APPENDIX D : Drug Interactions of Significance to Dentistry
Effect
Medical
Interacting Drug
TABLE D-1 Dental
Condition/Situation
Drug
ANTIBIOTICS
Decreased
Contraception
Oral contraceptives
Antibiotics
effectiveness of oral
(BCP)
contraceptives has
been suggested for
several antibiotic
classes because of
the potential for
lowering plasma
levels of the
contraceptive drug.
However, most welldesigned studies do
not show any
reduction in estrogen
serum levels in
patients taking
antibiotics (except
rifampin).
RECOMMENDATION: Okay to use dental antibiotics. Provide advice to patient as to the
potential risk and for consideration of additional contraceptive measures.
Incidence of minor
Gout
Allopurinol (Lopurin, Beta lactams
allergic reactions to
Zyloprim)
(penicillins,
ampicillin is
cephalosporins)
increased. Other
penicillins have not
been implicated.
RECOMMENDATION: Avoid ampicillin.
Serum levels of atenolol are
Hypertension
Beta blockers (e.g.,
reduced after prolonged use
Tenormin, Lopressor, Inderal,
of ampicillin. Anaphylactic
Corgard)
reactions to penicillins or
other drugs
Effect
Medical
Interacting Drug
Dental Drug
Condition/Situation
may be more severe in patients taking beta blockers because of increased mediator release
from mast cells.
RECOMMENDATION: Use ampicillin cautiously, advise patient of potential reaction.
Effectiveness of penicillins
and cephalosporins may be
Infection, acne, or
periodontal disease
Tetracyclines and other
bacteriostatic antibiotics
reduced by bacteriostatic
agents.
RECOMMENDATION: Avoid interaction.
Antacids, dairy
Dyspepsia,
Antacids
Tetracyclines
products, and other
gastroesophageal
Fluoroquinolones
agents containing
reflux, peptic ulcer
divalent (calcium,
iron) and trivalent
cations will chelate
these antibiotics and
limit their absorption.
Doxycycline is least
influenced by this
interaction.
RECOMMENDATION: Avoid interaction.
Doxycycline and
Diabetes mellitus
Insulin
oxytetracycline have been
documented as enhancing the
hypoglycemic effects of
exogenously administered
insulin.
RECOMMENDATION: Select a different
Effect
Medical
Interacting Drug
Dental Drug
Condition/Situation
antibiotic, or increase carbohydrate intake.
In patients taking
Immunosuppression Methotrexate
Doxycycline
high-dose
methotrexate,
interaction can lead
to increased
methotrexate
concentrations,
making toxicity likely.
RECOMMENDATION: Select different antibiotic.
Severe disulfiram-like Alcohol use or abuse Ethanol
Metronidazole
reactions are well
documented.
RECOMMENDATION: Avoid interaction.
Inhibits renal excretion of
Manic depression
Lithium
lithium, leading to
elevated/toxic levels of
lithium. Lithium toxicity
produces confusion, ataxia,
and kidney damage.
RECOMMENDATION: Avoid interaction.
Delayed metabolism
of benzodiazepine,
increasing the
pharmacologic
effects, can result in
excessive sedation
and irrational
behavior.
Anxiety
Benzodiazepines
Antibiotics/Antifungals metabolized
by CYP3A4 and
CYP1A2 (e.g.,
macrolide antibiotics
[erythromycin,
clarithromycin], and
antifungals
[ketoconazole,
RECOMMENDATION: Reduce dose of benzodiazepine
Effect
Medical
Condition/Situation
Depression
Interacting Drug
Dental Drug
Delayed metabolism
Buspirone
itraconazole])
of buspirone,
increasing
pharmacologic
effect.
RECOMMENDATION: Avoid interaction.
Increased blood levels of
Seizure disorder
Carbamazepine (Tegretol)
carbamazepine, leading to
toxicity; symptoms include
drowsiness, dizziness,
nausea, headache, and
blurred vision.
Hospitalization has been
required.
RECOMMENDATION: Avoid interaction.
Delayed metabolism of
Gastroesophageal reflux
Cisapride
cisapride, increasing the
pharmacologic effects and
risk for cardiac arrhythmia
and sudden death.
