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Polypharmacy Program - Drug-Disease Interactions Appropriateness Evaluation (MAE) tool

Drug-disease interactions (regardless of patient age)

Condition Interacting Drug(s) Potential Complication(s) Recommendation(s)

CHF Most calcium CCBs with negative inotropic • Most CCBs should be avoided channel blockers effects can worsen CHF in patients whenever possible in patients (CCBs) (except with reduced ejection fraction.1 with heart failure, even when ) used for the treatment of angina or hypertension.1 • Amlodipine is the only CCB to not adversely affect survival in CHF patients.1

CHF Class I/III • These drugs are known to • These antiarrhythmics are not antiarrhythmics adversely affect the clinical status recommended in CHF patients of patients with current or prior for the prevention of ventricular symptoms of heart failure and arrhythmias.1 reduced LVEF.1 • May consider or • Nearly all antiarrhythmics have dofetilide for patients with negative inotropic effects. The symptomatic arrhythmias.1 risk of serious arrhythmia is increased in CHF patients.1

Abbreviations: CHF — congestive heart failure. CCB — calcium channel blocker. LVEF — left ventricular ejection fraction. NSAID — non-steroidal anti-inflammatory drug. NYHA — New York Heart Association. TCA — . SSRI — selective reuptake inhibitor. SNRI — selective reuptake inhibitor. COPD — chronic obstructive pulmonary disease. BPH — benign prostatic hyperplasia. COX-2 — cyclooxygenase-2. CNS — central nervous system. MI – myocardial infarction.

OptumRx | optumrx.com Polypharmacy Program – Drug-Disease Interactions Medication Appropriateness Evaluation (MAE) tool

CHF Non-steroidal • NSAIDs are known to adversely NSAIDs should be used with anti-inflammatory affect the clinical status of patients caution or avoided in the CHF drugs (NSAIDs) with current or prior symptoms of population when possible.1 heart failure and reduced LVEF.1 • NSAIDs cause a blunted response to exogenous diuretics and may increase systemic vascular resistance.1

CHF Thiazolidinediones Fluid retention may occur with • Boxed warning: (e.g., pioglitazone, thiazolidinediones. This may lead to Thiazolidinediones are rosiglitazone) or exacerbate heart failure. The risk contraindicated in patients with is increased in patients concurrently NYHA functional class III-IV CHF. taking insulin.1 They should be used cautiously in any CHF class.1 • Patient should be monitored for new or increased CHF symptoms.1

CHF metformin Patients with unstable or • Due to the risk of developing acute CHF who are at risk of lactic acidosis, metformin should hypoperfusion and hypoxia are at be avoided in hospitalized patients increased risk of lactic acidosis.2 or those with unstable CHF.3 • Metformin may be used in patients with stable CHF if renal function is normal.3

CHF cilostazol • Cilostazol and several of its Contraindication: Cilostazol is metabolites are inhibitors of contraindicated in patients with phosphodiesterase III, resulting CHF of any severity.4 Avoid use in in ventricular tachycardia and this population. premature ventricular complexes.5 • Other drugs that inhibit phosphodiesterase III have caused death in patients with class III-IV CHF.5

History of NSAIDs • NSAIDs may increase the risk of Consider alternative therapies if MI cardiovascular thrombotic events, clinically appropriate or prescribing such as MI and stroke. Patients the lowest effective NSAID dose for who have had a prior MI may be the shortest duration possible to at an increased risk.18 minimize the risk.18

Abbreviations: CHF — congestive heart failure. CCB — calcium channel blocker. LVEF — left ventricular ejection fraction. NSAID — non-steroidal anti-inflammatory drug. NYHA — New York Heart Association. TCA — .. SSRI — selective serotonin reuptake inhibitor. SNRI — selective norepinephrine reuptake inhibitor. COPD — chronic obstructive pulmonary disease. BPH — benign prostatic hyperplasia. COX-2 — cyclooxygenase-2. CNS — central nervous system. MI – myocardial infarction.

