Vol. 112 No. 2 August 2011

MEDICAL MANAGEMENT AND PHARMACOLOGY UPDATEEditors: F. John Firriolo and Nelson I. Rhodus

Potentially serious drug-drug interactions amongcommunity-dwelling older adult dental patientsDaniel D. Skaar, DDS, MS, MBA,a and Heidi O’Connor, MS,b Minneapolis, MinnesotaDEVELOPMENTAL AND SURGICAL SCIENCES, UNIVERSITY OF MINNESOTA

Objectives. Reducing adverse drug events, including those resulting from drug-drug interactions, will be a healthsafety issue of increasing importance for dental practitioners in the coming decades as greater numbers of older adultsseek oral health care. The purpose of this study was to identify prescription drugs with the potential for seriousinteractions and estimate prevalent use among older adults visiting the dentist.Study design. The Medicare Current Beneficiary Survey is an ongoing series of nationally representative surveys ofMedicare beneficiaries. Potentially serious drug interactions were selected with the use of published work byPartnership to Prevent Drug-Drug Interactions. Drug interactions were identified and prevalence estimates made forcommunity-dwelling older adults visiting the dentist. Analyses were completed to test associations betweensociodemographic and health-related variables and the use of prescription drugs with the potential for seriousinteractions.Results. Overall, 3.4% of those visiting the dentist were estimated to have been prescribed drugs with the potential fora serious drug interaction. Drugs commonly prescribed in dentistry with the potential for serious interactions includethe benzodiazepines, macrolide antibiotics, and nonsteroidal antiinflammatory analgesics.Conclusions. Understanding potentially harmful drug combinations, their clinical consequences, and the frequencywith which implicated drugs are being prescribed will assist practitioners in clinically managing patients and avoiding

inappropriate prescribing. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2011;112:153-160)

The recent Institute of Medicine report “PreventingMedication Errors” again raises the issue of drug safetyand the importance of reducing medication errors andadverse drug events, including those resulting fromdrug interactions.1 This will be a health safety issue ofincreasing importance for dental practitioners in thecoming decades as greater numbers of older Americansseek oral health care because of population growth,declining edentulism, more complex dental needs, andgreater treatment expectations.2-4 The number of Amer-icans aged �65 years is expected to grow from anestimated 37 million in 2006 to 71.5 million by 2030,representing nearly 20% of the U.S. population.5 Sec-

aAssistant Professor.bResearch Associate.Received for publication Jan. 12, 2011; returned for revision Mar. 2,2011; accepted for publication Mar. 14, 2011.1079-2104/$ - see front matter© 2011 Mosby, Inc. All rights reserved.

doi:10.1016/j.tripleo.2011.03.048

ular trends in tooth loss for older adults predict acontinuing drop in edentulism as the percentage with-out any teeth has declined from �46% in the early1970s to 26% by 2006.6

This impending wave of older adult dental patients willpresent with a higher prevalence of chronic diseases, suchas hypertension, stroke, and diabetes that typically requireextensive medication therapies.7,8 The prevalence of pre-scription drug use increases dramatically with age.9,10

Adverse drug experience risk, including drug-drug inter-actions, rises with greater consumption of prescriptiondrugs.11-13 Drug interactions are likely to be exacerbatedin this population by age-related physiologic, pharmaco-kinetic, and pharmacodynamic changes in drug absorp-tion, distribution, metabolism, and excretion.14-16 It willbe incumbent on dental practitioners to monitor their olderpatients’ increasingly complicated prescription drug pro-files to identify possible clinically relevant drug interac-tions and to avoid prescribing drugs that may cause a

significant new interaction.

