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Practical Approach to Complex Pharmacological
Needs: Polypharmacy, Drug/Drug Interactions
Rhonda Cooper-DeHoff, PharmD
Eileen Handberg, PhD, ANP-BC
Jane Linderbaum, ANP-BC
David Parra, PharmD
Case Study 1
Patient is a, 70 year old African American male, has HFrEF (EF 28%), exhibiting NYHA class III
symptoms.
ADR: Lisinopril (angioedema)
Vitals: BP: 120/70 mmHg
HR: 70 bpm
Labs: Scr: 0.9 mg/dL
K+: 4.5 mEq/L
What is the best change in heart failure therapy
for this patient?
A.
B.
C.
D.
Switch valsartan to sacubitril/valsartan
Add hydralazine/isosorbide dinitrate
Add digoxin
Add ivabradine
Medications (no changes since 2014):
Furosemide 20mg daily (no significant edema presently)
Metoprolol succinate 200mg daily
Valsartan 180mg bid
Spironolactone 50mg daily
Case Study 2
Patient is a 63 year old white female, with HFrEF (EF 30% on Echo 12/2015) with NYHA class
II symptoms. Patient took all her medications this morning.
ADR: Dizziness with high dose carvedilol
Vitals: BP: 124/74 mmHg
HR: 60 bpm
Labs: Scr: 1.2 mg/dL
K+: 4.8 mEq/L
proBNP (NT-proBNP) 740 pg/mL
Medications (no medication changes since 3/2016):
Furosemide 40mg daily (no edema presently)
Carvedilol 12.5mg bid (max tolerated dose)
Lisinopril 20mg daily
Spironolactone 50mg daily
You have decided to switch lisinopril to
sacubitril/valsartan. What should the next step
be?
A.
Instruct patient to take sacubitril/valsartan
tomorrow morning, replacing lisinopril.
B.
Instruct patient to discontinue lisinopril and
initiate sacubitril/valsartan the morning
after tomorrow.
C.
Continue all medications as prescribed and
add sacubitril/valsartan.
Case Study 3
A 68yowm with HFpEF, improved presents to clinic. After
institution of GDMT his LVEF is now 49% (previously 30%). No
symptoms and he feels well. Currently on carvedilol 25mg bid,
sacubitril/valsartan 97/103mg bid, spironolactone 25mg daily,
digoxin 0.125mg daily, furosemide 20mg prn
He complains he simply cannot stand taking this many
medications nor afford it.
What do you think about reducing or discontinuing some of the
above now that his LVEF has normalized?
4
Case Study 4
68 yo white male new to your clinic presents with a history of
heart failure (EF 30%), AICD/PM, CAD (post MI 1999), HTN,
Dyslipidemia, DM, PAD with intermittent claudication, CKD
Currently, quite stable with no complaints. Able to do ADL
without symptoms and no changes in medications in the last
18 months. No edema. No PND/Orthopnea. No dizziness or
lightheadedness. No chest pain.
5
Case Study 4
Medications: ASA 81mg daily, carvedilol 25mg bid, furosemide
80mg daily, KCL 20meq daily, enalapril 20mg bid, simvastatin
40mg qhs, digoxin 0.25mg daily, cilostazol 100mg bid
BP 110/70mmHg, BUN/Cr 30/1.6mg/dl, Digoxin level
1.4ng/ml, K+ 4.8meq/L
Do you want to make any changes?
6
Case 5
A primary care colleague inquires what to do with a patient
(HFrEF in NSR) who has a digoxin level of 2.8ng/ml. Level was
obtained at 10am, patient takes all medications at one time
upon arising at 7am.
Your options:
A. Continue current dose
B. Reduce dose to target a level < 1ng/ml
and repeat level in 1-2 weeks
C. Reduce dose to target a level < 1ng/ml
and repeat level in 1-2 days
D. Repeat level
Case 6
A 52 year old female with chronic heart failure with reduced ejection fraction
(EF 15%) awaiting heart transplant. Patient is currently NYHA Class III/IV, and
not responding with an adequate diuresis/relief of congestive symptoms
despite furosemide 80mg bid. Patient has no prescription coverage.
What may help overcome diuretic resistance?
A. Review low salt diet
B. Change to torsemide 40-80mg daily
C. Have patient lay down after taking furosemide
D. Instruct patient to take furosemide on an empty stomach
E. A, C, & D
Case 7
An 65 y/o woman with CAD, s/p anterior wall MI, with left ventricular
dysfunction with an EF of 30%, and chronic kidney disease stage 3 (eGFR
35 ml/min/1.73m2) is found to be in heart failure during routine office
visit.
She has been taking ibuprofen for arthritic pain. Her medications include:
furosemide 40 mg daily, lisinopril 5 mg daily, metoprolol tartrate 25 mg
BID, aspirin 81 mg daily, atorvastatin 10 mg daily. Chest X-ray reveals
pulmonary vascular congestion. She also has bilateral lower extremity
edema.
Case 7
What actions would you take?
A.
B.
C.
D.
E.
F.
G.
