Vol. 112 No.

2 August 2011

MEDICAL MANAGEMENT AND PHARMACOLOGY UPDATE

Editors: F. John Firriolo and Nelson I. Rhodus

Potentially serious drug-drug interactions among

community-dwelling older adult dental patients
Daniel D. Skaar, DDS, MS, MBA,a and Heidi O’Connor, MS,b Minneapolis, Minnesota
DEVELOPMENTAL AND SURGICAL SCIENCES, UNIVERSITY OF MINNESOTA

Objectives. Reducing adverse drug events, including those resulting from drug-drug interactions, will be a health
safety issue of increasing importance for dental practitioners in the coming decades as greater numbers of older adults
seek oral health care. The purpose of this study was to identify prescription drugs with the potential for serious
interactions 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 of
Medicare beneficiaries. Potentially serious drug interactions were selected with the use of published work by
Partnership to Prevent Drug-Drug Interactions. Drug interactions were identified and prevalence estimates made for
community-dwelling older adults visiting the dentist. Analyses were completed to test associations between
sociodemographic and health-related variables and the use of prescription drugs with the potential for serious
interactions.
Results. Overall, 3.4% of those visiting the dentist were estimated to have been prescribed drugs with the potential for
a serious drug interaction. Drugs commonly prescribed in dentistry with the potential for serious interactions include
the benzodiazepines, macrolide antibiotics, and nonsteroidal antiinflammatory analgesics.
Conclusions. Understanding potentially harmful drug combinations, their clinical consequences, and the frequency
with 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 “Preventing
Medication Errors” again raises the issue of drug safety
and the importance of reducing medication errors and
adverse drug events, including those resulting from
drug interactions.1 This will be a health safety issue of
increasing importance for dental practitioners in the
coming decades as greater numbers of older Americans
seek oral health care because of population growth,
declining edentulism, more complex dental needs, and
greater treatment expectations.2-4 The number of Amer-
icans aged ⱖ65 years is expected to grow from an
estimated 37 million in 2006 to 71.5 million by 2030,
representing nearly 20% of the U.S. population.5 Sec-
a
Assistant Professor.
b
Research 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 a
continuing drop in edentulism as the percentage with-
out any teeth has declined from ⬃46% in the early
1970s to 26% by 2006.6
This impending wave of older adult dental patients will
present with a higher prevalence of chronic diseases, such
as hypertension, stroke, and diabetes that typically require
extensive 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 prescription
drugs.11-13 Drug interactions are likely to be exacerbated
in this population by age-related physiologic, pharmaco-
kinetic, and pharmacodynamic changes in drug absorp-
tion, distribution, metabolism, and excretion.14-16 It will
be incumbent on dental practitioners to monitor their older
patients’ 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

