Adherence to asthma controller medication regimens.

BACKGROUND: Improved adherence to inhaled corticosteroids (ICS) is recognized as an important factor in reduced morbidity, mortality and consumption of health care resources. The present study was designed to replicate previous reports of patient adherence with fluticasone/salmeterol in a single inhaler (FSC), fluticasone and salmeterol in separate inhalers (FP+SAL), fluticasone and montelukast (FP+MON), fluticasone alone (FP) and montelukast alone (MON). METHODS: A 24-month observational retrospective study was conducted using administrative claims data. Subjects were 12 years old with 24 months of continuous enrollment; had 1 asthma claim (ICD-9: 493), 1 short-acting beta(2)-agonist claim, and 1 FSC, FP, SAL, or MON claim. Outcomes included asthma medication refill rates and persistence measured by treatment days. This study was designed with a unique population of patients with asthma from different health plans to validate previous findings. RESULTS: A total of 3,503 subjects were identified based on their index medication: FSC (996), FP+SAL (259), FP+MON (101), FP (1254) and MON (893). Mean number of prescription refills for FSC (3.98) was significantly higher than FP (2.29) and the FP component of FP+SAL (2.36), and FP+MON (2.15), P<0.05. No significant differences were observed between FSC and MON fill rates (4.33). Mean number of treatment days was greater for FSC compared to FP, FP+SAL, and FP+MON (P<0.0001). CONCLUSION: This study confirms a previous report that adherence profiles of fluticasone and salmeterol in a single inhaler are significantly better when compared to the controller regimens of fluticasone and salmeterol in separate inhalers, fluticasone and montelukast, or fluticasone alone and similar to montelukast alone.

Cost-efficacy comparison of inhaled fluticasone propionate and budesonide in the treatment of asthma.

BACKGROUND: The results of a recent meta-analysis comparing 2 inhaled corticosteroids, fluticasone propionate (FP) and budesonide, demonstrated that FP had an improved efficacy-to-safety ratio compared with budesonide. However, limited data are available on the relative economic benefits of these 2 regimens. OBJECTIVE: This pharmacoeconomic analysis used individual patient data from studies in the meta-analysis to compare the relative cost-efficacy of 2 asthma regimens from the perspective of a US third-party payer. METHODS: This analysis included all 7 studies in the meta-analysis that compared budesonide with FP dosed at approximately half the dose of budesonide and that included measurement of daily morning peak expiratory flow (PEF). RESULTS: The total daily per-person cost of asthma management was higher for patients treated with budesonide than with FP ($3.00 vs $2.25, respectively). Treatment with FP had greater cost-efficacy than treatment with budesonide, based on a range of outcome measures that included improvement in morning PEF, symptom-free days, and episode-free days. The daily cost per effectively treated patient (an increase in PEF of > or = 10%) was $5.62 with FP and $10.05 with budesonide. The cost per symptom-free day was $4.36 with FP, compared with $6.67 with budesonide. The cost per episode-free day was $5.60 with FP and $9.42 with budesonide. The pharmacoeconomic difference continued to favor FP as the criteria for success were made more stringent and the cost of budesonide was lowered. CONCLUSION: Based on data from the 7 randomized, controlled trials, treatment of asthma with FP was more effective and less expensive, using US health care assumptions and costs, than treatment with budesonide.

Torsades de pointes associated with chlorpromazine: case report and review of associated ventricular arrhythmias.

PURPOSE: To present a case of chlorpromazine-associated torsades de pointes, review established cases of ventricular arrhythmias associated with chlorpromazine, and describe the proarrhythmic characteristics of this drug. DATA SOURCES: Articles identified through a search of MEDLINE and IDIS from January 1966-November 2000 and thorough review of the article bibliographies. Patient cases also were identified from a search of the Food and Drug Administration's Adverse Event Reporting System database (November 1997-March 2001). Cases involving intentional overdoses of chlorpromazine were excluded. RESULTS: In addition to the case reported herein, 12 cases of documented, chlorpromazine-associated ventricular arrhythmias were identified; five had characteristic features of torsades de pointes. Chlorpromazine delayed repolarization and produced electrocardiographic abnormalities; although, whether chlorpromazine induced torsades de pointes through a mechanism of early afterdepolarizations is unclear. Similar to other instances of drug-induced torsades de pointes, concurrent factors such as electrolyte deficiencies may place the patient at increased risk for arrhythmia. CONCLUSIONS: Chlorpromazine can delay repolarization and produce electrocardiographic abnormalities. These can result infrequently in ventricular arrhythmias and torsades de pointes, particularly in patients with confounding factors.

