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Ahmad M Adel - One of the best experts on this subject based on the ideXlab platform.
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jadenu substituting exjade in iron overloaded β thalassemia major btm patients a preliminary report of the effects on the Tolerability serum ferritin level liver iron concentration and biochemical profiles
Mediterranean Journal of Hematology and Infectious Diseases, 2018Co-Authors: Mohamed A Yassin, Vincenzo De Sanctis, Ashraf T Soliman, Radwa M Hussein, Randa Alokka, Nancy Kassem, Rula Ghasoub, Ahmed Basha, Abdulqadir J Nashwan, Ahmad M AdelAbstract:Introduction Due to the chronic nature of chelation therapy and the adverse consequences of iron overload, patient adherence to therapy is an important issue. Jadenu ® is a new oral formulation of deferasirox (Exjade ®) tablets for oral suspension. While Exjade® is a dispersible tablet that must be mixed in liquid and taken on an empty stomach, Jadenu ® can be taken in a single step, with or without a light meal, simplifying administration for the treatment of patients with chronic iron overload. This may significantly improve the compliance to treatment of patients with β-thalassemia major (BMT). The aim of this study was to evaluate the Drug Tolerability and the effects of chelation therapy on serum ferritin concentration, liver iron concentration (LIC) and biochemical profiles in patients with BMT and iron overload. Patients and Methods Twelve selected adult patients BMT (mean age: 29 years; range:15-34 years) were enrolled in the study. All patients were on monthly regular red cell transfusion therapy to keep their pre-transfusional hemoglobin (Hb) level not less than 9 g/dL. They were on Exjade® therapy (30 mg/kg per day) for two years or more before starting Jadenu® therapy (14-28 mg/kg/day). The reason for shifting from Deferasirox® to Jadenu® therapy was lack of Tolerability, as described by patients, such as nausea, vomiting, diarrhea, stomach pain. Most of them also reported that Deferasirox® was not palatable. Lab investigations included monthly urine analysis and measurement of their serum concentrations of creatinine, fasting blood glucose (FBG), serum ferritin, alkaline phosphatase (ALP), alanine transferase (ALT), aspartate transferase (AST) and albumin concentrations. LIC was measured using FerriScan ®. Thyroid function, vitamin D and serum parathormone, before and one year after starting Jadenu ® therapy, were also assessed. Results Apart from some minor gastrointestinal complaints reported in 3 BMT patients that did not require discontinuation of therapy, other side effects were not registered during the treatment. Subjectively, patients reported an improvement in the palatability of Jadenu® compared to Exjade® therapy in 8 out of 12 BMT patients. A non-significant decrease in LIC measured by FerriScan® and serum ferritin levels was observed after one year of treatment with Jadenu®. A significant positive correlation was found between serum ferritin level and LIC measured by the FerriScan® method. LIC and serum ferritin level correlated significantly with ALT level (r = 0.31 and 0.45 respectively, p < 0.05). No significant correlation was detected between LIC and other biochemical or hormonal parameters. Conclusions Our study shows that short-term treatment with Jadenu ® is safe but is associated with a non-significant decrease in LIC and serum ferritin levels. Therefore, there is an urgent need for adequately-powered and high-quality trials to assess the clinical efficacy and the longterm outcomes of new deferasirox formulation.
Vincenzo De Sanctis - One of the best experts on this subject based on the ideXlab platform.
