Usage Pattern of Fixed-dose Combinations at ICMR Network of Rational Use of Medicine Centres across India: Recommendations for Policymakers and Prescribers.

AIM: Irrational use of medicines is a global problem. In India, one contributing factor is the availability of a large number of fixed-dose combinations (FDCs). To improve rational use and to strengthen policies, it is important to assess the usage patterns and rationality of FDCs. METHODS: This study was conducted as part of a 1-year prospective cross-sectional analysis of prescriptions in the outpatient clinics of broad specialities from 13 tertiary care hospitals across India. Five most commonly prescribed FDCs in each center were analyzed. In addition, all the prescribed FDCs were classified as per the Kokate Committee classification and it was noted whether any of the FDCs were irrational or banned as per the reference lists released by regulatory authorities. RESULTS: A total of 4,838 prescriptions were analyzed. Of these, 2,093 (43.3%) prescriptions had at least one FDC. These 2,093 prescriptions had 366 different FDCs. Of the 366 FDCs, 241 were rational; 10 were irrational; 14 required further data generation; and the remaining 96 FDCs could not be categorized into any of the above. Vitamins and minerals/supplements, antibacterial for systemic use, and drugs for gastroesophageal reflux disease (GERD) and peptic ulcer were the most used FDCs. CONCLUSION: Based on the finding that some prescriptions contained irrational FDCs, it is recommended that a rigorous, regular, and uniform method of evaluation be implemented to approve/ban FDCs and that prescribers be periodically notified about the status of the bans.

Price Dispersion of Vitamin D Supplements Over Time: An Initiative for Prescriber Education.

OBJECTIVES: High prevalence of vitamin D deficiency mandates prescribing an appropriate form of vitamin D that allows attainment of sufficiency in a cost-effective manner. We aimed to compare vitamin D products in Indian market in terms of composition and cost in 2020 with 2013 to understand price dispersion over 7 years. METHODS: Constituents, formulations, and prices of 'branded' and generic vitamin D products were sourced from various drug information compendia and online sources. Price per defined daily dose (DDD), percentage cost variation, and change in prices over 7 years (2020 vs. 2013) was determined. RESULTS: There has been a disproportionate increase in the number of brands and cost variation of cholecalciferol and calcitriol in the last 7 years. The percentage cost variation increased almost 10 times for calcitriol and 4.4 times for alfacalcidiol tablets and cholecalciferol granules. An analysis of >1,100 products in 2020 showed that the predominant form was calcitriol which was combined with calcium in >90% of the products with huge cost variation (>3000%). Ergocalciferol and cholecalciferol were available in 22 and 15 different strengths respectively. Median price/unit of cholecalciferol (60,000IU) was lower for tablets/capsules compared to other formulations; but with >1000% cost variation. CONCLUSION: A wide cost variation exists with the use of different vitamin D brands and preparations with conventional cholecalciferol tablets and capsules being a low-priced alternative. Quality control measures and strict enforcements of existing regulations are essential to ensure that competitive prices of branded generics are translated into availability and affordability for the population.

Spaced education and student learning: Results from a medical school.

BACKGROUND: It is critical for medical students to retain and apply their knowledge of basic sciences to become competent prescribing physicians. Poor long-term retention is a pervasive concern. We investigated the impact of 'spaced education' teaching modules to improve knowledge retention in medical students on a topic of public health: vitamin D and its role in health and disease. It is critical for medical students to retain and apply their knowledge of basic sciences to become competent prescribing physicians METHODS: In a self-matched design, 148 medical students were randomised and evaluated on vitamin D-related topics to assess reinforced and non-reinforced knowledge in a multiple-choice question format. Initial learning and long-term retention were assessed with an estimation of Cohen's effect size at 24 and 72 weeks, respectively. RESULTS: The administration of spaced educational material significantly improved composite formative test scores at 24 weeks (p < 0.001, effect size = 1.33). Although the scores dipped, there was a retention of knowledge at 72 weeks (effect size = 0.48). DISCUSSION: Spaced reinforcement and testing statistically improved knowledge retention among our medical students. Gaps in the present teaching could be bridged by motivating the students to extend their learning time by appropriate spacing intervals and to understand the relevance of course content in different scenarios as a physician. Further research could be instrumental in optimising interventions to enhance learning opportunities for medical students.

