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Long-term Safety (long-term + safety)

Distribution by Scientific Domains

Medical Sciences	97%

Distribution within Medical Sciences

Dermatology	9%
Cardiovascular Disease	6%
18 Other Subdomains	70%

Selected Abstracts

Long-Term Safety and Efficacy of Tadalafil 5 mg Dosed Once Daily in Men with Erectile Dysfunction

THE JOURNAL OF SEXUAL MEDICINE, Issue 9 2008
Hartmut Porst MD
ABSTRACT Introduction., With once-daily administration of tadalafil, dosing and sexual activity would no longer need to be temporally linked for patients with erectile dysfunction (ED). Aim., To evaluate long-term safety and efficacy of tadalafil 5 mg dosed once daily for the treatment of ED. Methods., Patients ,18 years of age with ED of any functional severity or etiology received tadalafil 5 mg once daily for 1 (N = 234) or 2 (N = 238) years during the open-label extensions of two previously reported studies. Patients who completed the 1-year open-label extension concluded with a 4-week ED treatment-free period. Baseline was defined as prior to receiving any study drug. Main Outcome Measures., Safety measures included adverse events, electrocardiograms, and clinical laboratory measures. Efficacy measures included the International Index of Erectile Function (IIEF)-Erectile Function (-EF), -Intercourse Satisfaction (-IS), and -Overall Satisfaction (-OS) domain scores, and the Global Assessment Questions (GAQ1: improved erections; GAQ2: improved ability to engage in sexual activity). Results., Overall, 208/234 (88.9%) and 139/238 (58.4%) patients completed the 1- and 2-year open-label extensions, respectively. No study drug-related serious adverse events were observed. Treatment-emergent adverse events observed in ,5% of the patients during the first year of either open-label extension were dyspepsia, headache, back pain, and influenza. No clinically meaningful abnormalities associated with tadalafil were observed for electrocardiograms or clinical laboratory measures. Mean IIEF domain scores improved from baseline to the conclusions of the 1- and 2-year open-label extensions, respectively: -EF, +10.4 and +10.8; -IS, +4.0 and +3.7; and -OS, +3.0 and +3.2. At the conclusion of the 2-year open-label extension, 95.7% and 92.1% of the patients reported positive responses to GAQ1 and GAQ2, respectively. Conclusions., In these long-term, open-label, once-daily dosing studies, tadalafil 5 mg was well tolerated and effective, making it a viable alternative to the current on-demand dosing of tadalafil for men with ED. Porst H, Rajfer J, Casabé A, Feldman R, Ralph D, Vieiralves LF, Esler A, Wolka AM, and Klise SR. Long-term safety and efficacy of tadalafil 5 mg dosed once daily in men with erectile dysfunction. J Sex Med 2008;5:2160,2169. [source]

Long-term safety of biologics in dermatology

DERMATOLOGIC THERAPY, Issue 1 2009
Xinaida T. Lima
ABSTRACT The use of biologics in dermatology has increased rapidly. Although most are relatively safe when correctly used and monitored, there are known side effects and adverse events that occur. Selection of patients should be done on a case-by-case basis. Severity of disease, comorbidity profile, drug profile, and cost-effectiveness should be all taken into consideration while deciding to start and/or maintain one of these therapies. Dermatologists should be aware of the benefits and limitations of this class of drugs, as well as the appropriate monitoring. The authors propose a concise overview of the safety profiles of some of the biologics currently used in the dermatologic field. [source]

Long-term safety and efficacy of long-acting risperidone in elderly psychotic patients

HUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 8 2007
Werner Kissling
Abstract This subgroup analysis of the 6-month, open-label Switch to Risperidone Microspheres (StoRMi) trial evaluated long-term safety and efficacy of a direct conversion to risperidone long-acting injectable (RLAI) in 52 elderly patients (,65 years) with psychosis stabilized on oral or depot antipsychotic. Study outcomes included adverse events, movement disorder severity, psychiatric symptoms, functional ability, quality of life and patient satisfaction. Change in the Positive and Negative Syndrome Scale at endpoint was the primary efficacy measure. The most common dosage of RLAI used at endpoint was 25,mg every 14 days (60%). The trial was completed by 81% of patients, with six patients discontinuing treatment due to an adverse event. Tolerability was good and most side effects were mild to moderate. Serious adverse events occurred in 11 patients. Two of these (suicidal attempt, n,=,1; exacerbation of disease, n,=,1) were considered possibly related to RLAI. Conversion to RLAI resulted in significant improvements in movement disorder severity, psychiatric symptoms, functional status and patient satisfaction. Mean PANSS total decreased by 15.8 at endpoint, with 23 patients (46.9%) experiencing a ,20% improvement. This post-hoc analysis supports that RLAI is well tolerated and safe in elderly patients with psychotic illnesses switched from stable antipsychotic regimens, and suggests possible efficacy, although inferences are limited. Copyright © 2007 John Wiley & Sons, Ltd. [source]

Long-term safety of botulinum toxin type A

MOVEMENT DISORDERS, Issue 9 2003
Markus Naumann MD
[source]