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jadenu substituting exjade in iron overloaded β thalassemia major btm patients a preliminary report of the effects on the Tolerability serum ferritin level liver iron concentration and biochemical profiles
Mediterranean Journal of Hematology and Infectious Diseases, 2018Co-Authors: Mohamed A Yassin, Vincenzo De Sanctis, Ashraf T Soliman, Radwa M Hussein, Randa Alokka, Nancy Kassem, Rula Ghasoub, Ahmed Basha, Abdulqadir J Nashwan, Ahmad M AdelAbstract:Introduction Due to the chronic nature of chelation therapy and the adverse consequences of iron overload, patient adherence to therapy is an important issue. Jadenu ® is a new oral formulation of deferasirox (Exjade ®) tablets for oral suspension. While Exjade® is a dispersible tablet that must be mixed in liquid and taken on an empty stomach, Jadenu ® can be taken in a single step, with or without a light meal, simplifying administration for the treatment of patients with chronic iron overload. This may significantly improve the compliance to treatment of patients with β-thalassemia major (BMT). The aim of this study was to evaluate the Drug Tolerability and the effects of chelation therapy on serum ferritin concentration, liver iron concentration (LIC) and biochemical profiles in patients with BMT and iron overload. Patients and Methods Twelve selected adult patients BMT (mean age: 29 years; range:15-34 years) were enrolled in the study. All patients were on monthly regular red cell transfusion therapy to keep their pre-transfusional hemoglobin (Hb) level not less than 9 g/dL. They were on Exjade® therapy (30 mg/kg per day) for two years or more before starting Jadenu® therapy (14-28 mg/kg/day). The reason for shifting from Deferasirox® to Jadenu® therapy was lack of Tolerability, as described by patients, such as nausea, vomiting, diarrhea, stomach pain. Most of them also reported that Deferasirox® was not palatable. Lab investigations included monthly urine analysis and measurement of their serum concentrations of creatinine, fasting blood glucose (FBG), serum ferritin, alkaline phosphatase (ALP), alanine transferase (ALT), aspartate transferase (AST) and albumin concentrations. LIC was measured using FerriScan ®. Thyroid function, vitamin D and serum parathormone, before and one year after starting Jadenu ® therapy, were also assessed. Results Apart from some minor gastrointestinal complaints reported in 3 BMT patients that did not require discontinuation of therapy, other side effects were not registered during the treatment. Subjectively, patients reported an improvement in the palatability of Jadenu® compared to Exjade® therapy in 8 out of 12 BMT patients. A non-significant decrease in LIC measured by FerriScan® and serum ferritin levels was observed after one year of treatment with Jadenu®. A significant positive correlation was found between serum ferritin level and LIC measured by the FerriScan® method. LIC and serum ferritin level correlated significantly with ALT level (r = 0.31 and 0.45 respectively, p < 0.05). No significant correlation was detected between LIC and other biochemical or hormonal parameters. Conclusions Our study shows that short-term treatment with Jadenu ® is safe but is associated with a non-significant decrease in LIC and serum ferritin levels. Therefore, there is an urgent need for adequately-powered and high-quality trials to assess the clinical efficacy and the longterm outcomes of new deferasirox formulation.
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JADENU® SUBSTITUTING EXJADE® IN IRON OVERLOADED Β- THALASSEMIA MAJOR (BTM) PATIENTS: A PRELIMINARY REPORT OF THE EFFECTS ON THE Tolerability, SERUM FERRITIN LEVEL, LIVER IRON CONCENTRATION AND BIOCHEMICAL PROFILES
PAGEPress Publications, 2018Co-Authors: Vincenzo De SanctisAbstract:Abstract. Introduction: Due to the chronic nature of chelation therapy and the adverse consequences of iron overload, patient adherence to therapy is an important issue. Jadenu ® is a new oral formulation of deferasirox (Exjade ®) tablets for oral suspension. While Exjade® is a dispersible tablet that must be mixed in liquid and taken on an empty stomach, Jadenu ® can be taken in a single step, with or without a light meal, simplifying administration for the treatment of patients with chronic iron overload. This may significantly improve the compliance to treatment of patients withβ-thalasemia major (BMT). The aim of this study was to evalute the Drug Tolerability and the effects of chelation therapy on serum ferritin concentration, liver iron concentration (LIC) and biochemical profiles in patients with BMT and iron overload. Patients and Methods: Twelve selected adult patients BMT (mean age: 29 years; range:15-34 years) were enrolled in the study. All patients were on monthly regular packed cell transfusion therapy to keep their pre-transfusional hemoglobin (Hb) level not less than 9 g/dL. They were on Exjade ® therapy (30 mg/kg per day) for 2 years or more before starting Jadenu ® therapy (14-28 mg/kg/day). The reason for shifting from Deferasirox ® to Jadenu ® therapy was lack of Tolerability, since most of the patients described Deferasirox ® as not palatable. Lab investigations included montly urine analysis and measurement of their serum concentrations of creatinine, fasting blood glucose (FBG), serum ferritin, alkaline phosphatase (ALP), alanine transferase (ALT), aspartate transferase (AST) and albumin concentrations. LIC was measured using FerriScan ®. Thyroid function, vitamin D and serum parathormone, before and one year after starting Jadenu ® therapy, were also assessed. Results: Apart from some minor gastrointestinal complaints reported in 3 BMT patients that did not require discontinuation of therapy, other side effects were not registered during the treatment. Subjectively, patients reported an improvement in the palatability of Jadenu® compared to Exjade ® therapy in 8 out of 12 BMT patients. A non-significant decrease in LIC and serum ferritin levels was observed after 1 year of treatment with Jadenu ® . A positive significant correlation was found between serum ferritin level and LIC measured by FerriScan ® method. LIC and serum ferritin level correlated significantly with ALT level (r = 0.31 and 0.45 respectively, p < 0.05). No significant correlation was detected between LIC and other biochemical or hormonal parameters. Conclusion: Our study shows that short-term treatment with Jadenu ® is safe but is associated with a non-significant decrease in LIC and serum ferritin levels. Therefore, there is an urgent need for adequately-powered and high-quality trials to assess the clinical efficacy and the long-term outcomes of new deferasirox formulation
Mohamed A Yassin - One of the best experts on this subject based on the ideXlab platform.
