Irrational ophthalmic fixed-dose combinations for dry eye syndrome

Dry eye syndrome (DES) is a common disorder with rising incidence due to increased use of digital devices. While multiple treatment options are available, some are not efficacious or sometimes even safe for use in DES. This is particularly true for Fixed Dose Combinations (FDCs) that may contain ingredients having no rational for their use or may actually be harmful. Various committees appointed by the Government have reviewed several FDCs marketed in India and found some of them to be irrational and recommended for their removal. This paper discusses the contents of some of these FDCs marketed for DES with an aim to ensure that prescribers are mindful of their ingredients and whether there is adequate data about their efficacy and safety and prescribe them only if they consider them necessary for managing the patient.

Evaluation of prescribing pattern and rationality of fixed dose combinations in patients of general medicine department

Background: Fixed dose combinations are widely used in India, they are either irrational or prescribed irrationally. Moreover, the government has recently banned over 300 fixed dose combinations (FDCs) because of a lack of therapeutic justification. This study was conducted to study the prescribing pattern of FDCs in a tertiary care teaching hospital and to highlight the rationality of FDCs, and adverse drug reactions (ADRs) associated with them.Methods: In the present prospective observational study, a total of 500 inpatients were evaluated for prescribing pattern, cost analysis, and adverse drug reactions (ADRs) of FDCs. The FDCs were assessed for their rationality. The ADRs and severity were assessed using the WHO causality scale, Hartwig severity scale respectively.Results: Out of total 103 FDCs, 58 were approved, 86 were rational and 17 were irrational. 5 FDCs were banned and irrational. 48.54% of rational FDCs had rationality score from 7 to 9. The most commonly prescribed FDCs belonged to the anatomic therapeutic and chemical class of respiratory system, followed by anti-infectives in younger age group and cardiovascular FDCs in the elderly. The 886 ADRs occurred in 500 patients with a mean of 1.81�9. Banned FDCs contributed to 76 ADRs. According to causality and severity assessment, most of the ADRs were possible (62.53%) and mild (70.77%) respectively.Conclusions: Although FDCs were rational in most cases but banned FDCs were also prescribed. As these FDCs were associated with ADRs, monitoring of patients is necessary. Knowledge and attitude of healthcare professionals can be assessed through awareness programs.

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.

Drug Utilization Study In Geriatric Patients Visiting The Outpatient Department In Tertiary Care Rural Hospital.

Aim & Objective:The study aimed to evaluate the disease pattern, drugs used & the prescribing patterns to the geriatric patients at rural hospital.Materials and Methods: Atotal of 300 patients were enrolled in the prospective, cross sectional study. The demographic details, drugs used condition for which the drugs were prescribed and other related factors; names by which they were prescribed, use of fixed dose combinations were recorded and subjected to analysis. Observation and Results: Enrolled patients belonged to the age between 65 to 74 years, who presented with cardiovascular (21.22%) followed by musculoskeletal conditions (17.44%). Medicines were mostly prescribed by brand names 72.11%, Ranitidine was most frequently prescribed followed by Aceclofenac. About 20.35% were prescribes as FDCs for ex; Aceclofenac + Paracetamol was most commonly prescribed FDC followed by Amoxicillin + Clavulanic Acid.Conclusion: Cautious use of medicines in geriatric patients is essential which can be provided by rational prescribing.

Comparative study about knowledge, attitude and practice study of fixed dose combination among junior residents and interns of a tertiary care hospital

Background: Fixed Dose Combinations (FDCs) are defined by the World Health Organization (WHO) as combination of two or more active ingredients in a fixed ratio of doses. According to the FDA, “two or more drugs may be combined in a single dose when each component makes a contribution to the claimed effects, and the dosage of each component (i.e., amount, frequency, and duration) is such that the combination is safe and effective for significant patient population requiring such concurrent therapy. However, certain disadvantages like incompatible pharmacokinetics, inflexible dose ratio, increased toxicity and cost, contraindication of one component of the FDC decreased their utility. Adverse effect of any one component also limits their use. The aim of the study is to compare and evaluate the knowledge, attitude and practices about prescribing fixed dose combinations among junior resident doctors (JRs) and interns (INTs) at SDM College of Medical Sciences and Hospital Dharwad.Methods: A cross-sectional study was carried out in 134 doctors using pre-validated 10 item questionnaire with details of participant’s information followed by questions regarding knowledge, attitude and prescribing practice of fixed dose combinations was used as a tool, administrated to all the resident doctors and the collected data was analysed.Results: Our study revealed that knowledge about FDCs was lacking in JRs and INTs. They were not able to point out the actual advantages and disadvantages of FDCs. Knowledge about rational/irrational, banned FDCs and availability of WHO EML was also lacking.Conclusions: There is need to improve knowledge about rationality, essential medicine list, usage and banned FDCs in undergraduate medical students to promote the rational use of drugs.