153

OOOOE154 Skaar and O’Connor August 2011

Oral health clinicians are faced with the daily chal-lenge of assessing and interpreting the potential clinicalrelevance of adverse drug-drug interactions. The num-ber of these interactions reported in compendia, such asthe Physicians’ Desk Reference, can appear to be over-whelming. Although theoretic drug-drug interactionsare extensively covered in the clinical pharmacologyliterature, assessing clinical relevance is confusing ow-ing to a lack of consistent rating systems and consid-erable disagreement regarding clinical importance.16-18

Nevertheless, as an aging ambulatory population seeksdental care, clinicians attempting to improve prescrib-ing practices will be confronted with the challenge ofinterpreting the extensive available drug information,identifying possible drug interactions, and determiningthe clinical relevance of specific potential interactionsfor their patients.19-21

Although published studies have estimated the prev-alence of potentially serious drug interactions in ambu-latory older adults, little is known about the prevalenceof potentially serious drug interactions in community-dwelling older adults seeking dental care.13,17 The ob-jectives of the present study included the following: 1)to raise dental awareness of an example of a previouslydeveloped list of potentially serious drug interactions;2) to use a nationally representative administrative dataset, the Medicare Current Beneficiary Survey (MCBS),to estimate the prevalence of possible drug interactionsin community-dwelling older adults with dental visits;3) to assess the value of predictors that may help alertdental professionals to older adults that may be athigher risk for having a drug-drug interaction; and 4) toprovide examples of drug interactions that may have adeleterious effect on oral health. Knowledge of poten-tial serious drug interactions can assist dental profes-sionals in assessing health histories, identifying exist-ing patient adverse experiences needing consultation,and improving prescribing practices.

MATERIALS AND METHODSThe annual MCBS is a continuous nationally repre-

sentative longitudinal panel survey of the Medicarepopulation sponsored by the Centers for Medicare andMedicaid Services through a contract with WestatCorp. (www.westat.com). The survey creates a com-prehensive file of sociodemographic, health care ser-vice utilization, including dental services, and prescrip-tion drug information. Data were analyzed with the useof the 2006 MCBS Cost and Use files of community-dwelling beneficiaries age �65 years.

In the MCBS survey, prescription drug data arecollected during quarterly interviews. The prescriptionfiles include new and refill prescription medications

with drug names, National Drug Codes, number of

prescriptions, limited quantity information, and theyear in which the prescription was reported. All drugbrand and generic name entries were reviewed foraccuracy and linked appropriately. The analysis of pre-scription drugs with the potential for serious drug in-teractions likely to occur in the community setting wasbased on the published work of the Partnership toPrevent Drug-Drug Interactions.22 A total of 25 drug-drug or drug class–drug interactions most likely tocause harm if undetected were identified with the use ofa 3-stage review process. Candidate interactions wereidentified from reviews of drug interaction compendiafollowed by systematic literature reviews developingevidence for drug interactions. Finally, using a modi-fied Delphi process, a group of pharmacology expertscreated a list of potentially serious drug-drug interac-tions for community and ambulatory settings. For eachdrug-drug interaction, the precipitant drug is responsi-ble for influencing the therapeutic effect of the objectdrug. For example, the azole antifungal drug flucona-zole (Diflucan) (precipitant drug) inhibits CYP3A4 me-tabolism of alprazolam (Xanax), a benzodiazepine (ob-ject drug). A separate file was created to identify andlink the drugs with the potential for serious drug-druginteractions.

Analyses were computed with the use of WestVarsoftware, which incorporates the complex design of theMCBS using replicate weights. Standard errors wereestimated using Fay variant of balanced repeated rep-lication methods (WestVar software). National popula-tion estimates were calculated and comparisons madefor all community-dwelling older adults with and with-out dental visits. Demographic and socioeconomic vari-ables included age, gender, race, income, education,population density, marital status, and U.S. CensusBureau region. Health-related variables included self-reported general health and comorbidities and dentalvisits (yes/no). Potential clinically important prescrip-tion drug interactions (yes/no) were coded along withthe medication names.

We used multiple logistic regression to identify andestimate characteristics predictive of being prescribeddrugs which may result in clinically significant druginteractions for community-dwelling older adults re-ceiving dental care. Independent variables tested in-cluded demographic and socioeconomic characteristics,health status, dental visits, drug insurance coverage,and prescription drug counts.

