Efforts to reduce the incidence of acute vestibular adverse events (AVAEs) associated with minocycline have resulted in a novel, once-daily extended release oral formulation for the management of acne vulgaris. In trials, the rate of AVAEs associated with extended-release (ER) minocycline hydrochloride (Solodyn, Medicis) 1mg/kg was similar to the rate seen among placebo controls. The low rate of AVAEs is thought to result from a combination of the low dose and its extended release.
In a multicenter, 12-week, double-blinded, placebo-controlled, dose-ranging study, 233 subjects with moderate to severe facial acne vulgaris were randomized to receive once-daily treatment with ER minocycline 1mg/kg, 2mg/kg, 3mg/kg or placebo.1 Patients in the active treatment groups had approximately a 50 percent reduction from baseline in the number of inflammatory lesions. While the difference in the percentage reduction in inflammatory lesions was statistically significant between the 1mg/kg group and controls, there was no statistically significant difference in the percent reduction between any of the dosage groups. The rate of AVAEs in the 1mg/kg dosing group was 24 percent, compared to 26 percent in the placebo group.
Individual and pooled analysis of data from phase 2 and 3 trials of ER minocycline 1mg/kg confirm its safety and efficacy.2 The studies were prospective, multicenter, randomized, double-blinded, and placebo-controlled, involving a total of 1,038 subjects with moderate to severe acne. Treatment was associated with statistically significant reduction in inflammatory lesions and improvement in the Evaluator's Global Assessment scores. The percentage of subjects reporting AVAEs was about 10 percent in those receiving ER-minocycline 1- mg/kg and in those receiving placebo. Based on the data, researchers concluded that the once-daily ER formulation delivers consistent levels of drug.
Studies of the bioavailability of the formulation show that the extended-release (ER) minocycline hydrochloride tablet formulation demonstrates delayed time of maximum concentration (tmax, 3.5-4 hours) compared with a nonmodified-release minocycline (tmax, 2.25-3 hours), and a lower maximum concentration of drug (cmax) in the blood (90 percent) compared with nonmodified- release formulations.3 According to the reported data, at steady state (Day 6), the ER minocycline formulation had a 0- to 24-hour area under the curve (AUC(0-24)) and cmax of 33.32 microg x h/mL and 2.63 microg/mL, respectively, compared with 46.35 micro x h/mL and 2.92 microg/mL, respectively, for the nonmodified- release minocycline.
Concomitant food intake, including dairy, did not alter the pharmacokinetic profile of the ER minocycline tablets. Tablets are available in 45, 65, 90, 115, and 135mg doses.