FDA Approved Drugs » 1999
Medical Areas: Dental and Oral Health
View By:Year | Company | Conditions | Therapeutic Areas | Drug Names
The following drug information is obtained from various newswires, published
medical journal articles, and medical conference presentations.
Company: Atrix Laboratories
Approval Status: Approved January 1999
Treatment Area: Dental/Maxillofacial Surgery
ATRIDOX is indicated for use in the treatment of chronic adult
periodontitis for a gain in clinical attachment, reduction in
probing depth, and reduction in bleeding on probing.
The ATRIDOX product is a subgingival controlled-release product
composed of a two syringe mixing system. Syringe A contains 450 mg
of the ATRIGEL® Delivery System, which is a bioabsorbable, flowable
polymeric formulation composed of 36.7% poly(DL-lactide) (PLA)
dissolved in 63.3% N-methyl-2-pyrrolidone (NMP). Syringe B contains
doxycycline hyclate which is equivalent to 42.5 mg doxycycline. The
constituted product is a pale yellow to yellow viscous liquid with
a concentration of 8.5% w/w of doxycycline.
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
- Scaling and Root Planing
- Vehicle Control
- 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
- ATRIDOX was superior to Vehicle Control and Oral Hygiene
- ATRIDOX 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).
A single-center, single-blind, randomized, clinical study in 45
subjects with periodontal disease demonstrated that a single
treatment with ATRIDOX 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. 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 therapy may
result in the overgrowth of nonsusceptible organisms including
Clinicians should note that the studies were of nine months
duration. Additional research would be necessary to establish long
term comparability to SRP.
ATRIDOX should not be used in patients who are hypersensitive to
doxycycline or any other drug in the tetracycline class.
In clinical trials involving a total of 1436 patients, adverse
experiences were monitored across treatment groups.
In the Circulatory System category, 10 subjects (1.6%) in the
ATRIDOX group were reported as having unspecified essential
hypertension. Only 1 subject (0.2%) in the Vehicle group, and none
in the Scaling and Root Planing or Oral Hygiene groups were
reported to have unspecified essential hypertension. In all cases,
the event occurred anywhere from 13 to 134 days post-treatment.
There is no known association of oral administration of
doxycycline with essential hypertension.
Two patients in the polymer vehicle group and none in the
ATRIDOX group (0.2% for both groups combined) reported adverse
events consistent with a localized allergic response.
Sex, age, race and smoking status did not appear to be
correlated with adverse events.
Mechanism of Action
Doxycycline is a broad-spectrum semisynthetic tetracycyline.1
Doxycycline is bacteriostatic, inhibiting bacterial protein
synthesis due to disruption of transfer RNA and messenger RNA at
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.