Transitioning from brand to generic with topical products and the importance of maintaining the formulation and therapeutic profiles of the original product: focus on clocortolone pivalate 0.1% cream.

Topical corticosteroids (TCSs) are a major part of the foundation of treatment for a wide variety of eczematous and inflammatory skin disorders in both adults and children. Mid-potency TCSs represent an important category as they are often used to treat eczematous dermatoses, such as atopic dermatitis. The TCS product must effectively release the active ingredient and promote cutaneous penetration so that therapeutic activity can occur. As many topical products eventually become available as generic formulations, it is important to recognize that although the active ingredient and its concentration are the same, the vehicle excipients may differ significantly, occasionally leading to potential differences in irritancy, in allergenicity, in effects on epidermal permeability barrier function, and, possibly, in efficacy. Clocortolone pivalate 0.1% cream is a mid-potency TCS formulated in an emollient formulation that has been shown to be effective and well-tolerated in the management of several corticosteroid-responsive dermatoses. This article outlines the pharmacologic and clinical data achieved with the original brand formulation of clocortolone pivalate 0.1% cream, and discusses the establishment of an authorized generic formulation that is identical in formulation to the original brand.

A study to assess the occlusivity and moisturization potential of three topical corticosteroid products using the skin trauma after razor shaving (STARS) bioassay.

Dysfunction of the epidermal barrier is generally considered a precursor of cutaneous inflammation that can directly contribute to the pathogenesis of skin diseases, notably atopic dermatitis (AD). We also know that topical corticosteroids may actually impair the epidermal barrier by interfering with epidermal lipid synthesis. Therefore, it is important to utilize topical corticosteroids in vehicles that will help at least to enhance the already disrupted epidermal barrier in atopic dermatitis patients. Two studies of identical design were conducted to determine and compare the occlusivity and moisturizing potential of three topical corticosteroid products when applied to skin whose barrier integrity has been disrupted by dry shaving. Findings in both studies showed the clocortolone pivalate cream decreased TEWL better than non-treatment or treatment with hydrocortisone butyrate lotion. Skin surface hydration increased significantly (P<0.001) in all three treated sites, compared to the non-treated damaged control and non-treated normal skin. Clocortolone pivalate cream increased skin surface hydration significantly (P<0.001) better than hydrocortisone butyrate lipocream or hydrocortisone butyrate lotion. These studies showed that clocortolone pivalate cream enhances barrier function by providing occlusion. While understanding of the structure and function of the stratum corneum (SC) and epidermal barrier function has evolved tremendously over the last several decades, and especially over the last 15 years,1 confusion and misinformation still persist. Dysfunction of the epidermal barrier is generally considered a precursor of cutaneous inflammation that can directly contribute to the pathogenesis of skin diseases, notably atopic dermatitis (AD).2,3 Topical steroids are standard of care in treatment of atopic dermatitis. However, we also know that topical corticosteroids may actually impair epidermal barrier by interfering with epidermal lipid synthesis.4,5 In addition to that, various penetration enhancers in the topical steroid formulations also contribute to the impairment of the epidermal barrier.4 Therefore, it is important to utilize topical corticosteroids in vehicles that will help at least to enhance the already disrupted epidermal barrier in atopic dermatitis patients. In this regard, these studies were designed to determine the hydrating effects of clocortolone pivalate cream 0.1% (Cloderm Cream, Promius Pharma).

The role of a midpotency topical corticosteroid and the clinical relevance of formulation characteristics in the management of commonly encountered eczematous and inflammatory dermatoses in adults and children: focus on the pharmacologic properties of clocortolone pivalate 0.1% cream.

Midpotency topical corticosteroids (TCSs) are frequently used for the treatment of common eczematous and inflammatory skin disorders in both adults and children. There are several commercially available products in this category, and many vehicles and formulations for the clinician to choose from. Clocortolone pivalate 0.1% cream is a midpotency TCS formulated in an emollient formulation that has been shown to be effective and well tolerated when used appropriately in the management of several corticosteroid-responsive dermatoses. This article discusses the physiochemical properties of the compound; the characteristics of its emollient cream formulation; the functions of individual excipients; and the efficacy, tolerability, and safety data supporting its use in adults and children, including for facial involvement.

Adherence to clocortolone pivalate cream 0.1% in a pediatric population with atopic dermatitis.