2 OptumRx | optumrx.com Asthma or Non-selective Non-selective beta-blockers may • Contraindication: Most COPD beta-blockers cause bronchoconstriction by non-selective beta-blockers are (e.g., ) counteracting the bronchodilation contraindicated or should be produced by catecholamine avoided in patients with bronchial stimulation of beta-2 receptors.4,7 asthma, bronchospasm, or COPD.2,7 • Cardioselective beta-blockers (e.g., , ) or another class of antihypertensives (e.g., diuretics, angiotensin- converting enzyme inhibitors, angiotensin II receptor blockers) may be used cautiously.7,8

Parkinson’s Metoclopramide has Metoclopramide should be used disease antidopaminergic effects and with caution in patients with may exacerbate Parkinsonian- Parkinson’s disease.2 like symptoms, such as akinesia, tremors and cogwheel rigidity.5,6,9

Seizure or Bupropion may lower the • Contraindication: Bupropion is epilepsy threshold. The incidence of contraindicated in patients with increases at higher dosages.5,6 a seizure disorder and should be used with extreme caution in patients with a history of seizures or those with other predisposing factors for seizures.4 • Consider with lower risk for seizure, such as , , and SSRIs (e.g., ), as well as other alternatives for smoking cessation and/or weight loss if clinically appropriate.4,5

BPH - Select antimuscarinics with highly • Highly containing drugs anticholinergic properties may are not recommended for use in benztropine aggravate BPH symptoms and/or patients with BPH. mesylate lead to .5,6,10 • Topical (transdermal dicyclomine patch, topical gel) have less anticholinergic effects than oral formulations although caution oxybutynin is still advised when used in BPH patients.4,5

Abbreviations: CHF — congestive heart failure. CCB — calcium channel blocker. LVEF — left ventricular ejection fraction. NSAID — non-steroidal anti-inflammatory drug. NYHA — New York Heart Association. TCA — tricyclic antidepressant.. SSRI — selective serotonin reuptake inhibitor. SNRI — selective norepinephrine reuptake inhibitor. COPD — chronic obstructive pulmonary disease. BPH — benign prostatic hyperplasia. COX-2 — cyclooxygenase-2. CNS — central nervous system. MI – myocardial infarction.

3 Polypharmacy Program – Drug-Disease Interactions Medication Appropriateness Evaluation (MAE) tool

BPH Select TCAs have highly • Highly anticholinergic medications anticholinergic properties.11 are not recommended for use in Their use in patients with BPH may patients with BPH. aggravate BPH symptoms and/or • Alternative antidepressant lead to urinary retention.5,9 drugs with less anticholinergic activity include trazodone, nefazodone and the SSRIs (e.g., fluoxetine).4,5 Secondary amine TCAs (, , ) have the least amount of anticholinergic activity among the TCAs.11,12

BPH with highly Highly anticholinergic medications anticholinergic properties may are not recommended for use in aggravate BPH symptoms and/or patients with BPH. lead to urinary retention.5,6,10

BPH with highly • Highly anticholinergic medications anticholinergic properties may are not recommended for use in aggravate BPH symptoms and/or patients with BPH. lead to urinary retention.5,6,10 • Consider antihistamines with less anticholinergic activity, such as and .4,5

BPH with highly Highly anticholinergic medications anticholinergic properties may are not recommended for use in aggravate BPH symptoms and/or patients with BPH. lead to urinary retention.5,6,10

Gallbladder Fibric acid derivatives Fibric acid derivatives may increase • Contraindication: Fibric acid disease cholesterol into the derivatives are contraindicated bile, thereby increasing the risk of in patients with gallbladder developing gallstones.4 disease.4 • In patients with pre-existing gallstones, consider the use of other agents for the treatment of hypertriglyceridemia.2

Gout Thiazides and Thiazide diuretics decrease uric For patients with frequent gout thiazide-like diuretics acid excretion, thus increasing the attacks, consider another class of risk of precipitating gout attacks or antihypertensives (e.g., angiotensin- developing hyperuricemia in certain converting enzyme inhibitors, patients.2,5 angiotensin II receptor blockers).2

Abbreviations: CHF — congestive heart failure. CCB — calcium channel blocker. LVEF — left ventricular ejection fraction. NSAID — non-steroidal anti-inflammatory drug. NYHA — New York Heart Association. TCA — tricyclic antidepressant.. SSRI — selective serotonin reuptake inhibitor. SNRI — selective norepinephrine reuptake inhibitor. COPD — chronic obstructive pulmonary disease. BPH — benign prostatic hyperplasia. COX-2 — cyclooxygenase-2. CNS — central nervous system. MI – myocardial infarction.

