Polypharmacy in Geriatrics Home for the Summer Notre-Dame de Lourdes. Janine Grenier

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1 Plypharmacy in Geriatrics Hme fr the Summer Ntre-Dame de Lurdes Janine Grenier 2016

2 Plypharmacy in the geriatric ppulatin is becming a cmmn cncern, with many patients being prescribed multiple medicatins fr multiple medical cnditins. With the changing physilgy f an aging bdy (such as decreased renal functin and muscle mass), pharmaceuticals may nt have the same effects as they wuld n the bdy f a yunger patient, pssibly causing txicity due t accumulatin r inadequate respnses due t lack f metablizatin. Elderly individuals n multiple medicatins are als predispsed t cnfusin, delirium, and falls, which can lead t increased mrbidity and mrtality. Patients experiencing plypharmacy may experience a pill burden (taking many pills thrughut the day) which can make adherence challenging and can lead t wrsening f medical cnditins. Plypharmacy can als lead t the prescribing cascade: when ne interprets a side effect f medicatin as a separate medical cnditin, leading t the prescriptin f an additinal medicatin, which may nt even help alleviate that symptm. Plypharmacy can als lead t numerus drug interactins, which can have adverse effects n the patient. There are multiple screening tls that can be used by primary care prviders when assessing the pharmaclgical needs f their geriatric patients including the STOPP criteria (Screening Tl f Older Persns Prescriptins) and the START criteria (Screening Tl t Alert t Right Treatment). The STOPP and START criteria were develped in Ireland in 2008 by Gallagher, Ryan, Byrne, Kennedy, and O Mahny t prvide straightfrward, evidencebased rules t avid cmmn instances f ptentially inapprpriate prescribing, as well as ptential prescribing missins i. There are 65 criteria in the STOPP list and 22 in the START list. Methds Using the Accur EMR prgram, 5 patients were selected at randm with the fllwing requirements: - Age >65 years - Prescribed 10 r mre medicatins - Willing t attend ne appintment t assess their adherence and cncerns. Fur patients attended an appintment (ne was unable t attend) where their infrmed cnsent was btained and their drug adherence and medical cnditins were discussed. During the appintment, a relevant physical examinatin was perfrmed. Afterward, their medical cnditins and medicatins were reviewed examining indicatins, ptential drug interactins, prescribing cascades, and STOPP/START criteria. Cases and Discussin Discussin thrughut in italics. Case 1 Patient 1 is a 67-year-ld male wh takes medicatins frm bttles and uses his phne alarm as a reminder. He can list his medical cnditins and can identify their crrespnding medicatins. His diabetes mellitus is currently at target (6.3%). Past medical histry: Cellulitis f leg Pulmnary emblism Ostearthritis Vitamin B deficiency Hiatus hernia Type 2 Diabetes mellitus

3 Obstructive sleep apnea (CPAP) Benign Prstatic Hypertrphy DVT (L) Hypthyridism COPD Atrial fibrillatin Medicatins: Cephalexin 500 mg PO QID fr 14 days Rivarxaban 20 mg PO OD Metfrmin HCL 500 mg PO BID Levthyrxine sdium 175 mcg PO OD Dutasteride 0.5 mg PO OD Titrpium 18 mcg PO OD Tamsulsin CR 0.4 mg PO OD EC ASA 81 mg PO OD Salbutaml 1-2 puffs PRN Vitamin B mg PO OD Advair (Fluticasne/salmeterl 500 diskus) 1 puff BID On examinatin: BP 118/80 HR 80 irregular Heart: nrmal S1/S2, irregular rate Lungs: clear, slight decrease in air entry t left side. Relevant bldwrk: Creatinine 104 uml/l Randm bld sugar 5.8 mml/l TSH 3.08 mu/l HbA1C 6.3% Urine ACR 0.5 mg/mml (nrmal <2.0) INR 1.2 ( ) Fasting glucse 6.8 mml/l ( ) PTT 13.2 secnds ( ) Match medicatins t crrespnding medical cnditins Cellulitis Cephalexin Type II Diabetes mellitus Metfrmin DVT (prphylaxis) Rivarxaban Pulmnary emblism (prphylaxis) Atrial fibrillatin COPD Salbutaml Titrpium Fluticasne/Salmeterl Benign prstatic hypertrphy Tamsulsin Dutasteride Hypthyridism L-thyrxine Vitamin B deficiency Vitamin B12 Cardiac preventin EC ASA Pssible drug interactins: - Aspirin Rivarxaban (D cnsider therapy mdificatin) Aspirin can increase bleeding risk f rivarxaban. Carefully cnsider risks and benefits f this cmbinatin. The aspirin is at a dse f 81mg and is nt particularly cncerning fr bleeding risk. - Advair Salbutaml (C Mnitr therapy) Sympathmimetics may enhance the adverse/txic effects f ther sympathmimetics.

