Potentially serious drug-drug interactions among community-dwelling older adult dental patients

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    Ob resultsaf s in thsee tify pint visitinStu an ongMedicare 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 seriousintRea stheCowiina






    Vol. 112 No. 2 August 2011

    NTEditoeractions.sults. Overall, 3.4% of those visiting the dentist were estimated to have been prescribed drugs with the potential forerious drug interaction. Drugs commonly prescribed in dentistry with the potential for serious interactions includebenzodiazepines, macrolide antibiotics, and nonsteroidal antiinflammatory analgesics.nclusions. Understanding potentially harmful drug combinations, their clinical consequences, and the frequencyth which implicated drugs are being prescribed will assist practitioners in clinically managing patients and avoidingppropriate prescribing. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2011;112:153-160)

    e recent Institute of Medicine report Preventingedication Errors again raises the issue of drug safetyd the importance of reducing medication errors andverse drug events, including those resulting fromg interactions.1 This will be a health safety issue ofreasing importance for dental practitioners in the

    ming decades as greater numbers of older Americansk oral health care because of population growth,

    clining edentulism, more complex dental needs, andater treatment expectations.2-4 The number of Amer-ns aged 65 years is expected to grow from an

    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.9,10Adverse drug experience risk, including drug-drug inter-otentially serious drug-drug interacticommunity-dwelling older adultDaniel D. Skaar, DDS, MS, MBA,a and Heidi ODEVELOPMENTAL AND SURGICAL SCIENCES, UNIV

    jectives. Reducing adverse drug events, including thoseety issue of increasing importance for dental practitionerk oral health care. The purpose of this study was to ideneractions and estimate prevalent use among older adultsdy design. The Medicare Current Beneficiary Survey is

    MEDICAL MANAGEMEimated 37 million in 2006 to 71.5 million by 2030,resenting nearly 20% of the U.S. population.5 Sec-


    sistant Professor.search Associate.

    ceived for publication Jan. 12, 2011; returned for revision Mar. 2,1; accepted for publication Mar. 14, 2011.9-2104/$ - see front matter

    2011 Mosby, Inc. All rights reserved.:10.1016/j.tripleo.2011.03.048amongtal patientsnor, MS,b Minneapolis, MinnesotaY OF MINNESOTA

    ing from drug-drug interactions, will be a healthe coming decades as greater numbers of older adultsrescription drugs with the potential for seriousg the dentist.oing series of nationally representative surveys of

    AND PHARMACOLOGY UPDATErs: F. John Firriolo and Nelson I. Rhodusions, rises with greater consumption of prescriptiongs.11-13 Drug interactions are likely to be exacerbatedthis population by age-related physiologic, pharmaco-etic, and pharmacodynamic changes in drug absorp-n, distribution, metabolism, and excretion.14-16 It willincumbent on dental practitioners to monitor their oldertients increasingly complicated prescription drug pro-s to identify possible clinically relevant drug interac-ns and to avoid prescribing drugs that may cause anificant new interaction.


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    OOOOE154 Skaar and OConnor August 2011Oral health clinicians are faced with the daily chal-ge of assessing and interpreting the potential clinicalevance of adverse drug-drug interactions. The num-r of these interactions reported in compendia, such as

    Physicians Desk Reference, can appear to be over-elming. Although theoretic drug-drug interactionsextensively covered in the clinical pharmacology

    rature, assessing clinical relevance is confusing ow-to a lack of consistent rating systems and consid-

    ble disagreement regarding clinical importance.16-18vertheless, as an aging ambulatory population seeksntal care, clinicians attempting to improve prescrib-

    practices will be confronted with the challenge oferpreting the extensive available drug information,ntifying possible drug interactions, and determiningclinical relevance of specific potential interactionstheir patients.19-21

    Although published studies have estimated the prev-nce of potentially serious drug interactions in ambu-ory older adults, little is known about the prevalencepotentially serious drug interactions in community-elling older adults seeking dental care.13,17 The ob-tives of the present study included the following: 1)raise dental awareness of an example of a previouslyveloped list of potentially serious drug interactions;to use a nationally representative administrative data, the Medicare Current Beneficiary Survey (MCBS),estimate the prevalence of possible drug interactionscommunity-dwelling older adults with dental visits;to assess the value of predictors that may help alertntal professionals to older adults that may be ather risk for having a drug-drug interaction; and 4) tovide examples of drug interactions that may have a

    leterious effect on oral health. Knowledge of poten-l serious drug interactions can assist dental profes-nals in assessing health histories, identifying exist-

    patient adverse experiences needing consultation,d improving prescribing practices.

    ATERIALS AND METHODSThe annual MCBS is a continuous nationally repre-tative longitudinal panel survey of the Medicare

    pulation sponsored by the Centers for Medicare andedicaid Services through a contract with Westatrp. (www.westat.com). The survey creates a com-hensive file of sociodemographic, health care ser-e utilization, including dental services, and prescrip-n drug information. Data were analyzed with the usethe 2006 MCBS Cost and Use files of community-elling beneficiaries age 65 years.In the MCBS survey, prescription drug data arellected during quarterly interviews. The prescriptions include new and refill prescription medications

    th drug names, National Drug Codes, number ofscriptions, limited quantity information, and thear in which the prescription was reported. All drugnd and generic name entries were reviewed for

    curacy and linked appropriately. The analysis of pre-iption drugs with the potential for serious drug in-actions likely to occur in the community setting wassed on the published work of the Partnership toevent Drug-Drug Interactions.22 A total of 25 drug-g or drug classdrug interactions most likely to

