Asthma and COPD Patients' Perception of Appropriate Metered-Dose Inhaler Technique.

OBJECTIVES: Asthma and chronic obstructive pulmonary disease (COPD) are chronic illnesses of the airways affecting a good number of people in Lebanon and the Middle East. Pressurized metered-dose inhalers (pMDIs) are important drug delivery systems used to treat such pulmonary diseases. Drugs proven to be valuable and effective may fail to act effectively if such inhalers are used incorrectly. The purpose of this study was to assess the technical use of pMDIs by patients with pulmonary diseases presenting to the community pharmacies in Lebanon. METHODS: A structured questionnaire was developed to collect data. A total of 601 patients using drugs delivered through pMDIs and presenting to 12 Lebanese community pharmacies were recruited to participate in the research project. The questionnaire items were divided into 3 subscales: subscale 1-assessing the device preparation; subscale 2-investigating the device use; and subscale 3-examining the knowledge and use of spacers. After confirming the reliability and validity of the survey tool, patients' responses were analyzed and compared according to many variables. RESULTS: Many patients answered inaccurately to questions assessing both the device preparation and use. Around 40% of patients said they do not coordinate the inhalation with pressing the canister down. The mean scores were 1.72 (± 0.73) over 6 and 5.67 (± 1.44) over 7 for subscales 1 and 2, respectively. The mean total score on all questions was 7.39 over 13, with a standard deviation of 1.75. While patients' age did not impact the results, asthmatic, well-educated, male patients had fewer wrong answers when it comes to preparing and using the device (P < .01). CONCLUSIONS: Our study showed that many patients with asthma and COPD might not be properly using their pMDIs. Appropriate inhaler use is crucial for successful pulmonary disease management. As pMDIs are one of the most difficult devices to use, proper and tailored instructions should be given to patients.

Fixed-dose combination of umeclidinium and vilanterol for patients with chronic obstructive pulmonary disease: A systematic review.

Chronic obstructive pulmonary disease (COPD) is a common respiratory disease that is predicted to be one of the leading causes of death worldwide. Pharmacologic treatment options of COPD are bronchodilators, using either long-acting ß2-agonists (LABAs), or long-acting muscarinic antagonists (LAMAs), or a combination of two. Anoro Ellipta (umeclidinium + vilanterol) dry powder inhaler, a fixed-dose combination of LAMA and LABA, was Food and Drug Administration (FDA) approved in 2013 for COPD. The objective of this study is to evaluate the efficacy and safety of once daily umeclidinium/vilanterol (62.5 mcg/25 mcg) in COPD patients, focusing on pharmacodynamic and pharmacokinetic characteristics, efficacy and safety in clinical studies and cost. Literature search was done through PubMed (2004-2017) using the terms umeclidinium, vilanterol, COPD, LABA and LAMA. Recent and significant clinical trials about the monocomponents and their combination were identified, in addition to reviews, guidelines for COPD, data from manufacturer and FDA product labels. The search was limited to English language studies on human subjects. Clinical data published on the combination of umeclidinium/vilanterol in patients with COPD have shown greater improvements in lung function compared to monotherapies. However, further studies comparing umeclidinium/vilanterol FDC (ANORO) to other LABA/LAMA combinations are needed.

Adherence to International Guidelines for the Treatment of Uncomplicated Urinary Tract Infections in Lebanon.

OBJECTIVE: The purpose of this study is to evaluate antibiotic-prescribing practices and adherence to IDSA guidelines for the treatment of uncomplicated urinary tract infections in Lebanon. METHODS: This observational prospective study was conducted in 15 community pharmacies in Lebanon over 1 year in adult females. A regimen of nitrofurantoin 100 mg bid for 5 days or fosfomycin 3 grams single dose were considered appropriate. For the bivariate analysis, the chi-square test was used. RESULTS: A total of 376 patients were included in this study. The prescribed antibiotic was appropriate in 35 percent of the patients. Age (more than 50 years) did not significantly affect the appropriateness of the prescribed antibiotic (p=0.508). The frequency of attacks per year (more than 3) negatively affected the choice of antibiotic (p=0.025). The dose and duration of the prescribed antibiotic was appropriate in 73 and 58 percent of the patients, respectively, with a significant inappropriate dose and duration with fluoroquinolones as compared to nitrofurantoin and fosfomycin (p < 0.001 for the dose and p=0.014 for the duration of therapy). CONCLUSIONS: In an era of increasing bacterial resistance, interventions that improve physicians' prescribing practices for uncomplicated urinary tract infections are needed.