154 Skaar and O’Connor
Oral health clinicians are faced with the daily chal-
lenge of assessing and interpreting the potential clinical
relevance of adverse drug-drug interactions. The num-
ber of these interactions reported in compendia, such as
the Physicians’ Desk Reference, can appear to be over-
whelming. Although theoretic drug-drug interactions
are extensively covered in the clinical pharmacology
literature, 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 seeks
dental care, clinicians attempting to improve prescrib-
ing practices will be confronted with the challenge of
interpreting the extensive available drug information,
identifying possible drug interactions, and determining
the clinical relevance of specific potential interactions
for 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 prevalence
of 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 previously
developed list of potentially serious drug interactions;
2) to use a nationally representative administrative data
set, the Medicare Current Beneficiary Survey (MCBS),
to estimate the prevalence of possible drug interactions
in community-dwelling older adults with dental visits;
3) to assess the value of predictors that may help alert
dental professionals to older adults that may be at
higher risk for having a drug-drug interaction; and 4) to
provide examples of drug interactions that may have a
deleterious 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 METHODS
The annual MCBS is a continuous nationally repre-
sentative longitudinal panel survey of the Medicare
population sponsored by the Centers for Medicare and
Medicaid Services through a contract with Westat
Corp. (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 use
of the 2006 MCBS Cost and Use files of community-
dwelling beneficiaries age ⱖ65 years.
In the MCBS survey, prescription drug data are
collected during quarterly interviews. The prescription
files include new and refill prescription medications
with drug names, National Drug Codes, number of
OOOOE
August 2011
prescriptions, limited quantity information, and the
year in which the prescription was reported. All drug
brand and generic name entries were reviewed for
accuracy and linked appropriately. The analysis of pre-
scription drugs with the potential for serious drug in-
teractions likely to occur in the community setting was
based on the published work of the Partnership to
Prevent Drug-Drug Interactions.22 A total of 25 drug-
drug or drug class– drug interactions most likely to
cause harm if undetected were identified with the use of
a 3-stage review process. Candidate interactions were
identified from reviews of drug interaction compendia
followed by systematic literature reviews developing
evidence for drug interactions. Finally, using a modi-
fied Delphi process, a group of pharmacology experts
created a list of potentially serious drug-drug interac-
tions for community and ambulatory settings. For each
drug-drug interaction, the precipitant drug is responsi-
ble for influencing the therapeutic effect of the object
drug. 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 and
link the drugs with the potential for serious drug-drug
interactions.
Analyses were computed with the use of WestVar
software, which incorporates the complex design of the
MCBS using replicate weights. Standard errors were
estimated using Fay variant of balanced repeated rep-
lication methods (WestVar software). National popula-
tion estimates were calculated and comparisons made
for 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. Census
Bureau region. Health-related variables included self-
reported general health and comorbidities and dental
visits (yes/no). Potential clinically important prescrip-
tion drug interactions (yes/no) were coded along with
the medication names.
We used multiple logistic regression to identify and
estimate characteristics predictive of being prescribed
drugs which may result in clinically significant drug
interactions 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.
RESULTS
According to the MCBS, in 2006 there were an
estimated 31 million community dwelling Americans
aged ⱖ65 years. High use of prescription drugs was
found, with 94.3% reporting ⱖ1 prescriptions with an
OOOOE
Volume 112, Number 2 Skaar and O’Connor 155

Table I. Drug-drug interactions of clinical importance in ambulatory setting*

Object drug or class Precipitant drug or class
Anticoagulants (anisindione, dicumarol, warfarin) Thyroid hormones (levothyroxine, liothyronine, liotrix, thyroid,
dextrothyroxine)
Benzodiazepines (alprazolam, triazolam)† Azole antifungal agents (fluconazole, itraconazole,
ketoconazole)†
Carbamazepine Propoxyphene†
Cyclosporine Rifamycins (rifampin, rifabutin, rifapentine)
Dextromethorphan MAO inhibitors (isocarboxazid, phenelzine, safegilene,
tranylcypromine)
Digoxin Clarithromycin†
Ergot alkaloids (dihydroergotamine, ergotamine, methylsergide) Macrolide antibiotics (clarithromycin, erythromycin,
troleandomycin)†
Estrogen-progestin products (oral contraceptives) Rifampin
Ganciclovir Zidovudine
MAO inhibitors (isocarboxazid, phenelzine, selegiline, tranylcypromine) Anorexiants (amphetamine, benzphetamine, dexfenfluramine,
dextroamphetamine, Diethylpropion, fenfluramine, mazindol,
methamphetamine, phendimetrazine, phentermine,
phenlpropanolamine, albutramine)
MAO inhibitors (isocarboxazid, phenalzine, selegiline, tranylcypromine) Sympathomimetics (dopamine, ephedrine, isometheptene,
mucate, mephentermine, metaraminol, phenylephrine,
pseudoephedrine)
Meperidine† MAO inhibitors (isocarboxazid, phenalzine, selegiline,
tranylcypromine)
Methotrexate Trimethoprim (trimethoprim-sulfamethoxazole, trimethoprim)
Nitrates (nitroglycerin, isosorbide dinitrate/mononitrate) Sildenafil
Pimozide Macrolide antibiotics (clarithromycin, dirithromycin,
erythromycin, troleandomycin)†
Pimozide Azole antifungal agents (fluconazole, itraconazole,
ketoconazole)†
SSRIs (citalopram, fluoxetine, fluvoxamine, nefazodone, paroxetine, MAO inhibitors (isocarboxazid, phenelzine, salegiline,
sertraline, ventalaxine)‡ tranylcypromine)
Theophyllines Quinolones (ciprofloxacin, enoxacin)†
Theophyllines Fluvoxamine
Thiopurines (azathloprine, mercaptopurine) Allopurinol
Warfarin Sulfinpyrazone
Warfarin Nonsteroidal antiinflammatory drugs (celecoxib, diclofenac,
etodolac, flubiprofen, fenoprofen, ibuprofen, indomethacin,
ketoprofen, ketorolac, meclofenamate, mefenarmic acid,
nabumetone, naproxen, oxaprozin, piroxlcam, rofecoxib,
sulindac, tolmetin)†
Warfarin Cimetidine
Warfarin Fibric acid derivatives (clofibrate, fenofibrate, gemfibrozil)
Warfarin Barbiturates (amobarbital, butabarbital, butabital, mephobarbital,
phenobarbital, secobarbital)
MAO, Monoamine oxidase; SSRI, selective serotonin reuptake inhibitor.
*Malone DC, Abarca J, Hansten PD, Grizzle AJ, Armstrong EP, van Bergen RC, et al. Identification of serious drug-drug interactions: results of
the partnership to prevent drug-drug interactions. J Am Pharm Assoc 2004;44:142-51.
†Drugs that may be prescribed in dentistry.
‡Non-SSRIs included with SSRIs because of similar pharmacologic profiles.

