POTENTIALLY INAPPROPRIATE MEDICATIONS FOR THE GERIATRIC

POPULATIONIN THE PRACTICE OF DENTISTRY

Arwa Farag, BDS, DMSc, DipABOM, DipABOP, FRCSEdApril 6th, 2017

DISCLOSURES

GRANT/RESEARCH SUPPORT: NOVARTIS, GLAXOSMITHKLINE, BIOGEN

IDEC, PROCTER & GAMBEL, & PRIVO

I WILL BE DISCUSSING OFF-LABEL USES OF THE FOLLOWING FDA APPROVED

MEDICATIONS:

DOXEPIN, GABAPENTIN, PREGABALIN, DULOXETINE& MILNACIPRAN

CONSUMPTION OF MEDICATIONS IN GERIATRIC POPULATION

Geriatrics adult population aged 65 & above

Represent 13% of the US population but consume

40% of prescription drugs 35% of all OTC drugs

Task force on Aging Research: Meds & Errors. https://www.ascp.com/sites/default/files/file_Task_Force_2009_FINAL-3.pdf Accessed June 15,2015

http://www.cdc.gov/nchs/data/databriefs/db42.htm

Percentage of Prescription Medications Consumption in the US, by Age (CDC; 2007-2008)

INCREASED RISK FOR ADE & DRUG INTERACTIONS

Co-existence of health-related comorbidities

Polypharmacy

Pharmacokinetic activities diminished GI absorption, drug distribution, hepatic metabolism & renal clearance

Pharmacodynamic functions compromised drug-receptor interaction, signal transduction, protein transcription &

cellular response

Akhtar S, Ramani R. Anesthesiol Clin 2015;33(3):457-69Wehling M. J Am Geriatr Soc 2011;59(2):376-7

AS DENTISTS, WHY SHOULD WE CARE?

ARE THERE GUIDELINES?

The Centers for Medicare/Medicaid Services (CMS) uses the National Committee for Quality

Assurance (NCQA) & Pharmacy Quality Alliance (PQA)

Evaluate the quality of care provided to their beneficiaries

Monitor the use of high-risk medications in the elderly

Both are based on the AGS Beers Criteria

http://www.ncqa.org/hedis-quality-measurement/hedis-measures/hedis-2016/hedis-2016-ndc-license/hedis-2016-final-ndc-lists

http://pqaalliance.org/images/uploads/files/2017_HRM.pdf

DESIGNATIONS OF QUALITY OF EVIDENCE

Quality of Evidence CriteriaHigh Evidence 2 higher-quality RCT or consistent observational studies

with no methodological flaws

Moderate Evidence 1 higher-quality RCT2 higher-quality RCT with some inconsistency 2 consistent observational studies with no flaws

Low Evidence Major inconsistenciesSignificant methodological flaws

American Geriatrics Society Beers Criteria Update Expert P. J Am Geriatr Soc 2015;63(11):2227-46

DESIGNATIONS OF STRENGTH OF RECOMMENDATION

Strength of Recommendation

Rational

Strong Harms, risks & adverse events clearly outweigh benefits

Weak Inadequate evidence to determine net harms, adverse events & risks

American Geriatrics Society Beers Criteria Update Expert P. J Am Geriatr Soc 2015;63(11):2227-46

TRICYCLIC ANTIDEPRESSANTS

TRICYCLIC ANTIDEPRESSANTSIndication Depression, anxiety disorders, PTSD, & panic attacks Chronic neuropathic pain

Amitriptyline, nortriptyline, doxepin & imipramine

In the H & N region Post-herpetic neuropathy Persistent dento-alveolar pain (PDAP) Burning mouth syndrome

Attal N, et al. Eur J Neurol 2010;17(9):1113-e88Finnerup NB,et al. Pain 2005;118(3):289-305List T, et al. J Orofac Pain 2003;17(4):301-10

http://pharmacologycorner.com/differences-between-tricyclic-antidepressants-and-selective-serotonin-norepinephrine-reuptake-inhibitors-mechanism-of-action/

WHY NOT SUITABLE FOR GERIATRICS? Hyposalivation Constipation Urine retention

(-) Muscarinic receptors

Sedation Hypotension

(-) H1 histamine & 1-adrenergic receptors

Muscle weakness Cognitive impairment Cardiotoxicity

(-) Na+ & Ca++ channels

Hepatotoxicity Drug interactionCYP450

Gillman PK. Br J Pharmacol 2007;151(6):737-48Christensen P, Thomsen HY, Pedersen OL, et al. Psychopharmacology (Berl) 1985;87(2):212-5

TRICYCLIC ANTIDEPRESSANTS

Beers Criteria

STOPP List

AvoidEvidence HighRecomdStrong

Coupland C, et al.. BMJ 2011;343:d4551Nelson JC, Devanand DP. J Am Geriatr Soc 2011;59(4):577-85

