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Aim. To assess the efficacy and safety of Vamloset (amlodipine/valsartan 5/80, 5/160, 10/160 mg) and Co-Vamloset (amlodipine/valsartan/hydrochlorothiazide 10/160/12.5, 10/160/25 mg) in achieving the target levels of blood pressure (BP) in patients with stage 23 arterial hypertension (AH). The article discusses indicators affecting adherence to antihypertensive therapy (AHT). Material and methods. The VICTORY II Russian study in 8 clinical centers of the Russian Federation included 103 patients over 18 years of age with stage 23 essential AH (who havent been previously treated and have office systolic BP160 mm Hg and/or diastolic BP100 mm Hg or who havent reached the target office blood pressure with mono- or double AHT). The Full Analysis Set (FAS) for efficacy analysis included 99 patients, a FAS population with the restoration of data missed using Last Observation Carried Forward. The SF-36 questionnaire for assessing the quality of life, the effect on erectile function in men, the convenience of current therapy from the point of view of patients were analyzed after 16 weeks of treatment. The Per Protocol (PP) population included 80 patients completing the study without major protocol deviations to assess the primary parameters of efficacy. All patients with stage 2 hypertension were prescribed Vamloset (amlodipine/valsartan 5/80 mg), with stage 3 hypertension amlodipine/valsartan 5/160 mg. Dose titration of Vamloset and Co-Vamloset (LLC Krka-RUS) was carried out every 4 weeks according to the AHT schemes. Results. The studys active phase included 100 patients aged 59.510.9 years (women 59%) with AH duration of 83.48.4 months; 83% of patients received AHT prior inclusion in the study. In the PP population, 16 week- AHT with Vamloset or Co-Vamloset allowed reaching the target BP in 90.0% of patients (95% confidence interval [CI] 81.295.6). Overall clinical efficacy was achieved in 98.8% of patients (95% CI 93.2100.0). All treatment regimens were characterized by high patient compliance. In the total group, 50% of patients rated their AHT as more convenient than they had previously used; of them, in the stage 2 AH group 47.8%, in the stage 3 AH group 53.3%. Metabolic neutrality with regard to at least one indicator was observed in 100% of patients, with regard to 6 indicators in 43.9% [33.9; 54.9]. For all 98 patients included in the analysis, changes in all SF-36 scales, except for physical functioning (p=0.339), were statistically significant (p0.05). The effect of AHT on erectile function was rated as positive in 51.3% of men. Good tolerance data are consistent with the established drug safety profile. Conclusion. In the VICTORY II study, high antihypertensive efficacy and an improvement in a set of indicators of optimal adherence to AHT by Vamloset and Co-Vamloset within 16 weeks were proved in patients with stage 23 AH. Patients high rating for quality improvement in the quality of life, safety of therapy and ease of use ensured optimal compliance of Vamloset and Co-Vamloset therapy throughout the study.

Allergic rhinitis in childhood has been often missed, mistreated and misunderstood. It has significant comorbidities, adverse effects upon quality of life and educational performance and can progress to asthma or worsen control of existing asthma. Accurate diagnosis and effective treatment are important. The new EUFOREA algorithm provides a succinct but wide- ranging guide to management at all levels, based on previous guidelines with updated evidence and has been adjusted and approved by experts worldwide. ispartof: FRONTIERS IN ALLERGY vol:2 ispartof: location:Switzerland status: published

