DIFFICULT CASES: CRACKING THE CODE:

WORST CASE SCENARIO:

MANAGING SIDE EFFECTS
SATURDAY/3:15-4:15PM

ACPE UAN: 0107-9999-16-039-L01-P 0.1 CEU/1 hr

Activity Type: Application-Based

Learning Objectives for Pharmacists: Upon completion of this CPE activity participants should be able to:
1. Discuss the prevalence of medication-related side effects
2. Describe the mechanism by which select medication-related side effects occur
3. Review strategies for optimal management of medication-related side effects through a case-
based approach
4. Identify alternate treatment options for a patient who experiences a medication-related side effect

Speaker: Michelle Bottenberg, PharmD, BCPS

Michelle Bottenberg is an Associate Professor of Pharmacy Practice in the Department of Clinical
Sciences at Drake University College of Pharmacy and Health Sciences in Des Moines, Iowa. She
serves as the Director of the Pharmacy Skills and Applications course series and is currently the
co-chair of the Des Moines Area Interprofessional Education Collaborative Planning Committee. Her
primary areas of interest include interprofessional education, using simulation as an educational
pedagogy, and scholarship of teaching and learning. After graduating from Drake University in
2005, Michelle completed a PGY-1 pharmacy practice residency with an emphasis in internal
medicine at Iowa Methodist Medical Center in Des Moines. She earned her Board Certification in
Pharmacotherapy (BCPS) in 2007. She is a member of IPA, AACP, ACCP, and the Rho Chi Honor
Society, for which she currently serves as the Alpha Sigma Chapter faculty advisor at Drake. Michelle
lives in Waukee, IA, with her husband Charlie, their three kids, Liam, Alaina, and Landon, and two
beagles, Ajax and Violet.

Speaker Disclosure: Michelle Bottenberg reports no actual or potential conflicts of interest in relation
to this CPE activity. Off-label use of medications will not be discussed during this presentation.

FEBRUARY 13, 2016 | IOWA EVENTS CENTER | DES MOINES, IOWA

 Worst- Case Scenario: Managing
Medication-related Side Effects
Michelle M. Bottenberg, PharmD, BCPS
Associate Professor of Pharmacy Practice
Drake University College of Pharmacy and Health Sciences

Disclosure
Michelle M. Bottenberg reports no actual or
potential conflicts of interest associated with this
presentation

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 Learning Objectives
Upon successful completion of this activity, pharmacists
should be able to:
Discuss the prevalence of medication-related side
effects
Discuss the mechanism by which select medication-
related side effects occur
Review strategies for optimal management of
medication-related side effects through a case-based
approach
Identify alternate treatment options for a patient who
experiences a medication-related side effect

Medication-related Side Effects

Any substance that is capable of generating a therapeutic effect
can also yield unwanted or adverse effects
Adverse drug reaction (ADR):
An appreciably harmful or unpleasant reaction, resulting from an
intervention related to the use of a medicinal product, which predicts hazard
from future administration and warrants prevention or specific treatment, or
alteration of the dosage regimen, or withdrawal of the product1
Tens of millions of people in the US use prescription & OTC
medications2
Institute of Medicine (IOM) estimates at least 1.5 million
preventable ADR effects occur within the healthcare system each
year3
1 Edwards IR, Aronson JK. Adverse drug reactions: definitions, diagnosis and management. Lancet. 2000; 356:
125559
2 FDAs Safe Use Initiative. http://www.fda.gov/downloads/Drugs/Drug Safety/UCM188961.pdf (accessed
January 17, 2016)
3 Institute of Medicine 2007. Preventing Medication Errors. Washington, DC: The National Academies Press.

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 Medication-related Side Effects
In 2004 to 2005, data from National Electronic Injury Surveillance
System-Cooperative Adverse Drug Event Surveillance Project
(NEISS-CADES)1
Documented at least 117,000 hospitalizations
More than 700,000 ED visits
More recent estimates are 130,000 hospitalizations and more
than a million ED visits per year2
Adverse drug events - caused by (about a third each)2
Allergic reactions
Non-allergic side effects
Unintentional overdoses

1 Budnitz, et al. National surveillance of emergency department visits for outpatient adverse drug events. JAMA.

2006 Oct 18;296(15):1858-66.

2 FDAs Safe Use Initiative. http://www.fda.gov/downloads/Drugs/Drug Safety/UCM188961.pdf (accessed

January 17, 2016)

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 CASE 1

Patient Case 1: My legs hurt

55-year-old Caucasian male calls into the pharmacy
complaining of muscle pain. I remember being told
something about this with one of my meds.

