Generic versus brand-name drugs used in cardiovascular diseases

This meta-analysis aimed to compare the efficacy and adverse events, either serious or mild/moderate, of all generic versus brand-name cardiovascular medicines. We searched randomized trials in MEDLINE, Scopus, EMBASE, Cochrane Controlled Clinical Trial Register, and ClinicalTrials.gov (last update December 1, 2014). Attempts were made to contact the investigators of all potentially eligible trials. Two investigators independently extracted and analyzed soft (including systolic blood pressure, LDL cholesterol, and others) and hard efficacy outcomes (including major cardiovascular adverse events and death), minor/moderate and serious adverse events. We included 74 randomized trials; 53 reported ≥1 efficacy outcome (overall sample 3051), 32 measured mild/moderate adverse events (n = 2407), and 51 evaluated serious adverse events (n = 2892). We included trials assessing ACE inhibitors (n = 12), anticoagulants (n = 5), antiplatelet agents (n = 17), beta-blockers (n = 11), calcium channel blockers (n = 7); diuretics (n = 13); statins (n = 6); and others (n = 3). For both soft and hard efficacy outcomes, 100 % of the trials showed non-significant differences between generic and brand-name drugs. The aggregate effect size was 0.01 (95 % CI -0.05; 0.08) for soft outcomes; -0.06 (-0.71; 0.59) for hard outcomes. All but two trials showed non-significant differences in mild/moderate adverse events, and aggregate effect size was 0.07 (-0.06; 0.20). Comparable results were observed for each drug class and in each stratified meta-analysis. Overall, 8 serious possibly drug-related adverse events were reported: 5/2074 subjects on generics; 3/2076 subjects on brand-name drugs (OR 1.69; 95 % CI 0.40-7.20). This meta-analysis strengthens the evidence for clinical equivalence between brand-name and generic cardiovascular drugs. Physicians could be reassured about prescribing generic cardiovascular drugs, and health care organization about endorsing their wider use

Effects of 'Authorized-Generics' on Canadian Drug Prices

This paper examines how the use of ‘authorized-generics’ (AGs) influences Canadian prescription drug prices. An authorized-generic is the actual brand name drug product, manufactured by the brand firm, but sold as a generic by a licensee or subsidiary of the brand, competing with independent generics (IGs), which operate independently from the brand firm. In theory, AGs have offsetting effects on drug prices. On the one hand, AGs compete against IGs and increases in the number of generic competitors should lower prices. On the other hand, the threat of AG entry into a therapeutic market might deter entry by IGs and this would lessen competition. Moreover, brand firms might increase prices of their brand drugs to increase demand for their AG. I find that when AGs are first to enter a drug market, average drug prices drop by about 12%; average prices drop by smaller amounts, the larger the AG share of the generic market. I could not directly assess whether the threat of AG entry into a market might deter entry by IGs. IG executives, however, state that the threat of AG entry has decreased their incentive to challenge ‘marginal’ drug markets. In particular the threat of AG entry has increased from $5m to$10m the threshold market size – the value of brand drug sales in the 10th year that it has been on the market, below which the IG firm will not attempt to enter. IG executives also stated that AGs have seriously reduced IG retained earnings. The reduction in retained earnings has hampered their ability to challenge brand drugs with annual sales well above $10m, but which have particularly high entry costs. Finally, the IG executives claimed that brand firms have attempted to use the threat of AG entry to negotiate agreements with the IG to delay entry (or not enter at all). A comprehensive evaluation of the competitive effects of AGs would need to verify and quantify these costs and compare these to the benefits of AG competition.authorized-generic drugs, independent generic drugs, drug prices, Canada

Interchangeability and Comparative Effectiveness between Micronized and Non-micronized Products of Glibenclamide Tablets

