With nearly one fifth of the population experiencing depression sometime during their lives, plus the recent finding that depression rivals smoking in its association with mortality, the search for effective pharmacological treatments for depression remains urgent. However, despite this heavy disease burden upon society, the various waves of antidepressants developed in the last 40 years have shown significant side effects and little specific efficacy over placebo. One potential treatment may be via re-establishment of glutamate and GABA neurotransmitter systems that have been shown to malfunction in depressed patients. The literature describing possible causal links between GABA and/or glutamate malfunction and depression is reviewed, plus those studies which provide experimental data to confirm this hypothesis. While there is plausible support for the links between malfunction of these neurotransmitters and depression, few data exist yet regarding development of effective antidepressant medications based upon these findings.
{"title":"Malfunction in GABA and Glutamate as Pathways to Depression: A Review of the Evidence:","authors":"C. Sharpley","doi":"10.4137/CMT.S3481","DOIUrl":"https://doi.org/10.4137/CMT.S3481","url":null,"abstract":"With nearly one fifth of the population experiencing depression sometime during their lives, plus the recent finding that depression rivals smoking in its association with mortality, the search for effective pharmacological treatments for depression remains urgent. However, despite this heavy disease burden upon society, the various waves of antidepressants developed in the last 40 years have shown significant side effects and little specific efficacy over placebo. One potential treatment may be via re-establishment of glutamate and GABA neurotransmitter systems that have been shown to malfunction in depressed patients. The literature describing possible causal links between GABA and/or glutamate malfunction and depression is reviewed, plus those studies which provide experimental data to confirm this hypothesis. While there is plausible support for the links between malfunction of these neurotransmitters and depression, few data exist yet regarding development of effective antidepressant medications based upon these findings.","PeriodicalId":10428,"journal":{"name":"Clinical Medicine and Therapeutics","volume":"14 1","pages":"1511-1519"},"PeriodicalIF":0.0,"publicationDate":"2009-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75911289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Thrombocytopenia is the most common hematological abnormality in patients with chronic, advanced liver disease. In these patients, the presence of severe thrombocytopenia is an obstacle to the performance of invasive diagnostic and therapeutic procedures, and the current standard treatment for these patients is platelet transfusions, a remedy whose characteristics are far from being ideal. Furthermore, thrombocytopenia in patients with chronic hepatitis C virus infection may render the patients ineligible to antiviral treatment or may limit its efficacy because of premature discontinuation. Although the cause of thrombocytopenia in patients with chronic liver disease is likely multi-factorial, decreased thrombopoietin production by the liver undoubtedly plays a significant role. In this regard, eltrombopag, a non-peptide, orally bioavailable thrombopoietin receptor agonist has been shown to safely increase platelet count in a dose-dependent fashion in both healthy subjects and thrombocytopenic patients with chronic hepatitis C. Furthermore, in this latter group of patients, it has been shown to be superior to placebo in counteracting the myelosuppressive effect of short-term pegylated interferon treatment.
