Minocycline Hydrochloride

6 ADVERSE REACTIONS The most commonly observed adverse reactions (incidence ≥ 5%) are headache, fatigue, dizziness, and pruritus. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Ascend Laboratories, LLC at 1-877-ASC-RX01 (877-272-7901) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trial 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. The following table summarizes selected adverse reactions reported in clinical trials at a rate of ≥ 1% for Minocycline hydrochloride extended-release tablets. Table 2: Selected Treatment-Emergent Adverse Reactions in at least 1% of Clinical Trial Subjects Adverse Reactions MINOCYCLINE HYDROCHLORIDE EXTENDED-RELEASE TABLETS (1 mg/ Kg) N=674(%) PLACEBO N=364 (%) At least one treatment-emergent event 379 (56) 197 (54) Headache 152 (23) 83 (23) Fatigue 62 (9) 24 (7) Dizziness 59 (9) 17 (5) Pruritus 31 (5) 16 (4) Malaise 26 (4) 9 (3) Mood alteration 17 (3) 9 (3) Somnolence 13 (2) 3 (1) Urticaria 10 (2) 1 (0) Tinnitus 10 (2) 5 (1) Arthralgia 9 (1) 2 (0) Vertigo 8 (1) 3 (1) Dry mouth 7 (1) 5 (1) Myalgia 7 (1) 4 (1) 6.2 Postmarketing Experience Adverse reactions that have been reported with Minocycline hydrochloride use in a variety of indications include: Skin and hypersensitivity reactions : fixed drug eruptions, balanitis, erythema multiforme, Stevens-Johnson syndrome, anaphylactoid purpura, photosensitivity, pigmentation of skin and mucous membranes, hypersensitivity reactions, angioneurotic edema, anaphylaxis, DRESS syndrome [see Warnings and Precautions (5.9) ] . Autoimmune conditions : polyarthralgia, pericarditis, exacerbation of systemic lupus, pulmonary infiltrates with eosinophilia, transient lupus-like syndrome. Central nervous system : pseudotumor cerebri, 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 : reversible acute renal failure. Hematology : hemolytic anemia, thrombocytopenia, eosinophilia. Preliminary studies suggest that use of minocycline may have deleterious effects on human spermatogenesis [see Nonclinical Toxicology (13.1) ] .

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

11 DESCRIPTION Minocycline hydrochloride, a semi synthetic derivative of tetracycline, is [4 S -(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: C23H27N3O7•HCl M. W. 493.95 Minocycline hydrochloride extended-release tablets, USP for oral administration contain minocycline hydrochloride USP equivalent to 45 mg, 55 mg, 65 mg, 80 mg, 90 mg, 105 mg, 115 mg, and 135 mg of minocycline. In addition, 45 mg, 55 mg, 65 mg, 80 mg, 90 mg, 105 mg, 115 mg, and 135 mg tablets contain the following inactive ingredients: lactose monohydrate, hypromellose type 2910, hypromellose type 2208, colloidal silicon dioxide, magnesium stearate, titanium dioxide and triacetin. The 45 mg tablets also contain iron oxide black. The 65 mg tablets also contain FD&C blue #1/brilliant blue FCF aluminium lake, polyethylene glycol 3350, FD&C blue #2/indigo carmine aluminum lake and D&C yellow #10 aluminum lake. The 55 mg tablets also contain macrogol, FD&C RED #40. The 80 mg tablets also contain macrogol, FD&C blue #2, FD&C red #40, FD&C yellow #6. The 90 mg tablets also contain iron oxide yellow and polyethylene glycol 3350. The 105 mg tablets also D&C red #27, macrogol, FD&C blue #1. The 115 mg tablets also contain D&C yellow #10 aluminum lake, FD&C blue #1/brilliant blue FCF aluminium lake and FD&C blue #2/indigo carmine aluminum lake. The 135 mg tablets also contain polyethylene glycol 3350 and iron oxide red. The USP Dissolution Test is pending

