EMROSI

1 INDICATIONS AND USAGE EMROSI is indicated to treat inflammatory lesions (papules and pustules) of rosacea in adults. Limitations of Use This formulation of minocycline has not been evaluated in the treatment or prevention of infections. To reduce the development of drug-resistant bacteria as well as to maintain the effectiveness of other antibacterial drugs, use EMROSI only as indicated. EMROSI is a tetracycline-class drug indicated to treat inflammatory lesions (papules and pustules) of rosacea in adults. ( 1 ) Limitations of Use This formulation of minocycline has not been evaluated in the treatment or prevention of infections. To reduce the development of drug-resistant bacteria and to maintain the effectiveness of other antibacterial drugs, use EMROSI only as indicated. ( 1 )

2 DOSAGE AND ADMINISTRATION The recommended dosage of EMROSI is one capsule taken orally, once daily. Higher doses have not shown to be of additional benefit in the treatment of rosacea. EMROSI may be taken with or without food [see Clinical Pharmacology (12.3) ] . Ingestion of food along with EMROSI may help to reduce the risk of esophageal irritation and ulceration. Swallow the capsule whole. Do not crush or chew the extended-release capsule. The recommended dosage of EMROSI is 40 mg orally, once daily. ( 2 )

5 WARNINGS AND PRECAUTIONS Serious Skin/Hypersensitivity Reactions: Minocycline has been associated with anaphylaxis, serious skin reactions, erythema multiforme, and drug rash with eosinophilia and systemic symptoms (DRESS) syndrome. Discontinue EMROSI immediately if symptoms occur. ( 5.1 ) Tooth Discoloration and Enamel Hypoplasia: The use of EMROSI during tooth development (second and third trimesters of pregnancy, infancy, and childhood up to the age of 8 years) may cause permanent discoloration of the teeth (yellow-gray-brown). ( 5.2 ) Inhibition of Bone Growth: Use during the second and third trimesters of pregnancy, infancy, and childhood up to the age of 8 years may cause reversible inhibition of bone growth. ( 5.3 ) Clostridioides difficile -Associated Diarrhea (Antibiotic-Associated Colitis): Discontinue if Clostridioides difficile -associated diarrhea (antibiotic-associated colitis) occurs. ( 5.4 ) Hepatotoxicity: Discontinue EMROSI if liver injury is suspected. ( 5.5 ) Central Nervous System Effects: May cause central nervous system side effects including light-headedness, dizziness, or vertigo. ( 5.6 ) Idiopathic Intracranial Hypertension: May cause idiopathic intracranial hypertension in adults and adolescents. Discontinue EMROSI if symptoms occur. ( 5.7 ) Autoimmune Syndromes: Minocycline has been associated with autoimmune syndromes; discontinue EMROSI immediately if symptoms occur. ( 5.8 ) Metabolic Effects: If renal impairment exists, monitor serum levels of EMROSI during treatment, discontinue EMROSI if necessary. ( 5.9 ) 5.1 Hypersensitivity Reaction and Serious Skin Reactions Cases of anaphylaxis, serious skin reactions (e.g., Stevens-Johnson syndrome), erythema multiforme, and drug rash with eosinophilia and systemic symptoms (DRESS) syndrome have been reported postmarketing with minocycline use in patients with acne. DRESS syndrome consists of cutaneous reaction (such as rash or exfoliative dermatitis), eosinophilia, and one or more of the following visceral complications such as: hepatitis, pneumonitis, nephritis, myocarditis, and pericarditis. Fever and lymphadenopathy may be present. In some cases, death has been reported. If this syndrome is recognized, discontinue EMROSI immediately. 5.2 Tooth Discoloration and Enamel Hypoplasia The use of tetracycline class drugs, including EMROSI during tooth development (second and third trimesters of pregnancy, infancy, and childhood up to the age of 8 years) may cause permanent discoloration of the teeth (yellow-gray-brown). Permanent discoloration of the teeth is more common during long-term use of tetracycline-class drugs but has been observed following repeated short-term courses. Enamel hypoplasia has also been reported. Use of EMROSI is not recommended during tooth development. Advise the patient of the potential risk to the fetus if EMROSI is used during the second or third trimester of pregnancy [see Use in Specific Populations (8.1 , 8.4 )]. 5.3 Inhibition of Bone Growth The use of tetracycline-class drugs, including EMROSI, during the second and third trimesters of pregnancy, infancy, and childhood up to the age of 8 years may cause reversible inhibition of bone growth. All tetracyclines, including EMROSI, form a stable calcium complex in any bone-forming tissue. A decrease in fibula growth rate has been observed in premature human infants given oral tetracycline in doses of 25 mg/kg every 6 hours. This reaction was shown to be reversible when the drug was discontinued. Advise the patient of the potential risk to the fetus if EMROSI is used during the second or third trimester of pregnancy [see Use in Specific Populations (8.1 , 8.4 )]. 5.4 Clostridioides difficile -Associated Diarrhea (Antibiotic-Associated Colitis) Clostridium difficile associated diarrhea (CDAD) has been reported with nearly all antibacterial agents, including minocycline, and may range in severity from mild diarrhea to fatal colitis. C. difficile produces toxins A and B which contr…

4 CONTRAINDICATIONS EMROSI is contraindicated in patients with a history of hypersensitivity to any of the tetracyclines [see Warnings and Precautions (5.1) ]. Known hypersensitivity to any of the tetracyclines. ( 4 )

7 DRUG INTERACTIONS Patients who are on anticoagulant therapy may require downward adjustment of their anticoagulant dosage. ( 7.1 ) 7.1 Anticoagulants Because tetracyclines have been shown to decrease plasma prothrombin activity, patients who are on anticoagulant therapy may require downward adjustment of their anticoagulant dosage. 7.2 Penicillin Because bacteriostatic drugs may interfere with the bactericidal action of penicillin, avoid giving EMROSI in conjunction with penicillin. 7.3 Antacids and Iron Preparations Absorption of tetracyclines is impaired by antacids containing aluminum, calcium or magnesium and iron-containing preparations. 7.4 Drug/Laboratory Test Interactions False elevations of urinary catecholamine levels may occur due to interference with the fluorescence test.

