AMZEEQ

1 INDICATIONS AND USAGE AMZEEQ is indicated for the topical treatment of inflammatory lesions of non-nodular moderate to severe acne vulgaris in adults and pediatric patients 9 years of age and older [ see Clinical Studies ( 14 ) ]. Limitations of Use This formulation of minocycline has not been evaluated in the treatment of infections. To reduce the development of drug-resistant bacteria as well as to maintain the effectiveness of other antibacterial drugs, AMZEEQ should be used only as indicated [ see Warnings and Precautions ( 5.14 ) ]. AMZEEQ is a tetracycline-class drug indicated to treat inflammatory lesions of non-nodular moderate to severe acne vulgaris in patients 9 years of age and older. ( 1 ) Limitations of Use This formulation of minocycline has not been evaluated in the treatment of infections. To reduce the development of drug-resistant bacteria as well as to maintain the effectiveness of other antibacterial drugs, AMZEEQ should be used only as indicated. ( 5.14 )

2 DOSAGE AND ADMINISTRATION For topical use only, not for oral, ophthalmic or intravaginal use [ see Clinical Studies ( 14 ) ]. After shaking the can well, a small amount of topical foam (e.g. a cherry-sized amount) should be expressed from the can onto the fingertips of the hand and then rubbed into acne-affected parts of the face. This should be repeated as needed until all acne-affected parts of the face are treated. If acne is present on other parts of the patient’s body (neck, shoulders, arms, back or chest), additional amounts of topical foam should also be applied to these areas. The topical foam should be applied at approximately the same time each day at least 1 hour before bedtime. The patient should not bathe, shower or swim for at least 1 hour after application of the product. Apply AMZEEQ to affected areas once daily. AMZEEQ should be gently rubbed into the skin. ( 2 )

5 WARNINGS AND PRECAUTIONS The propellant in AMZEEQ is flammable. Instruct the patient to avoid fire, flame, and smoking during and immediately following application. ( 5.1 ) The use of tetracycline-class of drugs orally during the 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) and reversible inhibition of bone growth. ( 5.2 , 5.3 , 5.4 , 8.1 , 8.4 ) If Clostridioides difficile associated diarrhea occurs, discontinue AMZEEQ. ( 5.5 ) If liver injury is suspected, discontinue AMZEEQ. ( 5.6 ) If renal impairment exists, oral minocycline doses may need to be adjusted to avoid excessive systemic accumulations of the drug and possible liver toxicity. ( 5.7 ) Oral minocycline may cause central nervous system side effects including lightheadedness, dizziness, or vertigo. ( 5.8 ) Oral minocycline may cause intracranial hypertension in adults and adolescents. Discontinue AMZEEQ if symptoms occur. ( 5.9 ) Oral minocycline has been associated with autoimmune syndromes; discontinue AMZEEQ immediately if symptoms occur. ( 5.10 ) Photosensitivity can occur with oral tetracycline. Patients should minimize or avoid exposure to natural or artificial sunlight. ( 5.11 ) Oral minocycline has been associated with anaphylaxis, serious skin reactions, erythema multiforme, and DRESS syndrome. Discontinue AMZEEQ immediately if symptoms occur. ( 5.12 ) 5.1 Flammability The propellant in AMZEEQ is flammable. Instruct the patient to avoid fire, flame, and smoking during and immediately following application. Do not puncture and/or incinerate the containers. Do not expose containers to heat and/or store at temperatures above 120°F (49°C). 5.2 Teratogenic Effects Minocycline, like other tetracycline-class drugs, may inhibit bone growth when administered orally during pregnancy. Based on animal data, when administered orally, tetracyclines cross the placenta, are found in fetal tissues, and can cause skeletal malformation and retardation of skeletal development on the developing fetus [see Use in Specific Populations ( 8.1 ) and Nonclinical Toxicology ( 13 )] . 5.3 Tooth Discoloration The use of tetracycline class drugs orally 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). This adverse reaction is more common during long-term oral use of the tetracycline but has been observed following repeated short-term courses. Enamel hypoplasia has also been reported with oral tetracycline drugs. Use of tetracycline drugs is not recommended during tooth development. The safety and effectiveness of AMZEEQ have not been established in pediatric patients less than 9 years of age. 5.4 Inhibition of Bone Growth All tetracyclines 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. The safety and effectiveness of AMZEEQ have not been established in patients less than 9 years of age [see Use in Specific Populations ( 8.1 , 8.4 )]. Results of animal studies indicate that oral tetracyclines cross the placenta, are found in fetal tissues, and can cause retardation of skeletal development on the developing fetus. Evidence of embryotoxicity has been noted in animals treated orally early in pregnancy [see Use in Specific Populations ( 8.1 )]. 5.5 Clostridioides difficile Associated Diarrhea Clostridioides difficile associated diarrhea (CDAD) has been reported with nearly all antibacterial agents, including oral minocycline, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile . C. difficile produces toxins A an…

