ARESTIN® (minocycline hydrochloride) Microspheres, 1 mg is the leading locally administered antibiotic (LAA) that delivers a sustained dose of minocycline—a broad-spectrum, semisynthetic tetracycline derivative—directly to infected pockets, helping to kill the bacteria that SRP can leave behind.†
A. ARESTIN® is indicated as an adjunct to scaling and root planing (SRP) 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.4
A. ARESTIN® contains the antibiotic minocycline, a member of the tetracycline class of antibiotics. Minocycline exerts its antimicrobial activity by inhibiting protein synthesis and has been shown to be effective against the pathogens associated with periodontal disease.
A. Microspheres are bioadhesive, bioresorbable, sustained-release polymers produced by a microencapsulation process and provided in powder form. ARESTIN® Microspheres contain minocycline hydrochloride. ARESTIN® is the only locally administered antibiotic (LAA) that delivers minocycline to periodontal pockets using powdered Microsphere technology.
A. Gingival crevicular fluid hydrolyzes the polymer, causing water-filled channels to form inside the Microspheres. These holes provide "escape routes" for sustained release of the encapsulated antibiotic. The active drug dissolves and diffuses out of the Microspheres, through the channels, and into the surrounding periodontal tissue. Upon administration, ARESTIN® immediately adheres to the periodontal pocket.
A. ARESTIN® Microspheres are fragmented through polymer hydrolysis and, over time, are completely bioresorbed. Clinical evidence shows that ARESTIN® maintains therapeutic drug concentrations for up to 21 days after administration.5
A. Minocycline is a broad-spectrum, semisynthetic tetracycline derivative that is bacteriostatic. It has been shown to be effective in inhibiting the periodontal pathogens implicated in periodontal disease.4
A. Yes. ARESTIN® requires no preparation before administration. ARESTIN® is premeasured and premixed and does not need refrigeration.4 ARESTIN® is bioadhesive and so does not require retention dressings to prevent it from falling out4.
ARESTIN® is also easy for the patient. Application is painless and does not require the use of anesthesia.4 ARESTIN® is completely resorbed, which leaves nothing to be removed.4 Patients can resume brushing 12 hours after administration.4
A. In clinical trials, ARESTIN® has been proven to kill the pathogens most commonly associated with periodontal disease, including red complex bacteria.4 Minocycline achieves minimum inhibitory concentration (MIC) levels well above those reported for common periodontal pathogens.20
A. In 2 single-blind studies (N=748) and 1 open-label (N=173) study, ARESTIN® was applied to more than 27,000 oral sites. Periodontitis was characterized by a mean probing depth of 5.90 mm and 5.81 mm, respectively.1,21
Patients enrolled in the trials were required to have 4 teeth with periodontal pockets of 6 mm to 9 mm that bled upon probing. Treatment was administered to all sites with probing depths of >5 mm. Retreatment occurred at Month 3 and Month 6, and any new site with a pocket depth of >5 mm received treatment.
In the >5 mm sites, clinical results were demonstrated by using the following course of therapy:
Initial visit |
ARESTIN® + SRP |
3-month retreatment |
ARESTIN® |
6-month retreatment |
ARESTIN® |
These clinical findings demonstrate that patients treated with ARESTIN® + SRP experienced a statistically significant reduction in probing pocket depth compared to patients treated with SRP alone or SRP + placebo.
Further evidence to support adjunctive treatment with ARESTIN® has been reported in a Phase 3 clinical trial. A total of 499 patients with moderate to advanced chronic periodontitis were enrolled in a multicenter trial and randomized to either SRP alone (250 patients;7,365 pockets) or SRP + ARESTIN® (249 patients;7,713 pockets). Complete probing examinations were conducted at baseline, 1 month, and 3 months.
Significantly more sites treated with ARESTIN® + SRP exhibited probing depths <5 mm at month 1 (P=0.0009) and at month 3 (P=0.01) vs SRP alone. In addition, at both months 1 and 3, significantly more periodontal pockets were reduced by 1 mm, 2 mm, or 3 mm in the ARESTIN® + SRP group (P<0.05) vs the SRP group. These findings were true for both the overall population and smokers.
