JOURNAL OF PALLIATIVE MEDICINE

Volume 21, Number 7, 2018 Palliative Care Specialists Series

ª Mary Ann Liebert, Inc.
DOI: 10.1089/jpm.2018.0187 Feature Editors: Christopher A. Jones and Arif H. Kamal

Ten Tips Palliative Care Pharmacists Want the Palliative

Care Team to Know When Caring for Patients

Tanya J. Uritsky, PharmD, BCPS, CPE,1 Rabia S. Atayee, PharmD, BCPS,2

Christopher M. Herndon, PharmD, BCPS, CPE, FASHP,3 Kashelle Lockman, PharmD, MA,4
Mary Lynn McPherson, PharmD, MA, MDE, BCPS, CPE,5 and Christopher A. Jones, MD, MBA6,7
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Abstract
As palliative care (PC) moves upstream in the course of serious illness and the development of drugs and their
indications rapidly expand, PC providers must understand common drug indications and adverse effects to ensure
safe and effective prescribing. Pharmacists, experts in the nuances of medication management, are valuable
resources and colleagues for PC providers. This article will offer PC providers 10 useful clinical pharmacy tips that
PC pharmacists think all PC providers should know for safe and effective symptom management. Close collab-
oration with or addition of a trained pharmacist to your PC team can improve clinical care for all PC patients.

Keywords: adverse effects to medication; benzodiazepines; corticosteriods; fentanyl; olanzapine; opioid

selection; palliative pharmacology; pharmacokinetics

Introduction specialized training in PC, this highly specialized level of

medication review and team support is not a resource that all

P harmacists possess a wealth of knowledge about

pharmacology and the clinical application of pharma-
cotherapy and can share that knowledge with care teams and
the patients they care for across clinical settings. Pharmacists
have unique training in the pharmacology and nuances of
medications, helping guide therapeutic decision making and
ensuring safe and effective use of pharmaceuticals. The
American Society of Health Systems Pharmacy Guideline on
the Pharmacist’s Role in Palliative and Hospice Care1 out-
lines the essential and desired roles for the pharmacist in the
palliative care (PC) and hospice setting. One of the key roles
includes optimizing symptom management for PC patients
through the expert provision of evidence-based, patient-
centered medication therapy and serving as an authoritative
resource on the optimal use of medications in symptom
management and PC.1 While more pharmacists are receiving
teams can access.
As the number of drugs and indications for their use expands
rapidly and as many drugs are used effectively off-label as
well, it is difficult for practicing clinicians to keep up. As PC is
moving upstream in serious illness, PC providers need to un-
derstand a wider array of drug indications and side effects. We
present here a list of 10 tips that will help PC clinicians to
manage commonly encountered symptoms. These tips were
chosen by specialty-trained and experienced PC pharmacists
from different practice sites across the United States. This
information is applicable to patients receiving PC in any set-
ting, and general pharmacologic principles can be applied to
any patient being treated with the medications being discussed.
We hope these tips will provide clarity around commonly
asked pharmacy questions and provide some insight into the
clinical expertise of your pharmacy colleagues.

1
Clinical Pharmacy Specialist in Pain Management and Palliative Care, Hospital of the University of Pennsylvania, Philadelphia,
Pennsylvania.
2
Department of Pharmacy, San Diego Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, La Jolla,
California.
3
Department of Pharmacy Practice, School of Pharmacy, Southern Illinois University, Edwardsville, Illinois.
4
Division of Applied Clinical Sciences, Department of Pharmacy Practice and Science, University of Iowa College of Pharmacy,
Iowa City, Iowa.
5
Department of Pharmacy Practice and Science, University of Maryland School of Pharmacy, Baltimore, Maryland.
6
Department of Medicine, Perelman School of Medicine and Palliative and Advanced Illness Research Center, University of Pennsylvania,
Philadelphia, Pennsylvania.
7
Palliative and Advanced Illness Research Center, University of Pennsylvania, Philadelphia, Pennsylvania.
Accepted April 11, 2018.