RECOMMENDATION: Avoid interaction.
Enhanced
Organ transplant
Cyclosporine
immunosuppression and
nephrotoxicity.
RECOMMENDATION: Avoid interaction.
Inhibits CYP3A4 metabolism, Cardiac arrhythmias
Disopyramide, Quinidine
resulting in large increases in
antiarrhythmia drug that can
lead to arrhythmias
Effect
Medical
Interacting Drug
Dental Drug
Condition/Situation
RECOMMENDATION: Avoid interaction.
Muscle (eosinophilia)
Hyperlipidemia
Lovastatin, pravastatin,
myalgia and rhabdomyolysis
simastatin, and other statins
(muscle breakdown and
pain) and acute renal failure.
RECOMMENDATION: Avoid interaction.
Increased risk of
Autoimmune disorders,
Prednisone,
immunosuppression
organ transplant
methylprednisolone
RECOMMENDATION: Monitor patient, and shorten duration of antibiotic administration if
possible.
Erythromycins inhibit the
Asthma
metabolism of theophylline,
leading to toxic serum levels
(symptoms of toxicity:
headache, nausea, vomiting,
confusion, thirst, cardiac
arrhythmias, and
convulsions). Conversely,
theophylline reduces serum
levels of erythromycin.
RECOMMENDATION: Avoid prescribing erythromycin.
Alters
gastrointestinal flora
and retards
metabolism of
digoxin in roughly
10% of
Effect
Congestive heart
failure
Anticoagulant effect
of warfarin may be
increased by several
antibiotic classes.
Reduced synthesis of
vitamin K by gut
flora is a putative
mechanism, but
Atrial fibrillation,
myocardial
infarction, post major
surgery, stroke
prevention
Theophylline (Theodur)
Digoxin (Lanoxin)
Antibiotics
(especially
erythromycin and
Medical
Interacting Drug
Dental Drug
Condition/Situation
patients, resulting in dangerously high
tetracycline)
digoxin serum levels that may persist for
several weeks after discontinuation of
antibiotic. Strongest documentation has been
acquired for erythromycin and tetracycline.
Patients should be cautioned to report any
signs of digitalis toxicity (salivation, visual
disturbances, and arrhythmias) during
antibiotic therapy.
RECOMMENDATION: Safe in 90%, should have digoxin levels monitored during
antimicrobial therapy.
Warfarin (Coumadin)
Antibiotics,
cephalosporins,
erythromycin,
clarithromycin,
metronidazole
several antibiotics
have antiplatelet and
anticoagulant
activity.
Cephalosporins, macrolide antibiotics, and metronidazole have the most convincing
documentation, monitor INR.
RECOMMENDATION: Penicillins, tetracyclines,
Effect
Medical
Interacting Drug
Dental Drug
Condition/Situation
and clindamycin would be preferred choices but must be used cautiously.
ANALGESICS
Increased risk of liver Alcohol use and
Alcohol
Acetaminophen
toxicity, especially
abuse
during fasting state
or ≥4 g of
acetaminophen per
day.
RECOMMENDATION: Use lower dose of acetaminophen and encourage discontinuation of
alcohol use.
Increased risk of
Atrial fibrillation,
Warfarin (Coumadin)
bleeding if
thrombosis
acetaminophen is
given at a dose of >2
g/day for ≥1 week.
RECOMMENDATION: Limit acetaminophen dosing and monitor INR.
Acetaminophen
Increased
hypoglycemic effects.
Aspirin
Diabetes type 2
Oral hypoglycemics
(e.g., sulfonylureas:
Glyburide,
chlorpropamide,
acetohexamide)
RECOMMENDATION: Avoid interaction.
Increased risk of
Atrial fibrillation,
Anticoagulants
Aspirin, NSAIDs
bleeding (GI, oral).
myocardial
(Coumarin)
infarction, post
surgery
Effect
Medical
Interacting Drug
Dental Drug
Condition/Situation
RECOMMENDATION: Avoid interaction.
Increases risk of
Alcohol use and
Alcohol
Aspirin, NSAIDs
gastrointestinal
abuse
bleeding.
RECOMMENDATION: Lower dose; encourage discontinuation of alcohol use.
