Arestin - Pharmacology Minocycline Hydrochloride

Pharmacology refers to the chemical makeup and behavior of ARESTIN (minocycline hydrochloride powder).

Description

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 C23H27N3O7 ·HCl, and the molecular weight is 493.94. The structural formula of minocycline hydrochloride is:

image 01.jpg

Clinical Pharmacology

mechanism of action

The mechanism of action of ARESTIN as an adjunct to scaling and root planing procedures for reduction of pocket depth in patients with adult periodontitis is unknown.

microbiology

Minocycline, a member of the tetracycline class of antibiotics, has a broad spectrum of activity. It is bacteriostatic and exerts its antimicrobial activity by inhibiting protein synthesis. In vitro susceptibility testing has shown that the organisms Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum, Eikenella corrodens, and Actinobacillus actinomycetemcomitans, which are associated with periodontal disease, are susceptible to minocycline at concentrations of ≤8 mcg/mL; qualitative and quantitative changes in plaque microorganisms have not been demonstrated in subjects with periodontitis, using this product.

The emergence of minocycline-resistant bacteria in single-site plaque samples was studied in subjects before and after treatment with ARESTIN at 2 centers. There was a slight increase in the numbers of minocycline-resistant bacteria at the end of the 9-month study period; however, the number of subjects studied was small and the clinical significance of these findings is unknown.

The emergence of minocycline-resistant bacteria and changes in the presence of Candida albicans and Staphylococcus aureus in the gastrointestinal tract were studied in subjects treated with ARESTIN in one phase 3 study. No changes in the presence of minocycline-resistant bacteria or Candida albicans or Staphylococcus aureus were seen at the end of the 56-day study period.

pharmacokinetics

In a pharmacokinetic study, 18 subjects (10 men and 8 women) with moderate to advanced chronic periodontitis were treated with a mean dose of 46.2 mg (25 to 112 unit doses) of ARESTIN. After fasting for at least 10 hours, subjects received subgingival application of ARESTIN (1 mg per treatment site) following scaling and root planing at a minimum of 30 sites on at least 8 teeth. Investigational drug was administered to all eligible sites ≥5 mm in probing depth. Mean dose normalized saliva AUC and Cmax were found to be approximately 125 and 1000 times higher than those of serum parameters, respectively.

clinical studies

In 2 well-controlled, multicenter, investigator-blind, vehicle-controlled, parallel-design studies (3 arms), 748 subjects (study OPI-103A=368, study OPI-103B=380) with generalized moderate to advanced adult periodontitis characterized by a mean probing depth of 5.90 and 5.81 mm, respectively, were enrolled. Subjects received 1 of 3 treatments: (1) scaling and root planing (SRP), (2) SRP + vehicle (bioresorbable polymer, PGLA), and (3) SRP + ARESTIN. To qualify for the study, subjects were required to have 4 teeth with periodontal pockets of 6 to 9 mm that bled on probing. However, treatment was administered to all sites with mean probing depths of 5 mm or greater. Subjects studied were in good general health. Subjects with poor glycemic control or active infectious diseases were excluded from the studies. Retreatment occurred at 3 and 6 months after initial treatment, and any new site with pocket depth ≥5 mm also received treatment. Subjects treated with ARESTIN were found to have statistically significantly reduced probing pocket depth compared with those treated with SRP alone or SRP + vehicle at 9 months after initial treatment, as shown in Table 1.

Table 1: Probing Pocket Depth at Baseline and Change in Pocket Depth at 9 Months from 2 Multicenter US Clinical Trials
Time Study OPI-103A
N=368
Study OPI-103B
N=380
SRP
Alone
n=124
SRP +
Vehicle n=123
SRP + ARESTIN n=121 SRP
Alone
n=126
SRP +
Vehicle n=126
SRP + ARESTIN n=128
SE = standard error; SRP = scaling and root planing; PD = pocket depth
Significantly different from SRP: *(P ≤0.05); **(P ≤0.001)
Significantly different from SRP + vehicle: ††(P ≤0.001)

PD (mm) at Baseline

5.88
±0.04

5.91
±0.04

5.88
±0.04

5.79
±0.03

5.82
±0.04

5.81
±0.04

[Mean ± SE]

PD (mm) Change from Baseline at 9
Months [Mean ± SE]

-1.04
±0.07

-0.90

±0.54

-1.20*††

±0.07

-1.32

±0.07

-1.30

±0.07

-1.63**††

±0.07

In these 2 studies, an average of 29.5 (5-114), 31.7 (4-137), and 31 (5-108) sites were treated at baseline in the SRP alone, SRP + vehicle, and SRP + ARESTIN groups, respectively. When these studies are combined, the mean pocket depth change at 9 months was -1.18 mm, -1.10 mm, and -1.42 mm for SRP alone, SRP + vehicle, and SRP + ARESTIN, respectively.

