tiotropium-bromide and Drug-Related-Side-Effects-and-Adverse-Reactions

This article reviews findings from recently published randomized controlled trials and systematic reviews to provide an up-to-date assessment of the efficacy and safety of tiotropium, the only currently available long-acting muscarinic antagonist, when used alone or in conjunction with other respiratory medications in the treatment of chronic obstructive pulmonary disease (COPD).. Results of recent clinical trials support findings from earlier trials in patients with moderate to very severe COPD demonstrating significant benefits of tiotropium compared to placebo, including sustained increases in lung function, reductions in exacerbations and risk of exacerbation-related hospitalizations, and improvement in health status. These benefits were particularly noted in the 4-year UPLIFT study that included 5993 COPD patients, including a large percentage with moderate severity. Whereas the cardiovascular safety of tiotropium has been questioned, results of the UPLIFT trial and a recent pooled analysis of data from 30 trials of tiotropium demonstrated that tiotropium is associated with reductions in the risk of all-cause mortality, cardiovascular mortality and cardiovascular events.. Recent findings confirm the benefits of tiotropium in COPD management and provide reassurance regarding its safety. Moreover, the recent UPLIFT trial provides supportive evidence for the efficacy of tiotropium in COPD patients already receiving treatment with long-acting inhaled beta-agonists and inhaled corticosteroids, suggesting advantages of 'triple' therapy in advanced disease. Further, well designed, adequately powered studies should explore the potential advantages and disadvantages of various combinations of currently available long-acting respiratory medications in COPD, particularly in different clinical phenotypes of this heterogeneous disease.

Topics: Cholinergic Antagonists; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Humans; Pulmonary Disease, Chronic Obstructive; Scopolamine Derivatives; Tiotropium Bromide; Treatment Outcome

Tiotropium is a long-acting inhaled anticholinergic developed for the treatment of chronic obstructive pulmonary disease (COPD) and has been available since 2002. We sought to update an evaluation of the safety of tiotropium in the HandiHaler formulation as significant clinical trial data have become available over time.. Pooled analysis of adverse event reporting from phase III and IV tiotropium HandiHaler clinical trials with the following characteristics was performed: randomized, double-blind, parallel group, placebo-controlled design, tiotropium 18 microg once-daily dosing, COPD indication, duration of at least four weeks. Incidence rates by treatment group, rate differences (tiotropium-placebo), and 95% confidence intervals were determined.. Twenty-six trials were identified involving 17,014 patients. Mean age was 65 years, mean forced expiratory volume in one second was 1.16 L (41% predicted), 76% men. Total exposure to study drug was 11,958 patient-years (tiotropium) and 10,578 patient-years (placebo). Tiotropium was associated with a reduced risk (expressed as rate difference [95% confidence interval] per 100 patients-years at risk) for an adverse event (-17.5 [-22.9, -12.2]), serious adverse event (-1.41 [-2.81, -0.00]) and a fatal event (-0.63 [-1.14, -0.12]). A reduced risk was present for adverse events that were cardiac (-0.79 [-1.48, -0.09]), lower respiratory (-14.2 [-17.0, -11.5]) and for a composite endpoint of major adverse cardiovascular events (-0.45 [-0.85, -0.05]). Typical expected inhaled anticholinergic effects such as dry mouth, constipation, and urinary difficulties were observed in the safety database.. The safety data review does not indicate an increased risk for death or cardiovascular morbidity during tiotropium treatment in patients with COPD.

Topics: Aged; Cholinergic Antagonists; Clinical Trials as Topic; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Male; Middle Aged; Nebulizers and Vaporizers; Pulmonary Disease, Chronic Obstructive; Scopolamine Derivatives; Tiotropium Bromide; Treatment Outcome

