MINOCYCLINE HYDROCHLORIDE - minocycline hydrochloride tablet, film coated, extended release 
Ascend Laboratories, LLC

----------

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use MINOCYCLINE HYDROCHLORIDE EXTENDED RELEASE TABLETS safely and effectively. See full prescribing information for MINOCYCLINE HYDROCHLORIDE EXTENDED RELEASE TABLETS.
MINOCYCLINE HYDROCHLORIDE extended-release tablets, for oral use
Initial U.S. Approval: 1971

INDICATIONS AND 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)

DOSAGE AND ADMINISTRATION


The recommended dosage of Minocycline hydrochloride extended-release tablets is approximately 1 mg/kg once daily for 12 weeks. (2)

DOSAGE FORMS AND STRENGTHS

Extended release tablets: 45 mg, 55 mg, 65 mg, 80 mg, 90 mg, 105 mg, 115 mg, and 135 mg (3) (3)

CONTRAINDICATIONS


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

WARNINGS AND PRECAUTIONS

  • The use of Minocycline hydrochloride extended-release tablets during tooth development (last half of pregnancy, infancy, and childhood up to the age of 8 years) may cause permanent discoloration of the teeth (yellow-gray-brown). (5.1)
  • If pseudomembranous colitis occurs, discontinue Minocycline hydrochloride extended-release tablets.(5.2)
  • If liver injury is suspected, discontinue Minocycline hydrochloride extended-release tablets. (5.3)
  • If renal impairment exists, Minocycline hydrochloride extended-release tablets doses may need to be adjusted to avoid excessive systemic accumulations of the drug and possible liver toxicity. (5.4)
  • Minocycline may cause central nervous system side effects including light- headedness, dizziness, or vertigo. Advise patients. (5.5)
  • Minocycline may cause pseudotumor cerebri (benign intracranial hypertension) in adults and adolescents. Discontinue Minocycline hydrochloride extended-release tablets if symptoms occur. (5.6)
  • Minocycline has been associated with autoimmune syndromes; discontinue Minocycline hydrochloride extended-release tablets immediately if symptoms occur. (5.7)
  • Minocycline has been associated with anaphylaxis, serious skin reactions, erythema multiforme, and DRESS syndrome. Discontinue Minocycline hydrochloride extended-release tablets immediately if symptoms occur. (5.9)

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
  
   

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)

USE IN SPECIFIC POPULATIONS


• 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)

See 17 for PATIENT COUNSELING INFORMATION.

Revised: 9/2019

FULL PRESCRIBING INFORMATION: CONTENTS*

1 INDICATIONS & USAGE

1.1 Indication

1.2 Limitations of Use

2 DOSAGE & ADMINISTRATION

3 DOSAGE FORMS & STRENGTHS

4 CONTRAINDICATIONS

5 WARNINGS AND PRECAUTIONS

5.1 Teratogenic Effects

5.2 Pseudomembranous Colitis

5.3 Hepatotoxicity

5.4 Metabolic Effects

5.5 Central Nervous System Effects

5.6 Benign Intracranial Hypertension

5.7 Autoimmune Syndromes

5.8 Photosensitivity

5.9 Serious Skin/Hypersensitivity Reaction

5.10 Tissue Hyperpigmentation

5.11 Development of Drug-Resistant Bacteria

5.12 Superinfection

5.13 Laboratory Monitoring

6 ADVERSE REACTIONS

6.1 Clinical Trial Experience

6.2 Postmarketing Experience

7 DRUG INTERACTIONS

7.1 Anticoagulants

7.2 Penicillin

7.3 Methoxyflurane

7.4 Antacids and Iron Preparations

7.5 Low Dose Oral Contraceptives

7.6 Drug/Laboratory Test Interactions

8 USE IN SPECIFIC POPULATION

8.1 Pregnancy

8.3 Nursing Mothers

8.4 Pediatric Use

8.5 Geriatric Use

10 OVERDOSAGE

11 DESCRIPTION

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

12.2 Pharmacodynamics

12.3 Pharmacokinetics

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis & Mutagenesis & Impairment Of Fertility

14 CLINICAL STUDIES

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

16.2 Storage

16.3 Handling

17 PATIENT COUNSELING INFORMATION

*
Sections or subsections omitted from the full prescribing information are not listed.

