Use Of Fixed-dose Combinations Research Articles

Risk factors for pulmonary tuberculosis recurrence, relapse and reinfection: a systematic review and meta-analysis

BackgroundThe rate of pulmonary tuberculosis (TB) recurrence is substantial. Identifying risk factors can support the development of prevention strategies.MethodsWe retrieved studies published between 1 January 1980 and 31 December 2022...

EE528 Analysis of Non-Pharmacological Cost Savings Derived from the Use of Fixed-Dose Combination of Pertuzumab and Trastuzumab for Subcutaneous Injection in Patients with HER2-Positive Breast Cancer in Spain

EE528 Analysis of Non-Pharmacological Cost Savings Derived from the Use of Fixed-Dose Combination of Pertuzumab and Trastuzumab for Subcutaneous Injection in Patients with HER2-Positive Breast Cancer in Spain

The use of a combination drug with adapalene/metronidazole for acne

The latest advances in the research of the effect of skin microbiome on the occurrence of acne raised the need for the development of new effective treatments for the long-term use in persistent or recurrent disease. The review presents an analysis of foreign and domestic studies on the issues of pathogenesis and treatment of acne. The latest data on the role of skin microbiome imbalance in the occurrence of acne are presented. The Cutibacterium acnes phylotypes diversity loss acts as a trigger for innate immunity activation and chronic inflammation in acne. We show the main directions in the treatment of  acne based on international and Russian clinical guidelines. Today, a  new solution in  acne therapy lies in a multimodal approach to the impact on various links in the pathogenesis of acne to increase therapeutic efficacy, safety, and patient adherence to therapy. The place of topical fixed-dose combination drugs in the treatment of mild to moderate acne has been determined. Due to the growing resistance to antibiotics and their more limited use, it was observed that there is a need to develop new effective treatments for the long-term use. The studies showed that the fixed combination of adapalene/metronidazole is a highly effective treatment for moderate to moderately severe papulopustular acne. The comparative analysis of the use of fixed-dose combinations of adapalene/metronidazole and adapalene/clindamycin in the treatment of patients with acne revealed the comparable efficacy and good tolerability of both combinations. The findings of foreign and domestic studies have proved that the adapalene/metronidazole combination is an effective and safe drug to treat mild to moderate acne.

Assessment of Potential Drug-drug Interactions (pDDIs) and Their Risk Factors Among Hospitalized Cardiac Patients in a Tertiary-care Center of Central India: A Retrospective Record-based Study.

Background: Patients with cardiovascular disorders (CVD) possess multiple comorbidities and are prone to be prescribed multiple drugs, thus predisposing them to various drug-drug interactions (DDIs). Objective: This study was carried out to assess the potential-DDIs (pDDIs) among the drugs prescribed to hospitalized patients with CVD and associated factors. Method: It was a retrospective study conducted with the help of the medical records department. Medical records of all the patients admitted to the cardiology department of our tertiary care center from January 1st, 2019, to December 31st, 2019, were included for analysis using Lexicomp, an up-to-date drug interaction screening tool. The pDDIs were divided into classes A, B, C, D, and X, and those belonging to classes D or X were considered clinically significant. Multiple logistic regression was used to analyze the association between the factors associated with and the occurrence of clinically significant pDDIs, with a P-value < .05 considered statistically significant. Results: Almost all the records reflected (335/338) at least 1 pDDI. A total of 4966 pDDIs were detected, of which the majority belonged to category C (75.3%), and 5.1% of pDDIs were clinically significant. The patients who were prescribed more than 10 drugs per day (OR = 2.46; 95% CI: 1.27-4.82; P = .008), prescribed parenteral formulation (OR = 1.84; 95% CI: 1.57-2.21; P < .0001), or had a diagnosis of acute coronary syndrome (OR = 2.33; 95% CI:1.1-5.12; P = .03) were associated with clinically significant pDDIs. Other factors, that is, female sex, use of fixed-dose combinations, and the triad of diabetes mellitus, hypertension, and dyslipidemia, were positively associated with clinically significant pDDIs. Conclusion: Even though every patient had at least 1 pDDI, the prevalence of clinically significant pDDIs was relatively less. Use of >10 drugs/day, parenteral formulation, patients with acute coronary syndrome were significantly associated with clinically significant pDDIs.