Patterns of use of dry powder inhalers versus pressurized metered-dose inhalers devices in adult patients with chronic obstructive pulmonary disease or asthma: An observational comparative study.

Numerous patients with chronic obstructive pulmonary disease (COPD) and asthma do not use inhaler devices properly, which can contribute to poor disease control. The objective of this study is to assess the technical and safety use of dry powder inhalers (DPIs) versus pressurized metered-dose inhalers (MDIs) in adult patients with COPD or asthma in Lebanon. A concurrent, prospective comparative observational study was conducted at one hospital and 15 community pharmacies in Lebanon. Over a period of 18 months, 246 questionnaires were filled. Patients included were adults with COPD or asthma. Answers were entered into the Statistical Package for Social Sciences software and excel sheet. T-test and correlation were used to analyze the results; 67.8% and 38.4% of those using DPIs and MDIs, respectively, performed the exact technical steps adequately ( p = 0.003, relative risk: 2.134, 95% confidence interval: 0.910-4.842). When compared to MDI, a higher percentage of DPI users found their devices easy to use. Moreover, 81.4% of the MDI users found difficulty in coordinating between pressing the canister and inhaling. Rates of exacerbations were significantly higher in MDIs vs. DPI users (59.4% vs. 21.7%). Overall, 44.31% of patients did not receive education from their healthcare professionals about the devices. A significant number of COPD/asthma adult patients do not use their devices properly. Even though DPIs were significantly easier to use, proper education on the technical use of all types of inhalers is needed.

Prescription patterns of benzodiazepines in the Lebanese adult population: a cross-sectional study.

This study assessed the profile of benzodiazepine (BDZ) users in Lebanon. Adult patients visiting the pharmacies with prescriptions of BDZs were included in the study. Seven hundred and eighty-six current BDZ users were included, of whom 54.2% were females. Twenty-three percent reported being alcohol consumers and were mostly males. The two most commonly used BDZs were alprazolam (34.6%) and bromazepam (33.6%). The indication for use was mainly anxiety (44.4%), insomnia (22.5%), and depression (15.9%). The prescribing physicians were primarily psychiatrists (43.2%), followed by general practitioners (29.7%). Forty percent had been taking the drug for more than a year. Among those using BDZs for at least 1 month, 35.5% increased the dose with time. Thirty-three percent reported having experienced side effects. Eighteen patients (2.3%) reported taking more than one BDZ concomitantly, while 18.3% were taking drugs that should not be prescribed along with BDZs. In conclusion, the use of BDZs is highest among females, especially for the treatment of anxiety. Moreover, continuous use of the drugs for more than a year as well as significant potential drug interactions was identified.

Olodaterol for the treatment of chronic obstructive pulmonary disease.

