Fixed Drug Combinations Research Articles

Magnitude, characteristics and consequences of topical steroid misuse in rural North India: an observational study among dermatology outpatients

IntroductionCurrent evidence indicates an alarming increase in topical steroid (TS) misuse in India. Data regarding the magnitude and characteristics of this problem in rural India, where 68% of the population...

Asian management of hypertension: Current status, home blood pressure, and specific concerns in Thailand.

The prevalence of hypertension is increasing, but rates of awareness, treatment, and blood pressure (BP) control are also increasing. In terms of cardiovascular disease, the prevalence of coronary artery disease (CAD) and stroke is similar, but stroke mortality is higher than that from CAD. Home BP monitoring (HBPM) is an important tool for determining the presence of white-coat or masked hypertension, facilitating drug cost savings or effective cardiovascular risk management strategies, respectively. However, there are a number of barriers to use of HBPM in Thailand. These include lack of availability (particularly in lower socioeconomic groups), lack of awareness of the importance of white-coat and masked hypertension, and concerns about device reliability. The latest Thai Hypertension Society guidelines recommend that physicians and nurses encourage their patients to use their HBPM devices, and these are increasingly being utilized in clinical practice for both diagnostic purposes and therapeutic monitoring. Calcium channel blockers are the most commonly used antihypertensive agents in Thailand, followed by angiotensin receptor blockers, ß-blockers, and diuretics. Angiotensin-converting enzyme inhibitors are used less often due to drug-related cough, and the use of fixed drug combinations is low because of their high cost and more complex reimbursement process. Ongoing work is needed to improve the primary prevention and effective treatment of hypertension in Thailand.

Efficacy of brinzolamide 1% / brimonidine 0.2% fixed combination versus brimonidine 0.2% / timolol 0.5% fixed combination in patients with primary open-angle glaucoma: A comparative study

Purpose: The aim of the study was to compare the intraocular pressure (IOP)-lowering efficacy of brinzolamide 1%/brimonidine tartrate 0.2% fixed combination versus brimonidine tartrate 0.2%/timolol maleate 0.5% fixed combination.Materials and Methods: A prospective, randomized, comparative, interventional study was conducted on forty patients of primary open-angle glaucoma attending the outpatient department of the department of ophthalmology at a tertiary institution in North India. Patients fulfilling the inclusion criteria and having none of the exclusion criteria were enrolled in the study after obtaining written informed consent. Patients were then randomized into two groups (Groups 1 and 2) with twenty patients in each group. Group 1 patients were given a brinzolamide 1%/brimonidine tartrate 0.2% fixed drug combination (BBFC) one drop twice daily and Group 2 patients were given a brimonidine tartrate 0.2%/timolol maleate 0.5 % fixed drug combination (BTFC) one drop twice daily for 6 weeks, and IOP was recorded at baseline and after 6 weeks at 9 am and 11 am.Results: The mean age was 61.05 years in Group 1 and 60.20 years in Group 2; there were 11 males in Group 1 and 14 males in Group 2, and the rest were female. Baseline mean IOP values were similar among treatment groups at all time points. At 6 weeks, the mean IOP of Group 1 was 18.32 mmHg and Group 2 was 18.45 mmHg with a reduction of 7.58 mmHg (29.26%) and 8.15 mmHg (31.83%) in Group 1 and Group 2, respectively. The difference in the IOP lowering at the end of the study between the two groups was not statistically significant (P > 0.05). Conclusion: Our study shows that BBFC seems to be an effective, safe, noninferior, and β-blocker-free fixed combination.

Comparison of Two Combinations of Maximum Medical Therapy for Lowering Intraocular Pressure in Primary Open-angle Glaucoma.