4 OptumRx | optumrx.com Glaucoma atropine- Select antimuscarinics with highly Highly anticholinergic medications (closed- containing drugs anticholinergic properties may are not recommended for use angle) benztropine lead to ocular hypertensive crisis in patients with closed-angle mesylate in patients with closed-angle glaucoma.13,14 glaucoma.5,9,10,19 dicyclomine hyoscyamine oxybutynin trospium

Glaucoma amitriptyline TCAs have highly anticholinergic • Highly anticholinergic (closed- clomipramine properties.11 Use in patients with medications are not angle) closed-angle glaucoma may lead recommended for use in patients doxepin to ocular hypertensive crisis.5,9,19 with closed-angle glaucoma.13,14 imipramine • Alternative antidepressant trimipramine drugs with less anticholinergic activity include trazodone, nefazodone and the SSRIs (e.g., fluoxetine).4,5 Secondary amine TCAs (nortriptyline, protriptyline, desipramine) have the least amount of anticholinergic activity among the TCAs.11,12

Glaucoma chlorpromazine Phenothiazines with highly Highly anticholinergic medications (closed- perphenazine anticholinergic properties may are not recommended for use angle) lead to ocular hypertensive crisis in patients with closed-angle in patients with closed-angle glaucoma.13,14 thioridazine glaucoma.5,9,10,19

Glaucoma hydroxyzine Antihistamines with highly • Highly anticholinergic (closed- meclizine anticholinergic properties may medications are not angle) lead to ocular hypertensive crisis recommended for use in patients in patients with closed-angle with closed-angle glaucoma. glaucoma.5,9,10,19 • Consider antihistamines with less anticholinergic activity, such as loratadine and fexofenadine.4,5

Glaucoma loxapine Antipsychotics with highly Highly anticholinergic medications (closed- anticholinergic properties may lead to are not recommended for use angle) ocular hypertensive crisis in patients in patients with closed-angle with closed-angle glaucoma.5,10 glaucoma.13,14

Mechanical dabigatran Dabigatran is associated with Contraindication: Dabigatran is heart valve increased thromboembolic events contraindicated in patients with (e.g., stroke, transient ischemic mechanical heart valves.4,5,20 attack, myocardial infarction) and bleeding in patients with mechanical heart valves.4,5,20 Abbreviations: CHF — congestive heart failure. CCB — calcium channel blocker. LVEF — left ventricular ejection fraction. NSAID — non-steroidal anti-inflammatory drug. NYHA — New York Heart Association. TCA — tricyclic antidepressant.. SSRI — selective serotonin reuptake inhibitor. SNRI — selective norepinephrine reuptake inhibitor. COPD — chronic obstructive pulmonary disease. BPH — benign prostatic hyperplasia. COX-2 — cyclooxygenase-2. CNS — central nervous system. MI – myocardial infarction.

5 Polypharmacy Program – Drug-Disease Interactions Medication Appropriateness Evaluation (MAE) tool

Drug-disease interactions in patients > 65 years of age

Condition Interacting Drug Potential Complication(s) Recommendation(s)

Chronic COX-2 inhibitors NSAIDs and COX-2 inhibitors may Avoid use of NSAIDs or COX-2 (e.g., celecoxib) lead to a reduction in renal blood inhibitors in elderly patients with disease NSAIDs flow, suboptimal renal perfusion chronic kidney disease. Consider (except aspirin) and potential renal failure.5,15 alternative therapies if possible. If an NSAID or COX-2 inhibitor must be prescribed, use with caution and monitor renal function.

