can be
longer exposure to an active drug, producing adverse drug effects. Drugs metabolized
in the liver to an active form may have less therapeutic effect or a delay in onset
of action (Hurria & Lichtman, 2007; Schwartz, 2006).
Excretion
Age-related changes in renal function have a significant impact on drug clearance.
Renal changes in the older adult include reduction in renal blood flow, decrease in
renal tubular clearance, and reduction in creatinine clearance (He, Clarke, & McLachlan,
2011; Lacasse, 2011). Older adults with decreased renal function as well as decreased
drug clearance are at risk for increased toxicities often associated with drug therapy.
Pharmacodynamics
Pharmacodynamics is the pharmacologic activity of a drug, defined as the drug concentration
at the target organ (Schwartz, 2006). Alterations in pharmacodynamics and end-organ
response are affected by age-related changes in effector system function, organ function,
and impaired homeostatic control or from multiple concomitant pathophysiologic changes
(He, Clarke, & McLachlan, 2011). For the older adult with cancer, efficacy and toxicity
of chemotherapy agents may be affected with increased risk of short- and long-term
complications such as myelosuppression, mucositis, cardiomyopathy, and peripheral
neuropathy.
The Role of the Advanced Practitioner in Oncology
The oncology AP can significantly affect the care of the older adult with cancer in
providing optimal pharmaceutical care and drug safety. The AP plays a key role in
monitoring symptom management of oncologic therapy and can prevent adverse drug reactions
through ongoing assessment and close follow-up.
Although a comprehensive medicine evaluation should be performed with all older adults,
certain key characteristics can place some individuals at higher risk for medication
problems (Planton & Edlund, 2010). These characteristics include age ≥ 85, renal insufficiency,
low body weight, 6 or more comorbidities, more than 12 dosages of medications per
day, more than 9 different medications, and a history of adverse drug reactions.
Several tools are also available to systematically assess medication use. These tools
include START (Screening Tool to Alert Doctors to the Right Treatment) and STOPP (Screening
Tool of Older Person’s Potentially Inappropriate Prescriptions; Lam & Cheung, 2012)
and ARMOR (Assess, Review, Minimize, Optimize, Reassess) (Haque, 2009). The START
tool is organized by organ systems and attempts to prevent omission of appropriate
medications. The STOPP tool is a useful guide to identify potentially inappropriate
medications. The ARMOR tool is a systematic approach to evaluate medications, taking
into account functional status and altered physiologic states. This tool emphasizes
quality of life and maintenance of functional status in making decisions on medication
use, with a consideration of a medication’s impact on bowel and bladder function and
appetite.
The AP can also develop an individualized clinical strategy to evaluate medication
use in the older adult. Websites are available for additional resources in assessing
medications in the older adult and are listed in Table 3. Key components of an assessment
should include the following:
Review of the patient’s complete medication list including prescription, over-the-counter
medications, herbs, and supplements
Evaluation of each medication’s indications, benefits, and side effects
Review of the Beers criteria
Review of potential drug interactions
Cognitive function
Assessment of activities of daily living
Assessment of nutritional status
Assessment of hepatic and renal function
Financial resources and prescription coverage
Social support resources
Table 3
Table 3. Resources for Assessment and Evaluation of Medication Use in Older Adults
In the oncology setting, the evaluation of medication use in the older adult with
cancer is even more critical because of the addition of potentially toxic antineoplastic
therapy and supportive care medications. The AP should assume a primary role in medication
assessment and make appropriate changes as needed. Medications should be reviewed
at each visit, especially noting any adverse side effects that the older adult may
be experiencing. Patients should be instructed to bring their complete medication
list, or the AP may also utilize the "brown bag method," in which patients are instructed
to put all medications that they are taking in a brown bag and bring to each visit.
The AP should actively involve the patient and caregiver in the review of medications
and give verbal and written instructions to prevent medication errors and promote
drug safety in this vulnerable population.
Summary
Having an awareness and understanding of strategies for managing medication regimens
in older adults with cancer has become critical for APs as a result of the aging population
and prevalence of comorbidities and multiple medications. Knowledge of polypharmacy;
effects of normal aging on pharmacotherapeutics; and thorough, ongoing assessment
of medications in the older adult with cancer by the AP will ensure optimal drug therapy
and prevent adverse drug reactions.