4 CONTRAINDICATIONS This drug is contraindicated in persons who have shown hypersensitivity to any of the tetracyclines or any other ingredients within AMZEEQ. This drug is contraindicated in persons who have shown hypersensitivity to any of the tetracyclines or any of the ingredients within AMZEEQ. ( 4 )

7 DRUG INTERACTIONS Patients who are on anticoagulant therapy may require downward adjustment of their anticoagulant dosage. ( 7.1 ) Penicillin: avoid coadministration. ( 7.2 ) 7.1 Anticoagulants Because tetracyclines have been shown to depress plasma prothrombin activity, patients who are on anticoagulant therapy may require downward adjustment of their anticoagulant dosage. 7.2 Penicillin Since bacteriostatic drugs may interfere with the bactericidal action of penicillin, it is advisable to avoid giving tetracycline-class drugs in conjunction with penicillin. 7.3 Drug/Laboratory Test Interactions False elevations of urinary catecholamine levels may occur due to interference with the fluorescence test.

8.1 Pregnancy Risk Summary Available data with AMZEEQ use in pregnant women are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. Systemic absorption of AMZEEQ in humans is low following once daily topical administration of AMZEEQ for 21 days [see Clinical Pharmacology ( 12.3 )] . Because of low systemic exposure, it is not expected that maternal use of AMZEEQ will result in significant fetal exposure to the drug. Tetracycline-class drugs may cause permanent discoloration of teeth and reversible inhibition of bone growth when administered orally during pregnancy [see Warnings and Precautions ( 5.2 , 5.3 , 5.4 ) and Use in Specific Populations ( 8.4 )] . Animal reproduction studies were not conducted with AMZEEQ. In animal reproduction studies, oral administration of minocycline administered to pregnant rats and rabbits during the period of organogenesis induced skeletal malformations in fetuses at systemic exposures of 750 and 500 times, respectively, the maximum recommended human dose (MRHD; based on AUC comparison) of AMZEEQ ( see Data ). The estimated 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 2-4% and 15-20%, respectively. Data Animal Data Results of animal studies indicate that tetracyclines cross the placenta, are found in fetal tissues, and can cause retardation of skeletal development of the developing fetus [ see Warnings and Precautions ( 5.2 ) ]. Minocycline induced skeletal malformations (bent limb bones) in fetuses when orally administered to pregnant rats and rabbits during the period of organogenesis at doses of 30 mg/kg/day and 100 mg/kg/day, respectively, (750 and 500 times, respectively, the systemic exposure at the MRHD based on AUC comparison). Reduced mean fetal body weight was observed when minocycline was orally administered to pregnant rats during the period of organogenesis at a dose of 10 mg/kg/day (250 times the systemic exposure at the MRHD based on AUC comparison). Minocycline 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 (650 times the systemic exposure at 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 F1 pups (offspring of animals that received oral minocycline) 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 F1 pups, and there was no effect on gross appearance of F2 pups (offspring of F1 animals).

6 ADVERSE REACTIONS The most commonly observed adverse reaction is headache. ( 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 3 randomized, double-blind, vehicle-controlled trials, subjects age 9 years and older applied AMZEEQ or vehicle once daily for 12 weeks. A total of 1,356 subjects were treated with AMZEEQ and 1,058 with vehicle. The majority of subjects were White (74%) and female (60%). Approximately 34% were Hispanic/Latino and 49% were younger than 18 years of age. The most common adverse reaction reported by ≥1% of subjects treated with AMZEEQ and more frequently than in subjects treated with vehicle was headache, which was reported in 3% of subjects treated with AMZEEQ and 2% of subjects treated with vehicle. Local tolerability evaluations were conducted at each study visit in the clinical trial by assessment of erythema, dryness, hyperpigmentation, skin peeling and itching. Table 1 presents the active assessment of the signs and symptoms of local facial tolerability at Week 12 in subjects treated with AMZEEQ. Local tolerability signs and symptoms occurred in similar frequency and severity as subjects treated with the vehicle component of AMZEEQ. Table 1: Facial Cutaneous Tolerability Assessment AMZEEQ, % (N=1,377) Symptom/Severity Mild Moderate Severe Erythema 14.2 1.5 0 Dryness 6.8 0.6 0 Hyperpigmentation Hyperpigmentation was most frequently assessed as characteristic of inflammatory and post-inflammatory changes associated with acne. 12.4 2.8 0.1 Skin Peeling 3.2 0.2 0 Itching 5.1 0.8 0.1 In a 40-week open-label extension safety study (for a total of up to 52 weeks of treatment), frequency and severity of local tolerability signs and symptoms at Week 52 were comparable to those reported at Week 12.