PurposeWe sought to compare the efficacy as well as the safety of two maximum medical therapy combinations applied to lower the intraocular pressure (IOP) in different primary open-angle glaucoma (POAG) age groups.MethodsThis was a retrospective, consecutive case series study that included 60 eyes of 60 subjects with POAG, specifically 20 subjects aged 40 to 54 years, 21 aged 55 to 69 years, and 19 aged 70 years or older. All had been treated for at least 12 months with triple maximum medical therapy (TMT; dorzolamide/timolol, brimonidine, and latanoprost) to lower their IOP, which subsequently was changed to double maximum medical therapy (DMT, fixed drug combinations of tafluprost/timolol and brinzolamide/brimonidine). The rate of IOP change and adverse drug reactions were compared amongst the three age groups.ResultsThe mean IOP change at three months after converting from TMT to DMT was −0.65 ± 1.42 mmHg (−3.84% ± 9.31%) among the overall study group, but this finding was not statistically significant (p = 0.108). In the 40 to 54 years and 55 to 69 years groups, the mean IOP change rates were +0.29 ± 0.96 mmHg (+2.40% ± 6.85%, p = 0.087) and −0.50 ± 0.99 mmHg (−3.05% ± 6.40%, p = 0.084) respectively. In the 70 years or older group, the mean IOP change, interestingly, was −1.80 ± 1.46 mmHg (−11.29% ± 9.31%, p < 0.001) and nine (47.4%) of the 19 subjects showed additional IOP reductions of 10% or more after converting from TMT to DMT. In all three age groups, the incidence rate of dry eye was significantly lower for DMT than for TMT (p = 0.031).ConclusionsIn POAG patients, DMT was proven to be both effective and safe for lowering the IOP, especially in those 70 years or older group, when compared with the TMT protocol.

Оптимизация амбулаторной лекарственной помощи пациентам с артериальной гипертензией в условиях здравоохранения Республики Казахстан на основе фармакоэкономического анализа

Abstract In the Republic of Kazakhstan, as in the whole world, cardiovascular diseases make the first place in terms of the “contribution” to the morbidity and mortality of the population. Arterial hypertension is the leading modifiable cause of cardiovascular and overall mortality in the world. Purpose of the study: To assess the pharmacoeconomic feasibility of using fixed combinations in the treatment of patients with arterial hypertension in the Republic of Kazakhstan. Methods. Review of domestic and foreign literature on the state of the management of patients with arterial hypertension, ABC / VEN- and frequency analyzes of the consumption of antihypertensive drugs, questioning patients for adherence to therapy and identifying their opinions about convenient therapy regimens, pharmacoeconomic analysis of the use of amlodipine in combination with lisinopril and their fixed combination. Results. In the updated version of the 2018 European Society of Cardiology guidelines, fixed combinations of two drugs in the form of one tablet strengthened their position as first-line therapy. Preferred dual combinations are those of the renin-angiotensin-aldosterone system blockers with calcium channel blockers or diuretics. Analysis of financing and coverage of the population with drugs at the outpatient level within the guaranteed volume of free medical care showed that arterial hypertension is the most costly nosology, while a tendency to inadequate provision of patients with antihypertensive drugs was revealed. The highest costs were associated with fixed combinations, despite the fact that they ranked only 5th in frequency of prescriptions, the most popular was the combination of an angiotensin-converting enzyme inhibitor with a calcium channel blocker (amlodipine / lisinopril). The results of the pharmacoeconomic analysis showed the feasibility of using a fixed combination of amlodipine / lisinopril, which makes it possible to assume the same trend in relation to other fixed combinations. Conclusions. The results obtained indicate the need to provide access for patients with arterial hypertension to fixed combination drugs. At the same time, the inclusion of these drugs in state drug supply programs may be accompanied by an increase in the burden on the health care system budget due to their high cost. The results of pharmacoeconomic studies should be the basis for making managerial decisions in the field of drug circulation. Key words: arterial hypertension, combined antihypertensive therapy, fixed combinations, pharmacoeconomic analysis

Pattern of use of anti-hypertensive drugs amongst hypertensive patients in a tertiary care hospital: a cross sectional, observational study