FULL PRESCRIBING INFORMATION

1 INDICATIONS & USAGE

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)].

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)].

3 DOSAGE FORMS & STRENGTHS

4 CONTRAINDICATIONS


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

5 WARNINGS AND PRECAUTIONS

5.1 Teratogenic Effects


A. MINOCYCLINE, LIKE OTHER TETRACYCLINE-CLASS DRUGS, CAN CAUSE FETAL HARM WHEN ADMINISTERED TO A PREGNANT WOMAN. IF ANY TETRACYCLINE IS USED DURING PREGNANCY OR IF THE PATIENT BECOMES PREGNANT WHILE TAKING THESE DRUGS, THE PATIENT SHOULD BE APPRISED OF THE POTENTIAL HAZARD TO THE FETUS.
Minocycline hydrochloride extended-release tablets should not be used during pregnancy or by individuals of either gender who are attempting to conceive a child [see Nonclinical Toxicology (13.1) & Use in Specific Populations (8.1)].

B. THE USE OF DRUGS OF THE TETRACYCLINE CLASS DURING TOOTH DEVELOPMENT (LAST HALF 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 use of the drug but has been observed following repeated short-term courses. Enamel hypoplasia has also been reported. TETRACYCLINE DRUGS, THEREFORE, SHOULD NOT BE USED DURING TOOTH DEVELOPMENT.

C. 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.
Results of animal studies indicate that 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 early in pregnancy [see Use in Specific Populations (8.1)].

5.2 Pseudomembranous 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. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.


C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.


If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

5.3 Hepatotoxicity


Post-marketing cases of serious liver injury, including irreversible drug-induced hepatitis and fulminant hepatic failure (sometimes fatal) have been reported with minocycline use in the treatment of acne.

5.4 Metabolic Effects


The anti-anabolic action of the tetracyclines may cause an increase in BUN. While this is not a problem in those with normal renal function, in patients with significantly impaired function, higher serum levels of tetracycline-class drugs may lead to azotemia, hyperphosphatemia, and acidosis. If renal impairment exists, even usual oral or parenteral doses may lead to excessive systemic accumulations of the drug and possible liver toxicity. Under such conditions, lower than usual total doses are indicated, and if therapy is prolonged, serum level determinations of the drug may be advisable.

5.5 Central Nervous System Effects


Central nervous system side effects including light-headedness, dizziness or vertigo have been reported with minocycline therapy. Patients who experience these symptoms should be cautioned about driving vehicles or using hazardous machinery while on minocycline therapy. These symptoms may disappear during therapy and usually rapidly disappear when the drug is discontinued.

5.6 Benign Intracranial Hypertension


Pseudotumor cerebri (benign intracranial hypertension) in adults and adolescents has been associated with the use of tetracyclines. Minocycline has been reported to cause or precipitate pseudotumor cerebri, the hallmark of which is papilledema. Clinical manifestations include headache and blurred vision. Bulging fontanels have been associated with the use of tetracyclines in infants. Although signs and symptoms of pseudotumor cerebri resolve after discontinuation of treatment, the possibility for permanent sequelae such as visual loss that may be permanent or severe exists. Patients should be questioned for visual disturbances prior to initiation of treatment with tetracyclines. If visual disturbance occurs during treatment, patients should be checked for papilledema. Concomitant use of isotretinoin and minocycline should be avoided because isotretinoin, a systemic retinoid, is also known to cause pseudotumor cerebri.

5.7 Autoimmune Syndromes


Tetracyclines have been associated with the development of autoimmune syndromes. The long-term use of minocycline in the treatment of acne has been associated with drug-induced lupus-like syndrome, autoimmune hepatitis and vasculitis. Sporadic cases of serum sickness have presented shortly after minocycline use. Symptoms may be manifested by fever, rash, arthralgia, and malaise. In symptomatic patients, liver function tests, ANA, CBC, and other appropriate tests should be performed to evaluate the patients. Use of all tetracycline-class drugs should be discontinued immediately.

