An evaluation of fixed dose combinations and it’s practices at medicine department of tertiary care hospital, Nepal

Background:A large proportion of fixed dose combinations (FDCs) are manufactured and used widely in Nepal. This study aimed to evaluate the FDCs and its utilization in medicine department of tertiary care hospital. Methods:A cross-sectional study was conducted for 50 days among admitted patients in the medicine department of tertiary care hospital, Nepal. A predesigned form was used to collect the data at the time of patient discharge. Only the oral FDCs were selected for study.Microsoft Excel 2007 was used for statistical analysis and data were presented as number and percentage in tabulated and figure forms.Results:Oral FDCs were used in 27.08% of admitted patients. A total of 295 FDCs were prescribed in 208 patients with 44 FDC items in 58 different brand names. Categorically, the most commonly used FDCs were of analgesics (34.24%) followed by antibiotics (25.76%) and vitamin supplements (22.71%). The 27.27% of FDCs prescribed contain more than two active pharmaceutical ingredients (APIs) up to nine and the highest number of APIs were found in vitamin supplements. All FDCs were prescribed in the brand names. The very few 2.27% and 4.55% of FDCs were prescribed from the essential medicine list of Nepal and world health organization, respectively.Conclusions:The use of FDCs listed in essential medicine list was very poor. Similarly, generic prescribing was also zero. The regulatory body must study the rationality of FDC before production, marketing, importing, and utilization in hospital.

A comparison of treatment outcomes among HIV positive tuberculosis patients receiving DOTS and fixed dose combination in Visakhapatnam

Background: Tuberculosis is a communicable disease which requires special attention in HIV patients. According to newer guidelines, the treatment regimen for tuberculosis has been changed from intermittent DOTS to daily FDC. This study was taken up to explore effectiveness of fixed dose combination in comparison to intermittent DOTS. Objective was to compare the treatment outcomes for tuberculosis among HIV positive TB patients receiving intermittent DOTS with those receiving daily fixed dose combination (FDC).Methods: A retrospective cohort study was done during November 2017. The data was collected from patient records in an ART centre, attached to King George Hospital, Visakhapatnam. All the HIV patients newly registered for anti-tubercular treatment at the ART center, during 1st quarter of 2016(intermittent DOTS) were compared with those registered during 1st quarter of 2017(FDC). The treatment outcomes include (1) treatment success (completed/ cured), and (2) other treatment outcomes (lost to follow up (LFU), Death). Data was analysed using MS Excel. Association of factors affecting treatment outcomes was tested using chi-square test.Results: Out of a total 83 patients, 34 were on intermittent DOTS and 49 on FDC. The percentage of treatment success in intermittent DOTS was higher than FDC (p=0.06, chi-square value=3.42). The percentage of deaths in FDC is high when compared to intermittent DOTS (P=0.74, chi-square=3.1762). In subject receiving FDC, it was observed that more females had treatment success as compared to males (p=0.28, chi square=1.13).Conclusions: There is no statistically significant difference in the TB treatment outcomes of intermittent DOTS and FDC.

Prescribing pattern of fixed dose combinations of antibiotics in a post-operative surgical ward of tertiary care teaching hospital

Background: Fixed dose drug combinations (FDCs), are combinations of two or more active drugs. It should be used when the combination has an established advantage over single drug in efficacy, safety and compliance. The World Health Organization (WHO) lists only 19 of such combinations. But Indian market is filled with hundreds of FDCs which were not approved leading to irrational use. This study was focused on finding out the fixed dose combination of antimicrobial agents used in the post-operative general surgery ward of a tertiary care teaching hospital.Methods: After getting approval from institutional human ethics committee the prescriptions of patients admitted during April 2013 to March 2014 were analyzed. Demographic data, FDC prescribed by surgeons, Dose, Frequency, Duration, Route, Formulation, Brand or generic drugs, Adverse events due to use of FDC were collected and SPSS version 17 was used for statistical analysis. Fixed dose combinations were used in 90 Patients. The most commonly used FDC were ampicillin with Cloxacillin (43) followed by amoxicillin with clavulanic acid (22), cefoperazone with sulbactam (19) and piperacillin with tazobactam (6). A common drug used in combination along with FDC was metronidazole and aminoglycoside. The irrational combination seen in this study was ampicillin with Cloxacillin (8.88%) of the total FDC which is not approved by DCGI or FDA.Results: In this study out of 145 drugs used, 41drugs were administered three times a day, 90 drugs were given two times a day and 14 drugs were given once a day dosing. 53 patients received FDCs for prophylaxis and 37 patients for treatment purpose. All FDCs were prescribed in brand names. No adverse drug reaction was observed in this study.Conclusions: Consultants should undergo continuing medical education (CME) on newer drug combinations and their adverse drug reactions which will be evidence-based rather than to rely on representatives.