4 Mnitr fr increased effects f sympathmimetics (e.g. bld pressure, heart rate) during cncmitant use. The patient s bld pressure and heart rate were nrmal, cntinue t mnitr. - Cephalexin Metfrmin (C mnitr therapy) Cephalexin may increase serum cncentratin f Metfrmin Mnitr fr signs and symptms f metfrmin txicity taking bth metfrmin and cephalexin, particularly in patients wh may have ther risk factrs fr metfrmin txicity (e.g. renal impairment). The cephalexin is a shrt term dse (14 days) s any interactin wuld be f shrt term. STOPP criteria - (Antiplatelet/Anticagulant drugs) Stp aspirin in cmbinatin with vitamin K agnist, direct thrmbin inhibitr r factr Xa inhibitrs (rivarxaban) in patients with chrnic atrial fibrillatin (n added benefit frm aspirin). - (Antiplatelet/Anticagulant drugs) Stp vitamin K agnist, direct thrmbin inhibitr r factr Xa inhibitrs fr first DVT withut cntinuing prvking risk factrs fr >6 mnths (n prven added benefit) Patient is a lng distance truck driver with lng sedentary perids, which put him at risk fr DVT, cntinue management. - (Antiplatelet/Anticagulant drugs) Stp vitamin K agnist, direct thrmbin inhibitr r factr Xa inhibitrs fr first pulmnary emblism withut cntinuing prvking risk factrs fr >12 mnths (n prven added benefit) As abve. - (Respiratry) Antimuscurarinic brnchdilatrs (titrpium Spiriva) with a histry f narrw angle glaucma (may exacerbate glaucma) r bladder utflw bstructin (may cause urinary retentin). Pssible prescribing cascade as patient is n bth tamsulsin and dutasteride fr BPH. START criteria - (Cardivascular) Start Vitamin K antagnists r direct thrmbin inhibitrs r factr Xa inhibitrs in the presence f chrnic atrial fibrillatin. Has been dne n rivarxaban. - (Respiratry) Start regular inhaled B2 agnist r antimuscarinic brnchdilatr (e.g. ipratrpium, titrpium) fr mild t mderate asthma r COPD. Has been dne n titrpium. - (Urgenital) Start alpha-1-receptr blcker with symptmatic prstatism, where prstatectmy is nt cnsidered necessary. Has been dne n tamsulsin. - (Urgenital) Start 5-alpha reductase inhibitr with symptmatic prstatism, where prstatectmy is nt cnsidered necessary. Has been dne n dutasteride. - (Vaccines) Start seasnal trivalent influenza vaccine annually Recmmend. - (Vaccines) Start pneumcccal vaccine at least nce after age 65 accrding t natinal guidelines. Has been dne February 2016 Recmmendatins

5 - Discntinue 81mg aspirin as there is n added benefit since patient is already n a factr Xa inhibitr and there is a slight increase in risk f bleeding. - Evaluate need fr titrpium inhaler depending n severity f COPD as it may be cntributing t increased urinary retentin requiring 2 medicatins. - Recmmend annual influenza vaccine. Case 2 Patient 2 is a 76-year-ld female wh takes medicatins frm bubble packs. She can list her medical cnditins but cannt name her medicatins r what they are used fr. This patient has been evaluated several times fr plypharmacy and presents ften t clinic (twice a week) fr reassurance. The patient has increased pain perceptin, due likely t her anxiety and seeks additinal medicatins when she presents, t help alleviate this r t give her mre energy. Past medical histry: Atrphic vaginitis Athersclersis Ampullary stensis Depressin disrder Chrnic bstructive pulmnary disease Recurrent UTI Hypertensin GERD Central hearing lss Degenerative spine change L5-S1 Granulmatus lung disease Dermatitis Anxiety Ostearthritis?Plymyalgia rheumatica Insmnia Medicatins: Zpiclne 5mg PO OD Valsartan 160mg PO OD Omeprazle 20mg PO OD Nifedipine 60mg PO OD Vitamin B mcg PO OD Vitamin D IU PO OD Buprpin HCL 150mg PO OD Acetminphen 1000mg PO QID Fentanyl 25mcg/hur patch Premarin mg/g, tpical Ipratrpium 20mcg inhaler, 2 puffs QID Salbutaml 100mcg 2 puff, q4h PRN Advair (Fluticasne/Salmeterl 250 diskus) 2 puff BID Prednisne slw taper beginning June 8, 2016: 12.5 mg PO OD fr 2 weeks 10 mg PO OD fr 2 weeks 9 mg PO OD fr 2 weeks 8 mg PO OD fr 2 weeks 7 mg PO OD fr 2 weeks 6 mg PO OD fr 2 weeks 5 mg PO OD fr 2 weeks 4.5 mg PO OD fr 2 weeks 4 mg PO OD fr 2 weeks 3.5 mg PO OD fr 2 weeks 3 mg PO OD fr 2 weeks 2.5 mg PO OD fr 2 weeks 2 mg PO OD fr 2 weeks 1.5 mg PO OD fr 2 weeks 1 mg PO OD fr 2 weeks 0.5 mg PO OD fr 2 weeks On exam: - BP 162/82 Match medicatin t crrespnding cnditin: Hypertensin COPD Nifedipine Valsartan Salbutaml Ipratrpium Fluticasne/Salmeterl

