AMZEEQ

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.

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 )

11 DESCRIPTION Minocycline hydrochloride, a semi-synthetic derivative of tetracycline, is [4S‑ (4α,4aα,5aα,12aα)]-4,7-Bis(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a‑ tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide mono hydrochloride. The structural formula is represented below: C 23 H 27 N 3 O 7 •HCl M. W. 493.94 Each gram of AMZEEQ contains micronized minocycline 40 mg equivalent to 43 mg minocycline hydrochloride in a yellow suspension foam. In addition, the 4% AMZEEQ topical foam contains the following inactive ingredients: soybean oil, coconut oil, light mineral oil, cyclomethicone, cetostearyl alcohol, stearic acid, myristyl alcohol, hydrogenated castor oil, white wax (beeswax), stearyl alcohol, docosanol. AMZEEQ topical foam is dispensed from an aluminum container (can) pressurized with propellant (butane + isobutane + propane). Structural Formula

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 )

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 )

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.

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action The mechanism of action of AMZEEQ for the treatment of acne is unknown. 12.2 Pharmacodynamics The pharmacodynamics of AMZEEQ for the treatment of acne are unknown. 12.3 Pharmacokinetics In a pharmacokinetic study, male and female subjects 18 years of age or older with acne vulgaris (N=30) applied approximately 4 grams of AMZEEQ topically to the face, neck, upper chest, upper back, shoulder and upper arms once daily for 21 days. The mean ± SD C max and AUC 0-24h were 1.3 ± 0.6 ng/mL and 23.0 ± 10.8 ng·h/mL, respectively at Day 21 for AMZEEQ. After daily application of AMZEEQ in subjects with acne for 21 days, steady-state was reached by Day 6 and systemic accumulation of minocycline was not evident. Specific Populations Age: Pediatric Population Pharmacokinetics of minocycline was evaluated in 20 subjects 10 years to less than 17 years of age with acne vulgaris following application of approximately 4 grams of AMZEEQ topically to the face, neck, upper chest, upper back, shoulder and upper arms once daily for 7 days. Minocycline was detected in all samples obtained on Day 7. Pharmacokinetic results are presented by age group in Table 2 . The overall pediatric population showed 2.4-fold and 2.7-fold higher C max and AUC 0-24h compared to the adult population. Table 2: Clinical Pharmacokinetics of Minocycline when treated with AMZEEQ (~4 g) in Pediatric Subjects Aged 10 to <17 years with Acne Vulgaris Age Group (years) Mean ± SD C max (ng/mL) Mean ± SD AUC 0-24h (ng·h/mL) 10 - 11 4.5 ± 4.0 90.9 ± 90.2 12 - 14 2.8 ± 2.2 54.0 ± 46.2 15 - <17 2.0 ± 1.2 40.8 ± 23.8 10 - <17 3.1 ± 2.7 61.1 ± 59.2 12.4 Microbiology Resistance Propionibacterium acnes strains displayed a low propensity for the development of resistance to minocycline, with spontaneous mutation frequencies being <10 −8 at 2 to 16 × MIC. Antimicrobial Activity Minocycline is active in vitro against most isolates of Propionibacterium acnes ; however, the clinical significance is unknown.