1017
 1018
Tip 1: Fentanyl is a tricky medication to use due to the
variable pharmacokinetics of each of its different formula-
tions and the many available methods and charts for con-
version.
Fentanyl is often used inappropriately.2–6 All fentanyl
formulations except injectable fentanyl require patients to be
opioid tolerant.7 Transmucosal immediate-release fentanyl
(TIRF) formulations have a quick onset of action and are
indicated only for breakthrough cancer pain via the TIRF
Risk Evaluation and Mitigation Strategy (REMS, www
.TIRFREMSaccess.com). TIRF formulations are not inter-
changeable on a microgram to microgram basis.
Transdermal fentanyl is FDA-approved for opioid-tolerant
patients with severe pain requiring daily, around-the-clock
chronic opioids. However, patients with cachexia display
impaired absorption of transdermal fentanyl, and recent
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studies indicate patients with albumin levels <2.5 g/dL may
experience decreased analgesic effectiveness when converted
to transdermal fentanyl.7,8 Heat may increase absorption of
transdermal fentanyl, making it a risky choice for patients with
fevers. Opioid conversion to transdermal fentanyl can be
challenging due to multiple conversion charts and formulas.
The FDA-approved label for transdermal fentanyl provides
a conservative dose conversion chart, which may result in
uncontrolled pain and/or withdrawal symptoms. Alternatively,
postmarketing studies in patients with cancer suggest 2 to
2.5 mg of oral morphine per day is approximately equia-
nalgesic to 1 mcg/h of transdermal fentanyl.9,10 Of note, the
12 mcg/hour transdermal fentanyl patch was approved by
the FDA in an effort to provide flexibility when titrating doses,
not as a starting dose.
Transdermal and continuous infusion fentanyl conversions
require consideration of timing to design effective and safe
analgesic regimens. The onset of effect for transdermal fen-
tanyl is 12–24 hours with peak plasma concentrations be-
tween 24 and 36 hours. Fentanyl is highly lipophilic, and
equilibrium must be achieved between plasma and tissues,
including fat and skeletal muscle, whether it is given as a
continuous infusion or via the transdermal route. Steady-state
levels with transdermal fentanyl are not reached until three to
six days after patch initiation. Therefore, transdermal fentanyl
is not a safe or effective therapeutic choice for a patient with
unstable, changing pain. When stopping transdermal fentanyl,
the average elimination half-life is 20 to 27 hours due to on-
going absorption from a subcutaneous depot in addition to the
tissue reservoir of fentanyl. In contrast, the half-life when
stopping a continuous infusion is 9 to 16 hours.11
Tip 2: Drug-induced QT interval prolongation is dose and
route related and uncommon at doses typically used in PC;
QT interval prolongation is associated with an increased risk
of Torsade de Pointes (TdP) and can progress to ventricular
fibrillation and sudden cardiac death.
It has been shown that many PC patients, at baseline, have
a prolonged QTc (interval between the start of the Q wave
and end of the T wave on electrocardiogram, corrected for
heart rate), but that severe prolongation is rare.12 There is a
two- to threefold increased risk of TdP when QTc >500
milliseconds (ms) or with a change of greater than 60 ms,
although there is no threshold where TdP is likely to occur.
Predictors of QT prolongation include use of QTc-prolonging
medications, hypokalemia, elevated serum creatinine, female
gender, structural heart disease, advanced age, prolonged
URITSKY ET AL.
baseline QTc, bradycardia, and drug interactions.13 Always
consider interactions with supplements and herbals such as
grapefruit juice, which may increase risk due to inhibition
of the cytochrome P450 system.
When considering a potentially QTc-prolonging medica-
tion, implement the lowest effective dose and administer
orally whenever possible. Dose-dependent risk is associ-
ated with tricyclic antidepressants, chlorpromazine at doses
>100 mg, and ondansetron at one to two hours after intrave-
nous administration.14 Intravenous administration of haloper-
idol has as much as a twofold greater risk of QTc prolongation
than does PO administration and higher risk is associated with
daily doses of greater than 15 mg.14 QTc prolongation is rare
with atypical antipsychotics, with virtually no QTc prolonga-
tion from aripiprazole.14 One open-label randomized study
found a fourfold increased risk with PO haloperidol versus
olanzapine.15 Commonly used doses of metoclopramide for
motility are not associated with QTc prolongation nor are
sertraline, paroxetine, and duloxetine.14 Mirtazapine and tra-
zodone have a low-risk profile at therapeutic dosing. Metha-
done has been associated with QTc prolongation and TdP in
very high doses (>100 mg/day), with interacting medications,
or when other risk factors are present.16 Exercise caution and
assess risk factors as described above, based on the clinical
situation.
Tip 3: There are many corticosteroids and choice of agent
should be based on the pharmacology of the individual agent,
with dexamethasone, the preferred drug in the management
of many PC patients for its relative potency and lack of
mineralocorticoid activity.
Corticosteroids (also referred to as glucocorticoids or
steroids) are among the most commonly used medications
in hospice and PC. Indications include pain (including met-
astatic bone pain), anorexia, cachexia, fatigue, nausea and
vomiting, depression, brain metastases, hypercalcemia, ma-
lignant bowel obstruction, spinal cord compression, superior
vena cava syndrome, and more. Steroids modulate proin-
flammatory mediators, reduce peritumor edema, and alter
adrenergic activity in the dorsal horn (lessening fatigue).17
There is no clear evidence to support selecting one steroid
over another, aside from differences in duration of action
and glucocorticoid (anti-inflammatory) and mineralocorti-
coid activity (sodium and fluid retention). See Table 1 for
characteristics of individual steroids.18 Given its high glu-
cocorticoid potency and low mineralocorticoid propensity,
dexamethasone is commonly selected in PC. Doses vary ac-
cording to data, expert opinion, and patient tolerability, but a
typical dexamethasone dose is 8 mg per day. This may be
Table 1. Comparable Steroid Dosing and Relative
Mineralocorticoid Activity
Relative
Comparable mineralocorticoid
Steroid dose (mg) activity
Cortisol 20 1
Prednisone 5 0.8
Methylprednisolone 4 0.5
Dexamethasone 0.75 0
Adapted from Becker.18
 PALLIATIVE CARE PHARMACIST TIPS 1019

