August 24, 2016
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"Introduction to dental medications

There are several types of medications that are used to manage a variety of diseases involving the oral cavity (mouth) that are part of good dental care. The medications discussed in this article h"...





Doxycycline is a broad-spectrum semisynthetic tetracycline.1 Doxycycline is bacteriostatic, inhibiting bacterial protein synthesis due to disruption of transfer RNA and messenger RNA at ribosomal sites.1 In vitro testing has shown that Porphyromonas gingivalis, Prevotella intermedia, Campylobacter rectus, and Fusobacterium nucleatum, which are associated with periodontal disease, are susceptible to doxycycline at concentrations ≤ 6.0 μg/mL.2 A single-center, single-blind, randomized, clinical study in 45 subjects with periodontal disease demonstrated that a single treatment with ATRIDOX (doxycycline hyclate) ® resulted in the reduction in the numbers of P. gingivalis, P. intermedia, C. rectus, F. nucleatum, Bacteroides forsythus, and E. corrodens in subgingival plaque samples. Levels of aerobic and anaerobic bacteria were also reduced after treatment with ATRIDOX (doxycycline hyclate) ®. The clinical significance of these findings, however, is not known. During these studies, no overgrowth of opportunistic organisms such as Gram-negative bacilli and yeast were observed. However, as with other antibiotic preparations, ATRIDOX (doxycycline hyclate) ® therapy may result in the overgrowth of nonsusceptible organisms including fungi. (See PRECAUTIONS)


In a clinical pharmacokinetic study, subjects were randomized to receive either ATRIDOX (doxycycline hyclate) ® covered with Coe-Pak™ periodontal dressing (n=13), ATRIDOX (doxycycline hyclate) ® covered with Octyldent™ periodontal adhesive (n=13), or oral doxycycline (n=5) (according to package dosing instructions). The doxycycline release characteristics in gingival crevicular fluid (GCF), saliva, and serum were evaluated.

Doxycycline levels in GCF peaked (~1,500 μg/mL and ~2000 μg/mL for Coe-Pak™ and Octyldent™ groups, respectively) 2 hours following treatment with ATRIDOX (doxycycline hyclate) ®. These levels remained above 1000 μg/mL through 18 hours, at which time the levels began to decline gradually. However, local levels of doxycycline remained well above the minimum inhibitory concentration (MIC90) for periodontal pathogens ( ≤ 6.0 μg/mL)2 through Day 7. In contrast, subjects receiving oral doxycycline had peak GCF levels of ~2.5 μg/mL at 12 hours following the initial oral dosing with levels declining to ~0.2 μg/mL by Day 7. High variability was observed for doxycycline levels in GCF for both oral and ATRIDOX (doxycycline hyclate) ® treatment groups.

The ATRIDOX (doxycycline hyclate) ® doxycycline release profile in GCF is illustrated in the figure below.

Mean Doxycycline Concentrations in GCF (0-7 Days) - Illustration

The maximum concentration of doxycycline in saliva was achieved at 2 hours after both treatments with ATRIDOX (doxycycline hyclate) ®, with means of 4.05 μg/mL and 8.78 μg/mL and decreased to 0.36 μg/mL and 0.23 μg/mL at Day 7 for the Coe-Pak™ group and the Octyldent™ group, respectively.

The concentration of doxycycline in serum following treatment of ATRIDOX (doxycycline hyclate) ® never exceeded 0.1 μg/mL.

Clinical Studies

In two well-controlled, multicenter, parallel-design, nine-month clinical trials, 831 patients (Study 1=411; Study 2=420) with chronic adult periodontitis characterized by a mean probing depth of 5.9 to 6.0 mm were enrolled. Subjects received one of four treatments: 1) ATRIDOX (doxycycline hyclate) ®, 2) Scaling and Root Planing, 3) Vehicle Control, or 4) Oral Hygiene. Treatment was administered to sites with probing depths 5 mm or greater that bled on probing. Subjects with detectable subgingival calculus on greater than 80% of all tooth surfaces were excluded from enrollment. All subjects received a second administration of the initially randomized treatment four months after their Baseline treatment. Changes in the efficacy parameters, attachment level, pocket depth, and bleeding on probing, between Baseline and Month 9 showed that: 1) ATRIDOX (doxycycline hyclate) ® was superior to Vehicle Control and Oral Hygiene, and 2) ATRIDOX (doxycycline hyclate) ® met the decision rule of being at least 75% as good as Scaling and Root Planing (SRP) (the standard of at least 75% as good as SRP is required for any product approved as a stand alone therapy for periodontitis). Clinicians should note that the studies were of nine months duration. Additional research would be necessary to establish long term comparability to SRP. The results of Studies #1 and 2 for efficacy parameters of attachment level gain and probing depth reduction are included in the following graphs.

Clinical Studies - illustration 1

Clinical Studies - illustration 2

* denotes statistically significant superiority of ATRIDOX (doxycycline hyclate) ® and Sc/RP vs. Vehicle and Oral Hygiene
† denotes statistically significant superiority of ATRIDOX (doxycycline hyclate) ® vs. Vehicle and Oral Hygiene
Data were not collected at months 3 and 7

Clinical Studies - illustration  3 & 4

* denotes statistically significant superiority of ATRIDOX (doxycycline hyclate) ® and Sc/RP vs. Vehicle and Oral Hygiene
† denotes statistically significant superiority of ATRIDOX (doxycycline hyclate) ® vs. Vehicle and Oral Hygiene
Data were not collected at months 3 and 7

A third clinical trial was conducted to determine whether the product can be left in the pocket to bioabsorb or be expelled naturally and achieve comparable clinical results. In this study the product was retained with Octyldent™ dental adhesive rather than Coe-Pak™ periodontal dressing as in the previously mentioned studies. This was a 3-arm, randomized, controlled, parallel group, single blind trial that enrolled 605 subjects. The patient population studied and study design were comparable to that in Studies 1 and 2. Subjects received one of three treatments: 1) ATRIDOX (doxycycline hyclate) ® with Coe-Pak™ removed after 7 days as in the pivotal trials, 2) ATRIDOX (doxycycline hyclate) ® retained with Octyldent™ and left to bioabsorb or be expelled naturally or 3) Vehicle Control with Octyldent™ left to bioabsorb or be expelled naturally. Changes in the efficacy parameters, attachment level, pocket depth and bleeding on probing were equivalent to those observed in Studies 1 and 2. The results of the third study support the use of ATRIDOX (doxycycline hyclate) ® retained with Octyldent™ and left to bioabsorb or be expelled naturally.


1. Stratton CW, Lorian V. Mechanisms of action for antimicrobial agents: general principles and mechanisms for selected classes of antibiotics. Antibiotics in Laboratory Medicine, 4th edition, Williams and Wilkins, Baltimore, MD, 1996.

2. Slots J, Rams TE. Antibiotics in periodontal therapy: advantages and disadvantages. J Clin Periodontol 1990; 17:479-493.

Last reviewed on RxList: 4/11/2011
This monograph has been modified to include the generic and brand name in many instances.

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