6 Ostearthritis Plymyalgia rheumatica Premarin Depressin Anxiety GERD Insmnia Acetminphen Fentanyl Acetminphen Fentanyl Prednisne Irritatin f vulva and perineum Buprpin Omeprazle Zpiclne Pssible Drug Interactins: - Advair Salbutaml (C Mnitr therapy) Sympathmimetics may enhance the adverse/txic effect f ther sympathmimetics. Mnitr fr increased effects f sympathmimetics (e.g. bld pressure, heart rate) during cncmitant use. - Ipratrpium Fentanyl (C Mnitr therapy) Antichlinergic agents may enhance the adverse/txic effects f piid analgesics. Specifically the risk f cnstipatin and urinary retentin wuld be increased with this interactin. Increase mnitring fr evidence f cnstipatin and/r urinary retentin in patients using this cmbinatin. Advise patients t prmptly reprt signs and symptms suggestive f such adverse effects. Patient is nt currently experiencing cnstipatin but shuld be recmmended t fllw up if thse symptms ccur. STOPP Criteria - (Musculskeletal) Stp crticsterids (ther than peridic intra-articular injectins fr mn-articular pain) fr stearthritis (risk f systemic crticsterid side effects). Is currently being dne (slw taper). - (Drugs increasing risk f falls) Stp hypntic Z-drugs e.g. zpiclne, zlpidem, zalepln (may cause prtacted daytime sedatin, ataxia). Cnsider discntinuing zpiclne due t increase risk f falls, delirium, and cnfusin as patient has already had a fall in the past and imprvement in sleep latency and duratin is minimal with this medicatin iii. - (Analgesic drugs) Stp use f regular piids withut cncmitant laxative (risk f severe cnstipatin). Patient nt currently experiencing cnstipatin. START Criteria - (Cardivascular) Start antihypertensive therapy where systlic bld pressure cnsistently >160mmHg and/r diastlic bld pressure cnsistently >90 mmhg. Mnitr bld pressure and pssibly add anther agent if systlic persistently >160mmHg. - (Respiratry) Start regular inhaled beta2 agnist r antimuscarinic brnchdilatr (e.g. ipratrpium, titrpium) fr mild t mderate asthma r COPD. Has been dne n ipratrpium.

7 - (Gastrintestinal) Start PPI with severe gastr-esphageal reflux disease r peptic stricture requiring dilatatin. Has been dne n meprazle. - (Musculskeletal) Start bisphsphnates and vitamin D and calcium in patients taking lng-term systemic crticsterid therapy. Patient being weaned frm systemic crticsterid. May nt need bisphsphnate treatment. I wuld advise a BMD test. - (Musculskeletal) Start vitamin D supplement in lder peple wh are husebund r experiencing falls r with stepenia (bne mineral density >-1.0 but <-2.5 in multiple sites). Has had a fall in the past. Is currently n vitamin D. - (Urgenital) Start tpical vaginal estrgen r vaginal estrgen pessary fr symptmatic atrphic vaginitis Has been dne n premarin cream. - (Analgesics) Start high-ptency piids in mderate-severe pain, where paracetaml, NSAIDs r lw-ptency piids are nt apprpriate t the pain severity r have been ineffective. Has been dne n maximum dse f paracetaml and is n fentanyl. - (Analgesics) Start laxatives in patients receiving piids regularly. N current cnstipatin. Start plyethylene glycl if becming an issue. - (Vaccines) Start seasnal trivalent influenza vaccine annually. Recmmend. - (Vaccines) Start pneumcccal vaccine at least nce after age 65 accrding t natinal guidelines. Dne in Recmmendatins: - Cnsider discntinuatin f zpiclne t prevent falls, delirium, and cnfusin. - Start a regular laxative if cnstipatin due t piids becmes an issue. - Mnitr bld pressure. - D a bne mineral density test t assess the risk f steprsis. - Recmmend yearly influenza vaccine. Case 3: Patient 3 is a 70 year-ld male wh takes medicatins frm bubble packs. He will ccasinally have lw bld sugars but has never gne uncnscius. He can list his medical cnditins and can identify mst f their crrespnding medicatins. Had cncerns abut his memry s an MMSE was perfrmed during his visit. His diabetes mellitus is nt currently at target (7.5%). Past Medical Histry: Hyperlipidemia Hypertensin Diabetes mellitus (type II) Hypthyridism Ulcerative prctitis Peripheral vascular disease Sciatica Atrial fibrillatin Crnary athersclersis (duble bypass June 2012) Medicatins: Warfarin 5mg PO OD Amidarne HCL 300mg PO OD Atrvastatin 40mg PO OD Levthyrxine sdium 88mcg PO OD Hydrchlrthiazide 25mg PO OD Ramipril 5mg PO OD