Dementia prochlorperazine antiemetic Use with caution in elderly medications with anticholinergic patients with history of dementia. properties have been associated Consider alternate therapies with cognitive impairment in if clinically appropriate. elderly patients. The concomitant use of anticholinergic drugs may reduce the effectiveness of drugs used to treat dementia, such as inhibitors.5,6,15,16

Dementia Tricyclic TCAs have been associated with • Use with caution in elderly antidepressants cognitive impairment in elderly patients with history of dementia. patients. The concomitant use Consider alternate therapies if of anticholinergic drugs may clinically appropriate. reduce the effectiveness of drugs • Alternative antidepressant used to treat dementia, such as drugs with less anticholinergic cholinesterase inhibitors.5,6,15,16 activity include trazodone, nefazodone and the SSRIs (e.g., fluoxetine).4,5 Secondary amine TCAs (nortriptyline, protriptyline, desipramine) have the least amount of anticholinergic activity among the TCAs.11,12

Dementia Antihistamines with anticholinergic • Use with caution in elderly properties have been associated patients with history of dementia. with cognitive impairment in Consider alternate therapies if chlorpheniramine elderly patients. The concomitant clinically appropriate. use of anticholinergic drugs may • Consider antihistamines with less reduce the effectiveness of drugs anticholinergic activity, such as used to treat dementia, such as and fexofenadine.4,5 5,6,15 cholinesterase inhibitors. hydroxyzine loratadine meclizine

Abbreviations: CHF — congestive heart failure. CCB — calcium channel blocker. LVEF — left ventricular ejection fraction. NSAID — non-steroidal anti-inflammatory drug. NYHA — New York Heart Association. TCA — tricyclic antidepressant.. SSRI — selective serotonin reuptake inhibitor. SNRI — selective norepinephrine reuptake inhibitor. COPD — chronic obstructive pulmonary disease. BPH — benign prostatic hyperplasia. COX-2 — cyclooxygenase-2. CNS — central nervous system. MI – myocardial infarction.

6 OptumRx | optumrx.com Dementia benztropine Antiparkinson medications with Use with caution in elderly patients anticholinergic properties have been with history of dementia. Consider associated with cognitive impairment alternate therapies if clinically in elderly patients. The concomitant appropriate. use of anticholinergic drugs may reduce the effectiveness of drugs used to treat dementia, such as cholinesterase inhibitors.5,6,15,16

Dementia atropine- medications with Use with caution in elderly patients containing drugs anticholinergic properties have been with history of dementia. Consider belladonna associated with cognitive impairment alternate therapies if clinically in elderly patients. The concomitant appropriate. dicyclomine use of anticholinergic drugs may reduce the effectiveness of drugs hyoscyamine- used to treat dementia, such as containing drugs cholinesterase inhibitors.5,6,15,16 propantheline

Dementia Urinary antispasmodic medications • Use with caution in elderly fesoterodine with anticholinergic properties patients with history of dementia. have been associated with Consider alternate therapies if cognitive impairment in elderly clinically appropriate. oxybutynin patients. The concomitant use • Topical oxybutynin (transdermal of anticholinergic drugs may patch, topical gel) have less tolterodine reduce the effectiveness of drugs anticholinergic effects than oral trospium used to treat dementia, such as formulations, although caution cholinesterase inhibitors.5,6,15,16 is still advised for use in dementia patients.4,5

Dementia carisoprodol Skeletal muscle relaxants with Use with caution in elderly patients anticholinergic properties have been with history of dementia. Consider associated with cognitive impairment alternate therapies if clinically in elderly patients. The concomitant appropriate. use of anticholinergic drugs may reduce the effectiveness of drugs used to treat dementia, such as cholinesterase inhibitors.5,6,15,16

Dementia H2-receptor antagonists Use with caution in elderly patients have been associated with with history of dementia. Consider cognitive impairment in elderly alternate therapies if clinically patients and may exacerbate appropriate. dementia5,6,15,17

Abbreviations: CHF — congestive heart failure. CCB — calcium channel blocker. LVEF — left ventricular ejection fraction. NSAID — non-steroidal anti-inflammatory drug. NYHA — New York Heart Association. TCA — tricyclic antidepressant.. SSRI — selective serotonin reuptake inhibitor. SNRI — selective norepinephrine reuptake inhibitor. COPD — chronic obstructive pulmonary disease. BPH — benign prostatic hyperplasia. COX-2 — cyclooxygenase-2. CNS — central nervous system. MI – myocardial infarction.