Pediatric Off-Label and Unlicensed Drug Use and Its Implications.

BACKGROUND: Worldwide, in the absence of standard pediatric prescribing information, clinicians often use medicines in children in a dosage form or for an indication that has not been approved for use. Inadequate clinical trials increase exposure to drugs that lack safety-efficacy data in pediatric population. Hence, off-label and unlicensed drug use must be regarded as a patient safety-issue that is known to be associated with increased risks of adverse drug reactions apart from under- or overdosing due to lack of pharmacokinetic data. This review aims to give an overview of the worldwide reported rates of off-label and unlicensed drug use in different patient populations in pediatric settings, with a brief summary of the related adverse drug reactions (ADRs) and a discussion of the existing regulatory provisions and possible solutions for ensuring safe use of medicines in children. METHOD: Literature searches were conducted and we included studies that evaluated unlicensed or off-label drug use in various pediatric patient populations. The definition of off-label drug use and unlicensed drug varied between different studies. RESULTS: Fourteen studies from different countries were included in the review and were grouped as: studies conducted in the patients admitted in neonatal intensive care units, in pediatric wards, in hospitalized children and in pediatric outpatient settings. The number of patients studied ranged from 34 in neonatal intensive care units to 355 409 hospitalized children. Many studies reported high rates of off-label (9% to 78.7%) and unlicensed (0.3% to 35%) drug use in different pediatric patient settings. CONCLUSION: Given the prevalence of unlicensed and off-label drug use, the cooperation of various stakeholders including health professionals, pediatric population and their parents/caregivers, regulatory authorities, and the pharmaceutical industry is integral to instituting individual measures to avoid exposing children to unnecessary risks and avoid depriving them of potentially effective pharmacotherapy. Initiatives to encourage clinical trials for licensing drug use in children by providing market exclusivity and patent extension could aid in bridging the gap between approval and contemporary drug prescribing practices. Enforcement of legislations in the drug development process and subsequent pharmacovigilance could improve the quality of information and accountability of pharmaceutical industry to support and facilitate drug research in children.

Belimumab: targeted therapy for lupus.

Systemic lupus erythematosus (SLE), a complex autoimmune disease with multisystem involvement, is characterised by recurring flares and remissions throughout the course of illness. The agents currently being used for management include corticosteroids, antimalarials and various immunosuppressants. Belimumab, a B lymphocyte stimulator (BLyS) inhibitor has been recently approved for the treatment of SLE. This review aims to discuss the role of belimumab in the treatment of SLE and the trials leading to its FDA approval. Belimumab demonstrated high degree of activity in patients with autoantibody-positive active SLE disease on a stable treatment regimen. There was a significantly greater response compared to placebo as assessed with the SLE Responder Index (SRI) in two randomized, double-blind, phase III trials (BLISS-52 and BLISS-76). The treatment was well tolerated. Additional studies are required to evaluate belimumab in special populations and assess its long-term safety. This therapy could change the focus of management from symptomatic treatment to targeting an important step in the disease pathogenesis. It could enable development of treatment which could halt long-term progression, minimize target organ damage and thus provide a better quality of life for these patients.

An assessment of vitamin supplements in the Indian market.

We aimed to study the composition and availability of various vitamin preparations in the Indian market, data about which was collected from an annual Drug Compendium. The preparations were assessed for total number, different formulations, constituents and amount of each constituent present in the formulation. A large number of vitamin supplements are available in the Indian market. It includes single-ingredient products and various combinations of vitamins, minerals, and other constituents. Among single products, the maximum number was that of vitamin D3 (n=150). Most of the supplements are available as combinations (76.49%), with vitamin-minerals combinations constituting the maximum number. In a large number of products, amount of the vitamins was not specified. The most common formulation for oral administration was capsules (34.1%). In our research, majority of the supplements contained nutrient amounts higher than the recommended intakes recommended dietary allowance. Unsupervised intake of vitamins can pose a serious health risk in the susceptible population. The composition and amount of each constituent in the dietary supplement should be detailed and properly labelled for each preparation. Availability of a large number of preparations with unknown composition as 'over the counter' agents requires a serious review of the legal provisions in India for drug manufacturing and marketing. There is a need for proper guidelines and regulations for the manufacturing, labelling and marketing of dietary supplements in India. Strict enforcement of such provisions is essential to safeguard the health of the population at large.