Background: Hypertension is one of the primary modifiable risk factors for cardiac and renal diseases and is the single most important risk factor for stroke. Despite different guidelines for management of hypertension like Joint National Committee, British Hypertension Society, National Institute for Health and Care Excellence; there are still the clouds of controversy. The objective of the study was to evaluate the prescribing pattern of antihypertensive drugs among the patients attending medicine outpatient department of a tertiary care teaching hospitalMethods: A cross-sectional, observational study was conducted in our hospital over a period of six months. Relevant information was collected from medical records of 209 hypertensive patients fulfilling inclusion criteria. The collected data were sorted and analyzed.Results: Out of 209 patients, maximum were of age group of 45-65 years (55.02%). 115 (55.02%) were male and 94 (44.97%) were female. Diabetes mellitus (24.4%) was the most common associated disease with hypertension. Most of the patients had received single antihypertensive drugs (49.28%). Among the monotherapy category calcium channel blocker (82.78%) was the most commonly prescribed antihypertensive drug class followed by angiotensin receptor blocker (36.36%). Amlodipine (81.82%) was the most common among calcium channel blockers. The most frequent fixed drug combination prescribed consisted of amlodipine and atenolol. Most of the drugs were prescribed in generic name (90.9%).Conclusions: The treatment pattern, in general, conformed to standard treatment guidelines.

Clinical-hemodynamic efficiency of fixed combined hypotensin therapy for patients with heavy arterial hypertension

The efficacy of treatment was evaluated by the fixed combination drug «Exforge-H» in 40 patients suffering from grade 3 arterial hypertension. All patients underwent general clinical and laboratory and instrumental examination (electrocardiography, echocardiography, 24-hour blood pressure monitoring) before and after 6 months of treatment. It was established that treatment with «Exforge-H» statistically reliably reduces the level of blood pressure, normalizes the variability and daily blood pressure profile. So, two weeks after the start of treatment, the systolic and diastolic pressure levels during clinical measurement decreased by 32,1±2,7 and 30,4±1,9 mm Hg. Art. respectively. After 3 months of treatment, 60% of patients showed achievement of the target level of blood pressure, and after 6 months - 96%. High hypotensive efficacy of treatment was also demonstrated during the daily monitoring of blood pressure in all its indicators. A significant decrease in systolic and diastolic pressure was observed during the day and night hours. The amplitudes of systolic and diastolic pressure variability have also been improved. At the same time, the variability of systolic pressure during the day was reduced by 46%, diastolic - by 49%, and at night by 59,3 and 52,8%, respectively, indicating a normalization of blood pressure during the day. All this was also accompanied by a decrease in the clinical manifestations of the disease. So, after 6 months of treatment, 84% of patients had positive clinical dynamics: a decrease in cardiac and cerebral symptoms, as well as emotional lability, which positively correlated with a decrease in the level of clinical blood pressure. The cardioprotective effect of the drug is expressed in the form of regression of left ventricular hypertrophy. In general, the use of the three-component fixed drug «Exforge-H» (valsartan - 80 mg, amlodipine - 5 mg and hydrochlorothiazide - 12,5 mg) is manifested by an increased antihypertensive effect due to the influence of its constituents side effects and the development of metabolic changes.

Asian management of hypertension: Current status, home blood pressure, and specific concerns in Taiwan.

Approximately 25% of the population in Taiwan has hypertension, and the rate has increased over time. Although age-standardized cardiovascular mortality has decreased over the last 25years, the annual stroke incidence has increased, and national health insurance reimbursement for cardiovascular disease (CVD) has grown by 22% over the last 10years. Automatic oscillometric sphygmomanometer devices are increasingly available and affordable in Taiwan, making this the main method of out-of-office blood pressure (BP) measurement. Furthermore, home blood pressure monitoring (HBPM), along with shared informed decision making, could be beneficial in driving changes in health behavior and hypertension management. The 2015 Guidelines of the Taiwan Society of Cardiology and the TaiwanHypertension Society for the Management of Hypertension recognize that home BP is a stronger predictor of CVD than office BP. Therefore, HBPM is recommended and implementation instructions provided. However, a home BP target that corresponds to the office BP used in the majority of clinical studies has yet to be clearly defined. Care for hypertension in Taiwan takes place more often in the hospital versus primary care setting. Combination therapy, often fixed drug combinations, is needed in 60% of patients to achieve BP control. Calcium channel blockers are the most commonly prescribed agents, followed by angiotensin receptor blockers. Overall, there is still substantial room for improvement in the awareness, treatment, and control rateof hypertension in Taiwan. HBPM has a central diagnostic and prognostic role in the management of hypertension.