RESULTSAccording to the MCBS, in 2006 there were an

estimated 31 million community dwelling Americansaged �65 years. High use of prescription drugs was

found, with 94.3% reporting �1 prescriptions with an

profile

OOOOEVolume 112, Number 2 Skaar and O’Connor 155

average of 8.2 drugs. Dental visits were reported by anestimated 14.4 million older adults, and prescriptiondrug use was similarly high, with 96.2% reportingreceiving �1 prescription with an average of 8.0 drugstaken.

Table I summarizes the 25 drug or drug class inter-actions of clinical importance identified by the Partner-ship to Prevent Drug-Drug Interactions. Benzodiazepines,

Table I. Drug-drug interactions of clinical importanceObject drug or class

Anticoagulants (anisindione, dicumarol, warfarin)

Benzodiazepines (alprazolam, triazolam)†

CarbamazepineCyclosporineDextromethorphan

DigoxinErgot alkaloids (dihydroergotamine, ergotamine, methylsergide)

Estrogen-progestin products (oral contraceptives)GanciclovirMAO inhibitors (isocarboxazid, phenelzine, selegiline, tranylcyprom

MAO inhibitors (isocarboxazid, phenalzine, selegiline, tranylcyprom

Meperidine†

MethotrexateNitrates (nitroglycerin, isosorbide dinitrate/mononitrate)Pimozide

Pimozide

SSRIs (citalopram, fluoxetine, fluvoxamine, nefazodone, paroxetine,sertraline, ventalaxine)‡

TheophyllinesTheophyllinesThiopurines (azathloprine, mercaptopurine)WarfarinWarfarin

WarfarinWarfarinWarfarin

MAO, Monoamine oxidase; SSRI, selective serotonin reuptake inhib*Malone DC, Abarca J, Hansten PD, Grizzle AJ, Armstrong EP, vanthe partnership to prevent drug-drug interactions. J Am Pharm Asso†Drugs that may be prescribed in dentistry.‡Non-SSRIs included with SSRIs because of similar pharmacologic

macrolide antibiotics, and nonsteroidal antiinflammatory

drugs (NSAIDs) are commonly prescribed in dentistry.Table II identifies the most prevalent drugs listed in TableI that were reported for older adults seeking dental care.

For 2006 community-dwelling older adults with adental visit, national prevalence estimates for possibleserious drug-drug interactions are reported in Table IIIby demographic, socioeconomic, and health-relatedcharacteristics. Overall, 3.4% of those visiting the den-

bulatory setting*Precipitant drug or class

Thyroid hormones (levothyroxine, liothyronine, liotrix, thyroid,dextrothyroxine)

Azole antifungal agents (fluconazole, itraconazole,ketoconazole)†

Propoxyphene†

Rifamycins (rifampin, rifabutin, rifapentine)MAO inhibitors (isocarboxazid, phenelzine, safegilene,

tranylcypromine)Clarithromycin†

Macrolide antibiotics (clarithromycin, erythromycin,troleandomycin)†

RifampinZidovudineAnorexiants (amphetamine, benzphetamine, dexfenfluramine,

dextroamphetamine, Diethylpropion, fenfluramine, mazindol,methamphetamine, phendimetrazine, phentermine,phenlpropanolamine, albutramine)

Sympathomimetics (dopamine, ephedrine, isometheptene,mucate, mephentermine, metaraminol, phenylephrine,pseudoephedrine)

MAO inhibitors (isocarboxazid, phenalzine, selegiline,tranylcypromine)

Trimethoprim (trimethoprim-sulfamethoxazole, trimethoprim)SildenafilMacrolide antibiotics (clarithromycin, dirithromycin,

erythromycin, troleandomycin)†

Azole antifungal agents (fluconazole, itraconazole,ketoconazole)†

MAO inhibitors (isocarboxazid, phenelzine, salegiline,tranylcypromine)

Quinolones (ciprofloxacin, enoxacin)†

FluvoxamineAllopurinolSulfinpyrazoneNonsteroidal antiinflammatory drugs (celecoxib, diclofenac,

etodolac, flubiprofen, fenoprofen, ibuprofen, indomethacin,ketoprofen, ketorolac, meclofenamate, mefenarmic acid,nabumetone, naproxen, oxaprozin, piroxlcam, rofecoxib,sulindac, tolmetin)†

CimetidineFibric acid derivatives (clofibrate, fenofibrate, gemfibrozil)Barbiturates (amobarbital, butabarbital, butabital, mephobarbital,

phenobarbital, secobarbital)

RC, et al. Identification of serious drug-drug interactions: results of44:142-51.