12.1 Mechanism of Action The mechanism of action of AMZEEQ for the treatment of acne is unknown.

12.2 Pharmacodynamics The pharmacodynamics of AMZEEQ for the treatment of acne are unknown.

12.3 Pharmacokinetics In a pharmacokinetic study, male and female subjects 18 years of age or older with acne vulgaris (N=30) applied approximately 4 grams of AMZEEQ topically to the face, neck, upper chest, upper back, shoulder and upper arms once daily for 21 days. The mean ± SD C max and AUC 0-24h were 1.3 ± 0.6 ng/mL and 23.0 ± 10.8 ng·h/mL, respectively at Day 21 for AMZEEQ. After daily application of AMZEEQ in subjects with acne for 21 days, steady-state was reached by Day 6 and systemic accumulation of minocycline was not evident. Specific Populations Age: Pediatric Population Pharmacokinetics of minocycline was evaluated in 20 subjects 10 years to less than 17 years of age with acne vulgaris following application of approximately 4 grams of AMZEEQ topically to the face, neck, upper chest, upper back, shoulder and upper arms once daily for 7 days. Minocycline was detected in all samples obtained on Day 7. Pharmacokinetic results are presented by age group in Table 2 . The overall pediatric population showed 2.4-fold and 2.7-fold higher C max and AUC 0-24h compared to the adult population. Table 2: Clinical Pharmacokinetics of Minocycline when treated with AMZEEQ (~4 g) in Pediatric Subjects Aged 10 to <17 years with Acne Vulgaris Age Group (years) Mean ± SD C max (ng/mL) Mean ± SD AUC 0-24h (ng·h/mL) 10 - 11 4.5 ± 4.0 90.9 ± 90.2 12 - 14 2.8 ± 2.2 54.0 ± 46.2 15 - <17 2.0 ± 1.2 40.8 ± 23.8 10 - <17 3.1 ± 2.7 61.1 ± 59.2

20230125

2

3 DOSAGE FORMS AND STRENGTHS Topical foam, 4% Each gram of AMZEEQ contains 40 mg of minocycline equivalent to 43 mg of minocycline hydrochloride and is supplied as a yellow suspension in a pressurized aluminum aerosol container (can). Foam, 4% ( 3 )

AMZEEQ Minocycline MINOCYCLINE HYDROCHLORIDE MINOCYCLINE HYDROGENATED SOYBEAN OIL COCONUT OIL LIGHT MINERAL OIL CYCLOMETHICONE CETOSTEARYL ALCOHOL STEARIC ACID MYRISTYL ALCOHOL HYDROGENATED CASTOR OIL WHITE WAX STEARYL ALCOHOL DOCOSANOL BUTANE ISOBUTANE PROPANE

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility In a carcinogenicity study in which minocycline hydrochloride was orally administered to male and female rats once daily for up to 104 weeks at dosages up to 200 mg/kg/day, minocycline hydrochloride was associated in both sexes with follicular cell tumors of the thyroid gland, including increased incidences of adenomas, carcinomas and the combined incidence of adenomas and carcinomas in males, and adenomas and the combined incidence of adenomas and carcinomas in females. In a carcinogenicity study in which minocycline hydrochloride was orally administered to male and female mice once daily for up to 104 weeks at dosages up to 150 mg/kg/day, exposure to minocycline hydrochloride did not result in a significantly increased incidence of neoplasms in either males or females. Minocycline was not mutagenic in vitro in a bacterial reverse mutation assay (Ames test) or CHO/HGPRT mammalian cell assay in the presence or absence of metabolic activation. Minocycline was not clastogenic in vitro using human peripheral blood lymphocytes or in vivo in a mouse micronucleus test. Male and female reproductive performance in rats was unaffected by oral doses of minocycline of up to 300 mg/kg/day (10,000 times the systemic exposure at the MRHD based on AUC comparison). However, oral administration of 100 or 300 mg/kg/day of minocycline to male rats (3,800 or 10,000 times, respectively, the systemic exposure at the MRHD based on AUC comparison), adversely affected spermatogenesis. Effects observed at 300 mg/kg/day of oral minocycline included a reduced number of sperm cells per gram of epididymis, an apparent reduction in the percentage of sperm that were motile, and (at 100 and 300 mg/kg/day) increased numbers of morphologically abnormal sperm cells. Morphological abnormalities observed in sperm samples included absent heads, misshapen heads, and abnormal flagella.