7 Polypharmacy Program – Drug-Disease Interactions Medication Appropriateness Evaluation (MAE) tool

Dementia Select nonbenzodiazepine Use with caution in elderly patients hypnotics have been associated with history of dementia. Consider with cognitive impairment in alternate therapies if clinically elderly patients.5,6,15,17 appropriate.

Dementia alprazolam have been Use with caution in elderly patients chlordiazepoxide associated with cognitive with history of dementia. Consider clonazepam impairment in elderly patients and alternate therapies if clinically clorazepate may exacerbate dementia 5,6,15,17 appropriate. diazepam estazolam flurazepam lorazepam midazolam oxazepam quazepam temazepam triazolam

Dementia • Antipsychotics with • Boxed warning: Antipsychotics anticholinergic properties are associated with increased have been associated with mortality when used in chlorpromazine cognitive impairment in elderly patients with dementia-related patients. The concomitant use psychosis.16 of anticholinergic drugs may • Use with caution in elderly reduce the effectiveness of drugs patients with history of dementia. used to treat dementia, such as Consider alternate therapies if loxapine cholinesterase inhibitors.5,6,15 clinically appropriate. perphenazine thioridazine thiothixene trifluoperazine

Abbreviations: CHF — congestive heart failure. CCB — calcium channel blocker. LVEF — left ventricular ejection fraction. NSAID — non-steroidal anti-inflammatory drug. NYHA — New York Heart Association. TCA — tricyclic antidepressant.. SSRI — selective serotonin reuptake inhibitor. SNRI — selective norepinephrine reuptake inhibitor. COPD — chronic obstructive pulmonary disease. BPH — benign prostatic hyperplasia. COX-2 — cyclooxygenase-2. CNS — central nervous system. MI – myocardial infarction.

8 OptumRx | optumrx.com History alprazolam Benzodiazepines may increase Use with caution in elderly patients of falls chlordiazepoxide the risk of cognitive impairment, with history of falls. Caution delirium, dizziness and syncope. patients about the potential for clonazepam This may increase the risk for falls in impaired motor function and clorazepate susceptible individuals, especially in increased risk for falls. diazepam patients with a history of falls.5,6,15,17 estazolam flurazepam lorazepam midazolam oxazepam quazepam temazepam triazolam

History may increase the Use with caution in elderly patients of falls clobazam risk of confusion, disturbances of with history of falls. Caution divalproex coordination, drowsiness, dizziness patients about the potential for ethosuximide and syncope. This may increase impaired motor function and ethotoin the risk for falls in susceptible increased risk for falls. For new- ezogabine individuals, especially in patients onset epilepsy, newer agents are felbamate with a history of falls.5,6,15,17 preferred (e.g., lamotrigine and fosphenytoin levetiracetam). For neuropathic gabapentin pain, consider an SNRI, gabapentin, lacosamide pregabalin, topical capsaicin and lamotrigine lidocaine patch.6 levetiracetam methsuximide pregabalin primidone rufinamide tiagabine valproic acid vigabatrin zonisamide

Abbreviations: CHF — congestive heart failure. CCB — calcium channel blocker. LVEF — left ventricular ejection fraction. NSAID — non-steroidal anti-inflammatory drug. NYHA — New York Heart Association. TCA — tricyclic antidepressant.. SSRI — selective serotonin reuptake inhibitor. SNRI — selective norepinephrine reuptake inhibitor. COPD — chronic obstructive pulmonary disease. BPH — benign prostatic hyperplasia. COX-2 — cyclooxygenase-2. CNS — central nervous system. MI – myocardial infarction.