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itor.Bergenc 2004;

tist were estimated to have been prescribed drugs with

OOOOE156 Skaar and O’Connor August 2011

the potential for a serious drug interaction if takenconcurrently. Based on �2 analyses, the prescribing of 2drugs with the potential for a serious interaction wasmost strongly associated with increasing age, race,poorer self-reported health, and higher comorbiditycounts. Of those with a dental visit, the prevalence forpossible multiple interactions was estimated to be0.5%. Nationally, this represents �500,000 elderlydental patients taking medications during 2006 thatpotentially could have �1 harmful interactions.

Multiple logistic regression analysis of MCBS datafor those with a dental visit identified characteristicsassociated with use of prescription drugs with the po-tential for serious interactions. Independent variables inthe model included age, gender, education, race, in-come, drug insurance, comorbidities, general healthstatus, geographic region, and drug counts. Significantvariables associated with a medication profile indicat-ing the potential for serious interactions included age�85 years (odds ratio [OR] 2.48, 95% confidence in-terval [CI] 1.26-4.87), annual income �$50,000 (OR2.42, 95% CI 1.34-4.38), and higher numbers of pre-scribed drugs: 8-10 drugs (OR 26.83, 95% CI 1.87-384.52); �11 drugs (OR 53.19, 95% CI 3.76-752.51).

DISCUSSIONHarmful drug-drug interactions are an important type

of adverse drug event and a health safety issue thatdental practitioners should be aware of.13,23 Seriousadverse events have been reported for a number of druginteractions. Elderly patients hospitalized for digoxintoxicity were found to be 12 times more likely to havereceived clarithromycin, and diabetics admitted for hy-poglycemia while taking glyburide were 6 times more

Table II. Prevalence estimates for drugs with potentialfor drug-drug interactions of clinical importance forcommunity-dwelling Medicare beneficiaries* with adental visit in 2006 (estimated n � 14,361,198; SE �230,745)

% SE

Thyroid hormones 17.64 0.68NSAIDs 17.60 0.65SSRIs 10.05 0.41Benzodiazepines 9.61 0.47Anticoagulants 8.45 0.48Quinolones 8.21 0.42Nitrates 7.18 0.42Propoxyphene 6.77 0.39Digoxin 4.27 0.32

NSAIDs � nonsteroidal antiinflammatory drugs; SSRI � selectiveserotonin reuptake inhibitor.*�65 years of age, enrolled for the entire year of 2006.

likely to have taken cotrimoxazole.24 Bleeding risk has

been reported to increase considerably with concurrentNSAID and coumarin therapy compared with coumarintherapy alone.25 Drug interaction risk is likely to in-crease as new drugs continue to be introduced, addi-tional interactions are discovered, and an aging popu-lation with declining physiologic capacity consumesmore prescription drugs.26

Complicating the identification of serious interac-tions is the need to interpret a vast drug interactionliterature and the lack of standardized methodologies torate clinical risk among various drug compendia.18 Tofocus on serious interactions with clinical relevance,the present study used a previously identified list of 25clinically important interactions likely to occur in acommunity setting that was developed with a system-atic literature review and expert panel process.22