Rationality verses irrationality in fixed dose combinations: at a tertiary teaching hospital of rural Chhattisgarh, India

Background: Rational drug prescribing can be defined as appropriate drugs prescribed in the right dose, at correct time intervals and for a sufficient duration. Irrational drug use is a common problem in many countries of the world.Methods: A prospective observational study was conducted, total 300 patients attending various outpatient departments of tertiary health care rural hospital in Rajnandgaon district were interviewed and their prescriptions were analysed.Results: Total 350 drugs were prescribed 60 (17.14%) were prescribed by generic name and the rest 290 (82.86%) were prescribed by brand name. Only 18 (5.14%) drugs were not prescribed from hospital formulary. 264 (75.43%) drugs were dispensed from hospital pharmacy. On the basis of rationality score 53% prescriptions were rational, 30% semi rational and 17% irrational.Conclusions: In a rural hospital, where hospital formulary is based on WHO Essential medicine list, hundred percent utilization of hospital pharmacy service doctors and patients would ensure rational prescribing benefits of the patients coming from rural and uneducated background.

Recurrent Follicular Dendritic Cell Sarcoma of the Parotid Gland Imaged with 18F-FDG PET/CT / 대한핵의학회잡지

Follicular dendritic cell sarcoma (FDCS) is an extremely rare tumor with only 67 cases of head and neck FDCS reported in the literature. A 65-year-old female had a 6-cm follicular dendritic cell sarcoma resected from the left parotid gland with close margins. It recurred 1 year later as a 5-cm mass that was intensely [18F] fluoro-2-deoxy-D-glucose (18F-FDG) avid on positron emission tomography/computed tomography (PET/CT) and was re-excised. A follow-up PET/CT did not show any metastatic disease. The use of 18F-FDG PET/CT in the management of FDCS warrants further research. We present the 18F-FDG PET/CT imaging findings of this rare tumor.

Fixed Dose Combination Of Drugs: Are They Justified.

Abstracts: Background:Fixed Dose Combinations (FDCs) are combinations of two or more active drugs in a single form. Prescribing FDCs has become a routine affair in medical practice. Combination drugs increase the compliance of patient to the treatment, decrease the pill burden, but may also lead to increase in the cost of the treatment and side effects. There has been increase in the irrational FDCs in the recent past. The rationality of a fixed dose combination is the most controversial and debated issue in today’s clinical practice. The eighteenth essential medicine list (EML) of WHO includes 25 FDCs while as the 2011 national list of essential medicines (NLEM) of India includes only18 FDCs. Contrary to this Indian market is flooded with FDCs, the scientific rationale for most of these remains unknown. In India, a fixed dose combination of drugs is considered a “NEW DRUG” and has to be approved by Drugs Controller General, India (DCGI). However, the Indian laws governing the approval and marketing of FDCs are not properly defined, the pharmaceutical manufactures take advantage of these loopholes and market combination that have no pharmacological rationale.

An Acute Therapeutic Evaluation of Three Regimens of Tiotropium and Formoterol in COPD Patients: A Randomized, Double-blind, Placebo-Controlled Clinical Study.

Aims: To evaluate therapeutic rationality of combining long-acting β2-agonists (formoterol) with duration of action of 12 hours and anticholinergics (tiotropium) with 24 hours as fixed dose inhaled combination (FDC) still widely prescribed in developing countries in COPD patients. Study Design: A randomized, double-blind, placebo-controlled, parallel design study. The three regimens that were used; tiotropium 18 μg once a day in the morning along with the formoterol matched placebo in the evening, the FDC of tiotropium 18 μg plus formoterol 12 μg once a day in the morning and formoterol matched placebo in the evening and the same FDC of the two drugs once a day in the morning and once a day formoterol 12 μg in the evening in patients of COPD without any co-morbidity. Place and Duration of Study: Tertiary care pulmonary medicine university teaching government hospital of Delhi, India; 1 year. Methodology: Sixty COPD patients (Male, Avg. age 56±11 years) divided into 3 groups of 20 each without any comorbidity were admitted in the hospital for 24 hours. The spirometry, perception of dyspnea on Borg's scale and vitals such as blood pressure (BP) and pulse rate (PR) were recorded at the following interval 30 minutes, 2 hours, 12 hours after the morning dose and 30 minutes and 12 hours after the evening dose. Results: Addition of formoterol in the evening along with the FDC in the morning enhanced the peak effects in percentage predicted FEV1 (82.55+/-12.639), FEV1/FVC (0.592±0.097) that remained till the next dose (24 hours) which was statistically (P=.05) superior to the tiotropium alone group (75.55+/-17.981) as well as FDC alone group (74.55+/-12.655). Conclusion: There is no advantage of FDC once a day over tiotropium alone. However addition of evening dose of formoterol has shown therapeutic superiority over once a day FDC of the two in COPD.