PURPOSE: Published data on the pharmacology, pharmacokinetics, efficacy, and safety of the once-daily, long-acting ß2-agonist (LABA) olodaterol are reviewed. SUMMARY: Olodaterol (Striverdi Respimat, Boehringer Ingelheim), a LABA with high selectivity for ß2-adrenergic receptors, is indicated for the treatment of chronic obstructive pulmonary disease (COPD); the recommended dose is 5 µg, to be delivered once daily via the Respimat inhaler. In 48- and 6-week Phase III clinical trials of olodaterol evaluating various lung function and symptomatic outcomes in patients with moderate to very severe COPD, olodaterol use was associated with significant improvements in spirometry outcomes, such as postbronchodilator forced expiratory volume in one second (FEV1), as well as dyspnea severity and quality-of-life measures. Other clinical trials demonstrated that olodaterol produced beneficial effects on FEV1 measures throughout the 24-hour dosing interval. A meta-analysis of data from 20 published research reports indicated that olodaterol's efficacy was comparable to that of the once-daily LABA indacaterol and that the combination of olodaterol and tiotropium provided improvements in lung function greater than those provided by tiotropium alone. Analysis of pooled data from four long-term trials showed that olodaterol's safety profile was comparable to that of formoterol; the most frequently reported adverse effects associated with olodaterol use were bronchitis, nasopharyngitis, and upper respiratory tract infection. CONCLUSION: Once-daily olodaterol 5 µg is an effective therapy in improving lung function and symptomatic outcomes in patients with moderate to very severe COPD receiving other maintenance therapy, with a satisfactory safety profile.

Herbal Products and Dietary Supplements: A Cross-Sectional Survey of Use, Attitudes, and Knowledge Among the Lebanese Population.

There has been a marked increase in use of herbal products and dietary supplements (HP/DS) in many developed and developing countries. However, data about consumption patterns and awareness about these products in the Lebanese population is scarce. The present study aimed to examine the determinants of HP/DS use in Lebanese adults, identify potential interactions and safety concerns and assess the knowledge and attitudes of consumers towards the efficacy and safety of these products. A face-to-face, 28-item survey was administered to Lebanese adults (n = 726) in community pharmacies across the country. Thirty-five percent of participants reported to be currently consuming at least one HP/DS including 23 % who were consuming vitamins and/or mineral supplements and 18 % consuming herbal products. Significant safety concerns were identified among consumers in the form of disease-supplement, drug-supplement as well as supplement-supplement interactions. Logistic multivariate regression analysis indicated that use of supplements was positively associated with the female gender and increasing age. The majority of respondents falsely believed that HP/DS pose no risk to the general population and that they must be safe to be sold in Lebanon. Moreover, most participants were consuming these products based on recommendations from friends or relatives rather than from healthcare professionals. Substantial misconceptions about HP/DS exist among Lebanese adults, indicating a need for consumers' education from professional and reliable sources on the efficacy and safety of such products.

Combined bronchodilators (tiotropium plus olodaterol) for patients with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD), a respiratory disease characterized by a progressive decline in lung function, is considered to be a leading cause of morbidity and mortality. Long-acting inhaled bronchodilators, such as long-acting ß2 agonists (LABAs) or long-acting muscarinic antagonists (LAMAs), are the cornerstone of maintenance therapy for patients with moderate-to-very-severe COPD. For patients not sufficiently controlled on a single long-acting bronchodilator, a combination of different bronchodilators has shown a significant increase in lung function. Tiotropium, a once-daily dosing LAMA, demonstrated sustained improvements in lung function as well as improved health-related quality of life, reduced exacerbations, and increased survival without altering the rate of decline in the mean forced expiratory volume in 1 second (FEV1) with fairly tolerable side effects. Olodaterol is a once-daily dosing LABA that has proven to be effective in improving lung function, reducing rescue medication use, and improving dyspnea and health-related quality of life, as well as improving exercise endurance with an acceptable safety profile. The combination of olodaterol and tiotropium provided additional improvements in lung function greater than monotherapy with each drug alone. Several well-designed randomized trials confirmed that the synergistic effect of both drugs in combination was able to improve lung function and health-related quality of life without a significant increase in adverse effects. The objective of this paper is to review available evidence on the clinical efficacy and safety of tiotropium, olodaterol, and their combination in patients with COPD.

Optimizing clopidogrel dose response: a new clinical algorithm comprising CYP2C19 pharmacogenetics and drug interactions.

