Minocycline Hydrochloride - Pharmacology TABLET, EXTENDED RELEASE

Pharmacology refers to the chemical makeup and behavior of MINOCYCLINE HYDROCHLORIDE (tablet, extended release).

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:

Minocycline hydrochloride extended-release tablets for oral administration contain minocycline hydrochloride, USP equivalent to 45 mg, 90 mg, or 135 mg of minocycline. In addition, 45 mg, 90 mg, and 135 mg tablets contain the following inactive ingredients: colloidal silicon dioxide, hypromellose, lactose monohydrate, and magnesium stearate.

The 45 mg extended-release tablets also contain opadry grey, which contains: titanium dioxide, triacetin, iron oxide black, and iron oxide yellow.

The 90 mg extended-release tablets also contain opadry orange, which contains: titanium dioxide, triacetin, iron oxide yellow, FD&C yellow # 6, and iron oxide red.

The 135 mg extended-release tablets also contain opadry yellow, which contains: titanium dioxide, triacetin and iron oxide yellow.

Clinical Pharmacology

mechanism of action

The mechanism of action of minocycline hydrochloride extended-release tablets for the treatment of acne is unknown.

pharmacodynamics

The pharmacodynamics of minocycline hydrochloride extended-release tablets for the treatment of acne are unknown.

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 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 to 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 Minocin® capsules, respectively. These parameters are based on dose adjusted to 135 mg per day for both products.

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 55 mg, 80 mg, and 105 mg were shown to be dose-proportional to minocycline hydrochloride 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.

Nonclinical Toxicology

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.

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, studies 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 Caplet Strength (mg)

Actual mg/kg

Dose

99 – 131

45 – 59

45

1 – 0.76

132 – 199

60 – 90

90

1.5 – 1

200 – 300

91 – 136

135

1.48 – 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

Trial 1

Trial 2

Minocycline Hydrochloride

Extended-Release Tablets

Placebo

Minocycline Hydrochloride Extended-Release Tablets

Placebo

(1 mg/kg)

N=300

N = 151

(1 mg/kg)

N= 315

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%)

 *Evaluator’s Global Severity Assessment

Minocycline hydrochloride extended-release tablets did not demonstrate any effect on non-inflammatory lesions (benefit or worsening).

This drug label information is as submitted to the Food and Drug Administration (FDA) and is intended for informational purposes only. If you think you may have a medical emergency, immediately call your doctor or dial 911. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Search Drugs and Medication

Or Browse by Name

Top Reads
  • Learn about drugs going generic in 2021 and how you may be able to save money on common prescription medication by switching to drugs coming off-patent.
    November 20, 2019
  • To make sure your medicines work as they should, here are some of the most common food-and-drug combinations to avoid.
    October 22, 2015
  • Get a list of the top 50 prescription drugs out of the annual 3 billion prescriptions filled at U.S. pharmacies.
    September 5, 2019
  • While medications are extremely useful in treating various diseases and conditions, sometimes they can cause unwanted side effects—one of which can be sexual dysfunction. Talk to your doctor if you’re taking any of these common medications that affect sex drive.
    September 23, 2016
  • Here’s a look at the most commonly abused prescription drugs.
    October 30, 2014

Love the Doctor Who Prescribed This Medication?

Top Drugs
  • Digestive health drugs manage diseases, disorders and conditions of the gastrointesinal system. They provide treatment and symptom relief for functional and structural problems with digestive organs.
  • Antibiotic, antifungal and antiviral drugs treat infectious diseases. They kill or stop the growth of microorganisms, including bacteria, fungi and viruses.
  • Birth control medications are a form of contraception. They contain either a combination of estrogen and progestin or progestin alone. There are several forms of these hormones, but most combination products contain estrogen, ethinyl estradiol, and a progestin. They work by preventing ovulation and inhibiting fertilization and implantation.
  • Mental health drugs treat conditions that affect emotional, psychological and social well-being. Doctors frequently use mental health drugs in combination with various forms of therapy to help people manage these conditions.