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jadenu substituting exjade in iron overloaded β thalassemia major btm patients a preliminary report of the effects on the Tolerability serum ferritin level liver iron concentration and biochemical profiles
Mediterranean Journal of Hematology and Infectious Diseases, 2018Co-Authors: Mohamed A Yassin, Vincenzo De Sanctis, Ashraf T Soliman, Radwa M Hussein, Randa Alokka, Nancy Kassem, Rula Ghasoub, Ahmed Basha, Abdulqadir J Nashwan, Ahmad M AdelAbstract:Introduction Due to the chronic nature of chelation therapy and the adverse consequences of iron overload, patient adherence to therapy is an important issue. Jadenu ® is a new oral formulation of deferasirox (Exjade ®) tablets for oral suspension. While Exjade® is a dispersible tablet that must be mixed in liquid and taken on an empty stomach, Jadenu ® can be taken in a single step, with or without a light meal, simplifying administration for the treatment of patients with chronic iron overload. This may significantly improve the compliance to treatment of patients with β-thalassemia major (BMT). The aim of this study was to evaluate the Drug Tolerability and the effects of chelation therapy on serum ferritin concentration, liver iron concentration (LIC) and biochemical profiles in patients with BMT and iron overload. Patients and Methods Twelve selected adult patients BMT (mean age: 29 years; range:15-34 years) were enrolled in the study. All patients were on monthly regular red cell transfusion therapy to keep their pre-transfusional hemoglobin (Hb) level not less than 9 g/dL. They were on Exjade® therapy (30 mg/kg per day) for two years or more before starting Jadenu® therapy (14-28 mg/kg/day). The reason for shifting from Deferasirox® to Jadenu® therapy was lack of Tolerability, as described by patients, such as nausea, vomiting, diarrhea, stomach pain. Most of them also reported that Deferasirox® was not palatable. Lab investigations included monthly urine analysis and measurement of their serum concentrations of creatinine, fasting blood glucose (FBG), serum ferritin, alkaline phosphatase (ALP), alanine transferase (ALT), aspartate transferase (AST) and albumin concentrations. LIC was measured using FerriScan ®. Thyroid function, vitamin D and serum parathormone, before and one year after starting Jadenu ® therapy, were also assessed. Results Apart from some minor gastrointestinal complaints reported in 3 BMT patients that did not require discontinuation of therapy, other side effects were not registered during the treatment. Subjectively, patients reported an improvement in the palatability of Jadenu® compared to Exjade® therapy in 8 out of 12 BMT patients. A non-significant decrease in LIC measured by FerriScan® and serum ferritin levels was observed after one year of treatment with Jadenu®. A significant positive correlation was found between serum ferritin level and LIC measured by the FerriScan® method. LIC and serum ferritin level correlated significantly with ALT level (r = 0.31 and 0.45 respectively, p < 0.05). No significant correlation was detected between LIC and other biochemical or hormonal parameters. Conclusions Our study shows that short-term treatment with Jadenu ® is safe but is associated with a non-significant decrease in LIC and serum ferritin levels. Therefore, there is an urgent need for adequately-powered and high-quality trials to assess the clinical efficacy and the longterm outcomes of new deferasirox formulation.
Beverly M K Biller - One of the best experts on this subject based on the ideXlab platform.