PURPOSE: Response to clopidogrel varies widely with nonresponse rates ranging from 4% to 30%. A reduced function of the gene variant of the CYP2C19 has been associated with lower drug metabolite levels, and hence diminished platelet inhibition. Drugs that alter CYP2C19 activity may also mimic genetic variants. The aim of the study is to investigate the cumulative effect of CYP2C19 gene polymorphisms and drug interactions that affects clopidogrel dosing, and apply it into a new clinical-pharmacogenetic algorithm that can be used by clinicians in optimizing clopidogrel-based treatment. METHOD: Clopidogrel dose optimization was analyzed based on two main parameters that affect clopidogrel metabolite area under the curve: different CYP2C19 genotypes and concomitant drug intake. Clopidogrel adjusted dose was computed based on area under the curve ratios for different CYP2C19 genotypes when a drug interacting with CYP2C19 is added to clopidogrel treatment. A clinical-pharmacogenetic algorithm was developed based on whether clopidogrel shows 1) expected effect as per indication, 2) little or no effect, or 3) clinical features that patients experience and fit with clopidogrel adverse drug reactions. RESULTS: The study results show that all patients under clopidogrel treatment, whose genotypes are different from *1*1, and concomitantly taking other drugs metabolized by CYP2C19 require clopidogrel dose adjustment. To get a therapeutic effect and avoid adverse drug reactions, therapeutic dose of 75 mg clopidogrel, for example, should be lowered to 6 mg or increased to 215 mg in patients with different genotypes. CONCLUSION: The implementation of clopidogrel new algorithm has the potential to maximize the benefit of clopidogrel pharmacological therapy. Clinicians would be able to personalize treatment to enhance efficacy and limit toxicity.

Enzalutamide for patients with metastatic castration-resistant prostate cancer.

OBJECTIVE: To review and evaluate current literature on the US Food and Drug Administration (FDA)-approved drug enzalutamide (XTANDI(®)) in metastatic castration-resistant prostate cancer. DATA SOURCES: Literature search was done through PubMed using the terms enzalutamide, MDV3100, abiraterone, and castration-resistant prostate cancer. Data from FDA product labels were also used. STUDY SELECTION AND DATA EXTRACTION: Recent and relevant studies were included in the review. Collected clinical trials were screened and evaluated. DATA SYNTHESIS: Enzalutamide is an androgen receptor (AR) inhibitor with high selectivity and affinity to the AR. It was approved by the FDA to treat metastatic castration-resistant prostate cancer in patients previously treated with docetaxel, after a Phase III trial (AFFIRM) that showed a 4.8-month survival benefit in this population. Recently, the FDA expanded the approval of enzalutamide as first-line therapy for metastatic castration-resistant prostate cancer (mCRPC) who did not receive chemotherapy. Moreover, enzalutamide is shown to be associated with an acceptable safety profile. CONCLUSION: Enzalutamide has been shown to be both safe and effective in improving overall survival in metastatic castration-resistant prostate cancer postchemotherapy with docetaxel and as a first line treatment before initiation of chemotherapy. However, additional studies and head-to-head trials are needed.

Evaluation of the appropriate use of commonly prescribed fluoroquinolones and the risk of dysglycemia.