2 DOSAGE & ADMINISTRATION The recommended dosage of Minocycline hydrochloride extended-release tablets is approximately 1 mg/kg once daily for 12 weeks. Higher doses have not shown to be of additional benefit in the treatment of inflammatory lesions of acne, and may be associated with more acute vestibular side effects. The following table shows tablet strength and body weight to achieve approximately 1 mg/kg. Table 1: Dosing Table for Minocycline hydrochloride extended-release tablets Patient's Weight (lbs.) Patient's Weight (kg) Tablet Strength (mg) Actual mg/kg Dose 99 to 109 45 to 49 45 1 to 0.92 110 to 131 50 to 59 55 1.10 to 0.93 132 to 157 60 to 71 65 1.08 to 0.92 158 to 186 72 to 84 80 1.11 to 0.95 187 to 212 85 to 96 90 1.06 to 0.94 213 to 243 97 to 110 105 1.08 to 0.95 244 to 276 111 to 125 115 1.04 to 0.92 277 to 300 126 to 136 135 1.07 to 0.99 Minocycline hydrochloride extended-release tablets may be taken with or without food [see Clinical Pharmacology ( 12.3 )] . Ingestion of food along with Minocycline hydrochloride extended-release tablets may help reduce the risk of esophageal irritation and ulceration. In patients with renal impairment, the total dosage should be decreased by either reducing the recommended individual doses and/or by extending the time intervals between doses [see Warnings and Precautions (5.4 )] . The recommended dosage of Minocycline hydrochloride extended-release tablets is approximately 1 mg/kg once daily for 12 weeks. ( 2 )

1 INDICATIONS & USAGE Minocycline hydrochloride extended-release tablets is a tetracycline-class drug indicated to treat only inflammatory lesions of non-nodular moderate to severe acne vulgaris in patients 12 years of age and older. 1.1 Indication Minocycline hydrochloride extended-release tablets is indicated to treat only inflammatory lesions of non-nodular moderate to severe acne vulgaris in patients 12 years of age and older. 1.2 Limitations of Use Minocycline hydrochloride extended-release tablets did not demonstrate any effect on non-inflammatory acne lesions. Safety of Minocycline hydrochloride extended-release tablets has not been established beyond 12 weeks of use. This formulation of minocycline has not been evaluated in the treatment of infections [see Clinical Studies (14) ] . To reduce the development of drug-resistant bacteria as well as to maintain the effectiveness of other antibacterial drugs, Minocycline hydrochloride extended-release tablets should be used only as indicated [see Warnings and Precautions (5.11) ] .

10 OVERDOSAGE In case of overdosage, discontinue medication, treat symptomatically and institute supportive measures. Minocycline is not removed in significant quantities by hemodialysis or peritoneal dialysis.

7 DRUG INTERACTIONS Patients who are on anticoagulant therapy may require downward adjustment of their anticoagulant dosage. (7.1) The concurrent use of tetracycline and methoxyflurane has been reported to result in fatal renal toxicity. (7.3) To avoid contraceptive failure, female patients are advised to use a second form of contraceptive during treatment with minocycline. (7.5) 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 Methoxyflurane The concurrent use of tetracycline and methoxyflurane has been reported to result in fatal renal toxicity. 7.4 Antacids and Iron Preparations Absorption of tetracyclines is impaired by antacids containing aluminum, calcium or magnesium and iron-containing preparations. 7.5 Low Dose Oral Contraceptives In a multi-center study to evaluate the effect of Minocycline hydrochloride extended-release tablets on low dose oral contraceptives, hormone levels over one menstrual cycle with and without Minocycline hydrochloride extended-release tablets 1 mg/kg once-daily were measured. Based on the results of this trial, minocycline-related changes in estradiol, progestinic hormone, FSH and LH plasma levels, of breakthrough bleeding, or of contraceptive failure, cannot be ruled out. To avoid contraceptive failure, female patients are advised to use a second form of contraceptive during treatment with minocycline. 7.6 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 Minocycline hydrochloride extended-release tablets for the treatment of acne is unknown. 12.2 Pharmacodynamics The pharmacodynamics of Minocycline hydrochloride extended-release tablets for the treatment of acne is unknown. 12.3 Pharmacokinetics Minocycline hydrochloride extended-release tablets are not bioequivalent to non-modified release minocycline products. Based on pharmacokinetic studies in healthy adults, Minocycline hydrochloride extended-release tablets produce a delayed T max at 3.5 to 4.0 hours as compared to a non-modified release reference minocycline product (T max at 2.25 to 3 hours). At steady-state (Day 6), the mean AUC(0-24) and C max were 33.32 mcg×hr/mL and 2.63 mcg/mL for minocycline hydrochloride extended release tablets and 46.35 mcg×hr/mL and 2.92 mcg/mL for minocycline hydrochloride capsules, respectively. These parameters are based on dose adjusted to 135 mg per day for both product. A single-dose, four-way crossover study demonstrated that Minocycline hydrochloride extended-release tablets used in the study (45 mg, 90 mg, 135 mg) exhibited dose-proportional pharmacokinetics. In another single-dose, five-way crossover pharmacokinetic study, Minocycline hydrochloride extended-release tablets 55mg,80 mg, and 105 mg were shown to be dose-proportional to Minocycline hydrochloride extended-release tablets 90 mg and 135 mg. When Minocycline hydrochloride extended-release tablets were administered concomitantly with a meal that included dairy products, the extent and timing of absorption of minocycline did not differ from that of administration under fasting conditions. Minocycline is lipid soluble and distributes into the skin and sebum.