Enhanced antiplatelet
Hypertension, angina
Diltiazem
Aspirin
activity of aspirin.
RECOMMENDATION: Monitor for risk of prolonged bleeding with the use of PFA-100.
Decreased
Hypertension, post
Beta blockers, ACE
NSAIDs
antihypertensive
myocardial infarction inhibitors
effect.
RECOMMENDATION: Limit duration of NSAID dosage to about 4 days.
Produces symptoms
Manic depression
Lithium
NSAIDs
of lithium toxicity,
including nausea,
vomiting, slurred
speech, and mental
confusion.
RECOMMENDATION: NSAIDs should not be prescribed to patients who take lithium.
It can result in toxic levels of lithium, or consult with physician to reduce
Effect
Medical
Condition/Situation
Interacting Drug
lithium dose.
Increased risk for
Osteoporosis,
Alendronate
gastric ulcers.
multiple myeloma
RECOMMENDATION: Use acetaminophen products.
Dental Drug
NSAIDs (Naproxen)
Toxic level of
Connective tissue
Methotrexate (MTX) NSAIDs
methotrexate may
disease, cancer
accumulate.
therapy
RECOMMENDATION: Avoid interaction if on high-dose MTX for cancer therapy.
Low-dose MTX for arthritis is not a concern.
ANESTHETICS
Additive effect of these two
Bupivacaine
Lidocaine
local anesthetics increases
the risk of central nervous
system toxicity.
RECOMMENDATION: Limit dose of each.
Sedation with opioids may
Meperidine (Demerol)
Mepivacaine
increase risk of local
anesthetic toxicity; especially
in children.
RECOMMENDATION: Reduce anesthetic dose.
SEDATIVES
Effect
Medical
Interacting Drug
Dental Drug
Condition/Situation
Barbiturates bind
Congestive heart
Digoxin,
Barbiturates
P450 cytochrome
failure, asthma,
theophylline,
system in liver and
autoimmune disease, corticosteroids, oral
enhance the
atrial fibrillation
anticoagulants
metabolism of many
drugs.
RECOMMENDATION: Limit dose, and observe for adverse effects.
Additive effects for sedation
Anxiety, alcohol use and
Benzodiazepines, alcohol,
and respiratory depression.
abuse, seasonal allergies
antihistamines
RECOMMENDATION: Reduce dose, and administer combination of sedatives with extreme
caution.
Delayed metabolism Peptic ulcer disease, Cimetidine, oral
of BZDP, increasing
depression,
contraceptives,
the pharmacologic
tuberculosis, alcohol fluoxetine, isoniazid
effects, can result in
use and abuse
(INH), alcohol
excessive sedation
and adverse
psychomotor effects.
RECOMMENDATION: Reduce dose of benzodiazepine.
Benzodiazepines
(BZDP) (e.g.,
alprazolam,
chlordiazepoxide,
diazepam)
Serum concentrations of
Congestive heart failure,
Digoxin (Lanoxin), phenytoin,
digoxin and phenytoin may
epilepsy, asthma
theophylline (Theodur)
be increased, resulting in
toxicity.
Antagonize sedative effects of benzodiazepine.
RECOMMENDATION: Avoid interaction.
Effect
Medical
Interacting Drug
Dental Drug
Condition/Situation
Increased bioavailability and
HIV and AIDS
Protease inhibitors (Indinavir,
effects of benzodiazepines,
Nelfinavir)
especially triazolam and oral
midazolam.
RECOMMENDATION: Avoid interaction.
VASOCONSTRICTOR
Unopposed effects— Angina pectoris,
Nonselective beta
Epinephrine and
Increased blood
hypertension,
blockers: Propranolol Levonordephrine
pressure with
glaucoma, migraine,
(Inderal), nadolol
(Neocobefrin)
secondary
headache,
(Corgard), penbutolol
bradycardia.
hyperthyroidism,
(Levatol), pindolol
panic syndromes
(Visken), sotalol
(Betapace), timolol
(Blocadren)
RECOMMENDATION: Initial dose is ½ carpule containing 1 :100,000 epinephrine; aspirate to
avoid intravascular injection, and inject slowly. Monitor vital signs, if no adverse
cardiovascular change; up to two cartridges containing a vasoconstrictor can be
administered. Provide a 5-minute interval between the first and second carpules with
continual monitoring. Avoid epinephrine-containing retraction
Effect
Medical
Interacting Drug
Dental Drug
Condition/Situation
cord and higher concentrations of epinephrine in the dental anesthetic.
