Fixed-dose Combination Therapy Research Articles

Bioequivalence of Elagolix/Estradiol/Norethindrone Acetate Fixed-Dose Combination Product: Phase 1 Results in Healthy Pre- and Postmenopausal Women.

Fixed-dose combination (FDC) therapies can enhance patient convenience and adherence to prescribed treatment regimens. Elagolix is a novel oral gonadotropin-releasing hormone receptor antagonist approved for management of moderate to severe pain associated with endometriosis and heavy menstrual bleeding associated with uterine fibroids. Hormonal add-back therapy can attenuate the reversible hypoestrogenic effects of elagolix. An FDC formulation containing elagolix/estradiol (E2)/norethindrone acetate (NETA) 300/1/0.5mg as the morning dose and an elagolix 300mg capsule as the evening dose, were evaluated in 2 bioequivalence studies including the effects of food. Study 1 in premenopausal women assessed the bioavailability of the elagolix 300-mg capsule relative to the commercially available elagolix 300-mg tablet. Study 2 in postmenopausal women, elagolix/E2/NETA (300mg/1mg/0.5mg) FDC capsule was assessed relative to the elagolix 300-mg tablet coadministered with E2/NETA 1-mg/0.5-mg tablet, the regimen that was studied in Phase 3 uterine fibroid studies. Under fasting conditions, the test elagolix 300-mg capsule was bioequivalent to the reference elagolix 300-mg tablet. Under fasting conditions, the elagolix/E2/NETA FDC capsule was bioequivalent to the coadministered elagolix 300-mg tablet and E2/NETA 1/0.5-mg tablet. Following administration of elagolix/E2/NETA FDC capsule after a high-fat breakfast, elagolix mean maximum concentration (Cmax) and area under the plasma concentration-time curve (AUC) were 38% and 28% lower, relative to fasting conditions. NETA mean Cmax was 51% lower and AUC from time 0 to infinity was 20% higher, while baseline-adjusted total estrone mean Cmax and AUC were 46% and 14% lower, respectively. No safety concerns were identified. These results enabled bridging the elagolix/E2/NETA FDC capsule.

Fixed-dose combination therapy in pulmonary arterial hypertension: Pros & cons

Quality of life of patients suffering from chronic diseases is inevitably conditioned by the number of pills taken during the day. To improve patients' tolerability, compliance and quality of life and reduce healthcare costs, pharmaceutical companies are focusing on the commercialization of fixed-dose combination (FDC) therapies.The last ESC/ERS guidelines for the treatment of pulmonary arterial hypertension (PAH) recommend initial dual combination therapy for newly diagnosed patients at low or intermediate mortality risk. In this regard, polypills including an endothelin receptor antagonist (ERA) and a phosphodiesterase 5 inhibitor (PDE5-i) could represent an useful therapeutic strategy, although with some limitations. To date, evidence about the use of FDCs in PAH is limited but future studies evaluating their safety and efficacy are welcome.

Fixed-dose combination therapy for the prevention of atherosclerotic cardiovascular disease.

Fixed-dose combination (FDC) therapy, also known as polypill therapy, targets risk factors for atherosclerotic cardiovascular disease (ASCVD) and has been proposed as a strategy to reduce global ASCVD burden. Here we conducted a systematic search for relevant studies from 2016-2022 to assess the effects of FDC therapy for prevention of ASCVD. The studies selected include randomized trials evaluating FDC therapy with at least one blood pressure-lowering drug and one lipid-lowering drug. The study data were independently extracted, the quality of evidence was appraised by multiple reviewers and effect estimates were pooled using a fixed-effect meta-analysis when statistical heterogeneity was low to moderate. The main outcomes of the analysis were all-cause mortality, fatal and nonfatal ASCVD events, adverse events, systolic blood pressure, low-density lipoprotein cholesterol and adherence. Among 26 trials (n = 27,317 participants, 43.2% female and mean age range 52.9-76.0), FDC therapy was associated with lower low-density lipoprotein cholesterol and systolic blood pressure, with higher rates of adherence and adverse events in both primary and mixed secondary prevention populations. For studies with a mostly primary prevention population, FDC therapy was associated with lower risk of all-cause mortality by 11% (5.6% versus 6.3%; relative risk (risk ratio) of 0.89; 95% confidence interval 0.78 to 1.00; I2 = 0%; four trials and 16,278 participants) and risk of fatal and nonfatal ASCVD events by 29% (6.1% versus 8.4%; relative risk (risk ratio) of 0.71; 95% confidence interval 0.63 to 0.79; I2 = 0%; five trials and 15,503 participants). One adequately powered trial in an exclusively secondary prevention population showed that FDC therapy reduced the risk of major adverse cardiovascular events by 24%. These findings support adoption and implementation of polypills to lower risk for all-cause mortality and ASCVD.