    use harm if undetected were identified with the use of-stage review process. Candidate interactions werentified from reviews of drug interaction compendialowed by systematic literature reviews developingidence for drug interactions. Finally, using a modi-d Delphi process, a group of pharmacology expertsated a list of potentially serious drug-drug interac-ns for community and ambulatory settings. For eachg-drug interaction, the precipitant drug is responsi-for influencing the therapeutic effect of the objectg. For example, the azole antifungal drug flucona-

    le (Diflucan) (precipitant drug) inhibits CYP3A4 me-olism of alprazolam (Xanax), a benzodiazepine (ob-t drug). A separate file was created to identify andk the drugs with the potential for serious drug-drugeractions.Analyses were computed with the use of WestVarftware, which incorporates the complex design of theCBS using replicate weights. Standard errors wereimated using Fay variant of balanced repeated rep-ation methods (WestVar software). National popula-n estimates were calculated and comparisons madeall community-dwelling older adults with and with-

    t dental visits. Demographic and socioeconomic vari-les included age, gender, race, income, education,pulation density, marital status, and U.S. Censusreau region. Health-related variables included self-orted general health and comorbidities and dentalits (yes/no). Potential clinically important prescrip-n drug interactions (yes/no) were coded along withmedication names.

    We used multiple logistic regression to identify andimate characteristics predictive of being prescribedgs which may result in clinically significant drug

    eractions for community-dwelling older adults re-iving dental care. Independent variables tested in-ded demographic and socioeconomic characteristics,

    alth status, dental visits, drug insurance coverage,d prescription drug counts.

    SULTSAccording to the MCBS, in 2006 there were animated 31 million community dwelling Americansed 65 years. High use of prescription drugs wasnd, with 94.3% reporting 1 prescriptions with an

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    OOOOEVolume 112, Number 2 Skaar and OConnor 155erage of 8.2 drugs. Dental visits were reported by animated 14.4 million older adults, and prescriptiong use was similarly high, with 96.2% reportingeiving 1 prescription with an average of 8.0 drugsen.Table I summarizes the 25 drug or drug class inter-tions of clinical importance identified by the Partner-p to Prevent Drug-Drug Interactions. Benzodiazepines,crolide antibiotics, and nonsteroidal antiinflammatory

    ble I. Drug-drug interactions of clinical importance inObject drug or class

    ticoagulants (anisindione, dicumarol, warfarin)

    nzodiazepines (alprazolam, triazolam)


    oxinot alkaloids (dihydroergotamine, ergotamine, methylsergide)

    rogen-progestin products (oral contraceptives)nciclovirO inhibitors (isocarboxazid, phenelzine, selegiline, tranylcypromine

    O inhibitors (isocarboxazid, phenalzine, selegiline, tranylcypromine


    thotrexaterates (nitroglycerin, isosorbide dinitrate/mononitrate)ozide


    RIs (citalopram, fluoxetine, fluvoxamine, nefazodone, paroxetine,ertraline, ventalaxine)

    eophyllineseophyllinesiopurines (azathloprine, mercaptopurine)rfarinrfarin


    O, Monoamine oxidase; SSRI, selective serotonin reuptake inhibitoalone DC, Abarca J, Hansten PD, Grizzle AJ, Armstrong EP, van Bepartnership to prevent drug-drug interactions. J Am Pharm Assoc 2

    rugs that may be prescribed in dentistry.on-SSRIs included with SSRIs because of similar pharmacologic prgs (NSAIDs) are commonly prescribed in dentistry.ble II identifies the most prevalent drugs listed in Tablehat were reported for older adults seeking dental care.For 2006 community-dwelling older adults with antal visit, national prevalence estimates for possibleious drug-drug interactions are reported in Table IIIdemographic, socioeconomic, and health-related

    aracteristics. Overall, 3.4% of those visiting the den-t were estimated to have been prescribed drugs with

    ulatory setting*Precipitant drug or class

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

    Azole antifungal agents (fluconazole, itraconazole,ketoconazole)

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

    tranylcypromine)ClarithromycinMacrolide 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)

    C, et al. Identification of serious drug-drug interactions: results of:142-51.druTaI t





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    OOOOE156 Skaar and OConnor August 2011potential for a serious drug interaction if takenncurrently. Based on 2 analyses, the prescribing of 2gs with the potential for a serious interaction wasst strongly associated with increasing age, race,

    orer self-reported health, and higher comorbidityunts. Of those with a dental visit, the prevalence forssible multiple interactions was estimated to be%. Nationally, this represents 500,000 elderly

    ntal patients taking medications during 2006 thattentially could have 1 harmful interactions.Multiple logistic regression analysis of MCBS data

    those with a dental visit identified characteristicsociated with use of prescription drugs with the po-tial for serious interactions. Independent variables inmodel included age, gender, education, race, in-

    me, drug insurance, comorbidities, general healthtus, geographic region, and drug counts. Significantriables associated with a medication profile indicat-

    the potential for serious interactions included age5 years (odds ratio [OR] 2.48, 95% confidence in-

    val [CI] 1.26-4.87), annual income $50,000 (OR2, 95% CI 1.34-4.38), and higher numbers of pre-ibed drugs: 8-10 drugs (OR 26.83, 95% CI 1.87-4.52); 11 drugs (OR 53.19, 95% CI 3.76-752.51).

    SCUSSIONHarmful drug-drug interactions are an important typeadverse drug event and a health safety issue that

    ntal practitioners should be aware of.13,23 Seriousverse events have been reported for a number of drugeractions. Elderly patients hospitalized for dig...


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