Amorolfine 0.25% cream

Onychomycosis, a fungal infection affecting the nails, accounts for approximately 50% of nail disorders and up to 30% of cutaneous fungal infections worldwide. It is mainly caused by dermatophytes ( Trichophyton rubrum ), yeasts ( Candida spp.), and non-dermatophyte fungi ( Fusarium , Aspergillus ). This condition is associated with factors such as advanced age, diabetes, immunosuppression, and prolonged exposure to moisture. Despite its high prevalence, accurate diagnosis and effective treatment remain challenging due to fungal resistance and frequent recurrence. This review evaluated the effectiveness of diagnostic methods (microscopy, culture, and PCR) and therapeutic approaches (topical antifungals, oral antifungals, and combination therapy) for onychomycosis, considering cure rates, recurrence, and adverse effects. A total of 45 studies published between 2013 and 2023 were analyzed, retrieved from PubMed, Embase, and Cochrane databases. Randomized clinical trials, systematic reviews, and cohort studies comparing treatments and diagnostic methods were included. Data were stratified by etiologic agent and severity of infection. Conventional diagnostic methods (KOH and culture) showed moderate sensitivity (50–70%), whereas molecular techniques (PCR) achieved 85–95% accuracy, albeit at higher cost. Regarding treatment, oral terbinafine demonstrated the highest efficacy against dermatophytes (70–80% cure rate), followed by itraconazole (60–70%). For Candida spp., fluconazole was superior (65% cure rate). Topical formulations (ciclopirox, amorolfine) showed limited efficacy (20–40%), except in superficial infections. Combination therapy (oral + topical + laser) increased cure rates to 85–90% and reduced recurrence. Gastrointestinal adverse effects and hepatotoxicity were reported in 5–10% of patients using oral antifungals. Onychomycosis remains a challenging infection, requiring accurate diagnosis—prioritizing PCR in recalcitrant cases—and a personalized therapeutic approach. Oral terbinafine is first-line therapy for dermatophytes, while combined therapies with topical agents or laser improve outcomes. Preventive strategies, such as proper foot drying and avoiding the sharing of nail clippers, are essential to reduce recurrence. Future studies should explore new antifungal agents and reduced-dose regimens to minimize adverse effects.

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Dermatomycosis has a significant impact on the quality of life of patients of any age in all socio-economic regions and requires therapy. Aim of the review — to compare the effectiveness of topical therapy of dermatomycosis with amorolfine, azole (clotrimazole, ketoconazole) and allylamine (terbinafine, naftifine) groups using a systematic review of randomized clinical trials and synthesis of its results based on a network meta-analysis. The review includes non-placebo-controlled randomized trials of the efficacy of amorolfine, clotrimazole, ketoconazole, terbinafine, and naftifine with a therapy duration of up to four weeks. The percentage of patients who achieved a mycological and clinical cure was chosen as the endpoint of effectiveness. The assessment of the effect size in the analysis is represented by the risk difference. The drugs in question are ranked based on surface under the cumulative ranking curve (SUCRA). The data from 7 studies involving about 769 patients with dermatomycosis were statistically analyzed. The results showed almost equivalent efficacy of amorolfine and terbinafine, superior to ketoconazole, and clotrimazole in cream formulations. Ranking the effectiveness of drugs using SUCRA revealed amorolfine as the most effective therapy among other drugs. The analysis of the study results included in the systematic review showed the advantage of amorolfine in the formulation of cream over terbinafine, ketoconazole, clotrimazole, naftifine.