8 Insulin NPH 60 units daily at HS Aspirin 81 mg PO OD Vitamin B mg PO BID Vitamin D 2000 IU PO BID Insulin Lispr units TID (depending n bld sugar reading) On examinatin: - MMSE 27/30 - Bld pressure: 135/60 - Heart rate: 60 irregular - Lungs: air entry clear symmetrically - Heart: irregular S1 and S2. - Slight decrease in sensatin t right ft in tes 2-4. N charct jint, gd pedal pulses. Relevant recent bldwrk: Electrlytes: Sdium 140 mml/l Ptassium 4.7 mml/l Chlride 101 mml/l Urea 8.9 mml/l ( ) Creatinine 108 uml/l ( ) egfr 59 ml/min/1.73m 2 ( ) INR 2.4 ( ) therapeutic HbA1C 7.5% ( ) Fasting glucse 8.6 ( ) Urine albumin/creatinine 1.6 mg/mml (nrmal <2.0) Match medicatin t crrespnding cnditin: Hyperlipidemia Hypertensin Diabetes mellitus Hypthyridism Crnary athersclersis Atrial fibrillatin Atrvastatin Ramipril Hydrchlrthiazide Insulin NPH Insulin Lispr Levthyrxine Ramipril Atrvastatin Aspirin Warfarin Amidarne Pssible drug interactins: - Amidarne Atrvastatin (D Cnsider therapy mdificatin) Amidarne may decrease the metablism f HMG-CA Reductase inhibitrs. Cnsider using a nn-interacting HMG-CA reductase inhibitr (pravastatin, pitavastatin) in patients receiving amidarne. If ptentially interacting drugs are used cncmitantly, mnitr fr evidence f txicity (e.g. myalgia, liver functin elevatins, rhabdmylysis, etc.). Dse reductin f the HMG-CA reductase inhibitr may be necessary with cncurrent amidarne therapy (e.g. limit simvastatin t 20mg/day, limit lvastatin t 40mg/day). Cnsider discntinuing amidarne due t ptential txicity and drug interactins. In patients >65, rate cntrl is preferred t rhythm cntrl in atrial fibrillatin. Cnsider using a beta-blcker r a calcium channel blcker instead iv. - Amidarne Warfarin (D Cnsider therapy mdificatin)

9 Amidarne may enhance the anticagulant effect f Vitamin K antagnists. Amidarne may increase the serum cncentratin f Vitamin K antagnists. Mnitr patients very clsely fr evidence f increased anticagulant effects if amidarne is initiated/dse increased, r decreased effects if amidarne is discntinued/dse decreased, thugh due t the lng half-life f amidarne, any interactin may persist fr several days/weeks fllwing any dse decrease r discntinuatin. An empiric warfarin dsage reductin f 30-50% at the initiatin f amidarne might be cnsidered, with clse mnitring f anticagulant effect t further refine ptimal dsing. Cnsider discntinuing amidarne as abve. - Amidarne Hydrchlrthiazide (C Mnitr therapy) Bld pressure lwering agents may enhance the hyptensive effect f hyptensin-assciated agents. Althugh the cncmitant use f tw r mre drugs that may lwer bld pressure (either as a therapeutic intentin r as an adverse effect) is ften clinically apprpriate, use f such cmbinatins ften substantially increases the risk fr hyptensin. Mnitr patients clsely fr additive hyptensive effects if tw r mre f these agents are cmbined. Cnsider discntinuing amidarne as abve. If replaced by a beta-blcker r calcium channel blcker, cntinue t mnitr bld pressure. - Amidarne Ramipril (C Mnitr therapy) Bld pressure lwering agents may enhance the hyptensive effect f hyptensin-assciated agents. Althugh the cncmitant use f tw r mre drugs that may lwer bld pressure (either as a therapeutic intentin r as an adverse effect) is ften clinically apprpriate, use f such cmbinatins ften substantially increases the risk fr hyptensin. Mnitr patients clsely fr additive hyptensive effects if tw r mre f these agents are cmbined. As abve. - Insulin Lispr Insulin NPH (C Mnitr therapy) Antidiabetic agents may enhance the hypglycemic effect f ther antidiabetic agents. Althugh the cncmitant use f antidiabetic agents and drugs that cause hypglycemia is ften clinically apprpriate, use f such cmbinatins ften substantially increases the risk f hypglycemia. Mnitr patients clsely fr hypglycemic effects if these agents are cmbined. - Insulin Lispr Hydrchlrthiazide (C Mnitr therapy) Insulin NPH Hydrchlrthiazide (C Mnitr therapy) Thiazide diuretics may diminish the therapeutic effect f antidiabetic agents. Increase mnitring f bld glucse cntrl when using thiazide diuretics in patients being treated with antidiabetic agents. In particular, mnitr clsely when starting/stpping a thiazide r when increasing a thiazide dse. STOPP Criteria - (Cardivascular) Thiazide diuretic with current significant hypkalemia (i.e. serum K+ <3.0 mml/l), hypnatremia (i.e. serum Na+ <130 mml/l), hypercalcemia (i.e. crrected serum calcium >2.65 mml/l) r with a histry f gut (hypkalemia, hypnatremia, hypercalcemia and gut can be precipitated by a thiazide diuretic). N hypnatremia r hypkalemia. Mnitr with bldwrk every 3-6 mnths. - (Cardivascular) ACE inhibitr r ARB in patients with hyperkalemia.

