Actisite fiber has been studied in 1437 patients distributed as follows over pivotal, controlled, and open- label studies.

The most frequently reported adverse reactions in the 226 patients in the pivotal clinical trials were discomfort on fiber placement (10%) and local erythema following removal (11%).

In controlled and open-label trials patients, the following adverse reactions have been reported in less than 1% of patients: oral candidiasis, glossitis, possible allergic response, staining of the tongue, severe gingival inflammation, throbbing pain, pain following placement in an abscessed area, and minor throat irritation.

The use of the tetracycline class during tooth development (last half of pregnancy, infancy and childhood to age of 8 years) may cause permanent discoloration of the teeth. Tetracycline drugs should not be used in this age group unless other treatment is not likely to be effective or if alternative therapy is contraindicated.

Tetracyclines as a class are associated with photosensitivity. Treatment should be discontinued at the first sign of cutaneous erythema.

Accumulations of tetracycline associated with renal failure can lead to liver toxicity. These effects have not been studied in the plasma concentration range associated with Actisite®.

General

Actisite fibers must be removed after 10 days. Packing fibers tightly into a draining abscess without allowance for drainage might result in the formation of a lateral fistula. Fibers should not be used in an acutely abscessed periodontal pocket. Their use in chronic abscesses has not been evaluated.

As with other antibiotic preparations, Actisite (tetracycline hydrochloride) periodontal fiber therapy may result in overgrowth of nonsusceptible organisms, including fungi. Actisite should be used with caution in patients with a history of or predisposition to oral candidiasis.

The safety and effectiveness of Actisite fiber have not been established for the treatment of periodontitis in patients with coexistent oral candidiasis.

Use of antibiotic preparations may result in the development of resistant bacteria. Resistance has not been observed during 10 days of Actisite fiber therapy. The effects of prolonged treatment have not been studied.

Management of patients with periodontal disease should include a consideration of potentially contributing medical disorders.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Animal studies with Actisite fiber have not been performed to evaluate carcinogenic potential, mutagenic potential, or effects on fertility.

Pregnancy Category C

Administration of tetracycline during pregnancy may cause permanent discoloration of teeth of offspring. Animal studies indicate that tetracyclines can cause retardation of fetal skeletal development. Actisite fiber should be administered to a pregnant woman only if clearly needed. Animal reproduction studies have not been conducted with Actisite fiber. It is also not known whether Actisite fiber can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity.

Nursing Mothers

Tetracycline appears in breast milk following oral administration. It is not known whether tetracycline is excreted in human milk following use of Actisite® (tetracycline hydrochloride) periodontal fiber. Because of the potential for serious adverse reactions from tetracycline HCl in nursing infants, Actisite fiber should be used in a nursing woman only if clearly needed.

Pediatrics

The safety and effectiveness of Actisite fiber in children have not been established. Oral doses of tetracycline in children up to 8 years of age have caused permanent discoloration of teeth.

See DOSAGE AND ADMINISTRATION.

Actisite fiber should not be used in patients who are hypersensitive to any tetracycline.

Microbiology

The clinical significance of the microbiological findings with Actisite is not known. The tetracyclines are primarily bacteriostatic and are thought to exert their antimicrobial effect by inhibiting protein synthesis. In vitro testing has shown that probable periodontal pathogens, including Fusobacterium nucleatum, Porphyromonas (Bacteroides) gingivalis, Prevotella intermedia (Bacteroides intermedius), Eikenella corrodens, Campylobacter rectus (Wolinella recta), and Actinobacillus actinomycetemcomitans, are susceptible to local 32 µg/mL tetracycline concentrations achieved in the periodontal pocket with the use of Actisite® (tetracycline hydrochloride) periodontal fiber.

Pharmacokinetics

Actisite fiber releases tetracycline in vitro at a rate of approximately 2 µg/cm-h. In the periodontal pocket, the system provides for a per site mean gingival fluid concentration of 1590 µg/mL tetracycline throughout the 10-day treatment period.

Concentration in saliva immediately after fiber placement (9 teeth) was 50.7 µg/mL and declined to 7.6 µg/mL at the end of 10 days.

During fiber treatment of up to 11 teeth per patient (average tetracycline dose of 105 mg) mean tetracycline concentrations in plasma were below the lower limit of assay detection (<0.1 µg/mL). This lower assay limit is 20- to 25-fold lower than that expected during a regimen of 250 mg by oral capsule every 6 hours.

Clinical Studies

In a controlled 60-day clinical trial, 113 adult patients with periodontitis (56 men and 57 women; age range 25-88; 95 Caucasian, 11 Black, 3 Hispanic and 4 Asian) entered with a mean pocket depth of 7.2 mm (98% of pocket depths were within the range of 4 mm to 11 mm). Subjects received supragingival cleaning followed by one of four treatments, randomized to a single tooth per quadrant. These treatments were: 1) Actisite fiber for 10 ± 2 days, 2) control fiber for 10 ± 2 days, 3) scaling and root planing under local anesthesia, or 4) no treatment. Teeth treated with Actisite fiber were later found to have significantly reduced probing depth and bleeding on controlled force probing. Probing depth reductions were greater in deep (> or equal to 7 mm) than in moderate (< or equal to 6 mm) sites.

In a randomized, single-blind 6-month study of 113 adult periodontal maintenance patients (57 men and 56 women; age range 32-75; 111 Caucasian, 2 Black), the effects of scaling and root planing alone, and scaling and root planing followed by Actisite fiber treatment, were compared. Subjects entered with a baseline pocket depth mean of 6.4mm (97% of the pockets were within a range of 4 mm to 11 mm). Two non-adjacent sites with pockets with bleeding on probing were selected for treatment and follow-up at 1, 3, and 6 months. A longitudinal multi-variate analysis showed that adjunctive fiber therapy with scaling and root planing provided significantly greater reductions in probing depth and bleeding on probing than scaling and root planing alone at follow-up visits. The results are summarized in the following table:

* Significant difference between treatment groups (p<0.05)
** Significant difference between treatment groups (p<0.01)
^aS/RP = scaling and root planing

Microbiology - In the 60-day study, immediately following therapy, both Actisite fiber and scaling and root planing produced significant reductions in the number of sites infected with probable periodontal pathogens compared to untreated controls. The clinical significance of these findings is not known.

When Actisite® fiber is in place, patients should avoid actions that may dislodge the fiber. Patients should receive the following instructions:

1. Do not chew hard, crusty, or sticky foods.
   
2. Do not brush or floss near any treated areas. (Continue to clean other teeth.)
   
3. Do not engage in any other hygienic practices that could potentially dislodge the fibers.
   
4. Do not probe at the treated area with tongue or fingers.
   
5. Notify the dentist promptly if the fiber is dislodged or falls out before the scheduled recall visit, or if pain or swelling or other problems occur.