5.8 Photosensitivity


Photosensitivity manifested by an exaggerated sunburn reaction has been observed in some individuals taking tetracyclines. This has been reported rarely with 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.

5.9 Serious Skin/Hypersensitivity Reaction


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, the drug should be discontinued immediately.

5.10 Tissue Hyperpigmentation


Tetracycline-class antibiotics are known to cause hyperpigmentation. Tetracycline therapy may induce hyperpigmentation in many organs, including nails, bone, skin, eyes, thyroid, visceral tissue, oral cavity (teeth, mucosa, alveolar bone), sclerae and heart valves. Skin and oral pigmentation has been reported to occur independently of time or amount of drug administration, whereas other tissue pigmentation has been reported to occur upon prolonged administration. Skin pigmentation includes diffuse pigmentation as well as over sites of scars or injury.

5.11 Development of Drug-Resistant Bacteria


Bacterial resistance to the tetracyclines may develop in patients using Minocycline hydrochloride extended-release tablets, therefore, the susceptibility of bacteria associated with infection should be considered in selecting antimicrobial therapy. Because of the potential for drug-resistant bacteria to develop during the use of Minocycline hydrochloride extended-release tablets, it should be used only as indicated.

5.12 Superinfection


As with other antibiotic preparations, use of Minocycline hydrochloride extended-release tablets may result in overgrowth of nonsusceptible organisms, including fungi. If superinfection occurs, Minocycline hydrochloride extended-release tablets should be discontinued and appropriate therapy instituted.

5.13 Laboratory Monitoring


Periodic laboratory evaluations of organ systems, including hematopoietic, renal and hepatic studies should be performed. Appropriate tests for autoimmune syndromes should be performed as indicated.

6 ADVERSE REACTIONS

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)].

7 DRUG INTERACTIONS

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.

8 USE IN SPECIFIC POPULATION

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.

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.

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:


mino-struc

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

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 Tmax at 3.5 to 4.0 hours as compared to a non-modified release reference minocycline product (Tmax at 2.25 to 3 hours). At steady-state (Day 6), the mean AUC(0-24) and Cmax 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.

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.

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:

  1. Mean percent change in inflammatory lesion counts from Baseline to 12 weeks.
  2. 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).

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 45 mg, 55 mg, 65 mg, 80 mg, 90 mg, 105 mg, 115 mg or 135 mg minocycline, are supplied as follows.

The 45 mg extended release tablets are grey coloured capsule shaped film coated tablets, debossed with “45” on one side, plain on other side. Each tablet contains Minocycline hydrochloride equivalent to 45 mg minocycline, supplied as follows:


NDC 67877-578-14
Carton of 140 (10 x 14 unit-dose)
NDC 67877-578-30
Bottle of 30
NDC 67877-578-01
Bottle of 100
NDC 67877-578-05
Bottle of 500

The 55 mg extended release tablets are Pink colored capsule shaped film coated tablets, debossed with "55" on one side, plain on other side. Each tablet contains Minocycline hydrochloride equivalent to 55 mg minocycline, supplied as follows:

NDC 67877-436-14
Carton of 140 (10 x 14 unit-dose)
NDC 67877-436-30
Bottle of 30
NDC 67877-436-01
Bottle of 100
NDC 67877-436-05
                       Bottle of 500

The 65 mg extended release tablets are blue coloured capsule shaped film coated tablets, debossed with “65” on one side, plain on other side. Each tablet contains Minocycline hydrochloride equivalent to 65 mg minocycline, supplied as follows:

NDC 67877-643-14
Carton of 140 (10 x 14 unit-dose)
NDC 67877-643-30
Bottle of 30
NDC 67877-643-01
Bottle of 100
NDC 67877-643-05
Bottle of 500

The 80 mg extended release tablets are Greyish brown colored capsule shaped film coated tablets, debossed with "80'' on one side, plain on other side. Each tablet contains Minocycline hydrochloride equivalent to 80 mg minocycline, supplied as follows:

NDC 67877-437-14
Carton of 140 (10 x 14 unit-dose)
NDC 67877-437-30
Bottle of 30
NDC 67877-437-01
Bottle of 100
NDC 67877-437-05
Bottle of 500