10 N hyperkalemia. Mnitr with bldwrk. - (Antiplatelet/Anticagulant drugs) Aspirin in cmbinatin with vitamin K antagnist, direct thrmbin inhibitr r factr Xa inhibitrs in patients with chrnic atrial fibrillatin (n added benefit frm aspirin). Patient has a past histry f crnary athersclersis s an antiplatelet agent may be indicated. START Criteria - (Cardivascular) Vitamin K antagnists r direct thrmbin inhibitrs r factr Xa inhibitrs in the presence f chrnic atrial fibrillatin. Has been dne n warfarin. - (Cardivascular) Aspirin ( mg nce daily) in the presence f chrnic atrial fibrillatin, where Vitamin K antagnists r direct thrmbin inhibitrs r factr Xa inhibitrs are cntraindicated. Aspirin nt required fr atrial fibrillatin due t warfarin. - (Cardivascular) Antiplatelet therapy (aspirin r clpidgrel r prasugrel r ticagrelr) with a dcumented histry f crnary, cerebral, r peripheral vascular disease. Is currently n aspirin. - (Cardivascular) Statin therapy with a dcumented histry f crnary, cerebral, r peripheral vascular disease, unless the patient s status is end-f-life r age is >85 years. Currently n atrvastatin. - (Cardivascular) ACE inhibitr with systlic heart failure and/r dcumented crnary artery disease. Currently n ramipril fr crnary athersclersis. - (Vaccine) Seasnal trivalent influenza vaccine annually. Recmmend. - (Vaccine) Pneumcccal vaccine at least nce after age 65 accrding t natinal guidelines. Recmmend. Recmmendatins: - Cnsider discntinuing amidarne due t ptential txicity and drug interactins. In patients >65, rate cntrl is preferred t rhythm cntrl in atrial fibrillatin. Cnsider using a beta-blcker r a calcium channel blcker instead then mnitr patient fr hyptensin/rthstatic hyptensin (since he wuld be n 3 anti-hypertensives). If that ccurs, cnsider discntinuing hydrchlrthiazide. - Recmmend annual influenza vaccine, as well as the pneumcccal vaccine. Case 4: Patient 4 is an 82-year-ld female wh takes medicatins frm dsing cntainers. She can list his medical cnditins and can identify their crrespnding medicatins. She has reduced the frequency f her diclfenac due t fluid retentin. The patient makes an effrt t live healthily by eating well and walking every day. She des nt like being n s many medicatins but had experienced wrsening depressin after the lss f several family members, including her husband. Past medical histry: Osteprsis Ostearthritis

11 Rheumatid arthritis Insmnia Bile acid diarrhea Asthma Mild cngestive heart failure DVT secndary t pelvic fracture Pelvic fracture Depressin disrder Tinnitus Hypthyridism GERD Medicatins: Alendrnate 70mg PO nce weekly Omeprazle 20mg PO OD Hydrxyzine 25mg PO OD PRN Levthyrxine 100 mcg PO OD Fursemide 20mg PO OD Hydrmrphne 3mg PO OD at HS Hydrmrphne 1mg PO BID Diclfenac 75mg PO 2-3x weekly PRN Chlestyramine PRN Salbutaml 100mcg 1-2 puff QID PRN Trazdne 50mg PO OD at HS Fluticasne 50mcg 2 spray OD PRN Citalpram 40mg PO OD Zpiclne 2.5-5mg PO OD at HS PRN Alprazlam 0.25mg PO PRN Dmperidne 10mg PO QID Premarin 0.625mg/g tpical PRN Advair (Fluticasne/salmeterl 250/25mcg) 3x/week On examinatin: - Bld pressure: 128/62 Match cnditin t crrespnding medicatin: Osteprsis Ostearthritis Rheumatid arthritis Bile acid diarrhea Asthma Mild cngestive heart failure Allergies Depressin Insmnia Hypthyridism GERD Alendrnate Hydrmrphne Diclfenac Chlestyramine Salbutaml Advair (Fluticasne/Salmeterl) Fursemide Hydrxyzine Lratadine Fluticasne Citalpram Trazdne Alprazlam Zpiclne Levthyrxine Omeprazle Dmperidne Pssible interactins: - Citalpram Dmperidne (X Avid cmbinatin) Highest risk QTc-prlnging agents may enhance the QTc-prlnging effect f ther highest risk QTc-prlnging agents. The cncmitant use f highest risk QTc-prlnging agents with any ther QTc-prlnging agent shuld be avided. Cncmitant use is expected t substantially increase the risk fr serius txicities, including the develpment f trsades the pintes (TdP) r ther significant ventrical tachyarrhythmias.