given as a single dose, but is more commonly administered as
4 mg twice daily (with breakfast and lunch, to avoid causing
insomnia). Conveniently, dexamethasone is available as a
1 mg/mL oral solution for patients who have difficulty swal-
lowing tablets or capsules.
Acute adverse effects associated with corticosteroids in-
clude increased risk of infection (including thrush), edema,
dyspepsia and gastrointestinal (GI) ulceration, glucose in-
tolerance, insomnia, delirium, and anxiety. Longer courses of
therapy may cause steroid facies (moon-like), fat redistribution
(buffalo hump), adrenal suppression, skin fragility, impaired
wound healing, proximal muscle weakness, and osteoporosis.
Short-term use of corticosteroids does not warrant GI prophy-
laxis with proton pump inhibitors unless steroids are copre-
scribed with nonsteroidal anti-inflammatory drugs (NSAIDs).19
If therapy persists longer than two weeks, it is advised that the
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If warranted by the continued ‘‘as needed’’ opioid use, fentanyl
may be titrated up to the intended transdermal fentanyl dose
after 48 hours.
Methadone’s unique plasma distribution phase is about 3
to 4 hours with a long and variable elimination half-life of
15 to 60 hours, with reports as long as 150 hours.25 For
analgesia, methadone should be dosed between every 6 to
12 hours to account for the plasma distribution phase and
methadone should not be titrated any sooner than four to
seven days. Furthermore, methadone should be initiated and
monitored by clinicians who are familiar with and appre-
ciate its unique pharmacology beyond just its half-life.
Tip 5: When patients report adverse effects to a medication
that seem unexpected, it is important to remember uncommon
but potential side effects of palliative drugs, such as head-
aches and constipation with ondansetron, lower extremity

