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Tolerability Profile (tolerability + profile)
Kinds of Tolerability Profile Selected AbstractsVildagliptin plus metformin combination therapy provides superior glycaemic control to individual monotherapy in treatment-naive patients with type 2 diabetes mellitusDIABETES OBESITY & METABOLISM, Issue 5 2009E. Bosi Aim:, To compare the efficacy and safety of vildagliptin and metformin initial combination therapy with individual monotherapies in treatment-naive patients with type 2 diabetes mellitus (T2DM). Methods:, This was a 24-week, randomized, double-blind, active-controlled study. Treatment-naive patients with T2DM who had a glycated haemoglobin (HbA1c) of 7.5,11% (N = 1179) were randomized equally to receive vildagliptin plus high-dose metformin combination therapy (50 mg + 1000 mg twice daily), vildagliptin plus low-dose metformin combination therapy (50 mg + 500 mg twice daily), vildagliptin monotherapy (50 mg twice daily) or high-dose metformin monotherapy (1000 mg twice daily). The primary objective was to demonstrate that HbA1c reduction from baseline with either combination therapy is superior to both monotherapies at the week 24 endpoint. Patients who failed glycaemic-screening criteria [HbA1c >11% or fasting plasma glucose (FPG) >15 mmol/l (270 mg/dl)] could enter a 24-week, single-arm substudy. These patients (N = 94) received open-label vildagliptin plus high-dose metformin combination therapy (100 mg + 1000 mg twice daily). Results:, From comparable baseline values (8.6,8.7%), HbA1c decreased in all four treatment groups, to the greatest extent with vildagliptin plus high-dose metformin combination therapy. Mean (SE) HbA1c change from baseline was ,1.8% (0.06%), ,1.6% (0.06%), ,1.1% (0.06%) and ,1.4% (0.06%) with vildagliptin plus high-dose metformin combination therapy, vildagliptin plus low-dose metformin combination therapy, and vildagliptin and metformin monotherapies respectively. The between-group difference was superior with vildagliptin plus high-dose metformin combination therapy (p < 0.001 vs. both monotherapies) and vildagliptin plus low-dose metformin combination therapy (p < 0.001 and p = 0.004, vs. vildagliptin and metformin monotherapies, respectively). Higher baseline HbA1c values were linked to greater HbA1c reductions, with changes of ,3.2% (0.22%), ,2.7% (0.22%), ,1.5% (0.24%) and ,2.6% (0.26%) respectively, occurring in patients with baseline HbA1c,10%. Reductions in FPG were superior with vildagliptin plus high-dose metformin combination therapy [change from baseline ,2.63 (0.13) mmol/l] compared with both monotherapies [,1.26 (0.13) mmol/l and ,1.92 (0.13) mmol/l, respectively; p < 0.001]. There was no incidence of hypoglycaemia or severe hypoglycaemia with either combination therapy, and neither was associated with weight gain. All treatments were well tolerated and displayed a comparable incidence of adverse events overall. Despite superior HbA1c lowering, the vildagliptin plus low-dose metformin combination therapy group demonstrated a favourable gastrointestinal (GI) tolerability profile compared with metformin monotherapy. Conclusions:, In treatment-naive patients, combinations of vildagliptin and both high-dose and low-dose metformin provide superior efficacy to monotherapy treatments with a comparable overall tolerability profile and low risk of hypoglycaemia. The potential dose-sparing effect of adding vildagliptin to low-dose metformin in preference to the up-titration of metformin may allow patients to achieve equivalent or superior HbA1c lowering without the GI tolerability issues associated with higher doses of metformin. [source] Reflecting on Type 2 Diabetes Prevention: More Questions than Answers!DIABETES OBESITY & METABOLISM, Issue 2007J. Rosenstock Given the enormous public health and economic burden posed by the global epidemic of type 2 diabetes mellitus (T2DM), intervention in the prediabetes stage of disease to prevent progression to T2DM and its vascular complications seems the most sensible approach. Precisely how best to intervene remains the subject of much debate. Prudent lifestyle changes have been shown to significantly reduce the risk of progression in individuals with impaired fasting glucose (IFG) and impaired glucose tolerance (IGT). Although lifestyle modifications are notoriously difficult to maintain, there is evidence that intensive intervention results in continued preventive benefit after the stopping of structured counselling. A number of drug therapies, including metformin, acarbose, orlistat and rosiglitazone, have also been proven effective in preventing progression from IFG/IGT, but unresolved issues still remain. Specifically, whether large numbers of individuals with glucose dysregulation who may never progress to T2DM should be exposed to the risk of pharmacological adverse effects is a topic of discussion and debate. Furthermore, there are limited data on the effectiveness of implementing interventions during the prediabetic state to prevent cardiovascular complications that may be hyperglycaemia related. A recent American Diabetes Association (ADA) consensus statement on IFG/IGT recommends lifestyle modification for individuals with IFG or IGT. Of note, the ADA consensus statement introduces the option of adding metformin treatment to lifestyle changes in those individuals who have combined IFG/IGT plus an additional risk factor for progression and who also have some features that increase the likelihood of benefiting from metformin treatment. The dipeptidyl peptidase-4 inhibitors are a new class of oral antidiabetic agents that, in addition to being effective in improving glycaemic control, may exert beneficial effects in preserving ,-cell function. These characteristics, combined with a low risk of hypoglycaemia, weight neutrality and what appears , so far , to be a relatively benign tolerability profile, make these agents intriguing candidates for preventive treatment. [source] Melatonin therapy for headache disordersDRUG DEVELOPMENT RESEARCH, Issue 6 2007Mario F.P. Peres Abstract Even though efficacy is often the most important consideration for patient preference in migraine prevention, currently available medications do not meet patient expectation. Efficacy is in the range of 50% reduction in migraine attacks in 50% of patients studied for the best medications. Therefore, new options for migraine treatment are needed. Melatonin has been considered a good candidate for migraine and other headaches prevention due to its favorable mechanisms of action and excellent tolerability profile. In this article, we review the putative role of the pineal gland and melatonin in migraine pathophysiology and treatment. Drug Dev Res 68:329,334, 2007. © 2007 Wiley-Liss, Inc. [source] Ultimate success in epilepsy , the patient's perspectiveEUROPEAN JOURNAL OF NEUROLOGY, Issue 2005J. W. Sander Most people with epilepsy can live outwardly normal lives, but fear about impending seizures, driving restrictions, lack of independence, employment and social problems, medication-related adverse effects and the presence of cognitive or psychiatric complications are all concerns readily identified by affected individuals. While seizure control is the overriding goal of treatment, it is essential to realize the importance that patients place on other aspects of daily functioning. While many of the concerns identified by patients can only be managed by improved social support, others (e.g. neuropsychological impairment, medication-related adverse events, cognitive impairment, sleep disturbance) may be amenable to therapy (if available) or to the selection of a more appropriate