Background: During the last few years there was wide debate about the interchangeability and effectiveness between circulated products containing Glibenclamide in the market.Objectives: This study aimed to compare the effectiveness of this product “non-micronized” to the originator’s product of Glibenclamide tablets “of micronized” sulfonylurea.Methods: 12 volunteers received a dose of 5mg of Glibenclamide (from test and standard products) under fasting conditions in two separate sessions using randomized crossover design. Blood glucose level for the volunteers was monitored to avoid the development of hypoglycemia. Plasma samples were collected over 24 hours and analyzed using HPLC.Results: The maximum concentration Cmax for the test and reference products were 2.508 ± 0.104 and 3.526 ± 0.118 (ìg/ml) respectively and the area under the curve AUC0-[ were 3.511 ± 0.153 4.572 ± 0.202 (ìg.h/ml) for these products respectively, with a difference of about 24% between the test and reference products in its AUC.Conclusions: The results indicate that the test product is not bioequivalent to reference product. The difference in formulation between micronized product and non-micronized product of Glibenclamide tablets has impact on clinical outcomes.Key words:sulfonylurea,Blood glucose,hypoglycemia

Microbiological Assay of Two Selected Products of Ceftriaxone Powder for Injection from Pharmaceuticals' Market in Sudan

Background: Different techniques have classically been used to evaluate and assure the quality of medicines circulated on the market; one of the commonly uses is chemical analysis. However, some evidence has shown that there are other important indicators (e.g. bioequivalence, relative potency, etc.) that should also be considered when evaluating the quality of pharmaceutical products.Materials and Methods: A microbiological assay was conducted to compare the relative potency of two Ceftriaxone products (with a third one used as standard product) from the market using 3 reference bacteria including Streptococcus pneumoniae, Klebsiella pneumoniae and Staphylococcus aureus. Serial dilutions were made with the corresponding 1, 4, 8, 16 and 32-fold Minimum Inhibitory Concentration (MIC) of Ceftriaxone against the bacteria under investigation.Results: The relative potency of one product compared to the standard product was estimated to be within the acceptable range of bioequivalence (89.6%), while the other product showed unacceptable relative potency (72.3%).Conclusions: The microbiological assay is an effective and simple method for comparing the equivalency of injectable products. A complaint reporting system about quality and effectiveness problems needs to be considered as a priority source of such information to inform decision-makers.Keywords: Microbiological assay, Ceftriaxone, quality assurance, relative potency and genericmedicines

The prescribing of generic medicines in Nigeria : knowledge, perceptions and attitudes of physicians

Generic medicines have the same efficacy and safety as originators at lower prices. However, there are concerns with their utilization in Nigeria. Evaluate physicians’ understanding and perception of generics. Questionnaire among physicians working in tertiary healthcare facilities in four geo-political regions of Nigeria. Response was 74.3% (191/257) among mainly males (85.9%). The mean knowledge score regarding generics was 5.3 (maximum of 9) with 36.6%, 36.1% and 27.2% having poor, average and good knowledge respectively. Cross-tabulation showed statistical significance (P = 0.047) with the duration of practice but not with position, subspecialty or sex. The majority did not agree that generic medicines are of lower quality than branded medicines. Therapeutic failure was a major concern in 82.7%, potentially discouraging prescribing of generics. Majority (63.9%) did not support generic substitution by pharmacists. Knowledge gaps were identified especially with the perception of generics. These need to be addressed

