Drug interaction in Dentistry

Dr. Benjamin Zeitlin

Learning objectives
Review drug metabolism
Understand cytochrome system
Know dentally relevant substrates for
cytochrome system
Know major dental drugs affected by and
affecting cytochrome drug metabolism

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Competition for
Transport sites
Plasma protein
binding
Metabolic enzymes

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Phase I - Cytochrome system

DRUG DEACTIVATION
DRUG ACTIVATION
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SUBSTRATES
INDUCERS
INHIBITORS

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Benzodiazepine effects
potentially increased by
macrolide antibiotics,
SSRIs, azole antifungals
and grapefruit juice
Narcotic analgesics are
prodrugs activated by
CYP, potentially
inhibited by quinidine,
SSRIs and NSAIDs
Lidocaine, little
evidence of clinically
significant interaction
NSAID GI tract and renal
toxicities potentially
enhanced but unlikely
except in chronic use
Corticosteroids and
acetaminophen complicated

Barbiturates less
commonly used,
narrow therapeutic
window, risk of
abuse
Barbiturates induce
CYP synthesis,
increase metabolism
of quinidine, azole
anti-fungals,
nifedipine,
contraceptives,
immunosuppressives
,
HIV drugs
CYP interactions
unlikely for acute
dental use of
barbiturate

Dental drugs that are

inhibitors of CYP - all
antibiotics
Chronic use increases
chance of clinically
significant CYP
inhibition
Ciprofloxacin is very
potent inhibitor
resulting in elevation
of drugs such as
clozapine
Metronidazole
increases blood
Coumadin & phenytoin
levels
Erythromycin clarithromycin, broad CYP substrate effects increase levels of
benzodiazepine, midazolam, methylprednisolone, nifedipine, Coumadin,
cylosporine

Adverse drug event reporting

Voluntary
Who?
Healthcare professionals
Consumers
Family members, lawyers
If reported to manufacturer it is required
to send report to FDA
WHERE?

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MEDWATCH
FDA safety and adverse event reporting
program
MedWatch

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What to report
Prescription or over-the-counter medicines, as well
as medicines administered to hospital patients or at
outpatient infusion centers
Biologics (including blood components, blood and
plasma derivatives, allergenic, human cells, tissues,
and cellular and tissue-based products (HCT/Ps))
Medical devices (including in vitro diagnostic products)
Combination products
Special nutritional products (dietary supplements,
infant formulas, and medical foods)
Cosmetics
Foods/beverages (including reports of serious allergic
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reactions)

Federal Adverse Event Reporting

System - FAERS
Database of info from MedWatch and
other sources
No proof required to report
Adverse event may not be due to drug
Cannot be used to calculate adverse event
incidence

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Summary
Drug interactions can occur anywhere
Most clinically relevant interactions during
metabolism
Cytochrome system primary interaction
source
CYP substrates can be CYP inhibitors
Antibiotics are potent CYP inhibitors
Report adverse events - MedWatch
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