Assessment of antimicrobial prescribing and rationality of drug usage in general practitioners in Pune city, India.

Background: Most of the common ailments are managed by general practitioners (GPs). GPs prescribe major bulk of the drugs sold in the market. Naturally, irrational use of drugs at this level could lead to disastrous consequences. So this study was undertaken to determine prescribing pattern of Antimicrobials (AMA) and the rationality of drug usage by GPs in Pune city. Methods: It was a cross-sectional study. Pune city was divided into 5 zones. MBBS, BAMS and BHMS GPs doing Allopathic practice were selected randomly. 2 GPs of each specialty per zone were selected; this gave us 10 GPs of each degree – so total 30 GPs.30 Prescriptions at each GP were collected – total 900 prescriptions. The following parameters were studied- Diagnosis of patient, Average no. of drugs/prescription Percentage of AMAs prescribed, Rationality of AMA, Selection of AMAs diagnosis wise, Rationality of Prescription. Results: More than 75% patients coming to GPs were suffering from communicable diseases. Average no. of drugs / prescription and percentage of prescription with AMAs was high in all GPs. Macrolides was the most common group of AMA used by MBBS whereas Cephalosporins was used by BAMS and BHMS. Irrational use of AMAs was high in BHMS GPs. Use of irrational FDCs, banned drugs, steroids was high in BAMS GPs. Conclusions: There are deficiencies in prescription practices among all GPs. Not only are GPs prescribing the highest number of AMAs per prescription anywhere, their prescription practices for common health problems are highly inappropriate. High level of irrational use of drugs by BAMS and BHMS GPs are cause of concern.

Role of FDCs-miR-548m-CDK6 axis in clonogenicity of mantle cell lymphoma / 中国肿瘤临床

Objective:To study the role of FDCs-miR-548m-CDK6 axis on clonogenicity in mantle cell lymphoma. Methods:RT-qPCR and Western blot were used respectively to test the expression of miR-548m and CDK6. Bioinformatics assay was applied to predict the targets of miR-548m, and Western Blot was used to test the expression level of CDK6 after miR-548m overexpression or in-hibition. Luciferase report assay was performed to test whether CDK6 was a direct target of miR-548m. Colony forming assay was used to test the colony forming activity in MCL after overexpression of miR-548m or knockdown of CDK6. Results:Cell adhesion to FDCs induced downregulation of miR-548m and CDK6 expression in MCL. Bioinformatics assay revealed that miR-548m could target the 3'-UTR of CDK6 and that a negative correlation exists between the level of miR-548m and the CDK6 expression. Luciferase report as-say confirmed that miR-548m directly targeted 3'-UTR of CDK6. Colony forming assay showed that overexpression of miR-548m or knockdown of CDK6 significantly suppressed MCL colony formation. Conclusion:This study reveals that FDC-enhanced mantle cell lymphoma clonogenicity is mediated by the miR-548m/CDK6 axis.

Evaluation of prescribing patterns of teaching and non teaching hospitals by undergraduate medical students in Pune, India.

Background: This study was carried out in various hospitals to analyze the use of rational fixed dose combinations (FDCs) in Pune. Methods: 279 prescriptions were evaluated in this study. Information about age, sex, names of the all the drugs prescribed by doctor/ physician, diagnosis for the use of prescriptions and adverse effects were noted in the audit form from the prescriptions of the patients. Rationality of fixed dose combination is evaluated according to WHO Model List of Essential Drugs, 17th updated version, 2011. Results: 56.98 % doctor’s prescriptions in this study were containing of fixed dose combinations and out of this 10.69 % prescriptions were including two or more FDCs in their prescriptions. Only 13.20% FDCs were in accordance with WHO Model List of Essential Drugs. FDCs from antiinflammatory and antirheumatic products, vitamins, minerals, antianaemic preparations, drugs for acid related disorders, antibacterials for systemic use and cough and cold preparations were used more by private non teaching hospitals as compared to SKNMC & GH teaching hospital. 64.61 % prescriptions of private hospitals and 34.08 % prescriptions of teaching hospital were containing more than one drug. Conclusions: This study has shown that about every alternate prescription contains FDC. More than 80 % of prescribed FDCs are not in accordance with Essential Drugs List. Vitamins, minerals, antianaemic preparation FDCs should be prescribed judiciously as they are not free from ADRs. More number of drugs (poly-pharmacy) and FDCs were prescribed by non teaching private hospitals.

