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.

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.

The treatment of inflammatory facial dermatoses with topical corticosteroids: focus on clocortolone pivalate 0.1% cream.

OBJECTIVE: Study results evaluating the efficacy and safety of clocortolone pivalate 0.1% cream in the treatment of adults, young children, and infants with inflammatory facial dermatoses are reported in this article. Clocortolone pivalate 0.1% cream, indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses, is a mid-potency topical corticosteroid (Class 4) that has been studied and used extensively to treat a variety of corticosteroid-responsive inflammatory dermatoses, many of which often involve facial skin in both adults and children. METHODS: Clocortolone pivalate 0.01% cream was applied to affected facial skin in subjects presenting with seborrheic dermatitis, contact dermatitis, atopic dermatitis, or psoriasis. Application was completed three times daily for 21 days. Assessments of erythema, edema, transudation, lichenification, scaling, pruritus and/or pain were completed at baseline and Days 4, 7, 14, and 21. Overall therapeutic response was assessed at all follow-up visits. Forty-nine subjects were entered, ranging in age from 1 month to 88 years of age. Thirty-eight subjects completed the studies, with 11 subjects lost to follow-up after the first visit. Individuals between the ages of 13 and 19 years were pre-emptively excluded to avoid potential application of a corticosteroid to acne-affected or acne-prone skin. RESULTS: Treatment with clocortolone pivalate 0.1% cream resulted in decreases in erythema, edema, transudation, lichenification, scaling, and pruritus/pain in 76% of treated study subjects. The overall therapeutic response in approximately two-thirds of the subjects (68%) was rated as good to excellent. There were 7 adverse events noted over the course of the study that were judged to be related to treatment, all of which were cutaneous and localized to the site of application (acneiform eruptions, burning, and folliculitis). CONCLUSION: Clocortolone pivalate 0.1% cream was effective in relieving the signs and symptoms of corticosteroid-responsive inflammatory dermatoses involving facial skin, including seborrheic dermatitis, contact dermatitis, atopic dermatitis, and psoriasis. Overall, the safety profile was favorable and devoid of any treatment-related serious adverse events.

[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.

Combined treatment with corticosteroids and moclobemide favors normalization of hypothalamo-pituitary-adrenal axis dysregulation in relapsing-remitting multiple sclerosis: a randomized, double blind trial.

Hyperresponsiveness of the hypothalamo-pituitary-adrenal (HPA) axis in multiple sclerosis (MS), an autoimmune inflammatory disease of the central nervous system, is presumably due to diminished corticosteroid receptor function. It probably influences the immune response, but its clinical significance is not clear. Similar HPA dysregulation occurs in depression and is reversible with successful antidepressant treatment. We conducted a double blind, placebo-controlled trial to evaluate the neuroendocrine effect of cotreatment with the antidepressant moclobemide as an adjunct to oral corticosteroids in MS. Twenty-one patients with definite relapsing-remitting MS (11 females, aged 33.9 +/- 2.0 yr; Expanded Disability Status Scale score of neurological impairment, 2.0--6.5) in acute relapse were treated with placebo (n = 13) or 300 mg moclobemide (reversible monoamine oxidase A inhibitor; n = 8) for 75 days. All received oral fluocortolone from day 7 on, and the dose was tapered until day 29. Effects were evaluated using the combined dexamethasone-CRH test and clinically on days 1, 30, and 75. At baseline, the HPA axis was mildly activated, comparably for treatment groups [area under the curve for cortisol (AUC-Cort), 213.8 +/- 76.8 arbitrary units in the moclobemide group vs. 225.8 +/- 65.1 in the steroid alone group; mean +/- SEM]. In a group of healthy controls with comparable demographic characteristics, the AUC-Cort was 107.4 +/- 14.1. Moclobemide cotreatment resulted in normalization of the HPA axis response, whereas the HPA system hyperresponse was maintained with steroids alone (AUC-Cort on day 30, 85.9 +/- 22.8 vs.177.1 +/- 68.5; on day 75, 111.0 +/- 46.0 vs. 199.2 +/- 64.6). The change in Expanded Disability Status Scale was comparable for both groups. Although corticosteroids alone had no effect on the HPA response using the dexamethasone-CRH test, treatment with moclobemide combined with corticosteroids favors normalization of the HPA response in relapsing-remitting MS.

[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.

[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.

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.

Intranasal fluocortin butyl in patients with perennial rhinitis: a 12-month efficacy and safety study including nasal biopsy.

Fluocortin butyl (FCB) is a recently developed topical intranasal corticosteroid that is inhaled as a powder and has been demonstrated to be well tolerated and to improve symptoms and signs of perennial rhinitis in previous short-term studies. This multicenter, open-label study evaluated the efficacy and safety of FCB during a 12-month treatment period in patients with perennial rhinitis. Treatment was initiated with one inhalation of FCB in each nostril three times a day (total dosage, 3 mg/day). In subsequent months, one third of the patients was maintained at the dosage of 3 mg/day, one third at a lower dosage of 2 mg/day, and the remaining one third of the patients at a larger dosage of 4 to 8 mg/day. Of 109 patients enrolled in the study, 90 patients (82.6%) completed all 12 months of treatment. Symptom and sign scores decreased significantly (p less than 0.001) at the 2-month evaluation compared to scores at baseline, and the improvement was maintained throughout the 12-month study period. After 12 months, greater than 80% of the patients had substantial control of symptoms. Specimens of nasal biopsies, performed at the beginning and end of treatment, revealed a decrease in eosinophils and other cellular infiltrates, a slight tendency of an increase in mast cell counts, and a trend toward normalization of the nasal mucosa. There were few adverse effects. Mean plasma cortisol levels were normal before and after corticotropin stimulation at baseline and after 12 months of FCB therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

[Development of multiple precancerous conditions and malignant skin tumors in immunosuppressive therapy]. / Entwicklung multipler Präkanzerosen und maligner Hauttumoren unter immunsuppressiver Therapie.