Innovation and Competitive Capacity in Bangladeshs Pharmaceutical Sector

The global pharmaceutical sector is highly patent intensive, and firms rely on product, process and formulation patents to protect their innovations. Intellectual property rights on pharmaceutical products, as contained in the Agreement on Trade Related Aspects of Intellectual Property Rights (hereafter, the TRIPS Agreement) have been defended on grounds of extensive R&D investments required to discover and develop new drugs. But at the same time, grant of uniform pharmaceutical patents in all developing and least developed countries that are members of the World Trade Organization in accordance with the TRIPS Agreement, raises a range of issues for access to medicines. These issues can be framed under three broad areas: the restriction of reverse engineering possibilities for firms in developing countries and its implications for catch-up in this sector, higher prices of drugs and access to medicines as well as access to technologies due to patents on upstream technologies. The transitional arrangements under the TRIPS Agreement specifically mandated that all developing countries that are members to the WTO enact national laws that are TRIPS-compliant by 2005. As a result, from 2005 onwards, several countries like India, which played an important role as producers and exporters of generic copies of brand name products patented outside the country, can no longer produce such drugs due to the introduction of TRIPS-compliant patent regimes in their countries. Least developed countries have an extension until 2016 to implement the pharmaceutical patent provisions of the TRIPS Agreement under the Doha Declaration on TRIPS and Public Health. However, such legal flexibility is quite meaningless for least developed countries in the absence of local technological capabilities to produce generic drugs amongst least developed countries. Bangladesh, although a least developed country, is an exception in this regard with thriving domestic processing sectors that are actively engaged in producing textiles and ready made garments (RMGs), processed food products and generic drugs. Therefore, the question that looms large in the global access to medicines debate is whether Bangladesh's pharmaceutical sector can gradually evolve to provide low-cost substitutes of important patented drugs to other developing and least developed countries? This study is an original empirical investigation into issues of innovative capacity and competitiveness of the local pharmaceutical sector in Bangladesh.Bangladesh, WTO, TRIPs, Intellectual Property Rights, Pharmaceutical Industry, Public Health

Biopharmaceutics classification system: importance and inclusion in biowaiver guidance

O tratamento farmacológico é essencial frente a várias patologias e é fundamental que a política de medicamentos tenha por objetivo oferecer à população tratamento seguro, eficaz e de preço acessível. Uma forma de alcançar esse objetivo é por meio da bioisenção, definida como a substituição de estudos de bioequivalência in vivo por estudos in vitro. Para bioisentar novos medicamentos sob a forma farmacêutica sólida oral de liberação imediata são utilizados dados de permeabilidade intestinal e solubilidade do fármaco, bem como sua dissolução a partir da forma farmacêutica. O Sistema de Classificação Biofarmacêutica (SCB) é um esquema científico que divide os fármacos em classes de acordo com a solubilidade e permeabilidade e vem sendo utilizado como critério para bioisenção em diversas legislações. O presente artigo faz uma avaliação da aplicação da bioisenção, abordando os conceitos gerais e parâmetros utilizados pelo SCB, fazendo um relato histórico da aplicação da bioisenção, das exigências pertinentes às legislações vigentes, dos benefícios e riscos inerentes a uma tomada de decisão sobre bioisenção baseada neste critério. Os resultados revelaram que a utilização do SCB como critério amplia enormemente as possibilidades de bioisenção, contribuindo para o maior acesso da população em geral a medicamentos com garantida eficácia, segurança e menor custo.Pharmacological therapy is essential in many diseases treatment and it is important that the medicine policy is intended to offering safe and effective treatment with affordable price to the population. One way to achieve this is through biowaiver, defined as the replacement of in vivo bioequivalence studies by in vitro studies. For biowaiver of new immediate release solid oral dosage forms, data such as intestinal permeability and solubility of the drug are required, as well as the product dissolution. The Biopharmaceutics Classification System (BCS) is a scientific scheme that divides drugs according to their solubility and permeability and has been used by various guides as a criterion for biowaiver. This paper evaluates biowaiver application, addressing the general concepts and parameters used by BCS, making a historical account of its use, the requirements pertaining to the current legislation, the benefits and risks associated with this decision. The results revealed that the use of BCS as a biowaiver criterion greatly expands the therapeutics options, contributing to greater therapy access of the general population with drug efficacy and safety guaranteed associated to low cost

Nutraceutical-based integrative medicine: adopting a mediterranean diet pyramid for attaining healthy ageing in veterans with disabilities