12 Patients with ther risk factrs present (e.g. lder age, female sex, bradycardia, hypkalemia, hypmagnesemia, heart disease, and higher drug cncentratins), wuld be at an even higher risk fr these ptentially life threatening txicities. Due t the risk f prlnged QTc, cnsider discntinuing citalpram and replacing with sertraline (a different SSRI with less risk f QTc prlngatin) v. Als cnsider discntinuing dmperidne if patient can tlerate GERD treatment with meprazle as the single agent. D an EKG t assess length f QTc and cmpare t baseline EKG if available. - Advair Citalpram (D Cnsider therapy mdificatin) Advair Dmperidne (D Cnsider therapy mdificatin) QTc prlnging agents may enhance the QTc-prlnging effect f highest risk QTc-prlnging agents. The cncmitant use f highest risk QTc-prlnging agents with any ther QTc-prlnging agent shuld be avided. The drugs listed in the indeterminate risk/risk mdifier grup have an uncertain effect n the QT interval, but have been assciated with individual reprts f QT prlngatin, trsades de pintes (TdP), and/r are likely t increase the risk fr QT prlngatin and/r TdP via anther mechanism. Patients with ther risk factrs present (e.g. lder age, female sex, bradycardia, hypkalemia, hypmagnesemia, heart disease, and higher drug cncentratins), wuld be at an even higher risk fr these ptentially life threatening txicities. The use f such a cmbinatin shuld be accmpanied by clse mnitring fr evidence f QT prlngatin r ther alteratins f cardiac rhythm. As abve. - Citalpram Omeprazle (D Cnsider therapy mdificatin) CYP2C19 inhibitrs may increase the serum cncentratin f citalpram. Limit citalpram dse t a maximum f 20 mg/day if used with a mderate CYP2C19 inhibitr. Patients using this cmbinatin shuld be mnitred clsely fr evidence f citalpram txicity (e.g. sertnin syndrme, QT prlngatin, etc.) Cnsider discntinuatin f citalpram as abve. - Citalpram Hydrxyzine (D Cnsider therapy mdificatin) Citalpram Trazdne (D Cnsider therapy mdificatin) Citalpram Salbutaml (D Cnsider therapy mdificatin) Dmperidne Hydrxyzine (D Cnsider therapy mdificatin) Dmperidne Trazdne (D Cnsider therapy mdificatin) Dmperidne Salbumatl (D Cnsider therapy mdificatin) QTc prlnging agents may enhance the QTc prlnging effect f highest risk QTc prlnging agents. The cncmitant use f highest risk QTc prlnging agents with any ther QTc-prlnging agent shuld be avided. The drugs listed in the indeterminate risk/risk mdifier grup have an uncertain effect n the QT interval, but have been assciated with individual reprts f QT prlngatin, trsades de pintes, and/r are likely t increase the risk fr QT prlngatin and/r TdP via anther mechanism. Any use f such cmbinatins shuld nly be undertaken with cautin and shuld be avided if pssible. Cncmitant use may substantially increase the risk fr serius txicities, including TdP r ther significant ventricular tachyarrhythmias. Patients with ther risk factrs present (e.g. lder age, female sex, bradycardia, hypkalemia,

13 hypmagnesemia, heart disease, and higher drug cncentratins), wuld be at an even higher risk fr these ptentially life-threatening txicities. The use f such a cmbinatin shuld be accmpanied by clse mnitring fr evidence f QT prlngatin r ther alteratins f cardiac rhythm. Cnsider discntinuatin f citalpram and dmperidne as abve. - Citalpram Diclfenac (D Cnsider therapy mdificatin) SSRIs may enhance the antiplatelet effect f NSAID (nn-selective). NSAID may diminish the therapeutic effect f SSRIs. T minimize the risk f bleeding assciated with this cmbinatin, cnsider using alternative analgesics, when apprpriate, and/r additin f a gastrprtective agent, such as a PPI fr the time that cmbined SSRIs and NSAIDs is necessary. Minimally, clse mnitring fr increased risk f bleeding and/r decreased SSRI clinical effectiveness during cncmitant SSRI-NSAID use is recmmended. Patient had decreased her diclfenac t 2-3x weekly (PRN) due t fluid retentin that she gets when using it. She is als n meprazle which makes this interactin less cncerning. - Citalpram Trazdne (D Cnsider therapy mdificatin) SSRIs may enhance the sertnergic effect f antidepressants (Sertnin reuptake inhibitr/antagnist). This may cause sertnin syndrme. Cnsider alternatives t the use f a SSRI and sertnin reuptake inhibitr/antagnist in cmbinatin. Cnservative initial dsing is warranted. Mnitr fr evidence f sertnin syndrme (e.g. agitatin, cma, cnfusin, fever, diaphresis, hypertensin, muscle rigidity, seizures, tremrs) if an SSRI and a sertnin reuptake inhibitr/antagnist are used cncmitantly, r ne is used fllwing the discntinuatin f the ther. Mnitr fr sertnin syndrme when changes t medicatins are made. - Diclfenac Fursemide (D Cnsider therapy mdificatin) NSAIDs may diminish the diuretic effect f lp diuretics. Lp diuretics may enhance the nephrtxic effect f NSAIDs. Mnitr fr decreased therapeutic effects f lp diuretics with cncurrent use f NSAIDs. Cnsider using an NSAID that hlds a lesser ptential fr interacting with the lp diuretic (e.g. diflunisal, flurbiprgen, ketprfen, ketrlac). Patients with heart failure r cirrhsis may be mre sensitive t alteratins in fluid balance, in which case cnsideratin shuld be given t aviding the cncmitant use f NSAIDs and lp diuretics. Patients shuld als be mnitred clsely fr evidence f acute kidney injury with this cmbinatin, particularly if als used tgether with an ACE inhibitr and an ARB as the use f such a three-drug cmbinatin may cnvey a particularly high risk fr AKI. Patient has decreased her diclfenac t 2-3x weekly. - Advair Fursemide (C Mnitr therapy) Salbutaml Fursemide (C Mnitr therapy) Beta2 agnists may enhance the hypkalemic effect f lp diuretics. Mnitr fr increased risk f hypkalemia, and the assciated effects (e.g. cardiac cnductin prblems) in patients receiving cncmitant therapy with beta2-agnists and lp diuretics. Patients with lw baseline serum ptassium cncentatins are likely at increased risk f negative effects. Mnitr with bldwrk. - Advair Salbutaml (C Mnitr therapy)