BACKGROUND: Fluoroquinolones are among the most widely prescribed antibiotics. However, concerns about increasing resistant microorganisms and the risk of dysglycemia associated with the use of these agents have emerged. OBJECTIVE: The primary objective of the study was to evaluate the appropriate use of commonly prescribed fluoroquinolones, including appropriate indication, dose, dose adjustment in renal impairment, and duration of treatment. The secondary objective was to investigate the dysglycemic effect of fluoroquinolone use (hypoglycemia and/or hyperglycemia) in diabetic and nondiabetic patients. METHODS: A prospective observational study at a teaching hospital in Lebanon was conducted over a 6-month period. A total of 118 patients receiving broad-spectrum fluoroquinolones (levofloxacin, ciprofloxacin, and moxifloxacin) were identified. Patients were mainly recruited from internal medicine floors and intensive care units. RESULTS: The final percentage for the appropriate indication, dose, and duration of fluoroquinolone therapy was 93.2%, 74.6%, and 57.6%, respectively. A total of 57.1% of the patients did not receive the appropriate dose adjustment according to their level of renal impairment. In addition, dysglycemia occurred in both diabetic and nondiabetic patients. Dysglycemia was more frequently encountered with ciprofloxacin (50.0%), followed by levofloxacin (42.4%) and moxifloxacin (7.6%). Hyperglycemia was more common than hypoglycemia in all groups. The highest incidence of hyperglycemia occurred with levofloxacin (70.0%), followed by ciprofloxacin (39.0%) and moxifloxacin (33.3%). In contrast, hypoglycemia did not occur in the ciprofloxacin group, but it was more common with moxifloxacin (11.1%) and levofloxacin (6.0%). CONCLUSION: The major clinical interventions for the future will adjust the dose and duration of therapy with commonly prescribed fluoroquinolones. The incidence of hypoglycemia was less common than hyperglycemia.

Emtricitabine/rilpivirine/tenofovir disoproxil fumarate for the treatment of HIV-1 infection in adults.

This paper reviews the current literature and information on the combination drug Complera(™) (rilpivirine/emtricitabine/tenofovir disoproxil fumarate) that was approved by the Food and Drug Administration (FDA) in August 2011. PubMed, Cochrane and Embase (2001-2014) were searched for primary and review articles on rilpivirine, emtricitabine, and tenofovir disoproxil fumarate, individually or in combination. Data from drug manufacturer and product label was also used. Clinical trial reports were selected, extracted and analyzed to include relevant and recent ones. Selected English-language trials were limited to those with human subjects and included both safety and efficacy outcomes. Results from two phase 3 randomized double blind trials (ECHO and THRIVE) showed that rilpivirine is non-inferior to efavirenz in suppressing viral load below 50 copies/mL in anti-retroviral therapy (ART) naïve human immunodeficiency virus (HIV) infected patients. In addition, psychiatric disturbances, rash and increase in lipid levels occurred less frequently with rilpivirine when compared to efavirenz. However, virological failure and drug resistance were higher with rilpivirine in patients with baseline viral load >100,000 copies/mL. Rilpivirine showed cross resistance to efavirenz and etravirine. Efavirenz, on the other hand, did not demonstrate cross resistance to rilpivirine and etravirine, leaving the latter drugs as options for use in case of virological failure with efavirenz. Complera(™) remains an acceptable alternative treatment to Atripla(™) in ART naïve patients who have a pre-ART plasma HIV RNA <100,000 copies/mL and CD4 count >200 cells/mm(3) with non-inferior efficacy and better safety and tolerability.

Simplicity, safety, and acceptability of insulin pen use versus the conventional vial/syringe device in patients with type 1 and type 2 diabetes mellitus in Lebanon.

BACKGROUND: The aim of the study was to evaluate the simplicity, safety, patients' preference, and convenience of the administration of insulin using the pen device versus the conventional vial/syringe in patients with diabetes. METHODS: This observational study was conducted in multiple community pharmacies in Lebanon. The investigators interviewed patients with diabetes using an insulin pen or conventional vial/syringe. A total of 74 questionnaires were filled over a period of 6 months. Answers were entered into the Statistical Package for Social Sciences (SPSS) software and Excel spreadsheet. t-test, logistic regression analysis, and correlation analysis were used in order to analyze the results. RESULTS: A higher percentage of patients from the insulin pen users group (95.2%) found the method easy to use as compared to only 46.7% of the insulin conventional users group (P 0.001, relative risk [RR]: 2.041, 95% confidence interval [CI]: 1.178-3.535). Moreover, 61.9% and 26.7% of pen users and conventional users, respectively, could read the scale easily (P 0.037, RR 2.321, 95% CI: 0.940-5.731), while 85.7% of pen users found it more convenient shifting to pen and 86.7% of the conventional users would want to shift to pen if it had the same cost. Pain perception was statistically different between the groups. A much higher percentage (76.2%) of pen users showed no pain during injection compared to only 26.7% of conventional users (P 0.003, RR 2.857, 95% CI: 1.194-6.838). CONCLUSION: The insulin pen was significantly much easier to use and less painful than the conventional vial/syringe. Proper education on the methods of administration/storage and disposal of needles/syringes is needed in both groups.

