Solodyn (Minocycline Hydrochloride) - Description and Clinical Pharmacology

Rx Only

KEEP OUT OF REACH OF CHILDREN

To reduce the development of drug-resistant bacteria as well as to maintain the effectiveness of other antibacterial drugs, SOLODYN™ should be used only as indicated.

SOLODYN™ is indicated to treat only inflammatory lesions of non-nodular moderate to severe acne vulgaris.

This formulation of minocycline has not been evaluated in the treatment of infections.

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:

SOLODYN™ 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: lactose monohydrate NF, hypromellose type 2910 USP, magnesium stearate NF, colloidal silicon dioxide NF, and carnauba wax NF. The 45 mg tablets also contain opadry II gray which contains: lactose monohydrate NF, hypromellose type 2910 USP, titanium dioxide USP, triacetin USP, and iron oxide black JPE. The 90 mg tablets also contain opadry II yellow which contains: hypromellose type 2910 USP, lactose monohydrate NF, titanium dioxide USP, iron oxide yellow NF, polyethylene glycol 3350 NF, and triacetin USP. The 135 mg tablets also contain opadry II pink which contains: hypromellose type 2910 USP, lactose monohydrate NF, titanium dioxide USP, polyethylene glycol 3350 NF, iron oxide red NF, and triacetin USP.

CLINICAL PHARMACOLOGY

Pharmacokinetics

SOLODYN™ tablets are not bioequivalent to minocycline products. Based on pharmacokinetic studies in healthy adults, SOLODYN™ tablets produce a delayed T_max at 3.5–4.0 hours as compared to a non-modified release reference minocycline product (T_max at 2.25–3 hours). At steady-state (Day 6), the mean AUC(0–24) and C_max were 33.32 µg×hr/mL and 2.63 µg/mL for SOLODYN™ tablets and 46.35 µg×hr/mL and 2.92 µg/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 all strengths of SOLODYN™ tablets (45 mg, 90 mg, 135 mg) exhibited dose-proportional pharmacokinetics.

When SOLODYN™ 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.

Microbiology

Minocycline is bacteriostatic exerting its antimicrobial effect by the inhibition of bacterial protein synthesis. Minocycline is lipid soluble and distributes in to the skin and sebum. Minocycline has been shown to have in vitro activity against Propionibacterium acnes, an organism associated with acne vulgaris, however, the clinical significance of this activity against P. acnes in patients with acne vulgaris is not known.

CLINICAL STUDIES

The safety and efficacy of SOLODYN™ 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 1 mg/kg of SOLODYN™ or placebo for a total of 12 weeks. 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 1.

Table 1 – Efficacy Results at Week 12

	Study 1		Study 2
	SOLODYN™ (1 mg/kg) N = 300	Placebo N = 151	SOLODYN™ (1 mg/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 EGSAEvaluator's Global Severity Assessment	52 (17.3%)	12 (7.9%)	50 (15.9%)	15 (9.5%)

SOLODYN™ did not demonstrate any effect on non-inflammatory lesions (benefit or worsening).