antiepileptic drug. Each antiepileptic drug has a unique pharmacodynamic and tolerability profile. Awareness by the treating clinician of the pharmacological profile of each drug may help to minimize unwanted treatment-related effects and possibly improve the outcome of treatment from an epilepsy patient's perspective. Therefore, in order to achieve true treatment success, clinicians need to understand how individuals perceive their disorder and, where possible, address those factors that adversely affect patient quality of life. For the person with epilepsy, successful treatment involves beneficial effects on social, vocational and psychological function. This extends beyond seizure control to freedom from the fear associated with seizures, confidence in pharmacological therapy and improvements in health-related quality of life. [source] Divalproex Sodium Extended-Release for the Prophylaxis of Migraine Headache in Adolescents: Results of a Stand-Alone, Long-Term Open-Label Safety StudyHEADACHE, Issue 1 2009George Apostol MD Objective., The objective of this long-term open-label study in adolescents was to assess the safety and tolerability of divalproex sodium extended-release in the prophylaxis of migraine headaches. Background., Two formulations of divalproex sodium have demonstrated efficacy in the prevention of migraine headaches in adults. However, no medications are currently approved for this indication in adolescents, and long-term safety data on agents for migraine prevention are lacking for this younger population. Therefore, the current study was conducted to assess the long-term safety and tolerability of divalproex extended-release in adolescents with migraine headaches. Methods., This was a 12-month, phase 3, open-label, multicenter study of adolescents aged 12 to 17 years with migraine headaches diagnosed by International Headache Society criteria. Divalproex sodium extended-release was initiated at 500 mg/day for 15 days then increased to 1000 mg daily, with subsequent adjustments permitted within a dosing range of 250-1000 mg daily. Study visits were conducted at days 1 and 15 and months 1, 2, 3, 6, 9, and 12. Safety was evaluated by adverse event collection, laboratory assessments, physical and neurological examinations, vital signs, electrocardiograms, the Udvalg for Kliniske Undersøgelser Side Effect Rating Scale, the Wechsler Abbreviated Scale of Intelligence, and the Behavioral Assessment Scale for Children. Efficacy was evaluated by following the number of migraine headache days reported in subjects' headache diaries over sequential 4-week intervals for the duration of the trial. Results., A total of 241 subjects were enrolled and treated. The most frequently reported adverse events were nausea (19%), vomiting (18%), weight gain (12%), nasopharyngitis (11%), migraine (10%), and upper respiratory tract infection (10%). Ten (4%) subjects experienced serious adverse events, and 40 (17%) subjects discontinued because of an adverse event. Increases in ammonia levels were observed. No other clinically significant changes were observed in laboratory values, vital signs, rating scales, or electrocardiograms. Median 4-week migraine headache days decreased 75% between the first and the fourth months of the study (from 4.0 to 1.0) and remained at or below this level for the remainder of the study. Conclusions., In this long-term open-label study of adolescents with migraine, the safety and tolerability profile of divalproex sodium extended-release was consistent with findings from previous trials in adults, as well as 2 studies recently completed in adolescents. In general, divalproex sodium extended-release was well-tolerated in adolescents with migraine. [source] Fluvoxamine in obsessive-compulsive disorder: similar efficacy but superior tolerability in comparison with clomipramineHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 6 2001Emanuela Mundo Abstract Some meta-analyses have suggested that the selective serotonin reuptake inhibitors (SSRIs) are less effective than clomipramine in the treatment of obsessive-compulsive disorder (OCD). The aim of this double-blind, randomised, multicentre study was to directly compare the efficacy and safety of fluvoxamine and clomipramine in patients with OCD. A total of 227 patients were randomised to flexible doses of fluvoxamine or clomipramine (both 150,300,mg/day) for 10 weeks. Fluvoxamine and clomipramine were both clinically effective and there were no statistically significant differences between the two treatment groups, at any visit, on the National Institute of Mental Health Obsessive-Compulsive global rating scale, the Yale-Brown Obsessive-Compulsive scale (total score and obsession and compulsion subscores), the Clinical Global Impression severity of illness and global improvement subscales, the Clinical Anxiety Scale and the 17-item Hamilton Depression Rating Scale. However, there were differences in safety between the two treatments. Compared with fluvoxamine-treated patients, those treated with clomipramine had more anticholinergic side effects (dry mouth, constipation and tremor) and premature withdrawals due to adverse events (18 versus 9). The results from this controlled study indicate that fluvoxamine is as effective as clomipramine in the treatment of OCD but has a better tolerability profile. Copyright © 2001 John Wiley & Sons, Ltd. [source] Long-term efficacy and safety of ezetimibe 10 mg in patients with homozygous sitosterolemia: a 2-year, open-label extension studyINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 10 2008D. Lütjohann Summary Objective:, To assess the long-term efficacy and safety profile of ezetimibe 10 mg/day in patients with homozygous sitosterolemia. Methods:, This was an extension of a multi-centre, randomised, double-blind, placebo-controlled base study in which patients with homozygous sitosterolemia and plasma sitosterol concentrations > 5 mg/dl were randomised 4 : 1 to ezetimibe 10 mg/day (n = 30) or placebo (n = 7) for 8 weeks. Patients who successfully completed the base study with > 80% compliance to study medication were eligible to enter two, successive, 1-year extension studies in which ezetimibe 10 mg/day was administered in an open-label manner. Patients remained on their current treatment regimen (e.g. bile salt-binding resins, statins and low-sterol diet) during the base and extension studies. Patients had to be off ezetimibe therapy for , 4 weeks prior to entering the first extension. Efficacy and safety/tolerability parameters were evaluated every 12 and 26 weeks in the first and second years respectively. The primary efficacy end-point was mean percentage change in plasma sitosterol from baseline to study end for the cohort of patients (n = 21) who successfully completed the second extension study. Results:, Treatment with ezetimibe 10 mg/day led to significant mean percentage reductions from baseline in plasma concentrations of sitosterol (,43.9%; p < 0.001), campesterol (,50.8%; p < 0.001), low-density lipoprotein (LDL) sterols (,13.1%; p < 0.050), total sterols (,10.3%; p < 0.050) and apolipoprotein (apo) B (,10.1%; p < 0.050). No significant changes from baseline were observed for lathosterol, high-density lipoprotein sterol, triglycerides or apo A-1. Maximal reductions in sitosterol and campesterol occurred within the first 52 weeks of treatment and were sustained for the duration of the study. For LDL sterol, total sterols and apo B, maximal reductions were achieved early (by weeks 4 or 16) and waned slightly through the remainder of the study. Overall ezetimibe 10 mg was well tolerated. Conclusion:, In patients with homozygous sitoserolemia, long-term