Current scenario of rational usage of various drugs in indoor patients.

Background: Irrational prescribing of drugs is of common occurrence in clinical practice. Rational drug prescribing is defined as “the use of the least number of drugs to obtain the best possible effects in the shortest period and at a reasonable cost”. The present study was designed to evaluate the practice of rational prescription in patients (cases) admitted in various wards of G.S.V.M. Medical College and associated hospitals at Kanpur. Methods: This study was carried out on patients admitted in different wards. For the study of drug prescribing patterns, each prescribed drug was counted only once for a patient, irrespective of change in dose and route of administration. WHO guidelines were taken into consideration. Both distribution of type of drug as well as drug category were evaluated in different departments thereafter. The characteristics chosen on each prescription provided the incidence of poly pharmacy and frequencies of prescribing of individual drug were analyzed. The data obtained were subsequently categorized systematically and analyzed by taking WHO guidelines into consideration. Results: The most commonly prescribed drugs were vitamins and tonics (57.5%) followed by anti-microbial agents (12.7%), non-steroidal anti-inflammatory drugs (10.5%), anti-hypertensive (5.2%), anti cough remedies and acid peptic disease drugs. Generic drug prescription was very low as most of drugs prescribed were proprietary. A low number of Fixed Dose Combinations (FDCs) were prescribed, this finding was in accordance with the WHO recommended list of FDCs. Items on the WHO model list of essential drugs were prescribed frequently. The use of drugs has been found to be in accordance with the disease, the patient had. Conclusions: Present study highlighted that there was a high incidence of irrational prescribing practice that increased with the total number of drugs per prescription.

Pharmacokinetics of lamivudine & stavudine in generic fixed-dose combinations in HIV-1 infected adults in India.

Background & objectives: Antiretroviral drug concentrations are important determinants of clinical response to a drug accounting for both toxicity and efficacy. Several factors such as age, ethnicity, body weight and patients’ immune status may influence antiretroviral drug concentrations. The aim of the study was to determine the influence of immunological status, sex and body mass index on the steady state pharmacokinetics of lamivudine (3TC) and stavudine (d4T) in HIV-infected adults, who were undergoing treatment with generic fixed dose combinations (FDC) of these drugs in India. Methods: Twenty seven HIV-1 infected patients receiving antiretroviral treatment (ART) for at least two weeks at the Government ART clinic at Tambaram, Chennai, took part in the study. Serial blood samples were collected predosing and at different time points after drug administration. Plasma 3TC and d4T levels were estimated by HPLC. Results: The patients’ immune status, sex or body mass index had no impact on the pharmacokinetics of 3TC. In the case of d4T, peak concentration was significantly lower in patients with CD4 cell counts < 200 cells/μl than those with ≥ 200 cells/ μl (P < 0.05), but were within the therapeutic range. The mean CD4 cell counts increased from 101 cells/μl at initiation of ART to 366 cells/μl at 12 months of treatment. Interpretation & conclusions: Blood levels of 3TC and d4T drugs that are part of generic FDCs commonly used by HIV-infected individuals in India were within the therapeutic range and not influenced by nutritional or immune status. There was a significant improvement in CD4 cell counts over 12 months of treatment. Indian generic FDCs manufactured and used widely in the developing world provide effective concentrations of antiretroviral drugs.

Quality problems of anti-tuberculosis Fixed-dose Combinations (FDCS) A way forward.

Fixed dose combinations (FDCs) of anti-tuberculosis drugs (Rifampicin, Isoniazid, Pyrazinamide and Ethambutol hydrochloride) have several advantages over loose combinations of these drugs. Hence, the use of FDCs in the short course chemotherapy of tuberculosis is being promoted internationally. However, these products are associated with quality problems such as loss of bio-availability of Rifampicin and instability of the drugs in the combination. Recent research in Indian laboratories has helped in identification of the major reasons behind these problems, which suggest that an entirely different approach is required to that currently being recommended by the world bodies. The purpose of this article is to briefly discuss the twin quality problems and to highlight the potential forward ways.