1 Drug interactions in an elderly patient with significant polypharmacy
1 Drug interactions in an elderly patient with significant polypharmacy
1 Drug interactions in an elderly patient with significant polypharmacy
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<strong>Drug</strong> Interactions Case Study: Polypharmacy <strong>in</strong> Elderly <strong>with</strong> Chronic Kidney Disease Avapro Vasotec prodrug <strong>in</strong>sul<strong>in</strong> Procardia XL aspir<strong>in</strong> Some Some None None None labetalol, aspir<strong>in</strong>, <strong>in</strong>sul<strong>in</strong>, Lasix labetalol, <strong>in</strong>sul<strong>in</strong>, Lasix, aspir<strong>in</strong>, Zocor Vasotec, Avapro, clonid<strong>in</strong>e, labetalol, gemfibrozil labetalol, hydralaz<strong>in</strong>e, aspir<strong>in</strong>, clonid<strong>in</strong>e Vasotec, metabolite enalaprilat, hydralaz<strong>in</strong>e, Avapro, Lasix, Zocor Allegra None sodium citrate (from Bicitra) None Phoslo Gelcaps None clonid<strong>in</strong>e None labetalol, <strong>in</strong>sul<strong>in</strong>, Procardia XL, digox<strong>in</strong> hydralaz<strong>in</strong>e Lasix citric acid (from Bicitra) None None Metabolism unknown Procardia XL, aspir<strong>in</strong>, digox<strong>in</strong> digox<strong>in</strong>, labetalol, metabolite enalaprilat, Vasotec, Zocor, aspir<strong>in</strong>, Avapro, albuterol <strong>in</strong>halation 3
6 <strong>Drug</strong> Interactions Case Study: Polypharmacy <strong>in</strong> Elderly <strong>with</strong> Chronic Kidney Disease Table 3: Labetalol metabolism 27 Contribut<strong>in</strong>g to this <strong>patient</strong>’s s<strong>in</strong>us bradycardia, a meta-‐<strong>an</strong>alysis concluded that beta-‐blockers used for the treatment of hypertension are associated <strong>with</strong> <strong>in</strong>creased risk for new-‐onset diabetes mellitus, hypertriglyceridemia, bronchial asthma exacerbations, higher basel<strong>in</strong>e blood sugar <strong>an</strong>d masks hypoglycemic state 3, 23 . The <strong>patient</strong>’s history of MI <strong>an</strong>d uncontrolled hypertension currently requires multiple comb<strong>in</strong>ed <strong>an</strong>ti-‐hypertensive drugs for long-‐term m<strong>an</strong>agement. Moreover, some recent studies have argued aga<strong>in</strong>st rout<strong>in</strong>e beta-‐blocker use <strong>in</strong> <strong>patient</strong>s <strong>with</strong> hypertension despite current guidel<strong>in</strong>es, especially when comorbid contra<strong>in</strong>dications are present 15 . The most recent reports of the Jo<strong>in</strong>t National Committee (JNC VI) <strong>an</strong>d the World Health Org<strong>an</strong>ization recommend beta-‐blockers <strong>an</strong>d diuretics as first-‐l<strong>in</strong>e therapy for uncomplicated essential hypertension 11, 25 . Similar recommendations have been issued over the past few years by m<strong>an</strong>y authoritative sources <strong>an</strong>d research published <strong>in</strong> <strong>in</strong>fluential journals. These recommendations were supposedly based on multiple prospective r<strong>an</strong>domized trials attest<strong>in</strong>g that only beta-‐blockers <strong>an</strong>d diuretics, both <strong>in</strong> monotherapy <strong>an</strong>d comb<strong>in</strong>ed, reduced morbidity <strong>an</strong>d mortality <strong>in</strong> hypertension. Ever s<strong>in</strong>ce the Veter<strong>an</strong>s Adm<strong>in</strong>istration study <strong>in</strong> the 1970s 18 , multiple <strong>an</strong>d prospective r<strong>an</strong>domized trials have documented that diuretic-‐based therapy reduces the risk of stroke <strong>an</strong>d, to a lesser extent, of heart attacks <strong>an</strong>d cardiovascular morbidity <strong>an</strong>d mortality. However, the data are much less conv<strong>in</strong>c<strong>in</strong>g for beta-‐blockers 16 . In fact, no trial has shown that lower<strong>in</strong>g blood pressure <strong>with</strong> a beta-‐blocker reduces the risk of a heart attack or cardiovascular event <strong>in</strong> <strong>patient</strong>s <strong>with</strong> essential hypertension compared <strong>with</strong> placebo. In contrast, several prospective studies are now available show<strong>in</strong>g that blood pressure reduction <strong>with</strong> calcium ch<strong>an</strong>nel blockers dim<strong>in</strong>ishes cardiovascular morbidity <strong>an</strong>d mortality <strong>an</strong>d, at least <strong>in</strong> meta-‐<strong>an</strong>alysis, all-‐cause mortality. Therefore, this <strong>patient</strong> should benefit from stroke prevention <strong>an</strong>d <strong>an</strong>ti-‐hypertensive effects of diuretics (i.e. Lasix) <strong>an</strong>d optimize <strong>an</strong>tihypertensive therapy <strong>with</strong> current medications, but avoid<strong>in</strong>g the use of beta-‐blockers. We also f<strong>in</strong>d 100% <strong>in</strong>hibition of gemfibrozil metabolism when concurrently adm<strong>in</strong>istered <strong>with</strong> both: Procardia XL <strong>an</strong>d aspir<strong>in</strong> s<strong>in</strong>ce gemfibrozil is also metabolized through glucuronidation (table 4). Fibrates are a ma<strong>in</strong>stay <strong>in</strong> treat<strong>in</strong>g <strong>patient</strong>s <strong>with</strong> a subst<strong>an</strong>tial hypertriglyceridemic lipid abnormality. Seems logical to reconsider alternative therapy or adjust doses <strong>an</strong>d follow up <strong>with</strong> drug serum levels <strong>an</strong>d lipid p<strong>an</strong>els.
7 <strong>Drug</strong> Interactions Case Study: Polypharmacy <strong>in</strong> Elderly <strong>with</strong> Chronic Kidney Disease Table 4: Gemfibrozil metabolism 27<strong>Drug</strong> reconciliation S<strong>in</strong>ce the ADR profile was signific<strong>an</strong>t <strong>an</strong>d as m<strong>an</strong>y a five different drugs <strong>an</strong>d a pro-‐drug showed signific<strong>an</strong>t concern (table 1); we reevaluated the list of medications <strong>an</strong>d considered some alternate approaches. <strong>Drug</strong> reconciliation considerations <strong>in</strong> this <strong>patient</strong> <strong>in</strong>cluded research<strong>in</strong>g guidel<strong>in</strong>es for alternative therapy <strong>an</strong>d substitut<strong>in</strong>g drugs <strong>with</strong><strong>in</strong> a same family, but <strong>with</strong> different metabolic routes. Dose adjustments are always possible <strong>in</strong> all <strong>patient</strong>s <strong>with</strong> assumed borderl<strong>in</strong>e toxic levels or sub-‐therapeutic doses, but this is usually cl<strong>in</strong>ically determ<strong>in</strong>ed <strong>an</strong>d regular measurement of multiple drug levels for periodic optimization is neither practical, nor economically feasible. However, we emphasize the import<strong>an</strong>ce of drug measurements <strong>an</strong>d monitor<strong>in</strong>g as a research tool for positive confirmation <strong>an</strong>d metabolic feedback <strong>an</strong>alyses. In the absence of specific drug <strong>in</strong>formation to confirm software predictions, we utilize the onl<strong>in</strong>e tool to design new drug treatments <strong>in</strong> order to m<strong>in</strong>imize ADIs <strong>an</strong>d reduce possible drug <strong><strong>in</strong>teractions</strong> <strong>an</strong>d ch<strong>an</strong>g<strong>in</strong>g this <strong>in</strong>dividual’s out<strong>patient</strong> drugs (table 5). These recommendations do not <strong>in</strong>clude <strong>an</strong>y genetic profil<strong>in</strong>g <strong>in</strong>formation, which could also be critical to ADR evaluation. Table 5: Recommended drug list for pharmacotherapy after ADR evaluation 27