treatment with ezetimibe 10 mg/day for 2 years was effective in reducing plasma plant sterol concentrations with an overall favourable safety and tolerability profile. [source] Current safety and tolerability issues in men with erectile dysfunction receiving PDE5 inhibitorsINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 9 2007W. J. G. Hellstrom Summary Aims:, Treatment of erectile dysfunction (ED) has been greatly advanced by the advent of phosphodiesterase type-5 (PDE5) inhibitors. Upon the introduction of these agents, their cardiovascular (CV) safety was a major concern, mainly due to their vasodilatory effects. We conducted an electronic literature review of data concerning the safety and tolerability issues of men with ED receiving PDE5 inhibitors. Results:, Although safety concerns have been raised, evaluation of CV safety and related adverse events in clinical trials has not revealed any atypical safety issues. Discussion:, No causal association has been established to date between non-arteritic anterior ischaemic optic neuropathy (NAION) and PDE5 inhibitors. In addition, there are established guidelines which provide recommendations for the safe and effective use of these agents in treating men with ED and associated comorbidities. Conclusions:, Clinical trial and postmarketing surveillance data confirm the safety and tolerability profile of the PDE5 inhibitors, even in patients with endothelial dysfunction-associated comorbidities. [source] Clinical efficacy and safety of oral terbinafine in fungal mycetomaINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 2 2006Bassirou N'Diaye MD Objectives, An open-label study was performed to assess the efficacy and safety of terbinafine in the treatment of eumycetoma. Methods, Single-center, open-label study, including 27 patients with signs and symptoms of eumycetoma which had developed within 5 years and was confirmed by mycological examination. The intention-to-treat population (n = 23) received 500 mg of terbinafine bid for 24,48 weeks. Efficacy evaluations included clinical signs and symptoms (e.g. sinuses open or closed, degree of tumefaction, and emission of grains either present or absent); mycological examinations from Week 24 onwards; and investigators' overall assessment of efficacy (cure, improved since baseline, unchanged since baseline, or deterioration since baseline). Safety evaluations included monitoring of adverse events, laboratory assessments, vital signs and physical examinations. Results, Good clinical improvement was seen in patients who completed the study (n = 20). Tumefaction was absent or improved in 80% of patients; sinuses were closed in 50% of patients, and grain emissions were absent in 65% of patients. Of the 16 patients who had repeat mycological assessment, four (25%) were mycologically cured. In the investigators' overall opinion at the end of the study, five (25%) were cured and 11 (55%) were clinically improved. The majority of adverse events reported were mild to moderate, and consistent with the known tolerability profile of terbinafine. Conclusion, High-dose terbinafine (1000 mg/day) is well tolerated and clinically effective in patients with eumycetoma, a difficult-to-treat subcutaneous mycoses. [source] Continuation and long-term maintenance treatment with Hypericum extract WS® 5570 after successful acute treatment of mild to moderate depression , rationale and study designINTERNATIONAL JOURNAL OF METHODS IN PSYCHIATRIC RESEARCH, Issue 3 2004Chairman, S. Kasper Professor Abstract Unipolar major depression is often a chronic disease that may require lifelong prophylaxis. Recovery from an acute episode is followed by 4-6 months of relapse prevention. After that, long-term maintenance treatment is administered to avoid recurrence. We present the rationale and design of an ongoing double-blind, randomized, placebo-controlled trial investigating the efficacy of Hypericum extract WS® 5570 in relapse prevention in recurrent unipolar depression. An estimated sample of 425 adults with recurrent, mild to moderate major depression (ICD-10 and DSM-IV criteria), ,3 previous episodes (last 5 years) and a total score ,20 points on the 17-item Hamilton Rating Scale for Depression (HAMD) will be included. After a one-week wash out patients receive 3 × 300 mg/day WS® 5570 single-blind for 6 weeks. Responders are randomized to 26 weeks of double-blind continuation treatment with 3 × 300 mg/day WS® 5570 or placebo. Patients completing continuation treatment without relapse enter 52 weeks of double-blind maintenance treatment, where those treated with WS® 5570 are re-randomized to 3 × 300 mg/day WS® 5570 or placebo. The primary outcome measure is the time to relapse during continuation treatment (HAMD ,16, clinical diagnosis of depression, or premature treatment termination for inefficacy). Hypericum extract, with its favourable tolerability profile, could be an interesting option for long-term prophylaxis. The trial was designed according to current consensus and guidance. Notably, it includes long-term prophylactic treatment with the same drug and the same therapeutic dose applied during acute treatment, uses well-defined outcome measures and provides a clear distinction between relapse and recurrence. Copyright © 2004 Whurr Publishers Ltd. [source] Itraconazole oral solution and intravenous formulations: a review of pharmacokinetics and pharmacodynamicsJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 3 2001L. Willems Itraconazole is a triazole antifungal agent with a broad spectrum of activity. It is well tolerated and highly efficacious, particularly because its main metabolite, hydroxy-itraconazole, also has considerable antifungal activity. Two new formulations of itraconazole, an oral solution and an intravenous formulation, have recently been developed, which combine lipophilic itraconazole with cyclodextrin. These formulations have improved the solubility of itraconazole, leading to enhanced absorption and bioavailability compared with the original capsule formulation, without having an impact on the tolerability profile of itraconazole. The oral solution and intravenous formulations of itraconazole produce consistent plasma concentrations and are ideal for the treatment of systemic fungal infections in a wide range of patient populations. The additional flexibility offered by the different routes of administration means that itraconazole treatment can be specifically tailored for use in all patients, including children and those requiring intensive care. [source] A Double-Blind, Placebo-Controlled Study With Quetiapine as Adjunct Therapy With Lithium or Divalproex in Bipolar I Patients With Coexisting Alcohol DependenceALCOHOLISM, Issue 10 2010Mary Stedman Background:, This study evaluated the efficacy of quetiapine versus placebo as an adjunct to lithium or divalproex in reducing alcohol consumption in patients with bipolar I disorder and coexisting alcohol dependence. Methods:, Male and female outpatients (21 to 60 years) with a history of bipolar I disorder and alcohol dependence were included in this 12-week, placebo-controlled study. Patients treated with lithium or divalproex (ongoing or assigned at screening) were randomized to receive quetiapine (dosed up to 400 mg/d over 7 days, followed by 300 to 800 mg/d flexible dosing until study end) or placebo. The primary outcome measure was the change in the proportion of heavy drinking days from baseline to Week 12 (as derived from the Timeline Followback method). Secondary outcome measures included time to the first consecutive 2 weeks of abstinence, changes from baseline to Week 12 in the proportion of nondrinking days, mean number of