Scharf M, et al. J Clin Psychiatry 2008;69(10):1557-64

ALTERNATIVESMedication Indication Precautions

Doxepin BMS & PHN Max 6 mg/day

Gabapentin TN, PHN, PDAP & BMS Moderate* & severe renal impairment (RI) 700 mg/day

Pregabalin TN, PHN, PDAP & BMS Moderate* RI 75 mg/daySevere RI 25-50 mg/day

Duloxetine BMS & PDAP Moderate* RI 60 mg/daySevere* RI avoid all SNRIs

Milnacipran BMS & PDAP Moderate* RI 100 mg/daySevere* RI avoid all SNRIs

Topical capsaicin PHN & BMS Intraoral concentration 0.01%-0.025% combined with 2%-5% lidocaine

* Moderate renal impairment = eGFR of 30-59 mL/min Severe renal impairment = eGFR of 15-29 mL/min

BENZODIAZEPINES

BENZODIAZEPINES

Indications Sedative, hypnotic, anticonvulsant & anxiolytic

Anxiety disorders, PAs, muscle spasms, seizures & insomnias

In the H & N region BMS, PDAP & some TMDs

Clonazepam & sometimes diazepam

Heckmann SM, Kirchner E, Grushka M, Wichmann MG, Hummel T. Laryngoscope 2012;122(4):813-6Gremeau-Richard C, Woda A, Navez ML, et al. Pain 2004;108(1-2):51-7

Martin WJ, & Forouzanfar T. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2011;111(5):627-33

http://intranet.tdmu.edu.ua/data/kafedra/internal/pharmakologia/classes_stud/en/pharm/prov_pharm/ptn/Pharmacology/3%20year/09%20General%20CNS%20depressants.htm

BENZODIAZEPINES

Beers Criteria

STOPP List

AvoidEvidenceModerate

Recomd Strong

llain H, Bentue-Ferrer D, Polard E, Akwa Y, Patat A. Drugs Aging 2005;22(9):749-65Finkle WD, Der JS, Greenland S, et al. J Am Geriatr Soc 2011;59(10):1883-90

Paterniti S, Dufouil C, Alperovitch. J Clin Psychopharmacol 2002;22(3):285-93

WHY NOT SUITABLE FOR GERIATRICS?

Increased susceptibility to drug interaction Increased susceptibility to AEs:

cognitive impairment, dizziness, delirium, fatigue, falls, & mind cloudiness

WHY? CYP3A4 interactions long-acting agents:

clonazepam T 21-70 hours diazepam T 19-60 hours

Berlin A, Dahlstrom H. Eur J Clin Pharmacol 1975;9(2-3):155-9Cloyd JC, Lalonde RL, Beniak TE, Novack GD. Epilepsia 1998;39(5):520-6

Kaplan SA, Jack ML, Alexander K, Weinfeld RE. J Pharm Sci 1973;62(11):1789-96 Riss J, Cloyd J, Gates J, Collins S. Acta Neurol Scand 2008;118(2):69-86

IMPACT OF MEDICATION CLASSES ON FALLS IN GERIATRICS

Drug class Odds ratio 95% CIAntihypertensive agents 1.24 1.011.50Diuretics 1.07 1.011.14 blockers 1.01 0.861.17Sedatives and hypnotics 1.47 1.351.62

Neuroleptics/antipsychotics 1.59 1.371.83

Antidepressants 1.68 1.471.91Benzodiazepines 1.57 1.431.72Narcotics 0.96 0.781.18

Woolcott J., Richardson K., Wiens M., Patel B., Marin J., Khan K., et al. . (2009. Arch Intern Med 169: 19521960

https://www.drugabuse.gov/related-topics/trends-statistics/overdose-death-rates

ALTERNATIVES

Moderate renal impairment = creatinine clearance of 30-59 mL/min* Severe renal impairment = creatinine clearance of 15-29 mL/min

Medication Indication Precautions

Doxepin BMS & PHN Max 6 mg/day

Gabapentin PHN, PDAP & BMS Moderate* & severe RI 700 mg/day

Pregabalin PHN, PDAP & BMS Moderate* RI 75 mg/daySevere RI 25-50 mg/day

Duloxetine BMS & PDAP Moderate* RI 60 mg/daySevere* RI avoid all SNRIs

Milnacipran BMS & PDAP Moderate* RI 100 mg/daySevere* RI avoid all SNRIs

Topical capsaicin

PHN & BMS Intraoral concentration 0.01%-0.025% combined with 2%-5% lidocaine

SKELETAL MUSCLE RELAXANTS

SKELETAL MUSCLE RELAXANTS

Indication in the H & N region Regional myofascial pain & myospasm

Tension type headache & tardive dyskinesia

Cyclobenzaprine, carisoprodol, metaxalone & methocarbamol

Mechanism of action Incompletely elucidated CNS conductivity (brain stem & spinal cord)

cyclobenzaprine inhibit alpha motor neurons activity + TCA

Katzung, Bertram G., Susan B. Masters, and Anthony J. Trevor. 2012. Basic & clinical pharmacology. New York: McGraw-Hill Medical