Long-Term Safety and Efficacy of Tadalafil 5 mg Dosed Once Daily in Men with Erectile Dysfunction

Long-term safety and efficacy of abatacept in children with juvenile idiopathic arthritis,

ARTHRITIS & RHEUMATISM, Issue 6 2010
Nicolino Ruperto
Objective We previously documented that abatacept was effective and safe in patients with juvenile idiopathic arthritis (JIA) who had not previously achieved a satisfactory clinical response with disease-modifying antirheumatic drugs or tumor necrosis factor blockade. Here, we report results from the long-term extension (LTE) phase of that study. Methods This report describes the long-term, open-label extension phase of a double-blind, randomized, controlled withdrawal trial in 190 patients with JIA ages 6,17 years. Children were treated with 10 mg/kg abatacept administered intravenously every 4 weeks, with or without methotrexate. Efficacy results were based on data derived from the 153 patients who entered the open-label LTE phase and reflect ,21 months (589 days) of treatment. Safety results include all available open-label data as of May 7, 2008. Results Of the 190 enrolled patients, 153 entered the LTE. By day 589, 90%, 88%, 75%, 57%, and 39% of patients treated with abatacept during the double-blind and LTE phases achieved responses according to the American College of Rheumatology (ACR) Pediatric 30 (Pedi 30), Pedi 50, Pedi 70, Pedi 90, and Pedi 100 criteria for improvement, respectively. Similar response rates were observed by day 589 among patients previously treated with placebo. Among patients who had not achieved an ACR Pedi 30 response at the end of the open-label lead-in phase and who proceeded directly into the LTE, 73%, 64%, 46%, 18%, and 5% achieved ACR Pedi 30, Pedi 50, Pedi 70, Pedi 90, and Pedi 100 responses, respectively, by day 589 of the LTE. No cases of tuberculosis and no malignancies were reported during the LTE. Pneumonia developed in 3 patients, and multiple sclerosis developed in 1 patient. Conclusion Abatacept provided clinically significant and durable efficacy in patients with JIA, including those who did not initially achieve an ACR Pedi 30 response during the initial 4-month open-label lead-in phase. [source]

Long-term safety and effectiveness of etanercept in children with selected categories of juvenile idiopathic arthritis,

ARTHRITIS & RHEUMATISM, Issue 9 2009
E. H. Giannini
Objective This study was undertaken to evaluate the long-term safety and effectiveness of etanercept alone or in combination with methotrexate (MTX) in children with selected categories of juvenile idiopathic arthritis (JIA). Methods Patients ages 2,18 years with rheumatoid factor (RF),positive or RF-negative polyarthritis, systemic JIA, or extended oligoarthritis were eligible for the study. Patients received MTX alone (,10 mg/m2/week [,0.3 mg/kg/week], maximum dosage 1 mg/kg/week), etanercept alone (0.8 mg/kg/week, maximum dose 50 mg), or etanercept plus MTX for 3 years in an open-label, nonrandomized study. Safety was assessed by measuring rates of adverse events, and effectiveness was assessed using the physician's global assessment of disease activity and the pediatric total joint assessment. Results A total of 197, 103, and 294 patients were enrolled in the MTX, etanercept, and etanercept plus MTX groups, respectively. Exposure-adjusted rates of adverse events were similar among the 3 treatment groups (18.3, 18.7, and 21.6 per 100 patient-years in the MTX, etanercept, and etanercept plus MTX groups, respectively). Respective rates per 100 patient-years of serious adverse events (4.6, 7.1, and 6.0) and medically important infections (1.3, 1.8, and 2.1) were also similar among the 3 treatment groups. Scores for physician's global assessment and total active joints improved from baseline, and improvement was maintained for the duration of the study. Conclusion These data confirm the findings of other long-term studies and suggest that etanercept or etanercept plus MTX has an acceptable safety and effectiveness profile in children with selected categories of JIA. Improvement was maintained for 3 years in those continuing to receive medication. [source]

Long-term safety of filgrastim (rhG-CSF) administration

BRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2007
Dennis L. Confer
No abstract is available for this article. [source]

Long-term safety and feasibility of arteriovenous fistulae as vascular accesses in children with haemophilia: a prospective study

BRITISH JOURNAL OF HAEMATOLOGY, Issue 3 2003
Elena Santagostino
Summary. Infectious and thrombotic complications limit the long-term use of subcutaneous ports as venous accesses for children with haemophilia. This study has evaluated for the first time the safety and feasibility of internal arteriovenous fistulae (AVF) as alternative accesses. During the 3-year study period, 27 severe haemophiliacs, 14 with factor VIII inhibitors (52%), underwent the creation of 31 proximal AVF in the forearm. Mild forearm haematomas were observed after five procedures (16%) in five patients who had or developed inhibitors after surgery. Inadequate AVF maturation was observed after five of 31 procedures (16%) in four children. AVF were first accessed after a median of 42 d and regularly used at home by 26 patients (96%) for a median follow-up period of 29 months. Thrombosis of a venous branch occurred in one AVF (3%) after 9 months of uncomplicated use in a child with inhibitor who spontaneously recovered from the symptoms and still used AVF for nine additional months. Mild symptoms, referable to distal ischaemia, were transiently reported by two children (7%) who needed no remedial intervention. This study demonstrates that the use of AVF in haemophiliacs enabled long-term treatment at home in all patients but one. [source]