average of 8.2 drugs. Dental visits were reported by an
estimated 14.4 million older adults, and prescription
drug use was similarly high, with 96.2% reporting
receiving ⱖ1 prescription with an average of 8.0 drugs
taken.
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,
macrolide antibiotics, and nonsteroidal antiinflammatory
drugs (NSAIDs) are commonly prescribed in dentistry.
Table II identifies the most prevalent drugs listed in Table
I that were reported for older adults seeking dental care.
For 2006 community-dwelling older adults with a
dental visit, national prevalence estimates for possible
serious drug-drug interactions are reported in Table III
by demographic, socioeconomic, and health-related
characteristics. Overall, 3.4% of those visiting the den-
tist were estimated to have been prescribed drugs with

156 Skaar and O’Connor
Table II. Prevalence estimates for drugs with potential
for drug-drug interactions of clinical importance for
community-dwelling Medicare beneficiaries* with a
dental visit in 2006 (estimated n ⫽ 14,361,198; SE ⫽
230,745)
% SE
Thyroid hormones 17.64
NSAIDs 17.60
SSRIs 10.05
Benzodiazepines 9.61
Anticoagulants 8.45
Quinolones 8.21
Nitrates 7.18
Propoxyphene 6.77
Digoxin 4.27
NSAIDs ⫽ nonsteroidal antiinflammatory drugs; SSRI ⫽ selective
serotonin reuptake inhibitor.
*⬎65 years of age, enrolled for the entire year of 2006.
the potential for a serious drug interaction if taken
concurrently. Based on ␹2 analyses, the prescribing of 2
drugs with the potential for a serious interaction was
most strongly associated with increasing age, race,
poorer self-reported health, and higher comorbidity
counts. Of those with a dental visit, the prevalence for
possible multiple interactions was estimated to be
0.5%. Nationally, this represents ⬃500,000 elderly
dental patients taking medications during 2006 that
potentially could have ⱖ1 harmful interactions.
Multiple logistic regression analysis of MCBS data
for those with a dental visit identified characteristics
associated with use of prescription drugs with the po-
tential for serious interactions. Independent variables in
the model included age, gender, education, race, in-
come, drug insurance, comorbidities, general health
status, geographic region, and drug counts. Significant
variables associated with a medication profile indicat-
ing the potential for serious interactions included age
ⱖ85 years (odds ratio [OR] 2.48, 95% confidence in-
terval [CI] 1.26-4.87), annual income ⬎$50,000 (OR
2.42, 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); ⱖ11 drugs (OR 53.19, 95% CI 3.76-752.51).
DISCUSSION
Harmful drug-drug interactions are an important type
of adverse drug event and a health safety issue that
dental practitioners should be aware of.13,23 Serious
adverse events have been reported for a number of drug
interactions. Elderly patients hospitalized for digoxin
toxicity were found to be 12 times more likely to have
received clarithromycin, and diabetics admitted for hy-
poglycemia while taking glyburide were 6 times more
likely to have taken cotrimoxazole.24 Bleeding risk has
OOOOE
August 2011
been reported to increase considerably with concurrent
NSAID and coumarin therapy compared with coumarin
therapy 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 consumes
0.68 more prescription drugs.26
0.65 Complicating the identification of serious interac-
0.41
tions is the need to interpret a vast drug interaction
0.47
0.48 literature and the lack of standardized methodologies to
0.42 rate clinical risk among various drug compendia.18 To
0.42 focus on serious interactions with clinical relevance,
0.39 the present study used a previously identified list of 25
0.32
clinically important interactions likely to occur in a
community setting that was developed with a system-
atic literature review and expert panel process.22
The present study reinforces the importance for oral
health 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 older
adults.9,10 Of the 2006 community-dwelling older
adults with dental visits, it was estimated that 96.2%
had a prescription for ⱖ1 drugs. Polypharmacy (use of
multiple medications) is common in older adults, and
this was confirmed for those seeking dental care; this
population had prescriptions for an estimated average
of 8 different drugs. A key finding is that overall 3.4%
of those presenting for dental visits had prescriptions
for drugs that, if taken concomitantly, could result in a
harmful interaction. Similarly, other studies using dif-
ferent methodologies have reported potential exposure
rates for ⱖ1 interactions in the ⬃1%-4% range.10,27
Logistic regression modeling identified those ⱖ85
years and those with increasing drug counts as most
strongly associated with possible drug interactions
identified by the Partnership to Prevent Drug-Drug
Interactions. Clearly, dentists should be especially vig-
ilant for interactions when reviewing the drug histories
of the ambulatory oldest old and those taking high
numbers of prescription drugs.
Consideration of drug interactions should be an in-
tegral part of prescribing practices in dentistry. The