The present study reinforces the importance for oralhealth care providers to remain current in their knowl-edge of clinical pharmacology as it updates and con-firms the extensive use of prescription drugs by olderadults.9,10 Of the 2006 community-dwelling olderadults with dental visits, it was estimated that 96.2%had a prescription for �1 drugs. Polypharmacy (use ofmultiple medications) is common in older adults, andthis was confirmed for those seeking dental care; thispopulation had prescriptions for an estimated averageof 8 different drugs. A key finding is that overall 3.4%of those presenting for dental visits had prescriptionsfor drugs that, if taken concomitantly, could result in aharmful interaction. Similarly, other studies using dif-ferent methodologies have reported potential exposurerates for �1 interactions in the �1%-4% range.10,27

Logistic regression modeling identified those �85years and those with increasing drug counts as moststrongly associated with possible drug interactionsidentified by the Partnership to Prevent Drug-DrugInteractions. Clearly, dentists should be especially vig-ilant for interactions when reviewing the drug historiesof the ambulatory oldest old and those taking highnumbers of prescription drugs.

Consideration of drug interactions should be an in-tegral part of prescribing practices in dentistry. Thelikelihood of adverse drug events increases as drugregimens become more complex.12 A number of drugscommonly prescribed by dentists have the potential fora serious drug interaction.22 Drugs listed in Table I thatdentists may prescribe include NSAIDs (e.g., ibupro-fen, naproxen), alprazolam (Xanax), triazolam (Hal-cion), propoxyphene (Darvon), erythromycin, clarithro-mycin (Biaxin), meperidine (Demerol), ciprofloxacin(Cipro), and fluconazole (Diflucan). In 2010, the Foodand Drug Administration requested the discontinuation

of marketing of all propoxyphene products in the U.S.

OOOOEVolume 112, Number 2 Skaar and O’Connor 157

owing to new evidence of interference with cardiacelectrical activity and higher risk of arrhythmias.

The risk of excessive bleeding or hemorrhage is aserious adverse event that dentists should be aware ofwhen performing invasive procedures or prescribinganalgesics for older patients. Approximately 10% ofolder adults seeking dental care had taken an anticoag-ulant for the treatment or prophylaxis of thromboem-bolic diseases. Bleeding risk is an established compli-cation of the coumarin derivatives which interfere withvitamin K cofactor functions and inhibit synthesis ofcoagulation factors (II, VII, IX, and X). Warfarin (cou-madin) is the most commonly prescribed oral antico-agulant, and its many drug interactions have been re-ported.28 Initiating or changing dosing for thyroidhormone replacement products will alter catabolism ofvitamin K–dependent clotting factors. Use of fibrinicacid derivatives may increase bleeding risk by compet-ing for coumarin plasma protein binding sites. Concur-rent prescribing of NSAIDs should be considered care-fully, because the combination may exacerbatebleeding complications by inhibiting cyclooxygenase-1(COX-1), resulting in reduced platelet aggregation, in-creasing warfarin serum levels through plasma proteindisplacement, and elevating gastrointestinal bleedingrisk by depletion of COX-1–produced prostaglandinsthat confer a protective effect by stimulating synthesisand secretion of mucus and bicarbonate.29,30

Dental providers should avoid or use caution withother drug combinations. Prescribing oral alprazolam(Xanax) or triazolam (Halcion) for anxiolysis in dentalcare should be avoided in patients taking azole antifun-gal agents. Azole antifungal drugs, such as fluconazole,inhibit cytochrome P450 (CYP) 3A4 metabolism ofbenzodiazepines, increasing plasma drug levels andpotentiating their sedative and psychomotor impair-ment effects.31 The cardiac glycoside digoxin, used totreat heart failure and supraventricular arrhythmias, andthe asthma drug theophylline have narrow therapeuticindexes or low margins of safety. Consideration ofpossible drug interactions is important, because suddenincreases in plasma levels of these drugs may lead toserious toxicities. The macrolide antibiotics erythromy-cin and clarithromycin (Biaxin), prescribed for oralinfections, may cause digitalis toxicity by increasingintestinal absorption and decreasing renal excre-tion.32,33 Possible mechanisms include increasing oralbioavailability by preventing gut bacterial metabolism,inhibiting p-glycoprotein active drug transport backinto the intestine, and reducing transporter p-glycopro-tein mediated renal tubular secretion. Quinolone anti-biotics, such as ciprofloxacin (Cipro), used for peri-odontal infections are potent inhibitors of CYP1A2