Blocks reuptake of
Illicit use, topical anesthetic
Cocaine
norepinephrine and
for mucous membrane
intensifies postsynaptic
procedures
response to epinephrine-like
drugs.
This potentiates the adrenergic effects on the heart, with the potential for a heart attack.
RECOMMENDATION: Recognize signs and symptoms of cocaine abuse; avoid use of
vasoconstrictors in these patients until cocaine has been withheld for at least 24 hours.
Stimulation of alpha and
General anesthetic for
Halothane
beta receptors, resulting in
surgical procedures
arrhythmia at doses that
exceed 2 g/kg.
RECOMMENDATION: Limit dose to remain below 2 μg/kg threshold, aspirate to avoid
intravascular injection. Monitor vital signs.
Avoid epinephrine-containing retraction cord and concentrations of epinephrine higher
Effect
Medical
Condition/Situation
than 1 : 100,000.
Blocks reuptake of
norepinephrine, resulting in
unopposed effects—
increased pressor response
(increased blood pressure,
increased heart rate)—and
potential cardiac
arrhythmias; effect is greater
with levonordefrin.
Interacting Drug
Depression, severe anxiety,
neuropathic pain, attention
deficit disorder
Dental Drug
Tricyclic antidepressants[*]
(amitriptyline [Elavil],
amoxapine, clomipramine
[Anafranil], desipramine
[Norpramin], doxepin
[Sinequan], imipramine
[Tofranil], nortriptyline
[Pamelor], protriptyline
[Vivactil], trimipramine
[Surmontil])
RECOMMENDATION: Avoid levonordefrin; limit dose to 2 carpules containing 1 : 100,000
epinephrine (36 μg), aspirate to avoid intravascular injection. Monitor vital signs. Avoid
epinephrine-containing retraction cord and higher concentrations of epinephrine in the
dental anesthetic.
Although no reports have
Depression
Monoamine oxidase (MAO)
documented the effects on
inhibitors (isocarboxazid
blood pressure or heart rate
[Marplan], phenelzine
after dental procedures, the
[Nardil], tranylcypromine
potential for increased
pressor response is present
Effect
Medical
Interacting Drug
Dental Drug
Condition/Situation
[Parnate])
RECOMMENDATION: Avoid levonordefrin; limit dose to 2 carpules containing 1 : 100,000
epinephrine (36 μg), and aspirate to avoid intravascular injection. Monitor vital signs.
Avoid epinephrine-containing retraction cord and higher concentrations of epinephrine in
the dental anesthetic.
Potential for increased
sensitivity of adrenergic
receptors to epinephrine and
levonordefrin.
Hypertension
Peripheral adrenergic
antagonists (reserpine
[Serpasil], guanethidine
[Ismelin], guanadrel
[Hylorel])
RECOMMENDATION: Administer cautiously.
Monitor vital signs during and after administration of first carpule. Limit dose to 2 carpules
containing 1 :100,000 epinephrine (36 g) or less depending on vital signs and patient
response. Aspirate to avoid intravascular injection. Avoid
Effect
Medical
Interacting Drug
Dental Drug
Condition/Situation
epinephrine-containing retraction cord and higher concentrations of epinephrine in the
dental anesthetic.
Potential for increased
sensitivity of adrenergic
receptors to epinephrine and
levonordefrin, resulting in
increased heart rate, blood
pressure, and arrhythmias.
Parkinson's disease
Catechol-O-methyltransferase inhibitors
(tolcapone [Tasmar],
entacapone [Comtan])
RECOMMENDATION: Administer cautiously. Monitor vital signs during and after
administration of first carpule. Limit dose to 2 carpules containing 1 :100,000 epinephrine
(36 g) or less, depending on vital signs and patient response. Aspirate to avoid intravascular
injection. Avoid epinephrine-containing retraction cord and higher concentrations of
epinephrine in the dental anesthetic.