Effectiveness of polypill for primary and secondary prevention of cardiovascular disease: a pragmatic cluster-randomised controlled trial (PolyPars)

BackgroundWe aimed to investigate the effectiveness of fixed-dose combination therapy (polypill) for primary and secondary prevention of major cardiovascular diseases in a typical rural setting.MethodsThe PolyPars Study is a two-arm...

The Rationale for Using Fixed-Dose Combination Therapy in the Management of Hypertension in Colombia: A Narrative Review.

Hypertension is a major risk factor for cardiovascular disease and the leading cause of death in Colombia. While the rate of hypertension awareness in Colombia is generally high, rates of treatment initiation, adherence, and blood pressure (BP) control are suboptimal. Major international hypertension guidelines recommend starting treatment with a combination of antihypertensive agents, and the use of a single-pill combination (SPC) to maximize adherence. In contrast, Colombian hypertension guidelines recommend starting treatment with diuretic monotherapy in most patients, and only initiating combination therapy in those with BP > 160/100 mmHg. Therefore, the aim of the current narrative review is to examine the rationale for using SPCs to treat hypertension in Colombia, in the context of the major issues for BP controlthere. There is evidence of widespread therapeutic inertia in hypertension management, particularly in primary care, in Colombia. Moreover, combination therapy, angiotensin-converting enzyme inhibitors, and long-acting calcium channel blockers, which are internationally recommended as first-line drug therapies, are underutilized there. Adherence to antihypertensive therapy is low in Colombia and may be enhanced by use of SPCs as well as better patient education and follow-up. While there are promising national initiatives to improve BP management, more needs to be done by individual physicians. Antihypertensive SPCs are available on the national essential medicines list and may help to overcome some of the problems with suboptimal adherence, therapeutic inertia, and low rates of BP control that contribute to the high cardiovascular death rate in Colombia.

Cost-effectiveness of cardiomyopathy ambulatory care with sacubitril/valsartan vs standard therapy after COVID-19 in Kazakhstan

The aim of this study is to evaluate the cost-effectiveness of 2 different therapies of cardiomyopathy (CM) after COVID -19. The focus of the study is fixed dose combination (FDC) of sacubitril/valsartan and standard therapy in Kazakhstan. This is written from the point of view of the health insurance institution. Information for the age, gender, CM therapy, number of hospitalizations, COVID-19 infection, and past cardiovascular surgeries of 237 patients with incidents of CM which required a hospitalization after a COVID-19 infection was collected. Selected patients were divided into two groups: the cost of FDC and standard therapy and the annual cost of their therapy was calculated. The incremental cost-effectiveness ratio was calculated by dividing the cost of medication therapy by the number of hospitalizations between the two compared groups. Robustness of the results was tested with deterministic and probabilistic sensitivity analyses. The study was performed in City cardiology centre of Almaty in Kazakhstan during 2020–2022. Results show that FDC is more costly but more effective, leading to fewer hospitalizations. ICER accounts for €-2,743.08 per hospitalization saved in the group on FDC vs standard of therapy. Sacubitril/valsartan is cost-effective in ambulatory conditions in comparison with standard therapy of cardiomyopathy after COVID-19 leading to savings due to the decrease in the number of hospitalizations.

Effectiveness of perindopril/amlodipine fixed-dose combination in the treatment of hypertension: a systematic review.