which metabolizes theophylline products.20 Toxic the-

ophylline levels may result in cardiac arrhythmias andcentral nervous system effects, including restlessnessand convulsions. The concurrent use of the analgesicmeperidine (Demerol) and monoamine oxidase inhibi-tor (MAOI) antidepressants should be avoided.30 Thiscombination has been associated with serotonin syn-drome, a potentially life-threatening adverse reactionwith clinical findings ranging from tremor and agitationto muscular hypertonicity and shock.34

The present study has several limitations. First,MCBS prescription data may be underreported.35 Re-porting is subject to recall errors because it is self- orproxy-reported; however, recall bias is likely reducedby periodic interviews with collection of receipts andclaim forms. Underreporting may be less likely forchronically used medications being regularly refilled,owing to periodic surveying. Nevertheless, the datareported could be incomplete and underestimate pre-scription drug use and, therefore, possible drug inter-actions. Second, for some drug interactions the preva-lence may be overestimated. The use of only 1 druginteraction classification methodology may result inunderreporting of serious interactions. The MCBS ex-cludes self-medication with over-the-counter drugs,supplements, and alternative medicines which are otherpotential sources of drug interactions.10 Each interac-tion selected by the Partnership to Prevent Drug-DrugInteractions was included regardless of length of treat-ment and without the complete ability to verify con-comitant use of the drugs. However, many of the drugsincluded in the analysis are typically taken long-termfor chronic conditions and could be presumed to beused concurrently. There may be situations when drugswith the potential for a serious interaction are consid-ered to be therapeutically necessary given the risks andmonitored clinically to prevent an unacceptable adverseeffect. Finally, as new prescription drugs are introducedand new prescribing information becomes available it islikely that this list of potentially serious drug interac-tions will need modification.

In the future, an increasingly ambulatory aging pop-ulation is more likely to seek dental care. These olderadults will present with more complex drug regimens asthey cope with a higher prevalence of chronic diseases,such as diabetes, hypertension, and stroke.7 Adversedrug effects may be exacerbated by age-related phar-macokinetic and pharmacodynamic changes, includingdeclining renal and hepatic clearance, which may in-crease and prolong toxic plasma drug levels. Under-standing potentially harmful drug combinations, theirclinical consequences, and the frequency with whichimplicated drugs are being prescribed will assist pro-viders in clinically managing patients and avoiding

inappropriate prescribing. Using a systematically deter-

OOOOE158 Skaar and O’Connor August 2011

Table III. Prevalence estimates for potential drug-drug interactions of clinical importance by sociodemographic andhealth-related characteristics for community-dwelling Medicare beneficiaries* with a dental visit in 2006 (estimatedn � 14,361,198; SE � 230,745)

Estimated population

�1 drug-druginteraction

(est. n � 490,874)

Demographic characteristics n SE % SE % SE

Age (y)†

65-69 3,099,903 128,864 21.59 0.71 2.02 0.6070-74 3,880,939 114,885 27.02 0.74 2.86 0.5775-79 3,263,967 103,956 22.73 0.66 3.46 0.6680-84 2,518,746 91,432 17.54 0.63 4.32 0.6185� 1,597,644 71,424 11.12 0.45 6.01 1.01

GenderMale 6,173,862 152,494 42.99 0.69 3.57 0.48Female 8,187,336 149,172 57.01 0.69 3.31 0.354

Race‡

Unknown 5,979 4,260 0.04 0.03 0.00 0.00White 13,297,859 220,737 92.60 0.42 3.59 0.32Black 608,748 45,441 4.24 0.32 1.27 0.91Other 142,460 26,269 0.99 0.18 0.00 0.00Asian 130,661 26,970 0.91 0.19 0.00 0.00Hispanic 133,129 22,134 0.93 0.15 3.92 2.81Native American 42,362 16,208 0.29 0.11 0.00 0.00