Long-term safety and efficacy of zonisamide in patients with refractory partial-onset epilepsy

ACTA NEUROLOGICA SCANDINAVICA, Issue 2 2008
S. J. Wroe
Objectives,,, To investigate whether zonisamide remains effective and well tolerated in the treatment of refractory partial epilepsy during long-term treatment and with flexible dosing in clinical practice. Materials and methods,,, Patients with refractory partial epilepsy who completed a fixed-dose, randomized, double-blind clinical trial were recruited in an open-label extension study with adjustment of zonisamide and other antiepileptic drug dosage according to the treating physician's usual clinical practice. Results,,, An intention-to-treat analysis of 317 patients showed that zonisamide was well tolerated with a predictable safety profile. Patient retention rates at 1, 2 and 3 years were 65.3%, 44.5% and 28.8%, respectively. Zonisamide treatment was associated with a maintained reduction in seizure frequency, with some patients achieving prolonged periods of seizure freedom. Conclusions,,, Flexible dosing with zonisamide demonstrated a good safety profile and sustained efficacy in the long-term adjunctive treatment of refractory partial epilepsy. [source]

Long-Term, Open-Label Safety Study of Oral Almotriptan 12.5 mg for the Acute Treatment of Migraine in Adolescents

HEADACHE, Issue 5 2010
Frank Berenson MD
(Headache 2010;50:795-807) Objectives., This study evaluated the long-term safety of oral almotriptan 12.5 mg for the treatment of multiple migraine episodes in adolescents over a 12-month period. Efficacy outcomes were assessed as a secondary objective. Methods., Adolescent migraineurs aged 12-17 years were enrolled in this 12-month, open-label study (Study ID CR002827). Patients were instructed to record their assessments on paper headache records whenever they experienced a migraine headache that they treated with study medication. Safety was assessed descriptively and assessments included adverse event (AE) recording, change in laboratory values, vital signs, and electrocardiogram parameters. Efficacy outcomes were assessed descriptively and outcomes included rates for 2- and 24-hour pain relief and sustained pain relief, 2- and 24-hour pain-free and sustained pain-free, and presence of migraine-associated symptoms of photophobia, phonophobia, nausea and vomiting. Results., Overall, 67.1% of patients reported ,1 AE over the course of the trial, 7.6% had an AE judged by the study investigator to be related to treatment with almotriptan, 2.4% discontinued because of an AE, and 1.9% reported serious AEs. The most commonly reported treatment-related AEs (occurring in ,1% of patients) were nausea (1.4%) and somnolence (1.4%). Pain relief responses for treated migraines of moderate or severe intensity at baseline were 61.7% and 68.6%, at 2 and 24 hours, respectively; the sustained pain relief rate was 55.5%. Pain-free responses were reported for 40.5% of all treated migraines at 2 hours and 65.9% of treated migraines at 24 hours; the sustained pain-free rate was 38.4%. The proportion of migraines that achieved the pain relief, sustained pain relief, pain-free and sustained pain-free endpoints were similar in the 12- to 14-year and 15- to 17-year age groups. Treating with almotriptan 12.5 mg when headache pain was mild was associated with higher rates of pain relief and pain-free at 2 and 24 hours, and sustained pain relief and sustained pain-free, compared with treatment initiated when pain was severe. Conclusions., Almotriptan 12.5 mg was well tolerated in this adolescent population over a 12-month period. No unexpected safety or tolerability concerns were revealed over the course of this study. The results are consistent with almotriptan 12.5 mg being effective for the acute treatment of pain and symptoms associated with migraine in both younger and older adolescents. [source]

Divalproex Sodium Extended-Release for the Prophylaxis of Migraine Headache in Adolescents: Results of a Stand-Alone, Long-Term Open-Label Safety Study

HEADACHE, Issue 1 2009
George 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]

Long-term efficacy and safety of adefovir dipivoxil for the treatment of hepatitis B e antigen,positive chronic hepatitis B,