The burden of COPD in the U.S.A.: results from the Confronting COPD survey.

Chronic obstructive pulmonary disease (COPD) is a progressive disorder of airflow limitation that is not fully reversible, with disabling symptoms including chronic cough and dyspnoea. Although a number of studies in the U.S.A. have assessed the impact of COPD on the healthcare system and society, data on healthcare resource utilization (particularly outpatient services and medication use) in patients with mild to moderate COPD, or patients who meet symptom criteria for COPD but have not received this diagnosis, are limited or unavailable. To fill gaps in current knowledge about the impact of this disease, an economic analysis was conducted on the data collected from patients enrolled in the U.S.A. sample of Confronting COPD in North America and Europe, the first large-scale international survey of the burden of the disease. The annual cost of healthcare resource utilization was estimated at US dollar 4119 per patient with COPD, with indirect (non-medical care) costs amounting to US dollar 1527 per patient. The annual estimated societal cost was therefore US dollar 5646 per patient. The majority of disease costs in the survey were associated with inpatient hospitalizations (US dollar 2891). The results of the survey suggest that interventions that improve COPD outcomes by decreasing symptoms and preventing acute exacerbations could substantially decrease the costs associated with this disease.

Cost analysis of the use of inhaled corticosteroids in the treatment of asthma: a 1-year follow-up.

A retrospective cohort using pharmacy and medical claims was analysed to determine whether the differences in efficacy of various inhaled corticosteroids demonstrated in clinical trials lead to differences in costs of care observed in clinical practice. Subjects that had an ICD-9 (493.XX) code for asthma and a new pharmacy claim for inhaled fluticasone propionate 44 mcg (FP), beclomethasone dipropionate (BDP), triamcinolone acetonide (TAA), budesonide (BUD) or flunisolide (FLU) were identified and followed for 12 months. Annual asthma care charges (pharmacy and medical) over the 12-month observation period were significantly (P < 0.03) higher in patients treated with BDPTAA, BUD and FLU compared to FP, 24%, 27%, 34% and 45% respectively In addition, patients treated with BDPTAA, and FLU were associated with significantly (P < 0.005) higher total healthcare (asthma + non-asthma) charges compared to patients on FP, 53%, 46% and 39% respectively Asthma care and total healthcare charges remained lower for FP after including FP110 mcg and excluding patients who were extreme cost outliers (+/- 2 SD from the mean) in a univariate sensitivity analysis. This analysis supports recent randomized control trials that FP offers a superior efficacy profile at lower asthma care as well as total healthcare charges compared to other inhaled corticosteroids.

Comparison of asthma costs in patients starting fluticasone propionate compared to patients starting montelukast.

An observational study using pharmacy and medical claims was used to determine whether there are differences in asthma care cost between patients that are newly started on montelukast and low-dose fluticasone propionate. Patients were identified who had at least one ICD-9 (493.XX) claim for asthma and were newly prescribed inhaled fluticasone propionate 44 microg (FP) or montelukast 5 or 10 mg (MON). Subjects could not have had a claim for any inhaled corticosteroid or oral leukotriene modifier in 9 months prior to the first prescription claim for either FP or MON. They were subsequently followed for 9 months. Multi-variate regression analysis was used to determine the influence of these single-controller therapies on post-index asthma related costs. Positively skewed cost variables were log-transformed prior to their inclusion into the multi-variate model. Asthma-related costs were adjusted for age, gender, health plan, co-morbidities, pre-index asthma medication use and pre-index asthma care costs. Multivariate regression analysis, adjusting for baseline covariates, indicated that compared to treatment with montelukast, treatment with FP had significantly (P<0.001) lower post-index total asthma related costs. Adjusted least squares mean total asthma care costs for the 9-month post-index period were $US649 for FP 44 microg compared to $US1028 for montelukast.

Cost-efficacy analysis of fluticasone propionate versus zafirlukast in patients with persistent asthma.

