Periodontitis
Minocycline hydrochloride, as a subgingival extended-release powder, is used as an adjunct to scaling and root planing procedures for the reduction of pocket depth in the treatment of adult periodontitis.1 Minocycline hydrochloride may be used as part of a periodontal maintenance program, which includes good oral hygiene and scaling and root planing.1
Efficacy for this use was established in 2 controlled clinical trials in 748 otherwise healthy adults with generalized moderate to advanced periodontitis.1 Patients received minocycline hydrochloride extended-release powder for subgingival administration in conjunction with scaling and root planing, subgingival vehicle in conjunction with scaling and root planing, or scaling and root planing alone.1 Treatment was administered initially into all periodontal pocket sites at which the probing depth was 5 mm or greater; at 3 and 6 months, all sites treated at baseline were retreated with subgingival minocycline hydrochloride or vehicle and any new sites with pocket depth of 5 mm or greater were also treated.1,2 At 9 months after initiation of therapy, patients receiving subgingival minocycline hydrochloride in conjunction with scaling and root planing had greater reductions in pocket depth and a higher percentage of periodontal pockets showing depth changes of 2 mm or greater and 3 mm or greater than did patients treated with scaling and root planing alone or scaling and root planing in conjunction with subgingival vehicle.1 Following treatment with minocycline hydrochloride extended-release powder for subgingival administration in conjunction with scaling and root planing, deeper pockets showed greater reductions in pocket depth than shallower pockets; reductions in pocket depth also were greater in treatment groups of nonsmokers than in smokers.1
For systemic uses of minocycline, see the Tetracyclines General Statement 8:12.24.
Administration 
Subgingival Administration
Minocycline hydrochloride extended-release powder is administered subgingivally.1 The extended-release powder is inserted subgingivally into periodontal pockets by a dental health-care provider.1
Minocycline hydrochloride extended-release powder for subgingival administration is commercially available in a unit-dose cartridge.1 The cartridge must be inserted into a spring-loaded cartridge handle prior to administration.1 The drug is administered by inserting the unit-dose cartridge into the base of the periodontal pocket and then pressing the thumb ring in the handle mechanism to expel the extended-release powder while gradually withdrawing the tip from the base of the pocket.1 The handle mechanism should be sterilized prior to reuse on another patient.1
Subgingival administration does not require local anesthesia.1 Dental adhesive or periodontal dressings are not required following subgingival administration.1
Minocycline hydrochloride extended-release powder for subgingival administration is a bioresorbable product and does not have to be removed.1
The manufacturer's literature should be consulted for additional information regarding subgingival administration of minocycline extended-release powder.1
Dosage
Dosage of minocycline hydrochloride extended-release powder for subgingival administration is expressed in terms of minocycline.1
Each commercially available unit-dose cartridge of minocycline hydrochloride extended-release powder delivers 1 mg of minocycline.1
Periodontitis
The usual adult dosage of subgingival minocycline hydrochloride varies depending on the size, shape, and number of periodontal pockets treated.1
In clinical trials, up to 122 unit-dose cartridges were administered during a single visit to treat all gingival pocket sites with a probing depth of 5 mm or greater and up to 3 treatments were provided at 3-month intervals.1
Special Populations
No special population dosage recommendations.1
Contraindications
Minocycline hydrochloride extended-release powder for subgingival administration is contraindicated in patients hypersensitive to minocycline or other tetracyclines.1
Warnings/Precautions
Warnings
Dental and Bone Effects
Tetracyclines should not be used during tooth development (e.g., pregnancy, infancy, childhood to the age of 8 years) because the drugs may cause permanent tooth discoloration (yellow-gray-brown).1 This adverse effect is more common with long-term tetracycline use, but has been reported following repeated short-term use.1 Enamel hypoplasia also has been reported.1