WHY NOT SUITABLE FOR GERIATRICS? Cognitive impairment Sedation Falls & fractures

CNS depression

Cardiotoxicity Hyposalivation Blurred vision

Anticholinergic/TCA-like

Average of 50 hours (cyclobenzaprine)Prolonged T1/2

Hepatotoxicity Drug interactionCYP450 (1A2 & 3A4)

SAMHSA. Choice: Current Reviews for Academic Libraries 2011;49(3):545-45Witenko C, Moorman-Li R, Motycka C, et al. P T. 2014;39(6):427-35

Dillon C, Paulose-Ram R, Hirsch R, Gu QP. (NHANES III). Spine 2004;29(8):892-96

Annually, 15% (300,000) of muscle relaxants prescribed in the US are given to patients over the age of 65

MS relaxants are associated with a 50% increased risk of ADEs majority related to CNS depression

& sedation [RR=2.04 (95% CI, 1.233.37)]

SKELETAL MUSCLE RELAXANTS

Beers Criteria

STOPP List

AvoidEvidence Moderate

Recomd Strong

Rudolph JL, Salow MJ, Angelini MC, McGlinchey RE. Arch Intern Med 2008;168(5):508-13American Geriatrics Society Beers Criteria Update Expert P. J Am Geriatr Soc 2015;63(11):2227-46

- Uncovering & addressing the underlying problem

Depression, anxiety, posture, parafunctional movements

- Conservative interventional modalities

Posture adjustment, physical therapy, passive & active muscle stretching exercises, oral appliance therapy, heat or cold application, low-level laser therapy, trigger point injections, acupuncture, & cognitive behavioral therapy

ALTERNATIVES

Alexandra Martin, et al. Arch Intern Med. 2006;166(10):1092-1097Christian JB, et al. Consult Pharm 2004;19:1011-28

ALTERNATIVELioresal Agonist of GABA-B receptor

Antagonist of neuronal Na+ channels

Dosage

Start at 5 mg TID

Increase gradually to max 40 mg/day*

Heetla HW, et al. Arch Phys Med Rehabil 2014;95(11):2199-206Zakrzewska JM. Expert Opin Pharmacother 2010;11(8):1239-54

Sommer C.. Schmerz 2002;16(5):381-8List T, Axelsson S. J Oral Rehabil 2010;37(6):430-51

Nicol CF. Headache 1969;9(1):54-7

Effectiveness Moderate effectiveness in regional

myofascial pain

Second-line therapy for refractory TN

Less side effects Minimal uptake across the BBB

Limited CYP450 interactions

Anticonvulsants

ANTICONVULSANTSIndication in the H & N region Trigeminal neuralgia Glossopharyngeal neuralgia & PHN (moderate success) PDAP (limited success)

Carbamazepine & oxcarbazepine

Mechanism of action Blocks voltage activated Na+ channels

Nicol CF. Headache 1969;9(1):54-7Campbell FG, Graham JG, Zilkha KJ. J Neurol Neurosurg Psychiatry 1966;29(3):265-7

Martin WJ, Forouzanfar T. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2011;111(5):627-33

WHY NOT SUITABLE FOR GERIATRICS?

Drowsiness Blurred vision Ataxia, falls & fractures

CNS depression

Hepatotoxicity Drug interactionCYP450

Oxcarbazapine Hyponatremia Carbamazepine agranulocytosis &

aplastic anemiaOther ADE

Gomez-Arguelles JM, et al. J. Clinical Neuroscience 2008;15(5):516-19Dong X, Leppik IE, White J, Rarick J. Neurology 2005;65(12):1976-8

Liamis G, Milionis H, Elisaf M. Am J Kidney Dis 2008;52(1):144-53

ANTICONVULSANTS

Beers Criteria

STOPP List

AvoidEvidence HighRecomdStrong

Shastry CS, et al. BJ. Indian J Pharmacol 2013;45(2):121-5Dong X, Leppik IE, White J, Rarick J. Neurology 2005;65(12):1976-8

Liamis G, Milionis H, Elisaf M. Am J Kidney Dis 2008;52(1):144-53

Safety & tolerability carbamazepine was associated with:Early onset of ADE, higher discontinuation rate & higher risk

of serious ADE

ALTERNATIVES

* Moderate renal impairment = creatinine clearance of 30-59 mL/min Severe renal impairment = creatinine clearance of 15-29 mL/min