standardized drinks per day, and Clinical Global Impressions-Severity of Illness score. Results:, Of 362 enrolled patients (mean 38.6 years), 176 were randomized to receive quetiapine and 186 to placebo. The mean proportion of heavy drinking days at baseline was 0.66 in the quetiapine group and 0.67 in the placebo group. At Week 12, the mean change in the proportion of heavy drinking days was ,0.36 with quetiapine and ,0.36 with placebo (p = 0.93). No statistically significant differences in any of the secondary outcome measures were noted between the quetiapine and placebo groups. The incidence of adverse events was consistent with the previously known tolerability profile of quetiapine. Conclusions:, The efficacy of quetiapine in the treatment of bipolar disorder is already well established. In this study, however, quetiapine added to lithium or divalproex did not result in significantly greater improvement compared with placebo in measures of alcohol use and dependence in patients with bipolar I disorder and alcohol dependence. [source] Improved efficacy and tolerability of retinoic acid in acne vulgaris: a new topical formulation with cyclodextrin complex ,JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 4 2004RY Anadolu ABSTRACT Objectives, Retinoic acid (RA) has long been used, both topically and systemically, for disorders of keratinization, acne and related disorders. In the present study, the efficacy and tolerability of topical RA prepared as a cyclodextrin beta complex (,-CD) is investigated in 66 acne vulgaris patients. Methods, This randomized, double-blind, placebo-controlled study compares nightly topical application of RA/,-CD complex hydrogel formulation (0.025%), RA/,-CD complex in moisturizing base (0.025%), hydrogel base, moisturizer base or a commercial RA gel (0.05%) in acne vulgaris patients. Improvement of acne was assessed using a 5-point improvement scale and by measuring sebum and moisture content of the skin using an SM 810 sebumeter/corneometer. Results, After 3 months of treatment, mean scores of acne improvement on the 5-point scale were 4 with the RA/,-CD complex hydrogel formulation, 4.1 with the RA/,-CD complex in moisturizing base, 1.2 with hydrogel placebo base, 1.1 with moisturizer placebo base and 3 with the commercial RA product. All patients treated with the commercial product experienced local side-effects. One patient discontinued due to severe irritation. None of the patients treated with the RA/,-CD complex in the moisturizing base and hydrogel formulation experienced significant local irritation, although the sebum content of the skin decreased after application of the RA/,-CD preparations. This change was not significant compared to controls. The moisture content of the skin was better preserved in the group treated with the RA/,-CD complex in the moisturizing base. Conclusion, The topical RA/,-CD complex, in hydrogel and moisturizing base, was more effective than the twice concentrated commercial RA product. There were few topical side-effects with this new formulation, which increases patient compliance. Topical RA/,-CD (0.025% RA) did not significantly reduce sebum secretion but may help to preserve optimum epidermal moisture content with the proper base formulation. This is the first study in the literature reporting efficacy and tolerability of the topical RA/,-CD complex in acne vulgaris. We conclude that the topical RA/,-CD complex displays an improved efficacy and tolerability profile and is an effective treatment alternative for acne vulgaris. [source] Placebo-controlled, double-blind dose-finding study of entacapone in fluctuating parkinsonian patients,MOVEMENT DISORDERS, Issue 1 2007Yoshikuni Mizuno MD Abstract We conducted a multicenter randomized, placebo-controlled double-blind parallel-group study in Japanese Parkinson's disease (PD) patients with wearing-off motor fluctuations to determine the clinical efficacy and safety of entacapone as an adjunct to concomitant treatment with levodopa and a dopa decarboxylase inhibitor (DCI). We randomized 341 patients to receive entacapone 100 or 200 mg or placebo per dose of levodopa/DCI for 8 weeks. The primary efficacy variable was on time change while awake, determined by patients' diaries. Mean baseline on time in each group was approximately 8 hours. Mean on time change at final assessment was 1.4 hours each for entacapone 100-mg and 200-mg groups and by 0.5 hours for the placebo group (P < 0.05). The two entacapone doses were equally efficacious. Adverse events occurred in 79 patients (69.9%) in placebo, 82 (72.6%) in 100 mg, and 98 (86.0%) in 200 mg. The most common adverse event with entacapone was an increase in dyskinesias. The overall safety profile was satisfactory in both entacapone groups. In conclusion, both entacapone 100 and 200 mg were equally effective in increasing on time of PD patients with wearing-off fluctuations, although the safety and tolerability profile appeared more favorable for the 100-mg dose. © 2006 Movement Disorder Society [source] Treatment of invasive candidiasis with echinocandinsMYCOSES, Issue 6 2009Andreas Glöckner Summary Blood stream infections by Candida spp. represent the majority of invasive fungal infections in intensive care patients. The high crude mortality of invasive candidiasis remained essentially unchanged during the last two decades despite new treatment options that became available. The echinocandins, the latest class of antifungals introduced since 2001, exhibit potent activity against clinically relevant fungi including most Candida spp. In several randomised multicentre phase III trials, anidulafungin, caspofungin and micafungin showed convincing efficacy when compared with standard treatment regimens. In all trials, echinocandins were at least non-inferior to standard treatments. Anidulafungin was shown to be superior to fluconazole. Echinocandins have a favourable tolerability profile and exhibit a minimal potential for drug interactions since their pharmacokinetics is independent of renal and , largely , hepatic function. As a result of these properties, echinocandins are appropriate drugs of choice for invasive candidiasis in intensive care where many patients experience organ failure and receive multiple drugs with complex interactions. [source] Opioids and the Management of Chronic Severe Pain in the Elderly: Consensus Statement of an International Expert Panel with Focus on the Six Clinically Most Often Used World Health Organization step III Opioids (Buprenorphine, Fentanyl, Hydromorphone, Methadone, Morphine, Oxycodone)PAIN PRACTICE, Issue 4 2008Joseph Pergolizzi MD ,,Abstract Summary of consensus: 1.,The use of opioids in cancer pain:, The criteria for selecting analgesics for pain treatment in the elderly include, but are not limited to, overall efficacy, overall side-effect profile, onset of action, drug interactions, abuse potential, and practical issues, such as cost and availability of the drug, as well as the severity and type of pain (nociceptive, acute/chronic, etc.). At any given time, the order of choice in the decision-making process can change. This consensus is based on evidence-based literature (extended data are not included and chronic, extended-release opioids are not covered). There are various driving factors relating to prescribing medication, including availability of the compound and cost, which may, at times, be the main driving factor. The transdermal formulation of buprenorphine is available in most European countries, particularly those with high opioid usage, with the exception of France; however, the availability of the sublingual formulation of buprenorphine in Europe is limited, as it is