Background Antibiotic resistance is an emerging problem caused due to antibiotic use. In countries with high rates of infectious diseases, antibiotic resistance is a frequent cause of mortality. The aim was to analyse antibiotic prescribing practices between 2008 and 2017 in a teaching (TH) and a non-teaching (NTH) hospital, as typical hospitals of low- and middle-income countries, and to compare antibiotic prescribing for severe infectious indications for which empiric antibiotic treatment is recommended. Methods Data from adult patients registered at two Indian private-sector hospitals with one of the following indications: epiglottitis, pneumonia, peritonitis, pyelonephritis, cellulitis, erysipelas, septic arthritis, endocarditis, meningitis or sepsis; were included and analysed. Antibiotic prescription data was analyzed using the World Health Organization’s (WHO) Anatomical Therapeutic Chemical classification system and the Defined Daily Doses. Chi-square and linear regression were used to compare the data between groups. Time series analyses were conducted using linear regression. P-values Results In total, 3766 patients were included, 2504 inpatients in the NTH and 1262 in the TH, of which 92 and 89% patients, respectively, were prescribed antibiotics. Sixty-one percent of total prescriptions in the TH and 40% in the NTH comprised the access category of antibiotics (i.e. the first-choice of treatment according to the WHO). The WHO’s second-choice of treatment, the watch category, comprised 29 and 40% of total prescriptions in the TH and NTH, respectively. Prescribing of fixed-dose combinations (FDCs) of antibiotics was significantly higher in the NTH (18%) than in the TH (8%, P watch antibiotics and FDCs increased significantly in both hospitals between 2008 and 2017 among patients with pneumonia, cellulitis and peritonitis (P Conclusions Prescribing of watch antibiotics and FDCs of antibiotics increased over time at both hospitals, indicating under prescribing of access antibiotics and more prescribing of second-choice antibiotics. The results can be used to highlight the areas of improvement in similar settings. Implementing diagnostic routines and local prescribing guidelines could improve the prescribing practices.

As a result of an aging population, the need for fixed dose combinations in the treatment of cardiovascular diseases, that are easy to swallow and administer, has been growing remarkably. In this work, the feasibility of coaxial electrospraying (CES) was investigated to manufacture in one single step, a powder of individually coated particles containing atenolol (ATE), lovastatin (LOV) and acetylsalicylic acid (ASA). To improve the dissolution rate of the poorly water soluble LOV, an amorphous solid dispersion (ASD) of LOV with Soluplus® (SOL) was formulated and Eudragit S100®, an enteric copolymer that only dissolves above pH 7, was applied as coating to avoid LOV hydrolysis in acidic medium. Furthermore, ATE was added to the inner ASD compartment and the acidic ASA was embedded in the coating layer. With regard to the uncoated ASD particles, which were prepared with single nozzle electrospraying, the rate and extent of the LOV dissolution was increased, even to an extent of 100% for the 1/1/6 (ATE/LOV/SOL) ratio. Hence, this ratio was selected and coated particles with proper release of the three APIs could be successfully produced via CES. However, a peculiar behaviour of the coating performance was observed. Regarding LOV, the enteric layer of the particles performed as expected in acidic medium and supersaturation was obtained after the switch to a neutral pH, but in contrast, over 50% of ATE was released after 90 min in acidic medium. Nonetheless, hardly any ATE was released under acidic circumstances from ATE tablets that were, as a benchmark, manually dip-coated with Eudragit S100®. Two different model APIs, namely paracetamol (well soluble) and fenofibrate (poorly soluble) were tested as well, revealing similar discrepancy in the coating performance. The coating layer formed during CES is most likely less dense as compared to the layer produced with tablet coating and consequently, more permeable for highly soluble APIs, but not for the poorly soluble compounds. ispartof: INTERNATIONAL JOURNAL OF PHARMACEUTICS vol:577 ispartof: location:Netherlands status: published

Medication adherence is a growing concern for public health and poor adherence to therapy has been associated with poor health outcomes and higher costs for patients. Interventions for improving adherence need to consider the characteristics of the individual therapeutic regimens according to the needs of the patients. In particular, geriatric and paediatric populations as well as dermatological patients have special needs/preferences that should be considered when designing drug products. Patient Centric Drug Product Pharmaceutical Design (PCDPD) offers the opportunity to meet the needs and preferences of patients. Packaging, orodispersible formulations, fixed dose combinations products, multiparticulate formulations, topical formulations and 3D printing are of particular relevance in a PCDPD process. These will be addressed in this review as well as their impact on medication adherence.