14 Sympathmimetics may enhance the adverse/txic effect f ther sympathmimetics. Mnitr fr increased effects f sympathmimetics (e.g. bld pressure, heart rate) during cncmitant use. Patient s bld pressure was nrmal, cntinue t mnitr. - Alprazlam Citalpram (C Mnitr therapy) Citalpram Hydrmrphne (C Mnitr therapy) Citalpram Zpiclne (C Mnitr therapy) CNS depressants may enhance the adverse/txic effects f SSRIs. Specifically, the risk f psychmtr impairment may be enhanced. Mnitr fr increased psychmtr impairment in patients wh initiate SSRIs during treatment with CNS depressants. Mnitr fr psychmtr impairment. - Alprazlam Hydrmrphne (C Mnitr therapy) Alprazlam Zpiclne (C - Mnitr therapy) Hydrmrphne Zpiclne (C Mnitr therapy) CNS depressants may enhance the adverse/txic effect f ther CNS depressants. Mnitir fr additive CNS-depressant effects whenever tw r mre CNS depressants are cncmitantly used. Advise patients t avid any unprescribed, illicit, r recreatinal use f ther CNS depressants. Mnitr fr CNS depressin, cunsel t avid ther CNS depressants (alchl, drugs). - Alprazlam Hydrxyzine (C Mnitr therapy) Hydrxyzine Hydrmrphne (C Mnitr therapy) Hydrxyzine Zpiclne (C Mnitr therapy) Hydrxyzine may enhance the CNS depressant effect f CNS depressants. Mnitr fr signs/symptms f CNS depressin in any patient receiving hydrxyzine tgether with anther CNS depressant. A reductin in the dse f any ther CNS depressants that are t be used in cmbinatin may be warranted. Mnitr fr CNS depressin will discuss hydrxyzine belw. - Citalpram Levthyrxine (C Mnitr therapy) SSRIs may diminish the therapeutic effects f thyrid prducts. Thyrid prduct dse requirements may be increased. Mnitr thyrid functin in patients receiving thyrid supplements fllwing initiatin, dse adjustment, r discntinuatin f a SSRI. Mnitr thyrid functin. - Citalpram Hydrmrphne (C Mnitr therapy) Hydrmrphne Trazdne (C Mnitr therapy) Analgesics (piid) may enhance the sertnergic effect f sertnin mdulatrs. This culd result in sertnin syndrme. Mnitr fr signs/symptms f sertnin syndrme (e.g. mental status changes, autnmic instability, neurmuscular hyperactivity) when piid analgesics are cmbined with sertnin mdulatrs. If symptms f sertnin syndrme develp, discntinuatin f bth the piid analgesic and the sertnin mdulatr is recmmended. Mnitr fr sertnin syndrme. - Diclfenac Alendrnate (C Mnitr therapy)

15 NSAIDs may enhance the adverse/txic effect f bisphsphnate derivatives. Bth an increased risk f GI ulceratin and an increased risk f nephrtxicity are f cncern. Mnitr fr signs/symptms f GI ersin/ulceratin. T minimize risk f renal dysfunctin, patients shuld be kept hydrated befre and during therapy, and renal functin (i.e. creatinine clearance, BUN, etc.) shuld be mnitred clsely. Mnitr fr renal dysfunctin and encurage hydratin. - Alendrnate Omeprazle (C Mnitr therapy) PPIs may diminish the therapeutic effect f bisphsphnate derivatives. Carefully cnsider need fr PPI therapy in patients being treated with a bisphsphnate derivative, and/r limit the PPI inhibitr dse/duratin f therapy when apprpriate. H2-receptr antagnists d nt appear t cnfer the same risk fr this pssible interactin. - Hydrmrphne Fursemide (C Mnitr therapy) Opiids may enhance the adverse/txic effect f diuretics. Patients shuld be mnitred fr reduced efficacy f diuretics, urinary retentin, and symptms r rthstasis when treated with bth a diuretic and an piid analgesic. Mnitr therapy. STOPP Criteria: - (CNS and psychtrpic drugs) SSRIs with current r recent significant hypnatremia i.e. serum Na+ <130 mml/l (risk f exacerbating r precipitating hypnatremia). D bldwrk fr electrlytes t assess this. - (CNS and psychtrpic drugs) Benzdiazepines fr >4 weeks (n indicatin fr lnger treatment; risk f prlnged sedatin, cnfusin, impaired balance, falls, rad traffic accidents; all benzdiazepines shuld be withdrawn gradually if taken fr mre than 4 weeks as there is a risk f causing a benzdiazepine withdrawal syndrme if stpped abruptly. Patient is nt taking a regular benzdiazepine, is taking it PRN when she is particularly distressed (which is nt ften). Cntinue current management. - (CNS and psychtrpic drugs) First generatin antihistamines (safer, less txic antihistamines nw widely available). Hydrxyzine is a first generatin antihistamine and has ptential fr several interactins in this patient. Cnsider discntinuing this medicatin and replace with lratadine (a secnd generatin antihistamine), which the patient was n previusly. - (Drugs increasing risk f falls) Benzdiazepines (sedative, may cause reduced sensrium, impair balance). Patient des nt use benzdiazepine regularly. - (Drugs increasing risk f falls) Hypntic Z-drugs e.g. zpiclne, zlpidem, zalepln (may cause prtracted daytime sedatin, ataxia). Cnsider discntinuing zpiclne due t increase risk f falls, delirium, and cnfusin as imprvement in sleep latency and duratin is minimal with this medicatin. - (Analgesics) Use f regular piids withut cncmitant laxative (risk f severe cnstipatin). Patient is nt currently experiencing cnstipatin (due t bile acid diarrhea). Reevaluate if this becmes a cncern.