9 Polypharmacy Program – Drug-Disease Interactions Medication Appropriateness Evaluation (MAE) tool

History Selective serotonin SSRIs may increase the risk of Use with caution in elderly patients of falls reuptake inhibitors ataxia, impaired psychomotor with history of falls. Caution (SSRIs) functions, and syncope. This patients about the potential for may increase the risk for falls in impaired motor function and susceptible individuals, especially in increased risk for falls. patients with a history of falls.5,6,15

History aripiprazole Select drugs may Use with caution in elderly of falls asenapine cause orthostatic , patients with history of falls. chlorpromazine dizziness and syncope. This Caution patients about the risk of clozapine may increase the risk for falls in orthostatic hypotension, dizziness fluphenazine susceptible individuals, especially and syncope. haloperidol in patients with a history of iloperidone falls.5,6,15,17 loxapine lurasidone molindone olanzapine paliperidone perphenazine pimozide quetiapine risperidone thioridazine thiothixene trifluoperazine ziprasidone

History prochlorperazine Select antiemetics may cause Use with caution in elderly patients of falls promethazine drowsiness, including CNS with history of falls. Consider depression and impaired motor alternative therapies if clinically skills. They pose a risk for falls in appropriate. older patients, especially those with a history of hip fractures.4,5,6,15

Abbreviations: CHF — congestive heart failure. CCB — calcium channel blocker. LVEF — left ventricular ejection fraction. NSAID — non-steroidal anti-inflammatory drug. NYHA — New York Heart Association. TCA — tricyclic antidepressant.. SSRI — selective serotonin reuptake inhibitor. SNRI — selective norepinephrine reuptake inhibitor. COPD — chronic obstructive pulmonary disease. BPH — benign prostatic hyperplasia. COX-2 — cyclooxygenase-2. CNS — central nervous system. MI – myocardial infarction.

10 OptumRx | optumrx.com History Tricyclic TCAs may impair motor skills • Use with caution in elderly of falls antidepressants and pose a risk for falls in older patients with a history of falls. patients, especially those with a Consider antidepressants with history of hip fractures.4,5,6,15 less anticholinergic activity, if clinically appropriate.4,5,6,15 • Alternative antidepressant drugs include SNRIs and bupropion. Alternatives for neuropathic pain include an SNRI, gabapentin, pregabalin, topical capsaicin and lidocaine patch.6

History Nonbenzodiazepine hypnotics can Consider alternative therapies of falls impair motor function and pose an if clinically appropriate. If a increased risk for falls, especially nonbenzodiazepine hypnotic must zolpidem in older patients with a history of be prescribed to elderly patients falls.4,5,6,15 with history of falls, caution them about the potential for impaired motor function and increased risk for falls.

History canagliflozin Canagliflozin can increase the risk Consider factors that contribute of falls of bone fractures and falls, and has to fracture risk and alternative been linked to decreases in bone therapies if clinically appropriate. If mineral density of the hip and canagliflozin must be prescribed to lower spine.21,22 elderly patients with history of falls, caution them about the increased risk of bone fractures and falls.

Ulcer/ flurbiprofen Nonsteroidal anti-inflammatory It is recommended to discontinue Gastritis indomethacin drugs (NSAIDs), particularly those the high GI-risk NSAID, switch ketoprofen with high gastrointestinal (GI) to an alternate (e.g. ketorolac toxicity, affect gastric acid secretion acetaminophen), or add a proton piroxicam leading to ulceration.23,24 pump inhibitor.23,24

Abbreviations: CHF — congestive heart failure. CCB — calcium channel blocker. LVEF — left ventricular ejection fraction. NSAID — non-steroidal anti-inflammatory drug. NYHA — New York Heart Association. TCA — tricyclic antidepressant.. SSRI — selective serotonin reuptake inhibitor. SNRI — selective norepinephrine reuptake inhibitor. COPD — chronic obstructive pulmonary disease. BPH — benign prostatic hyperplasia. COX-2 — cyclooxygenase-2. CNS — central nervous system. MI – myocardial infarction.