HOME BLOOD PRESSURE MONITORING IN SLOVAKIA IN 2022. WHO MANAGES THE PATIENTS WITH ARTERIAL HYPERTENSION THE BEST?

Objective: Home blood pressure monitoring (HBPM) is a reliable, convenient method for the diagnosis and management of arterial hypertension (AH). Moreover, HBPM can help improve the control of blood pressure in patients (pts). Design and method: To evaluate HBPM and office blood pressure (BP) measurements. To compare the efficacy of the AH treatment according to doctors‘ and patients‘ age and gender. Results: 4375 pts with AH were enrolled (2089 women, 51,8%), mean age 61,1 ± 19,1 years. The mean office BP was higher in male pts 136,7 ± 10,9/ 81,9 ± 7,2 mmHg, vs in female pts 135±7,2/ 80,2 ± 6,2 mmHg. Mean HBPM was also higher in male pts 134,1± 7,2/ 81,1± 6,3 mmHg. In our program participated 129 female doctors (72%), mean age of 49,6 ± 10,1 years, and the mean age of male doctors was 44,9 ± 7,2 years. The reduction in BP for 7 days of HBPM was documented. A greater reduction of HBPM was achieved when the female doctor treated female patients 132,01/78 mmHg p = 0,0081, contrary to a smaller reduction of BP when the female doctor treated male pts 134,18/81,32 mmHg p = 0,026. The highest office BP was measured in male pts treated by male doctors 136,59/81,59 mmHg, beyond the lowest office BP was measured when the female doctor treated female pts 132,01/78,74 mmHg p = 0,0081. Male doctors treated more frequently with a higher number of AH drugs. The proportion of use of fixed-dose AH drugs combination was highest when the male doctor treated male pts (70,7%), and the lowest use of fixed-dose combination was when the female doctor treated female patients 52,1%. Conclusions: In our project with HBPM and office BP measurement in 2022 in Slovakia we found that the most precise BP control both in the office and in HBPM was reached when female patients were treated by female doctors. On the other hand, male doctors have preferred to use fixed-dose AH combinations. These data show that better involvement and engagement of doctors, and patients could lead to better implementation of guidelines and better BP control.

Most Recent Trials and Advances in Hypertension.

Hypertension is one of the most prevalent cardiovascular risk factors and blood pressure control remains a clinical challenge, especially for patients with established cardiovascular disease. Late-breaking clinical trials and other evidence in hypertension have evolved to assess the most accurate ways to measure blood pressure, the use of combination therapies, considerations in special populations and evaluation of new techniques. Recent evidence supports the superiority of ambulatory or 24-hour blood pressure measurements, rather than office blood pressure measurements, for the assessment of cardiovascular risk. The use of fixed-dose combinations and polypills has been demonstrated to be valid and to provide clinical benefits beyond blood pressure control. There have also been advances in new approaches such as telemedicine, devices and the use of algorithms. Clinical trials have provided valuable data on blood pressure control in primary prevention, during pregnancy and in the elderly. The role of renal denervation remains unsolved but innovative techniques using ultrasound or alcohol injections are being explored. Current evidence and results of latest trials are summarised in this review.

Off-label use of fixed-dose combination of tramadol and dexketoprofen in primary health care. Evidence-based or cause for concern?

Introduction: The use of the fixed-dose combination of tramadol/dexketoprofen in Spain and in other countries has increased considerably. The authorized therapeutic indication for this medicinal product is the short-term symptomatic treatment of moderate to severe acute pain in adult patients. The objective of this study was to describe the pattern of use of tramadol/dexketoprofen in the field of primary health care. Method: A cross-sectional, descriptive and multicenter study was carried out. The study population included all patients from a Primary Care Department (53 Primary Care teams) with an active prescription of tramadol/dexketoprofen on March 28, 2018. The target population was those patients who were prescribed tramadol/dexketoprofen. dexketoprofen for &gt;20 days. Results: A total of 176 patients had an active prescription for tramadol/dexketoprofen. All patients (100%) had a duration of treatment greater than 5 days and 72.7% (N=128) greater than 20 days. The mean duration of treatment was 14±160.9 days in patients who had less than 20 days of treatment and 224±160.8 days in patients who had more than 20 days of treatment. 35.1% of the patients were treated with &gt;2 pain medications and concomitantly with tramadol/dexketoprofen. The general practitioner initiated 65.6% of the prescriptions. Conclusions: The fixed-dose combination of tramadol/dexketoprofen was frequently used off-label, according to the product characteristics and the available scientific evidence. This study warns about the potential risks associated with the use of this drug in clinical practice, such as lack of effectiveness and/or the appearance of adverse effects.