Banned Fixed Drug Combinations of NSAIDS:An Update for Dentists in India

Being the most common medical professionals in prescribing of Non-steroidal anti- inflammatory medications, Dentist in India are to be essentially aware of banned medications, that due to various reasons, still haven’t been withdrawn from market. Many fixed drug combinations are easily available without any scientific justification behind them. This article aims in creating an awareness among the dentist regarding banned fixed drug combinations of NSAIDS in India since September 2018.

Automatic Dissolution Testing with High-Temporal Resolution for Both Immediate-Release and Fixed-Combination Drug Tablets

Dissolution testing plays many important roles throughout the pharmaceutical industry, from the research and development of drug products to the control and evaluation of drug quality. However, it is a challenging task to perform both high-efficient separation and high-temporal detection to achieve accurate dissolution profile of each active ingredient dissolved from a drug tablet. In our study, we report a novel non-manual-operation method for performing the automatic dissolution testing of drug tablets, by combining a program-controlled sequential analysis and high-speed capillary electrophoresis for efficient separation of active ingredients. The feasibility of the method for dissolution testing of real drug tablets as well as the performance of the proposed system has been demonstrated. The accuracy of drug dissolution testing is ensured by the excellent repeatability of the sequential analysis, as well as the similarity of the evaluation of dissolution testing. Our study show that the proposed method is capable to achieve simultaneous dissolution testing of multiple ingredients, and the matrix interferences can be avoided. Therefore it is of potential valuable applications in various fields of pharmaceutical research and drug regulation.

Sofosbuvir–Velpatasvir Fixed Drug Combination for the Treatment of Chronic Hepatitis C Infection in Patients With End-Stage Renal Disease and Kidney Transplantation

India is witnessing high hepatitis C virus (HCV) infection burden in patients of chronic kidney disease. Due to unavailability of costlyKidney Disease Improving Global Outcomes-recommended directly acting antiviral drugs, a widely available pan-genotypic combination of Sofosbuvir and Velpatasvir can become an economical option. Data regarding treatment experience of sofosbuvir-velpatasvir combination in chronic kidney disease is scarce. No data from India have been published in patients on renal replacement therapies till now. This retrospective analysis included all patients of end-stage renal disease on maintenance hemodialysis with treatment-naïve chronic HCV infection treated with sofosbuvir (400mg) and velpatasvir (100mg) fixed-dose combination. Pretreatment routine investigations were performed, which includedHCV viral load, genotype, fibro scan, endoscopy for esophageal varices, and portal vein Doppler. The patients were followed up with HCV viral load to declare sustained virologic response. patients were included with a mean age of 39.8±10.8 years, and 77.4% were male. Genotype 1 was found to be most prevalent (67.7%), with a median viral load of 106copies/ml. Six (19.3%) patients had hepatitis B virus co-infection. Three (9.7%) patients had cirrhosis. Sustained virologic response (SVR12) was achieved in 30 (96.8%) patients, and one (3.2%) patient had relapse. Furthermore, 14 (45.2%) patients underwent renal transplantation, and none of them had relapsed. Dyspepsia (9.7%) was the most common side effect observed with no major adverse effect. Our study showed excellent efficacy with the safety profile of this drug combination in end-stage renal disease patients. However, larger prospective studies and multicenter randomized controlled trials are needed for further confirmation.

Adverse drug reactions due to fixed dose combinations: an observational cross sectional study

Background: In modern world, poor compliance has been the main reason of therapeutic failure. Many factors may be responsible for this. The reasons highlighted may be adverse drug reactions (ADRs), pill burden or economic reasons. Fixed drug combinations (FDC) have helped to solve this problem. The present study was conducted to see the ADR due to fixed dose combinations.Methods: After approval from institutional ethics committee, an observational study was conducted over a period of six months in December 2018 to May 2019 in adverse drug monitoring centre, GMC Jammu.Results: A total number of 112 ADRs were reported during the study period. FDCs were responsible for ADRs in 64 patients and single drug was responsible in 48 patients. As per latest WHO essential drug list, irrational FDC were responsible for ADRs in 44 patients and rational FDCs were responsible for ADRs in 20 patients.Conclusions: The results of present study underscores that drug combinations, FDC rational as well as irrational substantially contribute towards the pool of total ADRs.