likelihood of adverse drug events increases as drug
regimens become more complex.12 A number of drugs
commonly prescribed by dentists have the potential for
a serious drug interaction.22 Drugs listed in Table I that
dentists 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 Food
and Drug Administration requested the discontinuation
of marketing of all propoxyphene products in the U.S.
OOOOE
Volume 112, Number 2
owing to new evidence of interference with cardiac
electrical activity and higher risk of arrhythmias.
The risk of excessive bleeding or hemorrhage is a
serious adverse event that dentists should be aware of
when performing invasive procedures or prescribing
analgesics for older patients. Approximately 10% of
older 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 with
vitamin K cofactor functions and inhibit synthesis of
coagulation 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 thyroid
hormone replacement products will alter catabolism of
vitamin K– dependent clotting factors. Use of fibrinic
acid 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 exacerbate
bleeding complications by inhibiting cyclooxygenase-1
(COX-1), resulting in reduced platelet aggregation, in-
creasing warfarin serum levels through plasma protein
displacement, and elevating gastrointestinal bleeding
risk by depletion of COX-1–produced prostaglandins
that confer a protective effect by stimulating synthesis
and secretion of mucus and bicarbonate.29,30
Dental providers should avoid or use caution with
other drug combinations. Prescribing oral alprazolam
(Xanax) or triazolam (Halcion) for anxiolysis in dental
care should be avoided in patients taking azole antifun-
gal agents. Azole antifungal drugs, such as fluconazole,
inhibit cytochrome P450 (CYP) 3A4 metabolism of
benzodiazepines, increasing plasma drug levels and
potentiating their sedative and psychomotor impair-
ment effects.31 The cardiac glycoside digoxin, used to
treat heart failure and supraventricular arrhythmias, and
the asthma drug theophylline have narrow therapeutic
indexes or low margins of safety. Consideration of
possible drug interactions is important, because sudden
increases in plasma levels of these drugs may lead to
serious toxicities. The macrolide antibiotics erythromy-
cin and clarithromycin (Biaxin), prescribed for oral
infections, may cause digitalis toxicity by increasing
intestinal absorption and decreasing renal excre-
tion.32,33 Possible mechanisms include increasing oral
bioavailability by preventing gut bacterial metabolism,
inhibiting p-glycoprotein active drug transport back
into 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-
Skaar and O’Connor 157
ophylline levels may result in cardiac arrhythmias and
central nervous system effects, including restlessness
and convulsions. The concurrent use of the analgesic
meperidine (Demerol) and monoamine oxidase inhibi-
tor (MAOI) antidepressants should be avoided.30 This
combination has been associated with serotonin syn-
drome, a potentially life-threatening adverse reaction
with clinical findings ranging from tremor and agitation
to 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- or
proxy-reported; however, recall bias is likely reduced
by periodic interviews with collection of receipts and
claim forms. Underreporting may be less likely for
chronically used medications being regularly refilled,
owing to periodic surveying. Nevertheless, the data
reported 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 drug
interaction classification methodology may result in
underreporting of serious interactions. The MCBS ex-
cludes self-medication with over-the-counter drugs,
supplements, and alternative medicines which are other
potential sources of drug interactions.10 Each interac-
tion selected by the Partnership to Prevent Drug-Drug
Interactions 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 drugs
included in the analysis are typically taken long-term
for chronic conditions and could be presumed to be
used concurrently. There may be situations when drugs
with the potential for a serious interaction are consid-
ered to be therapeutically necessary given the risks and
monitored clinically to prevent an unacceptable adverse
effect. Finally, as new prescription drugs are introduced
and new prescribing information becomes available it is
likely 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 older
adults will present with more complex drug regimens as
they cope with a higher prevalence of chronic diseases,
such as diabetes, hypertension, and stroke.7 Adverse
drug effects may be exacerbated by age-related phar-
macokinetic and pharmacodynamic changes, including
declining renal and hepatic clearance, which may in-
crease and prolong toxic plasma drug levels. Under-
standing potentially harmful drug combinations, their
clinical consequences, and the frequency with which
implicated drugs are being prescribed will assist pro-
viders in clinically managing patients and avoiding
inappropriate prescribing. Using a systematically deter-
 OOOOE
158 Skaar and O’Connor August 2011