The cardiovascular safety of revefenacin, an anticholinergic indicated for the maintenance treatment of patients with chronic obstructive lung disease (COPD), was evaluated in phase 3 trials in patients with moderate to very severe COPD. No clinically meaningful changes in 12-lead electrocardiogram recordings were observed with up to 52 weeks of once-daily revefenacin 88 or 175 μg. In a pooled analysis of Studies 0126 and 0127, the incidence of prolonged QT interval corrected for heart rate using the Fridericia correction formula (QTcF; >450 msec) for revefenacin 88 μg (n = 23, 5.6%) and revefenacin 175 μg (n = 23, 5.9%) was similar to that for placebo (n = 22, 5.3%). In Study 0128, the incidence of prolonged QTcF was similar in the revefenacin 175 μg (n = 25, 7.7%) and tiotropium (n = 26, 7.3%) groups and lower in the revefenacin 88 μg (n = 15, 4.2%) group. There were four major adverse cardiac events (MACEs) in Study 0126 (one, two, and one in the placebo, revefenacin 88 μg, and revefenacin 175 μg groups, respectively), no MACEs in Study 0127 and 26 MACEs in Study 0128 (9, 10 and 7 in the revefenacin 88 μg, revefenacin 175 μg and tiotropium groups, respectively). In Study 0128, only one MACE was considered possibly/probably related to revefenacin (atrial fibrillation in the revefenacin 175 μg group). Thus, revefenacin may provide beneficial nebulized therapy for patients with COPD without further elevating their risk of cardiovascular events.

Topics: Administration, Inhalation; Adult; Aged; Aged, 80 and over; Benzamides; Bronchodilator Agents; Carbamates; Double-Blind Method; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Male; Middle Aged; Muscarinic Antagonists; Nebulizers and Vaporizers; Pulmonary Disease, Chronic Obstructive; Risk Assessment; Tiotropium Bromide

This was a multicenter, randomized, double-blind within device, parallel-group, dose-ranging study. COPD patients (n = 202; 86% male; mean age: 61 years) were randomized to receive tiotropium 1.25 microg, 2.5 microg, 5 microg, 10 microg, or 20 microg Respimat SMI (a novel, propellant-free device); tiotropium 18 microg HandiHaler; placebo Respimat; or placebo HandiHaler for 3 weeks. The primary endpoint was trough FEV1 on Day 21. Other assessments included FVC, PEFR, rescue medication use, safety, and pharmacokinetics. In general, all active treatments improved the primary and secondary endpoints on Day 21 (steady state) compared with placebo. Tiotropium 5 microg Respimat, 20 microg Respimat, and tiotropium 18 microg HandiHaler were statistically significantly higher than placebo for the primary endpoint (mean change in trough FEV1 was 150 mL (both Respimat doses) versus 20 mL (placebo Respimat); p < 0.05; and 230 mL (HandiHaler) versus -90 mL (placebo HandiHaler); p < or = 0.001). The urinary excretion (up to 2 hours post-dose) of tiotropium 5-10 microg Respimat was comparable with tiotropium 18 microg HandiHaler; the overall incidence of adverse events was comparable across treatment groups. Tiotropium 5 and 10 microg Respimat improve lung function in COPD patients and appear to be comparable with tiotropium 18 microg HandiHaler.

Topics: Aged; Bronchodilator Agents; Dose-Response Relationship, Drug; Drug-Related Side Effects and Adverse Reactions; Endpoint Determination; Female; Humans; Male; Metered Dose Inhalers; Middle Aged; Placebos; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Scopolamine Derivatives; Tiotropium Bromide

Long-acting bronchodilators, including long-acting beta. We identified a cohort of new users of long-acting bronchodilators between 2002 and 2012, age 55 or older, from the United Kingdom's Clinical Practice Research Datalink. Patients initiating tiotropium were matched on high-dimensional propensity scores and prior inhaled corticosteroid use with patients initiating LABAs, and followed for 1 year for the occurrence of acute myocardial infarction, stroke, heart failure, arrhythmia, and pneumonia.. A total of 26,442 tiotropium initiators were matched to 26,442 LABA initiators, mainly single inhalers combined with inhaled corticosteroids. The hazard ratio of acute myocardial infarction associated with tiotropium initiation, relative to LABA initiation, was 1.10 (95% CI, 0.88-1.38), whereas for stroke it was 1.02 (95% CI, 0.78-1.34), for arrhythmia 0.81 (95% CI, 0.60-1.09), and heart failure 0.90 (95% CI, 0.79-1.02). The incidence of pneumonia was significantly less with tiotropium (hazard ratio, 0.81; 95% CI, 0.72-0.92).. COPD treatment initiation with tiotropium compared with LABA does not increase cardiovascular risk in the first year of treatment. The risk of pneumonia is higher with LABA, a likely effect of the inhaled corticosteroids present in many LABA inhalers used in real world clinical practice.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Aged; Bronchodilator Agents; Canada; Cardiovascular Diseases; Delayed-Action Preparations; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Male; Middle Aged; Pneumonia; Propensity Score; Pulmonary Disease, Chronic Obstructive; Risk Assessment; Tiotropium Bromide