Introduction: Gastric problems are the most common diseases seen in many countries for which majority of the population prefer Proton Pump Inhibitors (PPI) and Histamine (H2) Blockers. They are prescribed most commonly for Gastroesophageal Reflux Disease (GERD), Dyspepsia, Peptic Ulcer Disease, along-with medications like Non-Steroidal Antiinflammatory Drugs (NSAIDs) and other drugs. Concerns have been raised about the increasing costs associated with prescription of these drugs as they are often prescribed for minor symptoms and without clear indications. Prescribing pattern should be evaluated periodically to promote rational use of medicines. Aim: To assess the prescribing pattern of PPIs and H2 Blockers in Surgery and Medicine Department of a Tertiary Care Hospital. Materials and Methods: An observational study was conducted in a Tertiary Care Hospital, Karamsad over a period of one year from November, 2018 to October, 2019, among patients visiting to Out Patient Department (OPD) and In Patient Department (IPD) of Medicine and Surgery Department that were prescribed PPI and H2 Blockers. Total 1100 prescriptions and 1265 PPI, H2 Blockers were analysed. The data were analysed for socio-demographic variables along with details of PPI and H2 Blockers. co-prescribing drugs, Fixed Dose Combinations (FDCs) and drug interactions of each prescription was analysed. Results: In the study, PPI and H2 Blockers were prescribed more in males (54.36%). The predominant age group was 18-40 years (42%). Among studied drugs, most commonly prescribed single drug was Pantoprazole and FDC was Ranitidine + Domperidone. The drugs were most commonly prescribed through oral route (90.9%). They were most commonly prescribed along with an NSAID for gastroprotection (28.9%). Pharmacokinetic drug interactions were observed more in the study. Conclusion: This study showed that physicians prescribe PPI and H2 Blockers as a co-medication for gastroprotection. There is a need to increase documentation for prescribing PPI and H2 Blockers.

We regret this article is behind a paywall., BACKGROUND:Government of India's Revised National TB Control Programme (RNTCP) has begun implementing daily fixed dose combination (FDC) anti-TB treatment regimen for drug sensitive TB patients in which ethambutol is given for six months. Prolonged ethambutol use is known to cause ocular adverse drug events (ADE). OBJECTIVES:To assess the magnitude of ocular ADEs in adult drug sensitive TB patients initiated on daily FDCs and to describe the demographic and clinical profile of patients with ocular ADEs. METHODS:We conducted a retrospective cohort study involving review of RNTCP records of all adult (age >14 years) drug sensitive TB patients initiated on daily FDCs between1st January 2018 and 31st July 2018 in Thiruvananthapuram district, Kerala State, India. RESULTS:714 patients were initiated on daily FDCs during the study period. It was unknown whether all patients had undergone assessment for ocular ADEs. However, of these 714 patients, 8 patients (1.1%) were documented to have had ocular ADEs. Seven of these 8 patients had received ethambutol more than 15 mg/kg body weight and had developed ocular symptoms (decreased/blurring of vision) 3 months after TB treatment initiation. Ethambutol was stopped in all these 8 patients. In 5 patients it was recorded that ocular ADEs had resolved following stoppage of ethambutol and in the remaining it was unknown. CONCLUSION:The study confirms the occurrence of ocular ADEs among drug sensitive TB patients on daily FDCs and recommends strengthening of systems for assessing, documenting and managing ocular ADE.

Objective: To analyse the rationality of various FDCs used in the treatment Diabetes Mellitus and to find out the irrational FDCs existing in Indian market. Material and Methods: Study Design: Analytical study. Data on FDC's available in the Indian market was collected from Current Index of Medical Specialities (CIMS) and Monthly Index of Medical Specialities (MIMS) and their rationality was analysed using a pretested tool based on FDCs listed in WHO essential list of medicines and National List of Essential Medicines (NLEM), others based on their pharmacodynamic activity, Pharmacokinetic parameters and significant drug interactions occurring due to API (Active pharmaceutical ingredients) contained within the product Result: A total of 18 combinations were analysed, among those 11 combinations were irrational. Conclusion: Predominantly irrational FDCs are being circulated in the Indian market hence through analyses by prescribers is needed before prescribing to patients in order to avoid ADR. This calls for a close scrutiny of marketed FDC's and educating prescribers to use them with great care and caution also indicates a serious review of regulatory framework for drug manufacturing and marketing. KEYWORDS: Fixed Dose Combinations; Antidiabetics; Irrational.