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a new therapeutic approach in the medical treatment of cushing s syndrome glucocorticoid receptor blockade with mifepristone
Endocrine Practice, 2013Co-Authors: Maria Fleseriu, Coleman Gross, Mark E Molitch, David E Schteingart, Brooks T Vaughan, Beverly M K BillerAbstract:OBJECTIVE Cushing's syndrome (CS) is a serious endocrine disorder caused by prolonged exposure to high cortisol levels. Initial treatment of this condition is dependent upon the cause, but is generally surgical. For patients whose hypercortisolism is not cured by surgery, medical therapy is often required. Drugs that have typically been used for CS medical therapy act by decreasing cortisol levels. Mifepristone is a glucocorticoid receptor antagonist now available for use in patients with CS. Unlike other agents, mifepristone does not decrease cortisol levels, but directly antagonizes its effects. Our objective is to review the pharmacology and clinical use of this novel agent and to discuss detailed guidance on the management of CS patients treated with mifepristone. METHODS We review the literature regarding mifepristone use in CS and recently published clinical trial data. Detailed information related to clinical assessment of mifepristone use, potential Drug interactions, Drug initiation and dose titration, and monitoring of Drug Tolerability are provided. RESULTS Clinical trial data have shown that mifepristone improves glycemic control and blood pressure, causes weight loss and a decrease in waist circumference, lessens depression, and improves overall wellbeing. However, adverse effects include adrenal insufficiency, hypokalemia, and endometrial thickening with vaginal bleeding. These findings are supported by the earlier literature case reports. CONCLUSION This article provides a review of the pharmacology and clinical use of mifepristone in Cushing's syndrome, as well as detailed guidance on the management of patients treated with this novel agent.
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a new therapeutic approach in the medical treatment of cushing s syndrome glucocorticoid receptor blockade with mifepristone
Endocrine Practice, 2013Co-Authors: Maria Fleseriu, Coleman Gross, Mark E Molitch, David E Schteingart, Brooks T Vaughan, Beverly M K BillerAbstract:ABSTRACT Objective Cushing’s syndrome (CS) is a serious endocrine disorder caused by prolonged exposure to high cortisol levels. Initial treatment of this condition is dependent upon the cause, but is generally surgical. For patients whose hypercortisolism is not cured by surgery, medical therapy is often required. Drugs that have typically been used for CS medical therapy act by decreasing cortisol levels. Mifepristone is a glucocorticoid receptor antagonist now available for use in patients with CS. Unlike other agents, mifepristone does not decrease cortisol levels, but directly antagonizes its effects. Our objective is to review the pharmacology and clinical use of this novel agent and to discuss detailed guidance on the management of CS patients treated with mifepristone. Methods We review the literature regarding mifepris-tone use in CS and recently published clinical trial data. Detailed information related to clinical assessment of mifepristone use, potential Drug interactions, Drug initiation and dose titration, and monitoring of Drug Tolerability are provided. Results Clinical trial data have shown that mifepris-tone improves glycemic control and blood pressure, causes weight loss and a decrease in waist circumference, lessens depression, and improves overall wellbeing. However, adverse effects include adrenal insufficiency, hypokalemia, and endometrial thickening with vaginal bleeding. These findings are supported by the earlier literature case reports. Conclusion This article provides a review of the pharmacology and clinical use of mifepristone in Cushing’s syndrome, as well as detailed guidance on the management of patients treated with this novel agent. (Endocr Pract. 2013;19:313-326)
Carlo Foresta - One of the best experts on this subject based on the ideXlab platform.