steroid dose be tapered down when discontinuing therapy.
Tip 4: Opioid selection should be based on the pharma-
cokinetics of the individual drug, with attention paid to onset,
formulation, half-life, and time to reach steady state levels,
particularly for drugs such as methadone and fentanyl.
Immediate release morphine, oxycodone, hydromorphone,
and fentanyl formulations have similar oral and, except
oxycodone, intravenous (IV) pharmacokinetic properties. IV
time to peak concentration is *10 minutes and oral peaks at
one hour; the average half-life is four hours (accounting for
active metabolites). Based on five half-lives, these drugs ul-
timately reach steady state concentrations in about 20 hours.
Steady state concentration is important for clinicians as
it indicates a safe time to reassess therapy and titrate the dose
if needed, and are particularly important with longer-acting
formulations.20 In the case of sustained release morphine,
generally, steady state is reached in two to three days.21,22
Controlled release oxycodone achieves steady state concen-
trations in one to two days.23 Serum concentrations for trans-
dermal fentanyl gradually increase following initial patch
application generally leveling off between 12 and 24 hours and
remain relatively constant with some fluctuation for the re-
mainder of the 72-hour application period, reaching steady
state serum concentrations by the end of the second 72-hour
period.24 Pharmacokinetic studies of transdermal fentanyl re-
veal peak levels between 36 and 48 hours.24 Accordingly, the
clinician may choose to start with a more conservative dose
than what was determined by the equianalgesic calculation.
swelling with gabapentin, and long-term side effects of opi-
oids, including immune system compromise and hormonal
shifts.
Rarely do medications exist without side effects. In all
healthcare settings, including PC, medications are utilized if
the ‘‘efficacy to adverse effects’’ ratio is high. More common
in PC is the off-label use of medications, often at doses lower
than the FDA approved indications. PC providers use medi-
cations often thought of as benign although side effects can
occur. Table 2 relates medications commonly used in PC and
their nonclassic, potential side effects.26 Understanding these
side effects should be considered before selecting therapy and
while monitoring patients on these agents.
Tip 6: Since refractory constipation is very challenging to
manage, it is essential to understand the onset and efficacy of
commonly used agents; nontraditional alternative options,
such as ‘‘Vaseline balls,’’ can be considered as well.
Constipation is defined as a reduction in the frequency
of bowel movements and/or the need to strain due to hard
stools.27 Patients with advanced illness frequently experi-
ence constipation due to their disease process, altered die-
tary habits, reduced physical activity, and as a side effect of
medications. Management of opioid-induced constipation
is commonly achieved with a stimulant laxative (senna or
bisacodyl) or an osmotic laxative (saline laxatives, sugars,
sugar alcohols, or polyethylene glycols). The onset of tra-
ditional laxatives at standard dosing can range from 30
minutes to 6 hours with magnesium hydroxide, 6 to 12 hours