16 START Criteria - (Musculskeletal) Vitamin D and calcium supplement in patients with knwn steprsis and/r previus fragility fractures and/r (Bne mineral density T- scres mre than -2.5 in multiple sites). Start vitamin D and calcium as patient is als n alendrnate. - (Musculskeletal) Bne anti-resrptive r anablic therapy (e.g. bisphsphnate, strntium ranelate, teriparatide, densumab) in patients with dcumented steprsis, where n pharmaclgical r clinical status cntraindicatin exists (bne mineral density T-scres ->2.5 in multiple sites) and/r previus histry f fragility fractures. Has been dne n alendrnate. - (Urgenital) Tpical vaginal estrgen r vaginal estrgen pessary fr symptmatic atrphic vaginitis. Has been dne n premarin. - (Analgesics) High ptency piids in mderate-severe pain, where paracetaml, NSAIDs r lw-ptency piids are nt apprpriate t the pain severity r have been ineffective. Has been dne n hydrmrphne. - (Analgesics) Laxatives in patients receiving piids regularly. Patient nt currently experiencing cnstipatin (due t bile acid diarrhea), reevaluate if becmes a prblem. - (Vaccines) Seasnal trivalent influenza vaccine annually. Recmmend. - (Vaccines) Pneumcccal vaccine at least nce after age 65 accrding t natinal guidelines. Has been dne Recmmendatins: - Cnsider discntinuatin f citalpram in favur f sertraline, which has less risk f QTc lengthening as the patient has numerus medicatins that culd ptentially lengthen the QTc. - Obtain an EKG t evaluate whether there is QTc lengthening in cmparisn with baseline EKG. - Cnsider discntinuatin f dmperidne if patient can tlerate meprazle as a single agent fr GERD since dmperidne may als cause QTc lengthening. - Cnsider discntinuatin f hydrxyzine (as first generatin antihistamine) in favur f lratadine (a secnd generatin antihistamine) as it may be a safer alternative since there is less effect f sedatin as cmpared t first generatin antihistamines. - Cnsider discntinuing zpiclne due t increase risk f falls, delirium, and cnfusin as imprvement in sleep latency and duratin is minimal with this medicatin. - Add regular plyethylene glycl fr piid-related cnstipatin if cnstipatin becmes an issue fr patient. - Start vitamin D and calcium fr bne health. - Recmmend annual influenza vaccine. Cnclusin With s many geriatric patients being prescribed multiple medicatins, it is imperative fr physicians t identify interactins, prescribing cascades, and side effects f thse medicatins. It is als imperative that physicians evaluate the indicatins fr

17 medicatins and identify ptentially inapprpriate prescriptins, as well as ptential missins. With many screening tls available such as STOPP/START, evaluatin f medicatins can be perfrmed mre quickly and efficiently. Many thanks t: Clinique Ntre-Dame Clinic Dr. Hlly Hamiltn Dr. Denis Frtier Dr. Frances Berard Dr. Emilie Cudiere Dr. Stefan Riel Dr. Sreshi Chawla Lysanne Delaquis Suthern Health Santé Sud Office f Rural and Nrthern Health i Ryan, C. The basics f the START/STOPP criteria. Retrieved August 12, 2016, frm ii Lexicmp Database f drug interactins (fr all drug interactins). iii Uptdate. (2016) Zpiclne: Drug Infrmatin. Retrieved August 12, 2016, frm iv Uptdate. (2016) Rhythm cntrl vs rate cntrl in atrial fibrillatin. Retrieved August 12, 2016, frm 7#H16 v Uptdate. (2016) Sertraline: Drug Infrmatin. Retrieved August 12, 2016, frm vi Gallagher, et al. (2014) Screening Tl f Older Persns Prescriptins (STOPP) versin 2. Age Ageing 44(2) pp vii Gallagher, et al. (2014) Screening Tl t Alert t Right Treatment (START), versin 2. Age Ageing. 44(2) pp