Extended-release Formulation of Minocycline in the Treatment of Moderate-to-severe Acne Vulgaris in Patients Over the Age of 12 Years.

Oral antibiotics continue to play an important role in the treatment of moderate-to-severe acne. Minocycline is widely used in moderate-to-severe acne. Minocycline has anti-inflammatory properties, activity against Propionibacterium acnes and lipophilicity. An extended-release formulation of minocycline has been introduced. Extended-release minocycline is not bioequivalent to nonmodified release minocycline products and exhibits dose-proportional pharmacokinetics. Food or dairy products did not influence absorption. Efficacy is not dose-dependent, while the incidence of acute vestibular adverse events increases with dose suggesting an optimal dose of 1mg/kg. In two Phase 3 clinical trials, mean percent improvement in inflammatory lesions after 12 weeks of treatment with extended-release minocycline was 43.1 and 45.8 percent compared to 31.7 and 30.8 percent with placebo (P=0.001 and P<0.001, respectively) while the incidence of acute vestibular adverse events was comparable to placebo.

Safety and efficacy of micronized tretinoin gel (0.05%) in treating adolescent acne.

Tretinoin is widely used in the treatment of acne. Despite significant advances in formulation development, irritation and dryness can be particularly bothersome, especially during the first 3-4 weeks, impacting adherence. Dose titration and adjunct use of moisturizers have been commonly employed. Co-prescribing with benzoyl peroxide (BPO) or a BPO/antibiotic combination is also common practice. The tretinoin molecule is unstable and can be degraded by BPO, further complicating treatment regimens. Lately, formulation technology has focused on providing more efficient penetration of the tretinoin into the skin layers so that lower concentrations of tretinoin might afford better tolerability, but maintain good efficacy; incorporating moisturizing excipients to minimize irritation; and providing greater stability to the tretinoin molecule. This approach would be particularly relevant in a pediatric acne population where efficacy/tolerability balance is important and treatment regimens must take into account lifestyles, but little data exist on the use of tretinoin in this patient population. A micronized formulation of tretinoin (0.05%) gel has been developed that provides a more efficient delivery of tretinoin, because of its optimal particle size, no degradation by BPO and better cutaneous tolerability than tretinoin microsphere (0.1%) gel without compromising efficacy in a pediatric population.

A comprehensive review of the long-term and short-term treatment of melasma with a triple combination cream.

Melasma is a common disorder of hyperpigmentation and generally involves areas of the face and neck. Hyperpigmentation is especially prevalent in darker complected patients and is often difficult to treat. Hydroquinone, tretinoin, and topical corticosteroids are well established monotherapeutic agents for treating melasma and hyperpigmentation; however, a stable, once-daily formulation triple combination cream containing 0.05% tretinoin, 4.0% hydroquinone, and 0.01% fluocinolone acetonide (Tri-Luma) represents the only commercially available combination of all three agents. This product is approved by the US FDA for the treatment of facial melasma. A number of publications have described the safety and efficacy of triple combination cream in over 2000 patients with melasma, some of whom were treated for >12 months. In the initial 8-week study, 29% of patients experienced complete clearing of melasma by week 8, and 77% were clear or almost clear by week 8. Similarly, good results were seen in the two long-term studies, with the clear/mild rate ranging from 78% to 84% of patients at month 6 and from 81% to 94% of patients at month 12. Adverse events were almost always mild in severity and typically occurred only at the application site. The primary concern for most physicians using corticosteroid-containing products on the face is skin atrophy. However, only two cases of skin atrophy were reported across the three published studies. Overall, the results of these extensive studies indicate that triple combination cream is efficacious in treating melasma and exhibits a safe profile with low potential for adverse events.

The Nicomide Improvement in Clinical Outcomes Study (NICOS): results of an 8-week trial.