Thus, the Phase 3 study of ARESTIN® further demonstrated that ARESTIN® + SRP is consistently more effective than SRP alone in patients with chronic periodontitis.
A. In clinical studies, ARESTIN® + SRP delivered meaningful pocket-depth reduction.1,21
Use of ARESTIN® as an adjunct therapy to SRP was shown to be significantly more effective in reducing pocket depth than SRP alone.1,21 Moreover, ARESTIN® was proven to maintain efficacy over 12 months.21
Over 60% of pockets that responded to ARESTIN® + SRP had a reduction of =2 mm.5,21
ARESTIN® + SRP maintained significant pocket-depth reduction over time.21
A. Yes. When ARESTIN® + SRP was used in clinical studies, 65% of patients with periodontal pockets =6 mm were reduced to <5 mm (P<0.01).1 In addition, these patients were nearly 3 times more likely to become maintainable <5 mm.1
A. ARESTIN® + SRP is nearly 3 times more likely to reduce mean probing depths from =6 mm to <5 mm vs SRP alone.1 ARESTIN® + SRP provided a greater therapeutic effect than SRP alone in difficult-to-treat patient groups.8,22-24
Based on pocket depth reduction scores at 9 months.†
Compared to SRP alone, the addition of ARESTIN® was more than 4 times more likely to reduce pockets to <5 mm in smokers.5‡
*Adapted from Williams RC, Paquette DW, Offenbacher S, et al. Treatment of periodontitis by local administration of minocycline microspheres: a controlled trial. J Periodontol 2001;72:1535-1544. Change in pocket depth from baseline to 9 months was recorded for ARESTIN® + SRP and SRP alone. Therapeutic effect was derived by calculating the percent difference between the 9-month scores.
†748 patients with moderate or advanced periodontitis with bleeding on probing. SRP was performed at baseline. Clinical assessments were conducted at baseline and 1, 3, 6, and 9 months. ARESTIN® was administered to all sites with pocket depths =5 mm.
‡ Multivariate analysis of the univariate, multicenter Phase III trials of ARESTIN® + SRP to SRP + placebo and SRP alone. Odds ratios were adjusted for the simultaneous effect of influential variable such as treatment center, smoking status, age, and baseline pocket depths.
A. As an LAA, ARESTIN® avoids the typical resistance development mechanism. Because there is minimal systemic absorption, there is very little chance of resistance development. A recent published review showed that there was no evidence of the development of resistant strains or the acquisition of multiantibiotic resistance with an LAA.25
A. Preparation and administration of ARESTIN® is quick and easy. In 1 clinical trial, the additional time to administer an LAA was less than 5 minutes per appointment.19
A. The most frequently reported non-dental treatment-emergent adverse events in the 3 multicenter US trials were headache, infection, flu syndrome, and pain.4
AEs reported by treatment group in =3% of the combined clinical trial population of multicenter US trials4
A. ARESTIN® should not be used in any patient who has a known sensitivity to minocycline or tetracyclines.
Because ARESTIN® contains minocycline, a tetracycline derivative, it should not be used in children and in pregnant or nursing women. The use of drugs of the tetracycline class during tooth development may cause permanent discoloration of the teeth.
A. THE USE OF DRUGS OF THE TETRACYCLINE CLASS DURING TOOTH DEVELOPMENT (LAST HALF OF PREGNANCY, INFANCY, AND CHILDHOOD TO THE AGE OF 8 YEARS) MAY CAUSE PERMANENT DISCOLORATION OF THE TEETH (YELLOW-GRAY BROWN). This adverse reaction is more common during long-term use of the drugs, but has been observed following repeated short-term courses. Enamel hypoplasia has also been reported. TETRACYCLINE DRUGS, THEREFORE, SHOULD NOT BE USED IN THIS AGE GROUP, OR IN PREGNANT OR NURSING WOMEN, UNLESS THE POTENTIAL BENEFITS ARE CONSIDERED TO OUTWEIGH THE POTENTIAL RISKS. Results of animal studies indicate that tetracyclines cross the placenta, are found in fetal tissues, and can have toxic effects on the developing fetus (often related to retardation of skeletal development). Evidence of embryotoxicity has also been noted in animals treated early in pregnancy. If any tetracyclines are used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Photosensitivity manifested by an exaggerated sunburn reaction has been observed in some individuals taking tetracyclines. Patients apt to be exposed to direct sunlight or ultraviolet light should be advised that this reaction can occur with tetracycline drugs, and treatment should be discontinued at the first evidence of skin erythema.