Table III. Prevalence estimates for potential drug-drug interactions of clinical importance by sociodemographic and
health-related characteristics for community-dwelling Medicare beneficiaries* with a dental visit in 2006 (estimated
n ⫽ 14,361,198; SE ⫽ 230,745)
ⱖ1 drug-drug
interaction
Estimated population (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 0.60
70-74 3,880,939 114,885 27.02 0.74 2.86 0.57
75-79 3,263,967 103,956 22.73 0.66 3.46 0.66
80-84 2,518,746 91,432 17.54 0.63 4.32 0.61
85⫹ 1,597,644 71,424 11.12 0.45 6.01 1.01
Gender
Male 6,173,862 152,494 42.99 0.69 3.57 0.48
Female 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 0.00
White 13,297,859 220,737 92.60 0.42 3.59 0.32
Black 608,748 45,441 4.24 0.32 1.27 0.91
Other 142,460 26,269 0.99 0.18 0.00 0.00
Asian 130,661 26,970 0.91 0.19 0.00 0.00
Hispanic 133,129 22,134 0.93 0.15 3.92 2.81
Native American 42,362 16,208 0.29 0.11 0.00 0.00
Income
0-$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
Education
Unknown 36,057 12,361 0.25 0.09 0.00 0.00
ⱕ8th grade 833,714 61,694 5.81 0.43 3.84 1.30
9th-12 grade/HS grad. 5,321,323 140,284 37.05 0.97 3.75 0.48
Post–high school 4,074,038 143,718 28.37 0.82 3.04 0.55
College grad./postgrad. 4,096,067 156,951 28.52 0.89 3.31 0.59
Population density
Nonmetropolitan 2,595,362 121,137 18.07 0.74 4.13 0.76
Metropolitan 11,765,837 197,297 81.93 0.74 3.26 0.33
Marital status
Unknown 5,952 4,154 0.04 0.03 0.00 0.00
Married 8,967,188 192,673 62.44 0.90 3.31 0.39
Widowed 3,799,328 127,771 26.46 0.85 4.17 0.58
Divorced 1,085,549 72,382 7.56 0.46 1.92 0.78
Separated 53,292 16,552 0.37 0.12 0.00 0.00
Never 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 0.90
Middle Atlantic 2,122,204 124,747 14.78 0.84 3.59 0.68
East North Central 2,678,716 191,421 18.65 1.26 4.34 0.94
West North Central 892,514 143,933 6.21 0.99 4.64 1.72
South Atlantic 2,633,520 215,837 18.34 1.52 3.57 0.62
East South Central 1,006,453 113,043 7.01 0.77 2.90 1.13
West South Central 1,213,799 251,194 8.45 1.74 3.86 0.92
Mountain 1,212,598 211,264 8.44 1.46 2.56 0.90
Pacific 1,934,796 215,684 13.47 1.49 2.56 0.80
Puerto 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 3.244
Excellent 2,763,712 112,755 19.24 0.66 1.76 0.601
Very good 5,011,704 140,775 34.90 0.84 2.58 0.475
Good 4,481,358 137,640 31.20 0.81 4.11 0.576
Fair 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
OOOOE
Volume 112, Number 2 Skaar and O’Connor 159