PMH: HTN (neg DM, non smoker); last BP 130/82 mmHg

hyperlipidemia (10 year ASCVD risk: 11.71%)

Meds: lisinopril/HCTZ 20/12.5mg daily

simvastatin 40mg daily
(both refilled regularly for past 5 years)

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 Case 1: Statin Induced Myopathy
Mechanism of action (therapeutic): 3-hydroxy-3-
methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors
(competitively inhibit the rate-limiting step in hepatic
cholesterol synthesis)
Mechanism of pathogenesis: unknown
Theories
Inhibition of HMG-CoA reductase reduces endogenous coenzyme Q10
levels (may block steps in muscle cell energy generation)
Interaction with cytochrome P450 enzyme system
Statin therapy causing exacerbation of exercise-induced skeletal injury
Low vitamin D levels (defined as 25-hydroxyvitamin D < 32 ng/mL)

Pasternak RC, Smith SC Jr, Bairey-Merz CN, et al. ACC/AHA/NHLBI Clinical Advisory on the Use and Safety
of Statins. Circulation. 2002 Aug 20;106(8):1024-8

Case 1: Statin Induced Myopathy

Factors that Increase Risk
Advanced age (> 80 years old)
Female gender
Small body frame/ frailty
Multisystem disease (CKD in DM)
Perioperative period
Alcohol abuse
Concomitant medication use (fibrates, cyclosporine, macrolides, azole
antifungals, protease inhibitors, verapamil, amiodarone, niacin
Hypothyroidism
Increased dose

Pasternak RC, Smith SC Jr, Bairey-Merz CN, et al. ACC/AHA/NHLBI Clinical Advisory on the Use and Safety
of Statins. Circulation. 2002 Aug 20;106(8):1024-8

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 Case 1: Statin Induced Myopathy
Strategies for optimal management
Instruct pts to report symptoms (muscle discomfort or
brown urine)
Check creatine kinase (CK) levels & compare to baseline
Discontinue statin if CK > 10 times upper limit of normal in
symptomatic pt
Consider dose reduction for pts with weakness/muscle
discomfort & have progressive CK elevations on serial
measurements
Advise moderation in activity

Pasternak RC, Smith SC Jr, Bairey-Merz CN, et al. ACC/AHA/NHLBI Clinical Advisory on the Use and Safety
of Statins. Circulation. 2002 Aug 20;106(8):1024-8

Case 1: Statin Induced Myopathy

Identify alternate treatment options
Switch to another statin not tried before1
Consider non-traditional dosing of statins (every other day
dosing of same or reduced dose, once weekly)2
Inconsistent evidence for coenzyme Q10 supplementation
Weak evidence for creatine and vitamin D supplementation
Consider switching to other LDL-C lowering medications
(ezetimibe, bile acid sequestrants, niacin, fibrates)

1 Pasternak RC, Smith SC Jr, Bairey-Merz CN, et al. ACC/AHA/NHLBI Clinical Advisory on the Use
and Safety of Statins. Circulation. 2002 Aug 20;106(8):1024-8.
2 Cornier MA, Eckel RH. Non-traditional dosing of statins in statin-intolerant patients is it worth a try?

Curr Atheroscler Rep (2015) 17:475.

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 Patient Case 1: My legs hurt
Options
A. Wait until symptoms subside (~2 months) and reduce
statin dose (simvastatin 20 mg)
B. Wait until symptoms subside (~2 months) and switch to
another statin (atorvastatin 10mg)
C. Wait until symptoms subside (~2 months) and initiate
every other day dosing (atorvastatin 10mg every other
day)
D. Wait until symptoms subside (~2 months) and
recommend to initiate coenzyme Q10 and vitamin D
supplementation

CASE 2

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Case 2: I prefer not to take my
depression medication anymore
40-year-old female comes to the pharmacy to pick up her
prescription refills and asks that you return one of them to
stock.