12.1 Mechanism of Action The mechanism of action of Minocycline hydrochloride extended-release tablets for the treatment of acne is unknown.

12.2 Pharmacodynamics The pharmacodynamics of Minocycline hydrochloride extended-release tablets for the treatment of acne is unknown.

12.3 Pharmacokinetics Minocycline hydrochloride extended-release tablets are not bioequivalent to non-modified release minocycline products. Based on pharmacokinetic studies in healthy adults, Minocycline hydrochloride extended-release tablets produce a delayed T max at 3.5 to 4.0 hours as compared to a non-modified release reference minocycline product (T max at 2.25 to 3 hours). At steady-state (Day 6), the mean AUC(0-24) and C max were 33.32 mcg×hr/mL and 2.63 mcg/mL for minocycline hydrochloride extended release tablets and 46.35 mcg×hr/mL and 2.92 mcg/mL for minocycline hydrochloride capsules, respectively. These parameters are based on dose adjusted to 135 mg per day for both product. A single-dose, four-way crossover study demonstrated that Minocycline hydrochloride extended-release tablets used in the study (45 mg, 90 mg, 135 mg) exhibited dose-proportional pharmacokinetics. In another single-dose, five-way crossover pharmacokinetic study, Minocycline hydrochloride extended-release tablets 55mg,80 mg, and 105 mg were shown to be dose-proportional to Minocycline hydrochloride extended-release tablets 90 mg and 135 mg. When Minocycline hydrochloride extended-release tablets were administered concomitantly with a meal that included dairy products, the extent and timing of absorption of minocycline did not differ from that of administration under fasting conditions. Minocycline is lipid soluble and distributes into the skin and sebum.

20230222

102

3 DOSAGE FORMS & STRENGTHS 45 mg extended release tablets: grey coloured capsule shaped film coated tablets, debossed with “45”on one side, plain on other side. 55 mg extended release tablets:Pink coloured capsule shaped film coated tablets, debossed with "55" on one side,plain on other side. 65 mg extended release tablets: blue coloured capsule shaped film coated tablets, debossed with “65”on one side, plain on other side. 80 mg extended release tablets:Greyish brown coloured capsule shaped film coated tablets, debossed with "80''on one side, plain on other side. 90 mg extended release tablets: yellow coloured capsule shaped film coated tablets, debossed with “90”on one side, plain on other side. 105 mg extended release tablets:Purple coloured capsule shaped film coated tablets, debossed with "105'' on one side, plain on other side. 115 mg extended release tablets: green coloured capsule shaped film coated tablets, debossed with “115”on one side, plain on other side. 135 mg extended release tablets: pink (orange-brown) coloured capsule shaped film coated tablets, debossed with “135”on one side, plain on other side Extended release tablets: 45 mg, 55 mg, 65 mg, 80 mg, 90 mg, 105 mg, 115 mg, and 135 mg (3)

Minocycline Hydrochloride Minocycline Hydrochloride MINOCYCLINE HYDROCHLORIDE MINOCYCLINE LACTOSE MONOHYDRATE HYPROMELLOSE 2208 (4000 MPA.S) HYPROMELLOSE 2910 (50 MPA.S) SILICON DIOXIDE MAGNESIUM STEARATE TITANIUM DIOXIDE TRIACETIN POLYETHYLENE GLYCOL 3350 FERRIC OXIDE YELLOW 90 mino-struc

13.1 Carcinogenesis & Mutagenesis & Impairment Of Fertility Carcinogenesis — In a carcinogenicity study in which minocycline HCl was orally administered to male and female rats once daily for up to 104 weeks at dosages up to 200 mg/kg/day, minocycline HCl was associated in both genders 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 HCl 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 HCl did not result in a significantly increased incidence of neoplasms in either males or females. Mutagenesis —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. Impairment of Fertility —Male and female reproductive performance in rats was unaffected by oral doses of minocycline of up to 300 mg/kg/day (which resulted in up to approximately 40 times the level of systemic exposure to minocycline observed in patients as a result of use of Minocycline hydrochloride extended-release tablets). However, oral administration of 100 or 300 mg/kg/day of minocycline to male rats (resulting in approximately 15 to 40 times the level of systemic exposure to minocycline observed in patients as a result of use of Minocycline hydrochloride extended-release tablets) adversely affected spermatogenesis. Effects observed at 300 mg/kg/day 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. Limited human studies suggest that minocycline may have a deleterious effect on spermatogenesis. Minocycline hydrochloride extended-release tablets should not be used by individuals of either gender who are attempting to conceive a child.