The comparisons of the efficacy of two fixed dose combinations, i.e. Salmeterol and Fluticasone vs. Formoterol and Tiotropium bromide in moderate to severe COPD patients

Background: Bronchodilators are essential for symptomatic management of all stages of chronic obstructive pulmonary disease (COPD). For patients whose COPD is not sufficiently controlled by monotherapy, combining a ß2-agonist with either inhaled steroid or anticholinergic drug is a convenient way of delivering treatment. Currently, there is no documentation to say that one drug is superior to other or the contrary, but a combination of two drugs is more effective than giving single drug alone in patients suffering from COPD.Methods: The study was prospective, open labelled, randomized, comparative interventional clinical study conducted by the Departments of Pharmacology and Medicine, Basaveshwara Medical College and Hospital, Chitradurga in 60 moderates to severe COPD patients.Results: Both the treatments i.e. Salmeterol/Fluticasone and Tiotropium/Formoterol were equally effective as far as the improvement of the lung functions and Borg dyspnoea score are concerned. The difference in improvement with the combination of Salmeterol/Fluticasone was not statistically significant (p>0.05) compared to the combination of Tiotropium/Formoterol. However, Salmeterol/Fluticasone was found to be better than Tiotropium/Formoterol in improving the lung function of moderate to severe COPD patients.Conclusions: Salmeterol/Fluticasone is efficacious and better than Tiotropium /Formoterol combination for maintenance therapy in moderate to severe COPD patients.

A Study Of Fixed Drug Eruption: Single Center Analysis From Central India

Background: Fixed drug eruption is a common cutaneous adverse drug reaction which is characterised by sharply demarcated skin lesions with recurrences at the same site with each subsequent exposure to the culprit drug. The causative drugs for fixed drug eruption (FDE) in any population changes depend on many factors. The knowledge of peculiar clinical features of FDE helps the treating physician to recognise at early stage and avoidance of mismanagement of such cases. Material and method:In this context, we did a descriptive-analytical study of patients who were diagnosed with FDE in single center between Feb 2013 to Sep 2017 from central India. Results: Ninety seven patients who developed FDE were studied in the study with 65% males and 35% females. Mean age at presentation in males and females were 34.95±16.90 and 37.12±12.98 years, respectively. Multiple lesions were present in 80.4% of patients. Seventy four percent of patients gave the history of prior episodes. In 68% patients, symptoms started and lesions developed within <24 hours of the drug exposure. Mucosal lesions were seen in 46.4% and skin lesions (non-mucosal) were seen in 36.1% and in rest 17.5% patients both mucosal and skin lesions were present. Antibiotics and NSAIDS were the most common group of medications to cause FDE. Thirty two percent of patients were caused by Fixed Dose Combinations of antibiotics and anti-protozoals. Conclusion: In conclusion, FDE is a common acute cutaneous drug eruption that if not diagnosed timely leads not only to recurrences but also causes apprehension and morbidity.