Table 2. Some Commonly Used Medications with ‘‘Secret Side Effects’’25

Medication Secret side effect (incidence if known)
Ondansetron Headache (9–27%), constipation (6–11%)
Metoclopramide Restlessness (10%), increased incidence of diarrhea
Tramadol Hypoglycemia
Gabapentin Peripheral edema (8%)
Scopolamine patch Anticholinergic, notably sedation, dizziness, constipation delirium
Promethazine Anticholinergic notably sedation, dizziness, constipation
TCAs Anticholinergic (dry mouth, constipation)
Fleet’s enema Hyperphosphatemia (93–96%)
Lactulose Flatulence (20%), abdominal pain (20%), eructation (20%)
Olanzapine Orthostatic hypotension (3– ‡20%)
Clonidine Hypotension, bradycardia, drowsiness (2–38%), headache (1–29%),
dizziness, 4–16%; skin rash (15–50%), xerostomia (£40%)
Opioids Long-term side effects: immunosuppression, hormonal/endocrine dysfunction
 1020
with senna, and as long as 24–48 hours with lactulose or
polyethylene glycol. Importantly, recent research has shown
that senna plus docusate is inferior to senna alone in patients
with cancer or advanced illness.28 New agents introduced to
the market include lubiprostone (a chloride channel activator),
linaclotide (guanylate cyclase C agonist), and several pe-
ripherally active mu-opioid receptor antagonists (e.g., nalox-
egol and methylnaltrexone).29 With a number needed to treat
to achieve the FDA-determined therapeutic endpoint of 3–13
and a monthly cost of $300–$1,500, newer agents are gener-
ally not considered first-line options.
Administration of laxatives by mouth as well as enemas or
suppositories per rectum may be necessary to provide effective
relief. If fecal impaction develops, manual disimpaction fol-
lowed by an enema is a commonly used approach. This can
be generally uncomfortable, and the FDA has issued a warn-
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ing about overuse of sodium phosphate products due to de-
hydration and electrolyte imbalance.30 One home remedy
commonly used to prevent constipation is ‘‘frozen Vaseline
balls.’’ A Vaseline ball is a solid formulation of mineral oil
making it less likely to be aspirated. Vaseline balls are home-
prepared pea-sized balls of chilled Vaseline, rolled in con-
fectioner’s sugar. The patient swallows two to three balls
several times a day. A survey of 353 hospice professionals
showed that over 2/3 of respondents were familiar with the
use of Vaseline balls, and 87% thought they were effective
or very effective in producing laxation.31
Tip 7: Immunotherapy drugs (often ending in -mab) and
oral oncology agents (often ending in -nib), while not che-
motherapy, can cause generally manageable adverse effects
such as rashes, diarrhea, or pain flare, but may also interact
with medications such as H2-receptor blockers and proton
pump inhibitors that patients use for chronic or other
medication-induced symptoms.
Adverse effects from immunotherapy may occur at any point
but are most common during the first 8 to 12 weeks of therapy.
Skin-related toxicities (rash, pruritus) are the most common
side effects of immune checkpoint inhibitors (e.g., ipilimumab,
pembrolizumab). Grade 1–3 (mild to moderately severe) skin
adverse effects can be managed with emollients, antihistamines,
and topical steroids. GI toxicity, including diarrhea and colitis,
is common with ipilimumab. Grade 1–2 (mild to moderate)
diarrhea can be managed with loperamide and electrolytes, but
persistent grade 2, 3, or 4 diarrhea usually requires an immu-
notherapy break and treatment with high-dose corticosteroids.
Refractory cases can be treated with infliximab.
Nivolumab and pembrolizumab most commonly cause
immune-related arthritis that can be palliated with NSAIDs
(cyclooxygenase [COX]-2 selective if thrombocytopenic) or
nonacetylated salicylates like choline magnesium trisalicy-
late or salsalate. Moderate symptoms may require 10–20 mg/
day of prednisolone and higher doses may be required for
severe symptoms.32 Use of systemic corticosteroids is not
absolutely contraindicated with immunotherapy, although