13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis & Mutagenesis & Impairment Of Fertility Carcinogenesis — In a carcinogenicity study in which minocycline HCl was orally administered to male and female rats once daily for up to 104 weeks at dosages up to 200 mg/kg/day, minocycline HCl was associated in both genders 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 HCl 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 HCl did not result in a significantly increased incidence of neoplasms in either males or females. Mutagenesis —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. Impairment of Fertility —Male and female reproductive performance in rats was unaffected by oral doses of minocycline of up to 300 mg/kg/day (which resulted in up to approximately 40 times the level of systemic exposure to minocycline observed in patients as a result of use of Minocycline hydrochloride extended-release tablets). However, oral administration of 100 or 300 mg/kg/day of minocycline to male rats (resulting in approximately 15 to 40 times the level of systemic exposure to minocycline observed in patients as a result of use of Minocycline hydrochloride extended-release tablets) adversely affected spermatogenesis. Effects observed at 300 mg/kg/day 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. Limited human studies suggest that minocycline may have a deleterious effect on spermatogenesis. Minocycline hydrochloride extended-release tablets should not be used by individuals of either gender who are attempting to conceive a child.

ANDA204453

Minocycline Hydrochloride

Minocycline Hydrochloride

63629-9215

HUMAN PRESCRIPTION DRUG

ORAL

Minocycline HCL 90 mg ER tab#30 Label

17 PATIENT COUNSELING INFORMATION [See FDA-approved patient labeling (Patient Information)] Patients taking Minocycline hydrochloride extended-release tablets should receive the following information and instructions: Minocycline hydrochloride extended-release tablets should not be used by pregnant women or women attempting to conceive a child [see Use in Specific Populations (8.1) , Nonclinical Toxicology (13.1) ]. It is recommended that Minocycline hydrochloride extended-release tablets not be used by men who are attempting to father a child [see Nonclinical Toxicology (13.1) ]. Patients should be advised that pseudomembranous colitis can occur with minocycline therapy. If patients develop watery or bloody stools, they should seek medical attention. Patients should be counseled about the possibility of hepatotoxicity. Patients should seek medical advice if they experience symptoms which can include loss of appetite, tiredness, diarrhea, skin turning yellow, bleeding easily, confusion, and sleepiness. Patients who experience central nervous system symptoms [see Warnings and Precautions (5.5) ] should be cautioned about driving vehicles or using hazardous machinery while on minocycline therapy. Patients should seek medical help for persistent headaches or blurred vision. Concurrent use of tetracycline may render oral contraceptives less effective [see Drug Interactions (7.5) ]. Autoimmune syndromes, including drug-induced lupus-like syndrome, autoimmune hepatitis, vasculitis and serum sickness have been observed with tetracycline-class drugs, including minocycline. Symptoms may be manifested by arthralgia, fever, rash and malaise. Patients who experience such symptoms should be cautioned to stop the drug immediately and seek medical help. Patients should be counseled about discoloration of skin, scars, teeth or gums that can arise from minocycline therapy. Photosensitivity manifested by an exaggerated sunburn reaction has been observed in some individuals taking tetracyclines, including minocycline. Patients should minimize or avoid exposure to natural or artificial sunlight (tanning beds or UVA/B treatment) while using minocycline. If patients need to be outdoors while using minocycline, they should wear loose-fitting clothes that protect skin from sun exposure and discuss other sun protection measures with their physician. Treatment should be discontinued at the first evidence of skin erythema. Minocycline hydrochloride extended-release tablets should be taken exactly as directed. Skipping doses or not completing the full course of therapy may decrease the effectiveness of the current treatment course and increase the likelihood that bacteria will develop resistance and will not be treatable by other antibacterial drugs in the future. Patients should be advised to swallow Minocycline hydrochloride extended-release tablets whole and not to chew, crush, or split the tablets. Manufactured by: Alkem Laboratories Limited, Mumbai - 400 013, INDIA Distributed by: Ascend Laboratories, LLC Parsippany, NJ 07054 Patient Information Minocycline hydrochloride extended-release tablets Rx only Read this Patient information Leaflet that comes with Minocycline hydrochloride extended-release tablets before you start taking it and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your doctor about your condition or treatment. What is Minocycline hydrochloride extended-release tablets? Minocycline hydrochloride extended-release tablets is a tetracycline-class drug. Minocycline hydrochloride extended-release tablets is prescription medicine used to treat pimples and red bumps (non-nodular inflammatory lesions) that happen with moderate to severe acne vulgaris in people 12 years and older. Minocycline hydrochloride extended-release tablets is not effective for acne that is not red-looking (this means acne that is not inflammatory). It is not known if Minocycline hydrochloride