Arestin Minocycline Hydrochloride 1 mg Powder, 1 powder — NDC 65976-100-01 (Billing 65976-0100-01)

WARNINGS 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.

ADVERSE REACTIONS 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.

PRECAUTIONS Hypersensitivity Reactions and Hypersensitivity Syndrome The following adverse events have been reported with minocycline products when taken orally. Hypersensitivity reactions and hypersensitivity syndrome that included, but were not limited to anaphylaxis, anaphylactoid reaction, angioneurotic edema, urticaria, rash, eosinophilia, and one or more of the following: hepatitis, pneumonitis, nephritis, myocarditis, and pericarditis may be present. Swelling of the face, pruritus, fever and lymphadenopathy have been reported with the use of ARESTIN.

Some of these reactions were serious. Post-marketing cases of anaphylaxis and serious skin reactions such as Stevens-Johnson syndrome and erythema multiforme have been reported with oral minocycline. Autoimmune Syndromes Tetracyclines, including oral minocycline, have been associated with the development of autoimmune syndromes including a lupus-like syndrome manifested by arthralgia, myalgia, rash, and swelling.

Sporadic cases of serum sickness-like reaction have presented shortly after oral minocycline use, manifested by fever, rash, arthralgia, lymphadenopathy and malaise. In symptomatic patients, liver function tests, ANA, CBC, and other appropriate tests should be performed to evaluate the patients. No further treatment with ARESTIN should be administered to the patient.

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, was noted during clinical studies, as with other antimicrobials, the use of ARESTIN may result in overgrowth of non-susceptible 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. The safety and effectiveness of ARESTIN have not been established for the treatment of periodontitis in patients with coexistent 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.

Information for Patients After treatment, patients should avoid chewing hard, crunchy, or sticky foods (i.e., carrots, taffy, and gum) with the treated teeth for 1 week, as well as avoid touching treated areas. Patients should also postpone the use of interproximal cleaning devices around the treated sites for 10 days after administration of ARESTIN. Patients should be advised that although some mild to moderate sensitivity is expected during the first week after SRP and administration of ARESTIN, they should notify the dentist promptly if pain, swelling, or other problems occur.

Patients should be notified to inform the dentist if itching, swelling, rash, papules, reddening, difficulty breathing, or other signs and symptoms of possible hypersensitivity occur. Carcinogenicity, Mutagenicity, Impairment of Fertility Dietary administration of minocycline in long-term tumorigenicity studies in rats resulted in evidence of thyroid tumor production. Minocycline has also been found to produce thyroid hyperplasia in rats and dogs.

In addition, there has been evidence of oncogenic activity in rats in studies with a related antibiotic, oxytetracycline (i.e., adrenal and pituitary tumors). Minocycline demonstrated no potential to cause genetic toxicity in a battery of assays which included a bacterial reverse mutation assay (Ames test), an in vitro mammalian cell gene mutation test (L5178Y/TK +/- mouse lymphoma assay), an in vitro mammalian chromosome abe… [Excerpted — this section continues on DailyMed.]