Fixed dose combination (FDC) dual bronchodilators that co-administer a long acting β2 -adrenoceptor agonist (LABA) and a long acting muscarinic antagonist (LAMA) are a new class of inhaled treatment for chronic obstructive pulmonary disease (COPD). This review focuses on the clinical evidence for the benefit of LABA/LAMA FDCs compared with monocomponent treatments, and also compared with active comparators that are widely used for the treatment of COPD, namely tiotropium and salmeterol-fluticasone. Novel FDC dual bronchodilators include QVA149 and umeclidinium/vilanterol (UMEC/VI). Long term clinical trials show that QVA149 and UMEC/VI are superior to monocomponent therapy in terms of trough forced expiratory volume in 1 s (FEV1), although the FEV1 improvement was limited to approximately 80-90% of the added monocomponent values. This suggests that the effect of combining a LABA and a LAMA is not fully additive. LABA/LAMA FDC were associated with the largest mean changes in symptoms and health status that were above the minimal clinically important difference, in contrast to the monocomponents. Furthermore, these LABA/LAMA FDCs demonstrated superiority over the active comparators tiotropium and salmeterol-fluticasone in terms of trough FEV1 and patient-reported outcomes. LABA/LAMA FDCs offer a simplified means of maximizing bronchodilation for COPD patients, with the improvements in lung function being mirrored by benefits in terms of symptoms and exacerbations. The use of LABA/LAMA FDCs in clinical practice is set to grow and further studies are needed to define their optimal place in treatment guidelines.

Background: The fixed dose combinations (FDCs) of muscle relaxants, non-steroidal anti-inflammatory drugs and paracetamol are commonly prescribed in the treatment of acute lower backache. Aim: The present study was undertaken with the aim of comparing the efficacy and safety of FDCs of thiocolchicoside and aceclofenac versus chlorzoxazone, aceclofenac and paracetamol in patients with acute lower backache associated with muscle spasm. Materials and Methods: A total of 100 patients between ages range from 18 and 55 years having low back pain of ≤7 days duration were randomly divided into two groups. Group A was prescribed thiocolchicoside (4 mg) + aceclofenac (100 mg) while Group B was prescribed chlorzoxazone (500 mg) + aceclofenac (100 mg) + paracetamol (325 mg) orally twice daily for 7 days. Severity of pain at rest and on movement was recorded using visual analogue scale. Muscle spasm was evaluated by hand-to-floor distance and Lasegue's maneuver. Readings were noted on day 1 (baseline), day 3 and day 7. Results: There was statistically significant reduction in severity of pain and muscle spasm on day 3 and day 7 in both groups. There was no statistically significant difference in pain relief and muscle spasm among the treatment groups but clinically showed better improvement in the Group A. The adverse drug reactions occurring during study showed a statistically significant better safety profile in the Group A than Group B . Conclusion: These findings confirm that FDC of thiocolchicoside and aceclofenac is a preferred option for patients with lower backache pain associated with muscle spasm.