extended-release tablets is: safe for use longer than 12 weeks. safe and effective for the treatment of infections. safe and effective in children under the age of 12 years. Who should not take Minocycline hydrochloride extended-release tablets? Do not take Minocycline hydrochloride extended-release tablets if you are allergic to tetracycline-class drugs. Ask your doctor or pharmacist for a list of these medicines if you are not sure. What should I tell my doctor before taking Minocycline hydrochloride extended-release tablets? Before you take Minocycline hydrochloride extended-release tablets tell your doctor if you: have kidney problems. Your doctor may prescribe a lower dose of medicine for you. have liver problems. have diarrhea or watery stools. have vision problems. plan to have surgery with general anesthesia. have any other medical conditions. are a male, and you and your female partner are trying to conceive a baby. You should not take Minocycline hydrochloride extended-release tablets. are pregnant or plan to become pregnant. Minocycline hydrochloride extended- release tablets may harm your unborn baby. Taking Minocycline hydrochloride extended-release tablets while you are pregnant may cause serious side effects on the growth of bone and teeth of your baby. Talk to your doctor before taking Minocycline hydrochloride extended- release tablets if you plan to become pregnant, or if you are already taking Minocycline hydrochloride extended-release tablets and plan to become pregnant. Stop taking Minocycline hydrochloride extended-release tablets and call your doctor right away if you become pregnant while taking Minocycline hydrochloride extended-release tablets. are breastfeeding or plan to breastfeed. Minocycline hydrochloride passes into your milk and may harm your baby. You and your doctor should decide if you will take Minocycline hydrochloride extended-release tablets or breastfeed. You should not do both. Tell your doctor about all the other medicines you take including prescription and nonprescription medicines, vitamins and herbal supplements . Minocycline hydrochloride extended-release tablets may affect the way other medicines work, and other medicines may affect how Minocycline hydrochloride extended-release tablets works. Especially tell your doctor if you take: birth control pills . Minocycline hydrochloride extended-release tablets may make your birth control pills less effective. You could become pregnant. You should use a second form of birth control while taking Minocycline hydrochloride extended-release tablets. a blood thinner medicine. a penicillin antibiotic medicine . Minocycline hydrochloride extended-release tablets and penicillins should not be used together. antacids that contain aluminum, calcium, or magnesium or iron-containing products . an acne medicine that contains isotretinoin (Amnesteem, Claravis, Sotret). Minocycline hydrochloride extended-release tablets and isotretinoin should not be used together. Ask your doctor or pharmacist if you are not sure if your medicine is one that is listed above. Know the medicines you take. Keep a list of them to show your doctor and pharmacist. How should I take Minocycline hydrochloride extended-release tablets? Take Minocycline hydrochloride extended-release tablets exactly as your doctor tells you. Skipping doses or not taking all doses of Minocycline hydrochloride extended-release tablets may: make the treatment not work as well. increase the chance that the bacteria will become resistant to Minocycline hydrochloride extended-release tablets. Minocycline hydrochloride extended-release tablets can be taken with or without food . Taking Minocycline hydrochloride extended-release tablets with food may lower your chances of getting irritation or ulcers in your esophagus. Your esophagus is the tube that connects your mouth to your stomach. Swallow Minocycline hydrochloride extended-release tablets whole. Do not chew, crush, or split the tablets. If you take too much Minocycline hydrochloride extended-release tablets, call your doctor or poison control center right away . Your doctor may do blood tests to check you for side effects during treatment with Minocycline hydrochloride extended-release tablets. What should I avoid while taking Minocycline hydrochloride extended-release tablets? Avoid sunlight, sunlamps, and tanning beds. Minocycline hydrochloride extended-release tablets can make your skin sensitive to the sun and the light from sunlamps and tanning beds. You could get severe sunburn. Protect your skin while out in sunlight. You should not drive or operate dangerous machinery until you know how Minocycline hydrochloride extended-release tablets affects you. Minocycline hydrochloride extended-release tablets may cause you to feel dizzy or lightheaded, or have a spinning feeling (vertigo). What are possible side effects of Minocycline hydrochloride extended-release tablets? Minocycline hydrochloride extended-release tablets may cause serious side effects, including: Harm to an unborn baby . See "What should I tell my doctor before taking Minocycline hydrochloride extended-release tablets?" Permanent teeth discoloration . Minocycline hydrochloride extended-release tablets may permanently turn a baby or child's teeth yellow-grey-brown during tooth development. Minocycline hydrochloride extended-release tablets should not be used during tooth development. Tooth development happens in the last half of pregnancy, and from birth to 8 years of age. See "What should I tell my doctor before taking Minocycline hydrochloride extended-release tablets?" Intestine infection (pseudomembranous colitis). Pseudomembranous colitis can happen with most antibiotics, including Minocycline hydrochloride extended-release tablets. Call your doctor right away if you get watery diarrhea, diarrhea that does not go away, or bloody stools. Serious liver problems . Stop taking Minocycline hydrochloride extended-release tablets and call your doctor right away if you get any of the following symptoms of liver problems: loss of appetite tiredness diarrhea yellowing of your skin or the whites of your eyes unexplained bleeding confusion sleepiness Central nervous system effects . See "What should I avoid while taking Minocycline hydrochloride extended-release tablets?" Central nervous system effects such as light headedness, dizziness, and a spinning feeling (vertigo) may go away during your treatment with Minocycline hydrochloride extended-release tablets or if treatment is stopped. Benign intracranial hypertension, also called pseudotumor cerebri . This is a condition where there is high pressure in the fluid around the brain. This swelling may lead to vision changes and permanent vision loss. Stop taking Minocycline hydrochloride extended-release tablets and tell your doctor right away if you have blurred vision, vision loss, or unusual headaches. Immune system reactions including a lupus-like syndrome, hepatitis, and inflammation of blood or lymph vessels (vasculitis ). Using Minocycline hydrochloride extended-release tablets for a long time to treat acne may cause immune system reactions. Tell your doctor right away if you get a fever, rash, joint pain, or body weakness. Your doctor may do tests to check your blood for immune system reactions. Serious rash and allergic reactions . Minocycline hydrochloride extended-release tablets may cause a serious rash and allergic reactions that may affect parts of your body such as your liver, lungs, kidneys and heart. Sometimes these can lead to death. Stop taking Minocycline hydrochloride extended-release tablets and get medical help right away if you have any of these symptoms: skin rash, hives, sores in your mouth, or your skin blisters and peels swelling of your face, eyes, lips, tongue, or throat trouble swallowing or breathing blood in your urine fever, yellowing of the skin or the whites of your eyes, dark colored urine pain on the right side of the stomach area (abdominal pain) chest pain or abnormal heartbeats swelling in your legs, ankles, and feet darkening of your nails, skin, eyes, scars, teeth, and gums The most common side effects of Minocycline hydrochloride extended-release tablets include: headache tiredness dizziness or spinning feeling itching Call your doctor if you have a side effect that bothers you or that does not go away. Your doctor may do tests to check you for side effects during treatment with Minocycline hydrochloride extended-release tablets. These are not all the side effects with Minocycline hydrochloride extended-release tablets. Ask your doctor or pharmacist for more information. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. How should I store minocycline hydrochloride extended-release tablets? Store minocycline hydrochloride extended-release tablets between 68°F to 77°F (20°C to 25°C). Keep Minocycline hydrochloride extended-release tablets in the container that it comes in and keep the container tightly closed. Keep Minocycline hydrochloride extended-release tablets dry. Keep Minocycline hydrochloride extended-release tablets and all medicines out of the reach of children. General information about Minocycline hydrochloride extended-release tablets Medicines are sometimes prescribed for purposes other than those listed in the Patient Information leaflet. Do not use Minocycline hydrochloride extended-release tablets for a condition for which it was not prescribed. Do not give Minocycline hydrochloride extended-release tablets to other people, even if they have the same symptoms you have. It may harm them. This Patient Information leaflet summarizes the most important information about Minocycline hydrochloride extended-release tablets. If you would like more information, talk to your doctor. You can ask your doctor or pharmacist for information about Minocycline hydrochloride extended-release tablets that is written for health professionals. For more information, call 1-877-ASC-RX01 (877-272-7901). What are the ingredients in Minocycline hydrochloride extended-release tablets? Active ingredient: minocycline HCl. Inactive ingredients: lactose monohydrate, hypromellose type 2910, hypromellose type 2208, colloidal silicon dioxide, magnesium stearate, titanium dioxide and triacetin. The 45 mg tablets also contain iron oxide black. The 65 mg tablets also contain FD&C blue #1/brilliant blue FCF aluminium lake, polyethylene glycol 3350, FD&C blue #2/indigo carmine aluminum lake and D&C yellow #10 aluminum lake. The 55 mg tablets also contain macrogol, FD&C RED #40. The 80 mg tablets also contain macrogol, FD&C blue #2, FD&C red #40, FD&C yellow #6. The 90 mg tablets also contain iron oxide yellow and polyethylene glycol 3350. The 105 mg tablets also D&C red #27, macrogol, FD&C blue #1. The 115 mg tablets also contain D&C yellow #10 aluminum lake, FD&C blue #1/brilliant blue FCF aluminium lake and FD&C blue #2/indigo carmine aluminum lake. The 135 mg tablets also contain polyethylene glycol 3350 and iron oxide red. This Patient Information has been approved by the U.S. Food and Drug Administration. Manufactured by: Alkem Laboratories Limited, Mumbai - 400 013, INDIA. Distributed by: Ascend Laboratories, LLC Parsippany, NJ 07054 Revised: September,2019 PT 3278-01