OBJECTIVE: To compare the relative value of an inhaled corticosteroid, fluticasone propionate 88 microg twice daily, versus an oral leukotriene receptor antagonist, zafirlukast 20 mg twice daily, in patients with persistent asthma currently receiving short acting beta2-agonists alone. STUDY DESIGN: A cost-efficacy analysis using resource utilisation and clinical data obtained prospectively from a multicentre, randomised, double-blind, double-dummy, placebo-controlled 12-week clinical trial conducted in the US. PERSPECTIVE: Third-party payor. PATIENTS AND METHODS: A total of 451 corticosteroid-naive patients with persistent asthma were treated with either fluticasone propionate 88 microg twice daily or zafirlukast 20 mg twice daily. All patients were given salbutamol (albuterol) to be used as rescue medication. Data were examined using intent-to-treat analysis. RESULTS: Mean daily per person cost-efficacy ratios using improvement in forced expiratory volume in 1 second (FEV1) [> or = 12% increase from baseline] were $US 3.47 for fluticasone propionate compared with $US 7.81 for zafirlukast (1999 values). The mean daily per person cost-efficacy ratios for symptom-free days obtained were $US 5.51 for fluticasone propionate compared with $US 14.98 for zafirlukast. These cost-efficacy ratios remained in favour of fluticasone propionate after a robust sensitivity analysis. CONCLUSIONS: Treatment with fluticasone propionate 88 kg twice daily was the most cost effective treatment compared with zafirlukast 20 mg twice daily in this 12-week clinical trial. This analysis supports the use of fluticasone propionate 88 microg twice daily as first-line treatment in patients with persistent asthma previously treated with short-acting beta2-agonist alone.

Propantheline bromide in the management of hyperhidrosis associated with spinal cord injury.

OBJECTIVE: To report 2 cases in which oral propantheline reduced the discomfort associated with sweating related to spinal cord injury (SCI), and to review the literature on the management of SCI-related sweating. CASE SUMMARIES: Case 1: A 27-year-old quadriplegic man with an American Spinal Injury Association (ASIA) Frankel class C injury to C5/C6 experienced profuse sweating and requested propantheline. He stated that he had received the medication previously and reported that propantheline 15 mg tid had controlled his sweating. Propantheline bromide was reinstituted, and within 24 hours, the patient's episodes of profuse sweating had decreased markedly in number and frequency. Case 2: A 35-year-old quadriplegic woman had an ASIA class D lesion at C3. Since her injury, she had experienced profuse sweating that worsened when she became cold and at night. She stated that her sweating was under control as long as she took propantheline. Propantheline therapy was continued and no further sweating episodes have occurred. DATA SOURCE: A MEDLINE search was used to identify pertinent literature including reviews. Standard texts and texts referenced in the pertinent literature also were examined. STUDY SELECTION: All available sources of information were reviewed. DATA SYNTHESIS: The earliest case reports of systemic therapy for hyperhidrosis described the use of the anticholinergic methantheline bromide. Methantheline in combination with ergoloid mesylates also was suggested for the treatment of congenital hyperhidrosis. Local topical therapy for hyperhidrosis, such as aluminum chlorohydrate and aluminum chloride, the active ingredients in some antiperspirants, have been tried with some success. Talc, starch, and other powders have been suggested to absorb excessive sweat. Formalin and glutaraldehyde also have been used. Topical propantheline bromide has been used successfully in treating palmar and plantar hidrosis. Clonazepam has been used successfully in a case of unilateral localized hyperhidrosis. Systemic phenoxybenzamine has been used with some success and there have been attempt at other systemic therapy using mecamylamine, atropine, propoxyphenel, and methenamine. Scopolamine patches also have been used successfully in a small number of patients. Other agents that have been used include dibenamine, piperoxan, and phentolamine. Systemic propantheline also has been listed as an agent with potential efficacy in treating the profuse sweating associated with SCI, but was not recommended primarily because of adverse effects and difficulty in titrating to the lowest effective dosage. However, studies or case reports specific to the use of propantheline in patients with SCI appear to be lacking, as are reports of direct comparison between propantheline and other agents. DISCUSSION: Concerning the mechanism of action of propantheline bromide for hyperhidrosis, it seems reasonable to attribute its effects to the drug's well-documented anticholinergic/antimuscarinic actions. At dosages used to effectively treat neurogenic bladder, propantheline bromide also should block the muscarinic receptors responsible for sweat gland stimulation. Central nervous system adverse effects should be minimal at usual clinical dosages, as propantheline does not cross the blood-brain barrier. CONCLUSIONS: It would appear that in some patients with SCI who are subject to incidental episodes of profuse sweating, oral propantheline may offer some relief and may, in fact, be well tolerated, as in the cases described. Additionally, propantheline would seem a good therapeutic choice in SCI patients with excessive sweating and neurogenic bladder dysfunction who may derive dual benefit from the agent.