Table III. (Continued)

ⱖ1 drug-drug
interaction
Estimated population (est. n ⫽ 490,874)
Demographic characteristics n SE % SE % SE
Comorbidity count‡
0 854,461 63,193 5.95 0.44 1.68 0.97
1 2,031,998 104,215 14.16 0.64 1.91 0.552
2 3,327,091 125,312 23.19 0.77 1.97 0.562
3 3,092,275 116,491 21.55 0.79 2.5 0.574
ⱖ4 5,043,119 141,481 35.15 0.83 5.85 0.603
Total % 3.42 0.31
*⬎65 years of age, enrolled for the entire year of 2006.
†P ⬍ .01; ‡P ⬍ .001.

mined list of potentially harmful drug interactions and
the nationally representative MCBS, the findings of the
present study should raise clinician awareness of the
need to carefully assess drug histories. In addition to
the initial examination review, drug profiles should be
updated for potential interactions on an ongoing basis
during patient care, because new drugs may be pre-
scribed and new interaction information may become
available. In addition to continually updating drug in-
teraction information, future research is needed to iden-
tify the prevalence and risks for harmful interactions
involving over-the-counter drugs, supplements, and
herbals in older adults seeking dental care.
The authors thank Scott Lunos, MS, for statistical analysis
support.
REFERENCES
1. Institute of Medicine. Preventing medication errors. 2006. Quality
chasm series. October 2010. Available at: http://www.iom.edu/Reports/
2006/Preventing-Medication-Errors-Quality-Chasm-Series.aspx.
2. U.S. Department of Health and Human Services. Oral Health in
America: a report of the Surgeon General. Rockville (MD):
National Institute of Dental and Craniofacial Research, National
Institute of Health; 2000.
3. Vargas CM, Kramarow EA, Yellowitz JA. The oral health of
older Americans. Aging trends, no. 3. Hyattsville (MD): National
Center for Health Statistics; 2001.
4. Centers for Disease Control. The state of aging and health in America
2007 report. October 2010. Available at: http://www.cdc.gov/aging/
saha.html.
5. Federal Interagency Forum on Aging Related Statistics. Older
Americans 2008: Key indicators of well-being. Available at:
www.agingstats.gov.
6. Weintraub JA, Burt BA. Oral health status in the United States:
tooth loss and education. J Dent Educ 1985;49:368-76.
7. CDC. Public health and aging: trends in aging—United States
and worldwide. Morb Mortal Wkly Rep 2003;52:101-6.
8. Baum BJ. Inadequate training in the biological sciences and
medicine for dental students. J Am Dent Assoc 2007;138:16-25.
9. Kaufman DW, Kelly JP, Rosenberg L, Anderson TE, Mitchell
AA. Recent patterns of medication use in the ambulatory adult
population of the United States. JAMA 2002;287:337-44.
10. Qato DM, Alexander GC, Conti RM, Johnson M, Schumm P,
Lindau ST, et al. Use of prescriptions and over-the-counter
medications and dietary supplements among older adults in the
United States. JAMA 2008;300:2867-78.
11. Henry J. Kaiser Family Foundation. Retail prescription drugs
filled at pharmacies, October 2010. Available at: http://www.
statehealthfacts.org.
12. Goldberg RM, Mabee J, Chan L, Wong S. Drug-drug and drug-
disease interactions in the ED: analysis of a high-risk population.
Am J Emerg Med 1996;14:447-50.
13. Aparasu R, Baer R, Aparasu A. Clinically important potential
drug-drug interactions in outpatient settings. Res Soc Admin
Pharm 2007;3:426-37.
14. Gurwitz JH, Field TS, Harrold LR, Rothschild J, Debellis K,
Seger AC, Fish LS, et al. Incidence and preventability of adverse
drug events among older persons in the ambulatory setting.
JAMA 2003;289:1107-16.
15. Yagiela JA, Dowd FJ, Johnson BS, Mariotti AJ, Neidle EA.
Pharmacology and therapeutics for dentistry. St. Louis, MO:
Mosby Elsevier; 2011. p. 834-41.
16. Wynn RL, Meiller TF, Crossley HL. Drug information handbook
for dentistry. Hudson, OH: Lexi-Comp; 2009.
17. Malone DC, Hutchins DS, Haupert H, Hansten P, Duncan B, van
Bergen RC, et al. Assessment of potential drug-drug interactions
with a prescription claims database. Am J Health Syst Pharm
2005;62:1983-91.
18. Abarca J, Malone DC, Armstrong EP, Grizzle AJ, Hansten PD,
van Bergen RC, Lipton RB. Concordance of severity ratings
provided in four drug interaction compendia. J Am Pharm Assoc
2004;44:136-41.
19. Moore PA, Gage TW, Hersh EV, Yagiela JA, Haas DA. Adverse
drug interactions in dental practice. J Am Dent Assoc 1999;
130:47-54.
20. Hersh EV, Moore PA. Drug interactions in dentistry: the importance
of knowing your CYPs. J Am Dent Assoc 2004;135:298-311.
21. Sims PJ, Sims KM. Drug interations important for periodontal
therapy. Periodontol 2000 2007;44:15-28.
22. Malone DC, Abarca J, Hansten PD, Grizzle AJ, Armstrong EP,
van Bergen RC, et al. Identification of serious drug-drug inter-
actions: results of the partnership to prevent drug-drug interac-
tions. J Am Pharm Assoc 2004;44:142-51.
23. Ament PW, Bertolino JG, Liszewski JL. Clinically significant
drug interactions. Am Fam Physician 2006;61:1745-54.
24. Juurlink DN, Mamdani M, Kopp A, Laupacis A, Redelmeier DA.
Drug-Drug interactions among elderly patients hospitalized for
drug toxicity. JAMA 2003;289:1652-8.
 OOOOE
160 Skaar and O’Connor August 2011