HEPATOLOGY, Issue 3 2008
Patrick Marcellin
Treatment of 171 patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) with adefovir dipivoxil (ADV) 10 mg over 48 weeks resulted in significant histological, virological, serological, and biochemical improvement compared with placebo. The long-term efficacy and safety of ADV in a subset of these patients was investigated for up to 5 years. Sixty-five patients given ADV 10 mg in year 1 elected to continue in a long-term safety and efficacy study (LTSES). At enrollment, the 65 LTSES patients were a median 34 years old, 83% male, 74% Asian, 23% Caucasian, median baseline serum hepatitis B virus (HBV) DNA 8.45 log10 copies/mL, and median baseline alanine aminotransferase (ALT) 2.0 × upper limit of normal. At 5 years on study, the median changes from baseline in serum HBV DNA and ALT for the 41 patients still on ADV were 4.05 log10 copies/mL and ,50 U/L, respectively. HBeAg loss and seroconversion were observed in 58% and 48% of patients by end of study, respectively. Fifteen patients had baseline and end of follow-up liver biopsies; improvements in necroinflammation and fibrosis were seen in 67% and 60% of these patients, respectively. Adefovir resistance mutations A181V or N236T developed in 13 LTSES patients; the first observation was at study week 195. There were no serious adverse events related to ADV. Conclusion: Treatment with ADV beyond 48 weeks was well tolerated and produced long-term virological, biochemical, serological, and histological improvement. (HEPATOLOGY 2008;48:750,758.) [source]

Long-term safety and efficacy of long-acting risperidone in elderly psychotic patients

Infliximab and the risk of latent viruses reactivation in active Crohn's disease

INFLAMMATORY BOWEL DISEASES, Issue 7 2007
Alessandro Lavagna MD
Abstract Background: Infliximab is used for refractory Crohn's disease but there are concerns regarding long-term safety. Recently, JC-polyomavirus (JCV) was studied after 3 cases of progressive multifocal leukoencephalopathy (PML) were found after treatment with natalizumab. The aim of this study was to investigate the short-term effect of infliximab on reactivation of several harmful latent viruses. Methods: Sixty consecutive patients scheduled for infliximab induction course were prospectively enrolled. Blood samples were taken before each infliximab infusion at 0, 2, 6, and 14 weeks. Specific polymerase chain reaction (PCR) analyses were performed to detect JCV, Epstein,Barr virus (EBV), human herpes virus-6, (HHV-6), -7, -8, and cytomegalovirus (CMV). Results: Indications to infliximab were luminal and fistulizing disease in 49 and 15 cases, respectively. Clinical improvement and remission were achieved in 54 (90%) and 39 (65%) of patients, respectively, at 6 weeks. No patient was JCV-positive at any timepoint. EBV serology was positive for 59/60 patients (98%); EBV-PCR tests were transiently positive (>40 copies/105 Peripheral blood mononuclear cells, PBMC) in 4 (7%) patients after infliximab, but in each case were negative at subsequent timepoints. All patients were negative for HHV-6, -7, and -8 at all timepoints. CMV serology was positive in 42 patients (70%), but no CMV-PCR-positive patient was observed. There was no association between concomitant treatments or clinical characteristics and viral status. Conclusions: Our results support the safety of short-term infliximab treatment with respect to latent virus reactivation. The long-term effects of infliximab, particularly for the issue of lymphoproliferative disorders, warrants further studies with larger populations, but so far data are reassuring. (Inflamm Bowel Dis 2007) [source]

How adherent to treatment with azathioprine are patients with Crohn's disease in long-term remission?

INFLAMMATORY BOWEL DISEASES, Issue 4 2007
Gerassimos J. Mantzaris MD
Abstract Background: Patients with longstanding quiescent Crohn's disease on azathioprine usually maintain an excellent quality of life but are also concerned about long-term safety. This may affect adherence to treatment. The aim of the present study was to assess the adherence to azathioprine in a cohort of patients with Crohn's disease in long-term remission. Methods: Thirty patients with Crohn's disease in remission on azathioprine for ,48 months were enrolled in the study. All were asked to record the number of azathioprine tablets they consumed daily. Notes were kept every other month for 6 months. Adherence was defined as consumption of ,80% of medication. Results: Most patients (18/28, 74.3%) were not adherent to treatment. The mean (±SD) daily dose of azathioprine in adherent and nonadherent patients was 145 ± 45 mg and 102 ± 20 mg, respectively. However, there were no significant differences between the 2 groups in the mean IBDQ score and mean Crohn's Disease Activity Index (CDAI) score, both throughout the entire study and at each time point of the study. Male gender, single status, and consumption of >5 concomitant medications were associated with nonadherence. Conclusions: Most patients with Crohn's disease in longstanding remission had low self-reported adherence to azathioprine. Both male gender and single status were associated with nonadherence to azathioprine, whereas disease factors were not related to self-reported adherence. Patients considered nonadherent to treatment maintained disease remission and a quality of life similar to patients who were adherent to treatment. (Inflamm Bowel Dis 2006) [source]

An open-label pilot study using thioguanine as a therapeutic alternative in Crohn's disease patients resistant to 6-mercaptopurine therapy