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sublingual administration of sildenafil oro dispersible film new profiles of Drug Tolerability and pharmacokinetics for pde5 inhibitors
Frontiers in Pharmacology, 2018Co-Authors: Luca De Toni, Maurizio De Rocco Ponce, Erica Franceschinis, Stefano Dallacqua, Roberto Padrini, Nicola Realdon, Andrea Garolla, Carlo ForestaAbstract:Objective. Type 5 phosphodiesterase inhibitors (PDE5i) are efficient Drugs used for treatment of erectile dysfunction (ED); however, a large discontinuation rate due to major side effects is reported. The aim of this study was to evaluate the possible improvement of sildenafil (Sild) pharmacokinetics associated to the sublingual administration of the new available oro-dispersible film (ODF), compared to both the oro-dispersible tablet (ODT) and the film coated tablet (FCT) as original per os formulation. Methods. In vitro disaggregation test, dissolution test and permeation test in specific devices to estimate the trans-mucosal absorption. In vivo analysis of serum Sild levels, by HPLC-MS/MS, was performed in 20 patients with psychogenic ED receiving alternatively per os FCT or sublingual ODT or ODF, at an equal dosage (50 mg). Pharmacokinetic parameters of Sild and adverse Drug reactions experienced after the dosing of each formulation were compared. Results. In vitro, ODF showed the highest time to disaggregation and an increased rate of permeation compared to both ODT and FCT (P=0,017 and P=0,008, respectively). In vivo, compared to both FCT and ODT, ODF showed a faster increase of serum Sild levels (serum levels at 15 min from dosing respectively: 2,24±1,4 ng/mL FCT, 0,5±0,3 ng/mL ODT and 13,5±9,1 ng/mL ODF; P<0,01 and P<0,05 vs ODF) together with a higher Drug bioavailability within 60 minutes from dosing (relative AUC60min vs FCT respectively: 100,0±44,9% FCT, 183,8±75,4% ODT and 304,2±156,0% ODF). A trend towards lower peak serum levels was observed for ODF. Finally, ODF showed a lower prevalence of headache compared to FCT (1% vs 35%; P<0,05) and improved pattern of flushing and nasal congestion. Conclusion. Sublingual Sild oro-dispersible film improves the Drug Tolerability through a likely modified pharmacokinetic, suggesting a possible implication also in the clinical efficacy profile. Sublingual administration of oro-dispersible formulations may represent a strategy to ameliorate the adherence to therapy with PDE5i, particularly in patients discouraged by side effects.
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Sublingual Administration of Sildenafil Oro-dispersible Film: New Profiles of Drug Tolerability and Pharmacokinetics for PDE5 Inhibitors
Frontiers Media S.A., 2018Co-Authors: Luca De Toni, Maurizio De Rocco Ponce, Erica Franceschinis, Roberto Padrini, Nicola Realdon, Andrea Garolla, Stefano Dall’acqua, Carlo ForestaAbstract:Objective: Type 5 phosphodiesterase inhibitors (PDE5i) are efficient Drugs used for treatment of erectile dysfunction (ED); however, a large discontinuation rate due to major side effects is reported. The aim of this study was to evaluate the possible improvement of sildenafil (Sild) pharmacokinetics associated to the sublingual administration of the new available oro-dispersible film (ODF), compared to both the oro-dispersible tablet (ODT) and the film-coated tablet (FCT) as original per os formulation.Methods:In vitro disaggregation test, dissolution test, and permeation test in specific devices to estimate the trans-mucosal absorption. In vivo analysis of serum Sild levels, by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), was performed in 20 patients with psychogenic ED receiving alternatively per os FCT or sublingual ODT or ODF, at an equal dosage (50 mg). Pharmacokinetic parameters of Sild and adverse Drug reactions experienced after the dosing of each formulation were compared.Results:In vitro, ODF showed the highest time to disaggregation and an increased rate of permeation compared to both ODT and FCT (P = 0.017 and P = 0.008, respectively). In vivo, compared to both FCT and ODT, ODF showed a faster increase of serum Sild levels (serum levels at 15 min from dosing, respectively: 2.24 ± 1.4 ng/ml FCT, 0.5 ± 0.3 ng/ml ODT, and 13.5 ± 9.1 ng/ml ODF; P < 0.01 and P < 0.05 vs. ODF) together with a higher Drug bioavailability within 60 min from dosing (relative AUC60min vs. FCT, respectively: 100.0 ± 44.9% FCT, 183.8 ± 75.4% ODT, and 304.2 ± 156.0% ODF). A trend toward lower peak serum levels was observed for ODF. Finally, ODF showed a lower prevalence of headache compared to FCT (1 vs. 35%; P < 0.05) and improved pattern of flushing and nasal congestion.Conclusion: Sublingual Sild ODF improves the Drug Tolerability through a likely modified pharmacokinetic, suggesting a possible implication also in the clinical efficacy profile. Sublingual administration of oro-dispersible formulations may represent a strategy to ameliorate the adherence to therapy with PDE5i, particularly in patients discouraged by side effects