Tetracyclines form a stable calcium complex in any bone-forming tissue.3 Reversible decrease in fibula growth rate has occurred in premature infants receiving oral tetracyclines.3
Sensitivity Reactions
Hypersensitivity Reactions
Hypersensitivity reactions and hypersensitivity syndrome have been reported in patients receiving oral tetracyclines.1 These reactions have included, but are not limited to, anaphylaxis, anaphylactoid reactions, angioedema, urticaria, rash, and eosinophilia;1 hepatitis, pneumonitis, nephritis, myocarditis, and/or pericarditis may also be present.1 Serious skin reactions, including Stevens-Johnson syndrome and erythema multiforme, have been reported with oral minocycline.1
Swelling of the face, pruritus, fever, and lymphadenopathy have been reported in patients receiving minocycline extended-release powder for subgingival administration.1 Some of these reactions were serious.1
Photosensitivity Reactions
Photosensitivity, manifested as an exaggerated sunburn reaction on areas of the body exposed to direct sunlight or ultraviolet light, has occurred in some patients receiving tetracyclines.1
Subgingival minocycline should be discontinued at the first sign of skin erythema.1
Other Warnings/Precautions
Autoimmune Syndrome
Tetracyclines, including oral minocycline, have been associated with the development of autoimmune syndromes, including a lupus-like syndrome manifested as arthralgia, myalgia, rash, and swelling.1
Sporadic cases of serum sickness-like reactions have presented shortly after oral minocycline use and were manifested as fever, rash, arthralgia, lymphadenopathy, and malaise.1
If symptoms of autoimmune syndrome develop in a patient receiving minocycline extended-release powder for subgingival administration, the drug should be permanently discontinued and the patient should be evaluated using appropriate tests, including liver function tests, antinuclear antibody (ANA) tests, and complete blood cell counts (CBCs).1
Acute Periodontitis
Use of subgingival minocycline in patients with acutely abscessed periodontal pockets has not been studied and is not recommended.1
Superinfection/Candidiasis
Overgrowth of opportunistic microorganisms, such as yeast, was not reported during clinical studies of minocycline extended-release powder for subgingival administration.1 However, as with other anti-infectives, use of the drug may result in overgrowth of nonsusceptible organisms, including fungi.1 Effects of subgingival minocycline treatment administered for longer than 6 months have not been studied.1 If superinfection is suspected, appropriate measures should be taken.1
Minocycline extended-release powder for subgingival administration should be used with caution in patients with a history of or predisposition to oral candidiasis.1 Safety and efficacy of the drug for the treatment of periodontitis in patients with concomitant oral candidiasis have not been established.1
Immunocompromised Patients
Minocycline extended-release powder for subgingival administration has not been studied in immunocompromised patients (e.g., those with diabetes mellitus or human immunodeficiency virus [HIV] infection, those receiving chemotherapy or radiation therapy).1
Dental Implants
Minocycline extended-release powder for subgingival administration has not been studied for use in the regeneration of alveolar bone, either in preparation for or in conjunction with placement of endosseous (dental) implants or in the treatment of failing dental implants.1
Specific Populations
Pregnancy
Minocycline extended-release powder for subgingival administration has not been evaluated in pregnant women.1 The effects of tetracyclines on labor and delivery are unknown.1
Tetracyclines should not be used during pregnancy.1 If a tetracycline is used during pregnancy, the patient should be apprised of potential hazards to the fetus.1
Lactation
Minocycline and other tetracyclines are distributed into milk.1
Tetracyclines should not be used in nursing women.1 Because of the potential for serious adverse reactions to tetracyclines in nursing infants, a decision should be made whether to discontinue nursing or minocycline, taking into account the importance of the drug to the woman.1
Pediatric Use
Safety and efficacy of minocycline extended-release powder for subgingival administration have not been established in pediatric patients younger than 18 years of age.1,2 (See Dental and Bone Effects under Warnings/Precautions: Warnings, in Cautions.)