14 CLINICAL STUDIES The safety and efficacy of Minocycline hydrochloride extended-release tablets in the treatment of inflammatory lesions of non-nodular moderate to severe acne vulgaris was assessed in two 12-week, multi-center, randomized, double-blind, placebo-controlled, trials in subjects ≥ 12 years. The mean age of subjects was 20 years and subjects were from the following racial groups: White (73%), Hispanic (13%), Black (11%), Asian/Pacific Islander (2%), and Other (2%). In two efficacy and safety trials, a total of 924 subjects with non-nodular moderate to severe acne vulgaris received Minocycline hydrochloride extended-release tablets or placebo for a total of 12 weeks, according to the following dose assignments. Table 3: Clinical Studies Dosing Table Subject's Weight (lbs.) Subject's Weight (kg) Available Tablet Strength (mg) Actual mg/kg Dose 99 to 131 45 to 59 45 1 to 0.76 132 to 199 60 to 90 90 1.5 to 1 200 to 300 91 to 136 135 1.48 to 0.99 The two primary efficacy endpoints were: Mean percent change in inflammatory lesion counts from Baseline to 12 weeks. Percentage of subjects with an Evaluator's Global Severity Assessment (EGSA) of clear or almost clear at 12 weeks. Efficacy results are presented in Table 4. Table 4: Efficacy Results at Week 12 *Evaluator's Global Severity Assessment Trail 1 Trail 2 Minocycline hydrochloride extended-release tablets (1mg/Kg) N=300 Placebo N=151 Minocycline hydrochloride extended-release tablets (1mg/Kg) N=315 Placebo N=158 Mean Percent Improvement in Inflammatory Lesions 43.1% 31.7% 45.8% 30.8% No. (%) of Subjects Clear or Almost Clear on the EGSA* 52 (17.3%) 12 (7.9%) 50 (15.9%) 15 (9.5%) Minocycline hydrochloride extended-release tablets did not demonstrate any effect on non-inflammatory lesions (benefit or worsening).