marketed in only a few countries, including Germany and Belgium. The opioid patch is experimental at present in U.S.A. and the sublingual formulation has dispensing restrictions, therefore, its use is limited. It is evident that the population pyramid is upturned. Globally, there is going to be an older population that needs to be cared for in the future. This older population has expectations in life, in that a retiree is no longer an individual who decreases their lifestyle activities. The "baby-boomers" in their 60s and 70s are "baby zoomers"; they want to have a functional active lifestyle. They are willing to make trade-offs regarding treatment choices and understand that they may experience pain, providing that can have increased quality of life and functionality. Therefore, comorbidities,including cancer and noncancer pain, osteoarthritis, rheumatoid arthritis, and postherpetic neuralgia,and patient functional status need to be taken carefully into account when addressing pain in the elderly. World Health Organization step III opioids are the mainstay of pain treatment for cancer patients and morphine has been the most commonly used for decades. In general, high level evidence data (Ib or IIb) exist, although many studies have included only few patients. Based on these studies, all opioids are considered effective in cancer pain management (although parts of cancer pain are not or only partially opioid sensitive), but no well-designed specific studies in the elderly cancer patient are available. Of the 2 opioids that are available in transdermal formulation,fentanyl and buprenorphine,fentanyl is the most investigated, but based on the published data both seem to be effective, with low toxicity and good tolerability profiles, especially at low doses. 2.,The use of opioids in noncancer-related pain:, Evidence is growing that opioids are efficacious in noncancer pain (treatment data mostly level Ib or IIb), but need individual dose titration and consideration of the respective tolerability profiles. Again no specific studies in the elderly have been performed, but it can be concluded that opioids have shown efficacy in noncancer pain, which is often due to diseases typical for an elderly population. When it is not clear which drugs and which regimes are superior in terms of maintaining analgesic efficacy, the appropriate drug should be chosen based on safety and tolerability considerations. Evidence-based medicine, which has been incorporated into best clinical practice guidelines, should serve as a foundation for the decision-making processes in patient care; however, in practice, the art of medicine is realized when we individualize care to the patient. This strikes a balance between the evidence-based medicine and anecdotal experience. Factual recommendations and expert opinion both have a value when applying guidelines in clinical practice. 3.,The use of opioids in neuropathic pain:, The role of opioids in neuropathic pain has been under debate in the past but is nowadays more and more accepted; however, higher opioid doses are often needed for neuropathic pain than for nociceptive pain. Most of the treatment data are level II or III, and suggest that incorporation of opioids earlier on might be beneficial. Buprenorphine shows a distinct benefit in improving neuropathic pain symptoms, which is considered a result of its specific pharmacological profile. 4.,The use of opioids in elderly patients with impaired hepatic and renal function:, Functional impairment of excretory organs is common in the elderly, especially with respect to renal function. For all opioids except buprenorphine, half-life of the active drug and metabolites is increased in the elderly and in patients with renal dysfunction. It is, therefore, recommended that,except for buprenorphine,doses be reduced, a longer time interval be used between doses, and creatinine clearance be monitored. Thus, buprenorphine appears to be the top-line choice for opioid treatment in the elderly. 5.,Opioids and respiratory depression:, Respiratory depression is a significant threat for opioid-treated patients with underlying pulmonary condition or receiving concomitant central nervous system (CNS) drugs associated with hypoventilation. Not all opioids show equal effects on respiratory depression: buprenorphine is the only opioid demonstrating a ceiling for respiratory depression when used without other CNS depressants. The different features of opioids regarding respiratory effects should be considered when treating patients at risk for respiratory problems, therefore careful dosing must be maintained. 6.,Opioids and immunosuppression:, Age is related to a gradual decline in the immune system: immunosenescence, which is associated with increased morbidity and mortality from infectious diseases, autoimmune diseases, and cancer, and decreased efficacy of immunotherapy, such as vaccination. The clinical relevance of the immunosuppressant effects of opioids in the elderly is not fully understood, and pain itself may also cause immunosuppression. Providing adequate analgesia can be achieved without significant adverse events, opioids with minimal immunosuppressive characteristics should be used in the elderly. The immunosuppressive effects of most opioids are poorly described and this is one of the problems in assessing true effect of the opioid spectrum, but there is some indication that higher doses of opioids correlate with increased immunosuppressant effects. Taking into consideration all the very limited available evidence from preclinical and clinical work, buprenorphine can be recommended, while morphine and fentanyl cannot. 7.,Safety and tolerability profile of opioids:, The adverse event profile varies greatly between opioids. As the consequences of adverse events in the elderly can be serious, agents should be used that have a good tolerability profile (especially regarding CNS and gastrointestinal effects) and that are as safe as possible in overdose especially regarding effects on respiration. Slow dose titration helps to reduce the incidence of typical initial adverse events such as nausea and vomiting. Sustained release preparations, including transdermal formulations, increase patient compliance.,, [source] Prevalence, incidence and persistence of antipsychotic drug prescribing in the Italian general population: retrospective database analysis, 1999,2002,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 6 2006Mersia Mirandola StatD Abstract Purpose To investigate the prevalence, incidence and persistence with antipsychotic drug therapy in a large and geographically defined catchment area of Italian general population. Methods All antipsychotic drug prescriptions dispensed during 1999, 2000, 2001 and 2002 were extracted from an administrative prescription database covering a population of 2,640,379 individuals. Antipsychotic drug users were defined as patients who had at least one recorded prescription in the current year. New users were defined as patients receiving a first prescription without any recorded antipsychotic drug treatment in the previous 12 months. Prevalence data were calculated by dividing users by the total number of male and female residents in each age group. Incidence data were calculated as the number of new users divided by the person-time free from antipsychotic drugs in the current year. The cumulative persistence of each medication was calculated by dividing the total prescribed amount of antipsychotic drug by the recommended daily dose, according to each agent's defined daily dose (DDD). Results A progressive rise in prevalence and incidence rates was observed during the 4-year period. In each