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 67877-576-14
Carton of 140 (10 x 14 unit-dose)
NDC 67877-576-30
Bottle of 30
NDC 67877-576-01
Bottle of 100
NDC 67877-576-05
Bottle of 500

The 105 mg extended release tablets are Purple colored capsule shaped film coated tablets, debossed with "105'' on one side, plain on other side.Each tablet contains Minocycline hydrochloride equivalent to 105 mg minocycline, supplied as follows:


NDC 67877-438-14
Carton of 140 (10 x 14 unit-dose)
NDC 67877-438-30
Bottle of 30
NDC 67877-438-01
Bottle of 100
NDC 67877-438-05
Bottle of 500

The 115 mg extended release tablets are green coloured capsule shaped film coated tablets, debossed with “115” on one side, plain on other side. Each tablet contains Minocycline hydrochloride equivalent to 115 mg minocycline, supplied as follows:

NDC 67877-644-14
Carton of 140 (10 x 14 unit-dose)
NDC 67877-644-30
Bottle of 30
NDC 67877-644-01
Bottle of 100
NDC 67877-644-05
Bottle of 500

The 135 mg extended release tablets are pink (orange brown) coloured capsule shaped film coated tablets, debossed with “135” on one side, plain on other side.  Each tablet contains Minocycline hydrochloride equivalent to 135 mg minocycline, supplied as follows:

NDC 67877-577-14
Carton of 140 (10 x 14 unit-dose)
NDC 67877-577-30
Bottle of 30
NDC 67877-577-01
Bottle of 100
NDC 67877-577 -05
Bottle of 500

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.

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:


 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:


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:


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:


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?


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?


What are possible side effects of Minocycline hydrochloride extended-release tablets?
Minocycline hydrochloride extended-release tablets may cause serious side effects, including:


The most common side effects of Minocycline hydrochloride extended-release tablets include:


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?