Background: Uncontrolled blood pressure is a major risk factor for cardiovascular diseases. Fixed-dose combination (FDC) therapy offers a promising approach to addressing this challenge by providing a convenient single-tablet solution that enhances the effectiveness of blood pressure control. In our systematic review, we assess the effectiveness of perindopril/amlodipine FDC in managing blood pressure. Methods: We conducted a comprehensive search across four primary electronic databases, namely, PubMed, Virtual Health Library (VHL), Global Health Library (GHL), and Google Scholar, as of 8 February 2022. Additionally, we performed a manual search to find relevant articles. The quality of the selected articles was evaluated using the Study Quality Assessment Tools (SQAT) checklist from the National Institute of Health and the ROB2 tool from Cochrane. Results: Our systematic review included 17 eligible articles. The findings show that the use of perindopril/amlodipine FDC significantly lowers blood pressure and enhances the quality of blood pressure control. Compared to the comparison group, the perindopril/amlodipine combination tablet resulted in a higher rate of blood pressure response and normalization. Importantly, perindopril/amlodipine FDC contributes to improved patient adherence with minimal side effects. However, studies conducted to date have not provided assessments of the cost-effectiveness of perindopril/amlodipine FDC. Conclusion: In summary, our analysis confirms the effectiveness of perindopril/amlodipine FDC in lowering blood pressure, with combination therapy outperforming monotherapy and placebo. Although mild adverse reactions were observed in a small subset of participants, cost-effectiveness assessments for this treatment remain lacking in the literature.

Fixed-Dose Combination Formulations in Solid Oral Drug Therapy: Advantages, Limitations, and Design Features.

Whilst monotherapy is traditionally the preferred treatment starting point for chronic conditions such as hypertension and diabetes, other diseases require the use of multiple drugs (polytherapy) from the onset of treatment (e.g., human immunodeficiency virus acquired immunodeficiency syndrome, tuberculosis, and malaria). Successful treatment of these chronic conditions is sometimes hampered by patient non-adherence to polytherapy. The options available for polytherapy are either the sequential addition of individual drug products to deliver an effective multi-drug regimen or the use of a single fixed-dose combination (FDC) therapy product. This article intends to critically review the use of FDC drug therapy and provide an insight into FDC products which are already commercially available. Shortcomings of FDC formulations are discussed from multiple perspectives and research gaps are identified. Moreover, an overview of fundamental formulation considerations is provided to aid formulation scientists in the design and development of new FDC products.

Implementation study to introduce clinical guidelines on lipid metabolism disorders into routine practice: results of the first stage

Despite widespread knowledge in the management of patients with lipid metabolism disorders, their application in clinical practice is insufficient. Identification of barriers to the implementation of key principles of clinical guidelines in routine practice is the first step of the implementation study.Aim. To assess the organization and quality of care for patients with dyslipidemia in order to identify barriers to the implementation of the main principles of clinical guidelines in practice.Material and methods. An implementation study was planned, the initial stage of which was to conduct an anonymous online questionnaire among health care representatives of various levels in all Russian subjects.Results. The study involved 788 physicians, 124 heads of medical organizations and 48 chief freelance specialists from 84 Russian subjects. A wide range of barriers was identified: low availability of lipoprotein (a) testing (66,6% of physicians), coronary calcium index (79,4% of physicians, 71,8% of heads of a medical organizations, 79,2% of chief freelance specialists) and CT angiography (70,0% of physicians, 71,0% of heads of a medical organizations, 85,4% of chief freelance specialists). Lack of funds to manage lipid service (55,6% of heads of a medical organizations, 35,4% of chief freelance specialists). The key barrier to regular lipid-lowering therapy and achieving target low-density lipoprotein cholesterol (LDL-C) levels is lack of perceived need for treatment in patients (58,1% of physicians, 80,0% of heads of a medical organizations, 87,5% of chief freelance specialists), for PCSK9-targeted therapy — high cost (44,1% of physicians, 34,7% of heads of a medical organizations, 23,0% of chief freelance specialists). The possible fixed-dose combination therapy for dyslipidemia was positively perceived (59,7% of physicians, 42,0% of heads of a medical organizations, 35,4% of chief freelance specialists). Inclusion of innovative therapy in medicine assistance program will improve the situation in achieving target LDL-C levels (85,6% of physicians, 91,1% of heads of a medical organizations, 95,8% of chief freelance specialists).Conclusion. A wide range of barriers to the implementation of clinical guidelines on lipid metabolism disorders into practice have been identified. Based on the results obtained, the second stage of the implementation study will identify strategies aimed at eliminating the identified barriers.