Veterans with disability represent a big burden worldwide and often require long-term rehabilitation. Unhealthy dietary and lifestyle habits, including smoke and alcohol abuse, are common in veterans. In the context of integrative medicine approaches, the "complementary and alternative medicine" has been suggested for the management of chronic diseases. However, the potential risk of interaction between herbal products, dietary supplements and drugs must be considered in veterans. The Mediterranean diet has been suggested as a natural, non-pharmacological nutraceutical for healthy ageing. Although there is a broad consensus on the positive effect of plant foods consumption, the presence of glucosinolates, flavonoids and furanocoumarins in some plant foods and beverages must be taken into consideration owing to their potential interfering with drugs metabolism and bioavailability. Albeit seasonality could ensure the maintenance of the single dose of phytochemical below that at which adverse effects in some individuals genetically predisposed or unpleasant drug interactions in diseased subjects can occur, a personalized nutrition is recommended in veterans who are in treatment for comorbidities. Furthermore, sports practice can lead veterans with motor disabilities and mental impairments to excel in some disciplines, giving rise to the phenomenon of the Paralympics and the development of "recreational therapy". Moreover, outdoor lifestyle, through vitamin D synthesis, and conviviality, improving socialization, could account for the Mediterranean lifestyle health benefits. In this work we propose for veterans a Mediterranean Pyramid, which could be the basis for integrative medicine for veterans with disabilities, patient-centered approaches and interprofessional (including physical medicine and rehabilitation clinicians, pharmacists and nutritionists) interventions

Generic Drug Switch in Epilepsy – Pharmacokinetic and Clinical Aspects

Background and aim: Generic drugs contain the same active ingredients as brand- name drugs, with the advantage of much lower costs. The aim of this thesis was to contribute new knowledge to the ongoing debate on the safety of generic antiseizure drug (ASD) substitutions. There was a particular emphasis on the pharmacokinetic and clinical outcomes.Methods: In papers I and II, a prospective naturalistic study of generic drug switching of levetiracetam (LEV) was conducted with repeated LEV serum concentration measurements and assessment of quality of life before and after the switch. In paper III, a cross-sectional survey study was conducted to explore associations between the characteristics of people with epilepsy (PWE) and their attitudes toward the generic substitution of ASDs. In paper IV, an online survey study of physicians’ perspectives on generic ASD substitution in epilepsy was conducted. Results: Paper I: Fluctuation of LEV serum concentrations was equal with branded LEV and the generic LEV. Within-subject variability was much larger than the small, non-significant differences between the two LEV products. No switchbacks occurred. Paper II: Irrespective of brand or generic treatment, subjects were less worried about seizures at the end of the study compared to at inclusion. Paper III: High proportions of PWE express concerns about generic substitution of ASDs. Survey respondents with prior experience of generic ASD substitution were more likely to accept a future switch. Paper IV: Neurologists in two major Swedish healthcare regions generally have positive attitudes toward the generic substitution of ASDs in epilepsy. Conclusions: Current evidence suggests that the pharmacokinetic consequences of generic substitutions of bioequivalent immediate release second-generation ASDs are negligible at group level. Data on clinical aspects of generic substitutions are not as robust, but real-world prospective data indicate that possible substitution risks are generally small to non-existent in treatment-adherent individuals. Future studies should elaborate on interventions to ensure treatment adherence and reduce worries in connection with a switch. A structured nurse-led follow-up could be a cost-effective example of such an intervention that could facilitate successful generic substitution and lead to substantial cost savings

Logistic planning and drug formularies : considerations for clinically effective drug substitution