Topical corticosteroids are first-line treatments for atopic dermatitis (AD) and their efficacy is well-established in randomized controlled clinical trials. When corticosteroids fail in clinical practice, it often is attributed to nonresponse. However, poor adherence also should be considered. With the advent of electronic monitoring systems, objective data on adherence can be obtained. The purpose of this study was to determine both self-reported and actual adherence to clocortolone pivalate cream 0.1% in the treatment of AD in a pediatric population. Six participants completed the 4-week study. Self-reported adherence was significantly higher than objectively measured adherence (P = .01). In general, adherence was best during the first week of treatment and tapered off thereafter. Clocortolone pivalate cream 0.1% was generally effective, with rapid improvement over the first week of treatment, even when adherence was limited. This study was limited by the small sample size and the failure of 2 participants to complete the study. Patients overestimate their adherence behavior. While some patients are adherent to treatment, others rapidly discontinue their use of medication over time. Midpotency topical corticosteroids such as clocortolone pivalate cream 0.1% are highly effective treatments for AD. Poor adherence should be considered when AD is not responding to topical corticosteroid treatment.

[Sudden hearing loss in a patient with a 3-mm acoustic tumor]. / Uç milimetrelik akustik tümörü olan bir hastada ani isitme kaybi.

Sudden sensorineural hearing loss (SNHL) accounts for 1% of all SNHL cases. It has been reported that acoustic neuroma may be present up to 47.5% of patients with sudden SNHL. A 55-year-old man presented with sudden hearing loss in his left ear of 45-day history. Audiologic and transient evoked otoacoustic emission tests showed near-total hearing loss and absence of emissions in the left ear, respectively. Electronystagmography showed left canal paralysis and lack of response to the Kobrak test. The interpeak interval I-V latency and interaural amplitude differences in wave V latency were prolonged in auditory brainstem response. Computed tomography showed an increase in the diameter of the left internal acoustic canal, and magnetic resonance imaging (MRI) revealed an intracanalicular mass, 3 mm in size, originating from the left cochlear nerve. Another mass (18x17 mm) was detected that filled the right pontocerebellar cistern, suggesting a meningioma, but this was not thought to exert an obvious shift effect contributing to the development of left-sided hearing loss. Despite treatment with a tapered course of fluocortolone for 18 days the patient's hearing level did not change. He was included in a follow-up with MRI at six-month intervals.

Oral and intralesional steroid therapy in giant cell granuloma.

Giant cell granulomas account for 7% of all benign tumors of the jaw. They are commonly seen as asymptomatic masses. A 4-year-old boy with an exophitic, crusty, hemorrhagic mass on the anterolateral region of the right maxilla was referred to our department. Pathological examination was reported as giant cell granuloma. A mixture of prednisolone, lidocaine and adrenaline was injected intralesionally once a week and oral fluocortone was added to this therapy. A limited surgery could be performed. Intralesional prednisolone and systemic fluocortone therapy seems to be effective, as the lesion stopped growing and increase in bony structures was observed radiologically.

Topical FK506 as immunoprophylaxis after allogeneic penetrating normal-risk keratoplasty: a randomized clinical pilot study.

The purpose of this study was to evaluate for the first time the efficacy and safety of topical FK506 in patients undergoing penetrating normal-risk keratoplasty in a prospectively randomized clinical trial. Twenty patients were treated with FK506 0.06% three times per day for 6 months postoperatively. An additional 20 patients received five drops of prednisolone acetate 1% tapered within 6 months. All patients received 1 mg/kg bodyweight/day of systemic fluocortolon tapered within 3 weeks postoperatively. Clear graft survival, ratio of immune reactions and side effects were the main outcome measures. One year postoperatively all patients of the FK 506 group were free from immune reactions, in contrast to 84% in the steroid group (Kaplan-Meier values; P = 0.9 in the log rank test). None of the patients developed irreversible graft failure so far. In eight patients of the FK506 group premature withdrawal of the drug was deemed appropriate because of local side effects. FK506 might turn out to become an effective immunoprophylaxis in subjects undergoing penetrating normal-risk keratoplasty. Local discomfort should be further reduced.

[Ranking of systemic steroids after normal-risk keratoplasty. Results of a randomized prospective study]. / Stellenwert der systemischen Steroidtherapie nach Normalrisikokeratoplastik. Eine randomisierte prospektive Pilotstudie.