INFLAMMATORY BOWEL DISEASES, Issue 3 2001
Dr. Marla C. Dubinsky
Abstract Background and Aims A substantial number of patients with inflammatory bowel disease (IBD) fail to achieve a complete clinical response with 6-mercaptopurine (6-MP) and azathioprine (AZA). Inability to achieve therapeutic 6-thioguanine nucleotide (6-TGN) levels due to the preferential overproduction of 6-methylmercaptopurine ribonucleotides (6-MMPR) upon dose escalation characterizes a newly described subgroup of IBD patients resistant to 6-MP/AZA therapy. Treatment with 6-thioguanine (6-TG), a related thiopurine, which forms 6-TGNs more directly may be beneficial in such patients. This pilot study evaluated the safety, tolerance, and efficacy of 6-TG in the subgroup of Crohn's disease (CD) patients failing to attain adequate disease control with traditional 6-MP/AZA therapy. Methods Ten CD patients with preferential 6-MMPR production upon 6-MP/AZA dose escalation were enrolled in an open-label pilot study. Seven of 10 patients had experienced dose-related 6-MP toxicities. Results Seventy percent of the patients (7 of 10) responded or were in remission at week 16. Clinical response was evident by week 4 in most. 6-TGN levels were nine-fold higher with 6-TG treatment than with 6-MP, whereas 6-MMPR levels were undetectable. No patient developed a recurrence of hepatic or hematological toxicity. Conclusions 6-TG was a safer and more efficacious thiopurine in this subgroup of IBD patients resistant to 6-MP therapy. Larger controlled trials are warranted to further evaluate both the short-and long-term safety and efficacy in this subgroup of patients as well as a broader spectrum of IBD patients. [source]

Prevention of relapse of Crohn's disease

INFLAMMATORY BOWEL DISEASES, Issue 4 2000
Dr. Lloyd R. Sutherland
Abstract Until a cure for Crohn's disease(s) is found, strategies that prolong the time spent in remission offer the greatest hope for reducing the morbidity and significant social costs associated with the disease. Medical therapy to date has been disappointing, and the search for a safe, effective therapy that could be offered at low cost continues. The aminosalicylates, so effective in ulcerative colitis, have shown, at best, minimal efficacy in maintaining remission in Crohn's disease. Conventional corticosteroids are not effective, and any reduction in time to relapse for budesonide-treated patients is measured in weeks not months. Azathioprine, 6-mercaptopurine, and methotrexate are effective in maintaining remission, but all three have significant side effects. Antibiotics may have a role to play. Biological therapy may be considered, but the issues of cost and long-term safety require evaluation. Future studies should segregate patients into two groups, those with a medically induced remission and patients whose concern is the prevention of postoperative recurrence. [source]

Safety and efficacy of ezetimibe monotherapy in 1624 primary hypercholesterolaemic patients for up to 2 years

INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 9 2008
C. A. Dujovne
Summary Aims:, This report examined the safety and efficacy of treatment for up to 2 years with the cholesterol absorption inhibitor, ezetimibe (EZE). Methods:, Two identical, randomised, double-blind trials (starting with 827 and 892 patients), evaluated the efficacy and safety of EZE 10 mg/day vs. placebo for 12 weeks in patients with primary hypercholesterolaemia [low-density lipoprotein cholesterol (LDL-C) 3.3,5.1 mmol/l]. Upon completion of these base studies, patients were offered a 2-year, open-label extension study. Adverse event (AE) reports for EZE monotherapy-treated patients were summarised for 3-month intervals to allow for comparison with the placebo group of the 3-month base studies. The primary end-point for this analysis was the evaluation of the long-term safety and tolerability of EZE 10 mg monotherapy dosed daily for up to 24 months. Results:, The incidences of new AEs, treatment-related (TR) AEs, serious AEs (SAEs), TRSAEs and discontinuations as a result of AEs during any 3-month interval were comparable with the respective observations in the placebo group of the base studies. The incidences of AEs, TRAEs, SAEs, TRSAEs and discontinuations as a result of AEs decreased in almost every interval compared with earlier intervals throughout the 2-year study. In addition, the incidences of , 3-fold consecutive elevations of liver transaminases (0.7%) or , 10-fold increases in creatine phosphokinase (0.4%) for the entire 2-year treatment period were comparable with those of the placebo group (0.7% and 0.2% respectively). LDL-C reductions of ,18% were maintained throughout the study. Conclusions:, Compared with placebo, treatment with EZE for up to 2 years in 1624 patients showed no evidence of increased incidence of AEs with increased treatment duration, while showing sustained effects on LDL-C reduction. [source]

Efficacy and Safety of Drug-Eluting Stents: Current Best Available Evidence

JOURNAL OF CARDIAC SURGERY, Issue 6 2006
Shahzad G. Raja M.R.C.S.
Drug-eluting coronary stents deliver effective local concentrations of antiproliferative drugs (thus avoiding systemic toxicities), without substantially modifying the technique of percutaneous coronary intervention. Studies involving several different stent platforms and antiproliferative drug coatings have recently demonstrated dramatic reductions in restenosis rates, compared to conventional bare metal stents. Although the clinical benefits of drug-eluting stents are increasingly evident, important concerns about their long-term safety and costs have been raised. Furthermore, drug-eluting stents are being claimed to replace coronary artery bypass surgery in the near future. This review article evaluates the current best available evidence on the efficacy and safety of drug-eluting stents with a focus on the impact of this "revolutionary" new technology on the practice of coronary artery bypass surgery. [source]