PMH: hypothyroidism (20 year history, currently controlled)

depression (diagnosed 4 months ago)

Meds: levothyroxine 25 mcg daily

sertraline 100mg daily

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Case 2: Antidepressant-Induced Sexual
Dysfunction
Antidepressant medication adversely affects one or more of
the 3 phases of sexual response (desire, arousal and orgasm)
Delayed ejaculation (most commonly reported)
Delayed and/or absent orgasm
Reduced and/or lack of sexual desire
Reduced and/or absent sexual arousal (erectile dysfunction and
insufficient vaginal lubrication)
Mechanism of pathogenesis: unknown
Evidence in the literature indicates a sexual inhibitory action is
expressed through the activation of 5HT2 receptors

La Torre A et al. Sexual Dysfunction Related to Psychotropic Drugs: A Critical Review Part 1:
Antidepressants. Pharmacopsychiatry 2013; 46: 191199

Percentage of Sexual Dysfunction

Reported
Class Drug Percentage
SSRI citalopram 79%
escitalopram 37%
fluoxetine 70%
paroxetine 71%
sertraline 80%
others mirtazapine 24%
bupropion 10%
SNRI venlafaxine 80%
duloxetine 42%

Serretti A , Chiesa A . Antidepressivi e disfunzione sessuale: epidemiologia,meccanismi e strategie di trattamento .

Giornale Italiano di Psicopatologia 2010 ; 16 : 104 113

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Case 2: Antidepressant-Induced Sexual
Dysfunction
Treatment strategies should be carefully evaluated on a case
by case basis with consideration given to
nonpharmacological interventions
Strategies for optimal management
Wait for a spontaneous reduction of side effects over time
Reduce dose
Arrange temporary drug reduction or suspension of drug for 2 days in
the week (drug holiday)
Switch to a different antidepressant with fewer sexual side effects
Add symptomatic therapy

La Torre A et al. Sexual Dysfunction Related to Psychotropic Drugs: A Critical Review Part 1:
Antidepressants. Pharmacopsychiatry 2013; 46: 191199

Case 2: Antidepressant-Induced Sexual

Dysfunction
Identify alternate treatment options symptomatic
treatment
Add other antidepressants (bupropion,* mirtazapine)
Add phosphodiesterase inhibitors* for erectile dysfunction
Add partial alphanoradrenergic antagonist (buspirone)
Add dopaminergic agonists (amantadine, bromocriptine)
Add psychostimulant dopamine agonists, (methylphenidate and
dextroamphetamine)
Only treatment to show benefit in randomized controlled
trials notated with *
Rudkin L , Taylor M J , Hawton KK E . Strategies for managing sexual dysfunction induced by
antidepressant medication (protocol) . The Cochrane Database of Systematic Reviews 2002 , Issue
4. Art. No.: CD003382. doi: 10.1002/14651858.CD003382

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Case 2: I prefer not to take my
depression medication anymore

Options
A. Decrease the dose of sertraline to 50mg daily
B. Switch to another antidepressant
(escitalopram)
C. Consider a drug holiday (not taking dose for
2 days during the week)
D. Add bupropion 150mg BID

CASE 3

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 Case 3: My son is losing weight
The mother of an 8-year-old boy who has been diagnosed
with ADHD 6 months ago calls into your pharmacy very
worried about her sons recent weight loss and how it may
affect his growth. She says his med has worked wonders
for him as far as behavior goes at home and school he
is more focused and getting better grades. However, she
has noticed a twitching in his face and he has lost 10
pounds this past month. She cant get him to eat
anything!

PMH: ADHD
Meds: Concerta ER 18mg daily

Case 3: Stimulants and Weight Loss

Attention-deficit/hyperactivity disorder (ADHD) most common
behavioral disorder in children
Treatment: behavioral therapy & pharmacotherapy
Medications recommended as first-line therapy in children six
years and older
Psychostimulants (methylphenidate and dextroamphetamine)
Affect central nervous system dopaminergic pathways
Most effective for core ADHD symptoms
Generally acceptable adverse effect profiles
Adverse effects: reduced appetite, abdominal discomfort, headache,
irritability, anxiousness, sleep problems, small reduction in height,
small increases in HR/BP, tic and Tourette syndrome symptoms

Felt BT et al. Diagnosis and management of ADHD in children. Am Fam Physician 2014;90(7):456-464.