Supersaturating drug delivery system of fixed drug combination: sulfamethoxazole and trimethoprim

ABSTRACTBackground: The drug supersaturation in the intestinal lumen for few hours could result in high bioavailability. The goal of this study was the development of a supersaturating drug delivery system containing sulfamethoxazole and trimethoprim at fixed dose combination (sulfamethoxazole:trimethoprim 5:1 w/w).Methods: The amorphous solid dispersions were formed at three different proportions containing 30, 50 and 70% of Eudragit EPO in the formulation.Results: The supersaturation state is formed by the amorphous drugs produced by spray drying technique, and the maintenance of this state is due to the chemical interactions between the drugs and the polymer selected, which was observed in the fluorescence interaction studies realized between the drugs and the polymer. The Formulation containing 70% of the polymer was able to produce and maintain the supersaturated state of both drugs for 24 h. Solid state characterization demonstrated the amorphization of the drugs in the solid dispersion and indicated the hydrogen bond formation responsible for the improvement in the apparent solubility. This formulation presented an improved antibacterial activity when compared to the combination of the drugs.Conclusion: For the first time, a supersaturating drug delivery system was developed to the complementary antibacterial drugs. This ternary formulation is a powerful alternative to improve oral absorption of recognized safety drugs, reducing the dose and consequently the antibiotic resistance emergence.

A study on drug utilization pattern of antihypertensive drugs in hypertensive diabetic patients

Background: Hypertension management is of paramount importance in diabetic patients for reduction of cardiovascular and other complications. The objective of the present study was to assess prescribing pattern of antihypertensive drugs in hypertensive type 2 diabetic patients and evaluate them by comparing with Eighth Joint National Committee (JNC-8) hypertension treatment guidelines.Methods: A prospective observational study was carried out on 110 hypertensive type 2 diabetic patients of age 41-80 years visiting outpatient department of Medicine at G.S. Medical College and Hospital, UP, India for 4 months. JNC-8 hypertension management guideline was considered while evaluating the prescribed drugs. All the relevant data was collected from the prescription card of the patient on a preformed performa and analyzed using descriptive statistics.Results: Total of 176 drugs was prescribed to the study patients among which two drug combination therapy (55.45%) was mostly used. The most common group prescribed was angiotensin receptor blocker (ARB) (29.45%) and ARB+CCB (calcium channel blockers) (34.92%) were the commonest fixed drug combination. Overall, it was amlodipine (21.47%) that was most frequently prescribed among all antihypertensive drugs.Conclusions: ARB was the most commonest class, ARB+CCB was the most frequent fixed drug combination prescribed to the study patient while amlodipine was the highly utilized individual antihypertensive drug in the study. Prescriptions evaluation revealed that 94.88% prescription were rational and were in accordance with the JNC-8 hypertension treatment guidelines except the use of beta blockers (5.12%).

A step in the global effort to control hypertension: Fixed dose combination antihypertensive drugs

Several fixed dose combinations (FDCs) of antihypertensive drugs have recently been added to the World Health Organization model list of essential medications. FDCs have advantages in the management of hypertension compared to single drug tablets including improved adherence, greater blood pressure lowering and are associated with reduced cardiovascular complications. FDCs can also reduce ethnic, and age-related variation in blood pressure lowering and have similar or reduced adverse effects relative to single-drug therapy. Best hypertension control practices from the World Health Organization HEARTS program advocates the use of FDC in simple directive treatment protocols. FDC in simple directive protocols was viewed as a key success factor in the control of chronic infections (eg, tuberculosis, HIV). Unfortunately, implementing simple directive protocols with FDC has had substantial opposition from hypertension experts. Hypertension organizations and experts need to familiarize themselves with best practices in hypertension control, their supporting evidence and to become advocates.