Discontinue ibuprofen
As the GFR becomes severe at 20 ml/min the dose of lisinopril should
be decreased
Furosemide reduces intravascular lung pressure and the dose should
be increased
Spironolactone 25 mg daily would be a good drug to add at this time
A, B, & C
A, C, & D
A&C
Case 7
What would you recommend for arthritic pain
control?
A.
B.
C.
D.
E.
F.
Nonacetylated salicylate (i.e. salsalate)
Tramadol
Naproxen
Celecoxib
A, B, or D
Any of the above are acceptable
AHA Scientific Statement
Use of Nonsteroidal Antiinflammatory Drugs
Stepped approach to pharmacologic therapy for
musculoskeletal symptoms in patients with known CVD or
risk factors for IHD (in order of preference)
Acetaminophen, ASA, tramadol, or narcotic analgesics (short
term)
Nonacetylated salicylates
Non COX-2 selective NSAIDs
NSAIDs with some COX-2 selectivity
COX-2 selective NSAIDs
Circulation. 2007;115:1634-1642
Case 8
You are asked to recommend antithrombotic therapy for a 76 year old male
with permanent non-valvular atrial fibrillation who presented 8 weeks ago with
an ischemic CVA. He is currently recovering in a rehab center and has a
feeding tube placed as a residual effect of the stroke.
PMH: Permanent atrial fibrillation, CVA, hypertension, s/p total colectomy for
colon cancer 2011
Which is the best option(s)?
A. Warfarin
B. Apixaban
C. Dabigatran
D. Rivaroxaban
Case 9
76 year old male with hypertension, heart failure, diabetes
mellitus, prior MI, PM/AICD, and transient ischemic attack
presents with atrial fibrillation on 3 month AICD interrogation (6
episodes > 15 minutes). He has also fallen 3 times in the last
month secondary to a gait imbalance.
Do you anticoagulate him and with what?
Audience Response Question
How often should a patient replace their bottle of SL
NTG once they have opened it?
1.
2.
3.
4.
3 months
6 months
12 months
Expiration date
Audience Response Question
Which of the following pose a significant drugdrug interaction when administered with
ranolazine?
A.
B.
C.
D.
Digoxin
Atorvastatin
Verapamil
Digoxin and verapamil
Drug Interactions with Ranolazine
Select drug-drug interactions with ranolazine
– Substrate of P-gp, CYP3A, CYP2D6 (lesser)
– Weak inhibitor CYP3A, moderate inhibitor of CYP2D6 and P-gp,
inhibitor of OCT2
– Limit doses of simvastatin to 20mg daily
– Adjust digoxin dose if needed (increases concentrations by 50%)
– Limit ranolazine to 500mg twice daily if receiving moderate
CYP3A inhibitors (e.g. diltiazem, verapamil)
Audience Response Question
Which of the following statements is true?
A. Drugs must physically interact with each other to cause a
drug-drug interaction
B. If food slows down the rate of absorption of a drug, but not
the extent, it is not considered a drug interaction
C. If a drug can worsen a patient’s comorbid medical
condition, one can say a drug interaction exists
Audience Response Question
Which of the following oral anticoagulants has/have a
drug-nutrient interaction
I.
II.
III.
IV.
A.
B.
C.
D.
I and II
I and III
I, II, III
I, III, ad IV
Warfarin
Rivaroxaban 10mg dose
Rivaroxaban 20mg dose
Dabigatran
Audience Response Question
Which of the following is true about amiodarone?
I.
II.
III.
A.
B.
C.
D.
I only
II only
I and III
II and III
Amiodarone is a weak CYP3A4 inhibitor
Amiodarone is a strong CYP3A4 inhibitor
Amiodarone is a P-gp inhibitor
Amiodarone and Drug Interactions
Selected drug-drug interactions with amiodarone
(a combined P-gp and weak-moderate CYP3A4
inhibitor)
– Digoxin (reduce dose by 50%)
– Statins
• Limit dose of simvastatin to 20mg
• Consider non CYP3A4 metabolized statins
– Warfarin (reduce dose by up to 50%)
– Target specific oral anticoagulants?
Audience Question
Which of the following oral anticoagulants
has/have a drug-nutrient interaction
I.
II.
III.
IV.
A.
B.
C.
D.
I and II
I and III
I, II, III
I, III, and IV
Warfarin
Rivaroxaban 10mg dose
Rivaroxaban 20mg dose
Dabigatran
Drug-nutrient interactions with
oral anticoagulants
Warfarin
•Green Leafy Vegetables
•Vitamin K
•Bioavailability is dose-dependent
Rivaroxaban •Doses > 10mg affected by food
•15-20mg doses should be taken
with evening meal
Dabigatran •Take with a full glass of water
Audience Question
Which of the following statements is true?
A.
B.
C.
Carvedilol does not have a significant drug-nutrient interaction
Vorapaxar and prasugrel BOTH have the same drug-disease
state interaction
Cilostazol does not have a drug-disease interaction with heart
failure
Select drug interactions with carvedilol
• Drug-nutrient
• Administer with food to reduce risk of
hypotension
• Food slows rate, but not extent, of absorption
• Drug-drug
• Digoxin trough concentrations increase by
about 15%
Audience Question
• Which of the following is correct?