25. Solberg LI, Hurley JS, Roberts MH. Measuring patient safety in 32. Hersh EV. Adverse drug interactions in dental practice: interac-
ambulatory care: potential for identifying medical group drug-drug tions involving antibiotics. J Am Dent Assoc 1999;130:236-50.
interaction rates using claims data. Am J Manag Care 2004; 33. Rengelshausen J, Goggelmann C, Burhenne J, Reidel K, Ludwig
10:753-9. J, Weiss J, et al. Contribution of increased oral bioavailability
26. Mangioni AA, Jackson SHD. Age-related changes in pharmaco- and reduced nonglomurular renal clearance of digoxin to the
kinetics and pharmacodynamics: basic principles and practical digoxin-clarithromycin interaction. Br J Clin Pharmacol 2003;
applications. Br J Clin Pharmacol 2003;57:6-14. 56:32-8.
27. Peng CC, Glassman PA, Marks IR, Fowler C, Castiglione B, 34. Boyer EW, Shannon M. The serotonin dyndrome. N Engl J Med
Good CB. Retrospective drug utilization review: incidence of 2005;352:1112-20.
clinically relevant potential drug-drug interaction rates in a large 35. Poisal JA. Reporting of drug expenditures in the MCBS. Health
ambulatory population. J Manag Care Pharm 2003;9:513-22. Care Finan Rev 2003;25:23-36.
28. Holbrook AM, Pereira JA, Labris R, McDonald H, Douketis JD,
Crowther M, Wells PS. Systematic overview of warfarin and its
drug and food interactions. Arch Intern Med 2005;165:1095-106.
29. Knijfff-Dutmer EA, Schut GA, van der Laar MA. Concomitant Reprint requests:
Coumarin-NSAID therapy and risk for bleeding. Ann Pharma-
cother 2003;37:12-6. Dr. Daniel D. Skaar
30. Haas DA. Adverse drug interactions in dental practice: inter- Developmental and Surgical Sciences
actions associated with analgesics. J Am Dent Assoc 1999; University of Minnesota
130:397-406. 7-368 Moos Tower
31. Moore PA. Adverse drug interactions in dental practice: interac- 515 Delaware St SE
tions associated with local anesthetics, sedatives and anxiolytics. Minneapolis, MN 55455
J Am Dent Assoc 1999;130:541-54. skaar003@umn.edu