census year, the prevalence and incidence of prescribing was higher in females than males, and progressively rose with age, with the highest rates in old and very old subjects. The analysis of persistence with therapy revealed that 3176 individuals (78.5%) were occasional antipsychotic drug users, and that occasional use was more frequent among individuals receiving conventional antipsychotic drugs than among individuals receiving novel antipsychotic drugs. This difference was not explained by differences in the occurrence of neurologic adverse reactions, as shown by the concurrent prescribing of anticholinergic drugs, which was fairly similar between the two groups of new drug users. Additionally, we found that conventioal antipsychotic drugs were more often used in older individuals, where occasional use is very frequent, while novel antipsychotic drugs were more often prescribed in young and adult individuals, where regular use is more frequent. Conclusions An epidemiologically relevant proportion of everyday individuals is annually exposed to antipsychotic drugs. The distribution of prevalence and incidence rates by age highlighted an emerging public health issue related to the adverse and beneficial consequences of antipsychotic drug exposure in the elderly. The finding that persistence with therapy was longer in new users of novel antipsychotic drugs compared with new users of conventional agents might be explained by the different demographic and clinical characteristics of individuals receiving these two drug classes and not by the different tolerability profile of these two drug classes. Copyright © 2005 John Wiley & Sons, Ltd. [source] Comparison of outcomes for elderly patients treated with weekly paclitaxel in combination with carboplatin versus the standard 3-weekly paclitaxel and carboplatin for advanced nonsmall cell lung cancer,CANCER, Issue 3 2008Suresh Ramalingam MD Abstract BACKGROUND. The purpose of this study was to compare the outcomes between elderly (aged ,70 years) patients treated with paclitaxel on a weekly basis and with carboplatin (every 4 weeks) versus the standard 3-weekly regimen of carboplatin and paclitaxel for first-line therapy of advanced nonsmall cell lung cancer. METHODS. Of the 444 patients enrolled, 136 (31%) were aged ,70 years. Seventy-two patients were randomized to the weekly schedule (paclitaxel, 100 mg/m2 weekly for 3 of 4 weeks; carboplatin, area under the curve [AUC] = 6 mg/mL·min on Day 1 every 4 weeks), and 64 patients were randomized to the standard schedule (paclitaxel, 225 mg/m2; carboplatin, AUC = 6 mg/mL·min on Day 1 every 21 days). Patients with stable disease or objective response after 4 cycles of therapy were eligible for maintenance therapy with weekly paclitaxel (70 mg/m2, 3 of 4 weeks). RESULTS. The response rate for elderly patients was 26% on the weekly regimen and 19% on the standard schedule. The median survival duration for the weekly and the standard schedules was 37 weeks and 31 weeks, respectively. The 1-year survival rates were similar at 31% and 33%. Grade 3 to 4 anemia was more common on the weekly schedule (16% vs 6%), whereas grade 3 neuropathy was less common (5.5% vs 9.5%). Nausea and emesis were also less frequent on the weekly schedule. CONCLUSIONS. Efficacy was similar between the weekly regimen and the standard regimen of carboplatin and paclitaxel for elderly patients with advanced NSCLC and may be advantageous based on its favorable tolerability profile. Cancer 2008. © 2008 American Cancer Society. [source] Experience with topiramate monotherapy in elderly patients with recent-onset epilepsyACTA NEUROLOGICA SCANDINAVICA, Issue 3 2005J. Gro Objectives,,, To evaluate the effect of topiramate in elderly patients with onset of epilepsy after the age of 60, treatment-naive or non-responding to an initial antiepileptic drug. Methods,,, Analysis of patients with epilepsy diagnosed in the preceding 5 years, aged ,65 years (n = 43), enrolled in a larger open-label trial (n = 692). After titration to topiramate 100 mg/day over 4 weeks, the dose was adjusted according to individual response (maximum 400 mg/day). Patients were followed up for at least 7 months. Results,,, After 7 months, 79% of patients remained in the study. Seizure frequency decreased significantly vs baseline (P < 0.001); ,50% reduction in seizure frequency was achieved in 87% of patients, 64% remained seizure-free. Both previously treated and naive patients responded. Fourteen per cent dropped out because of insufficient tolerability. No unexpected or unusual adverse events were observed. Conclusions,,, The results indicate that elderly patients respond well to topiramate monotherapy. The high patient retention rate reflects a favourable tolerability profile in this population. [source] Gemcitabine plus epirubicin in patients with advanced urothelial carcinoma who are not eligible for platinum-based regimensCANCER, Issue 7 2002Sergio Ricci M.D. Abstract BACKGROUND The objective of this study was to evaluate the efficacy and toxicity of gemcitabine plus epirubicin in previously untreated patients with advanced urothelial carcinoma who were not eligible for cisplatin-based regimens. METHODS Patients with advanced urothelial carcinoma and at least one of the following characteristics were eligible: impaired renal function (creatinine clearance < 60 mL per minute), an Eastern Cooperative Oncology Group performance status (PS) , 2, and age , 75 years. The treatment included epirubicin 70 mg/m2 as an intravenous bolus on Day 1 and gemcitabine 1000 mg/m2 over 30 minutes on Days 1 and 8 of a 21-day cycle. RESULTS Thirty-eight patients entered the study, and a total of 152 cycles were administered, with a median of 4 cycles per patient (range, 1,6 cycles per patient). The following Grade 3,4 hematologic toxicities were reported (percent of cycles): neutropenia, 22.4%; anemia, 11.2%; and thrombocytopenia, 6.5%. No cardiac, renal, or hepatic toxicities were observed. Dose intensities of epirubicin and gemcitabine were 19.6 mg/m2 per week (84%) and 532.2 mg/m2 per week (80%), respectively. There were 2 complete responses (5.3%), 13 partial responses (34.2%), 11 patients with stable disease (28.9%), and 12 patients with progressive disease (31.6%), for an overall response rate of 39.5% (95% confidence interval, 25.1,55.1). The median progression free survival (PFS) and overall survival (OS) rates were 4.8 months and 8.0 months, respectively. The 1-year survival rate was 38%, and the median PFS and OS were 6.4 months and 16.4 months, respectively, in patients with PS 0,1. Thirty patients were symptomatic: Seventeen patients (56.7%) achieved a complete response, and 5 patients (16.7%) achieved a partial symptomatic response. CONCLUSIONS At the doses given in this study, gemcitabine and epirubicin had a good tolerability profile with interesting activity in patients with advanced urothelial carcinoma who were not fit for cisplatin-based regimens. Cancer 2002;95:1444,50. © 2002 American Cancer Society. DOI 10.1002/cncr.10860 [source] Efficacy and Safety of Oral Lacosamide as Adjunctive Therapy in Adults with Partial-Onset SeizuresEPILEPSIA, Issue 7 2007Elinor Ben-Menachem Summary:,Purpose: To evaluate the efficacy and safety of lacosamide when added to 1 or 2 antiepileptic drugs (AEDs) in adults with uncontrolled partial-onset seizures, and assess plasma concentrations of concomitant AEDs to determine any potential for drug interactions. Methods: During this multicenter, double-blind, placebo-controlled trial, patients were randomized to placebo or lacosamide 200, 400, or 600 mg/day after an 8-week baseline period. Lacosamide was titrated in weekly increments of 