may theoretically decrease its effectiveness. Due to unclear
data on the impact of short term corticosteroid use on clinical
outcomes during immunotherapy treatment, concomitant
corticosteroid use should always be first discussed with the
treating oncologist.33–35
Oral tyrosine kinase inhibitors (TKIs—drugs often ending
in–nib) can cause skin-related toxicities, diarrhea, changes in
hair pigmentation, and neuropathy.36 Importantly, many oral
URITSKY ET AL.
TKIs require an acidic environment for absorption. While
data on clinical outcomes from this drug interaction are
limited, proton pump inhibitor use may decrease progression-
free and overall survival when used concomitantly with su-
nitinib or erlotinib.37–39 If using an H2 receptor antagonist or
oral antacid solution with oral TKIs, patients should take the
H2 receptor antagonist at least two hours after oral chemo-
therapy to minimize the risk for interaction.
Tip 8: Data around the benefits of olanzapine (Zyprexa)
to treat nausea, appetite, and insomnia are growing, but a
broad adverse effect profile and relatively high cost limit
widespread use.
Olanzapine is an atypical antipsychotic with a complex
receptor-binding profile. It has an established role in the
management of delirium and severe mental health disorders
with growing data supporting its use in nausea and vomiting.
Nausea and vomiting can lead to appetite and weight loss,
decreased mood, and overall poorer outcomes. Although
these disparate symptom clusters sometimes require man-
agement with several agents, one multimodal agent may be
preferable. Olanzapine’s affinity for the dopamine, hista-
mine, muscarinic, and 5HT-3 (serotonin) receptors is largely
responsible for its efficacy in the management of nausea/
vomiting.40 The data supporting use of olanzapine for
nausea and vomiting in oncology have led the American
Society of Clinical Oncology to add olanzapine to its anti-
emetic regimen for treatments involving highly emetogenic
chemotherapy and for breakthrough nausea and vomiting.41
Retrospective and case report data also demonstrate that
olanzapine is effective in treating nausea in PC patients.42
Clinical experience supports that olanzapine is effective for
the relief of refractory nausea and vomiting.
The same complex receptor-binding profile is responsible for
its many potential side effects, some of which can help treat
concomitant symptoms. With strong affinity for the muscarinic
and histaminergic receptor, olanzapine tends to be sedating, and
as a result can help patients suffering with insomnia. Its broad
effects on the serotonin, dopamine, adrenergic, histamine, and
cholinergic receptors are thought to be the underlying me-
chanism for associated weight gain as well.43 Finally, its effects
on depression and anxiety likely stem from its affinity for the
dopamine and serotonin receptors and potentially its gamma
amino butyric acid (GABA) and benzodiazepine-like ac-
tivity as well. Other common immediate side effects include
dry mouth, constipation, orthostasis, and dose-dependent
extrapyramidal symptoms. Longer term effects include glu-
cose changes, hyperprolactinemia, and alterations in liver
enzymes.44 Oral olanzapine is more expensive than oral hal-
operidol or prochlorperazine, and its orally disintegrating
formulation costs even more. Discontinuation of other anti-
emetics in favor of one medication may help justify the cost.
Tip 9: NSAIDs have the potential to improve somatic pain;
through optimal patient selection, duration, dosage, consid-
eration of COX-1 or COX-2-selectivity, and consideration of
the overall risk-benefit profile, risks for cardiac events, and
GI bleeding can be minimized.
NSAIDs are commonly used in palliative and end-of-life
care as adjuvant analgesics and are often first-line therapy for
cancer-related bone pain.45,46 Recent data call this practice
into question.47 The National Comprehensive Cancer Network
(NCCN) Adult Cancer Pain Guidelines caution against routine
NSAID use given the potential for additive toxicities when
 PALLIATIVE CARE PHARMACIST TIPS 1021