The Nicomide Improvement in Clinical Outcomes Study (NICOS) was an open-label, multicenter, prospective cohort study designed to assess the clinical utility of oral pharmacologic doses of nicotinamide and zinc in 198 patients with acne vulgaris and/or rosacea. The study's primary efficacy measures were patient global evaluation and patient evaluation of the percentage of reduction in inflammatory lesions after 4 and 8 weeks of treatment; overall patient satisfaction also was recorded. The study formulation consisted of nicotinamide 750 mg, zinc 25 mg, copper 1.5 mg, and folic acid 500 microg, marketed as Nicomide (Nic/Zn). Nic/Zn was designed to deliver adequate concentrations of nicotinamide and zinc to effectively treat inflammatory cutaneous conditions with a safety profile suitable for long-term administration. After a relatively short treatment period of 4 weeks, the number of patients enrolled in NICOS who reported improvement was significantly greater (P<.0001) than the number who reported either no change in or worsening of their condition. Of the patients studied, 79% reported their improvement in appearance as moderately better or much better, as measured by patient global evaluation, and 55% reported moderate (26%-50% reduction in lesions) or substantial (>50% reduction in lesions) improvement after 4 weeks of treatment (P<.0001). The percentage of patients who responded to therapy continued to increase through the 8 weeks of treatment. When comparing patients who received concomitant oral antibiotic therapy (51/198, 26%) with those who received Nic/Zn tablets as their only oral therapy (147/198, 74%), the percentage of patients who responded to treatment was not significantly different between treatment groups (P=. 13). This finding was particularly interesting given that most patients studied considered their condition to be of at least moderate severity (143/198, 72%). It appears that the addition of an oral antibiotic to a treatment regimen that includes Nic/Zn tablets may not be necessary because the combination did not significantly increase the percentage of patients responding. Nic/Zn tablets appear to be an effective oral therapy for the treatment of acne vulgaris and rosacea when used alone or with other topical therapies and should be considered a useful alternative approach to oral antibiotics for the treatment of acne vulgaris and rosacea.

Combination sodium sulfacetamide 10% and sulfur 5% cream with sunscreens versus metronidazole 0.75% cream for rosacea.

Topical metronidazole and combination sodium sulfacetamide and sulfur commonly are used to treat rosacea. Recently, the relative efficacy and safety of sodium sulfacetamide 10% and sulfur 5% cream with sunscreens (Rosac Cream) (n = 75) and metronidazole 0.75% cream (Metrocream) (n = 77) were compared in an investigator-blinded, randomized, parallel-group study at 6 sites. After 12 weeks of treatment with sodium sulfacetamide 10% and sulfur 5% cream with sunscreens, there was a significantly greater percentage reduction (80%) in inflammatory lesions compared with metronidazole 0.75% cream (72%)(P = .04), as well as a significantly greater percentage of subjects with improved erythema (69% vs 45%, respectively; P = .0007). In addition, the sodium sulfacetamide 10% and sulfur 5% cream with sunscreens group had a significantly greater proportion of subjects with success in global improvement at week 12 compared with the metronidazole 0.75% cream group (79% vs 59%, respectively; P = .01). There was no significant difference between treatment groups in the percentage of subjects with improvement in investigator global severity. Overall tolerance was good or excellent in 85% of subjects in the sodium sulfacetamide 10% and sulfur 5% cream with sunscreens group and in 97% of subjects in the metronidazole 0.75% cream group. Seven subjects had poor tolerance to the sodium sulfacetamide 10% and sulfur 5% cream with sunscreens, possibly caused by a sulfa drug allergy.

Clocortolone pivalate cream 0.1% used concomitantly with tacrolimus ointment 0.1% in atopic dermatitis.

This study was designed to evaluate the safety and efficacy of concomitant therapy with the corticosteroid clocortolone pivalate cream 0.1% (Cloderm Cream 0.1%) and the topical immunosuppressive agent tacrolimus ointment 0.1% (Protopic Ointment 0.1%) and to compare each drug alone for the treatment of atopic dermatitis in adolescents and adults. Concomitant therapy may minimize the potential adverse effects of both treatments taken alone and may potentially improve overall response. In this 21-day study with 57 patients with atopic dermatitis, groups of 19 patients were randomized to 1 of 3 treatments: concomitant treatment with clocortolone pivalate cream 0.1% and tacrolimus ointment 0.1% (CPC+ TO), monotherapy with clocortolone pivalate cream 0.1% (CPC), or monotherapy with tacrolimus ointment 0.1% (TO). CPC+ TO was statistically superior to TO alone in the percentage change for dermatologic sum score at days 14 (P = .024) and 21 (P = .033), excoriation at day 21 (P = .028), induration at day 21 (P = .033), and erythema at day 14 (P = .048). The dual therapy was also superior to CPC alone in excoriation at days 7 (P = .045) and 14 (P = .037), oozing or crusting at days 3 (P = .034) and 7 (P = .012), and lichenification at day 3 (P = .031). In addition, unlike the 2 single-therapy treatment groups, percentage reductions from baseline in scores for the sensation of transient pruritus and burning or stinging were statistically significant for the concomitant treatment at days 14 (P = .016) and 21 (P = .016).