I enjoyed reading Dr Dennis Flanagan's article entitled, “Oral Triazolam Sedation in Implant Dentistry.” The fact is that dental fear and anxiety remain pervasive throughout the public.1 Oral premedication with triazolam is an effective and safe treatment adjunct for these patients and has become a popular means to increase tolerance of invasive dental procedures.

In my reading of Dr Flanagan's article, I did find an area that seems contrary to published research on triazolam. It is stated on page 94, in the middle column, that azithromycin should not be given concomitantly with triazolam because this may cause “increased plasma concentration, and, therefore, increased clinical effects.”2 Although the inhibitory effects of erythromycin and clarithromycin on CYP 3A4 cannot be disputed, it has clearly been documented that azithromycin has no effects on the kinetics and dynamics of triazolam.3 Greenblatt et al4 state, “Coadministration of azithromycin had no significant effect on any of the pharmacokinetic variables for triazolam.” Furthermore, the package insert for Zithromax (Pfizer) states that no dosage adjustment is needed when azithromycin is coadministered with triazolam.5 

I feel that as the number of dentists utilizing triazolam (or other CYP 3A4 substrates like midazolam or alprazolam) increases, it is important to clarify the reaction between triazolam and azithromycin. Because a patient may have a penicillin allergy and cannot take a cephalosporin because of cross-allergy and may also be intolerant to clindamycin, azithromycin may be a last resort for antibiotic prophylaxis. Azithromycin is the logical choice for these patients while still being safe to use together with triazolam.

References

References
1
Dionne
,
R. A.
,
S. M.
Gordon
,
L. M.
McCullagh
, and
J. C.
Phero
.
Assessing the need for anesthesia and sedation in the general population.
J Am Dent Assoc
1998
.
129
:
167
173
.
2
Flanagan
,
D. F.
Oral triazolam sedation in implant dentistry.
J Oral Implantol
2004
.
30
:
93
97
.
3
Westphal
,
J. F.
Macrolide-induced clinically relevant drug interactions with cytochrome P-450A (CYP) 3A4: an update focused on clarithromycin, azithromycin, and dirithromycin.
Br J Clin Pharmacol
2000
.
50
:
285
295
.
4
Greenblatt
,
D. J.
,
L. L.
von Moltke
, and
J. S.
Harmatz
.
et al
.
Inhibition of triazolam clearance by macrolide antimicrobial agents: in vitro correlates and dynamic consequences.
Clin Pharmacol Ther
1998
.
64
:
278
285
.
5
Zithromax [package insert]. New York, NY: Pfizer Inc; 2004
.