Prescription Drugs

CLINICAL PHARMACOLOGY Microbiology The clinical significance of the microbiological findings with Actisite (tetracycline periodontal) 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 (tetracycline periodontal) 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 ( 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 (tetracycline periodontal) 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: Time (mo.) Probing Depth Reduction (mm) Bleeding on Probing (%) S/RPa S/RP + Fiber S/RP S/RP + Fiber 0 0.00 0.00 90 87 1 0.82 1.20* 48 30** 3 0.98 1.27* 48 34** 6 1.05 1.72** 51 38* * Significant difference between treatment groups (p

OVERDOSE See DOSAGE AND ADMINISTRATION. CONTRAINDICATIONS Actisite (tetracycline periodontal) fiber should not be used in patients who are hypersensitive to any tetracycline.

WARNINGS 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® (tetracycline periodontal) . PRECAUTIONS General Actisite (tetracycline periodontal) 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 (tetracycline periodontal) should be used with caution in patients with a history of or predisposition to oral candidiasis. The safety and effectiveness of Actisite (tetracycline periodontal) 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 (tetracycline periodontal) 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 (tetracycline periodontal) 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 (tetracycline periodontal) fiber should be administered to a pregnant woman only if clearly needed. Animal reproduction studies have not been conducted with Actisite (tetracycline periodontal) fiber. It is also not known whether Actisite (tetracycline periodontal) 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 (tetracycline periodontal) fiber should be used in a nursing woman only if clearly needed. Pediatrics The safety and effectiveness of Actisite (tetracycline periodontal) 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.