Adverse drug reactions is an important healthcare issue, it causes excess morbidity and mortality. The aim of this study was to determine the adverse drug reactions in patients who admitted to the outpatient clinic of respiratory diseases and to improve some clinical strategies if they are preventable.. This study is a prospective observational study which was performed to determine adverse drug reaction in patients who admitted to the outpatient clinic of respiratory diseases.. During the 15 months of study period a total of 114 adverse reactions were reported in 92 out of 18.130 patients. Most of the adverse reactions were related with gastrointestinal system, central nervous system and cardiovascular system. The most of the adverse events were associated with fixed inhaled formoterol-budesonide combination and inhaled tiotropium. The most frequently reported reactions were hoarseness, xerostomia, headache and dizziness. Poliuri and cough were less frequently reported reactions.. Most of the adverse reactions were of limited intensity but some of these side effects might effect patients compliance. Serious adverse events were not detected.

Topics: Administration, Inhalation; Bronchodilator Agents; Budesonide; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Ethanolamines; Female; Formoterol Fumarate; Humans; Male; Middle Aged; Outpatient Clinics, Hospital; Patient Compliance; Pharmacovigilance; Respiratory Tract Diseases; Scopolamine Derivatives; Tiotropium Bromide

Medication errors are widely reported for hospitalised patients, but limited data are available for medication errors that occur in community-based and clinical settings. Epidemiological data from poisons information centres enable characterisation of trends in medication errors occurring across the healthcare spectrum.. The objective of this study was to characterise the epidemiology and type of medication errors reported to the National Poisons Information Centre (NPIC) of Ireland.. A 3-year prospective study on medication errors reported to the NPIC was conducted from 1 January 2007 to 31 December 2009 inclusive. Data on patient demographics, enquiry source, location, pharmaceutical agent(s), type of medication error, and treatment advice were collated from standardised call report forms. Medication errors were categorised as (i) prescribing error (i.e. physician error), (ii) dispensing error (i.e. pharmacy error), and (iii) administration error involving the wrong medication, the wrong dose, wrong route, or the wrong time.. Medication errors were reported for 2348 individuals, representing 9.56% of total enquiries to the NPIC over 3 years. In total, 1220 children and adolescents under 18 years of age and 1128 adults (≥ 18 years old) experienced a medication error. The majority of enquiries were received from healthcare professionals, but members of the public accounted for 31.3% (n = 736) of enquiries. Most medication errors occurred in a domestic setting (n = 2135), but a small number occurred in healthcare facilities: nursing homes (n = 110, 4.68%), hospitals (n = 53, 2.26%), and general practitioner surgeries (n = 32, 1.36%). In children, medication errors with non-prescription pharmaceuticals predominated (n = 722) and anti-pyretics and non-opioid analgesics, anti-bacterials, and cough and cold preparations were the main pharmaceutical classes involved. Medication errors with prescription medication predominated for adults (n = 866) and the major medication classes included anti-pyretics and non-opioid analgesics, psychoanaleptics, and psychleptic agents. Approximately 97% (n = 2279) of medication errors were as a result of drug administration errors (comprising a double dose [n = 1040], wrong dose [n = 395], wrong medication [n = 597], wrong route [n = 133], and wrong time [n = 110]). Prescribing and dispensing errors accounted for 0.68% (n = 16) and 2.26% (n = 53) of errors, respectively.. Empirical data from poisons information centres facilitate the characterisation of medication errors occurring in the community and across the healthcare spectrum. Poison centre data facilitate the detection of subtle trends in medication errors and can contribute to pharmacovigilance. Collaboration between pharmaceutical manufacturers, consumers, medical, and regulatory communities is needed to advance patient safety and reduce medication errors.

Topics: Administration, Oral; Administration, Rectal; Adolescent; Adult; Aged, 80 and over; Child; Child, Preschool; Cholinergic Antagonists; Drug-Related Side Effects and Adverse Reactions; Female; Ferrous Compounds; Humans; Infant; Information Services; Ireland; Male; Medication Errors; Pharmaceutical Preparations; Pharmacists; Physicians; Poison Control Centers; Product Surveillance, Postmarketing; Prospective Studies; Scopolamine Derivatives; Telephone; Tiotropium Bromide; Young Adult