BACKGROUND: The aim of this study was to evaluate the efficacy of sole application of topical steroids after normal-risk keratoplasty. PATIENTS AND METHODS: This randomized prospective clinical study assessed 40 patients who had undergone penetrating normal-risk keratoplasty. Twenty patients were treated exclusively with prednisolone acetate 1% eye drops 5x/day for 6 months postoperatively. Another 20 patients additionally received systemic fluocortolone 1 mg/kg body weight per day tapered within 3 weeks postoperatively. The main outcome measures included clear graft survival, ratio of graft rejection, and side effects. RESULTS: The mean postoperative follow-up was 18+/-9 months. Three graft rejections were observed in the group receiving only topical steroids. Two graft rejections were observed in the group administered combined systemic and topical steroid therapy. None of the patients has developed irreversible graft failure so far. CONCLUSION: Sole topical steroid application seems to be an effective immune prophylaxis in patients undergoing penetrating normal-risk keratoplasty.

[Cyclosporin A therapy in severe anterior scleritis. 5 severe courses without verification of associated systemic disease treated with cyclosporin A]. / Ciclosporin-A-Therapie bei schweren anterioren Skleritiden. Fünf schwere Verläufe ohne nachgewiesene assoziierte Systemerkrankung unter systemischer Ciclosporin-A-Therapie.

BACKGROUND: Patients with severe scleritis who do not respond to high-dose corticosteroid therapy, or who require a daily corticosteroid maintenance dose higher than 30 mg prednisone should be treated by other immunosuppressants. PATIENTS AND METHODS: In five patients with various types of severe anterior scleritis a long-term high-dose steroid treatment failed to control scleral inflammation. They therefore received cyclosporin (CsA). Follow-up was 16-26 months. RESULTS: Scleral inflammation and ocular complications were controlled in all patients by a regimen of systemic CsA combined with a low maintenance steroid dose below the Cushing threshold. We observed no side effects under CsA serum levels of 120-150 ng/ml. In only one patient was scleral inflammation totally and lastingly eliminated. CONCLUSIONS: Systemic CsA therapy is of definite therapeutic value in the symptomatic management of steroid refractory severe anterior scleritis without associated systemic disease. Complete healing, however, is achieved only in a minority of cases.

Effects of systemic steroid treatment in chronic polypoid rhinosinusitis evaluated with magnetic resonance imaging.

BACKGROUND: The aim of this prospective study was to evaluate the efficacy of a combined (local and systemic) steroid therapy on the extent of chronic polypoid rhinosinusitis and patient symptoms. METHODS AND PATIENTS: Subjects of this study were 20 patients with severe chronic polypoid rhinosinusitis with total or subtotal narrowing of the all sinuses. A nasal budesonide spray (2 x 0.1 mg/day) and an oral fluocortolone medication with a daily reduction during a 12-day period (total dose: 560 mg = group 1) and a 20-day period (total dose: 715 mg = group 2), respectively, were administered. Before and after the steroid treatment we evaluated the extent of the sinusitis with MRI and patient symptoms with symptom-related questionnaires. RESULTS: A significant reduction (> 30%) of the chronic polypoid rhinosinusitis was observed in 50% of MRI findings. The steroid effect on polypoid masses was heterogeneous in different anatomic areas (maxillary sinus 40%, anterior ethmoid 19%, posterior ethmoid 33%, sphenoidal sinus 61%, frontal sinus 46%). Most sinusitis-related symptoms were distinctly diminished in most patients (80%). No major side effects were observed. CONCLUSIONS: A combined short-term steroid therapy is highly effective in chronic polypoid rhinosinusitis, reducing the mucosal inflammation mainly in the large sinuses and reducing the incidence of symptoms significantly. However, this therapy was insufficient in the anterior ethmoid and cannot replace the current surgical treatment concept of the osteomeatal complex in CPR. The indication for such a short-term steroid therapy is the preoperative treatment. It facilitates functional endoscopic sinus surgery by reducing the extent of surgical procedures, the time, and thereby the risks of sinus surgery.

