ARESTIN

ARESTIN (minocycline hydrochloride) microspheres, 1 mg is a subgingival sustained-release product containing the antibiotic minocycline hydrochloride incorporated into a bioresorbable polymer, Poly (glycolide-co-dl-lactide) or PGLA, for professional subgingival administration into periodontal pockets. Each unit-dose cartridge delivers minocycline hydrochloride equivalent to 1 mg of minocycline free base. The molecular formula of minocycline hydrochloride is C 23 H 27 N 3 O 7 ● HCl, and the molecular weight is 493.94. The structural formula of minocycline hydrochloride is: image-01.jpg

INDICATIONS AND USE ARESTIN is indicated as an adjunct to scaling and root planing procedures for reduction of pocket depth in patients with adult periodontitis. ARESTIN may be used as part of a periodontal maintenance program which includes good oral hygiene and scaling and root planing.

ARESTIN is provided as a dry powder, packaged in a unit-dose cartridge with a deformable tip (see Figure 1), which is inserted into a spring-loaded cartridge handle mechanism (see Figure 2) to administer the product. The oral health care professional removes the disposable cartridge from its pouch and connects the cartridge to the handle mechanism (see Figures 3-4 ). ARESTIN is a variable dose product, dependent on the size, shape, and number of pockets being treated. In US clinical trials, up to 122 unit-dose cartridges were used in a single visit and up to 3 treatments, at 3-month intervals, were administered in pockets with pocket depth of 5 mm or greater. The administration of ARESTIN does not require local anesthesia. Professional subgingival administration is accomplished by inserting the unit-dose cartridge to the base of the periodontal pocket and then pressing the thumb ring in the handle mechanism to expel the powder while gradually withdrawing the tip from the base of the pocket. The handle mechanism should be sterilized between patients. ARESTIN does not have to be removed, as it is bioresorbable, nor is an adhesive or dressing required. Arestin figures.jpg

ARESTIN should not be used in any patient who has a known sensitivity to minocycline or tetracyclines.

The most frequently reported non-dental, treatment-emergent adverse events in the 3 multicenter US trials were headache, infection, flu syndrome, and pain. Table 5: Adverse Events (AEs) Reported in ≥3% of the Combined Clinical Trial Population of 3 Multicenter US Trials by Treatment Group SRP Alone N=250 SRP + Vehicle N=249 SRP + ARESTIN ® N=423 Number (%) of Subjects Treatment-emergent AEs 62.4% 71.9% 68.1% Total Number of AEs 543 589 987 Periodontitis 25.6% 28.1% 16.3% Tooth Disorder 12.0% 13.7% 12.3% Tooth Caries 9.2% 11.2% 9.9% Dental Pain 8.8% 8.8% 9.9% Gingivitis 7.2% 8.8% 9.2% Headache 7.2% 11.6% 9.0% Infection 8.0% 9.6% 7.6% Stomatitis 8.4% 6.8% 6.4% Mouth Ulceration 1.6% 3.2% 5.0% Flu Syndrome 3.2% 6.4% 5.0% Pharyngitis 3.2% 1.6% 4.3% Pain 4.0% 1.2% 4.3% Dyspepsia 2.0% 0 4.0% Infection Dental 4.0% 3.6% 3.8% Mucous Membrane Disorder 2.4% 0.8% 3.3% The change in clinical attachment levels was similar across all study arms, suggesting that neither the vehicle nor ARESTIN compromise clinical attachment. Postmarketing Experience The following adverse reaction has been identified during postapproval use of minocycline products when taken orally. Because this reaction is reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Skin and subcutaneous tissue disorders: Acute febrile neutrophilic dermatosis (Sweet’s syndrome). To report SUSPECTED ADVERSE REACTIONS, contact OraPharma at 1-800-321-4576 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Storage Conditions Store at 20° to 25°C (68° to 77°F)/60% RH: excursions permitted to 15° to 30°C (59° to 86°F). Avoid exposure to excessive heat.