A Study of Prescribing Pattern in Patients of Hypertension

Introduction: Hypertension is a multi-factorial and complex disease that has both environmental and genetic determinants. It is the single most significant risk factor for heart diseases and kidney diseases. Hypertension is a leading contributor to global burden of morbidity and mortality. It is considered as a silent killer because most of the time it is asymptomatic and goes undetected. Hence, hypertensive patients should be prescribed properly. Objectives: To evaluate the prescribing pattern of anti-hypertensive drugs in patients of hypertension. Material and Methods: This was an observational, cross sectional study conducted over a period of 1 year on hypertensive patients attending the Cardiology out-patient department of Government Medical College and Rajindra Hospital, Patiala and fulfilling the inclusion and exclusion criteria. The prescriptions were evaluated. Results: 22% of prescriptions had monotherapy, amongst which beta-blockers were most commonly prescribed. Majority of prescriptions had two drug therapy (47%), among which ARB+ beta blockers (17%) were most frequently prescribed. Beta blockers +CCB (9%) was the most common Fixed Drug Combination (FDC) prescribed. ARB+beta blockers+diuretics (14%) and ACEI+ARB+beta blockers+diuretics (1%) were most commonly prescribed three drug combinations. Among four drug combinations, only ACEI+ARB+beta blockers+diuretics was prescribed to 1% patients. Hypolipidemic drugs (66%) were maximally co-prescribed. Conclusions: A high trend of polypharmacy was observed in hypertensive patients. So, emphasis is needed to reevaluate the prescribing trends in these patients.

Bioequivalence and Food Effect of Dapagliflozin/Saxagliptin/Metformin Extended-release Fixed-combination Drug Products Compared With Coadministration of the Individual Components in Healthy Subjects

PurposeFixed-combination drug products (FCDPs) for patients with type 2 diabetes mellitus (T2DM) may show efficacy comparable to their individual components (ICs) while improving adherence to treatment. This study evaluated the bioequivalence and safety of 2 dapagliflozin/saxagliptin/metformin extended-release (XR) FCDPs relative to their ICs: saxagliptin and dapagliflozin/metformin XR. MethodsThis randomized, open-label, single-dose, single-center crossover study was conducted in 84 healthy subjects aged 18–55 years. The primary objective was to evaluate the fed-state bioequivalence of a dapagliflozin 5-mg/saxagliptin 2.5-mg/metformin 1000-mg XR FCDP and a dapagliflozin 10-mg/saxagliptin 5-mg/metformin 1000-mg XR FCDP relative to the ICs. Secondary objectives included the evaluation of the effect of food on the pharmacokinetic (PK) parameters of saxagliptin, dapagliflozin, and metformin in both FCDPs and characterization of the PK parameters of the active metabolite of saxagliptin, 5-hydroxy saxagliptin, in healthy subjects. PK parameters (AUC0–∞, AUC0–t, and Cmax) were used to assess the bioequivalence of the 2 FCDPs with their ICs. The Cmax and AUC0–t of the study drugs were compared between female and male subjects to assess sex differences in exposure. Safety and tolerability of both FCDPs and ICs were also assessed with adverse events, vital signs (systolic and diastolic blood pressures and pulse rate), 12-lead ECG, physical examinations, and laboratory assessments. FindingsBoth dapagliflozin/saxagliptin/metformin XR FCDPs were bioequivalent to their ICs. For the dapagliflozin 5-mg/saxagliptin 2.5-mg/metformin 1000-mg XR FCDP, the 90% CI for the geometric mean ratio of dapagliflozin Cmax was slightly above the 80%–125% bioequivalence limit, which is unlikely to be clinically relevant. Food delayed the absorption of the study drugs in both FCDPs, which is unlikely to have a clinically relevant impact on efficacy. In both cohorts, exposure was higher in female subjects compared with male subjects, potentially due to the lower body weight of the female subjects. The safety profile and tolerability of the FCDPs were similar to those of their ICs, and no deaths or serious adverse events were reported. ImplicationsThese data support the use of the dapagliflozin/saxagliptin/metformin XR FCDP in patients with T2DM. ClinicalTrials.gov identifier: NCT03169959.

Pediatric TB Management under RNTCP: What and Why?