Table 3. Pharmacodynamic and Pharmacokinetic Properties of Select Benzodiazepines

Elimination Relative
Drug T1/2 (hours) potency (mg) Comments
Alprazolam 12–15 0.5 Risk of rebound anxiety; high abuse potential
Chlordiazepoxide 30–100 10 Active metabolite may accumulate
Clonazepam 30–40 0.25 CYP 3A4 substrate
Clorazepate 36–200 7.5 Prodrug of nordiazepam
Diazepam 20–80 5 Rapid redistribution, duration of action not represented by T1/2
Lorazepam 10–14 1 Sublingual administration pharmacokinetics similar to oral administration
Oxazepam 5–15 15 Delayed peak serum concentrations
Temazepam 8–15 5 High variability in T1/2
Table adapted from Dipiro (2014)60 and Lexicomp.61
CYP, cytochrome P450.
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NSAIDs and many chemotherapy agents are used together
(e.g., thrombocytopenia, renal impairment, hepatotoxicity,
and cardiovascular risk).48 COX-type selectivity may alter
relative bleeding risk or cardiovascular toxicity of the re-
spective agent. COX-I isoenzyme selectivity, seen most
strongly in ketorolac and indomethacin,49 is generally as-
sociated with less cardiac risk, but an increased risk of GI
bleeding. NSAIDs possessing higher selectivity for the
COX-II isoenzyme (celecoxib, meloxicam, etodolac, and
diclofenac) are associated with a lower risk of GI effects,
but may still predispose patients, especially those with un-
derlying risk (i.e., hypovolemia, diabetes, interstitial ne-
phritis, or papillary necrosis) to the same nephrotoxicity as
do traditional NSAIDs. Nonselective COX-I/COX-II in-
hibitors, including naproxen, ibuprofen, and nabumetone,
among others, can confer both GI and cardiac risks.49
Nonacetylated salicylates such as diflunisal and choline
magnesium trisalicylate have minimal to no effect on platelet
aggregation due to their thromboxane and prostaglandin
sparing effects.50,51 Analgesic and anti-inflammatory effects
of these agents have been called into question, but efficacy
has been exhibited in head to head studies with traditional
NSAIDs.52 The exact pharmacologic mechanism of these
agents in the inflammatory cascade remains unclear, but may
be attributed to the antagonism of nuclear factor (NF)-jB and
microglial nitrite secretion.53
Recently, topical application of NSAIDs, such as keto-
profen gel, has become more commonplace in the treatment
of small-joint osteoarthritis. The tolerability and adverse ef-
fect profile of this treatment modality mirrors placebo, po-
tentially improving utility in the palliative or end-of-life
patient.54 All NSAIDs require judicious monitoring and
careful consideration of additive drug-related adverse effects,
especially renal and bleeding risk.
Tip 10: Benzodiazepines, both high risk and high benefit
at the end of life, are utilized for the short-term treatment
of anxiety and can be a helpful adjunct for dyspnea and
insomnia.
Lorazepam is the most commonly used benzodiazepine in
PC given its numerous administration options and lack of
active metabolites. Alprazolam is frequently avoided due to
its risk of abuse, accumulation, and confusion in frail patients
and older adults. While benzodiazepines have many uses in
PC, safer treatment alternatives, such as selective serotonin
reuptake inhibitors, may be preferred when there is a longer
prognosis. Concomitant evidence-based, nonpharmacologic
strategies such as cognitive behavioral therapy55,56 and music
therapy57 should be considered as first-line interventions.
Provision of psychological support, attention to a patient’s
spiritual needs, and complementary treatments such as Reiki
are also important tools when managing anxiety.
Since anxiety frequently co-occurs with acute dyspnea, it
can be difficult to tease out the response to treatment. A
systematic review calls into question the routine practice of
treating dyspnea in the absence of anxiety with benzodiaze-
pines.58 Typical first-line therapy for dyspnea is an opioid;
therefore, the potential risk for additive central nervous sys-
tem and respiratory depression should be considered with
concurrent administration.59
Benzodiazepines, especially at low to moderate doses,
may produce paradoxical agitation. In fact, benzodiazepine
exposure represents a common underlying etiology for de-
lirium. There is also the risk of abuse, correlated directly with
faster and higher drug concentration peaks. A careful patient
and family history of substance use disorder risk factors
should be considered and a careful accounting of doses un-
dertaken.
Benzodiazepines are frequently categorized by their length
of activity, although elimination half-life (T1/2) may not
translate into duration of effect (Table 3). A short-acting
agent may result in anxiolytic gaps, while a long-acting agent
increases the risk for drug accumulation and adverse effects.
An easy to remember mnemonic is the short length of action
(LOA) with Lorazepam, Oxazepam, and Alprazolam. In
cases of hepatic compromise, the mnemonic LOT (lorazepam,
oxazepam, temazepam) helps clinicians recall those benzodi-
azepines that do not undergo Phase 1 metabolism.
Conclusion
There are important general principles that PC practitioners
should recall when recommending medications for symptom
management. It is not possible to predict exactly how any one
patient will react to a medication, but a general understanding of
the basic pharmacology and of nuances of the commonly used
agents will help to achieve rapid and effective symptom control.
The aforementioned tips are those our group of PC pharmacists
and practitioners consider to be essential clinical pearls that all
PC providers should be aware of to help provide safe and ef-
fective symptom management for their patients receiving PC.
 1022
Author Disclosure Statement
No competing financial interests exist.
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Address correspondence to:
Tanya J. Uritsky, PharmD, BCPS, CPE
Clinical Pharmacy Specialist in Pain Management
and Palliative Care
Hospital of the University of Pennsylvania
Ground Floor Rhodes
3400 Spruce Street
Philadelphia, PA 19104
E-mail: tanya.uritsky@uphs.upenn.edu