11 Polypharmacy Program – Drug-Disease Interactions Medication Appropriateness Evaluation (MAE) tool

References

1. Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the ACCF/AHA Task Force on Practice Guidelines. Circulation. 2013;128:e240-e327 2. Micromedex Healthcare Series. http://www.micromedexsolutions.com/home/dispatch. Accessed December 4, 2015. 3. American Diabetes Association. Standards of medical care in diabetes - 2015. Diabetes Care. 2015;38(S1):S11-S93. 4. Facts & Comparisons [database online]. http://online.factsandcomparisons.com. Accessed December 4, 2015. 5. Clinical Pharmacology. http://www.clinicalpharmacology-ip.com/Default.aspx. December 4, 2015. 6. American Geriatrics Society 2015 Beers Criteria Update Expert Panel (2015). American Geriatrics Society 2015 Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. J Am Geriatr Soc. Doi: 10.1111/jgs. 13702. 7. Expert panel report 3 (ERP–3) full report 2007: Guidelines for the diagnosis and management of asthma. National Heart, Lung, and Blood Institute. http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf. December 4, 2013. 8. Salpeter S, Ormiston T, Salpeter E. Cardioselective beta-blockers for reversible airway disease. Cochrane Database Syst Rev. 2002;(4):CD002992. 9. Lindblad CI, Hanlon JT, Gross CR, et al. Clinically important drug-disease interactions and their prevalence in older adults. Clin Ther. 2006;28(8):1133-43. 10. Rudolph JL, Salow MJ, Angelini MC, McGlinchey RE. The anticholinergic risk scale and anticholinergic adverse effects in older persons. Arch Int Med. 2008;168(5):508-513. 11. DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey ML. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. New York, NY: McGraw-Hill; 2011. 12. Antidepressant agents: comparison of usual adult dosage, mechanism of action, and adverse effects. Lexi-Comp OnlineTM. Lexi-Drugs OnlineTM, Hudson, Ohio: Lexi-Comp, Inc.; December 4, 2015. 13. PL Detail-Document, Drugs That Cause or Exacerbate Glaucoma. Pharmacist’s Letter/Prescriber’s Letter. November 2011. 14. Razeghinejad, MR, Myers JS, Katz LJ. Iatrogenic glaucoma secondary to medications. Am J Med. 2011;124(1):20-5. 15. National Committee for Quality Assurance (NCQA). HEDIS 2016 Technical Specifications, Volume 2. Washington DC:NCQA;2015:217-221. 16. PL Detail-Document, Drugs to Avoid in Patients with Dementia. Pharmacist’s Letter/Prescriber’s Letter. May 2008. 17. Potentially inappropriate medication use in older adults due to drug-disease or drug-syndrome interactions. http:// www.healthinaging.org/resources/resource:potentially-inappropriate-medication-use-in-older-adults/. Accessed December 4, 2015. 18. US Food and Drug Administration (FDA). Drug Safety Communication: FDA strengthens warning that non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) can cause heart attacks or strokes. Available at:http://www.fda.gov/ downloads/Drugs/DrugSafety/UCM453941.pdf. Accessed December 4, 2015. 19. Aspinall S, Sevick MA, Donohue J et al. Medication errors in older adults: a review of recent publications. Am J Geriatr Pharmacother. 2007 Mar;5(1):75-84. 20. Eikelboom J, Connolly S, Brueckmann M, et al. Dabigatran versus warfarin in patients with mechanical heart valves. New England Journal of Medicine. 2013 Sep:369(13):1206-1214. 21. US Food and Drug Administration (FDA). Drug Safety Communication: FDA revises label of diabetes drug canagliflozin (Invokana, Invokamet) to include updates on bone fracture risk and new information on decreased bone mineral density. Available at: http://www.fda.gov/downloads/Drugs/DrugSafety/UCM461790.pdf. Accessed November 2, 2015. 22. Invokana® prescribing information. Titusville, NJ: Janssen Pharmaceuticals, Inc; 2015. 23. Hunt RH, Yuan Y. Acid-NSAID/aspirin interaction in peptic ulcer disease. Dig Dis. 2011;29(5):465-8. 24. American International Health Alliance. Protocol for Diagnosis and Treatment of Peptic Ulcer in Adults. Washington, DC;2002:1-17.

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