National Trends in Antihypertensive Treatment Among Older Adults by Race and Presence of Comorbidity, 2008 to 2017.

In 2014, hypertension guidelines for older adults endorsed increased use of fixed-dose combinations, prioritized thiazide diuretics and calcium channel blockers (CCBs) for Black patients, and no longer recommend beta-blockers as first-line therapy. To evaluate older adults' antihypertensive use following guideline changes. Time series analysis. Twenty percent national sample of Medicare Part D beneficiaries aged 66 years and older with hypertension. Eighth Joint National Committee (JNC8) guidelines MAIN MEASURES: Quarterly trends in prevalent and initial antihypertensive use were examined before (2008 to 2013) and after (2014 to 2017) JNC8. Analyses were conducted among all beneficiaries with hypertension, beneficiaries without chronic conditions that might influence antihypertensive selection (hypertension-only cohort), and among Black patients, given race-based guideline recommendations. The number of beneficiaries with hypertension increased from 1,978,494 in 2008 to 2,809,680 in 2017, the proportions using antihypertensives increased from 80.3 to 81.2%, and the proportion using multiple classes and fixed-dose combinations declined (60.8 to 58.1% and 20.7 to 15.1%, respectively, all P<.01). Prior to JNC8, the use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and CCBs was increasing. Use of CCBs as initial therapy increased more rapidly following JNC8 (relative change in quarterly trend 0.15% [95% CI, 0.13-0.18%), especially among Black beneficiaries (relative change 0.44% [95% CI, 0.21-0.68%]). Contrary to guidelines, the use of thiazides and combinations as initial therapy consistently decreased in the hypertension-only cohort (13.8 to 8.3% and 25.1 to 15.7% respectively). By 2017, 65.9% of Black patients in the hypertension-only cohort were initiated on recommended first-line or combination therapy compared to 80.3% of non-Black patients. Many older adults, particularly Black patients, continue to be initiated on antihypertensive classes not recommended as first-line, indicating opportunities to improve the effectiveness and equity of hypertension care and potentially reduce antihypertensive regimen complexity.

Potential deleterious effects of paracetamol dose regime used in Nigeria versus that of the United States of America.

Paracetamol, also known as acetaminophen (N-acetyl-para-aminophenol, APAP) is the world's most used over-the-counter analgesic-antipyretic drug. Despite its good safety profile, acetaminophen can cause severe hepatotoxicity in overdose, and poisoning from paracetamol has become a major public health concern. Paracetamol is now the major cause of acute liver failure in the United States and Europe. This systematic review aims at examining the likelihood of paracetamol use in Nigeria causing more liver toxicity vis-à-vis the reduced maximum recommended daily adult dose of 3g for the 500mg tablet. Online searches were conducted in the databases of PubMed, Google Scholar and MEDLINE for publications using terms like "paracetamol toxicity," "acetaminophen and liver toxicity," "paracetamol and liver diseases in Nigeria," and other variants. Further search of related references in PubMed was carried out, and synthesis of all studies included in this review finalized. There were 94 studies that met the inclusion criteria. Evaluation of hepatic disorder was predicated mostly on a constellation of clinical features and limited clinical laboratory investigations. Determination of blood paracetamol concentration was rarely reported, thus excluding paracetamol poisoning as one of the likely causes of liver disorders in Nigeria. In Nigeria and elsewhere, several factors are known to increase paracetamol's predisposition to liver injury. They include: the over-the-counter status of paracetamol, use of fixed-dose combinations of paracetamol with other drugs, malnutrition, dose miscalculations, and chronic alcohol consumption. The tendency to exceed the new paracetamol maximum daily dose of 3g in Nigeria may increase its risk for hepatotoxicity than observed in the United States of America known for emphasizing lower dose of the drug. In addition to recommending the new maximal daily paracetamol dose allowance, the historical maximum daily adult dose of 4g should be de-emphasized in Nigeria.

Prescribing pattern of anti-diabetic drugs and adherence to the American Diabetes Association's (ADA) 2021 treatment guidelines among patients of type 2 diabetes mellitus: A cross-sectional study.