Management of complications after implantation of fillers

JOURNAL OF COSMETIC DERMATOLOGY, Issue 1 2004
Koenraad De Boulle
Summary Soft tissue augmentation is widely practised by a variety of different practitioners. A new classification of filler substances and procedures, taking into account long-term safety and reversibility of side effects, is proposed: i non-permanent and biodegradable, ii,semi-permanent and biodegradable, iii,permanent and reversible, iv,permanent and non-reversible. Complications and adverse effects occur with all fillers and all filler procedures. Insufficient experience is an important contributory factor. Underreporting is probably common. Commonest are haematomas, ecchymoses, infections, papulopustular or acneiform lesions, non-hypersensitivity related swelling and oedema, erythema, changes in pigmentation, palpability of the implant and necrosis of overlying tissue. Specific therapeutic approaches for these complications and practical recommendations to minimize or avoid them are discussed. Hypersensitivity reactions and granuloma formation are the most distressing adverse effects. They can occur with most fillers. Mostly these hypersensitivity reactions are local granulomas but, rarely, generalized reactions also occur. Case reports of systemic reactions after injection of hyaluronic acid are documented. Treatments include steroids, minocycline and immunomodulatory agents, such as cyclosporin, tacrolimus and ascomycin. In selected cases, surgical procedures are necessary to elimirate granulomatous reactions. Implant migration and facial lipoatrophy are encountered with certain compounds. Extreme caution is therefore advocated before using permanent and non-reversible products for soft tissue augmentation. Those who use fillers need to be familiar with the complications of fillers and with the treatment of those complications. [source]

Intravascular bioresorbable polymeric stents: A potential alternative to current drug eluting metal stents

JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 11 2007
Tahmer Sharkawi
Abstract Stent implantation following angioplasty is the standard treatment of coronary artery disease necessitating interventional procedures. The use of stents as a platform for local drug delivery is a popular strategy to achieve local pharmacological treatment to the diseased artery. Drug eluting stents (DES) are now largely preferred to bare metal stents when stent implantation is necessary. Lately, there have been several reports questioning the long-term safety of DES. An alternative to these drug eluting metal stents are bioresorbable polymeric stents (BPS) because of the many advantages of bioresorbable material. However, the fundamental differences in polymeric and metallic materials make the development of such an alternative a significant challenge. This review discusses the different advantages of BPS and the many constrains and requirements of such devices. An up to date commented review of published data concerning BPS is presented. Considerations are given on using BPS as local drug delivery systems as well as on evaluating BPS performances. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 2829,2837, 2007 [source]

Adalimumab sustains clinical remission and overall clinical benefit after 2 years of therapy for Crohn's disease

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 12 2010
R. PANACCIONE
Aliment Pharmacol Ther,31, 1296,1309 Summary Background, In the randomized, double-blind, placebo-controlled CHARM trial, adalimumab was more effective than placebo in maintaining clinical remission for patients with moderate-to-severe Crohn's disease (CD) through 56 weeks. Aim, To substantiate the long-term safety and clinical benefits of adalimumab through 2 years of therapy in CHARM and its open-label extension (ADHERE). Methods, Patients entering ADHERE on blinded therapy received adalimumab 40 mg every other week (eow). Patients who had already moved to open-label adalimumab eow or weekly in CHARM continued their regimens. Data were analysed by originally randomized treatment group at CHARM baseline (adalimumab 40 mg eow, adalimumab 40 mg weekly, or placebo), regardless of whether patients entered ADHERE or received open-label adalimumab (eow or weekly). Results, After up to 2 years of therapy, 37.6%, 41.9% and 49.8% of patients originally randomized to placebo, adalimumab eow and adalimumab weekly, respectively, were in clinical remission. All groups experienced sustained improvements on the Inflammatory Bowel Disease Questionnaire. Decreasing hazard rates for both all-cause and CD-related hospitalizations were observed over time. Over a 2-year period, the rates of serious adverse events and malignancies (33.3 and 1.1 events/100-patient-years respectively) were similar to those observed during the overall adalimumab CD clinical development programme. Conclusions, Adalimumab demonstrated sustained maintenance of clinical remission, improvements in quality of life and reductions in hospitalization during long-term treatment for CD, with no new safety concerns identified. [source]