[Generalized Mycobacterium avium-intracellulare infection due to immunosuppressive therapy of paraneoplastic dermatomyositis]. / Generalisierte Mycobacterium avium-intracellulare Infektion infolge immunsuppressiver Therapie einer paraneoplastischen Dermatomyositis.

The ubiquitous Mycobacterium avium-intracellulare (MAI) is the most frequent cause of disseminated atypical mycobacteriosis in AIDS patients. MAI infections may develop in patients with other acquired immune defects, such as connective tissue disorders. In adults, the gastrointestinal and respiratory systems are most frequently affected. We report a patient with dermatomyositis receiving immunosuppressive therapy in whom only the skin and the skeletal system were affected by MAI. Because it presented with polymyositis-like symptoms, the infection was initially not identified and treated. The MAI was cultured from a periarticular joint effusion from the right upper arm and from venous blood, as well as identified histologically in lesional skin. Resistance to antibiotics developed most likely because the patient failed to take oral antibiotics regularly. Because of an acute exacerbation of the tumor-associated dermatomyositis, immunosuppressive therapy was initiated, while the tuberculostatic therapy was continued. Using these therapies both diseases markedly improved. In patients with connective tissue disorders receiving longterm immunosuppressive therapy, especially when changes in symptoms and signs are observed, opportunistic infections such as MAI should be considered and included in the differential diagnosis.

Evaluation of the efficacy and toxicity of the cyclosporine A-flucortolone-methotrexate combination in the treatment of sarcoidosis.

Eleven patients with chronic sarcoidosis resistant to high-dose corticosteroids and other immunosuppressive treatments were treated with cyclosporine A at the initial daily dose of 5 mg per kg body weight (ideal weight in the case of overweight subjects) combined with flucortolone and methotrexate. A complete and lasting remission of the disease was obtained in all patients with total disappearance of pulmonary and extrapulmonary manifestations. In addition, the disease activity indexes normalized and remained normal for the rest of the follow-up period (24.82 +/- 8.22 months, range 12-33). No renal or hepatic toxicity was observed in any patient. Two of them presented hypertrichosis and one nausea.

Pharmacokinetic/pharmacodynamic modeling of cortisol suppression after oral administration of fluocortolone.

Fluocortolone is a potent corticosteroid used orally for the treatment of rheumatic diseases, asthma, and immunosuppression. A clinical study of nine healthy volunteers was conducted to determine the pharmacokinetics and cortisol suppression after administration of single oral doses of 20 mg, 50 mg, and 100 mg of fluocortolone. Blood samples were collected at 8:00 AM, 12:00 PM, and 4:00 PM on the day before treatment, and 0, 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 28, 32, 48, 52, and 56 hours after administration of the drug. Concentrations of fluocortolone and cortisol were measured in plasma by a reversed phase high-performance liquid chromatography system. Cortisol suppression was chosen as the pharmacodynamic parameter. Total concentrations were converted into unbound concentrations using a two-protein, one-ligand equation. The unbound concentrations were fitted using a one-compartment body model equation with first-order absorption. A linear release-rate model was used to characterize the cortisol data. The data were fitted using a common E50 value of 0.95 +/- 0.22 ng/mL for the mean data. The value of E50 was in close agreement with the prediction based on relative glucocorticoid receptor affinity.

Psychopathological and neuropsychological effects of 8-days' corticosteroid treatment. A prospective study.

Corticosteroids often induce a variety of psychiatric symptoms, such as alterations of mood, neuropsychological deficits and even psychotic states. To date, only a few studies have specifically addressed behaviour as well as cognitive functioning in patients under steroid treatment. Fifty ophthalmologic patients participated in this prospective study. They received methylprednisolone or fluocortolone at doses of 119 +/- 41 mg/day in the beginning and 75 +/- 22 mg after 8 days of treatment. Psychopathology and neuropsychological functioning were examined before and after steroid therapy, mood was self-rated on days 0, 3, 5 and 8. No marked psychopathological abnormalities such as psychosis, dementia or delirious states were observed. However, a significant proportion of patients suffered from an organic mood disorder, 26-34% experienced a hypomanic syndrome, 10-12% a depressive syndrome. Most neuropsychological tests did not reveal significant effects of steroid treatment. Performance of Word Fluency and Trail Making A improved, while the Auditory-Verbal-Learning and the Digit-Symbol showed a worsening. Psychopathological and neuropsychological effects were not significantly correlated.