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility In a carcinogenicity study in which minocycline hydrochloride was orally administered to male and female rats once daily for up to 104 weeks at dosages up to 200 mg/kg/day, minocycline hydrochloride was associated in both sexes with follicular cell tumors of the thyroid gland, including increased incidences of adenomas, carcinomas and the combined incidence of adenomas and carcinomas in males, and adenomas and the combined incidence of adenomas and carcinomas in females. In a carcinogenicity study in which minocycline hydrochloride was orally administered to male and female mice once daily for up to 104 weeks at dosages up to 150 mg/kg/day, exposure to minocycline hydrochloride did not result in a significantly increased incidence of neoplasms in either males or females. Minocycline was not mutagenic in vitro in a bacterial reverse mutation assay (Ames test) or CHO/HGPRT mammalian cell assay in the presence or absence of metabolic activation. Minocycline was not clastogenic in vitro using human peripheral blood lymphocytes or in vivo in a mouse micronucleus test. Male and female reproductive performance in rats was unaffected by oral doses of minocycline of up to 300 mg/kg/day (10,000 times the systemic exposure at the MRHD based on AUC comparison). However, oral administration of 100 or 300 mg/kg/day of minocycline to male rats (3,800 or 10,000 times, respectively, the systemic exposure at the MRHD based on AUC comparison), adversely affected spermatogenesis. Effects observed at 300 mg/kg/day of oral minocycline included a reduced number of sperm cells per gram of epididymis, an apparent reduction in the percentage of sperm that were motile, and (at 100 and 300 mg/kg/day) increased numbers of morphologically abnormal sperm cells. Morphological abnormalities observed in sperm samples included absent heads, misshapen heads, and abnormal flagella.

NDA212379

AMZEEQ

Minocycline

69489-201

HUMAN PRESCRIPTION DRUG

TOPICAL

12.4 Microbiology Resistance Propionibacterium acnes strains displayed a low propensity for the development of resistance to minocycline, with spontaneous mutation frequencies being <10 −8 at 2 to 16 × MIC. Antimicrobial Activity Minocycline is active in vitro against most isolates of Propionibacterium acnes ; however, the clinical significance is unknown.

PACKAGE/LABEL PRINCIPAL DISPLAY PANEL - 30g Trade (69489-201-30) AMZEEQ Trade Label NDC 69489- 201 -30 - Label amzeeq ® (minocycline) topical foam, 4% For topical use only, not for oral, ophthalmic or intravaginal use Rx only [logo -Journey Medical Corporation] 30 g NDC 69489- 201 -30 - Carton amzeeq ® (minocycline) topical foam, 4% For topical use only, not for oral, ophthalmic or intravaginal use Rx only [logo -Journey Medical Corporation] 30 g label - Amzeeq 30g carton - Amzeeq 30g

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use). Inform patients using AMZEEQ (minocycline) topical foam, 4% of the following information and instructions: Flammability The propellant in AMZEEQ is flammable. Instruct the patient to avoid fire, flame, and smoking during and immediately following application. Tooth Discoloration Advise caregivers of pediatric patients that AMZEEQ may cause permanent discoloration of deciduous and permanent teeth during tooth development (generally up to the age of 8 years) based on observations with oral tetracycline. Lactation Advise women that breastfeeding is not recommended during AMZEEQ therapy. Tissue Hyperpigmentation Inform patients that AMZEEQ may cause discoloration of skin, scars, teeth or gums based on observations with oral minocycline. Clostridioides difficile Associated Diarrhea Advise patients that Clostridioides difficile associated diarrhea can occur with oral minocycline therapy. Advise patients to seek medical attention if they develop watery or bloody stools while using AMZEEQ. Hepatotoxicity Inform patients about the possibility of hepatotoxicity reported with oral minocycline. Advise patients to seek medical advice if they experience symptoms or signs of hepatotoxicity, including loss of appetite, tiredness, diarrhea, jaundice, increased bleeding tendencies, confusion, and sleepiness. Central Nervous System Effects Inform patients that central nervous system adverse reactions including dizziness or vertigo have been reported with oral minocycline therapy. Caution patients about driving vehicles or using hazardous machinery if they experience such symptoms while on AMZEEQ. Intracranial Hypertension Inform patients that intracranial hypertension can occur with minocycline therapy. Advise patients to seek medical attention if they develop unusual headache, visual symptoms, such as blurred vision, diplopia, and vision loss. Photosensitivity Inform patients that photosensitivity manifested by an exaggerated sunburn reaction has been observed in some individuals taking oral tetracyclines, including minocycline. Advise patients to minimize or avoid exposure to natural or artificial UV light (tanning beds or UVA/B treatment) while using AMZEEQ. Discuss other sun protection measures, if patients need to be outdoors while using AMZEEQ. Advise patients to discontinue treatment at the first evidence of sunburn. Autoimmune Syndromes Inform patients that autoimmune syndromes, including drug-induced lupus-like syndrome, autoimmune hepatitis, vasculitis and serum sickness have been observed with oral tetracycline-class drugs, including minocycline. Symptoms may be manifested by arthralgia, fever, rash and malaise. Advise patients who experience such symptoms to stop the drug immediately and seek medical help. Other Information AMZEEQ should be applied exactly as directed. AMZEEQ may stain fabric. Manufactured by: ASM Aerosol-Service AG, Mohlin, Switzerland Manufactured for: Journey Medical Corporation, Scottsdale, AZ 85258 Product of Portugal or Switzerland AMZ-P01-R00 AMZEEQ is a registered trademark of Journey Medical Corporation All other trademarks are the properties of their respective owners. Copyright © 2022 Journey Medical Corporation. All rights reserved.