Glycemic control is the major therapeutic objective in diabetes. Poor glycemic control in diabetes mellitus can be prevented by using rational use of anti-diabetic medication, which needs to be evaluated for effectiveness by prescription pattern studies. The objective of this study was to assess the prescribing pattern and adherence to the American Diabetic Association's (ADA) treatment guidelines in type 2 diabetes mellitus patients in a tertiary care teaching hospital in Uttarakhand, India. This cross-sectional study was conducted on 206 type 2 diabetic patients who were prescribed anti-diabetic therapy. Patient's demographic details and drugs prescribed, with their dosage, were recorded to study the prescription pattern. Oral anti-diabetic drugs were most commonly prescribed in 149 (72.33%) type 2 diabetic mellitus patients. Five of these patients (3.35%) were on metformin monotherapy, whereas majority of patients (81, 54.36%) were on a fixed dose combination of Glimepiride (SU) + Metformin (MET). Forty-five patients (30.20%) were on MET + Dipeptidyl peptidase 4 inhibitors (DPP4I) combination; 5 (3.35%) were on MET + SU + alpha-glucosidase inhibitors (AGI) combination; 7 (4.69%) were on MET + SU + Pioglitazone (PIO) (Thiazolidinediones) combination; 6 (4.02%) were on sodium/glucose cotransporter-2 inhibitors (SGLT2I) and 57 (27.66%) were on insulin therapy. Out of 206 patients, the prescriptions of 185 patients (89.8%) were adherent and of 21 patients (10.19%) were not adhering to ADA 2021 treatment guidelines. Oral anti-diabetic agents predominate the prescribing pattern practices for type 2 DM but there was a shift in trend towards the use of fixed-dose combinations (FDC) in the management of type 2 DM, and majority of prescriptions were adherent to ADA treatment guidelines.

Трехкомпонентная комбинированная антигипертензивная терапия у больных артериальной гипертензией с абдоминальным ожирением. Данные 9-месячного наблюдения

Актуальность. Сочетанное течение первичной артериальной гипертензии (АГ) и абдоминального ожирения (АО) характеризуется рефрактерностью к антигипертензивной терапии и значительным повышением сердечно-сосудистого риска. Перспективным подходом к терапии данных больных является раннее применение фиксированных комбинаций антигипертензивных препаратов первой линии. Цель работы состояла в исследовании эффективности фиксированной комбинации периндоприла, индапамида и амлодипина в сравнении с нефиксированной комбинацией указанных препаратов у больных с АГ в сочетании с АО. Материалы и методы. Обследованы 75 больных с АГ II–III степени в сочетании с АО І–ІІ степени (45 мужчин и 30 женщин) в возрасте от 48 до 66 лет. Все больные были разделены на две подгруппы в зависимости от вида антигипертензивной терапии. Первая подгруппа больных (26 пациентов) получала нефиксированную комбинацию периндоприла, индапамида и амлодипина. Вторая подгруппа (29 больных) получала фиксированную комбинацию указанных препаратов. Обследование проводили до начала лечения и через 3, 6 и 9 месяцев. В качестве гиполипидемического препарата все больные получали аторвастатин в суточной дозе 20 мг. Указанная терапия проводилась на фоне рекомендаций по коррекции образа жизни. Результаты. Установлено, что частота достижения целевых уровней артериального давления (АД) у больных, которые получали фиксированную комбинацию препаратов, через 9 месяцев лечения была достоверно выше, чем у больных, которые получали нефиксированную комбинацию. По данным суточного мониторирования АД, фиксированная комбинация назначенных препаратов значительно лучше нормализовала такие параметры, как среднесуточное и среднедневное диастолическое АД (ДАД), средненочное систолическое АД (САД) и ДАД, а также степень ночного снижения и среднесуточную вариабельность САД и ДАД. Апробированная трехкомпонентная фиксированная комбинация давала возможность достичь целевых уровней АД на более низких дозах примененных компонентов, чем нефиксированная комбинация. Выводы. Фиксированная комбинация периндоприла, индапамида и амлодипина в сравнении с нефиксированной у больных АГ в сочетании с АО проявляет достоверно большую антигипертензивную эффективность по данным как офисного измерения АД, так и суточного мониторирования АД на фоне большей приверженности больных к лечению. Для достижения целевых уровней АД у больных АГ в сочетании с АО требуются более низкие дозы компонентов фиксированной комбинации, чем нефиксированной.