Evaluation of the appropriateness of imipenem/cilastatin prescription and dosing in a tertiary care hospital.

BACKGROUND: Imipenem/cilastatin is an antibacterial agent of the carbapenem class of ß-lactams that is known to have an extremely wide spectrum of activity against Gram-positive, Gram-negative, aerobic, anaerobic, and even multidrug-resistant strains. The objective of this study was to evaluate the appropriate use of imipenem/cilastatin in a local tertiary care hospital. The study assessed the indication both empirically and after the culture results were available, the dose and dose adjustment in renal failure, as well as the incidence of seizure in hospitalized patients receiving imipenem/cilastatin. METHODS: This observational study was conducted in a tertiary care hospital over a 3-month period. The treatment of 100 patients with imipenem/cilastatin was evaluated both empirically and after culture results were available. Analysis of the appropriateness of imipenem/cilastatin indication, dose, and monitoring of seizure frequency was based on the package insert, updated published guidelines, and clinical judgment. RESULTS: Patients from internal medicine and intensive care units comprised approximately 50% of the population in the study. The patients received imipenem/cilastatin mainly for urinary tract infections (27%) or for sepsis of an unknown focus (22%). The use of imipenem/cilastatin empirically was appropriate in 97.2% (n=69/71) of the cases, and its use postculture in 86% of the cases. There were 29% of the patients who were not started on imipenem/cilastatin empirically. Four patients out of the 29 patients (13.8%) who were not started on imipenem/cilastatin empirically inappropriately received imipenem/cilastatin post-culture results. Thirty-three patients (33%) were not dosed appropriately, 30 of whom had renal impairment and creatinine clearance fluctuations. Only one patient developed a seizure while on imipenem/cilastatin. CONCLUSION: The prescription of imipenem/cilastatin at our setting was mostly appropriate to what is recommended in the guidelines and the literature, although a few cases could have been managed better. Dosage adjustment, however, was not as appropriate, mainly in patients who did not have a stable creatinine clearance.

Sitagliptin/Simvastatin: a first combination tablet to treat type 2 diabetes and hypercholesterolemia--a review of its characteristics.

BACKGROUND: The purpose of this study was to review the current literature and information on the combination product Juvisync™ (sitagliptin + simvastatin), which was approved by the US Food and Drug Administration in October 2011. METHODS: PubMed (2001-2014) was searched for primary and review articles on sitagliptin, simvastatin, or the combination product. Drug manufacturing data and product labeling were also used. Studies of simvastatin, sitagliptin, or the combination were screened and analyzed to include relevant and recent papers. Selected English language trials were limited to those with human subjects and included both safety and efficacy outcomes. RESULTS: When compared with glipizide as add-on therapy to metformin, sitagliptin was noninferior but had lower rates of hypoglycemia and weight gain. In addition, when compared with insulin glargine, sitagliptin was less effective in decreasing glycosylated hemoglobin, but was associated with significantly lower rates of hypoglycemia. Further, trials have shown a beneficial effect of using statins in patients with diabetes mellitus with regard to decreasing cardiovascular risk, regardless of baseline lipid levels or the presence of a cardiac disease. Both medications have also demonstrated an acceptable side effect profile. However, caution is needed when coadministering with any drug that may increase simvastatin levels to reduce the risk of myopathy and rhabdomyolysis. CONCLUSION: Juvisync should be used in patients requiring both sitagliptin and simvastatin. Both agents have shown good efficacy and acceptable safety profiles. Sitagliptin is a good option for diabetic patients to improve glycemic control with a lower risk of hypoglycemia and weight gain.