14 CLINICAL STUDIES The safety and efficacy of AMZEEQ was assessed in three 12-week, multicenter, randomized, double-blind, vehicle-controlled studies (Study 1 [ NCT02815267 ], Study 2 [ NCT02815280 ], and Study 3 [ NCT03271021 ]) in subjects with moderate to severe acne vulgaris. Efficacy was assessed in a total of 2,418 subjects 9 years of age and older. AMZEEQ or its vehicle were applied once daily for 12 weeks; no other topical or systemic medication affecting the course of acne vulgaris was permitted for use during these studies.], and Study 3 [NCT03271021]) in subjects with moderate to severe acne vulgaris. Efficacy was assessed in a total of 2,418 subjects 9 years of age and older. AMZEEQ or its vehicle were applied once daily for 12 weeks; no other topical or systemic medication affecting the course of acne vulgaris was permitted for use during these studies.], Study 2 [NCT02815280], and Study 3 [NCT03271021]) in subjects with moderate to severe acne vulgaris. Efficacy was assessed in a total of 2,418 subjects 9 years of age and older. AMZEEQ or its vehicle were applied once daily for 12 weeks; no other topical or systemic medication affecting the course of acne vulgaris was permitted for use during these studies. Subjects were required to have an inflammatory and non-inflammatory lesion count in the range 20-50 lesions and 25-100 lesions respectively, and an Investigator Global Assessment (IGA) score of 3 (“moderate”) or 4 (“severe”) at baseline. Overall, 74% were Caucasian and 61% were female. Forty-two (2%) subjects were 9 to 11 years of age, 1,139 (47%) subjects were 12 to 17 years of age, and 1,237 (51%) subjects were 18 years or older. At baseline, subjects had a mean inflammatory lesion count of 31.2 and a mean non-inflammatory lesion count of 49.3. Additionally, approximately 85% of subjects had an IGA score of 3 (“moderate”). The co-primary efficacy endpoints were the absolute change from baseline in inflammatory lesion counts at Week 12 and the proportion of subjects with treatment success at Week 12, defined as an IGA score of 0 (“clear”) or 1 (“almost clear”), and at least a two-grade improvement (decrease) from baseline at Week 12. The efficacy results are presented in Table 3 . Table 3: Clinical Efficacy of AMZEEQ in Subjects with Acne Vulgaris at Week 12 a Treatment success is defined as an IGA score of 0 (“clear”) or 1 (“almost clear”), and at least a two-grade improvement (decrease) from baseline. b Means presented in table are Least Square (LS) means. Study 1 Study 2 Study 3 AMZEEQ (N=307) Vehicle (N=159) AMZEEQ (N=312) Vehicle (N=152) AMZEEQ (N=738) Vehicle (N=750) IGA Treatment Success a 8.1% 4.8% 15.8% 8.4% 30.8% 19.6% Difference from Vehicle (95% CI) 3.3% (-1.5%, 8.2%) 7.4% (0%, 13.7%) 11.2% (6.6%, 15.8%) Inflammatory Lesion Count Mean b Absolute Change from Baseline -14.0 -11.2 -13.7 -10.5 -16.4 -12.7 Difference from Vehicle (95% CI) -2.8 (-4.9, -0.7) -3.2 (-5.6, -0.9) -3.7 (-4.8, -2.5) Mean b Percent Change from Baseline -44% -34% -43% -34% -54% -42% Difference from Vehicle (95% CI) -10% (-17%, -3%) -10% (-17%, -2%) -12% (-16%, -8%)