Fixed triple combination of amlodipine, perindopril and atorvastatin in the focus of cardiovascular effectiveness and safety

The review outlines modern concepts of the relevance of fixed-dose combination therapy comprising angiotensin-converting enzyme inhibitor and dihydropyridine calcium channel antagonist as an antihypertensive component with the HMG-CoA reductase inhibitor when treating hypertensive patients. We have identified the realms of its possible clinical use taking into consideration the comorbidity peculiarities. In addition, we provide main features of the current drugs’ clinical pharmacodynamics and outline their role in real clinical practice. Nevertheless the emphasis was placed on the modern single-pill combination of amlodipin, atorvastatin and perindopril. We concisely report the results data collected from the large, randomized, double-blind major clinical trials regarding the effectiveness of single pill combination of amlodipine, atorvastatin and perindopril , primary focusing on their cardioprotective features and overall safety profile.

Fixed-Dose Combination Therapy for Prevention of Cardiovascular Diseases in CKD: An Individual Participant Data Meta-analysis.

Fixed-dose combination treatments reduce cardiovascular disease in primary prevention. We aim to explore whether those benefits differ in the presence of chronic kidney disease (CKD). We conducted an individual participant data meta-analysis in 18,162 participants on the efficacy and safety of treatment for the primary prevention of cardiovascular disease. Combination therapies consisted of at least two blood pressure lowering drugs, and a statin, with or without aspirin versus placebo or usual care. Here we examine the differential effect of fixed-dose combination treatment on the risk of developing cardiovascular disease in participants with a low estimated glomerular filtration rate (eGFR <60 ml/min/1.73m2; CKD-EPI formula) compared to a normal eGFR (≥60 ml/min/1.73m2). The primary composite outcome was time to first occurrence of a combination of cardiovascular death, myocardial infarction, stroke, or arterial revascularization. At baseline, mean level of eGFR was 76 ml/min/1.73m2 (17). 3,315 (18%) participants had low eGFR at baseline. During a median follow-up of 5 years, among participants with normal eGFR, the primary outcome occurred in 232 (3%) of participants in the treatment group compared with 339 (5%) in control group (hazard ratio [HR], 0.68; 95% confidence interval [95%CI], 0.57-0.81; P<0.001). In participants with low eGFR, the primary outcome occurred in 64 (4%) of participants in the treatment group compared with 130 (8%) in control group (HR, 0.49; 95%CI, 0.36-0.66; P<0.001; P for interaction 0.047). The relative risk reduction among participants with low eGFR was larger for combination strategies including aspirin compared to treatments without aspirin. Apart from dizziness, other side effects didn't differ between treatment and control groups regardless of the stage of their kidney function. A fixed-dose combination treatment strategy is effective and safe at preventing cardiovascular disease, irrespective of eGFR but relative and absolute risk reductions are larger in individuals with low eGFR.

EE268 Temporal Trends in Adverse Event Costs with Nivolumab + Relatlimab Combination Therapy or Nivolumab Monotherapy for Patients with Unresectable or Metastatic Melanoma

This study described hospitalization costs of grade 3/4 all-cause adverse events (AEs) and treatment-related AEs (TRAEs) of nivolumab plus relatlimab fixed-dose combination therapy (Nivo+Rela) and nivolumab monotherapy (Nivo) for unresectable or metastatic melanoma.

Fixed dose combination therapies in primary cardiovascular disease prevention in different groups: an individual participant meta-analysis

ObjectiveTo evaluate the effects of fixed dose combination (FDC) medications on cardiovascular outcomes in different age groups in an individual participant meta-analysis of three primary prevention randomised trials.MethodsParticipants at intermediate...