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Background. Tinea pedis is a common superficial fungal skin infection. Amorolfine is one of the topical agents that have demonstrated efficacy in the treatment of mycoses. Aims. To assess and compare the efficacy of a new agent amorolfine 0.25% cream (Glenmark Pharmaceuticals Ltd., India), versus amorolfine 0.25% cream (Galderma Laboratory, France), registered in the European Union, in the treatment of tinea pedis. Methods. This open-label, randomized, multicenter, phase III study was conducted with adult patients with tinea pedis. Patients had once-daily amorolfine 0.25% cream (Glenmark Pharmaceuticals Ltd., India) or amorolfine 0.25% cream (Galderma Laboratory, France) applications to the affected skin areas for 28 days. The primary efficacy analysis was performed on the 42nd (± 4) day from the start of therapy, evaluating mycological (based on the results of a potassium hydroxide examination of skin scraping) and clinical (based on the results of symptoms and signs severity assessment) recovery. Results. In this clinical study,101 patients were randomized to the group 1 — amorolfine 0.25% cream (Glenmark Pharmaceuticals Ltd., India) and 99 patients to the group 2 — amorolfine 0.25% cream (Galderma Laboratory, France). The therapeutic equivalence of the study drugs was confirmed by the percentage of participants recovering as a result of therapy (mycological and clinical) by day 42, amounted to 95.0% in the group 1 and 97.0% in the group 2. The intergroup difference was –1.97% (90% confidence interval: –6.54; 2.60). The upper and lower limits of 90% confidence interval were within the established equivalence margin of 0.2 (р 0,0001). Among all registered adverse events, there were only 3 treatment-related associated: reaction at the site of application, erythema, and itching in group 2. There were no statistically significant differences between the groups in the incidence of adverse events. Conclusions. This study demonstrated the therapeutic equivalence of amorolfine 0.25% cream (Glenmark Pharmaceuticals Ltd., India) and amorolfine 0.25% cream (Galderma Laboratory, France). The safety profiles of the study drugs were acceptable and comparable.

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BACKGROUND: Dermatophytosis, a major cause of superficial fungal infections, requires topical and systemic antifungals. Amorolfine, a morpholine derivative, is a new topical antifungal available in cream and lotion formulations. OBJECTIVE: To evaluate the efficacy and safety of amorolfine lotion 0.25% compared to amorolfine cream 0.25% in patients with dermatophytosis. METHODS: A multi-center randomized, two-arm, active-controlled, parallel, non-inferiority phase III clinical trial involving 284 dermatophytosis patients was conducted, with the test arm using amorolfine lotion and the reference arm using amorolfine cream. The study drugs were applied once daily in the evening for four weeks and patients were followed up for another two weeks. The primary endpoint was clinical cure, while secondary endpoints included mycological cure, composite cure, global efficacy assessment, and post-treatment relapse. Safety and tolerability were assessed. RESULTS: Amongst the enrolled patients, 69.9% and 68.1% of patients had tinea corporis, while 30.1% and 31.9% had tinea cruris. The majority of patients in both groups (99.3% test and 97% reference) achieved a clinical cure at the end of treatment. Mycological cure was achieved by 98.6% and 96.3% respectively. A composite cure was achieved by 98.6% in the test arm versus 96.3% in the reference arm. A total of two AEs were reported in two (1.4%) patients in the test group and three AEs were reported in three (2.1%) patients in the reference group, all of the AEs were mild and resolved within three days without supportive medication. No severe adverse effects were reported in any of the study subjects. CONCLUSION: Amorolfine lotion 0.25% w/v showed a non-inferior clinical, mycological, and composite cure in dermatophytosis patients, was well-tolerated, and had a similar safety profile to amorolfine cream 0.25% w/w.

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OBJECTIVES: To evaluate the efficacy of topical miconazole or amorolfine compared to placebo for mild to moderately severe onychomycosis. DESIGN: Randomised, double-blind, placebo-controlled trial, with computer-generated treatment allocation at a 1:1:1 ratio. SETTING: Primary care, recruitment from February 2020 to August 2022. PARTICIPANTS: 193 patients with suspected mild to moderately severe onychomycosis were recruited via general practices and from the general public, 111 of whom met the study criteria. The mean age of participants was 51 (SD 13.1), 51% were female and onychomycosis was moderately severe (mean OSI 12.1 (SD 8.0)). INTERVENTIONS: Once-daily miconazole 20 mg/g or once-weekly amorolfine 5% nail lacquer solution was compared with placebo (denatonium benzoate solution). MAIN OUTCOME MEASURES: Complete, clinical and mycological cure at 6 months. Secondary outcomes were clinical improvement, symptom burden, quality of life, adverse effects, compliance, patient-perceived improvement and treatment acceptability. RESULTS: Based on intention-to-treat analysis, none of the participants receiving miconazole or amorolfine reached complete cure compared with two in the placebo group (OR not estimable (n.e.), p=0.493 and OR n.e., p=0.240, respectively). There was no evidence of a significant difference between groups regarding clinical cure (OR n.e., p=0.493 and OR 0.47, 95% CI 0.04 to 5.45, p=0.615) while miconazole and amorolfine were less effective than placebo at reaching both mycological cure (OR 0.25, 95% CI 0.06 to 0.98, p=0.037 and OR 0.23, 95% CI 0.06 to 0.92, p=0.029, respectively) and clinical improvement (OR 0.26, 95% CI 0.08 to 0.91, p=0.028 and OR 0.25, 95% CI 0.07 to 0.85, p=0.021, respectively). There was no evidence of a significant difference in disease burden, quality of life, adverse reactions, compliance, patient-perceived improvement or treatment acceptability. CONCLUSIONS: Topical miconazole and amorolfine were not effective in achieving a complete, clinical or mycological cure of mild to moderately severe onychomycosis, nor did they significantly alleviate the severity or symptom burden. These treatments should, therefore, not be advised as monotherapy to treat onychomycosis. TRIAL REGISTRATION NUMBER: WHO ICTRP NL8193.