Summary Background GINA guideline recommends stepping down treatment of asthma patients where control is achieved. The aim of this analysis was to estimate the costs and health outcomes associated with step down of controlled patients on high dose fluticasone/salmeterol (FP/S 1000/100 μg daily) to either medium dose FP/S (500/100 μg) dry powder or extrafine beclometasone/formoterol (BDP/F 400/24 μg) pMDI in three European countries. Methods A patient-level simulation Markov model was constructed to enable the simulation of three comparative arms (FP/S 1000/100, FP/S 500/100, BDP/F 400/24). Transition probabilities and healthcare resources consumption were derived from a multinational clinical trial comparing BDP/F 400/24 μg vs. FP/S 500/100 μg as step down therapy in asthma. Direct costs and health state utilities were sourced from public source and published literature. The analysis was conducted from a health system perspective, based on six months horizon. Probabilistic sensitivity analyses were conducted. Results The ICER (Incremental Cost-Effectiveness Ratio) associated with high dose dry powder FP/S 1000/100 μg vs. extrafine BDP/F 400/24 μg was above 70,000 GBP and 200,000 €/QALY (Quality Adjusted Life Years). An ICER of 29,000 GBP/QALY and above 30,000 €/QALY was associated with medium dose dry powder FP/S 500/100 μg vs. BDP/F 400/24 μg. Conclusions It was found that maintaining controlled patients on high dose FP/S is not cost-effective. Extrafine BDP/F 400/24 μg daily can be considered to be a cost-effective option in the countries analyzed to maintain control of asthmatic patients stepped down from high dose FP/S 1000/100 μg daily dry powder or suspension formulations.

Aim: To assess the knowledge, attitude, and practices of fixed dose combination drugs among postgraduate dental students. Materials and Methods: A cross-sectional study was carried out among postgraduate dental students of dental colleges in coastal Andhra Pradesh. Three colleges were randomly selected and students of all the three years were included. Data was collected from the specialities of oral medicine and radiology, oral surgery, endodontics, pedodontics, periodontics, and public health dentistry. The total sample was 90 postgraduate students; informed consent was obtained from the participants, and a pretested questionnaire was distributed to them. Data was analyzed using the Statistical Package for the Social Sciences version 20 software. Results: Out of 90 postgraduates, 33 were males and 57 were females. Thirty-five percent were aware of the essential medical list (EML), among them 11% were from oral medicine and radiology and 6.7% were from pedodontics. However, most of them were unaware of the number of fixed dose combination drugs present in the World Health Organization EML. None of them were able to name at least a single banned fixed dose combination drug. Most of them were unaware of the advantages and disadvantages of using fixed dose combination drugs. Amoxicillin with clavulanic acid was the most common drug prescribed by students (73.3%) followed by ofloxacin with ornidazole (54.4%), ibuprofen with paracetamol (53.3%), and sulfamethoxazole with trimethoprim (6%). Most of them were unaware of the rationality in using fixed dose combination drugs. Common sources of information were medical representatives 43 (47.8%), internet 39 (43.3%), and 12 (13.3%) reported using WHO EML. Conclusion: There is an urgent need to improve knowledge on the rationality for using fixed dose combination, EML, and banned fixed dose combination in India to the promote rational use of fixed dose combination.

Nils von Hentig HIV Center, Medical Department II, Hospital of the JW Goethe-University, Frankfurt, BAG Darab-Kaboly/von Hentig, General Medicine and HIV Care, Frankfurt am Main, Germany Abstract: The pharmacoenhancement of plasma concentrations of protease inhibitors by coadministration of so-called boosters has been an integral part of antiretroviral therapy for human immunodeficiency virus (HIV) for 1.5 decades. Nearly all HIV protease inhibitors are combined with low-dose ritonavir or cobicistat, which are able to effectively inhibit the cytochrome-mediated metabolism of HIV protease inhibitors in the liver and thus enhance the plasma concentration and prolong the dosing interval of the antiretrovirally active combination partners. Therapies created in this way are clinically effective regimens, being convenient for patients and showing a high genetic barrier to viral resistance. In addition to ritonavir, which has been in use since 1996, cobicistat, a new pharmacoenhancer, has been approved and is widely used now. The outstanding property of cobicistat is its cytochrome P450 3A-selective inhibition of hepatic metabolism of antiretroviral drugs, in contrast with ritonavir, which not only inhibits but also induces a number of cytochrome P450 enzymes, UDP-glucuronosyltransferase, P-glycoprotein, and other cellular transporters. This article reviews the current literature, and compares the pharmacokinetics, pharmacodynamics, and safety of both pharmacoenhancers and discusses the clinical utility of cobicistat in up-to-date and future HIV therapy. Keywords: human immunodeficiency virus, fixed-dose combinations, pharmacoenhancers, drug safety