Use of Fixed-dose Combination Therapy with Remogliflozin and Vildagliptin as an Add-on Drug in Improving the Glycemic Control of Type 2 Diabetes Mellitus: An Observational Study

Objective To evaluate whether a fixed dose combination (FDC) with remogliflozin and vildagliptin as an add-on therapy can improve the glycemic control in the management of type 2 diabetes mellitus and also the non-glycemic effects on physical profile, blood pressure, lipids, and insulin resistance. Materials and Methods An observational study that included 50 poorly controlled diabetics from April 2021 to September 2021. Patients were divided into two groups – those who were prescribed this FDC by their treating physician as an add-on drug were formed as group 1 ( n = 28). Comparison group was age-matched patients who received other standard anti-diabetic medications, categorized as group 2 ( n = 22). Fasting and postprandial sugars were done at baseline, the third and sixth month; glycated hemoglobin, body mass index, blood pressure, and lipids were done at baseline and the sixth month. Changes in blood sugar levels and glycated hemoglobin (HbA1C) at the third and sixth month from the baseline were compared using the Mann-Whitney U test. P-value less than 5% was considered statistically significant. Results A statistically significant reduction in mean HbA1c was noted in group 1 [–1.80 (−3.20, −0.15)] when compared to group 2 [0.50 (0.05, 0.80)] at the end of the third month. At the end of the sixth month, a significant reduction in the HbA1c level was noted in group 1 [(7.83 ± 0.87 %) when compared to baseline (10.3 ± 1.75%)]. Change in PPBS value at the third month from baseline was also statistically significant between groups 1 and 2 (−62.0 mg%, 19.0, P = 0.003). With respect to the body mass index and blood pressure, we did not find any significant difference. Conclusion The fixed drug combination improves glycemic control by significantly reducing mean HbA1c at the third and sixth month from baseline and there was no significant effect on body mass index, blood pressure, and lipids.

Polypill protects MAFLD patients from cardiovascular events and mortality: a prospective trial.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a novel term that distinguishes patients at risk of adverse clinical outcomes with higher accuracy than those with non-alcoholic fatty liver disease (NAFLD). Cardiovascular mortality is the leading cause of death in MAFLD. The current literature lacks large-scale prospective studies that address preventive approaches for cardiovascular health in MAFLD. We investigated whether MAFLD patients benefit from a fixed-dose combination therapy (Aspirin, hydrochlorothiazide, atorvastatin, valsartan), known as a Polypill. Analysis was performed (stratified based on MAFLD status) of a clinical trial that included 1596 individuals randomly allocated to an intervention (polypill) or a control (usual care) group. Patients were followed up for five years for any adverse drug reaction, major cardiovascular events, and mortality. Univariable and multivariable survival analyses were performed, and the interaction level was assessed by R programming. Patients who consumed the polypill had significantly lower hazard ratios of major cardiovascular events incidence (HR 0.56, 95% CI 0.41-0.78) and cardiovascular mortality (HR 0.41, 95% CI 0.2-0.86) compared to the control group. Polypill showed significantly better results in lowering cardiovascular events in MAFLD patients than in the general population. (p-value for interaction: 0.028). Moreover, comparing those patients who had high adherence to the Polypill, with the control group, further enhanced the results. Major cardiovascular events are prevented in MAFLD patients who consume the Polypill. MAFLD patients benefit from the Polypill more than the general population.

Linagliptin in Combination with Emblica officinalis Gaertn Improves Glycemic Control through Alleviating Dyslipidemia and Oxidative Stress on Streptozotocin Induced Diabetic Rats

Objectives: Diabetes is a complex chronic metabolic disorder. Today, many diabetes patients are known to supplement their standard therapies with herbal medications that have antidiabetic characteristics. The purpose of the study was to examine the fixed dose combination of linagliptin and Emblica officinalis Gaertn (aq FE) for its hypoglycemic, hypolipidemic, and antioxidant properties.&#x0D; Methods: Streptozotocin (45 mg/kg b.w.) was administered intraperitoneally to Wister albino rats to cause diabetes. Linagliptin (5 mg/ 70kg b.w), aqueous fruit extract of Emblica officinalis Gaertn (200 mg/kg b.w.) and fixed dose combination therapy of linagliptin (2.5 mg /70kg b.w) with aqueous fruit extract of Emblica officinalis Gaertn (100 mg/kg b.w) were administered orally once daily for four weeks. After that fasting blood glucose level (FBG), low density lipoprotein (LDL), high density lipoprotein (HDL), total cholesterol (TC) and triglycerides (TG) were measured in serum with streptozotocin (STZ)-induced diabetes. Typical procedures were used to measure the antioxidant activity by the estimation of catalase (CAT) and superoxide dismutase (SOD) activity.&#x0D; Results: The combination therapy significantly (p&lt;0.05) reduced the FBG, TC, TG, LDL level in compared to the diabetic control group (p&lt;0.05). Significant (p&lt;0.05) increased of HDL was also observed. The antioxidant activity significantly increased after the administration of fixed dose combination therapy in compared to diabetic control group. These alterations were vastly superior to those of linagliptin with Emblica officinalis Gaertn (aqFE) monotherapy.&#x0D; Conclusion: This study suggests that the fixed dose combination therapy of linagliptin and Emblica officinalis Gaertn (aq FE) might be potent on antihyperglycemic antidyslipidemic and antioxidative effect.