Common Adverse Effects
Adverse effects occurring in 3% or more of patients receiving minocycline hydrochloride extended-release powder for subgingival administration include periodontitis, tooth disorder, tooth caries, dental pain, gingivitis, headache, infection, stomatitis, mouth ulceration, flu syndrome, pharyngitis, pain, dyspepsia, dental infection, and mucous membrane disorder.1
Pharmacokinetics
Absorption
Bioavailability
In a study in adults with moderate to advanced chronic periodontitis, subgingival administration of 1 mg (1 unit dose) of minocycline extended-release powder into each periodontal pocket site with a probing depth of 5 mm or greater resulted in mean dose-normalized area under the concentration-time curve (AUC) and peak concentration in saliva that were 125 and 1000 times higher, respectively, than values in serum.1,2 These patients had a minimum of 30 affected sites on at least 8 teeth and received a mean total dose of 46.2 mg of subgingival minocycline (range of 25-112 unit doses per patient).1
Description
Minocycline hydrochloride is a semisynthetic tetracycline antibiotic.1 Minocycline hydrochloride is commercially available for subgingival administration as an extended-release powder that contains the drug incorporated into a bioresorbable polymer (microspheres).1
The mechanism of action of the extended-release subgingival preparation of minocycline as an adjunct to scaling and root planing procedures in reduction of pocket depth in patients with adult periodontitis is unknown.1 Minocycline has antibacterial activity against some organisms associated with periodontal disease, but qualitative and quantitative changes in plaque microorganisms have not been demonstrated when the subgingival preparation of the drug was used in patients with periodontitis.1
Minocycline is bacteriostatic in action and exerts its antimicrobial activity by inhibiting protein synthesis in susceptible organisms.1 The drug is active in vitro against some organisms associated with periodontal disease.1 Porphyromonas gingivalis , Prevotella intermedia , Fusobacterium nucleatum , Eikenella corrodens , and Actinobacillus actinomycetemcomitans are inhibited in vitro by minocycline concentrations of 8 mcg/mL or less.1
At the conclusion of one clinical trial of 56 days' duration, there was no evidence of emergence of minocycline-resistant bacteria or changes in the presence of Candida albicans or Staphylococcus aureus in the GI tract in patients receiving minocycline hydrochloride extended-release powder for subgingival administration.1 However, in another clinical trial, at 9 months after initiation of subgingival minocycline hydrochloride therapy, the number of minocycline-resistant bacteria in the gingival crevicular fluid was increased slightly, but the clinical importance of this finding is not known.1,2
Advice to Patients
Advise patients to not eat hard, crunchy, or sticky foods (e.g., carrots, taffy, gum) and to not touch treated areas for 1 week after receiving subgingival minocycline.1 In addition, patients should avoid use of interproximal cleaning devices around treated sites for 10 days following subgingival administration of the drug.1
Patients should be advised that some mild to moderate sensitivity is expected during the first week following scaling and root planing and administration of subgingival minocycline, but a dental health-care professional should be contacted promptly if pain, swelling, or other problems occur.1
Advise patients of the importance of contacting a dental health-care professional if itching, swelling, rash, papules, reddening, difficulty breathing, or any other signs or symptoms of possible hypersensitivity occur.1
Advise patients that photosensitivity reactions have been reported with tetracyclines; importance of avoiding exposure to direct sunlight or ultraviolet light and importance of notifying dental health-care professional and discontinuing treatment at the first sign of skin erythema.1
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1
Importance of women informing clinicians if they are or plan to become pregnant or to breast-feed.1
Importance of advising patients of other important precautionary information.1 (See Cautions.)
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
1. OraPharma, Inc. Arestin® (minocycline hydrochloride) microspheres prescribing information. Bridgewater, NJ; 2017 May.
2. Reviewers' comments (personal observations).
3. Alvogen, Inc. Minocycline hydrochloride capsules, USP prescribing information. Pine Brook, NJ; 2016 Dec.