Income0-$25,000 5,029,440 137,098 35.02 0.78 3.07 0.41$25,001-$50,000 5,822,241 131,156 40.54 0.85 3.07 0.51�$50,000 3,509,518 150,700 24.44 0.86 4.49 0.73

EducationUnknown 36,057 12,361 0.25 0.09 0.00 0.00�8th grade 833,714 61,694 5.81 0.43 3.84 1.309th-12 grade/HS grad. 5,321,323 140,284 37.05 0.97 3.75 0.48Post–high school 4,074,038 143,718 28.37 0.82 3.04 0.55College grad./postgrad. 4,096,067 156,951 28.52 0.89 3.31 0.59

Population densityNonmetropolitan 2,595,362 121,137 18.07 0.74 4.13 0.76Metropolitan 11,765,837 197,297 81.93 0.74 3.26 0.33

Marital statusUnknown 5,952 4,154 0.04 0.03 0.00 0.00Married 8,967,188 192,673 62.44 0.90 3.31 0.39Widowed 3,799,328 127,771 26.46 0.85 4.17 0.58Divorced 1,085,549 72,382 7.56 0.46 1.92 0.78Separated 53,292 16,552 0.37 0.12 0.00 0.00Never married 449,889 44,492 3.13 0.30 3.32 1.75

United States Census‡

New England 526,645 95,168 3.67 0.66 0.85 0.90Middle Atlantic 2,122,204 124,747 14.78 0.84 3.59 0.68East North Central 2,678,716 191,421 18.65 1.26 4.34 0.94West North Central 892,514 143,933 6.21 0.99 4.64 1.72South Atlantic 2,633,520 215,837 18.34 1.52 3.57 0.62East South Central 1,006,453 113,043 7.01 0.77 2.90 1.13West South Central 1,213,799 251,194 8.45 1.74 3.86 0.92Mountain 1,212,598 211,264 8.44 1.46 2.56 0.90Pacific 1,934,796 215,684 13.47 1.49 2.56 0.80Puerto Rico 139,953 13,113 0.97 0.09 1.50 1.37

Self-reported health†

Unknown 94,566 23,248 0.66 0.16 3.08 3.244Excellent 2,763,712 112,755 19.24 0.66 1.76 0.601Very good 5,011,704 140,775 34.90 0.84 2.58 0.475Good 4,481,358 137,640 31.20 0.81 4.11 0.576Fair 1,590,259 64,806 11.07 0.44 5.62 1.07

Poor 419,599 43,979 2.92 0.31 8.73 2.909

OOOOEVolume 112, Number 2 Skaar and O’Connor 159

mined list of potentially harmful drug interactions andthe nationally representative MCBS, the findings of thepresent study should raise clinician awareness of theneed to carefully assess drug histories. In addition tothe initial examination review, drug profiles should beupdated for potential interactions on an ongoing basisduring patient care, because new drugs may be pre-scribed and new interaction information may becomeavailable. In addition to continually updating drug in-teraction information, future research is needed to iden-tify the prevalence and risks for harmful interactionsinvolving over-the-counter drugs, supplements, andherbals in older adults seeking dental care.

The authors thank Scott Lunos, MS, for statistical analysissupport.

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Table III. (Continued)

Esti

Demographic characteristics n S

Comorbidity count‡

0 854,461 631 2,031,998 1042 3,327,091 1253 3,092,275 116�4 5,043,119 141

Total %

*�65 years of age, enrolled for the entire year of 2006.†P � .01; ‡P � .001.

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�1 drug-druginteraction

(est. n � 490,874)

% SE % SE

5.95 0.44 1.68 0.9714.16 0.64 1.91 0.55223.19 0.77 1.97 0.56221.55 0.79 2.5 0.57435.15 0.83 5.85 0.603

3.42 0.31

mated

E

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Reprint requests:

Dr. Daniel D. SkaarDevelopmental and Surgical SciencesUniversity of Minnesota7-368 Moos Tower515 Delaware St SEMinneapolis, MN 55455

skaar003@umn.edu