Childhood tuberculosis does not get the attention it deserves, both in the general child health services and the TB specific services. The difficulty in identification of the organism due to lack of proper sample as well as lower sensitivity of the smear, made it harder to detect cases with ease in the community. Newer diagnostic methods like cartridge based nucleic acid amplification tests (CBNAAT) and line probe assays (LPA) have the capacity to rapidly identify Mycobacterium tuberculosis with an improved sensitivity over the smear testing and have been employed under Revised National Tuberculosis Control Programme (RNTCP) across the country. As the symptoms suggestive of TB are very common and overlapping, the final yield of TB testing is better if the microbiological confirmation is done on good quality specimen from cases suspected of TB based on clinical and radiological abnormalities. Newer tests also provide simultaneous detection of much critical Rifampicin resistance. A Rifampicin resistantcase is not only unlikely to respond to first-line standard therapy but such a treatment can result in further amplification of resistance to other companion drugs. Prevention of spread of the drug resistant disease thus requires that the treatment is guided byuniversal drug sensitivity testing (U-DST) of all TB cases. Furthermore, several changes have come up in the treatment of TB and are discussed.The dosages of anti TB drugs have been revised upwardly for optimal drug levels and now the fixed drug combinations are used under RNTCP. With the awareness about high initial Isoniazid (INH) resistance and its contribution to failure of retreatment regime, a companion third drug (Ethambutol) has been added to the continuation phase of the first-line therapy. The standard retreatment regime, better known as category II therapy, has been replaced by specific therapy as per the resistance pattern detected. The TB control activities have thus evolved a lot and the present article discusses the evolution and the current status of diagnostics and therapy of TB in children.

Comparison of different combinations of maximum medical therapy for lowering intraocular pressure in primary open angle glaucoma: 12-month retrospective consecutive case series.

To compare the efficacy and safety of two combinations of maximum medical therapy for lowering intraocular pressure (IOP) in primary open angle glaucoma (POAG). A retrospective consecutive case series. A retrospective consecutive case series study including 82 eyes of 82 subjects with POAG treated with maximum medical therapy to lower IOP. Enrolled patients were divided into 2 groups: the triple maximum medical therapy (TMT) group, comprising POAG patients who were treated with tafluprost, brimonidine and the fixed drug combination (FDC) brinzolamide/timolol; and the double maximum medical therapy (DMT) group, comprising POAG patients who were treated with the FDCs tafluprost/timolol and brinzolamide/brimonidine. We compared the demographics, baseline IOP, IOP reduction rate, and adverse drug reactions (ADRs) between the 2 groups. While the mean IOP reduction rate after 12 months was higher in the TMT group (52.7%) than in the DMT group (50.4%), the difference was not significant (p-value = 0.615). In the TMT group, the rate of proceeding to laser or surgical therapy was 22.2% (DMT group = 37.8%). In the TMT group, the time duration between beginning maximum medical therapy and proceeding to laser or surgical therapy was 10.7 ± 1.3 months (DMT group = 10.3 ± 1.5 months). No serious ADRs were reported in either group. However, the incidence rate of conjunctival hyperemia and dry eye was significantly lower in the DMT group than in the TMT group. DMT is safe and effective for lowering IOP in POAG patients. DMT is not inferior to TMT in POAG patients.

Approaches to Clinical Development of Combination Medicines in the Russian Federation and the Eurasian Economic Union in view of the Requirements of the Current Legislation

In recent years, there has been an increasing interest in the development of combination medicines (fixed drug combinations) containing two or more active ingredients in a single dosage form. Therefore, there is an urgent need to develop an optimal programme of pre-authorisation clinical trials for combination medicines. The aim of the paper was to summarise modern science-based approaches to clinical development of combination medicines and identify possible ways of their practical implementation, taking into account the requirements of the current legislation. The author reviewed scientific publications devoted to creation of fixed drug combinations and analysed the regulatory documents defining regulatory requirements for pre-authorisation clinical studies of medicines in the Eurasian Economic Union, the Russian Federation, and other countries. Based on the results of the analysis the author described the general regulatory requirements for planning clinical studies of combination medicines for the purpose of their subsequent authorisation in the Russian Federation (via the national procedure) and the Eurasian Economic Union (via the centralized procedure). The pre-authorisation clinical development programme should be designed individually for each combination medicine. The selection of an optimal clinical trial strategy will make it possible to obtain sufficient information on the efficacy and safety of a combination medicine for its subsequent authorisation.