1. Entresto is not associated with any drug-drug
interactions
2. Entresto could be administered with aliskiren
3. Entresto should not be administered to a
patient with ACE inhibitor angioedema
4. Entresto could be administered with
spironolactone
Selected drug-drug interactions with
Entresto (sacubitril, valsartan)
• Avoid combo with aliskiren especially in
diabetics
• Absolute contraindication in anyone with hx of
angioedema (ACE I or ARB or other)
• Concomitant use with K+sparing diuretics or K+
supplement can result in hyperkalemia
• Caution with NSAID use – risk worsening renal
fxn (sacubitril)
• Lithium toxicity observed (ARB)
Case Presentation
• 70 yo african american man seen on house call by NP and
consultant pharmacist
• PMH: hypertension, CHF, osteoarthritis hip, neuropathy,
depression, anxiety, BPH, gastritis
• CC: light headedness and worsening hip pain, feeling
depressed
• Exam: orthostatic hypotension, elevated pulse
• Meds: EC ASA, methadone, enalapril, furosemide,
pantoprazole, doxazosin, travoprost eye drops, sertraline
Case Presentation
• Prevention Magazine
– Herbal Medications can help conditions,
improve overall QOL
– St John Wart, Bilberry, Zing (gingko biloba,
ginseng etc), Hawthorne extract, CoQ10, Cataclear (bilberry, vitamins), Colon-Helper (aloe,
gentian, goldenseal, etc), Valerian, Saw
Palmetto
Cappuzzo K. Consultant Pharmacist 2006;11:911-915
Audience Response
Which of the following are potential drug-herb
interactions in this patient?
A) St John Wart – Methadone (decreased
activity)
B) St John Wart – SSRI (serotonin syndrome)
C) Ginkgo Biloba – ASA (platelet inhibition)
D) All of the above
Case Presentation
• At end of visit patient asked about whether
he could take Viagra to reduce stress on his
heart……..
• He had heard about it on the news………
Case Presentation
• 61 yo man w/ hx of hypercholesterolemia x
11 yrs, tx with multiple different statins (all
at 10mg dose) which was unsuccessful due
to muscle intolerance (w/in 1 week). Normal
CK, moderate LFT bumps. Patient drank 3
cups of green tea everyday “to reinforce his
health”.
Case Presentation
Prodrug
Active
Metabolite
Werba et al. Annals of Int Med 2008;149:286-288
Audience Response
The likely underlying mechanism for the green
tea – simvastatin interaction is
A) CYP3A4 induction
B) CYP3A4 inhibition
C) Unknown mechanism
Case Presentation
• DSB is a 42 yo police officer. He weighs 260 lbs, BP 143/92, TC
200, LDL 130mg/dl, glucose 105 mg/dl
• He takes a weight loss supplement (imported from Brazil) and loses
10 lbs
• Label: vitamin E, centella, senna, cascara, other “natural
ingredients”
• He undergoes routine, random drug screen
• He loses his job
NEJM 2009;361:1523-1525
Audience Response
• Which of the following could have
contributed to his losing his job?
1. “Natural Ingredient”
2. Cascara
3. Vitamin E
Natural Ingredient……..
AMPHETAMINE
Case Presentation
• 65yo wm with HTN hyperlipidemia and knee osteoarthritis
presents with chief complaint of fatigue, decreased exercise
tolerance and worsening bilateral leg swelling
• For 5 years he had been prescribed lisinopril, simvastatin and
meloxicam as needed for pain.
• He was traveling oversees, fell in the airport upon arrival and
experienced worsening knee pain during his vacation
• He ran out of the meloxicam he brought with him and bought
some diclofenac at the local drug store (OTC)
• Over the next 3 months his pain continues, his mobility is limited
and lisinopril dose was doubled to 20mg daily because his BP is
slowly rising.
Case Presentation
• Basic chemistry and UA reveal creatinine level of 3.51
mg/dl and BUN of 61 mg/dl (6 months prior 0.96 mg/dl, 18
mg/dl)
• Lisinopril and meloxicam / diclofenac held, BP monitored
• After 3 months, swelling and fatigue decreased, creatinine
2.17 mg/dl
• Amlodipine started and referred to nephrology for probably
NSAID induced nephropathy
Teaching Points
• NSAIDs – one of most commonly used drug classes
– ~19% of US adult population using at least one on a regular bases
• ~75% of US adult population have HTN
• NSAID use increases BP ~ 5 mm Hg (~14 mm Hg in those with HTN)
• NSAIDs increase aldosterone level
– render ACE inhibitors and ARBs less effective
– Combination of NSAIDs, ACE inhibitor and diuretic can increase risk of
acute kidney injury by 30%
• Need to individualize pain management
–
–
–
–
Physical therapy
Acetaminophen
Topical agents (capsaicin, diclofenac)
Monitor closely