{"title":"A Review on the Use of Eltrombopag in Patients with Advanced Liver Disease","authors":"E. Giannini, A. Greco, V. Savarino","doi":"10.4137/CMT.S2267","DOIUrl":"https://doi.org/10.4137/CMT.S2267","url":null,"abstract":"Thrombocytopenia is the most common hematological abnormality in patients with chronic, advanced liver disease. In these patients, the presence of severe thrombocytopenia is an obstacle to the performance of invasive diagnostic and therapeutic procedures, and the current standard treatment for these patients is platelet transfusions, a remedy whose characteristics are far from being ideal. Furthermore, thrombocytopenia in patients with chronic hepatitis C virus infection may render the patients ineligible to antiviral treatment or may limit its efficacy because of premature discontinuation. Although the cause of thrombocytopenia in patients with chronic liver disease is likely multi-factorial, decreased thrombopoietin production by the liver undoubtedly plays a significant role. In this regard, eltrombopag, a non-peptide, orally bioavailable thrombopoietin receptor agonist has been shown to safely increase platelet count in a dose-dependent fashion in both healthy subjects and thrombocytopenic patients with chronic hepatitis C. Furthermore, in this latter group of patients, it has been shown to be superior to placebo in counteracting the myelosuppressive effect of short-term pegylated interferon treatment.","PeriodicalId":10428,"journal":{"name":"Clinical Medicine and Therapeutics","volume":"92 2 1","pages":"1489-1496"},"PeriodicalIF":0.0,"publicationDate":"2009-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80791087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pitavastatin is an HMG-CoA reductase inhibitor that significantly reduces the plasma levels of total cholesterol, LDL-C and triglycerides, while also causing modest elevation of the plasma high-density cholesterol (HDL-C) level. This statin is minimally metabolized by the cytochrome P-450 (CYP) isozymes; it is glucuronized and converted to the inactive lactone form, which is also minimally metabolized by human hepatic microsomes; therefore, it is associated with a low frequency of drug interactions. Pitavastatin has also been shown to have various pleiotropic effects on platelets, monocytes/macrophages and endothelial cells. In addition, a new effect of pitavastatin of increasing the serum for adiponectin level has been reported recently. Pitavastatin has been reported to be associated with a lower frequency of adverse drug effects such as hepatic dysfunction and rhabdomyolysis, therefore, it may be judged as one of the safer among the strong statins. Several clinical trials of pitavastatin have been conducted. At present, its evaluation in actual clinical use by clinicians around the world is underway. Pitavastatin is an effective and safe drug for patients with hypercholesterolemia.
{"title":"Pitavastatin in the Management of Hypercholesterolemia","authors":"S. Nomura","doi":"10.4137/CMT.S2690","DOIUrl":"https://doi.org/10.4137/CMT.S2690","url":null,"abstract":"Pitavastatin is an HMG-CoA reductase inhibitor that significantly reduces the plasma levels of total cholesterol, LDL-C and triglycerides, while also causing modest elevation of the plasma high-density cholesterol (HDL-C) level. This statin is minimally metabolized by the cytochrome P-450 (CYP) isozymes; it is glucuronized and converted to the inactive lactone form, which is also minimally metabolized by human hepatic microsomes; therefore, it is associated with a low frequency of drug interactions. Pitavastatin has also been shown to have various pleiotropic effects on platelets, monocytes/macrophages and endothelial cells. In addition, a new effect of pitavastatin of increasing the serum for adiponectin level has been reported recently. Pitavastatin has been reported to be associated with a lower frequency of adverse drug effects such as hepatic dysfunction and rhabdomyolysis, therefore, it may be judged as one of the safer among the strong statins. Several clinical trials of pitavastatin have been conducted. At present, its evaluation in actual clinical use by clinicians around the world is underway. Pitavastatin is an effective and safe drug for patients with hypercholesterolemia.","PeriodicalId":10428,"journal":{"name":"Clinical Medicine and Therapeutics","volume":"37 1","pages":"1477-1488"},"PeriodicalIF":0.0,"publicationDate":"2009-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83856488","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anemia resulting from a relative deficiency of erythropoietin commonly complicates chronic kidney disease (CKD). With the introduction of recombinant erythropoietin two decades ago, there has been a dramatic reduction in the need for blood transfusions in CKD patients. Epoetin alpha is a first generation erythropoiesis stimulating agent (ESA) that needs to be administered frequently because of its short half-life. Methoxy ethylene glycol-epoetin beta is a longer acting ESA that acts as a continuous erythropoietin receptor activator and is given once every 2 to 4 weeks. In short term clinical studies, Methoxy polyethylene glycol-epoetin beta has been observed to be comparable with other ESAs with regard to safety and efficacy in maintaining hemoglobin levels in the target range. However, hemoglobin is no longer a clinically valid surrogate for safety i.e. correction of anemia does not translate into better clinical outcome. Long term studies evaluating hard end-points such as death and cardiovascular events are lacking. Methoxy polyethylene glycol-epoetin beta has been approved for use in the European Union since 2007 while its use in the United States is prohibited on legal grounds.