Table 2: Numbers (Percentage) of Pockets Showing a Change of Pocket Depth ≥2 mm at 9 Months from 2 Multicenter US Clinical Trials
                         Study OPI-103A Study OPI-103B
SRP
Alone
SRP +
Vehicle
SRP + ARESTIN SRP
Alone
SRP +
Vehicle
SRP + ARESTIN

Pockets

1046

(31.1%)

927

(25.7%)

1326

(36.5%)

1692

(42.2%)

1710

(40.0%)

2082

(51.0%)

≥2 mm
(% of Total)

Pockets

417

(12.4%)

315

(8.7%)

548

(15.1%)

553

(13.8%)

524

(12.3%)

704

(17.3%)

≥3 mm
(% of Total)

SRP + ARESTIN resulted in a greater percentage of pockets showing a change of PD ≥2 mm and ≥3 mm compared to SRP alone at 9 months, as shown in Table 2.

Table 3: Mean Pocket Depth Changes (SE) in Subpopulations, Studies 103A and 103B Combined

SRP
Alone

SRP +
Vehicle

SRP +
ARESTIN

Smokers

n=91
-0.96 (±0.09) mm

n=90
-0.98 (±0.07) mm

n=90
-1.24 (±0.09) mm**

Nonsmokers

n=159
-1.31 (±0.06) mm

n=159
-1.17 (±0.07) mm

n=159
-1.53 (±0.06) mm**

Subjects >50 YOA

n=21
-1.07 (±0.09) mm

n=81
-0.92 (±0.08) mm

n=107
-1.42 (±0.08) mm**

Subjects ≤50 YOA

n=167
-1.24 (±0.06) mm

n=168
-1.19 (±0.06) mm

n=142
-1.43 (±0.07) mm*

Subjects with CV Disease

n=36
-0.99 (±0.13) mm

n=29
-1.06 (±0.14) mm

n=36
-1.56 (±0.14) mm**

Subjects without CV Disease

n=214
-1.22 (±0.06) mm

n=220
-1.11 (±0.05) mm

n=213
-1.40 (±0.06) mm**

SRP = scaling and root planing; YOA = years of age; CV = cardiovascular
*SRP vs SRP + ARESTIN P ≤0.05; **SRP vs SRP + ARESTIN P ≤0.001

In both studies, the following patient subgroups were prospectively analyzed: smokers, subjects over and under 50 years of age, and subjects with a previous history of cardiovascular disease. The results of the combined studies are presented in Table 3.

In smokers, the mean reduction in pocket depth at 9 months was less in all treatment groups than in nonsmokers, but the reduction in mean pocket depth at 9 months with SRP + ARESTIN was significantly greater than with SRP + vehicle or SRP alone.

Table 4: Mean Pocket Depth Change in Subjects with Mean Baseline PD ≥5 mm, ≥6 mm, and ≥7 mm at 9 Months from 2 Multicenter US Clinical Trials
                         Study OPI-103A Study OPI-103B
Mean Baseline
Pocket Depth
SRP
Alone
SRP + Vehicle SRP + ARESTIN SRP
Alone
SRP + Vehicle SRP + ARESTIN

≥5 mm
(n)

-1.04 mm

(124)

-0.90 mm

(123)

-1.20 mm

Statistically significant comparison between SRP + ARESTIN and SRP alone

(121)

-1.32 mm

(126)

-1.30 mm

(126)

-1.63 mm

(128)

≥6 mm
(n)

-0.91 mm

(34)

-0.77 mm

(46)

-1.40 mm

(45)

-1.33 mm

(37)

-1.46 mm

(40)

-1.69 mm

(25)

≥7 mm
(n)

-1.10 mm

(4)

-0.46 mm

(5)

-1.91 mm

(3)

-1.72 mm

(3)

-1.11 mm

(3)

-2.84 mm

(2)

The combined data from these 2 studies also show that for pockets 5 mm to 7 mm at baseline, greater reductions in pocket depth occurred in pockets that were deeper at baseline.

This drug label information is as submitted to the Food and Drug Administration (FDA) and is intended for informational purposes only. If you think you may have a medical emergency, immediately call your doctor or dial 911. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Search Drugs and Medication

Or Browse by Name

Top Reads
  • Learn about drugs going generic in 2021 and how you may be able to save money on common prescription medication by switching to drugs coming off-patent.
    November 20, 2019
  • To make sure your medicines work as they should, here are some of the most common food-and-drug combinations to avoid.
    October 22, 2015
  • Get a list of the top 50 prescription drugs out of the annual 3 billion prescriptions filled at U.S. pharmacies.
    September 5, 2019
  • While medications are extremely useful in treating various diseases and conditions, sometimes they can cause unwanted side effects—one of which can be sexual dysfunction. Talk to your doctor if you’re taking any of these common medications that affect sex drive.
    September 23, 2016
  • Here’s a look at the most commonly abused prescription drugs.
    October 30, 2014

Love the Doctor Who Prescribed This Medication?

Top Drugs
  • Digestive health drugs manage diseases, disorders and conditions of the gastrointesinal system. They provide treatment and symptom relief for functional and structural problems with digestive organs.
  • Antibiotic, antifungal and antiviral drugs treat infectious diseases. They kill or stop the growth of microorganisms, including bacteria, fungi and viruses.
  • Birth control medications are a form of contraception. They contain either a combination of estrogen and progestin or progestin alone. There are several forms of these hormones, but most combination products contain estrogen, ethinyl estradiol, and a progestin. They work by preventing ovulation and inhibiting fertilization and implantation.
  • Mental health drugs treat conditions that affect emotional, psychological and social well-being. Doctors frequently use mental health drugs in combination with various forms of therapy to help people manage these conditions.