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

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

Ascend Laboratories, LLC

NDC 67877-578-30

Minocycline Hydrochloride Extended-Release Tablets, USP 

45 mg

30 Tablets

Rx Only

Ascend Laboratories, LLC


mino-45-30-count

NDC 67877-436-30

Minocycline Hydrochloride Extended-Release Tablets, USP

55 mg

30 Tablets

Rx Only

mino-55mg-30s

Ascend Laboratories, LLC
NDC 67877-643-30

Minocycline Hydrochloride Extended-Release Tablets, USP 

65 mg

30 Tablets

Rx Only
mino-65-30-countjpg
Ascend Laboratories, LLC

NDC 67877-437-30

Minocycline Hydrochloride Extended-Release Tablets, USP

80 mg

30 Tablets

Rx Only
mino-80mg-30s

Ascend Laboratories, LLC

NDC 67877-576-30

Minocycline Hydrochloride Extended-Release Tablets, USP 

90 mg

30 Tablets

Rx Only
mino-90-30-count

Ascend Laboratories, LLC


NDC 67877-438-30

Minocycline Hydrochloride Extended-Release Tablets, USP

105 mg

30 Tablets

Rx Only
mino-105mg-30s

Ascend Laboratories, LLC

NDC 67877-644-30

Minocycline Hydrochloride Extended-Release Tablets, USP 

115 mg

30 Tablets

Rx Only
mino-115-30-countjpg
Ascend Laboratories, LLC

NDC 67877-577-30

Minocycline Hydrochloride Extended-Release Tablets, USP 

135 mg

30 Tablets

Rx Only
mino-135-30-count

MINOCYCLINE HYDROCHLORIDE 
minocycline hydrochloride tablet, film coated, extended release
Product Information
Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC:67877-578
Route of AdministrationORAL
Active Ingredient/Active Moiety
Ingredient NameBasis of StrengthStrength
MINOCYCLINE HYDROCHLORIDE (UNII: 0020414E5U) (MINOCYCLINE - UNII:FYY3R43WGO) MINOCYCLINE45 mg
Inactive Ingredients
Ingredient NameStrength
LACTOSE MONOHYDRATE (UNII: EWQ57Q8I5X)  
HYPROMELLOSE 2208 (4000 MPA.S) (UNII: 39J80LT57T)  
HYPROMELLOSE 2910 (50 MPA.S) (UNII: 1IVH67816N)  
SILICON DIOXIDE (UNII: ETJ7Z6XBU4)  
MAGNESIUM STEARATE (UNII: 70097M6I30)  
TITANIUM DIOXIDE (UNII: 15FIX9V2JP)  
TRIACETIN (UNII: XHX3C3X673)  
FERROSOFERRIC OXIDE (UNII: XM0M87F357)  
Product Characteristics
ColorGRAYScoreno score
ShapeCAPSULESize10mm
FlavorImprint Code 45
Contains    
Packaging
#Item CodePackage DescriptionMarketing Start DateMarketing End Date
1NDC:67877-578-1410 in 1 CARTON09/30/2016
114 in 1 BLISTER PACK; Type 0: Not a Combination Product
2NDC:67877-578-3030 in 1 BOTTLE; Type 0: Not a Combination Product09/30/2016
3NDC:67877-578-01100 in 1 BOTTLE; Type 0: Not a Combination Product09/30/2016
4NDC:67877-578-05500 in 1 BOTTLE; Type 0: Not a Combination Product09/30/2016
Marketing Information
Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
ANDAANDA20445309/30/2016
MINOCYCLINE HYDROCHLORIDE 
minocycline hydrochloride tablet, film coated, extended release
Product Information
Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC:67877-576
Route of AdministrationORAL
Active Ingredient/Active Moiety
Ingredient NameBasis of StrengthStrength
MINOCYCLINE HYDROCHLORIDE (UNII: 0020414E5U) (MINOCYCLINE - UNII:FYY3R43WGO) MINOCYCLINE90 mg
Inactive Ingredients
Ingredient NameStrength
LACTOSE MONOHYDRATE (UNII: EWQ57Q8I5X)  
HYPROMELLOSE 2208 (4000 MPA.S) (UNII: 39J80LT57T)  
HYPROMELLOSE 2910 (50 MPA.S) (UNII: 1IVH67816N)  
SILICON DIOXIDE (UNII: ETJ7Z6XBU4)  
MAGNESIUM STEARATE (UNII: 70097M6I30)  
TITANIUM DIOXIDE (UNII: 15FIX9V2JP)  