One-year treatment of chronic urticaria with mizolastine: efficacy and safety

JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 2 2000
G Lorette
Abstract Aim,To assess the long-term safety and efficacy of the H1-receptor antagonist mizolastine in the symptomatic treatment of chronic urticaria (CU). Background,Mizolastine is a novel second generation antihistamine with additional anti-inflammatory properties which has been shown to be effective in this condition as well as in allergic rhinitis. As the drug is used for chronic treatment, a detailed study of its efficacy and safety over a prolonged period was warranted. Methods,This open label multicentre trial recruited 211 patients suffering from CU (67% female; mean age 40 ± 13 years), with , 1 episode/week if untreated. After a 7-day placebo run-in period, patients received mizolastine (10 or 15 mg) for 12 months. Efficacy was assessed by the patient using daily diary cards and overall condition evaluation at study visits. Clinicians also assessed the same parameters at each visit, and gave a global assessment at study termination. Safety was assessed by monitoring adverse events and laboratory parameters. Cardiac safety was monitored every 4 months using 12-lead ECGs, with particular attention to QT intervals. Results,The trial was completed by 127 patients. Mizolastine reduced overall discomfort from the second week of therapy, and reduced itching and the number and size of wheals, as assessed by the patients. The clinician's assessment of the proportion of patients with > 10 wheals decreased from 42% to 28% after 2 months. Clinical assessment also indicated that itch intensity and angioedema were improved by mizolastine, and the improvement was sustained throughout the trial. The investigators estimated that 70% of patients benefited from therapy. There were no drug-related serious adverse events during the study. The cardiac repolarization assessed according to the QTc intervals was not modified during prolonged administration. Conclusion,Mizolastine improves CU symptoms, and these improvements are sustained over 12 months with no loss of drug sensitivity. No specific side-effects are associated with its long-term use in the current study. [source]

Infliximab safety profile and long-term applicability in inflammatory bowel disease: 9-year experience in clinical practice

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2010
Y. ZABANA
Aliment Pharmacol Ther,31, 553,560 Summary Background, Most available data on infliximab therapy come from large, short-term, pivotal RCTs and concerns about long-term safety profile still remain. Aim, To evaluate the long-term safety profile of infliximab in inflammatory bowel disease (IBD) in a clinical practice setting. Methods, Since 1999, all IBD patients treated with infliximab were registered and clinical outcomes prospectively recorded up to March 2008, loss of follow-up or patient's death. Infliximab regimens and preventive measures were in accordance with the prevalent guidelines or with the manufacturer's recommendations. Results, One hundred fifty-two patients were included (121 Crohn's disease, 24 ulcerative colitis, 7 indeterminate colitis), with a median of 5 infliximab infusions (IQR 3,8) and 87% of patients received at least three infusions. Seventy-nine per cent of them received concomitant immunomodulators and 70% were pre-medicated with hydrocortisone from the first infusion. After a median follow-up of 142 weeks, 13% presented infusion reactions, 13% viral or bacterial infections and two patients developed neoplasia. The mortality rate was 2.6% (four patients). Conclusions, Infliximab therapy is safe when the recommended preventive measures are implemented, with a rate of serious adverse events less than 10%. No new safety signals were found. [source]

Oats in the treatment of childhood coeliac disease: a 2-year controlled trial and a long-term clinical follow-up study

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 10 2006
K. HOLM
Summary Background The exclusion of oats from the diet in coeliac disease is controversial. Aim To study the long-term safety of oats in the treatment of children with coeliac disease. Methods Altogether 32 children with coeliac disease were enrolled in a 2-year controlled trial. Twenty-three children in remission were randomized either to oats or gluten challenge; when small bowel histological relapse was evident after gluten challenge, a gluten-free diet including oats was started. Furthermore, nine newly detected coeliac patients adopted an oat-containing gluten-free diet. Small bowel mucosal morphology, CD3+, ,,+ and ,,+ intraepithelial lymphocytes, human leucocyte antigen (HLA) DR expression and coeliac serology were determined. After the trial, the children were allowed to eat oats freely; follow-up was extended up to 7 years. Results In coeliac children in remission, oats had no detrimental effect on intestinal histology or serology during the 2-year trial. In contrast, the gluten-challenge group relapsed after 3,12 months. Complete recovery from the disease was accomplished in all relapsed and newly detected patients on an oat-containing gluten-free diet. After the trial, 86% of the children preferred to consume oats and they all remained in remission. Conclusion In most children with coeliac disease, long-term consumption of oats is well tolerated, and it does not result in small bowel mucosal deterioration or immune activation. [source]

Modafinil and Zolpidem Use by Emergency Medicine Residents

ACADEMIC EMERGENCY MEDICINE, Issue 12 2009
Brian D. McBeth MD
Abstract Objectives:, The objective was to assess the prevalence and patterns of modafinil and zolpidem use among emergency medicine (EM) residents and describe side effects resulting from use. Methods:, A voluntary, anonymous survey was distributed in February 2006 to EM residents nationally in the context of the national American Board of Emergency Medicine in-training examination. Data regarding frequency and timing of modafinil and zolpidem use were collected, as well as demographic information, reasons for use, side effects, and perceived dependence. Results:, A total of 133 of 134 residency programs distributed the surveys (99%). The response rate was 56% of the total number of EM residents who took the in-training examination (2,397/4,281). Past modafinil use was reported by 2.4% (57/2,372) of EM residents, with 66.7% (38/57) of those using modafinil having initiated their use during residency. Past zolpidem use was reported by 21.8% (516/2,367) of EM residents, with 15.3% (362/2,367) reporting use in the past year and 9.3% (221/2,367) in the past month. A total of 324 of 516 (62.8%) of zolpidem users initiated use during residency. Side effects were commonly reported by modafinil users (31.0%),most frequent were palpitations, insomnia, agitation, and restlessness. Zolpidem users reported side effects (22.6%) including drowsiness, dizziness, headache, hallucinations, depression/mood lability, and amnesia. Conclusions:, Zolpidem use is common among EM residents, with most users initiating use during residency. Modafinil use is relatively uncommon, although most residents using have also initiated use during residency. Side effects are commonly reported for both of these agents, and long-term safety remains unclear. [source]