Chronic obstructive pulmonary disease and concurrent cardiovascular conditions: safety of tiotropium/olodaterol combination

One of the important features of the chronic obstructive pulmonary disease is the presence of concomitant chronic diseases in most of patients. And cardiovascular conditions occupy a special place among these comorbidities. The most common diseases associated with COPD are hypertension, coronary heart disease, and heart failure. They aggravate the clinical manifestations of the disease and have negative effect on the prognosis. In addition, concomitant cardiovascular conditions determine the need for a thorough safety assessment of the ongoing pharmacotherapy for COPD. Core of the treatment is bronchodilators. The priority pharmacological strategy is the use of fixed-dose combinations of long-acting β2 -agonists and long-acting anticholinergic medications.The purpose of this review was to evaluate the safety profile of tiotropium/olodaterol in COPD.Methods. This article presents the data obtained from studies of the safety of the use of tiotropium/olodaterol in patients with COPD and concomitant cardiovascular conditions.Results. The studies showed no increase in the risk of cardiovascular events when using this combination in patients of this category.Conclusion. А good safety profile of tiotropium/olodaterol was confirmed in patients with COPD and concomitant cardiovascular conditions.

Combined drugs in the treatment of acute respiratory viral infections: a review of research results

Acute respiratory infections are of the greatest economic significance among all infectious diseases in the Russian Federation. There are no drugs with a direct antiviral effect for most acute respiratory viral infections, which efficacy would have been proven in the numerous clinical trials and confirmed by the results of meta-analyses today. The use of various combinations of antipyretic, anti-inflammatory and antioxidant drugs is the most common method of symptomatic and pathogenetic therapy of acute respiratory viral infections (ARVI). The purpose of this review is to analyse and systematize the results of preclinical and clinical trials aimed at studying the safety and efficacy of fixed-doses combinations of paracetamol, pheniramine maleate, phenylephrine hydrochloride and ascorbic acid in the ARVI therapy. The search of scientific publications was carried out in the PubMed, ClinicalKey ELSEVIER and Google Scholar databases. The search depth was 10 years. The results of numerous comparative and placebo-controlled trials showed that the use of fixed-dose combinations of paracetamol, pheniramine maleate, phenylephrine hydrochloride and ascorbic acid in the ARVI therapy was pathogenetically justified, safe, and effective in relieving symptoms such as fever, rhinitis, cough, muscle and joint pain, sore throat, and headache. The combination drugs can ease the patient’s condition and help shorten the duration of the illness provided that they are administered in due time. Meanwhile, the pathogenetic effects of combination drugs aimed at localizing the focus of inflammation and minimizing the risk of complications warrant further research.

Psychological continuum of elderly hypertensive patients with metabolic syndrome receiving chronotherapy with a fixed-dose combination of amlodipine, lisinopril and rosuvastatin

Aim. To study the psychological continuum of elderly hypertensive patients with metabolic syndrome (MS) receiving chronotherapy with a fixed-dose combination of amlodipine, lisinopril and rosuvastatin.Material and  methods. In a  clinical setting, 63 hypertensive  patients with MS aged 60-74 years (experimental group) received chronotherapy with fixed-dose combination of amlodipine, lisinopril and rosuvastatin (Ekvamer®) at a dose of 5/10/10 mg in the evening (8 pm). The control group of hypertensive patients with MS aged 60-74 years old (n=58) received Ekvamer® in the morning (conventional therapy) at the same dosage.Results. With fixed-dose combination of amlodipine, lisinopril and rosuvastatin, the severity of psychological continuum abnormalities significantly decreases after 1 year in the chronotherapy regimen (evening intake) than with morning intake with an equivalent dosage of 5/10/10 mg per day in both cases. The dynamics of cognitive impairments in hypertensive patients aged 60-74 years with MS using chronotherapy regimen is characterized by a significant increase  in  the  mean MMSE score from the initial 17,8±0,3 to 23,5±0,4 points (p±0,001) vs 16,9±0,3 to 20,4±0,4 points (p&lt;0,001) when taking the drug in the morning. Situational anxiety decreased from 40,0±2,2 to 30,6±1,8 points (p&lt;0,05) vs 40,8±2,5 to 33,5±1,9 points (p&lt;0,05), personal anxiety from 48,8±2,0 to 26,4±1,9 (p&lt;0,001) vs from 44,9±1,9 to 30,7±1,7 (p&lt;0,01) points, respectively. Depressive disorders slightly decreased with chronotherapy (14,1%) vs 7,7% than with the conventional scheme, but despite this, they corresponded to depressive spectrum disorders in both groups.Conclusion. The results obtained indicate a greater efficiency of chronotherapy than the conventional use of fixed-dose combination of amlodipine, lisinopril and rosuvastatin in hypertensive patients with MS.