{"title":"Treatment of Anemia Associated with chronic Kidney Disease with Methoxy polyethylene Glycol- epoetin Beta","authors":"T. Patel, Ajay K. Singh","doi":"10.4137/CMT.S3339","DOIUrl":"https://doi.org/10.4137/CMT.S3339","url":null,"abstract":"Anemia resulting from a relative deficiency of erythropoietin commonly complicates chronic kidney disease (CKD). With the introduction of recombinant erythropoietin two decades ago, there has been a dramatic reduction in the need for blood transfusions in CKD patients. Epoetin alpha is a first generation erythropoiesis stimulating agent (ESA) that needs to be administered frequently because of its short half-life. Methoxy ethylene glycol-epoetin beta is a longer acting ESA that acts as a continuous erythropoietin receptor activator and is given once every 2 to 4 weeks. In short term clinical studies, Methoxy polyethylene glycol-epoetin beta has been observed to be comparable with other ESAs with regard to safety and efficacy in maintaining hemoglobin levels in the target range. However, hemoglobin is no longer a clinically valid surrogate for safety i.e. correction of anemia does not translate into better clinical outcome. Long term studies evaluating hard end-points such as death and cardiovascular events are lacking. Methoxy polyethylene glycol-epoetin beta has been approved for use in the European Union since 2007 while its use in the United States is prohibited on legal grounds.","PeriodicalId":10428,"journal":{"name":"Clinical Medicine and Therapeutics","volume":"65 1","pages":"1457-1463"},"PeriodicalIF":0.0,"publicationDate":"2009-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89701967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
It has been clarified in patients with CKD stage 3–4, cinacalcet can reduce PTH levels without severe adverse events, however calcium levels significantly decrease and phosphorus levels increase. Increase of serum phosphorus level by cinacalcet in patients with CKD stage 3–4 is a problematic issue. Undesirable decreases in serum calcium and increases in serum phosphorus caused by cinacalcet require further investigation. For patients with CKD stage 3–4 who suffer from severely advanced 2HPT which cannot be controlled by the usual medical treatment or PTx, cinacalcet can be a useful medication for managing 2HPT.
{"title":"Cinacalcet HCl Treatment in Patients with Chronic Kidney Disease Stage 3–4","authors":"Y. Tominaga","doi":"10.4137/CMT.S3211","DOIUrl":"https://doi.org/10.4137/CMT.S3211","url":null,"abstract":"It has been clarified in patients with CKD stage 3–4, cinacalcet can reduce PTH levels without severe adverse events, however calcium levels significantly decrease and phosphorus levels increase. Increase of serum phosphorus level by cinacalcet in patients with CKD stage 3–4 is a problematic issue. Undesirable decreases in serum calcium and increases in serum phosphorus caused by cinacalcet require further investigation. For patients with CKD stage 3–4 who suffer from severely advanced 2HPT which cannot be controlled by the usual medical treatment or PTx, cinacalcet can be a useful medication for managing 2HPT.","PeriodicalId":10428,"journal":{"name":"Clinical Medicine and Therapeutics","volume":"10 1","pages":"1465-1466"},"PeriodicalIF":0.0,"publicationDate":"2009-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80784099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ciclesonide is a novel inhaled corticosteroid (ICSs) approved in most countries for the management of persistent asthma. Although inhaled corticosteroids are first-line therapy in the treatment of asthma, long term use and high-doses of these products may result in significant side effects. When developing a new ICSs, the goal is to identify a drug with comparable (or superior) efficacy to active comparators, and an improved safety profile. Ciclesonide is a prodrug which is administered through a hydrofluoroalkane- propellant metered dose inhaler (HFA-MDI). Once it reaches the lungs, the parent compound is metabolized by esterases to des- isobutyryl ciclesonide (des-CIC), an active metabolite with a 100-fold greater affinity for the glucocorticoid receptor. Ciclesonide has a unique pharmacokinetic-pharmacodynamic profile which confers an improved therapeutic ratio. Several clinical trials have shown that its efficacy is superior to placebo and similar to several active comparators. However, its high pulmonary deposition and on-site activation minimizes the risk for local side effects. Also, its low oral bioavailability, high hepatic clearance, and extensive plasma protein binding, among other factors, decrease the risk for systemic side effects. Doses of ciclesonide as high as 1280 µg/day (ex-actuator) result in minimal hypothalamic-pituitary-adrenal (HPA) axis suppression, a measure commonly used to assess systemic bioavailability for an ICSs. This review will provide a summary of ciclesonide’s role in the management of asthma, including a discussion of relevant clinical trials designed to evaluate its efficacy and safety.