One-year claims analysis comparing inhaled fluticasone propionate with zafirlukast for the treatment of asthma.

BACKGROUND: Randomized clinical trials have demonstrated that fluticasone propionate (FP) has better objective as well as subjective clinical outcomes than zafirlukast (ZA) in the treatment of asthma. OBJECTIVE: The goal of this study was to determine whether the superiority of FP over ZA observed in clinical trials is supported under actual practice conditions. METHODS: A retrospective cohort analysis of pharmacy and medical claims for asthma was performed. Patients were identified who had at least 1 ICD-9 (493.XX) claim for asthma and were recently prescribed inhaled FP or ZA. Subjects could not have had a claim for any inhaled corticosteroid or oral leukotriene modifier in the 9 months before initiation of FP or ZA. They were subsequently observed for 12 months. RESULTS: A total of 725 persons were new users of FP and 309 of ZA. FP was associated with a 70% reduced risk for hospitalization (P =.0232), a 49% lower risk for an emergency department event (P =.0546), and a 51% reduction in combined emergency department events and hospitalizations (P =.0268) when compared with ZA. Adjusted annual asthma care costs declined significantly for FP and increased for ZA. The adjusted mean difference in annual asthma costs was $215 less per patient for FP (P <.0001). CONCLUSION: Asthma care costs decreased for patients treated with FP and increased for patients treated with ZA. Furthermore, FP-treated patients had significantly lower risks of asthma-related hospitalization than ZA patients. This study supports results seen in clinical trials comparing these two medications.

Fluticasone propionate versus zafirlukast: effect in patients previously receiving inhaled corticosteroid therapy.

BACKGROUND: The use of inhaled corticosteroids compared with leukotriene modifying drugs in the treatment of persistent asthma has not been extensively studied. OBJECTIVE: To compare the efficacy and safety of a low dose of fluticasone propionate (FP) and zafirlukast in patients previously maintained on inhaled corticosteroids. METHODS: Patients (> or = 12 years old; FEV1 = 60% to 85% of predicted) with persistent asthma who were previously treated with low doses of triamcinolone acetonide (TAA) 400 to 800 microg/day or beclomethasone dipropionate (BDP) 168 to 336 microg/day were randomized to treatment with FP aerosol 88 microg BID (FP, n = 221) or zafirlukast 20 mg BID (n = 216) over 6 weeks. RESULTS: Treatment with FP significantly increased the mean change at endpoint (the last post-baseline observation) in FEV1 (0.22 L versus 0.03 L, P < .001), morning PEF (17.8 versus 3.1 L/min, P = .004), evening PEF (16.7 versus 2.6 L/min, P = .002), the percentage of symptom-free days (16.2 versus 7.1%, P = .007), and the percentage of rescue-free days (23.4 versus 9.3%, P < .001), and significantly decreased rescue albuterol use (-0.66 puffs/day versus an increase of 0.27 puffs/day, P < .001) and combined symptom scores (-0.13 versus an increase of 0.08, P < .001) compared with zafirlukast. Treatment with FP maintained the percentage of awakening-free nights (-1.0 +/- 1.0); in contrast, treatment with zafirlukast reduced the percentage of awakening-free nights (-9.0 +/- 1.6, P < .001). A clinically meaningful difference (change of > or = 0.5; P < .001) was observed between FP and zafirlukast in the Asthma Quality of Life Questionnaire (AQLQ) global score and for each domain score except activity limitation (change of 0.3, P < .001). Significantly more patients in the zafirlukast group experienced an asthma exacerbation (n = 14) compared with FP-treated patients (n = 5, P = .035). Patients in the zafirlukast group were significantly more likely to be withdrawn due to lack of efficacy (P < .001). CONCLUSION: Switching patients from low doses of inhaled corticosteroids to a lower total microgram dose of FP improves pulmonary function, asthma symptoms, and quality of life, while switching to the leukotriene receptor antagonist zafirlukast may result in worsening of asthma control. This was indicated by the significant number of zafirlukast-treated patients who were dropped from the study due to lack of efficacy within 6 weeks of discontinuing inhaled corticosteroids.