8.5 Geriatric Use Clinical studies of Minocycline hydrochloride extended-release tablets did not include sufficient numbers of subjects aged 65 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. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant disease or other drug therapy.

8.3 Nursing Mothers Tetracycline-class antibiotics are excreted in human milk. Because of the potential for serious adverse effects on bone and tooth development in nursing infants from the tetracycline-class antibiotics, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother [see Warnings and Precautions (5.1) ] .

8.4 Pediatric Use Minocycline hydrochloride extended-release tablets is indicated to treat only inflammatory lesions of non-nodular moderate to severe acne vulgaris in patients 12 years and older. Safety and effectiveness in pediatric patients below the age of 12 has not been established. Use of tetracycline-class antibiotics below the age of 8 is not recommended due to the potential for tooth discoloration [see Warnings and Precautions (5.1) ].

8.1 Pregnancy Teratogenic Effects: Pregnancy category D [see Warnings and Precautions (5.1) ] Minocycline hydrochloride extended-release tablets should not be used during pregnancy. If the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus and stop treatment immediately. There are no adequate and well-controlled studies on the use of minocycline in pregnant women. Minocycline, like other tetracycline-class drugs, crosses the placenta and may cause fetal harm when administered to a pregnant woman. Rare spontaneous reports of congenital anomalies including limb reduction have been reported with minocycline use in pregnancy in post-marketing experience. Only limited information is available regarding these reports; therefore, no conclusion on causal association can be established. Minocycline induced skeletal malformations (bent limb bones) in fetuses when administered to pregnant rats and rabbits in doses of 30 mg/kg/day and 100 mg/kg/day, respectively, (resulting in approximately 3 times and 2 times, respectively, the systemic exposure to minocycline observed in patients as a result of use of Minocycline hydrochloride extended-release tablets). Reduced mean fetal body weight was observed in studies in which minocycline was administered to pregnant rats at a dose of 10 mg/kg/day (which resulted in approximately the same level of systemic exposure to minocycline as that observed in patients who use Minocycline hydrochloride extended-release tablets). Minocycline was assessed for effects on peri- and post-natal development of rats in a study that involved oral administration to pregnant rats from day 6 of gestation through the period of lactation (postpartum day 20), at dosages 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 (resulting in approximately 2.5 times the systemic exposure to minocycline observed in patients as a result of use of Minocycline hydrochloride extended-release tablets). 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 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 POPULATION • Minocycline like other tetracycline-class drugs can cause fetal harm when administered to a pregnant woman. ( 5.1 , 8.1 ) •The use of drugs of the tetracycline class during tooth development may cause permanent discoloration of teeth. ( 5.1 , 8.4 ) 8.1 Pregnancy Teratogenic Effects: Pregnancy category D [see Warnings and Precautions (5.1) ] Minocycline hydrochloride extended-release tablets should not be used during pregnancy. If the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus and stop treatment immediately. There are no adequate and well-controlled studies on the use of minocycline in pregnant women. Minocycline, like other tetracycline-class drugs, crosses the placenta and may cause fetal harm when administered to a pregnant woman. Rare spontaneous reports of congenital anomalies including limb reduction have been reported with minocycline use in pregnancy in post-marketing experience. Only limited information is available regarding these reports; therefore, no conclusion on causal association can be established. Minocycline induced skeletal malformations (bent limb bones) in fetuses when administered to pregnant rats and rabbits in doses of 30 mg/kg/day and 100 mg/kg/day, respectively, (resulting in approximately 3 times and 2 times, respectively, the systemic exposure to minocycline observed in patients as a result of use of Minocycline hydrochloride extended-release tablets). Reduced mean fetal body weight was observed in studies in which minocycline was administered to pregnant rats at a dose of 10 mg/kg/day (which resulted in approximately the same level of systemic exposure to minocycline as that observed in patients who use Minocycline hydrochloride extended-release tablets). Minocycline was assessed for effects on peri- and post-natal development of rats in a study that involved oral administration to pregnant rats from day 6 of gestation through the period of lactation (postpartum day 20), at dosages 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 (resulting in approximately 2.5 times the systemic exposure to minocycline observed in patients as a result of use of Minocycline hydrochloride extended-release tablets). 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 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). 8.3 Nursing Mothers Tetracycline-class antibiotics are excreted in human milk. Because of the potential for serious adverse effects on bone and tooth development in nursing infants from the tetracycline-class antibiotics, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother [see Warnings and Precautions (5.1) ] . 8.4 Pediatric Use Minocycline hydrochloride extended-release tablets is indicated to treat only inflammatory lesions of non-nodular moderate to severe acne vulgaris in patients 12 years and older. Safety and effectiveness in pediatric patients below the age of 12 has not been established. Use of tetracycline-class antibiotics below the age of 8 is not recommended due to the potential for tooth discoloration [see Warnings and Precautions (5.1) ]. 8.5 Geriatric Use Clinical studies of Minocycline hydrochloride extended-release tablets did not include sufficient numbers of subjects aged 65 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. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant disease or other drug therapy.

16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied Minocycline hydrochloride extended-release tablets, USP are supplied as aqueous film coated tablets containing Minocycline hydrochloride equivalent to 90 mg minocycline, are supplied as follows. The 90 mg extended release tablets are yellow coloured capsule shaped film coated tablets, debossed with 90 on one side, plain on other side. Each tablet contains Minocycline hydrochloride equivalent to 90 mg minocycline, supplied as follows: NDC 63629-9215-1 Bottle of 30 16.2 Storage Store at 20˚ to 25˚C (68˚ to 77˚ F) [See USP Controlled Room Temperature]. 16.3 Handling Keep out of reach of children. Protect from light, moisture, and excessive heat. Dispense in tight, light-resistant container with child-resistant closure.