8.5 Geriatric Use Clinical studies of AMZEEQ did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

8.4 Pediatric Use The safety and effectiveness of AMZEEQ have been established in pediatric patients 9 years of age and older for the treatment of inflammatory lesions of non-nodular moderate to severe acne vulgaris. Use of AMZEEQ for this indication is supported by three adequate and well controlled 12-week trials in patients 9 years of age and older; two of the trials included a 40-week open-label extension. Additional data was obtained from a 7-day open-label safety and pharmacokinetics study conducted in 20 patients 10 years to less than 17 years of age with acne vulgaris [see Clinical Pharmacology ( 12.3 ) and Clinical Studies ( 14 )] . A total of 686 subjects 9 years of age and older received AMZEEQ in these clinical trials. Safety and effectiveness for this indication have not been established in pediatric patients less than 9 years of age. The use of oral tetracycline drugs during tooth development below the age of 8 years may cause permanent discoloration of the teeth (yellow-gray-brown) and inhibition of bone growth [see Warnings and Precautions ( 5.2 , 5.3 )] .

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).

8 USE IN SPECIFIC POPULATIONS • Minocycline like other tetracycline-class drugs can cause fetal harm when administered orally to a pregnant woman. ( 5.2 , 8.1 ) • The use of drugs of the tetracycline class orally during tooth development may cause permanent discoloration of teeth. ( 5.3 , 8.2 , 8.4 ) • Lactation: Breastfeeding not recommended. ( 8.2 ) 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). 8.2 Lactation Risk Summary Tetracycline-class drugs, including minocycline, are present in breast milk following oral administration. It is not known whether minocycline is present in human milk after topical administration to the nursing mother. There are no data on the effects of minocycline on milk production. Because of the potential for serious adverse reactions, advise patients that breastfeeding is not recommended during treatment with AMZEEQ [see Warnings and Precautions ( 5.2 )]. 8.4 Pediatric Use The safety and effectiveness of AMZEEQ have been established in pediatric patients 9 years of age and older for the treatment of inflammatory lesions of non-nodular moderate to severe acne vulgaris. Use of AMZEEQ for this indication is supported by three adequate and well controlled 12-week trials in patients 9 years of age and older; two of the trials included a 40-week open-label extension. Additional data was obtained from a 7-day open-label safety and pharmacokinetics study conducted in 20 patients 10 years to less than 17 years of age with acne vulgaris [see Clinical Pharmacology ( 12.3 ) and Clinical Studies ( 14 )] . A total of 686 subjects 9 years of age and older received AMZEEQ in these clinical trials. Safety and effectiveness for this indication have not been established in pediatric patients less than 9 years of age. The use of oral tetracycline drugs during tooth development below the age of 8 years may cause permanent discoloration of the teeth (yellow-gray-brown) and inhibition of bone growth [see Warnings and Precautions ( 5.2 , 5.3 )] . 8.5 Geriatric Use Clinical studies of AMZEEQ did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied AMZEEQ ® (minocycline) topical foam, 4% is a yellow suspension supplied in a pressurized aluminum aerosol container (can). Each gram of AMZEEQ contains 40 mg of minocycline equivalent to 43 mg of minocycline hydrochloride, and is supplied as follows: NDC 69489-201-30 30 g Can Storage AMZEEQ must be stored at 2ºC - 8ºC (36ºF - 46ºF) until dispensed to the patient. Once dispensed, the patient is to store AMZEEQ at room temperature below 25ºC (77ºF) for 90 days. Do not store in the refrigerator. Handling Allow the can to warm to room temperature before first use. Shake can well before use. WARNING: Flammable. Avoid fire, flame, or smoking during and immediately following application. Contents under pressure. Do not puncture or incinerate. Do not expose to heat or temperatures above 49 o C (120 o F).