Pharmacokinetic Equivalence of the High Dose Strength Fixed-Dose Combination Tablet of Gemigliptin/Metformin Sustained Release (SR) and Individual Component Gemigliptin and Metformin XR Tablets in Healthy Subjects

BACKGROUND: In type 2 diabetes mellitus therapy, fixed-dose combination (FDC) can offer not only benefits in glucose control via the combined use of agents, but also increase patient compliance. The aim of this study was to assess the pharmacokinetic equivalence of the high dose of the FDC tablet (gemigliptin/metformin sustained release [SR] 50/1,000 mg) and a corresponding co-administered dose of individual tablets. METHODS: This study was randomized, open-label, single dose, two treatments, two-period, crossover study, which included 24 healthy subjects. Subjects received the FDC or individual tablets of gemigliptin (50 mg) and metformin XR (1,000 mg) in each period. Geometric mean ratios (GMRs) and 90% confidence intervals (CIs) of maximum plasma concentration (Cmax) and area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast) of the FDC tablet and co-administration of individual tablet for both gemigliptin and metformin were calculated. RESULTS: The GMRs (FDC tablets/co-administration; 90% CIs) for Cmax and AUClast of gemigliptin were 1.079 (0.986–1.180) and 1.047 (1.014–1.080), respectively. For metformin, the GMRs for Cmax, and AUClast were 1.038 (0.995–1.083) and 1.041 (0.997–1.088), respectively. The 90% CIs for GMRs of Cmax and AUClast for gemigliptin and metformin fell entirely within bounds of 0.800–1.250. Both administration of FDC tablet and co-administration of individual tablets were well tolerated. CONCLUSION: FDC tablet exhibited pharmacokinetic equivalence and comparable safety and tolerability to co-administration of corresponding doses of gemigliptin and metformin XR as individual tablets. Trial registry at ClinicalTrials.gov, NCT02056600.

Profile of Adverse Drug Reactions with Fixed Drug Combinations: How Big is the Problem.

The current study was undertaken to analyze the profile of adverse drug reaction (ADR) contributed by fixed drug combinations (FDC). A cross-sectional, retrospective study was conducted over a period of 2 years to evaluate the profile of ADR contributed by FDC using suspected ADR data collection form used under Pharmacovigiliance Programme of India (PvPI). A total number of 2242 ADRs were reported during the study period of two years out of which drug combinations responsible for ADRs were 589 (26.27%). Fixed drug combinations (FDC) contributing to ADRs were 88(3.9%). As per latest WHO essential drug list, irrational FDC were responsible for 83 (3.70%) accounting 94.3% of the total FDC. Whereas, only 5(0.2%) of rational FDC contributed to the total pool of ADRs. Most frequent drug combination contributing to ADR was of anticancer drugs leading to vomiting and alopecia, where as most common irrational FDC was aceclofenac plus thiocolchicoside and ofloxacin plus ornidazole leading insomnia & rash respectively. Levodopa plus carbidopa and trimethoprim plus sulphamethoxazole were two common rational FDC contributing to ADRs. The above results underscores that drug combinations and FDC as well as irrational FDC substantially contribute towards the pool of total ADRs.

Analytical quality-by-design approach for sample treatment of BSA-containing solutions / 药物分析学报

The sample preparation of samples containing bovine serum albumin (BSA), e.g., as used in transdermal Franz diffusion cell (FDC) solutions, was evaluated using an analytical quality-by-design (QbD) approach. Traditional precipitation of BSA by adding an equal volume of organic solvent, often successfully used with conventional HPLC-PDA, was found insufficiently robust when novel fused-core HPLC and/or UPLC-MS methods were used. In this study, three factors (acetonitrile (%), formic acid (%) and boiling time (min)) were included in the experimental design to determine an optimal and more suitable sample treatment of BSA-containing FDC solutions. Using a QbD and Derringer desirability (D) approach, combining BSA loss, dilution factor and variability, we constructed an optimal working space with the edge of failure defined as Do0.9. The design space is modelled and is confirmed to have an ACN range of 8373%and FA content of 170.25%.

Differential Diagnostic Value of Morphological Changes of Follicular Dendritic Cell Meshwork between Different Subtypes of Lymphoma / 现代检验医学杂志