100 mg/day over 6 weeks and maintained for 12 weeks. Results were analyzed on an intention-to-treat basis. Results: Four hundred eighteen patients were randomized and received trial medication; 312 completed the trial. The median percent reduction in seizure frequency per 28 days was 10%, 26%, 39%, and 40% in the placebo, lacosamide 200, 400, and 600 mg/day treatment groups, respectively. The median percent reduction in seizure frequency over placebo was significant for lacosamide 400 mg/day (p = 0.0023) and 600 mg/day (p = 0.0084). The 50% responder rates were 22%, 33%, 41%, and 38% for placebo, lacosamide 200, 400, and 600 mg/day, respectively. The 50% responder rate over placebo was significant for lacosamide 400 mg/day (p = 0.0038) and 600 mg/day (p = 0.0141). Adverse events that appeared dose-related included dizziness, nausea, fatigue, ataxia, vision abnormal, diplopia, and nystagmus. Lacosamide did not affect mean plasma concentrations of concomitantly administered AEDs. Conclusions: In this trial, adjunctive lacosamide significantly reduced seizure frequency in patients with uncontrolled partial-onset seizures. Along with favorable pharmacokinetic and tolerability profiles, these results support further development of lacosamide as an AED. [source] Quetiapine versus olanzapine for the treatment of negative symptoms in patients with schizophreniaHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 4 2006Pinkhas Sirota Abstract Negative symptoms are considered the most debilitating and refractory aspect of schizophrenia, being associated with poor social, occupational and global outcomes. Conventional antipsychotics have limited efficacy against these symptoms and poor tolerability profiles. Atypical antipsychotics are an alternative treatment, and this 12-week, randomised, flexibly dosed study compared the efficacy, safety and tolerability of quetiapine and olanzapine in this regard. Of the 40 patients who entered the study (32 male; 8 female), 19 were randomised to quetiapine (mean dose 637,mg/day, mean treatment duration 80 days) and 21 to olanzapine (mean dose 16,mg/day, mean treatment duration 78 days). Quetiapine and olanzapine were similarly effective: in each treatment group significant improvements at Week 12 were observed for negative symptom scores on the SANS and the PANSS, and for subscale scores of affective flattening and alogia on the SANS. Both treatments were well tolerated in this patient population, with no worsening of extrapyramidal symptoms in either case. Anxiety and insomnia were the most common adverse events (,7% of patients in each group), but were not drug-related. Although this is a small study with limited power, the results support the effectiveness of quetiapine and olanzapine in treating the negative symptoms of schizophrenia. Copyright © 2006 John Wiley & Sons, Ltd. [source] Opioids and the Management of Chronic Severe Pain in the Elderly: Consensus Statement of an International Expert Panel with Focus on the Six Clinically Most Often Used World Health Organization step III Opioids (Buprenorphine, Fentanyl, Hydromorphone, Methadone, Morphine, Oxycodone)PAIN PRACTICE, Issue 4 2008Joseph Pergolizzi MD ,,Abstract Summary of consensus: 1.,The use of opioids in cancer pain:, The criteria for selecting analgesics for pain treatment in the elderly include, but are not limited to, overall efficacy, overall side-effect profile, onset of action, drug interactions, abuse potential, and practical issues, such as cost and availability of the drug, as well as the severity and type of pain (nociceptive, acute/chronic, etc.). At any given time, the order of choice in the decision-making process can change. This consensus is based on evidence-based literature (extended data are not included and chronic, extended-release opioids are not covered). There are various driving factors relating to prescribing medication, including availability of the compound and cost, which may, at times, be the main driving factor. The transdermal formulation of buprenorphine is available in most European countries, particularly those with high opioid usage, with the exception of France; however, the availability of the sublingual formulation of buprenorphine in Europe is limited, as it is marketed in only a few countries, including Germany and Belgium. The opioid patch is experimental at present in U.S.A. and the sublingual formulation has dispensing restrictions, therefore, its use is limited. It is evident that the population pyramid is upturned. Globally, there is going to be an older population that needs to be cared for in the future. This older population has expectations in life, in that a retiree is no longer an individual who decreases their lifestyle activities. The "baby-boomers" in their 60s and 70s are "baby zoomers"; they want to have a functional active lifestyle. They are willing to make trade-offs regarding treatment choices and understand that they may experience pain, providing that can have increased quality of life and functionality. Therefore, comorbidities,including cancer and noncancer pain, osteoarthritis, rheumatoid arthritis, and postherpetic neuralgia,and patient functional status need to be taken carefully into account when addressing pain in the elderly. World Health Organization step III opioids are the mainstay of pain treatment for cancer patients and morphine has been the most commonly used for decades. In general, high level evidence data (Ib or IIb) exist, although many studies have included only few patients. Based on these studies, all opioids are considered effective in cancer pain management (although parts of cancer pain are not or only partially opioid sensitive), but no well-designed specific studies in the elderly cancer patient are available. Of the 2 opioids that are available in transdermal formulation,fentanyl and buprenorphine,fentanyl is the most investigated, but based on the published data both seem to be effective, with low toxicity and good tolerability profiles, especially at low doses. 2.,The use of opioids in noncancer-related pain:, Evidence is growing that opioids are efficacious in noncancer pain (treatment data mostly level Ib or IIb), but need individual dose titration and consideration of the respective tolerability profiles. Again no specific studies in the elderly have been performed, but it can be concluded that opioids have shown efficacy in noncancer pain, which is often due to diseases typical for an elderly population. When it is not clear which drugs and which regimes are superior in terms of maintaining analgesic efficacy, the appropriate drug should be chosen based on safety and tolerability considerations. Evidence-based medicine, which has been incorporated into best clinical practice guidelines, should serve as a foundation for the decision-making processes in patient care; however, in practice, the art of medicine is realized when we individualize care to the patient. This strikes a balance between the evidence-based medicine and anecdotal experience. Factual recommendations and expert opinion both have a value when applying guidelines in clinical practice. 3.,The use of opioids in neuropathic pain:, The role of opioids in neuropathic pain has been under debate in the past but is nowadays more and more accepted; however, higher opioid doses are often needed for neuropathic pain than for nociceptive pain. Most of the treatment data are level II or III, and suggest that incorporation of opioids earlier on might be beneficial. Buprenorphine shows a distinct benefit in improving neuropathic pain symptoms, which is considered a result of its specific pharmacological profile. 