TRIACETIN (UNII: XHX3C3X673)  
POLYETHYLENE GLYCOL 3350 (UNII: G2M7P15E5P)  
FERRIC OXIDE YELLOW (UNII: EX438O2MRT)  
Product Characteristics
ColorYELLOWScoreno score
ShapeCAPSULESize13mm
FlavorImprint Code 90
Contains    
Packaging
#Item CodePackage DescriptionMarketing Start DateMarketing End Date
1NDC:67877-576-1410 in 1 CARTON09/30/2016
114 in 1 BLISTER PACK; Type 0: Not a Combination Product
2NDC:67877-576-3030 in 1 BOTTLE; Type 0: Not a Combination Product09/30/2016
3NDC:67877-576-01100 in 1 BOTTLE; Type 0: Not a Combination Product09/30/2016
4NDC:67877-576-05500 in 1 BOTTLE; Type 0: Not a Combination Product09/30/2016
Marketing Information
Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
ANDAANDA20445309/30/2016
MINOCYCLINE HYDROCHLORIDE 
minocycline hydrochloride tablet, film coated, extended release
Product Information
Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC:67877-577
Route of AdministrationORAL
Active Ingredient/Active Moiety
Ingredient NameBasis of StrengthStrength
MINOCYCLINE HYDROCHLORIDE (UNII: 0020414E5U) (MINOCYCLINE - UNII:FYY3R43WGO) MINOCYCLINE135 mg
Inactive Ingredients
Ingredient NameStrength
LACTOSE MONOHYDRATE (UNII: EWQ57Q8I5X)  
HYPROMELLOSE 2208 (4000 MPA.S) (UNII: 39J80LT57T)  
HYPROMELLOSE 2910 (50 MPA.S) (UNII: 1IVH67816N)  
SILICON DIOXIDE (UNII: ETJ7Z6XBU4)  
MAGNESIUM STEARATE (UNII: 70097M6I30)  
TITANIUM DIOXIDE (UNII: 15FIX9V2JP)  
TRIACETIN (UNII: XHX3C3X673)  
POLYETHYLENE GLYCOL 3350 (UNII: G2M7P15E5P)  
FERRIC OXIDE RED (UNII: 1K09F3G675)  
Product Characteristics
ColorPINK (Orange Brown) Scoreno score
ShapeCAPSULESize16mm
FlavorImprint Code 135
Contains    
Packaging
#Item CodePackage DescriptionMarketing Start DateMarketing End Date
1NDC:67877-577-1410 in 1 CARTON09/30/2016
114 in 1 BLISTER PACK; Type 0: Not a Combination Product
2NDC:67877-577-3030 in 1 BOTTLE; Type 0: Not a Combination Product09/30/2016
3NDC:67877-577-01100 in 1 BOTTLE; Type 0: Not a Combination Product09/30/2016
4NDC:67877-577-05500 in 1 BOTTLE; Type 0: Not a Combination Product09/30/2016
Marketing Information
Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
ANDAANDA20445309/30/2016
MINOCYCLINE HYDROCHLORIDE 
minocycline hydrochloride tablet, film coated, extended release
Product Information
Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC:67877-643
Route of AdministrationORAL
Active Ingredient/Active Moiety
Ingredient NameBasis of StrengthStrength
MINOCYCLINE HYDROCHLORIDE (UNII: 0020414E5U) (MINOCYCLINE - UNII:FYY3R43WGO) MINOCYCLINE65 mg
Inactive Ingredients
Ingredient NameStrength
LACTOSE MONOHYDRATE (UNII: EWQ57Q8I5X)  
HYPROMELLOSE 2208 (4000 MPA.S) (UNII: 39J80LT57T)  
HYPROMELLOSE 2910 (50 MPA.S) (UNII: 1IVH67816N)  
SILICON DIOXIDE (UNII: ETJ7Z6XBU4)  
MAGNESIUM STEARATE (UNII: 70097M6I30)  
TITANIUM DIOXIDE (UNII: 15FIX9V2JP)  
TRIACETIN (UNII: XHX3C3X673)  
FD&C BLUE NO. 1 (UNII: H3R47K3TBD)  
POLYETHYLENE GLYCOL 3350 (UNII: G2M7P15E5P)  
FD&C BLUE NO. 2 (UNII: L06K8R7DQK)  
D&C YELLOW NO. 10 (UNII: 35SW5USQ3G)  
Product Characteristics
ColorBLUEScoreno score
ShapeCAPSULESize11mm
FlavorImprint Code 65
Contains    
Packaging
#Item CodePackage DescriptionMarketing Start DateMarketing End Date
1NDC:67877-643-1410 in 1 CARTON09/30/2016
114 in 1 BLISTER PACK; Type 0: Not a Combination Product