{"title":"ciclesonide in the Management of Asthma","authors":"D. Gonzalez, H. Derendorf","doi":"10.4137/CMT.S2133","DOIUrl":"https://doi.org/10.4137/CMT.S2133","url":null,"abstract":"Ciclesonide is a novel inhaled corticosteroid (ICSs) approved in most countries for the management of persistent asthma. Although inhaled corticosteroids are first-line therapy in the treatment of asthma, long term use and high-doses of these products may result in significant side effects. When developing a new ICSs, the goal is to identify a drug with comparable (or superior) efficacy to active comparators, and an improved safety profile. Ciclesonide is a prodrug which is administered through a hydrofluoroalkane- propellant metered dose inhaler (HFA-MDI). Once it reaches the lungs, the parent compound is metabolized by esterases to des- isobutyryl ciclesonide (des-CIC), an active metabolite with a 100-fold greater affinity for the glucocorticoid receptor. Ciclesonide has a unique pharmacokinetic-pharmacodynamic profile which confers an improved therapeutic ratio. Several clinical trials have shown that its efficacy is superior to placebo and similar to several active comparators. However, its high pulmonary deposition and on-site activation minimizes the risk for local side effects. Also, its low oral bioavailability, high hepatic clearance, and extensive plasma protein binding, among other factors, decrease the risk for systemic side effects. Doses of ciclesonide as high as 1280 µg/day (ex-actuator) result in minimal hypothalamic-pituitary-adrenal (HPA) axis suppression, a measure commonly used to assess systemic bioavailability for an ICSs. This review will provide a summary of ciclesonide’s role in the management of asthma, including a discussion of relevant clinical trials designed to evaluate its efficacy and safety.","PeriodicalId":10428,"journal":{"name":"Clinical Medicine and Therapeutics","volume":"42 1","pages":"1437-1449"},"PeriodicalIF":0.0,"publicationDate":"2009-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89904469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Paget’s disease of bone (PDB) is a condition characterized by excessive and abnormal bone remodelling. Due to a high rate of bone remodelling, bisphosphonates, and especially pamidronate and the newer zolendronate, are indicated in the treatment of PDB. The presence of asymptomatic, but active PDB represents an indication for treatment aimed at preventing later complications. An additional indication for treatment is the involvement of skeletal segments that may give rise to severe complications. Pamidronate has a long history in the treatment of PDB. The more utilised regimen is 3 to 6 i.v. infusion of 60 mg of pamidronate at an infusion rate of 1 mg/min within 3–21 days. Zolendronate (5 mg once yearly) is the most powerful amino-bisphosphonate currently used. This primacy recognizes both the ability to inhibit the farnesyl-pyrophosphate synthetase and the higher affinity to hydroxyapatite crystals as a cause. Both pamidronate and zolendronate are effective in PDB, with an evidence-based superiority of the latter.
{"title":"Pamidronate and Zoledronic Acid in the Treatment of Paget’s Disease of Bone","authors":"M. Colina, G. Ciancìo, F. Trotta","doi":"10.4137/CMT.S3310","DOIUrl":"https://doi.org/10.4137/CMT.S3310","url":null,"abstract":"Paget’s disease of bone (PDB) is a condition characterized by excessive and abnormal bone remodelling. Due to a high rate of bone remodelling, bisphosphonates, and especially pamidronate and the newer zolendronate, are indicated in the treatment of PDB. The presence of asymptomatic, but active PDB represents an indication for treatment aimed at preventing later complications. An additional indication for treatment is the involvement of skeletal segments that may give rise to severe complications. Pamidronate has a long history in the treatment of PDB. The more utilised regimen is 3 to 6 i.v. infusion of 60 mg of pamidronate at an infusion rate of 1 mg/min within 3–21 days. Zolendronate (5 mg once yearly) is the most powerful amino-bisphosphonate currently used. This primacy recognizes both the ability to inhibit the farnesyl-pyrophosphate synthetase and the higher affinity to hydroxyapatite crystals as a cause. Both pamidronate and zolendronate are effective in PDB, with an evidence-based superiority of the latter.","PeriodicalId":10428,"journal":{"name":"Clinical Medicine and Therapeutics","volume":"30 1","pages":"1451-1456"},"PeriodicalIF":0.0,"publicationDate":"2009-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77664518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J. Reginster, M. Hiligsmann, V. Rabenda, B. Zegels, A. Neuprez, O. Bruyère
Oral daily and weekly bisphosphonates were considered, for several years, as the mainstay for the treatment of postmenopausal osteoporosis. However, the inconvenience of frequent dosing is known to negatively affect adherence to therapy in the long-term, hence outcomes. This has prompted the development of convenient oral bisphosphonate regimens that feature simple, less frequent dosing schedules. Ibandronate is a potent, nitrogen-containing bisphosphonate which, uniquely, can be administered either orally, monthly, or as an intravenous injection, every 3 months. A positive impact for adherence has been observed with a reduction in the bisphosphonate dosing frequency. Anti-fracture efficacy of the various currently available regimens of ibandronate is documented in randomized controlled clinical trials, non-inferiority studies, meta-analyses and real-life settings studies. The present paper summarizes the pharmacology, efficacy and tolerability of oral and intravenous ibandronate, when administered with extended dosing intervals, in postmenopausal osteoporosis.
