Quality Resource Guide –

Drug Interactions: A Guide for Dentistry 5th Edition

www.metdental.com

Page 4

NSAIDs + Methotrexate

Nonsteroidal anti-inflammatory drugs have been

shown to decrease the clearance of methotrexate,

probably by the same mechanisms as the other

agents, i.e., a reduction in the vasodilating renal

prostaglandins.

NSAIDs + Warfarin

Medications such as aspirin and other nonsteroidal

anti-inflammatory drugs can increase the risk of

warfarin-related bleeding by inhibiting platelet

function. Aspirin poses the most significant risk

due to its common use and irreversible prolonged

effect on platelets. One proposed mechanism of

the interaction has been the possibility that these

drugs displace warfarin from plasma protein- binding

sites. Aspirin and NSAIDs also produce gastric

erosions that increase the risk of serious upper

gastrointestinal tract bleeding.

NSAIDs + Aspirin

The potential for ibuprofen and other NSAIDs to

interfere with the antiplatelet effect of aspirin, and

particularly low-dose aspirin (81 mg daily) has been

documented.

NSAIDs (a reversible inhibitor of

platelets) may interact with aspirin (an irreversible

inhibitor of platelets) by competitive inhibition of the

acetylation site of platelet cyclooxygenase (COX). As

NSAIDs and aspirin occupy nearby sites on platelet

COX, NSAIDs may prevent access and binding of

aspirin. Consequently, aspirin inhibition of platelet

aggregation may be reduced. Therefore, NSAIDs

should be administered either 30 minutes before

taking aspirin (particularly low dose aspirin), or 8

hours after taking aspirin to minimize the occurrence

of this interaction.

Acetaminophen

Since acetaminophen, like alcohol, may be toxic

to the liver, FDA labeling of OTC acetaminophen

products states that “patients who consume three

or more alcoholic drinks per day should contact

their physician before ingesting acetaminophen,

because the combination may increase the risk of

liver damage”.

Also liver toxicity may be increased

with administration of carbamazepine and phenytoin.

In addition, published recommendations limit the

maximum daily dose of acetaminophen to only 2

grams in alcoholics to avoid additional liver damage

that is already present. In contrast, the maximum

daily dose for use of acetaminophen without alcohol

consumption (or in the non-alcoholic patient) is

4 grams per day. Additionally, acetaminophen in

doses of 2 grams or more per day may increase

the anticoagulant effect of warfarin. This effect is

of concern mainly in patients taking the analgesic

for a week or more. The mechanism of this effect

is unclear. In general, short-term dosing with

acetaminophen of patients taking warfarin does not

result in a clinical problem.

Antibiotics

General Interactions

Antibiotics produce their antibacterial effect either by

a bactericidal or bacteriostatic mechanism of action.

Bacteriostatic antibiotics inhibit the growth and

multiplication of microorganisms while bactericidal

antibiotics kill or destroy microorganisms. In general,

bacteriostatic antibiotics alter the metabolic pathways

or synthesis of cellular components. In contrast,

bactericidal drugs interfere with the synthesis or

function of the cell wall, cell membrane or both.

When two bactericidal antibiotics are given together,

they may exert a greater effect than when each is

given separately. This is called antibiotic synergism.

However, when a bacteriostatic and a bactericidal

antibiotic are given together, their effectiveness

is negated or reduced. This is called antibiotic

antagonism. In the majority of dental infections,

combination therapy is not usually necessary.

However, since patients may present to an office

with a dental infection requiring an antibiotic and they

may already be taking an antibiotic for a systemic

infection, a drug interaction based on mechanism

of action may occur.

Table 2

some frequently

prescribed antibiotics are listed with their mechanism

of action. When concomitant usage of two or more

antibiotics is necessary, the general rule is to

administer bactericidal agents with bactericidal agent,

bacteriostatic agents with bacteriostatic agents, but

never bactericidal with bacteriostatic agents.

Macrolide Interactions

Macrolide antibiotics used in dentistry include

erythromycin, azithromycin and clarithromycin.

The primary mechanism by which they interact

with other drugs is inhibition of liver metabolism.

Certain macrolide antibiotics, such as erythromycin

and troleandomycin are fairly potent hepatic

enzyme inhibitors while other macrolides, including

clarithromycin are less effective enzyme inhibitors.

Azithromycin and dirithromycin do not appear

to cause significant clinical drug interactions.

Increased serum levels of the drugs shown in

Table 3

may occur when they are administered

with macrolide antibiotics, especially erythromycin.

Recently, it has been reported that erythromycin

may interact with the calcium channel blockers,

Diltiazem and Verapamil and result in cardiac

toxicity and death. The potential for a similar cardiac

effect may be present with concomitant use of some

antidepressants but which ones are not clear at

this time.

However, this interaction has not been

reported with Clarithromycin and Azithromycin. In

view of its highly interactive effects with a number

of medications, erythromycin should be prescribed

mainly when other antibiotics with a similar

antibacterial spectrum cannot be prescribed. Also,

erythromycin and clarithromycin can increase the

rhabdomolysis associated with some statins. This

interaction has not been observed with azithromycin.

Table 2

Antibiotics:

Mechanism of Action

Antibiotic

Bacteriostatic

Bactericidal

Amoxicillin/

Metronidazole



Augmentin



Cephalosporins



Clindamycin



Doxycycline



Erythromycins



Metronidazole



Minocycline



Nystatin



Penicillins



Tetracycline