Fixed-dose combinations in the treatment of hypertension to increase adherence

Despite a wide range of antihypertensive drugs, blood pressure (BP) control often remains unsatisfactory, and every year the number of people with uncontrolled high BP increases. One of the strategies aimed at improving medical adherence is the use of fixed-dose combinations of 2 antihypertensive drugs for starting therapy, and, if necessary, 3 drugs. Initiation of therapy with 2 drugs in one tablet is recommended for most patients. A review of algorithms for choosing combinations of antihypertensive drugs in different clinical situations, including in patients with various comorbid conditions, is presented. Simplification of treatment regimens makes it possible to choose the most optimal solutions in various clinical situations, in particular, with stage I-II hypertension, with a combination of hypertension with chronic kidney disease, as well as with a combination of hypertension with coronary artery disease and a number of other diseases.

PRS60 IMPACT of Health Technology Assessment (HTA) Recommendations on the Use of Fixed-Dose Combination (FDC) Triple Therapy for Patients with Chronic Obstructive Pulmonary Disease (COPD)

PRS60 IMPACT of Health Technology Assessment (HTA) Recommendations on the Use of Fixed-Dose Combination (FDC) Triple Therapy for Patients with Chronic Obstructive Pulmonary Disease (COPD)

Reducing and managing chronic obstructive pulmonary disease exacerbations with tiotropium + olodaterol

Objective The aim of this study was to review clinical evidence supporting the use of fixed-dose combination of tiotropium and olodaterol, a long-acting muscarinic antagonist (LAMA) and a long-acting β2-agonist (LABA), respectively, as the initial and follow-up treatment choice in patients with chronic obstructive pulmonary disease (COPD) as per Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2020 recommendations—the impact of this treatment strategy on the reduction in the risk of exacerbations—and the importance of early therapeutic interventions. Methods For this narrative review, the available literature was searched to identify studies including patients with COPD receiving tiotropium and olodaterol as either monotherapy or combination therapy and studies including patients with COPD receiving inhaled corticosteroids (ICS) in addition to long-acting bronchodilators. Relevant studies were included in the review. Results Patients with COPD are often prescribed ICS therapy, which, when used over a long term, can be associated with local and systemic adverse effects. The GOLD 2020 report recommends dual bronchodilator therapy as both an initial and follow-up treatment option. A LABA + LAMA combination is mechanistically synergistic, and cumulative evidence surrounding the efficacy and safety of fixed-dose combination of tiotropium and olodaterol supports therapeutic advantages over monotherapy in most patients with COPD. Conclusions The early stages of COPD may represent a “window of therapeutic opportunity” during which initiation of tiotropium and olodaterol dual bronchodilator therapy may improve lung function and quality of life and reduce exacerbations in patients with COPD.

1068-P: Adherence to Metformin Treatment in T2DM Subjects Is Higher Than Anticipated and Is Associated with the Use of Fixed-Dose Combinations but Not with XR Form