PhDDrug substitution is mainly economically not medically-driven; it can benefit healthcare services but does not directly benefit individual patients. Many healthcare providers have been promoting drug substitution in an attempt to contain their costs. This practice has been approved and supported on the basis of the presumption that the cheaper drug is not inferior to the more expensive one and the premise that any saving that does not compromise the quality of care is essentially appropriate. However, substitutions become problematic when the cheaper drug is known to have different effects and side effects, or even when there is just uncertainty about such effects. This thesis explores issues surrounding generic and therapeutic substitution from the ethical, patients’ and physicians’ point of view and from the potential differences in formulations between the branded and generic medicines. A series of studies such as a review of the ethical issues in drug substitution, multicentre surveys to explore patients’ and physicians’ views on drug substitution and other in-vitro and in-vivo comparisons between the actual formulations of the branded medicines and their generic counterparts were included in this thesis. The main objective was to encourage safe and effective generic and therapeutic substitution by validating the appropriateness and the potential impact of these substitutions on patients’ clinical outcomes and thus to promote high quality strategic logistic planning and effective management of drug formularies in hospitals. It was confirmed in this thesis that promoting generic and therapeutic substitution on economic grounds alone is unethical because it can be potentially harmful to patients and is incompatible with patient-centred medicine. As a consequence, multicentre surveys were conducted to assess patients’ views on generic substitution in hospital settings. A total of 163 renal transplant patients were surveyed using 36 multiple-choice questions at Barts and The London Renal Transplant Clinic, in the UK. This group of patients was specified because they may be particularly affected by drug substitution. Any small changes in the medicinal effect of this group of patients can negatively impact their clinical outcome. It was revealed in this survey that 84% of participating patients felt that generic medicines were not equivalent or only equivalent sometimes and they were uncertain that generics had the same quality as branded medicines. In addition, many patients admitted that they would refuse the generic substitution of ciclosporin when it became available in the UK. Another multicentre survey in the United Arab Emirates (UAE) using 188 renal patients revealed that 68% of participating patients felt that generics were not equivalent or only equivalent sometimes, and they were uncertain that generics had the same quality as branded medicines. Therefore, many patients admitted that they would refuse the generic substitution of ciclosporin when become available. These beliefs were highly marked in patients with less education, less communication with healthcare professionals and who suspected that the cheaper drug substitution was implemented only to save costs. In another prescription based survey in the UAE, a random sampling of 1000 written prescriptions was analysed to determine physicians’ attitudes towards generic medicines and prescribing. It was explored in this study that prescribers were not yet ready to promote appropriate generic substitution. They were still prescribing generic medicines on occasions where health complications may occur as well as increase healthcare expenditure. As a result, improving awareness and education among physicians is compulsory to implement appropriate generic prescribing and substitution. In-vitro dissolution study was also conducted in this thesis to detect any potential differences in dissolution behaviour between the branded medicines and their generic counterparts. A total of 37 medicines (13 innovator medicines and 24 generic counterparts) were collected locally and internationally and tested according to the British Pharmacopeia, European Pharmacopeia and the US Pharmacopeia with the rate of dissolution determined by ultra-violet Spectrophotometer. It was marked in this study that some generic medicines showed significant differences in dissolution rate at 60 and 120 minutes compared to their branded counterparts. Other generics violated the EMA and the FDA guidelines for industry when they failed to achieve 85% dissolution at 60 minutes and to keep the same dosage form as their branded counterparts. Moreover, a bioequivalence study was carried out in this thesis using 24 healthy volunteers under fasting conditions to compare Resclar 500 mg (Neopharma, UAE) with its branded Klacid® 500 mg (Abbott Laboratories Ltd, England), both are macrolide antibiotics contain 500 mg clarithromycin per tablet. It was confirmed in this study that Resclar 500 mg met the regulatory definition of bioequivalence with Klacid® 500 mg as the innovator product based on a single dose comparative bioavailability study under fasting conditions in the selected healthy volunteers. Therefore, Resclar 500 mg could provide an acceptable prescribable alternative to Klacic® 500 mg. In conclusion, the results presented in this thesis suggested that randomly and economically-driven drug substitution can be potentially deleterious to patients and should not be promoted. Factors such as physicians and patients education, monitoring, severity of the disease and efficacy of generic medicines are essential to promote safe and effective drug substitution. Thus, to achieve excellent strategic logistic planning and effective management of drug formularies in hospitals, generic and therapeutic substitution should be solely based on providing patients with the best possible care and quality medicines