{"title":"Ibandronate in the Management of Postmenopausal Osteoporosis","authors":"J. Reginster, M. Hiligsmann, V. Rabenda, B. Zegels, A. Neuprez, O. Bruyère","doi":"10.4137/CMT.S2354","DOIUrl":"https://doi.org/10.4137/CMT.S2354","url":null,"abstract":"Oral daily and weekly bisphosphonates were considered, for several years, as the mainstay for the treatment of postmenopausal osteoporosis. However, the inconvenience of frequent dosing is known to negatively affect adherence to therapy in the long-term, hence outcomes. This has prompted the development of convenient oral bisphosphonate regimens that feature simple, less frequent dosing schedules. Ibandronate is a potent, nitrogen-containing bisphosphonate which, uniquely, can be administered either orally, monthly, or as an intravenous injection, every 3 months. A positive impact for adherence has been observed with a reduction in the bisphosphonate dosing frequency. Anti-fracture efficacy of the various currently available regimens of ibandronate is documented in randomized controlled clinical trials, non-inferiority studies, meta-analyses and real-life settings studies. The present paper summarizes the pharmacology, efficacy and tolerability of oral and intravenous ibandronate, when administered with extended dosing intervals, in postmenopausal osteoporosis.","PeriodicalId":10428,"journal":{"name":"Clinical Medicine and Therapeutics","volume":"2005 1","pages":"1409-1421"},"PeriodicalIF":0.0,"publicationDate":"2009-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88350668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MMXTM mesalazine is a novel delayed release mesalazine formulation with a high-strength 1.2 g tablet for the treatment of active mild to moderate colitis and maintenance of remission. In vitro and in vivo studies show initiation of drug release in the terminal ileum and caecum with gradual release of 5-ASA as the tablet passes through the colon. Pharmacokinetic data are comparable to other 5-ASA formulations with low systemic absorption and high levels in feces and in mucosal biopsies in the left colon. Clinical trials have shown high rates of clinical and endoscopic remission in active mild to moderate colitis over 8 weeks with a 2.4 g once daily dose. There do not appear to be higher remission rates with the 4.8 g dose. Prolongation of treatment with a further 8 weeks of 2.4 g twice daily can induce remission in those failing the initial 8 weeks of therapy. A maintenance study enrolling patients who achieved remission in the acute studies showed high rates of remission maintained at one year with 1.2 g twice daily (68.5%) and 2.4 g once daily (64.4%) using the strict definition of remission (including mucosal healing) that was used in the active treatment trials. The drug is safe and effective in colitis. The high tablet strength, and once-daily dosage make this formulation a welcome addition to therapy options for patients with colitis.