New pharmacological agents and novel cardiovascular pharmacotherapy strategies in 2022.

Cardiovascular diseases (CVD) remain the leading cause of death worldwide and pharmacotherapy of most of them is suboptimal. Thus, there is a clear unmet clinical need to develop new pharmacological strategies with greater efficacy and better safety profiles. In this review, we summarize the most relevant advances in cardiovascular pharmacology in 2022 including the approval of first-in-class drugs that open new avenues for the treatment of obstructive hypertrophic cardiomyopathy (mavacamten), type 2 diabetes mellitus (tirzepatide), and heart failure (HF) independent of left ventricular ejection fraction (sodium-glucose cotransporter 2 inhibitors). We also dealt with fixed dose combination therapies repurposing different formulations of "old" drugs with well-known efficacy and safety for the treatment of patients with acute decompensated HF (acetazolamide plus loop diuretics), atherosclerotic cardiovascular disease (moderate-dose statin plus ezetimibe), Marfan syndrome (angiotensin receptor blockers plus β-blockers), and secondary cardiovascular prevention (i.e. low-dose aspirin, ramipril and atorvastatin), thereby filling existing gaps in knowledge, and opening new avenues for the treatment of CVD. Clinical trials confirming the role of dapagliflozin in patients with HF and mildly reduced or preserved ejection fraction, long-term evolocumab to reduce the risk of cardiovascular events, vitamin K antagonists for stroke prevention in patients with rheumatic heart disease-associated atrial fibrillation, antibiotic prophylaxis in patients at high risk for infective endocarditis before invasive dental procedures, and vutrisiran for the treatment of hereditary transthyretin-related amyloidosis with polyneuropathy were also reviewed. Finally, we briefly discuss recent clinical trials suggesting that FXIa inhibitors may have the potential to uncouple thrombosis from hemostasis and attenuate/prevent thromboembolic events with minimal disruption of hemostasis.

Efficacy and safety of fixed-dose combination of Bilastine-Montelukast in adult patients with allergic rhinitis: a phase III, randomized, multi-center, double-blind, active controlled clinical study

Background Histamine and cysteinyl leukotrienes (CysLTs) are potent inflammatory mediators in allergic rhinitis (AR). Studies involving other combinations of antihistaminics (Levocetirizine) and highly selective leukotriene receptor antagonist (LTA) (Montelukast) combination have shown additive benefits and are widely prescribed for AR. Objective Evaluate the efficacy and safety of Bilastine 20 mg and Montelukast 10 mg fixed-dose combination (FDC) therapy in patients with AR. Methods A randomized, double-blind, comparative, parallel, phase III study was conducted to evaluate efficacy and safety of Bilastine 20 mg and Montelukast 10 mg FDC at 16 tertiary care otolaryngology centres in India. Adult patients with AR for one year with IgE antibody positive and 12-h NSS score >36 in 3 days were randomized to receive either Bilastine 20 mg and Montelukast 10 mg or Montelukast 10 mg & Levocetirizine 5 mg tablets for 4 weeks. The change in total symptom score (nasal symptom scores (NSS) & non-nasal symptom scores (NNSS)) from baseline to week 4 was assessed as primary endpoint. Secondary endpoints included changes in TSS, NSS, NNSS, individual symptom scores (ISS), Rhinoconjunctivitis Quality of Life (RQLQ), discomfort due to rhinitis (VAS), and clinical global impression (CGI) scores. Results The change in mean TSS from baseline to week 4 in Test group (16.6 units) was comparable to reference group (17 units) (p= 0.8876). The difference in change in mean NSS, NNSS and ISS from baseline to day 7, 14, 28 were comparable. RQLQ improved from baseline to Day 28. Significant improvements were observed in discomfort due to AR measured by VAS and CGI scores from baseline to day 14 and 28. The safety and tolerability of patients were comparable between the groups. All adverse events (AEs) were mild to moderate in severity. No patient discontinued due to AEs. Conclusions The FDC of Bilastine 20 mg and Montelukast 10 mg was efficacious and well tolerated in Indian patients with AR.