Medication Indication Precautions

Doxepin PHN Max 6 mg/dayGabapentin TN, PHN Moderate* & severe RI 700 mg/day

Pregabalin TN, PHN Moderate* RI 75 mg/daySevere RI 25-50 mg/day

Lioresal Refractory TN Moderate* & severe RI 15 mg/day

Topical capsaicin PHN Intraoral concentration 0.01%-0.025% combined with 2%-5% lidocaine

LONG-TERM USE OF NSAIDS

NSAIDSIndications in Dentistry

- Odontogenic infections, traumas or invasive dental procedures

Ibuprofen, ketoprofen, meloxicam, piroxicam & nabumetone

- Acute TMJ pain symptoms & some chronic myofascial pain

Naproxen & diclofenac

- Chronic paroxysmal hemicrania and hemicrania continua

Indomethacin

Scrivani SJ, David A. Keith DA, Kaban LB. N Engl J Med 2008; 359:2693-2705Dodick DW et al, Curr Pain Headache Rep. 2004 Feb;8(1):19-26

WHY NOT SUITABLE FOR GERIATRICS?

Renal dysfunction GI ulcers GI bleeding

Cox1 inhibition

Hypertension Cardiovascular events

TXA2mediated vasoconstriction

Smalley WE, Ray WA, Daugherty JR et al. Am J Epidemiol. 1995, 141:539545Komhoff M, Grone HJ, Klein T, Seyberth HW, Nusing RM. Am J Physiol. 1997,272:F460F468

Mukherjee D, Nissen SE, Topol E. JAMA, 2001, 286:954959 Solomon DH, Schneeweiss S, Levin R, Avorn J. Hypertension, 2004; 44:140145

The use of non-selective NSAIDs & selective COX 2 NSAIDs was associated with 40% & 70% increase in

relative risk of atrial fibrillation or flutter

LONG-TERM NSAIDS

Beers Criteria

STOPP List

Avoid Chronic Use

Evidence ModerateRecom Strong

Shastry CS, et al. BJ. Indian J Pharmacol 2013;45(2):121-5Dong X, Leppik IE, White J, Rarick J. Neurology 2005;65(12):1976-8

Liamis G, Milionis H, Elisaf M. Am J Kidney Dis 2008;52(1):144-53

NO REAL ALTERNATIVE Avoid long-term use

Cautions if other perpetuating factors existed

systemic corticosteroids, anticoagulants, antiplatelets, etc..

Ibuprfen is the safest followed by naproxen, etodolac & diclofenac

ensure no heart failure or eGFR

GENERAL GUIDELINES FOR PRESCRIBING FOR GERIATRICS Carry out a regular medication review Avoid drugs that have known deleterious effects in elderly Start with topical application Use the recommended dosages for elderly patients Use simple drug regimens Consider non-pharmacological treatments Limit the number of people prescribing for each patient Avoid treating adverse drug reactions with further drugs

Milton J., Hill-Smith I, Jackson S., Prescribing for older people. BMJ. 2008 Mar 15; 336(7644): 606609

FUTURE UPDATES & DEBATE POINTS

Medication Beers Criteria STOPP ListSystemic steroids No mention Osteoporosis

Short-term use of opioids

Prefer using opioids over NSAIDS

Increase risk of cognitive impairment,

falls & fractures

Gallagher P1, O'Mahony D. Age Ageing. 2008 Nov;37(6):673-9

THANK YOU

QUESTIONS?

Potentially Inappropriate Medications for the Geriatric Population in the Practice of DentistrySlide Number 2Slide Number 3Consumption of Medications in geriatric populationSlide Number 5Increased risk for ADE & drug interactionsAs Dentists, Why Should We Care?Are there guidelines?Slide Number 8Slide Number 9Slide Number 10Designations of Quality of EvidenceDesignations of strength of recommendation Tricyclic antidepressantsTricyclic antidepressantsSlide Number 15Why not suitable for geriatrics? Tricyclic antidepressantsAlternativesBENZODIAZEPINESBenzodiazepinesSlide Number 21BenzodiazepinesWhy not suitable for geriatrics? impact of medication classes on falls in GeriatricsSlide Number 25AlternativesSkeletal Muscle RelaxantsSkeletal Muscle RelaxantsSlide Number 29Why not suitable for geriatrics? Slide Number 31Slide Number 32Skeletal Muscle RelaxantsAlternativesAlternativeSlide Number 36AnticonvulsantsWhy not suitable for geriatrics? AnticonvulsantsSlide Number 40AlternativesLong-term use of nsaidsnsaidsWhy not suitable for geriatrics? Slide Number 45Long-term nsaidsNo real alternativeGeneral Guidelines for Prescribing for geriatrics Future updates & debate pointsThank youquestions?