{"title":"A Review of Multimatrix System (MMX) Mesalazine in the Management of Ulcerative Colitis","authors":"A. Hawthorne","doi":"10.4137/CMT.S38","DOIUrl":"https://doi.org/10.4137/CMT.S38","url":null,"abstract":"MMXTM mesalazine is a novel delayed release mesalazine formulation with a high-strength 1.2 g tablet for the treatment of active mild to moderate colitis and maintenance of remission. In vitro and in vivo studies show initiation of drug release in the terminal ileum and caecum with gradual release of 5-ASA as the tablet passes through the colon. Pharmacokinetic data are comparable to other 5-ASA formulations with low systemic absorption and high levels in feces and in mucosal biopsies in the left colon. Clinical trials have shown high rates of clinical and endoscopic remission in active mild to moderate colitis over 8 weeks with a 2.4 g once daily dose. There do not appear to be higher remission rates with the 4.8 g dose. Prolongation of treatment with a further 8 weeks of 2.4 g twice daily can induce remission in those failing the initial 8 weeks of therapy. A maintenance study enrolling patients who achieved remission in the acute studies showed high rates of remission maintained at one year with 1.2 g twice daily (68.5%) and 2.4 g once daily (64.4%) using the strict definition of remission (including mucosal healing) that was used in the active treatment trials. The drug is safe and effective in colitis. The high tablet strength, and once-daily dosage make this formulation a welcome addition to therapy options for patients with colitis.","PeriodicalId":10428,"journal":{"name":"Clinical Medicine and Therapeutics","volume":"207 1","pages":"1423-1436"},"PeriodicalIF":0.0,"publicationDate":"2009-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74468381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Invasive fungal infections (IFIs) cause significant morbidity, mortality, and increased cost of care in patients with hematological malignancies, prolonged (i.e. >7–10 days) treatment induced neutropenia, and other disease states causing underlying immunosuppression. One strategy often used to combat the development of invasive infections is the use of antifungal agents as prophylaxis in at risk patients. Posaconazole is an oral triazole with a useful spectrum of activity against many fungal pathogens of concern in patients at risk for the development of IFIs. Posaconazole is only available in oral formulation and therapeutic drug monitoring may provide value due to variable absorption and serum concentrations. Clinical efficacy and pharmacoeconomic data have demonstrated the utility of posaconazole in the treatment of oropharyngeal candidiasis and for prophylaxis in patients at risk for development of IFIs. Several organizations or expert groups involved in developing guidelines for the management of IFIs recommend posaconazole anti-fungal prophylaxis in patients with AML or MDS and chemotherapy induced neutropenia or significant GVHD. In addition, nonrandomized studies (largely of salvage therapy) and case series suggest that posaconazole may be effective as treatment for invasive aspergillosis, zygomycosis, and coccidiomycosis. Further, small case series or individual case reports suggest activity against other less commonly encountered filamentous fungi and Histoplasma.
{"title":"Prophylaxis of Invasive Fungal Infections: A Review of the Use of Posaconazole","authors":"C. Collins, Jeannina A Smith, D. Kaul","doi":"10.4137/CMT.S1948","DOIUrl":"https://doi.org/10.4137/CMT.S1948","url":null,"abstract":"Invasive fungal infections (IFIs) cause significant morbidity, mortality, and increased cost of care in patients with hematological malignancies, prolonged (i.e. >7–10 days) treatment induced neutropenia, and other disease states causing underlying immunosuppression. One strategy often used to combat the development of invasive infections is the use of antifungal agents as prophylaxis in at risk patients. Posaconazole is an oral triazole with a useful spectrum of activity against many fungal pathogens of concern in patients at risk for the development of IFIs. Posaconazole is only available in oral formulation and therapeutic drug monitoring may provide value due to variable absorption and serum concentrations. Clinical efficacy and pharmacoeconomic data have demonstrated the utility of posaconazole in the treatment of oropharyngeal candidiasis and for prophylaxis in patients at risk for development of IFIs. Several organizations or expert groups involved in developing guidelines for the management of IFIs recommend posaconazole anti-fungal prophylaxis in patients with AML or MDS and chemotherapy induced neutropenia or significant GVHD. In addition, nonrandomized studies (largely of salvage therapy) and case series suggest that posaconazole may be effective as treatment for invasive aspergillosis, zygomycosis, and coccidiomycosis. Further, small case series or individual case reports suggest activity against other less commonly encountered filamentous fungi and Histoplasma.","PeriodicalId":10428,"journal":{"name":"Clinical Medicine and Therapeutics","volume":"48 1","pages":"1399-1408"},"PeriodicalIF":0.0,"publicationDate":"2009-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83381102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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