The use of ARESTIN® in an acutely abscessed periodontal pocket has not been studied and is not recommended.
While no overgrowth by opportunistic microorganisms, such as yeast, were noted during clinical studies, as with other antimicrobials, the use of ARESTIN® may result in overgrowth of nonsusceptible microorganisms including fungi. The effects of treatment for greater than 6 months have not been studied.
ARESTIN® should be used with caution in patients having a history of predisposition to oral candidiasis.
ARESTIN® has not been clinically tested in immunocompromised patients (such as those immunocompromised by diabetes, chemotherapy, radiation therapy, or infection with HIV).
If superinfection is suspected, appropriate measures should be taken.
ARESTIN® has not been clinically tested in pregnant women.
ARESTIN® has not been clinically tested for use in the regeneration of alveolar bone, either in preparation for or in conjunction with the placement of endosseous (dental) implants or in the treatment of failing implants.
A. Because ARESTIN® is a locally administered antibiotic (LAA), low systemic absorption was seen in clinical studies. A possible interaction with the use of oral tetracyclines and oral contraceptives has been reported. This interaction occurs at the intestinal level (in the gastrointestinal tract) when these products are given orally. ARESTIN® is not administered orally and does not affect intestinal flora. Based on the mechanism of this possible interaction, it does not appear to be relevant to ARESTIN® as a locally administered antibiotic. There are no reports of this type of interaction with locally delivered minocycline.
The use of whitening agents has not been clinically tested for use at the same time as ARESTIN® treatment. ARESTIN® is bioadhesive and sticks to the tooth and inside of the pocket subgingivally while whitening agents may not penetrate subgingivally.
A. Once ARESTIN® is inserted into the periodontal pocket, the crevicular fluid hydrolyzes the ARESTIN® polymer resulting in release of the active drug, minocycline. ARESTIN® maintains minocycline levels in crevicular fluid well above the minimum inhibitory concentration (MIC) levels of common periodontal pathogens for up to 21 days.5 Clinical trials with ARESTIN® have proven its effectiveness as an adjunct to scaling and root planing in treating periodontal disease.4
A. No. ARESTIN® does not contain gluten, red or yellow dye, or peanuts.
A. ARESTIN® comes in a box with 2 trays, each containing 12 cartridges. It is packaged in a specially designed unit-dose cartridge, which is inserted into a cartridge handle to administer the product. Each cartridge contains enough ARESTIN® for 1 periodontal pocket.4
A. ARESTIN® requires no preparation before administration. ARESTIN® is premixed, premeasured, and does not require refrigeration.21
A. Preparation is quick and easy: a cartridge is snapped into place on the ARESTIN® handle. Dental professionals remove the cap and insert the cartridge into the base of the periodontal pocket. Press down on the thumb ring to expel the powder, while the cartridge is gradually withdrawn from the base of the pocket. After administering ARESTIN®, the cartridge is easily removed and another cartridge can be immediately connected to the handle.
A. Unlike other treatments, ARESTIN® does not require adhesives or dressings and patients can resume tooth brushing 12 hours after treatment.
A. ARESTIN® does not “set.” It becomes a sticky paste once it mixes with the crevicular fluid, which then adheres to the root of the tooth and lining of the pocket.
A. Patients should be instructed to delay brushing the treated area for 12 hours after treatment with ARESTIN® and to abstain from using interproximal cleaning devices around the treated area for 10 days. Patients should also avoid foods that could traumatize the gingiva.
A. Occasionally a pocket is in a hard to reach place, or, the tissue may be "tight" around the tooth. Here are a few suggestions to make the placement of ARESTIN® easier:
A. In many states dental hygienists can deliver locally administered antibiotics (LAAs), such as ARESTIN®. Dental hygienists should check with their state boards about regulations specific to their state.