8.1 Pregnancy Risk Summary Tetracycline-class drugs, including EMROSI, may cause permanent discoloration of deciduous teeth and reversible inhibition of bone growth when administered during the second and third trimesters of pregnancy [see Warnings and Precautions (5.2 , 5.3 ) and Use in Specific Populations (8.4) ]. A few postmarketing cases of limb reductions have been reported over decades of use; however, the association is unclear. The limited data from postmarketing reports are not sufficient to inform a drug-associated risk for birth defects or miscarriage. In animal reproduction studies conducted in pregnant rats and rabbits, bent limb bones were observed following oral administration of minocycline hydrochloride during organogenesis at systemic exposure of approximately 7.1 and 4.8 times, respectively, the maximum recommended human dose (MRHD) based on AUC exposures (see Data ). If the patient becomes pregnant while taking this drug, advise the patient of the risk to the fetus and discontinue treatment. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Human Data The use of tetracycline class drugs, including EMROSI, during tooth development (second and third trimesters of pregnancy, infancy, and childhood up to the age of 8 years) may cause permanent discoloration of deciduous teeth (yellow-gray-brown). Permanent discoloration of the teeth is more common during long-term use of the drug but has been observed following repeated short-term courses [see Warnings and Precautions (5.2) ]. Animal Data Results of animal studies indicate that minocycline hydrochloride crosses the placenta, are found in fetal tissues, and can cause delayed skeletal development in the developing fetus. Evidence of embryotoxicity has been noted in animals treated early in pregnancy [see Warnings and Precautions (5.3) ]. Minocycline hydrochloride induced skeletal malformations (bent limb bones) in fetuses when administered to pregnant rats and rabbits during the period of organogenesis at doses of 30 mg/kg/day and 100 mg/kg/day, respectively, (7.1 and 4.8 times, respectively, the MRHD based on AUC comparison). Reduced mean fetal body weight was observed in studies in which minocycline hydrochloride was administered to pregnant rats at an oral dose of 10 mg/kg/day (2.4 times the MRHD based on AUC comparison). Minocycline hydrochloride was assessed for effects on peri- and post-natal development of rats in a study that involved oral administration to pregnant rats during the period of organogenesis through lactation at doses of 5, 10, or 50 mg/kg/day. In this study, body weight gain was significantly reduced in pregnant females that received 50 mg/kg/day (6 times the MRHD based on AUC comparison). No effects of treatment on the duration of the gestation period or the number of live pups born per litter were observed. Gross external anomalies observed in offspring of animals that received minocycline hydrochloride at 50 mg/kg/day included reduced body size, improperly rotated forelimbs, and reduced size of extremities. No effects were observed on the physical development, behavior, learning ability, or reproduction of the offspring of animals that received minocycline hydrochloride.

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Serious Skin/Hypersensitivity Reactions [see Warnings and Precautions (5.1) ] Clostridioides difficile -Associated Diarrhea (Antibiotic-Associated Colitis) [see Warnings and Precautions (5.4) ] Hepatotoxicity [see Warnings and Precautions (5.5) ] Central Nervous System Effects [see Warnings and Precautions (5.6) ] Idiopathic Intracranial Hypertension [see Warnings and Precautions (5.7) ] The most commonly observed adverse reaction (incidence ≥1%) is dyspepsia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Journey Medical Corporation at 1-855-531-1859 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In two clinical trials, MVOR-1 and MVOR-2, a total of 638 adult subjects were analyzed under the safety population with 243 subjects in EMROSI group, 237 subjects in doxycycline (40 mg) group and 158 subjects in placebo group [see Clinical Studies (14) ]. The most common adverse reaction reported by ≥1% of subjects treated with EMROSI and more frequently than in subjects receiving placebo was dyspepsia, which was reported in 2% of subjects treated with EMROSI and none of the subjects receiving placebo. 6.2 Postmarketing Experience The following adverse reactions have been reported with post-approval use of minocycline hydrochloride in a variety of indications. Because these reactions are 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 hypersensitivity reactions: anaphylaxis, angioedema, DRESS syndrome, erythema multiforme, Stevens-Johnson syndrome, acute febrile neutrophilic dermatosis (Sweet’s syndrome), fixed drug eruptions, balanitis, anaphylactoid purpura photosensitivity, pigmentation of skin and mucous membranes. Autoimmune conditions: polyarthralgia, pericarditis, exacerbation of systemic lupus, pulmonary infiltrates with eosinophilia, lupus-like syndrome. Central nervous system: idiopathic intracranial hypertension, bulging fontanels in infants, decreased hearing. Endocrine: brown-black microscopic thyroid discoloration, abnormal thyroid function. Oncology: thyroid cancer. Oral: glossitis, dysphagia, tooth discoloration. Gastrointestinal: enterocolitis, pancreatitis, hepatitis, liver failure. Renal: acute renal failure. Hematology: hemolytic anemia, thrombocytopenia, eosinophilia.