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Alzheimer’s disease (AD) is the major age-related form of dementia in which dysfunctional ubiquitin-proteasome system (UPS) and autophagy represent primary mechanisms leading to accumulation of misfolded proteins, dysfunction of astroglial cells, neuroinflammation and neurodegeneration. Alterations of the endoplasmic reticulum (ER)-mitochondria contact sites (MERCS), specifically the shortening of the distance between the organelles, was proposed as a key mechanism of cell dysfunction in AD. However, its link to the impairment of the proteolytic system in AD remains unexplored. We used, as a model, hippocampal astrocytes from 3xTg-AD mice expressing either control plasmid or synthetic linkers stabilizing ER-mitochondrial interaction at 10 nm (10 nm-EML) or at 20 nm (20 nm-EML). Alternatively, astrocytes were treated with mitochondrial Ca2+ uptake inhibitor benzethonium chloride or activator amorolfine. We used Western blot to assess protein expression and specific enzymatic activity tests for the analysis of proteasomal, autophagic and lysosomal activities. Single cell fluorescent Ca2+ imaging, using 4mtD3cpv probe targeted to the mitochondrial matrix, was used to assess mitochondrial Ca2+ uptake. Stabilization of MERCS at 20 nm (20 nm-MERCS), which promotes mitochondrial Ca2+ uptake, rescued protein ubiquitination, UPS composition and activity. Immunoproteasome components β2i and β5i, upregulated in AD astrocytes, and INFγ, a master-regulator of UPS remodelling in inflammatory conditions, were also rescued. Autophagic markers beclin 1, LC3II and p62, and lysosome-related marker cathepsin B, all upregulated in AD astrocytes, were significantly reduced, while autophagic flux was rescued, by stabilizing 20 nm-MERCS. Furthermore, stabilization of 20 nm-MERCS fully rescued previously reported deficit of mitochondrial Ca2+ uptake. Strikingly, application of a mitochondrial Ca2+ uptake positive modulator, amorolfine, partially rescued pathological remodelling of UPS and autophagy, suggesting that both mitochondrial Ca2+-related and Ca2+-unrelated mechanisms play a role in the beneficial effect of 20 nm-MERCS stabilization on protein dyshomeostasis. Our results suggest that disruption of ER-mitochondrial interaction is a key factor for AD-related dysregulation of protein degradation and provide a proof that stabilization of MERCS at a defined distance and/or pharmacological rescue of mitochondrial Ca2+ uptake represent valuable strategies for the development of future anti-AD therapy.

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BACKGROUND: Onychomycoses are difficult-to-treat fungal infections with high relapse rates. Combining oral and topical antifungal drugs is associated with higher success rates. Additive or synergistic modes of action are expected to enhance treatment success rates. OBJECTIVES: Investigation of the combined effects of antifungal drugs in vitro with different modes of action and application on clinical isolates from mycotic nails. METHODS: Isolates of Trichophyton rubrum, Trichophyton interdigitale and Scopulariopsis brevicaulis were collected from infected toenail specimens of patients with onychomycosis. Susceptibility testing was performed in 96-well polystyrene plates using a standard stepwise microdilution protocol. Additive or synergistic activity at varying concentrations was investigated by the checkerboard method. RESULTS: Combining terbinafine with amorolfine tended to be more effective than terbinafine in conjunction with ciclopirox. In most combinations, additive effects were observed. Synergy was detected in combinations with involving amorolfine in S. brevicaulis. These additive and synergistic interactions indicate that combined therapy with topical amorolfine and oral terbinafine is justified. Sublimation of amorolfine (and terbinafine) may enhance the penetration in and through the nail plate, and support treatment efficacy. CONCLUSIONS: These in vitro results support the notion that combining oral terbinafine and topical amorolfine is beneficial to patients with onychomycosis, particularly if the pathogen is a non-dermatophyte fungus such as S. brevicaulis.

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