Metformin is considered the first-line treatment in all subjects with type 2 diabetes mellitus (T2DM) not having a contraindication for its use. Patient compliance with metformin is not optimal; however, objective compliance data are scarce. The aim of our study was to analyse the adherence to metformin treatment by determining its plasma levels and to identify its determinants in a broad spectrum of T2DM patients. In total, 309 patients with T2DM from a single tertiary diabetes centre (mean age 66.5 ± 9.0 years, HbA1C 57.2 ± 13.1 mmol/mol, BMI 30.8 ± 4.9 kg/m2) using standard or XR (sustained release) form of metformin were included in the study. Blood sampling for metformin together with a short questionnaire were performed during a regular outpatient visit. Hydrophilic interaction chromatography and high-resolution mass spectrometry (Q Exactive Plus instrumentation) were used to quantify metformin levels. Values ​​below 100 ng/ml were deemed sub-therapeutic. Out of 309 patients, sub-therapeutic values were measured in 4.2% and zero levels in 1.9% of subjects. The use of XR form did not increase compliance (16.7 vs. 15.4 vs. 13.8% of subjects for zero vs. sub-therapeutic vs. therapeutic range, n.s.), while all subjects using combination preparation with another antidiabetic agent (11.0%) were in therapeutic range. Zero levels of metformin were associated with a trend to increased HbA1C, higher number of other antidiabetic drugs and more frequent insulin use, whereas age, BMI and diabetes duration had no effect on metformin compliance. Adherence to metformin also increased with education status while not being affected by smoking or alcohol use. In conclusion, in a tertiary diabetes centre the compliance with metformin treatment was greater than 93% and increased with the use of combination preparations, lower number of antidiabetic drugs and higher education status. The XR form was not associated with increased adherence rate. Disclosure I. Lankova: None. I. Miskova: None. S. Frankova: None. D. Kobrova: None. T. Cajka: None. J. Hricko: None. M. Paucova: None. V. Hrádková: None. Z. Vlasakova: None. T. Pelikanova: None. M. Mraz: None. M. Haluzik: Advisory Panel; Self; Lilly Diabetes, Sanofi. Consultant; Self; Ethicon US, LLC. Speaker’s Bureau; Self; AstraZeneca, Mundipharma International, Novartis AG, Novo Nordisk A/S. Funding Institute for Clinical and Experimental Medicine (00023001); RVOVFN64165

Pharmacology and Therapeutics of Bronchodilators Revisited.

Bronchodilators remain the cornerstone of the treatment of airway disorders such as asthma and chronic obstructive pulmonary disease (COPD). There is therefore considerable interest in understanding how to optimize the use of our existing classes of bronchodilator and in identifying novel classes of bronchodilator drugs. However, new classes of bronchodilator have proved challenging to develop because many of these have no better efficacy than existing classes of bronchodilator and often have unacceptable safety profiles. Recent research has shown that optimization of bronchodilation occurs when both arms of the autonomic nervous system are affected through antagonism of muscarinic receptors to reduce the influence of parasympathetic innervation of the lung and through stimulation of β 2-adrenoceptors (β 2-ARs) on airway smooth muscle with β 2-AR-selective agonists to mimic the sympathetic influence on the lung. This is currently achieved by use of fixed-dose combinations of inhaled long-acting β 2-adrenoceptor agonists (LABAs) and long-acting muscarinic acetylcholine receptor antagonists (LAMAs). Due to the distinct mechanisms of action of LAMAs and LABAs, the additive/synergistic effects of using these drug classes together has been extensively investigated. More recently, so-called "triple inhalers" containing fixed-dose combinations of both classes of bronchodilator (dual bronchodilation) and an inhaled corticosteroid in the same inhaler have been developed. Furthermore, a number of so-called "bifunctional drugs" having two different primary pharmacological actions in the same molecule are under development. This review discusses recent advancements in knowledge on bronchodilators and bifunctional drugs for the treatment of asthma and COPD. SIGNIFICANCE STATEMENT: Since our last review in 2012, there has been considerable research to identify novel classes of bronchodilator drugs, to further understand how to optimize the use of the existing classes of bronchodilator, and to better understand the role of bifunctional drugs in the treatment of asthma and chronic obstructive pulmonary disease.

Paliasa (Kleinhovia hospita L.) Hepatoprotector “Tea Bag” preparation as supporting therapy in the use of fixed-dose combination of antituberculosis drugs

The use of fixed-dose combination of antituberculosis drugs (FDC-TB) is used as firstline treatment in tuberculosis. These drugs also have side effects that can damage the liver and kidneys. This study aimed to determine the effect of the paliasa “Tea Bag” hepatoprotector preparation on ALT and AST levels in rats as a supporting therapy for the use of FDC-TB. 20 rats and were divided into 5 groups, Group I was given 1% NaCMC, group II was given FDC-TB suspension, group III was given paliasa tea, group IV was given paliasa tea, and group V was given curcuma suspension, 4 hours later in group III and IV was given FDC-TB suspension, after that 4 hours later again group IV was given paliasa tea. Treatment was given 28 days orally. After the last 24 hours of treatment, blood sampling and measurement using a humanolyzer were carried out. The results showed that the administration of Paliasa Tea Bag can be used as supporting therapy with the use of 2 times a day. It was concluded that the administration of paliasa “tea bag” showed hepatoprotective activity in reducing ALT and AST levels following administration of fixed-dose combination antituberculosis drugs for 28 days.