Objective To explore the differentiated diagnostic value of the morphological changes of follicular dendritic cell (FDC)meshwork between different subtype of lymphoma.Methods CD21 was stained by immunohistochemistry (IHC) method,FDC meshwork pattern was studied in 5 6 cases of various lymphomas(including 8 cases of diffuse large B cell lym-phoma,2 cases of burkitts lymphoma,6 cases of small lymphocytic lymphoma,6 cases of plasmacytoma,3 cases of MALT lymphoma,6 cases of peripheral T cell lymphoma,3 cases of anaplastic large cell lymphoma,8 cases of NK/T cell lympho-ma,4 cases of follicular lymphoma,3 cases of mantle cell lymphoma,3 cases of AITL,2 cases of FDC sarcoma).Results FDC meshwork in the morphological changes of various subtypes of lymphoma could be classified into four patterns:①FDC form a disappeared and disintegrated meshwork,most of the lymphoma FDC meshwork fully or partially destroyed,including diffuse large B cell lymphoma,burkitt lymphoma,small lymphocytic lymphoma,plasmacytoma,peripheral T cell lymphoma, anaplastic large cell lymphoma,NK/T cell lymphoma;②FDC meshtwork existence,even hyperplasia,including follicular lymphoma,mantle cell lymphoma,MALT lymphoma;③FDC meshtwork proliferation,disorder and deformation,such as AI-TL;④Full expression subtype:such as FDC sarcoma.Conclusion The morphologic pattern of the FDC meshwork in lym-phomas of follicular origin was differs according to the lymphoma subtypes,and it has important clinical value in lymphoma differential diagnostic.

Studies on the Determining Factors at Each Stage of Germinal Center B Cell Differentiation / 대한면역학회지

To delineate the individual role of follicular dendritic cells (FDC) and T cells at each stage of GC B cell differentiation at the clonal level and to analyze the signals required for the differentiation, we developed an experimental model using an FDC line, HK and a lymphoma cell line, L3055 for centroblasts. Phenotypic analysis of L 3055 revealed its origin of GC and the homogeneity. L3055 cells undergo spontaneous apoptosis when cultured in the absence of HK cells. L3055 cells proliferate continuously in the presence of HK cells, while they differentiate into a population with the phenotype of centrocytes after stimulation with CD40 ligand (CD 40L) plus IL-2, IL-4 and IL-10. L3055 undergo anti-Ig-mediated apoptosis, which is not protected by HK but by CD40L and the cytokines. These experimental results suggest that FDC provide signals for the survival and rapid proliferation of centroblasts and T cells trigger the differentiation of centroblasts into centrocytes.

STEREOLOGIC ANALYSIS OF THE LYMPHO CYTES LOCATED AT INTRA-AND EXTRAFOLLICULAR DENDRITIC CELL DISTRIBUTION AREA / 解剖学报

HRP-anti-HRP complex was injected into BALB/c mice through the tail vein. 24 hours later, the spleens of mice were removed, fixed and cut into slices. After incubation in DAB/H_2O_2 the follicular dendritic cell (FDC) distribution area could be defined at a certain part of lymph nodule. Light microscopic and stereologic analysis study on the lymphocytes at intra- and extra- FDC distribution area were carried out. The results revealed that lymphocytes at intra- and extra- FDC distribution area were composed of various lymphocytes populations of different sizes. The cell populations at intra-FDC distribution area were mainly composed of large and medium sized lymphocytes, while the populations at extra-FDC distribution area were mainly medium sized and small lymphocytes. As a result, FDC always exists on the location where lymphoblastic phenomenon appears. This indicates that FDC has certain relation with the lymphoblastic phenomenon.

THE ULTRASTRUCTURAL OBSERVATIONS ON THE CHANGES OF FOLLICULAR DENDRITIC CELLS IN THE SPLEEN OF THE POSTNATAL RATS AT THE AGES OF 21 TO 48 DAYS / 解剖学报

In this experiment, the PAP was used as a specific marker to label the follicular dendritic cells (FDC) and their possible precursors in the spleens of postnatal rats at 21, 27, 34, 41 and 48 days respectively, and the changes of the labeled cells were studied under TEM. In 21-day-old rats the labeled cells were of the histological feature resembling fibroblastic reticulum cells(FRC). As the rats getting elder, the shape and structure of the labeled cells changed. The shape of t he cells and nuclei changed from ellipse to irregular. The heterochromatin decreased and so did the microfilaments in the cytoplasm. The cytoplasmic processes increased in number, length and complexity. The relatively smooth cell surface became folding and invaginating. By the 48 days after birth the labeled cells possessed the features of the FDC. The result implys that the FDC might originate from FRC.