2NDC:67877-643-3030 in 1 BOTTLE; Type 0: Not a Combination Product09/30/2016
3NDC:67877-643-01100 in 1 BOTTLE; Type 0: Not a Combination Product09/30/2016
4NDC:67877-643-05500 in 1 BOTTLE; Type 0: Not a Combination Product09/30/2016
Marketing Information
Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
ANDAANDA20445309/30/2016
MINOCYCLINE HYDROCHLORIDE 
minocycline hydrochloride tablet, film coated, extended release
Product Information
Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC:67877-644
Route of AdministrationORAL
Active Ingredient/Active Moiety
Ingredient NameBasis of StrengthStrength
MINOCYCLINE HYDROCHLORIDE (UNII: 0020414E5U) (MINOCYCLINE - UNII:FYY3R43WGO) MINOCYCLINE115 mg
Inactive Ingredients
Ingredient NameStrength
LACTOSE MONOHYDRATE (UNII: EWQ57Q8I5X)  
HYPROMELLOSE 2208 (4000 MPA.S) (UNII: 39J80LT57T)  
HYPROMELLOSE 2910 (50 MPA.S) (UNII: 1IVH67816N)  
SILICON DIOXIDE (UNII: ETJ7Z6XBU4)  
MAGNESIUM STEARATE (UNII: 70097M6I30)  
TITANIUM DIOXIDE (UNII: 15FIX9V2JP)  
TRIACETIN (UNII: XHX3C3X673)  
FD&C BLUE NO. 1 (UNII: H3R47K3TBD)  
FD&C BLUE NO. 2 (UNII: L06K8R7DQK)  
D&C YELLOW NO. 10 (UNII: 35SW5USQ3G)  
Product Characteristics
ColorGREENScoreno score
ShapeCAPSULESize15mm
FlavorImprint Code 115
Contains    
Packaging
#Item CodePackage DescriptionMarketing Start DateMarketing End Date
1NDC:67877-644-1410 in 1 CARTON09/30/2016
114 in 1 BLISTER PACK; Type 0: Not a Combination Product
2NDC:67877-644-3030 in 1 BOTTLE; Type 0: Not a Combination Product09/30/2016
3NDC:67877-644-01100 in 1 BOTTLE; Type 0: Not a Combination Product09/30/2016
4NDC:67877-644-05500 in 1 BOTTLE; Type 0: Not a Combination Product09/30/2016
Marketing Information
Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
ANDAANDA20445309/30/2016
MINOCYCLINE HYDROCHLORIDE 
minocycline hydrochloride tablet, film coated, extended release
Product Information
Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC:67877-436
Route of AdministrationORAL
Active Ingredient/Active Moiety
Ingredient NameBasis of StrengthStrength
MINOCYCLINE HYDROCHLORIDE (UNII: 0020414E5U) (MINOCYCLINE - UNII:FYY3R43WGO) MINOCYCLINE55 mg
Inactive Ingredients
Ingredient NameStrength
LACTOSE MONOHYDRATE (UNII: EWQ57Q8I5X)  
HYPROMELLOSE 2208 (4000 MPA.S) (UNII: 39J80LT57T)  
HYPROMELLOSE 2910 (50 MPA.S) (UNII: 1IVH67816N)  
SILICON DIOXIDE (UNII: ETJ7Z6XBU4)  
MAGNESIUM STEARATE (UNII: 70097M6I30)  
TITANIUM DIOXIDE (UNII: 15FIX9V2JP)  
TRIACETIN (UNII: XHX3C3X673)  
POLYETHYLENE GLYCOL 3350 (UNII: G2M7P15E5P)  
FD&C RED NO. 40 (UNII: WZB9127XOA)  
ALUMINUM OXIDE (UNII: LMI26O6933)  
Product Characteristics
ColorPINKScoreno score
ShapeCAPSULESize10mm
FlavorImprint Code 55
Contains    
Packaging
#Item CodePackage DescriptionMarketing Start DateMarketing End Date
1NDC:67877-436-1410 in 1 CARTON12/23/2019
114 in 1 BLISTER PACK; Type 0: Not a Combination Product
2NDC:67877-436-3030 in 1 BOTTLE; Type 0: Not a Combination Product12/23/2019
3NDC:67877-436-01100 in 1 BOTTLE; Type 0: Not a Combination Product12/23/2019
4NDC:67877-436-05500 in 1 BOTTLE; Type 0: Not a Combination Product12/23/2019
Marketing Information
Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
ANDAANDA20445312/23/2019
MINOCYCLINE HYDROCHLORIDE 
minocycline hydrochloride tablet, film coated, extended release
Product Information
Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC:67877-437
Route of AdministrationORAL
Active Ingredient/Active Moiety
Ingredient NameBasis of StrengthStrength
MINOCYCLINE HYDROCHLORIDE (UNII: 0020414E5U) (MINOCYCLINE - UNII:FYY3R43WGO) MINOCYCLINE80 mg
Inactive Ingredients
Ingredient NameStrength
LACTOSE MONOHYDRATE (UNII: EWQ57Q8I5X)  
HYPROMELLOSE 2208 (4000 MPA.S) (UNII: 39J80LT57T)  
HYPROMELLOSE 2910 (50 MPA.S) (UNII: 1IVH67816N)  
SILICON DIOXIDE (UNII: ETJ7Z6XBU4)  
MAGNESIUM STEARATE (UNII: 70097M6I30)  
TITANIUM DIOXIDE (UNII: 15FIX9V2JP)  
TRIACETIN (UNII: XHX3C3X673)  
POLYETHYLENE GLYCOL 3350 (UNII: G2M7P15E5P)  
FD&C RED NO. 40 (UNII: WZB9127XOA)  
ALUMINUM OXIDE (UNII: LMI26O6933)  
FD&C BLUE NO. 2 (UNII: L06K8R7DQK)  
FD&C YELLOW NO. 6 (UNII: H77VEI93A8)  
Product Characteristics
ColorGRAY (Greyish Brown) Scoreno score
ShapeCAPSULESize13mm
FlavorImprint Code 80
Contains    
Packaging
#Item CodePackage DescriptionMarketing Start DateMarketing End Date
1NDC:67877-437-1410 in 1 CARTON09/30/2016
114 in 1 BLISTER PACK; Type 0: Not a Combination Product
2NDC:67877-437-3030 in 1 BOTTLE; Type 0: Not a Combination Product09/30/2016
3NDC:67877-437-01100 in 1 BOTTLE; Type 0: Not a Combination Product09/30/2016
4NDC:67877-437-05500 in 1 BOTTLE; Type 0: Not a Combination Product09/30/2016
Marketing Information
Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
ANDAANDA20445309/30/2016
MINOCYCLINE HYDROCHLORIDE 
minocycline hydrochloride tablet, film coated, extended release
Product Information
Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC:67877-438
Route of AdministrationORAL
Active Ingredient/Active Moiety
Ingredient NameBasis of StrengthStrength
MINOCYCLINE HYDROCHLORIDE (UNII: 0020414E5U) (MINOCYCLINE - UNII:FYY3R43WGO) MINOCYCLINE105 mg
Inactive Ingredients
Ingredient NameStrength
LACTOSE MONOHYDRATE (UNII: EWQ57Q8I5X)  
HYPROMELLOSE 2208 (4000 MPA.S) (UNII: 39J80LT57T)  
HYPROMELLOSE 2910 (50 MPA.S) (UNII: 1IVH67816N)  
SILICON DIOXIDE (UNII: ETJ7Z6XBU4)  
MAGNESIUM STEARATE (UNII: 70097M6I30)  
TITANIUM DIOXIDE (UNII: 15FIX9V2JP)  
TRIACETIN (UNII: XHX3C3X673)  
POLYETHYLENE GLYCOL 3350 (UNII: G2M7P15E5P)  
ALUMINUM OXIDE (UNII: LMI26O6933)  
D&C RED NO. 27 (UNII: 2LRS185U6K)  
FD&C BLUE NO. 1 (UNII: H3R47K3TBD)  
Product Characteristics
ColorPURPLEScoreno score
ShapeCAPSULESize14mm
FlavorImprint Code 105
Contains    
Packaging
#Item CodePackage DescriptionMarketing Start DateMarketing End Date
1NDC:67877-438-1410 in 1 CARTON09/30/2016
114 in 1 BLISTER PACK; Type 0: Not a Combination Product
2NDC:67877-438-3030 in 1 BOTTLE; Type 0: Not a Combination Product09/30/2016
3NDC:67877-438-01100 in 1 BOTTLE; Type 0: Not a Combination Product09/30/2016
4NDC:67877-438-05500 in 1 BOTTLE; Type 0: Not a Combination Product09/30/2016
Marketing Information
Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
ANDAANDA20445309/30/2016
Labeler - Ascend Laboratories, LLC (141250469)
Establishment
NameAddressID/FEIBusiness Operations
Alkem Laboratories Limited915628612MANUFACTURE(67877-436, 67877-437, 67877-438, 67877-576, 67877-577, 67877-578, 67877-643, 67877-644)

Revised: 12/2019
Document Id: 777bf7fb-e8e6-4e3f-8564-52e793f4f409
Set id: a8f95207-b259-4f50-87f2-3652d9268890
Version: 15
Effective Time: 20191223
 
Ascend Laboratories, LLC