9 <strong>Drug</strong> Interactions Case Study: Polypharmacy <strong>in</strong> Elderly <strong>with</strong> Chronic Kidney Disease Table 7: <strong>Drug</strong> Interaction Checker from Medscape 29 <strong>Drug</strong> reconciliation proceeded by elim<strong>in</strong>at<strong>in</strong>g the follow<strong>in</strong>g drugs: Aspir<strong>in</strong> 81mg, Procardia XL, Digox<strong>in</strong>, Zocor <strong>an</strong>d Labetalol; <strong>an</strong>d add<strong>in</strong>g Plavix. Adequate blood pressure control will be achieved by adjust<strong>in</strong>g doses of current <strong>an</strong>tihypertensive therapy (CCB, ACE<strong>in</strong>h, ARB, etc.) <strong>with</strong> the notable personalized consideration of beta-blocker avoid<strong>an</strong>ce <strong>in</strong> this diabetic <strong>an</strong>d asthmatic <strong>patient</strong> <strong>with</strong> AV block <strong>an</strong>d bradycardia. Also, optimization of CHF therapy should be made <strong>with</strong> ACE/ARB (Vasotec & Avapro) <strong>an</strong>d diuretics (Lasix) that are 1 st l<strong>in</strong>e treatment for CHF s<strong>in</strong>ce 1997, <strong>in</strong>stead of cardiac glycoside derivatives 9 . Other recommendations <strong>in</strong>clude: cardiology consult, monitor blood sugar levels, yearly Influenza shot, <strong>in</strong>itiation of erythropoiet<strong>in</strong> <strong>an</strong>alogues <strong>in</strong> addition to iron-‐conta<strong>in</strong><strong>in</strong>g vitam<strong>in</strong>s <strong>an</strong>d encourage lifestyle ch<strong>an</strong>ges to <strong>in</strong>clude: exercise, smok<strong>in</strong>g cessation, tight glycemic control <strong>an</strong>d other dietary modifications Table 8: <strong>Drug</strong> <strong><strong>in</strong>teractions</strong> after YouScript-‐aided <strong>Drug</strong> Reconciliation 27 Affected <strong>Drug</strong> Cl<strong>in</strong>ical Impact Causative Agentmetabolite enalaprilat(Vasotec's activeSome Lasix, Plavixmetabolite)<strong>in</strong>sul<strong>in</strong>Some >N
10 <strong>Drug</strong> Interactions Case Study: Polypharmacy <strong>in</strong> Elderly <strong>with</strong> Chronic Kidney Disease Vasotec prodrugSomeclonid<strong>in</strong>e, <strong>in</strong>sul<strong>in</strong>, Lasix,Plavixgemfibrozil Some <strong>in</strong>sul<strong>in</strong>albuterol <strong>in</strong>halation Some Lasixclonid<strong>in</strong>eSomeLasix, Vasotec, <strong>in</strong>sul<strong>in</strong>,Procardiahydralaz<strong>in</strong>e Some ProcardiaLasixSomeAvapro, Procardia,clonid<strong>in</strong>e, metaboliteenalaprilat, Vasotec, Plavix,albuterol <strong>in</strong>halationPlavix prodrugSomeProcardia, Avapro, Lasix,Vasotec, metaboliteenalaprilatclopidogrel metabolite(Plavix's activeNonemetabolite)AllegraNonesodium citrate (fromBicitra)NonePhoslo Gelcapscitric acid (fromBicitra)epoet<strong>in</strong> alfa <strong>in</strong>jectionNoneMetabolismunknownUnpredictablech<strong>an</strong>geResults after out<strong>patient</strong> drug reconciliation at the time of hospital discharge confirm the absence of serious <strong><strong>in</strong>teractions</strong> <strong>an</strong>d reduce the need for frequent drug level monitor<strong>in</strong>g <strong>in</strong> this <strong>patient</strong>. Nonetheless, all <strong>patient</strong>s whose medications have been recently ch<strong>an</strong>ged or dose-‐adjusted should be followed for: toler<strong>an</strong>ce, side effects, compli<strong>an</strong>ce <strong>an</strong>d therapeutic efficacy. Case summary: The case presented here is that of <strong>an</strong> <strong>elderly</strong> <strong>patient</strong> <strong>with</strong> multiple co-‐morbidities that was admitted to the Nephrology Ward because of renal compla<strong>in</strong>ts. He was under treatment for multiple conditions <strong>an</strong>d tak<strong>in</strong>g over 16 different drugs. Moreover, at the time of discharge, the qu<strong>an</strong>tity of out<strong>patient</strong> medications was close to double that of admission. Upon evaluation of this <strong>patient</strong>’s current pharmacotherapy for drug <strong>in</strong>teraction we found that there were major adverse drug reactions (ADR) among 6 drugs. To circumvent theses ADR we determ<strong>in</strong>ed that drugs concern<strong>in</strong>g this <strong>patient</strong>’s 4 major health concerns (uncontrolled hypertension, CHF, post-‐MI prophylaxis <strong>an</strong>d hypertriglyceridemia) required appropriate reconciliation. The follow<strong>in</strong>g drugs needed to be ch<strong>an</strong>ged, discont<strong>in</strong>ued or optimized: the "baby aspir<strong>in</strong>" was ch<strong>an</strong>ged for Plavix as a suitable substitute 7 , elim<strong>in</strong>ation of Labetalol for U-‐HTN, CHF <strong>an</strong>d MI prophylaxis