UNINTENTIONAL OVERDOSE WITH INTRATHECAL ZICONOTIDE

PAIN MEDICINE, Issue 2 2002
Article first published online: 4 JUL 200
Steven G. Charapata MD, Research Medical Center, Kansas City, MO; David Ellis MD, PhD, Elan Pharmaceuticals, South San Francisco, CA Ziconotide is a novel, N-type, voltage-sensitive calcium channel (VSCC) blocker, with well-documented efficacy as an intrathecal (IT) analgesic. Ziconotide has been administered to over 1000 chronic pain patients in nine clinical trials. Over 350 patients have been on ziconotide IT therapy for more than three months in a long-term safety and tolerability study. Common adverse events for ziconotide include dizziness, nausea, nystagmus, abnormal gait, constipation, urinary retention, somnolence, postural hypotension, vomiting, confusion and abnormal vision. Ziconotide adverse events are recognizable, reversible and manageable, by dose adjustment and slow dose titration. Case reports of unintentional overdose in six chronic pain patients treated with IT ziconotide are presented. These unintentional overdoses were attributable to pump programming or dilution errors; none were lethal. The patient who received the highest overdose was administered 31 mcg/hr over 24 hours, or nearly 750 mcg ziconotide, total. This hourly dose rate is 300-fold the current recommended initial dose rate of 0.1 mcg/hr. This patient was sedated, but arousable; vital signs were stable and patient had no change in blood pressure. His symptoms resolved within 24 hours. His Visual Analog Score of Pain Intensity (VASPI) was reduced from 82 at baseline to 2.5 at the end of the titration period. The patient elected to continue in the long-term IT ziconotide study. The other 5 cases of inadvertent overdose were less severe, with dose rate at 5 mcg/hr or less. Associated adverse events also resolved within 24-hours of discontinuing ziconotide infusion. Unlike an unintentional overdose with IT morphine, which slows respiration and could potentially lead to hypoxia, coma or death; ziconotide does not produce respiratory depression. No tolerance to the analgesic effect of ziconotide, or withdrawal symptoms after discontinuation of the drug have been reported. Ziconotide has a wide margin of safety as an IT analgesic. [source]

Anti-inflammatory treatment for recurrent wheezing in the first five years of life

PEDIATRIC PULMONOLOGY, Issue 4 2003
Athanasios G. Kaditis MD
Abstract Medications identified for the treatment of recurrent wheezing in preschool children by the Expert Panel Report of the NHLBI Guidelines for the Diagnosis and Management of Asthma include inhaled corticosteroids, chromones, theophylline, and leukotriene pathway modifiers. However, these various agents differ in their mechanism, extent of action on the airway inflammatory process, and degree of clinical efficacy. Inhaled corticosteroids can control symptoms in many young children with even severe persistent wheezing, but data on their long-term safety when administered in preschool-age children are scarce. There is some information on the uninterrupted use of inhaled corticosteroids in school-age children and the absence of an adverse effect on ultimate adult height. Despite laboratory evidence of adrenal suppression in some studies, few pediatric cases of clinical adrenal insufficiency have been reported. Low-dose inhaled corticosteroid (<400 mcg/day for beclomethasone), which is adequate for controlling mild persistent symptoms, is generally safe. Chromones have a remarkable safety profile, but they are most effective for symptoms of mild severity. Promising data have been published on the efficacy and safety of leukotriene pathway modifiers when used in young children with persistent symptoms. It is uncertain whether early introduction and long-term administration of inhaled corticosteroids prevent development of irreversible airway obstruction. Nevertheless, they may be especially useful for patients with moderate to severe disease in whom other agents (chromones or leukotriene pathway modifiers) will most likely fail to control symptoms. Pediatr Pulmonol. 2003; 35:241,252. © 2003 Wiley-Liss, Inc. [source]

Use of fibrates in diabetes: what does the FIELD trial tell us?

PRACTICAL DIABETES INTERNATIONAL (INCORPORATING CARDIABETES), Issue 3 2006
Consultant PhysicianArticle first published online: 24 MAY 200, Dr NI Jowett MD, FRCP Consultant in Cardiovascular Medicine
Abstract FIELD was the largest cardiovascular prevention trial using fibrates in type 2 diabetes. Whilst the primary endpoint was not achieved, fenofibrate therapy associated with fewer non-fatal myocardial infarctions and revascularisation procedures. Progress of renal and retinal microvascular disease appeared to be slowed. Although many patients were also taking statin therapy, FIELD does not provide evidence on efficacy or long-term safety when co-prescribed with fibrates. Statin monotherapy remains first line therapy for diabetic dyslipidaemia. Copyright © 2006 John Wiley & Sons, Ltd. [source]