Introduction: Fixed Dose Combinations (FDCs) are being increasingly used to improve compliance and achieve greater benefits of the two or more active ingredients given together than the corresponding individual drug components given separately. Aim: To analyse the rationality of Cardiovascular (CV) and Central Nervous System (CNS) FDCs available in Indian market. Materials and Methods: CVS and CNS FDCs, enlisted in Indian Drug Review, 2014, were analysed by a pretested validated eight point criteria tool. Each FDC was assessed for number of active pharmacological ingredients, approval by regulatory authority, listing in WHO Essential Medicine List. While efficacy, safety, pharmacokinetic, pharmacodynamic interactions and advantages of each FDC were analysed by literature search. The total score of the tool was 12 and score ≥7 was considered rational. FDCs were divided in four groups as per rationality and DCGI approval. ANOVA was used for statistical analysis and p

Insufficient control of blood pressure levels of the essential hypertension in Russia (less than 30% for women, less than 20% for men) was proven by epidemiology trials. This article is a review of the present opportunities to increase efficacy of treating hypertension by application of combined anti-hypertensive therapy and the advantages of fixed dose combinations (FDC). The authors scientifically prove the importance of using the combination, including angiotensin I-converting enzyme perindopril arginine and the long-half time dihydropyridine calcium channel blocker amlodipine in various clinical cases. Also the article summarizes the research of real clinical practice proving the high efficiency and safety of perindopril arginine /amlodipine FDC.

Objective: The aim of this study was to evaluate the pattern of fixed dose combinations (FDCs) in Ahmedabad, a city in western part of India. Materials and Methods: Over a period of 24 months, prescriptions were collected from 24 pharmacy stores across 6 zones of Ahmedabad city. The information was recorded in pre-formed Data Record Form after written consent from the patients (or relative (s) of the patients). The pattern of use of FDC, rationality and seasonal variation in their use were analyzed. At the end of study, results were analyzed using Chi-square test. Results: Out of the total 1170 prescriptions, 941 (80.3%) contained 1647 FDC formulations. The average number of FDCs prescribed was 1.41 ± 1.04 (mean ± SD). The FDCs were more frequently prescribed in the age group of 31 to 40 years (23.7%) and in males (54.4%). FDCs were most commonly prescribed by oral route (92.7%). As per drug category analysis, a higher number of FDCs containing nutritional supplements (20.2%), and those for CNS (18.1%) complaints were prescribed. A seasonal analysis showed that FDCs were commonly prescribed for respiratory complaints (23.4%), central nervous system (CNS) complaints (20.3%) and as nutritional supplements (22.4%) in winter, monsoon and summer months, respectively. Only 5.8%, 9.8% and 10.9% FDCs prescribed were included in WHO (2010), National (2011) and Gujarat State (2011) Essential Medicines Lists (EML), respectively (P < 0.0001). Irrational FDCs that are banned or FDCs containing irrational active ingredients were 1343 (81.5%) and 203 (12.3%), respectively. Conclusion: FDCs are widely prescribed with seasonal influence in their use. FDCs containing banned or controversial ingredients are prescribed widely.

For centuries tuberculosis remained as a complex socioeconomic problem impeding human development. Directly observed treatment short-course and fixed dose combinations were implemented in tuberculosis therapy for maximum success of treatment. However, drug shortages primarily hindered the expansion of directly observed treatment short-course, which lead to development of the global tuberculosis drug facility. Since large geographical area is covered by the global tuberculosis drug facility for global drug supply for tuberculosis eradication programs, a rapid quality control and assurance has become necessary to ensure the quality and performance of supplied antituberculosis drugs. In this manuscript a decision tree is proposed for facilitating rapid quality control (in vitro and in vivo) of antituberculosis formulations procured by the global tuberculosis drug facility. This decision tree also predicted to be applicable at every stages of anti tuberculosis drug product development, especially in identification of poor quality products and monitoring batch-to-batch variability. Further, it provides opportunity for effective quality control in resource poor settings and the gained knowledge is anticipated to be applicable for development and evaluation of antimalarial and antiAIDS fixed dose combinations.