12 <strong>Drug</strong> Interactions Case Study: Polypharmacy <strong>in</strong> Elderly <strong>with</strong> Chronic Kidney Disease pharmacological m<strong>an</strong>agement. Adherence, careful adm<strong>in</strong>istration <strong>an</strong>d dos<strong>in</strong>g may be <strong>an</strong> issue <strong>in</strong> most <strong>elderly</strong> <strong>patient</strong>s so a careful effort should be made to assess possible adverse drug reactions (ADRs), particularly, due to genetic <strong>an</strong>d metabolic susceptibility. Article <strong>an</strong>d Text References: 1. "The Effect of Digox<strong>in</strong> on Mortality <strong>an</strong>d Morbidity <strong>in</strong> Patients <strong>with</strong> Heart Failure. the Digitalis Investigation Group." The New Engl<strong>an</strong>d Journal of Medic<strong>in</strong>e. 336.8 (1997): 525-‐33. Pr<strong>in</strong>t. 2. Ball<strong>an</strong>tyne, CM, A Cors<strong>in</strong>i, MH Davidson, H Holdaas, TA Jacobson, E Leitersdorf, W März, JP Reckless, <strong>an</strong>d EA Ste<strong>in</strong>. "Risk for Myopathy <strong>with</strong> Stat<strong>in</strong> Therapy <strong>in</strong> High-‐Risk Patients." Archives of Internal Medic<strong>in</strong>e. 163.5 (2003): 553-‐64. Pr<strong>in</strong>t. 3. B<strong>an</strong>galore, S, S Parkar, E Grossm<strong>an</strong>, <strong>an</strong>d F.H Messerli. "A Meta-‐Analysis of 94,492 Patients <strong>with</strong> Hypertension Treated <strong>with</strong> Beta Blockers to Determ<strong>in</strong>e the Risk of New-‐Onset Diabetes Mellitus." The Americ<strong>an</strong> Journal of Cardiology. 100.8 (2007): 1254-‐1262. Pr<strong>in</strong>t. 4. Baselt, R<strong>an</strong>dall C. Disposition of Toxic <strong>Drug</strong>s <strong>an</strong>d Chemicals <strong>in</strong> M<strong>an</strong>. Davis, Calif: Biomedical Publications, 1982. Pr<strong>in</strong>t. 5. Ford, ES, C Li, G Zhao, WS Pearson, <strong>an</strong>d AH Mokdad. "Hypertriglyceridemia <strong>an</strong>d Its Pharmacologic Treatment Among Us Adults." Archives of Internal Medic<strong>in</strong>e. 169.6 (2009): 572-‐8. Pr<strong>in</strong>t. 6. Good, C B. "Polypharmacy <strong>in</strong> Elderly Patients <strong>with</strong> Diabetes." Diabetes Spectrum. 15.4 (2002): 240-‐248. Pr<strong>in</strong>t. 7. Greenhalgh, J, A Bagust, A Bol<strong>an</strong>d, C.M Saborido, J Oyee, M Blundell, Y Dundar, R Dickson, C Proudlove, <strong>an</strong>d M Fisher. "Clopidogrel <strong>an</strong>d Modified-‐Release Dipyridamole for the Prevention of Occlusive Vascular Events (review of Technology Appraisal No. 90): a Systematic Review <strong>an</strong>d Economic Analysis." Health Technology Assessment Southampton. 15.31 (2011). Pr<strong>in</strong>t. 8. Hilmer, SN, GM Shenfield, <strong>an</strong>d Couteur D. G. Le. "Cl<strong>in</strong>ical Implications of Ch<strong>an</strong>ges <strong>in</strong> Hepatic <strong>Drug</strong> Metabolism <strong>in</strong> Older People." Therapeutics <strong>an</strong>d Cl<strong>in</strong>ical Risk M<strong>an</strong>agement. 1.2 (2005): 151-‐6. Pr<strong>in</strong>t. 9. Hunt, SA. "ACC/AHA 2005 Guidel<strong>in</strong>e Update for the Diagnosis <strong>an</strong>d M<strong>an</strong>agement of Chronic Heart Failure <strong>in</strong> the Adult: a Report of the Americ<strong>an</strong> College of Cardiology/americ<strong>an</strong> Heart Association Task Force on Practice Guidel<strong>in</strong>es (writ<strong>in</strong>g Committee to Update the 2001 Guidel<strong>in</strong>es for the Evaluation <strong>an</strong>d M<strong>an</strong>agement of Heart Failure)." Journal of the Americ<strong>an</strong> College of Cardiology. 46.6 (2005): 1-‐82. Pr<strong>in</strong>t.
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