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 Case 3: Stimulants and Weight Loss
Strategies for optimal management of reduced
appetite/weight loss and reduction in height
Psychostimulant dosing should start low and increase once to twice
weekly based on feedback from parents, the patient, and teachers
No evidence shows that one psychostimulant agent is superior
Medication holidays are unnecessary unless adverse effects (e.g.,
decreased growth velocity) are a concern
Strategies to improve nutrition
Lower the dose
Take medication with or after meals
Have high calorie breakfast and snacks after school or at bedtime
Use stimulant only for high-priority needs (coordinating the timing of doses
and meals so that the child will be hungry for some meals)
Dietician referral
Christner J, OBrien JM, Felt BT, Harrison RV, Kochhar PK, Bierman B. Attention-deficit hyperactivity
disorder. Ann Arbor, Mich.: University of Michigan Health System; 2013.
http://www.guideline.gov/content. aspx?id=46415&search=adhd. January 3, 2014

Case 3: Stimulants and Weight Loss

Identify alternate treatment options

Switch medications
Last resort for children with ADHD who have experienced a robust
response to treatment
Risk of growth deficits must be balanced against the risk of
exacerbating ADHD symptoms
Non-stimulant options (not as effective)
atomoxetine
guanfacine
clonidine

Faraone SV, et al. Effect of stimulants on height and weight: a review of the literature. J Am Acad Child
Adolesc Psychiatry. 2008 Sep;47(9):994-1009.

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Case 3: My son is losing weight.

Options
A. Remain on ADHD medication and add
supplements
B. Decrease the dose of the current med
C. Switch to a different stimulant
D. Consider switching to a non-stimulant option
(atomoxetine)

CASE 4

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 Case 4: The case of the recurring
cough
54-year-old male comes to the pharmacy counter to pick up
a prescription for cough medicine. He mentions this is the
3rd time this month that hes been here. Nothing seems to
shake this annoying dry cough. I hope this stuff will do the
trick this time!

PMH: HTN, DM type 2

Meds: lisinopril 20mg daily
simvastatin 40mg daily
metformin 500mg BID
(all refilled regularly for past 6 months)

Case 4: ACE Inhibitor Cough

Class effect of angiotensin converting enzyme (ACE)
inhibitors
Incidence occurs in 535% of people
Mechanism of pathogenesis: release of bradykinin (normally
metabolized by ACE in the lungs) results in a tickling,
scratchy or itchy sensation in the throat; dry cough
Onset is variable from hours after first dose to months after
initiation of therapy
Not dose dependant
More common in women, non-smokers, and those of
Chinese origin
Irwin RS. Baumann MH, Bolser DC, et al. Diagnosis and management of cough executive
summary: ACCP evidence-based clinical practice guidelines. Chest 2006;129(1 Suppl):1S23S

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 Case 4: ACE Inhibitor Cough
Strategies for optimal management
Therapy with ACE inhibitor should be discontinued
Diagnosis is confirmed by resolution of cough (usually 1 to 4 weeks
after cessation of the offending agent)
If compelling reason to keep on ACE, a repeat trial may be attempted
Options to treat the cough (if cessation of ACE not an
options)
Theophylline
Sulindac
Indomethacin
CCB (amlodipine and nifedipine)
Ferrous sulfate
Irwin RS. Baumann MH, Bolser DC, et al. Diagnosis and management of cough executive summary:
ACCP evidence-based clinical practice guidelines. Chest 2006;129(1 Suppl):1S23S

Case 4: ACE Inhibitor Cough

Identify alternate treatment options
Switch to an Angtiotensin Receptor Blocker (ARB)

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Case 4: The case of the recurring
cough

Options
A. Decrease the dose of lisinopril
B. Remain on lisinopril & treat cough with
amlodipine
C. Switch to another ACE inhibitor, fosinopril
D. Switch to an ARB

Questions/Comments?

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