Prescription Patterns of New Use of Fixed-Dose Combination Inhalers in Patients with Chronic Obstructive Pulmonary Disease: Long-Acting β2 Agonists Plus Long-Acting Muscarinic Antagonists versus Long-Acting β2 Agonists Plus Inhaled Corticosteroids.

The clinical guideline recommends use of long-acting β2 agonists/long-acting muscarinic antagonists (LABA/LAMA) or long-acting β2 agonists/inhaled corticosteroids (LABA/ICS) combination therapies for patients with severe chronic obstructive pulmonary disease (COPD). The fixed-dose combination (FDC) inhalers of LABA/LAMA and LABA/ICS were reimbursed in Taiwan in 2015 and in 2002, respectively. This study aimed to examine prescription patterns of new use of either FDC therapy in real-world practice. We identified COPD patients who initiated LABA/LAMA FDC or LABA/ICS FDC between 2015 and 2018 from a population-based Taiwanese database with 2 million, randomly sampled beneficiaries enrolled in a single-payer health insurance system. We compared number of LABA/LAMA FDC and LABA/ICS FDC initiators in each calendar year, from different hospital accreditation levels, and cared for by different physician specialties. We also compared baseline patient characteristics between LABA/LAMA FDC and LABA/ICS FDC initiators. A total of 12,455 COPD patients who initiated LABA/LAMA FDC (n=4019) or LABA/ICS FDC (n=8436) were included. Number of LABA/LAMA FDC initiators increased apparently (n=336 in 2015 versus n=1436 in 2018), but number of LABA/ICS FDC initiators decreased obviously (n=2416 in 2015 versus n=1793 in 2018) over time. The preference of use of LABA/LAMA FDC varied across clinical environments. The proportions of LABA/LAMA FDC initiators were more than 30% in the setting of non-primary care clinics (eg, medical centers) and in the services of chest physicians; but were only less than 10% in primary care clinics and non-chest physicians' services (eg, family medicine physicians). LABA/LAMA FDC initiators appeared to be older, male, to have more comorbidities, and to utilize resources more frequently compared to LABA/ICS FDC initiators. This real-world study found evident temporal trends, variations in healthcare provider, and differences in patient characteristics among COPD patients who initiated LABA/LAMA FDC or LABA/ICS FDC.

Estimation of Pediatric Dosage of Antimalarial Drugs, Using Pharmacokinetic and Physiological Approach.

Most of the individuals who die of malaria in sub-Saharan Africa are children. It is, therefore, important for this age group to have access to the right treatment and correct dose. Artemether-lumefantrine is one of the fixed dose combination therapies that was approved by the World Health Organization to treat malaria. However, the current recommended dose has been reported to cause underexposure or overexposure in some children. The aim of this article was, therefore, to estimate the doses that can mimic adult exposure. The availability of more and reliable pharmacokinetic data is essential to accurately estimate appropriate dosage regimens. The doses in this study were estimated using the physiological information from children and some pharmacokinetic data from adults due to the lack of pediatric pharmacokinetic data in the literature. Depending on the approach that was used to calculate the dose, the results showed that some children were underexposed, and others were overexposed. This can lead to treatment failure, toxicity, and even death. Therefore, when designing a dosage regimen, it is important to know and include the distinctions in physiology at various phases of development that influence the pharmacokinetics of various drugs in order to estimate the dose in young children. The physiology at each time point during the growth of a child may influence how the drug is absorbed, gets distributed, metabolized, and eliminated. From the results, there is a very clear need to conduct a clinical study to further verify if the suggested (i.e., 0.34 mg/kg for artemether and 6 mg/kg for lumefantrine) doses could be clinically efficacious.