A 45-year-old patient developed squamous cell carcinoma 4 years after renal transplantation and immunosuppressive therapy with azathioprine and fluocortolone. During the following 3 years, the patient developed on sun-exposed skin several premalignant hyperkeratoses, Bowen's carcinoma, basal cell carcinoma, as well as squamous cell carcinoma and carcinoma of the eccrine sweat glands, both showing the clinical picture of keratoacanthoma.

[Effect of topical glucocorticoids on endogenous cortisol production]. / Einfluss topischer Glukokortikoide auf die körpereigene Cortisolproduktion.

In a randomized double blind study, we investigated the systemic effects of 3 different ointments containing corticoids. Every 7 patients out of a total of 21 patients suffering from various skin diseases were daily treated with 40 g of one of the 3 corticoid preparations over 8 days (group A: 0.05% clobetasol-17-propionate; group B: 0.25% fluocortolone trimethyl acetate; group C: 0.25% fluocortolone trimethyl acetate + 0.25% fluocortolone capronate). The plasma cortisol levels were determined by radioimmune assay. In group B and C, we did not observe any effect on the pituitary-adrenal axis, whereas in group A the plasma cortisol levels were extremely low already after 1 day of corticoid application. This adrenal suppression did not return to normal within 4 days after discontinuation of the corticoid. Our results suggest that highly potent topical corticoids are capable of adrenal suppression even without occlusive dressing and even in healthy persons.

[Treatment of severe aplastic anemia with a cyclosporin-corticosteroid combination]. / Traitement de l'anémie aplastique sévère par l'association ciclosporine/corticostéroïdes.

Four patients with severe aplastic anemia were treated with a combination of cyclosporin (5 mg/kg/day) and steroids (prednisone 0.2-0.8 mg/kg/day 3/4 days). A positive response (transfusions stopped, granulocytes greater than 1500/mm3, thrombocytes greater than 50,000/mm3) was achieved in three of these patients. The therapy had a rapid effect on reticulocytes and granulocytes (7-14 days) while platelet numbers took longer to correct (2-4 months). All patients presented signs of dyserythropoiesis with macrocytosis. Side effects of therapy were minor (tremor, water retention, gynecomastia, hirsutism). In this series, the combination of cyclosporin with steroids appears to be an effective treatment for severe aplastic anemia with a more rapid result and better tolerance in comparison to antilymphocyte serum.

Combined steroid-cyclosporin treatment of chronic autoimmune diseases. Clinical results and assessment of nephrotoxicity by renal biopsy.

Twenty-one patients suffering from different autoimmune diseases (14 from systemic lupus erythematosus, 4 from rheumatoid arthritis, one from Sjögren's syndrome, one from systemic hypersensitivity vasculitis, and one from diffuse proliferative glomerulonephritis) were treated with a combined immuno-suppressive regimen. Cyclosporin was given at a dose of 5 mg/kg/day together with steroids. In addition, the rheumatoid arthritis patients also received methotrexate. In all patients a kidney biopsy was performed after a treatment period of 17 to 42 months (mean duration 21.7 months). The cumulative cyclosporin dose at the time of biopsy varied from 1.071 to 4.587 mg/kg. Patients suffering from systemic lupus erythematosus and rheumatoid arthritis were assessed according to a scoring system set up for this purpose. The combined therapy proved useful in these patients as reflected in the diminution of the respective activity scores, improvement of kidney function, and diminution of proteinuria. Histological examination of the kidney biopsy specimens showed only minimal activity in patients with systemic lupus erythematosus. No unequivocal signs of renal toxicity could be detected. In the last group, the condition of the patient with Sjögren's syndrome was stabilized and the patient with systemic vasculitis improved clinically. Neither patient had signs of kidney lesions. The patient with diffuse proliferative glomerulonephritis, in whom kidney biopsy was performed before and after treatment, showed improvement of kidney function, diminution of proteinuria, and diminution of inflammatory activity within the kidney, and no signs of cyclosporin toxicity.

Adrenocortical responsiveness after discontinuous corticosteroid therapy.

Plasma cortisol levels and the response of the adrenal gland to 0.25 mg ACTH administration were measured in 12 patients receiving 15 mg or more of a short-acting steroid (fluocortolone or prednisone) on three out of four days, in 10 patients on daily steroid treatment (15 mg prednisone or more per day), and in 9 normal subjects. The basal plasma cortisol level of the first group was between that of patients on daily prednisone treatment and that of normal subjects. The adrenal function in patients on the three out of four day treatment schedule appeared to be slightly diminished, yet still within the accepted limits for adrenals capable of responding adequately to stress. The adrenal function proved insufficient in all patients on daily steroids. The three out of four day steroid regimen thus offers a solution with many advantages over continuous steroid treatment for patients refractory to the alternate-day schedule.