Minocycline Hydrochloride

MINOCYCLINE HYDROCHLORIDE- minocycline hydrochloride tablet, film coated, extended release
Amneal Pharmaceuticals of New York, LLC

1 INDICATIONS AND USAGE

1.1 Indication

Minocycline HCl 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 HCl did not demonstrate any effect on non-inflammatory acne lesions. Safety of Minocycline HCl 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 HCl should be used only as indicated [see Warnings and Precautions (5.11)].

2 DOSAGE AND ADMINISTRATION

The recommended dosage of Minocycline HCl 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 HCl

Patient’s Weight (lbs)	Patient’s Weight (kg)	Tablet Strength (mg)	Actual Dose (mg/kg)
* No longer distributed or sold. † Not distributed by Amneal.
99 – 109	45 – 49	45*	1 – 0.92
110 – 131	50 – 59	55†	1.10 – 0.93
132 – 157	60 – 71	65	1.08 – 0.92
158 – 186	72 – 84	80†	1.11 – 0.95
187 – 212	85 – 96	90*	1.06 – 0.94
213 – 243	97 – 110	105†	1.08 – 0.95
244 – 276	111 – 125	115	1.04 – 0.92
277 – 300	126 – 136	135*	1.07 – 0.99

Minocycline HCl Tablets may be taken with or without food [see Clinical Pharmacology (12.3)]. Ingestion of food along with Minocycline HCl 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 AND STRENGTHS

•

65 mg extended release tablets: blue, unscored, coated, and debossed with “DYN-065” on one side.

•

115 mg extended release tablets: green, unscored, coated, and debossed with “DYN-115” on one side.

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

1.

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 HCl should not be used during pregnancy or by individuals of either gender who are attempting to conceive a child [see Use in Specific Populations (8.1) and Nonclinical Toxicology (13.1)].

2.

THE USE OF DRUGS OF THE TETRACYCLINE CLASS DURING TOOTH DEVELOPMENT (i.e., LAST HALF OF PREGNANCY, INFANCY, AND CHILDHOOD UP TO THE AGE OF 8 YEARS) MAY CAUSE PERMANENT DISCOLORATION OF THE TEETH (i.e., 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.

3.

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 2 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.