4.,The use of opioids in elderly patients with impaired hepatic and renal function:, Functional impairment of excretory organs is common in the elderly, especially with respect to renal function. For all opioids except buprenorphine, half-life of the active drug and metabolites is increased in the elderly and in patients with renal dysfunction. It is, therefore, recommended that,except for buprenorphine,doses be reduced, a longer time interval be used between doses, and creatinine clearance be monitored. Thus, buprenorphine appears to be the top-line choice for opioid treatment in the elderly. 5.,Opioids and respiratory depression:, Respiratory depression is a significant threat for opioid-treated patients with underlying pulmonary condition or receiving concomitant central nervous system (CNS) drugs associated with hypoventilation. Not all opioids show equal effects on respiratory depression: buprenorphine is the only opioid demonstrating a ceiling for respiratory depression when used without other CNS depressants. The different features of opioids regarding respiratory effects should be considered when treating patients at risk for respiratory problems, therefore careful dosing must be maintained. 6.,Opioids and immunosuppression:, Age is related to a gradual decline in the immune system: immunosenescence, which is associated with increased morbidity and mortality from infectious diseases, autoimmune diseases, and cancer, and decreased efficacy of immunotherapy, such as vaccination. The clinical relevance of the immunosuppressant effects of opioids in the elderly is not fully understood, and pain itself may also cause immunosuppression. Providing adequate analgesia can be achieved without significant adverse events, opioids with minimal immunosuppressive characteristics should be used in the elderly. The immunosuppressive effects of most opioids are poorly described and this is one of the problems in assessing true effect of the opioid spectrum, but there is some indication that higher doses of opioids correlate with increased immunosuppressant effects. Taking into consideration all the very limited available evidence from preclinical and clinical work, buprenorphine can be recommended, while morphine and fentanyl cannot. 7.,Safety and tolerability profile of opioids:, The adverse event profile varies greatly between opioids. As the consequences of adverse events in the elderly can be serious, agents should be used that have a good tolerability profile (especially regarding CNS and gastrointestinal effects) and that are as safe as possible in overdose especially regarding effects on respiration. Slow dose titration helps to reduce the incidence of typical initial adverse events such as nausea and vomiting. Sustained release preparations, including transdermal formulations, increase patient compliance.,, [source] Role of photodynamic therapy in psoriasis: a brief reviewPHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE, Issue 5 2008Yasmeen K. Tandon Background and purpose: Photodynamic therapy (PDT) is a light treatment modality which involves either systemic or local application of a photosensitizing compound, which preferentially deposits in the target cells, and is then followed by selective illumination of the lesion with visible light. The purpose of this study was to review the literature to examine the success, side effects, and different protocols used thus far to treat psoriasis using PDT. Methods: A thorough review of the literature was performed and analyzed. Results and conclusions: After a thorough review of the literature, PDT remains a potential treatment for psoriasis. Clinical improvement has been observed in most studies. The major limiting factor seen in many of the studies was the side effect of pain and burning sensations associated with PDT. This highlights the need for other photosensitizers with better tolerability profiles. [source] Comparative pharmacokinetics, safety, and tolerability after subcutaneous administration of recombinant human erythropoietin formulated with different stabilizersBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 6 2000Wing K. Cheung Abstract This report summarizes the results of two double-blind, single-center, randomized studies that used a two-period crossover design. The objective of these two studies was to compare the safety, tolerability, pharmacokinetics, and pain score at the subcutaneous (sc) injection site of a phosphate-buffered recombinant human erythropoietin (EPREX®, epoetin alfa, r-HuEPO) formulated with a new stabilizer (glycine and Polysorbate 80) with the commercially available EPREX® formulations, which uses human serum albumin (HSA) as the stabilizer. Twenty-four healthy male volunteers were enrolled in each of the two studies. In the first study, subjects received a single 150 IU/kg sc dose of r-HuEPO using the 2000 IU/mL (2K) phosphate-buffered formulation with or without the new stabilizer (12 subjects/group). In the second study, subjects received a single 750 IU/kg sc dose of r-HuEPO using the 40,000 IU/mL (40K) phosphate-buffered formulation with or without the new stabilizer (12 subjects/group). In each study, r-HuEPO was administered over two separate dosing periods, each separated with a 28-day washout period. There were no significant differences in AUC and Cmax for either strength of r-HuEPO formulated with or without the new stabilizer, indicating that the absorption and disposition characteristics of the two formulations were similar after sc administration. Both r-HuEPO strengths with and without the new stabilizer were safe and well tolerated; the safety and tolerability profiles of both formulations for each r-HuEPO concentration were comparable. There were no statistically significant differences in pain score for either strength of r-HuEPO with and without the new stabilizer. It was concluded that the two phosphate-buffered r-HuEPO concentrations formulated with and without the new stabilizer are pharmacokinetically equivalent. Copyright © 2000 John Wiley & Sons, Ltd. [source] Epilepsy: from consensus to daily practiceACTA NEUROLOGICA SCANDINAVICA, Issue 2003E. Ben-Menachem Most clinicians would accept that epilepsy treatment should begin with monotherapy, and in the majority of cases this is the preferred drug maintenance option. The clinical choice of one antiepileptic drug (AED) over another should be based on firm evidence of efficacy and tolerability as evaluated in comparative monotherapy studies and pharmacokinetics. This paper presents the findings of evidence-based reviews of AED monotherapy in patients newly diagnosed with epilepsy. The main study was conducted in the United Kingdom and investigated the clinical evidence supporting AEDs used as first-line monotherapy. In this paper the general treatment recommendations will focus on valproate, one of the mainstay drugs used in the fight against epilepsy. Finally, with these recommendations in mind, the principles behind AED drug selection in clinical practice will be discussed. Factors for consideration that impact on AED decision-making include: seizure and syndrome diagnosis, AED tolerability profiles, patient characteristics and pharmacokinetic/pharmacodynamic AED interactions. [source] Discovery of Indolone Acetamides as Novel SV2A Ligands with Improved Potency Toward Seizure SuppressionCHEMMEDCHEM, Issue 2 2010Anne Frycia Capitalizing on the proven clinical efficacy of levetiracetam as an antiepileptic drug, a drug discovery program lead to the identification of a new generation of SV2A ligands with equal or better tolerability profiles than levetiracetam, and improved potency toward seizure suppression in animal models. [source] | |||||||||||||||||||||||||