PERIOCHIP — chlorhexidine gluconate insert, extended release
Adrian Pharmaceuticals, LLC


PerioChip® (chlorhexidine gluconate) is a small, orange-brown, rectangular chip (rounded at one end) for insertion into periodontal pockets. Each PerioChip weighs approximately 7.4 mg and contains 2.5 mg of chlorhexidine gluconate in a biodegradable matrix of hydrolyzed gelatin (cross-linked with glutaraldehyde). PerioChip also contains glycerin and purified water.

Chlorhexidine gluconate is an antimicrobial agent. Chemically, it is designated as 1,1’-hexamethylenebis [5-(p-chlorophenyl)biguanide] di-D-gluconate, and its molecular formula is C22 H30 Cl2 N10 .2C6 H12 O7 . The molecular weight is 897.8. The structural formula of chlorhexidine gluconate is:

Chlorhexidine gluconate structural formula
(click image for full-size original)



Chlorhexidine gluconate is active against a broad spectrum of microbes. The chlorhexidine molecule, due to its positive charge, reacts with the microbial cell surface, destroys the integrity of the cell membrane, penetrates into the cell, precipiates the cytoplasm, and the cell dies. Studies with PerioChip showed reductions in the numbers of the putative periodontopathic organisms Porphyromonas (Bacteroides) gingivalis, Prevotella (Bacteroides) intermedia, Bacteroides forsythus , and Campylobacter rectus (Wolinella recta) after placement of the chip. No overgrowth of opportunistic organisms or the adverse changes in the oral microbial ecosystem were noted. The relationship of the microbial findings to clinical outcome has not been established.


PerioChip releases chlorhexidine in vitro in a biphasic manner, initially releasing approximately 40% of the chlorhexidine within the first 24 hours and then releasing the remaining chlorhexidine in an almost linear fashion for 7-10 days. This enzymatic release rate assay is an experimental collagenase assay that differs from the Regulatory Specification’s Agar Release Rate Assay. This release profile may be explained as an initial burst effect, dependent on diffusion of chlorhexidine from the chip, followed by a further release of chlorhexidine as a result of enzymatic degradation.

In an in vivo study of 18 evaluable adult patients, there were no detectable plasma or urine levels of chlorhexidine following the insertion of 4 PerioChips under clinical conditions. The concentration of chlorhexidine released from the PerioChip was determined in the gingival crevicular fluid (GCF) of these same subjects. In these subjects, a highly variable biphasic release profile for chlorhexidine was demonstrated, with GCF levels 4 hours after chip insertion (mean: 1444 ± 783 µg/mL), followed by a second peak at 72 hours (mean: 1902 ± 1073 µg/mL). In a second study involving the insertion of 1 PerioChip under clinical conditions, the mean GCF level of chlorhexidine peaked at 1088 ± 678 µg/mL at 4 hours. The mean GCF levels then declined in a highly erratic fashion to levels of 482 ± 447 µg/mL at 72 hours without producing a true second peak.

The results of these studies confirm a high degree of intersubject variability in chlorhexidine release from the PerioChip matrix in vivo that was not seen in vitro. Due to the nature and clinical use of the PerioChip dosage form, dose proportionality was not and would not be expected to be demonstrated between the two studies.

Clinical Studies

SIn two double-blind, randomized, controlled clinical trials, 447 adult patients with periodontitis were entered who had at least 4 pockets with probing depth of 5-8 mm that bled on probing. Patients studied were in good general health. Diabetics were excluded from the studies. PerioChip was not studied in acutely abscessed periodontal pockets. Patients were free of supragingival calculus prior to baseline. In these two studies, the effects of scaling and root planing (SRP) alone, and SRP followed by PerioChip treatment, were compared. All patients received full mouth SRP at baseline. If the pocket depth remained ≥ 5 mm at 3 and/or 6 months after initial treatment, another chip was placed into the pocket. Teeth treated with PerioChip were found to have significantly reduced probing pocket depth (PD) compared with those treated with SRP alone at 9 months after initial treatment, as shown in Table 1

Table 1
Probing pocket depth (PD) at baseline and reduction in PD at 9 monthsfrom 2 five-center U.S.clinical trials (in mm, mean ± SE)
Study #94-002 Study #94-002 Study #94-003 Study #94-003
Time SRP alone SRP + PerioChip SRP alone SRP + PerioChip
PD at Baseline 5.69 ± 0.58(n = 107) 5.79 ± 0.61 (n = 108) 5.56 ± 0.54(n = 115) 5.67 ± 0.56(N = 117)
PD Reduction at9 months 0.78 ± 0.07 (n = 101) 1.06 ± 0.07* (n = 101) 0.52 ± 0.07 (n = 107) 0.84 ± 0.08** (n = 110)

SE = standard error; SRP = Scaling and Root PlaningSignificantly different from SRP alone: *(p = 0.006); **(p = 0.001)

PerioChip treatment resulted in a greater percentage of pockets and patients that showed an improvement in PD of 2 mm or more compared with SRP alone at 9 months, as shown in Table 2. The differences in improvement were statistically significant when analyzed on a per patient basis (p less than 0.005). PerioChip treatment maintained probing attachment level (PAL) compared with baseline or with SRP alone at 9 months. The effects of PerioChip on bleeding upon probing have not been established. In the two studies, there were no significant changes in plaque development or gingivitis. Smokers and non-smokers were enrolled in these studies; although non-smokers using PerioChip demonstrated significant improvement in PD, smokers demonstrated a trend towards improvement that did not reach statistical significance. This finding is consistent with the consensus that smoking is a risk factor in periodontal diseases.

Table 2
Number (percentage) of pockets and patients with an improvementin PD ≥ 2 mm at 9 months from 2 five-center U.S. clinical trials
Study #94-002 Study #94-002 Study #94-003 Study #94-003
SRP alone SRP + PerioChip SRP alone SRP + PerioChip
Pockets 21 / 202(11%) 44 / 202(22%) 12 / 214(6%) 36 / 220(16%)
Patients(one or both sites) 17 / 101(17%) 36 / 101(36%) 11 / 107(10%) 28 / 110(25%)

In the two clinical studies above and an additional study (619 patients), the adverse effects of tooth staining or altered taste perception were not reported after the use of PerioChip.


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


PerioChip should not be used in any patient who has a known sensitivity to chlorhexidine.



The use of PerioChip in an acutely abscessed periodontal pocket has not been studied and therefore is not recommended. Although rare, infectious events including abscesses and cellulitis, which have been reported after scaling and root planing alone, have also been reported with the adjunctive placement of the PerioChip post scaling and root planing. Management of patients with periodontal disease should include consideration of potentially contributing medical disorders, such as cancer, diabetes, and immunocompromised status.

Information for Patients

Patients should avoid dental floss at the site of PerioChip insertion for 10 days after placement, because flossing might dislodge the chip. All other oral hygiene may be continued as usual. No restrictions regarding dietary habits are needed. Dislodging of the PerioChip is uncommon; however, patients should be instructed to notify the dentist promptly if the PerioChip dislodges. Patients should be also be advised that, although some mild to moderate sensitivity is normal during the first week after placement of PerioChip, they should notify the dentist promptly if pain, swelling, or other problems occur.

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